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PMC5436409_01
Male
40
A 40-year-old Liberian man, who had been living in Elwa, Monrovia, travelled by air through Accra (Ghana) and Lome (Togo) to Lagos, Nigeria. Upon arrival at Lagos International Airport on 20 July 2014, he collapsed and was taken to a private hospital in the Obalende area of Lagos, Nigeria (Figure 1), where he was admitted. He presented with high fever, lymphadenopathy and sore throat and was treated for malaria and typhoid fever until he later developed diarrhoea, vomiting and microscopic haematuria. The culmination of the clinical presentation, the patient's non-response to treatment for malaria and typhoid, as well as his epidemiological link to Liberia, raised the suspicion for EVD. On 22 July 2014, blood samples in EDTA tubes and urine samples were collected and sent for viral investigations to the CMUL-LUTH Virology Unit Laboratory. Aliquots of the specimens were sent in parallel to the African Center of Excellence for Genomics of Infectious Diseases (ACEGID) at Redeemers University in Ogun State, Nigeria. No ethics approval was required for the diagnosis of an infection of great public health importance and which was part of the normal course of management of any infected patient. Due to the fact that no BSL-3 or BSL-4 facilities were available to handle the patient's specimens, all samples received were handled in a BSL-2 facility with extreme care and in line with US Centers for Disease Control and Prevention (CDC) safety guidelines. Personal protective equipment (PPE) was worn in accordance with the 'donning and doffing of PPE' protocol set out by the CDC. Sample carrier boxes were sprayed with 10% hypochlorite solution on a disposable laboratory absorbent mat in a biosafety class IIA cabinet. Specimen containers were removed from the carrier box and wrapped immediately with a laboratory paper towel soaked in 10% hypochlorite in order to disinfect any possible spillage around the specimen container. An identical process was used for removal of samples from the container box. Outer gloves were sprayed with 10% hypochlorite solution every time hands were withdrawn from the safety cabinet and then disposed of in double-jacketed bio-hazard waste bags if they were soiled during sample handling or at the end of the procedure. Aliquots of specimens used for viral assays were immediately inactivated in a guanidinium-thiocyanate lysis buffer for viral nucleic acid extraction (Qiagen, Germantown, Maryland, United States). For viral RNA extraction, neat (undiluted), 1:10 and 1:100 dilutions in sterile phosphate-buffered saline specimens of both blood and urine were processed using a Qiagen RNA extraction kit (Qiagen, Germantown, Maryland, United States). Segments of the L-gene of the Ebola virus, the S-gene of the Lassa virus and the 3' non-coding region of the Dengue fever virus were amplified in singleplex PCRs using the primers listed in Table 1. Separate master mixes for each queried virus were prepared and cycled as described in the AmbionAgPath-ID One-Step RT-PCR kit (Applied Biosystems, Foster City, California, United States) protocol. Subsequently, PCR amplicons were subjected to 1.5% agarose gel electrophoresis with 1X SYBR Safe DNA gel staining dye (Invitrogen, Carlsbad, California, United States) at 120V for 30 minutes and images were taken with a BioDocAnalyze 2.0 (Biometra, Goettingen, Germany). PCR amplicons on the agarose gel were purified using an agarose gel extraction kit (Jena Bioscience, Jena, Germany). Purified non-infectious PCR products, packaged and transported using triple-level packaging, were sequenced using the Filo A2.3 primer on the Sanger dideoxy sequencing technology platform with an Applied Biosystems 3130xl Genetic Analyser at Jena Bioscience in Jena, Germany. A sequence trace file was used for BLAST analysis in GenBank. The RNA-dependent RNA polymerase (L) gene, partial Coding sequence (CDS) for EBOV/Hsap/NGA/2014/LIB-NIG 01072014 was deposited in the National Center for Biotechnology Information (NCBI) with the accession number KM251803.1. A set of 30 different Filovirus genomes were selected from NCBI's GenBank. The FASTA format of the L-gene region of all the selected genomes was downloaded and aligned with the KM251803.1 sequence using the MUSCLE tool of MEGA-6 software (Figure 2). The Tamura 3 parameter (T92) was found to be the best maximum likelihood model to infer the phylogenetic tree. A discrete Gamma distribution was used to model evolutionary rate differences among sites (+G, parameter = 0.8048) and the rate variation model allowed for some sites to be evolutionarily invariable ([+I], 36.3524% sites). The reliability of each node on the phylogenetic tree was tested by bootstrapping with 1000 replicates. Investigations carried out on viral RNA purified from the blood and urine specimens of the patient revealed the presence of the expected amplicon size (300 bp) for Filoviruses (Figure 2). However, no signals were observed for Lassa or Dengue fever viruses. The filovirus amplicons were still detected in blood specimens with logscale dilutions of 1 (1:10) and 2 (1:100), whereas in urine samples the signal was no longer detectable at a log 3 dilution. Phylogenetic analysis of the L-gene partial CDS indicated that the virus evolved from the Guinea and Mano River isolates of the 2014 outbreak with a bootstraping value of 87% (Figure 3). Other isolates represented on the phylogenetic tree confirmed the evolutionary relationships between the different filoviruses.
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PMC9076885_01
Female
17
As part of her physical examination 17 months ago, a 58-year-old woman underwent chest computed tomography (CT), which showed no abnormalities. Six months ago, she began to experience a persistent cough and dyspnea, for which she was prescribed 20 mg of prednisolone, but there was no response. Then, she was prescribed concomitant cyclosporine, but her condition worsened. The patient was admitted to our hospital for examination. She had no past medical history or family history of PAP, and she did not smoke, but she was taking estradiol and raloxifene to prevent menopausal disorders. The patient's physical examination revealed the following: height 155 cm, weight 44.3 kg, temperature 36.6 C, blood pressure 150/101 mmHg, radial pulse 100 bpm, respiratory rate 14 bpm. Fine crackles were heard in both lungs. Lactate dehydrogenase (250 IU/L), Krebs von den Lungen-6 (KL-6 1329 U/mL), and lung surfactant protein D (211.5 ng/mL) levels were elevated. Arterial blood gas analysis in room air showed no hypoxemia (partial pressure of oxygen, 91.1 torr), and respiratory function tests revealed no abnormalities. Chest CT showed bilateral ground-glass opacities and reticular shadows, mainly distributed in the lower lobes. The abnormal shadows tended to enlarge over time after the initial examination (Fig. 1). Neither findings nor history were suggestive of hypersensitivity pneumonia, drug-induced pneumonia, eosinophilic pneumonia, or collagen vascular disease. Idiopathic interstitial pneumonia, including nonspecific interstitial pneumonia (NSIP), was suspected. Bronchoalveolar lavage was performed in the superior lingular segment of the left lobe, followed by a transbronchial lung biopsy (TBLB) of the left lower lobe. The BALF was transparent and did not have a milky appearance. The BALF cell count was unremarkable. The biopsy specimens contained eosinophilic bodies that strongly stained with periodic acid-Schiff (PAS) staining (Fig. 2). The serum level of anti-granulocyte macrophage colony-stimulating factor (anti-GM-CSF) antibody was high at 74.0 U/mL (normal level <1.7). Based on these findings, the diagnosis of APAP was confirmed.
anti-gm-csf antibody, autoimmune pulmonary alveolar proteinosis, bronchoalveolar lavage fluid, ground-glass opacities, nonspecific interstitial pneumonia
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PMC8709548_01
Male
61
Humans need to have relationships with others. Belonging needs are the feelings associated with a group, such as love, affection and so on, coming from family, friends, and other relationships. People are all eager to establish mutual connections with others, and to integrate into a certain group, as well as during the pandemic. Physical distancing and restrictions on gathering activities may lead to loneliness, anxiety, depression and other psychological outcomes. During the regular control periods when the fear of being infected is no longer the predominant emotion, the need for social interaction could trigger activities facilitating the spread of COVID-19 based on the analysis of the Hebei cases. In Hebei Province, a 61-year-old person was confirmed as the case of COVID-19 on January 2, 2021. Before that, there were hardly any infections in rural communities. The attention to fight against COVID-19 was paid more to cities. But after the New Year holiday, China reported clusters of infections in multiple provinces (eg, Hebei, Heilongjiang, and Jilin), the majority of which broke out in rural areas and many patients are elderly people. On January 13 of 2021, China reported its biggest jump of daily COVID-19 cases since March 5, 2020. The outbreak in Hebei shows the weakness of rural areas in combating COVID-19: poor health facilities and quarantine limitations could ravage whole rural communities. Figure 3 tries to identify the chain of vulnerabilities that led to the super spread in the rural areas from the very beginning. The rural elderly group has their needs and behavior patterns rooted from social customs, which have potential impacts on the COVID-19 control. Mahjong playing, neighbor visiting, square dancing and other gathering activities are important for the rural elderly to socialize. Frequent inside interactions, gathering activities such as regular fairs and occasional events (eg, funerals and weddings) are typical ways to spend daily time, which can be found in many confirmed cases of Hebei and Heilongjiang provinces. Multiple times of wedding attendances without wearing masks during the New Year holiday accelerated the virus spread. Moreover, the elderly people in China tend not to see the doctor when they are ill, and the utilization rate of hospitalization services of rural residents is much lower. Many patients had visited village clinics before they were confirmed. Rural residents prefer to choose the common practice in villages:intravenous therapy, which creates obstacles for early detections and may lead to cross-infections. From the management perspective, almost back to "normal" life combined with few earlier cases, gradually loosened the nerves of local government and rural residents. Lack of restrictions on indoor gatherings, loosened monitor of people returning home from risky regions and other management loopholes (eg, slackened management for the village screening and lack of public education for the COVID-19 infections) also contribute to the super spread. The worst scenario would be that rural elderly keep their intensive interactive gatherings without wearing masks and do not go to see a doctor when fever and cough symptoms are shown, meanwhile there are management loopholes of the epidemic control, which is just the Hebei case. Immediately after the outbreak, combination strategies were implemented such as restrictions on gatherings, screening measures at village entrances for checking temperature and health code, publicizing the importance of wearing masks, and mass testing to separate the virus carriers to stop the community transmission as early as possible. Village doctors and medicine shops are demanded to guide filtered villagers to fever clinics in a timely and standardized manner. To increase the screening efficiency of suspected patients, some local governments suggest township hospitals and village clinics should be integrated as epidemic monitoring and reporting sites. These measures tend to be effective and this wave of local transmission ceased on February 7 of 2021. When someone makes a contribution to the society, he or she feels self-worth or gains recognition and respect from others, and then his or her esteem needs are fulfilled. The pandemic has cut some group fun to satisfy esteem needs or some interactive opportunities for individuals to win others' recognition, but many citizens stand out by contributing as a volunteer or set up self-groups, which help people in need with supply delivery, medical assistance and in other means. In Beijing, the man, before confirmed on June 11 of 2020, went to the fever clinic by bike immediately after he showed up fever symptoms. Out of respect for self and others, he has a good habit of wearing a mask whenever necessary and also told others to do so. Therefore, none of his relatives and friends were confirmed. Due to his prompt report and clear recall of all the places he had been and a detailed name list he had contacted after he was confirmed, the exposed places and population could be separated earlier, and the source of this wave of outbreak-the Xinfadi market was soon located. His good memories out of sense of responsibility were cross-checked by the big data of his travel. It turns out that they do match. Surrounding the Xinfadi market, mass testing for COVID-19 and other control measures were performed to stop the transmission rapidly. The information and responsible behaviors of this first identified case provided the important basis for that. He also set an example for others to report self-travel histories and go to fever clinic with good self-protection without delay. Even experts said that the actions of the first confirmed person greatly increased their confidence in winning the COVID-19 fight. Indeed, containing the virus transmission cannot succeed without these self-disciplined and responsible actions of individuals. The epidemiological investigation and big data cannot function without the permission of citizens. Some people monitor their health conditions themselves at home consciously, some people choose not to travel unless necessary, some people follow local regulations strictly after traveling back from risky areas. Everyone matters in the fight against the pandemic (Figure 4). Affected by the pandemic, some people lose their jobs or could not earn more money or get promotion as usual. For self-development, many citizens choose to continue their studies. However, many examinations and learning activities have been cancelled or postponed, which further suppressed people's needs for self-improvement. On December 22 of 2020, a resident of Shunyi District in Beijing had the nucleic acid test as required for taking part in the postgraduate entrance examination. On the next day, he was confirmed positive for the coronavirus. Relevant departments contacted him immediately, hoping that he would recall his whereabouts and close contacts in the past 14 days and help locate the source of the virus as soon as possible. Emergency management was initiated immediately by Shunyi District. For example, the epidemiological investigation was carried out timely. As of December 23, 2020, a total of 260 close contacts (sub-close contacts included) including fellow passengers, passengers on the same flight, taxi drivers, hotel and restaurant service staff have been investigated, and 10 of them were from other cities. Various prevention and control measures such as centralized isolation control, nucleic acid testing, and trace tracking and co-investigation have been implemented. The first case identified of Shunyi District in Beijing has the need of self-development to continue his studies. He followed the corresponding regulations for the entrance examination and had the nucleic acid test as required. It shows that some screening measures could help identify the infections, especially for large group events to satisfy certain needs, otherwise cluster of cases might possibly surge. Due to the adoption of appropriate control measures in time, the transmission chain was clarified soon. Therefore, this case did not bring about too much panic or negative effects in a large scale.
covid-19, china, pandemic control experience, risk management
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PMC10183181_01
Male
48
In July 2020, a 48-year-old male presented with a "lung shadow of 1 week (1w) on physical examination" at the Fourth Affiliated Hospital, Zhejiang University School of Medicine, other hospital chest computed tomography (CT) results showed inflammatory lesions in the upper lobe of the right lung (exact report not available). The patient had no uncomfortable symptoms such as fever, cough, or hemoptysis, and thus he was given levofloxacin tablets as an anti-infection treatment. The results of the chest CT were re-examined after 10 days of treatment and revealed that mediastinal lymph nodes had calcification, the upper lobe of the right lung had a lamellar shadow with calcification, corresponding bronchial stenosis, and possibly chronic inflammatory lesions. The two lungs also had a few speckled and cord-like hyperdense shadows (Figure 1A and B). The patient had a history of hypertension, fatty liver, and abnormal liver function, with no history of glucocorticoids, cytotoxic drugs, or immunosuppressive therapy. Personal history: smoked 10 cigarettes per day for more than 20 years. He was admitted with a temperature of 36.8 C, a respiratory rate of 20 breaths per minute, a heart rate of 72 beats per minute, a blood pressure of 143/90 mmHg, and a body mass index (BMI) of 26.08 kg/m2. He was in a clear state of mind and had regular breath sounds in his lungs, no dry rales, and no pleural friction sounds on auscultation. Physical examination of the heart, abdomen, and peripheral vasculature revealed no obvious abnormalities. Immunoglobulin (Ig) and antibody results showed that IgG was 7.39 g/L and complement protein C4 was 0.11 g/L . Biochemical results revealed that alanine transaminase was 63 U/L and gamma-glutamyl transferase was 92 U/L . His routine blood test as well as other laboratory tests such as T, B, and natural killer lymphocyte subsets were normal. On the second day following admission, a bronchoscopy was performed. White pus was observed in the flushing of the right upper lobe lumen and a necrotic mass tissue was observed under a bronchoscope in the anterior portion of the right upper lobe (Figure 1C). The bronchial mucosa of the anterior segment of the right upper lobe was taken for pathological examination. Brushing and bronchoalveolar lavage fluid (BALF) examinations were also performed. Pathological biopsy showed fungal hyphae with necrotic calcification, the morphology was more consistent with Aspergillus (Figure 1D and E), indicating broncholithiasis and right upper lobe invasive aspergillosis. The BALF galactomannan (BALF-GM) test result was 1.4 mug/L (positive), fungal culture for Aspergillus fumigatus was found, bacterial culture was normal bacterial growth, Mtb DNA and tuberculosis (TB) smear examinations were negative, and no malignant cells were observed. The brush test results were also normal. A diagnosis of broncholithiasis and Aspergillus infection was made in conjunction with the examination results, and the patient was treated with voriconazole 200 mg bid antifungal therapy. Treatment was continued with oral voriconazole after discharge from the hospital. The chest CT was taken at each of the six follow-up visits, and the results revealed that the inflammatory lesions had been completely absorbed. During this period, the patient had no clinical symptoms and was in good general health. A secondary bronchoscopy was carried out in February 2021 to determine whether to discontinue antifungal medication after six months of treatment. The patient was no longer prescribed voriconazole after BALF-GM test results and accompanying pathogenic smear and culture examinations were negative. In February 2022, one year after the termination of the voriconazole, the patient underwent one more examination, and a CT scan showed bronchiectasis in the upper lobe of the right lung, in which nodules with calcification were observed, measuring about 3.1x1.7 cm, which was larger than before. A faint lamellar shadow was seen next to the right lung hilar, and therefore infection was considered. Multiple foci of calcification were seen in the right lung hilar, and calcified lymph nodes were seen in the mediastinum (Figure 2A). Because the patient had no subjective symptoms despite these findings, suggesting that his condition was progressing, a third bronchoscopy was carried out. A stone-like mass was discovered in the anterior section of the upper right lung on bronchoscopy (Figure 2B), and white pus was seen on flushing. Bronchoscopic stone extraction failed because the stone was firmly attached to the tracheal wall and could not be moved or totally detached. Mucosal biopsy pathology showed chronic inflammation of the mucosa with calcification (Figure 2C). BALF revealed that erythrocytes were >100/Hp, nucleated cells were 6-10/Hp, the neutrophil percentage was 92%, and fungal culture was negative, and the rest of the bacterial smear and bacterial culture results were not abnormal. The final diagnosis was as follows: (1) broncholithiasis and (2) obstructive pneumonia; hence, the patient was given cefixime for anti-infection. After a month, the chest CT was retested, and the results showed a good prognosis.
aspergillus infection, broncholithiasis, infection, obstructive pneumonia
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PMC3161662_01
Male
74
A 74-year-old man sought medical evaluation in May 2004, because of an increasing productive cough. He previously had noted productive cough, but did not become concerned until February 2004, when its frequency and intensity began to increase with no clear triggering episode or factor. He denied any history of hemoptysis, night sweats, pyrexia, or weight loss. Past medical history included pulmonary tuberculosis diagnosed at age 35 and a curative operation in 1995 for oropharyngeal carcinoma requiring reconstruction of the oropharyngeal wall with autologous grafts. Diagnosed with chronic obstructive pulmonary disease at the time of that he quit smoking. He underwent follow-up chest radiography at irregular intervals of 1 to 3 years. In May 2003 the patient was asymptomatic, but a cystic lesion in the right lung showed an increase in wall thickness compared with a previous radiograph obtained in 2000. Computed tomography (CT) of the chest in 2003 (ProSeed; GE Yokogawa Medical Systems, Tokyo) with a conventional protocol without enhancement (10-mm collimation, 10-mm intervals, 120 kVp, 200 mAs, gantry rotation time; 1.0 sec.) showed moderate wall thickening (Fig. 1a). The patient underwent repeated sputum examinations, and then bronchoscopic lung biopsy and bronchial washing targeting the right B6 segment. None of these specimens yielded evidence of cancer or bacterial or fungal pathogens. Further diagnostic procedures were declined. The patient was an office worker with no known history of dust exposure. He had smoked 1.5 packs of cigarettes daily for 42 years until he quit. He denied having undergone any blood transfusions or regular courses of medication. The patient was 172 cm tall and weighted 55 kg. Vital signs at presentation included body temperature of 36.5 C, blood pressure of 110/78 mmHg, and pulse rate of 72/min with a regular rhythm at resting. Physical examination disclosed a healed surgical scar of the neck and diminished breath sounds in both lungs. Heart sounds included no murmurs. The abdomen was unremarkable. No neurologic findings were present. Finger clubbing was absent. Laboratory data at evaluation in 2004 are summarized in the Table 1. Serologic tests were positive for galactomannan (latex agglutination) and anti-Aspergillus antibody (complement fixation). Chest CT, acquired by the same protocol as in 2003 without enhancement, disclosed diffuse thickening of the cyst wall (Fig. 1b). Infiltrative opacities were seen in the area proximal to the cystic lesion. Results of sputum cytologic examination were negative. Neither endoscopic trans-bronchial lung biopsy nor CT-guided transthoracic needle aspiration could establish a diagnosis. Surgical removal of the lung lesion initially was declined. When the patient was treated with the antifungal agents itraconazole and micafungin for presumed aspergillosis, the lesion continued to enlarge. The patient then agreed to undergo right lower lobectomy after the 2 months delay. Macroscopically the resected lesion was solid, but with an outer and inner component (Fig. 2a). Microscopically, the outer portion (labeled "O" in Fig. 2a) showed dense proliferation of atypical cells with focal "pearl" formation, characteristic of squamous cell carcinoma (Fig. 2b). The inner layer (labelled "I" in Fig. 2a) was composed of septate, branching hyphae (Fig. 2c). Branching at acute angles was suggestive of Aspergillus sp. The pathologic tumor stage of the resected lung cancer was T2N0M0. The patient was thus diagnosed as having lung cancer complicated by aspergillosis.
aspergillosis, cavitary lung lesion, lung cancer
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PMC4919328_01
Male
38
Maybe the most influential work published by Paul Blocq and Georges Marinesco was an article published in 1893 (Figure 2). It depicted the case of a 38 years-old man, suffering from tuberculosis, who was admitted to the Charcot's neurological ward because he also displayed signs of unilateral Parkinsonism (primarily muscle rigidity and left side tremor). Jean-Baptiste Charcot, the son of Jean Martin Charcot, treated the patient and detailed his clinical evolution (Parent and Parent,). The autopsy showed the cause of death to be pulmonary complications of tuberculosis. While examining the brain, the investigators found a tubercle that destroyed the right substantia nigra: "Its limits in the peduncle were: in front, by the foot of the peduncle, behind by the superior cerebellar peduncle, inward by the fibers of the common oculomotorius nerve, and outward, until the elements of the medial lemniscus (Untere-Schleife). Summarizing, the tumor affected the substance of Soemmering. It is to be remarked that various elements of the protuberance, besides being displaced and compressed, were not destroyed, as it was proven by the absence of degeneration of the pyramids at the base, and of the cerebellar peduncle, at the top." (Blocq and Marinesco,).
georges marinesco, parkinson’s disease, paul blocq, shaking palsy, substantia nigra
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PMC2642794_01
Male
30
A 30-year-old Caucasian male with, no prior medical history, presented at the Emergency Department with acute right upper quadrant pain, high grade fever (38.5 C) and vomit. Laboratory tests revealed marked leukocytosis (WBC: 19810/ml) and abnormal liver function tests (AST/ALT: 218/280 IU/L, ALP/gamma-GT: 123/147 IU/L, TBil: O,84 mg/dl). Serology profile for hepatitis B or C was negative. A previous history of alcohol abuse was not documented. Abdominal US revealed a 7 cm hyperechoic lesion at the right liver lobe. Computed tomography demonstrated a single lesion, located in segments V and VI, with hemorrhagic features. After contrast administration the lesion appeared to be encapsulated with peripheral enhancement, a necrotic core and contrast wash out at the venous phase. These findings were suspicious for adenoma or HCC although fever and leukocytosis suggested a possible infectious process. No dilatation of the intra- or the extra-hepatic biliary ducts was noted. A lateral displacement of the gallbladder was documented (Figure 1). The patient was admitted and initially treated with systemic broad spectrum antibiotics. However blood cultures and antibodies for Echinococcus and Entamoeba histolytica were negative. Tumor markers including CA 19-9, a-Fetoprotein and CEA were within normal range. A CT-guided core-needle biopsy was performed and revealed numerous lymphocytes and necrotic material but not atypia. Gram stain and Tissue cultures were negative. The patient was treated with intravenous antibiotics for 7 days until fever subsides with complete white cell count normalization and followed by CT scan two weeks later. Due to high suspicion for a malignant process, anatomic liver resection including segments V and VI was performed. Intraoperatively, the liver had a normal appearance and a solid mass, well encapsulated without gallbladder invasion was identified. Pathology was associated with hemorrhagic infarct and extensive hepatocellular necrosis, due to sinusoidal portal vein thrombosis. Furthermore hepatoportal sclerosis and non-cirrhotic portal vein fibrosis was identified. An eosinophil granular matter combined with calcifications, cholesterol, foam cells, and some inflammatory cells was noted. The patient had an uneventful course, discharged the 6th postoperative day and remains well 6 months postoperatively.
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PMC5915317_01
Female
13
"Jennifer" is a 13-year-old Caucasian female adolescent living in a middle-class family, with college-educated parents and a 16-year-old sibling. Her parents described her as "carefree" until the onset of irritability at age 11, the end of fifth grade. With the transition to middle school, increased academic demands, and more challenging peer relationships, Jennifer's irritability worsened, and she began having aggressive outbursts. Her parents first sought outpatient treatment at age 12 for Jennifer's verbally and physically aggressive behaviors at home. Prior to referral for IPT-MBD, she and her parents participated in weekly therapy focused on behavioral management for approximately 11/2 years. She also received pharmacological treatment. Past medication history included previous selective serotonin reuptake inhibitor (SSRI) and stimulant trials. During the course of this outpatient treatment, she had four psychiatric hospitalizations, for physical aggression toward parents and for suicidal ideation, and a day hospital admission following one of the inpatient admissions. Neuropsychological testing revealed average IQ on the major domains of the Wechsler Intelligence Scale for Children-Fourth Edition and a specific weakness in her visual-spatial processing abilities, as well as mild variability in performance on measures assessing attention, executive functioning, and memory. Jennifer also had been diagnosed recently with expressive and pragmatic language disorders. Her parents tried to maintain a unified approach to parenting; however, at times her father would take on the role of peacekeeper within the family, whereas Jennifer's mother felt they were too accommodating of Jennifer's behaviors. Her mother played a more nurturing role, and Jennifer turned to her for reassurance and support. Jennifer had a more joking/humor-based relationship with her father. Jennifer's sister felt resentful that Jennifer was the focus of the attention in the family due to her behavioral and mood symptoms and was critical of how Jennifer interacted with their parents. At times Jennifer's sister tried to take on a parenting role with Jennifer, which led to verbal altercations between them. Jennifer's parents struggled with how to manage her aggressive behaviors at home, resulting in crisis agency home visits, emergency room visits, and hospitalizations, in addition to outpatient treatment. K-SADS-PL diagnoses at the initial visit included current SMD, attention deficit/hyperactivity disorder (ADHD), generalized anxiety disorder, and a past history of major depressive disorder (two episodes). The autism spectrum disorder (ASD) screen was completed as part of the K-SADS-PL. The screening items include questions about development of language, stereotypes, inflexible adherence to routines/rituals, restricted interests, and impairment in nonverbal behaviors (i.e., eye contact, range of facial expressions). Jennifer did not meet criteria for having any ASD symptoms on the K-SADS-PL. Her baseline CGI-Severity was 5, "markedly ill." The outbursts consisted of physical aggression one or two times per month toward parents and verbally aggressive outbursts on average three times per week, with impairment in peer, school, and home settings. She had milder outbursts several times per day, which consisted of yelling at her parents. Her baseline CDRS-R T score was 61.5, with T scores 65 and above, indicating increasing likelihood of having a depressive disorder. In addition to attending a school with a small class size, Jennifer's teachers made accommodations regarding her academic work, such as extra time for testing, preferential seating near the teacher, regular check-ins with teachers regarding homework, and extended deadlines for missing work. She began IPT-MBD treatment on a stable dose of an SSRI:escitalopram 20 mg daily:and an atypical antipsychotic:risperidone 0.25 mg in the morning and 0.5 mg in the evening; neither was changed during the 20 weeks of therapy.
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PMC5451783_01
Male
45
The patient was a 45-year-old man who presented with a headache for 3 months which was progressive and had been intolerable for 2 weeks. However, the patient was a football player with good health. There was no such family history and family members were perfectly well. There were no other clinical symptoms reported by the patient. The patient was advised to do CT-scan and MRI. Interestingly both CT-scan and MRI revealed brilliantly enhancing left lateral ventricular lesion with unilateral hydrocephalus (Figure 1). T1 Image axial view postcontrast (Figure 3) and precontrast film (Figure 4) were also examined. T1 image of coronal view in postcontrast film was also evaluated (Figure 5). T2 image in sagittal view (Figure 6) also found the SOL. Flare image (Figure 7) was examined as well. All other investigations were within normal limit. Then the patient was advised for surgery for removal of the lesion. In this context, left parietal craniotomy was performed with total removal of the lesion through intraparietal approach. Reversal from GA and the postoperative period was uneventful and the patient had got rid of clinical symptom completely after surgery. The tumor was well defined preoperatively and was removed under microscopic surgery meticulously. The patient was very poor to bear the cost of postoperative CT-scan and hence it was not done. The biopsy was sent for histopathological examination. The lesion was nearly spherical measuring 3.0 cm + 2.5 cm, whitish, and firm. There was no evidence of necrosis. Microscopy revealed multicystic appearance with cyst lined by columnar epithelium with apical mucin. Few goblet cells were seen. Few areas had shown pseudostratified lining epithelium with nuclear hyperchromasia, nuclear enlargement, and increased mitosis. There was no evidence of stromal invasion. The mucinous material was seen within the lumen. Hemosiderin laden macrophages were present in the stroma. It was confirmed as a lateral ventricular enterogenous cyst. Then the patient was well in around one year. After about one year of the surgical removal of the lesion, there was a recurrence of a headache whose intensity was more than the previous one. Then the patient was advised to do a CT-scan which revealed lesion of the same pattern in the same location as before (Figure 2). The patient was reexplored surgically and the tumor was removed completely through the same route and histopathology was again revealed it as a case of the enterogenous cyst. Again the total removal of the lesion from the brain was confirmed by postoperative CT-scan. Then the patient was advised for radiotherapy. After completion of radiotherapy, the patient was perfectly well at 13th postoperative month (Figure 2).
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PMC10285455_01
Female
75
A 75-year-old woman presented with chest pain. She had a history of diabetes, dyslipidemia, and hypertension and was admitted for PCI of the left anterior descending artery (LAD). Figure 1 presents the case timeline. Chest pain was present for 7 years but was aggravated for 1 month after activity and was accompanied by dyspnea. No radiating pain occurred. There was no fever, dyspnea, palpitation, upright breathing, or syncope. Coronary angiography (CAG) 1 month before admission revealed insignificant atherosclerotic plaques in the right coronary artery but severe stenosis in both the left circumflex artery (LCX) and LAD. She underwent elective stent deployment in the left LCX at that time. Physical examination was unremarkable, except for hypertension (145/80 mmHg). The patient's complete blood count, biochemical analyses (including the myocardial enzymes), and coagulation tests were normal. An electrocardiogram showed sinus rhythm and nonspecific ST-T segment changes. Transthoracic echocardiography images revealed decreased left ventricular diastolic function. Elective PCI was performed with a 6 Fr guiding catheter and an Asahi Sion guidewire via a trans-radial sheath. After wiring, pre-dilatation was performed with a 2.0 x 20 mm compliant balloon at 10 atm and a 2.5 x 10 mm cutting balloon. Two drug-eluting stents of 2.75 x 33 mm and 3.0 x 18 mm were deployed from the mid to proximal segment of LAD. The overlapping stents were post-dilated at 18 atm with a 2.75 x 10 mm noncompliant balloon catheter. CAG showed a CP at the stent of the mid-LAD (Figure 2a). The patient complained of severe chest pain, and a drop in blood pressure and heart rate was noted a few minutes later, followed by Adams-Stokes syndrome. External cardiac massage was started, and the patient was intubated and ventilated. Large pericardial effusion restricting heartbeat was visualized by fluoroscopy during cardiopulmonary resuscitation (CPR). Repeat angiography confirmed an Ellis type III CP at the stent implantation site (Figure 2b). Pericardiocentesis was performed successfully, and about 400 ml of blood was suctioned and re-injected through a femoral vein. The patient's hemodynamics were stably restored, and the whole CRP lasted 15 minutes. The guidewire system dislocated during the rescue process, caused by the patient's unconscious agitation. It took some time to reset the guiding catheter and advance the guidewire. Repeat CAG showed a diffusive thrombus in the mid ostium of the LAD without contrast extravasation, indicating that the perforation had healed (Figure 2c). Considering the benefit of the anterior descending branch, we aspirated the thrombus to avoid further occlusion. After aspiration, the anterior descending artery recovered patency, but contrast agent extravasation occurred (Figure 2d). Prolonged balloon inflation was performed. A 2.75 x 12 mm balloon was inserted to tamponade the vessel at 6 atm on the leakage port. A contrast agent was administered to confirm that the blood vessel had been fully blocked (Figure 2e). The balloon was dilated for 15 minutes, with a 2-minute break for blood perfusion. Contrast agent extravasation persisted at the perforation site on the angiogram after 3 balloon occlusions (Figure 2f). We dragged the balloon to the proximal site of the CP and inflated it again to block the blood flow (Figure 2g). Simultaneously, we prepared a membrane-covered stent to standby. The balloon was dilated for about 10 minutes and subsequently deflated. Repeat angiography showed no contrast agent extravasation and no obvious thrombosis reformed in the stent (Figure 2h). The operation was completed, and the patient was sent to the intensive care unit (ICU) for monitoring and treatment. The patient suffered from cardiogenic shock and heart failure for several days. ECG showed sinus tachycardia without ST elevation. The highest cTNI was 14 ng/ml. Liver and kidney functions were not injured. The pericardial drainage tube was removed 1 week after no drainage within 48 hours. The patient gradually recovered 3 weeks later. Her brain was not damaged, and she was transferred to the general ward after cardiac function recovery. Protamine was not administered to neutralize heparin. The patient had no late bleeding post-PCI. The drainage of pericardial fluid gradually decreased from 20 ml per day to nil, and the indwelling tube was removed 1 week later. The patient recovered in good condition. The patient is being followed up once a month without symptoms.
coronary perforation, case report, prolonged balloon inflation
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PMC9038153_01
Male
27
A previously healthy 27-year-old male first presented to the outpatient department in Tongji Hospital due to right testis swelling and scattered skin erythema onset for approximately 1 month. There were no other concomitant symptoms, such as fever, night sweat, or loss of weight. On physical examination, painless enlargement of submandibular and cervical lymph nodes was palpable. Then, he was admitted to our department for further diagnosis and treatment. Routine laboratory evaluation demonstrated normal white blood cell (WBC) counts and hemoglobin and mildly increased platelet counts [376.0*109/L (normal: 150-350*109/L)], lactate dehydrogenase [234 U/L (normal:135-225 U/L)] and beta2 microglobulin [2.76 mg/L (normal:0.8-2.2 mg/L)]. Serology tests were negative for HIV, HBV, CMV and EBV infection. An abdominal ultrasound did not indicate hepatomegaly or splenomegaly. Bone marrow smear and histology revealed normal morphological, immunological flow cytometric (FCM), cytogenetic and molecular (MICM) results. No central nervous system infiltration was detected by cerebrospinal fluid flow cytometry. However, positron emission tomography/computed tomography (PET/CT) scans demonstrated abnormally increased metabolic activity in multiple lymph nodes (SUV max: 9.4), bones (right clavicle, left scapula, left 2nd rib, right accessory of 11th thoracic vertebra, 1st-2nd lumbar vertebra, bilateral femurs and bilateral superior tibial segment; SUV max: 6.2), the posterior walls of the nasopharynx (SUV max: 6.5), the bilateral ethmoid sinuses (SUV max: 5.0), and the bilateral testicular and right spermatic cords (SUV max: 7.3). There was also mildly increased metabolic activity in the subcutaneous nodules on the bilateral cheeks (SUV max: 2.8) (Figure 1A and B). The patient underwent ultrasound-guided fine-needle aspiration in the left enlarged supraclavicular lymph node. The pathological biopsy specimen was extensively replaced with tumor cells characterized by distinct nucleoli and scant cytoplasm. Immunohistochemical staining showed that representative B lymphoblastic tumor cells were positive for CD20 and terminal deoxynucleotidyl transferase (TdT) and negative for CD3, and approximately 90% of the neoplastic cells displayed nuclear Ki67 staining (Figure S1). Meanwhile, the cutaneous biopsy, also revealed consistency of the phenotype of the B lymphoblasts, were positive for CD20, CD19, PAX5, TDT, CD10, CD38, C-MYC, CD99, BCL-2 and CD43, but negative for CD3, CD34, CD7, BCL-6, MPO and MUM1, and Ki67 staining about 90% (Figure 2). Therefore, the diagnosis of B-LBL (Ann Arbor stage IIIA, IPI 3 scores) was confirmed. To control lymphoma in a timely manner, the patient received the high-risk chemotherapy protocol of CCCG-LBL-2016 (Induction I with prednisone, vincristine, daunorubicin, PEG-LASP, cyclophosphamide, cytarabine, 6-mercaptopurine plus prophylactic intrathecal infusion from Day 1 to Day 63). RNAseq, with reference to the GRCh37/hg19 genome and mainly to detect genetics disruption at the level of the human transcriptome, was performed on the left supraclavicular lymph node specimens as a part of routine diagnostic workup in our institution. Unexpectedly, IKZF1 deletions and BCR-ABL1 fusion transcripts were detected approximately 3 weeks after chemotherapy. Based on these results, we retrospectively validated BCR/ABL1 rearrangement in previous lymph node biopsy specimens by fluorescence in situ hybridization (FISH), which detected a 70% positive signal (Figure 3). Given that the modified diagnosis turned to Ph+ B-LBL, a combination of dasatinib (140mg, qd) was added to therapeutic regimen. PET/CT evaluation was carried out before Protocol M of CCCG-LBL-2016 began, and it showed complete remission (CR) (Figure 1C and D), Protocol M (5 g/m2 methotrexate and 6-mercaptopurine) combined with dasatinib proceeded as planned for 4 cycles. Then, the patient finally underwent allogeneic transplantation with granulocyte colony-stimulating factor-mobilized bone marrow cells plus peripheral blood hematopoietic stem cells from his father, who was mismatched for five loci in March 2021. He received a TBI/VP/CY/ATG conditioning regimen consisting of total body irradiation (Day -9), etoposide (15 mg/kg/day on Days -8 and -7), cyclophosphamide (1.8 g/m2/day on Days -6 and -5), and ATG (thymoglobulin, 2.0 mg/kg/day on Days -4 to -1). The procedure was well tolerated, and he achieved successful engraftment on Day 15 post-stem cell infusion (SCI). He did not undergo any grade of acute or chronic graft-versus-host disease (GVHD) but only had temporary and asymptomatic Epstein-Barr virus (EBV)-reactivated viremia. All immunosuppressants were tapered and stopped within 2 months after SCI, and he took dasatinib 50 mg daily for maintenance. Monthly follow-ups were regularly performed, including the monitoring of bone marrow chimerism and BCR/ABL1 copies by polymerase chain reaction amplification of short tandem repeats (PCR-STR) and RT-PCR, respectively. Sustained complete chimerism and negative BCR/ABL1 detection, along with recent PET/CT results (Figure 1E and F), indicated a satisfactory CR for more than 1 year.
b-cell lymphoblastic lymphoma, philadelphia chromosome, hematopoietic stem cell transplantation, tyrosine kinase inhibitor
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PMC8080446_01
Female
45
A 45-year-old woman (Patient V.) has been registered as outpatient since 2015 with a diagnosis of bronchial hyperreactivity. For two years periodically she was bothered by paroxysmal cough with scanty sputum, fever up to 38-39 C, shortness of breath during exertion. Since November 2016 episodes of dyspnea were added, the body temperature rose to 37.8 C, and the administration of Beclomethasone and Amoxicillin had no effect. In January 2017 she was admitted to the Pulmonary Department of the hospital in Barnaul with a diagnosis of nonspecific interstitial pneumonia and unspecified eosinophilia. On admission, the woman had a complaint of shortness of breath in unstable cold weather, a rare unproductive cough, flying pains and swelling of the joints (elbow, knee, wrist) which were relieved by taking NSAIDs. Diagnosis at hospital: "Community-acquired bilateral polysegmental pneumonia in the upper lobes, moderate severity, respiratory failure 0 stage. Unspecified eosinophilia". After an antibiotic therapy (Ceftriaxone + Azithromycin) normalization of body temperature and a chest X-ray improvement have happened. After discharge from the hospital, flying pains reappeared in joints (elbow, knee, wrist). On an outpatient basis, in blood serum the antibodies against Opisthorchis, Toxocara canis, Giardia lamblia was examined by ELISA and Mycobacterium tuberculosis by PCR -with the negative results of all tests. Multi-slice computed tomography (MSCT) revealed the multiple areas of ground-glass interstitial infiltration with indistinct contours, irregular shape, thickening of the peribronchovascular and interlobular interstitium in the form of linear cords in both lungs, mainly in the upper lobes in the cortical and subpleural regions. The patient was admitted to the Pulmonary Department. On admission to the pulmonary department, general condition was satisfactory. Body temperature was 36.7 C. The skin was a normal color without rashes. Peripheral lymph nodes were not palpable. Auscultation of the lung showed vesicular breath sound with breath rate 20/min., SatO2 - 97 %. Heart boundaries were displaced to the left by 1.5 cm lateral of the midclavicular line, the tones of heart were muffled, the rhythm was correct, heart rate was 90 per minute, blood pressure - 120/80 mm Hg. Edge of the liver was near the costal margin. There was no edema, urination was not frequent, stool was normal. Results of the blood test presented in Table 1 and revealed some abnormalities: leukocytosis up to 12.9 x 109 / L (reference range: 4.0-9.0 x 109 / L), 56 %-24 % eosinophilia (reference range: (1-5 %) and ALT up to 229.2 U/L (reference range: 0-40 U/L), AST up to 110.7 U/L (reference range: 0-40 U/L), ALP up to 967 U/L (reference range: 0-130 U / L). Abdominal ultrasound showed diffuse homogeneous changes in the walls of the intrahepatic bile ducts, signs of bile thickening. X-ray examination revealed intrathoracic lymphadenopathy and bilateral areas of compaction of the lung tissue in the form of infiltrates. According to the lungs and mediastinum MSCT data, pronounced interstitial changes in the lungs which are characteristic of nonspecific interstitial pneumonia (sarcoidosis?) were revealed. No pathology was established by video bronchoscopy. Stool ova and parasite examination using concentration method (3-x negative results), studies of blood serum by ELISA (detection of IgM, IgG antibodies against Opisthorchis, Toxocara canis, Giardia lamblia) (Helminths-IgG-ELISA-BEST No. FSR 2009/04032, a set of reagents for enzyme detection of IgG to antigens of Opisthorchis, Toxocara canis, Trichinella, and Echinococcus in serum (plasma) of blood) (negative tests) were performed. Multiple organ lesions: signs of allergic pneumonitis revealed by MSCT, arthralgic syndrome, hypereosinophilia (up to 56 % in the blood test), involvement of the hepatobiliary system, and anamnesis (accommodation from birth to the present time in an area where opisthorchiasis is endemic, the constant use of insufficiently heat treated fish) were the basis for a targeted search for parasitic invasion, primarily opisthorchiasis, as well as the exclusion of diffuse connective tissue diseases. When carrying out the recommended set of examinations a month after discharge from the hospital, a large number of leukocytes, epithelial cells, and Opisthorchis felineus eggs were found in the duodenal contents. Complex therapy aimed at deworming (Praziquantel 75 mg / kg) followed by rehabilitation (taking cholagogue drugs - Ursodeoxycholic acid 10 mg / kg per day for up to 1 month), desensitizing (Levocetirizine 5 mg per day, up to 10 days) ensured a full clinical recovery and restoration of the quality of life (18 months follow-up period).
eosinophilia, opisthorchiasis, polymorphism of the clinical picture, western siberia
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PMC7255269_01
Female
68
A 68-year-old woman presented to the emergency department of a referral hospital in Tehran, Iran, complaining of persistent non-productive cough, fever, and myalgia of three-day duration. She denied any history of rhinorrhea, sore throat, dyspnea, abdominal pain, vomiting, or diarrhea. She had a medical history of poorly controlled diabetes mellitus, end-stage renal disease for which she received hemodialysis three times a week, and rheumatoid arthritis. She had undergone coronary artery bypass grafting 13 years ago. Her medications included rosuvastatin 10 mg daily, prednisolone 5 mg daily, hydroxychloroquine 200 mg daily, aspirin 80 mg daily, and losartan 50 mg twice a day. She was also on a single daily injection of 18 units of lantus (insulin glargine) for diabetes mellitus. Vital signs were as follows: body temperature 39.9 C, blood pressure 140/60 mmHg, pulse 105 beats per minute, respiratory rate 24 breaths per minute, and oxygen saturation 90% on room air. Lung auscultation revealed mild bilateral rales. The remainder of the examination was unremarkable, and no weakness or sensory disturbance was noted at that time. A chest CT scan was performed, which revealed mild bilateral patchy high-density shadows in both lungs (Fig. 1A). Considering the clinical presentation of viral pneumonia in a patient at the time of the 2019 novel coronavirus outbreak, she was admitted to the hospital with a high suspicion for SARS-CoV-2 infection. An upper respiratory tract swab tested positive for SARS-CoV-2 on real-time RT-PCR assays within 48 h. Laboratory investigation on admission reflected white blood cells 8.5 x 103/uL with lymphopenia, hemoglobin 11.5 g/dL, platelets 175 x 103/uL, potassium 5.3 mEq/L, sodium 133 mEq/L, creatinine 12 mg/dl, ESR 15 mm/hr, and CRP 121 mg/L. Her blood sugar level was 400 mg/dL at the time of admission. Hepatic transaminases and bilirubin were within the normal range. After admission, the patient received supportive care and management of symptoms, including oxygen supplementation, and compassionate therapy consisting of lopinavir/ritonavir 400/100 twice a day, and oseltamivir 30 mg daily as per the Iranian interim guidelines for the management of COVID-19 at that time. Other than her routine medications, novaRapid (insulin aspart) 4 units three times a day was added to her regimen. On day 3 of hospitalization, while the patient's vital signs remained stable and O2 saturation was 94% breathing room air, she started to develop generalized hypotonia in lower extremities. There was bilateral weakness on motor examinations, and deep tendon reflexes were absent. Her cranial nerves were normal, and other neurological examinations were unremarkable. Lumbar puncture was performed by a neurologist, which failed to yield any CSF in two repeated attempts. MRI of the whole spine, nerve conduction velocity (NCV), and electromyographic (EMG) studies were requested. After discussion, the neurologist decided to proceed with the administration of methylprednisolone 250 mg IV for possible virus-related immune reaction provided that her blood sugar and electrolytes were controlled. On day 6, she started having difficulty breathing, and her O2 saturation dropped to 78% as her respiratory status deteriorated gradually. A chest CT scan taken at the time demonstrated severe bilateral ground-glass opacities consistent with acute respiratory distress syndrome (ARDS, Fig. 1B). She was intubated and mechanically ventilated in response to respiratory distress. However, she developed cardiac arrest and, unfortunately, died on the same day after multiple resuscitations attempts.
covid-19, nervous system, pneumonia, polyneuropathy, sars-cov-2
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PMC3033098_02
Female
87
In January 2001, an 87-year-old female resident of the same long-term care facility was transported to hospital with fever (index case-patient 2), and GAS was isolated from blood cultures drawn at admission. Several days later, GAS was isolated from the wound of another facility resident. Screening cultures performed on 195 residents and staff with a history of contact with one of these two infected persons indicated that seven residents and one staff member were colonized with GAS. PFGE showed that the strains from all resident carriers were identical to the wound and blood isolates, and to the isolate obtained from index case 1. The bacterial isolate obtained from the staff member was determined by PFGE to be unrelated to the outbreak strain. Colonized residents and staff were treated with cephalexin as had been done with the previous patient. Cultures obtained from treated persons 1 month after completion of therapy were again negative. In May 2001, another resident of this nursing home was transported to hospital with GAS bacteremia (index case-patient 3). At this time, all 386 residents and 135 staff of the facility were screened for GAS carriage by culturing nasopharynx specimens. Eleven residents and three staff members were identified as carrying group A streptococcus. Thirteen of these (11 residents and two staff members) subsequently proved to be carrying strains identified by PFGE analysis to be identical to the strain obtained from index case-patient 2 (Figure 1) (prevalence of colonization or infection among residents was 2.8% vs. prevalence of colonization 1.5% among staff , p=0.38 by chi-square test).
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PMC3033098_05
Male
89
Due to the lack of any epidemiologic link between case-patients and the population mixing that had occurred at the holiday party, swab cultures were collected on all facility residents and all available staff members. Epidemic control measures were introduced and included restriction of new admissions to the facility and reinforcement of infection control practices. Based on the rapidity of events, the apparent high case-fatality rate, and recent experience with the failure of targeted culturing and treatment (as described in outbreak 1), a decision was made to initiate mass antibiotic treatment for all facility residents and staff. After that decision, but before mass antibiotic treatment could be initiated, an 89-year-old male resident was admitted to the hospital with "congestive heart failure." Gram stain of sputum indicated gram-positive cocci in chains. This man died 36 h after admission; GAS was isolated from blood cultures taken at hospital admission (Figure 3). Mass antibiotic treatment was initiated approximately 48 h after the start of the investigation, with azithromycin, 250 mg orally each day, administered for 5 days to residents and to staff who wished to be treated at the facility. Staff who wished to receive antibiotic treatment from their personal physicians were permitted to do so. Subsequently, GAS was isolated from nasal and pharyngeal cultures of two staff members and five residents of the facility. GAS was also isolated from a wound culture from a facility resident. All colonized residents were negative for GAS on repeat cultures, 4 weeks after receiving antibiotics. One staff member remained culture positive 2 weeks after completing a course of cephalexin provided by her personal physician; she received two additional courses of beta-lactam antibiotics and was documented to be culture negative for GAS 4 weeks after she completed the second antibiotic course. PFGE performed on the three GAS strains from case-patients and the seven strains from colonized residents and staff showed that four colonized persons had isolates identical to those from the deceased case-patients; all were serotype M1 T1 and were serum opacity factor negative (Figure 4). The remaining three isolates represented two distinct strains unrelated to the outbreak strain. The proportion of residents colonized or infected with the outbreak strain was significantly higher than the proportion of staff colonized (4.7% vs. 0.7%, p=0.03 by chi-square test).
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PMC5841117_01
Female
64
A 64-year-old postmenopausal woman presented to the emergency department at 10 am in the morning with chest pain and shortness of breath of approximately 12 hours duration. Her medical history included right breast invasive ductal carcinoma with bilateral mastectomies in 2015, recently diagnosed bladder cancer with TURBT and intravesical mitomycin C instillation three days prior to current presentation, type 2 diabetes mellitus, hypertension, obstructive sleep apnea, chronic obstructive pulmonary disease, and prothrombin G20210A mutation. She had quit smoking 5 years ago, prior to that she had smoked 2 packs per day for 45 years. She was asymptomatic until about 10 pm the night before presentation, when she developed shortness of breath and sharp pleuritic chest pain while she was lying in bed. The patient reported that her chest pain was located in the substernal region, radiating to the back, aggravated by deep breaths and by lying down, and alleviated by sitting up and leaning forward. She said that she had taken some ibuprofen which had reduced the intensity of pain. She did endorse that she was also experiencing a less prominent pressure like sensation in addition to the sharp pleuritic type of pain. She denied fevers, chills, cough, diaphoresis, palpitations, dizziness, abdominal pain, heartburn, nausea or vomiting, flu-like symptoms, recent illnesses, or any history of chest pain in the past. Her family history was significant for her brother having an episode of myocardial infarction at age 55. On detailed inquiry of the patient's history of bladder cancer, the patient reported that she was diagnosed in 2012 after undergoing cystoscopy for an episode of gross hematuria and was found to have a low-grade bladder cancer. She underwent transurethral bladder tumor resection and 1 cycle of intravesical BCG treatment in 2012 and was asymptomatic after that with regular follow-up with urology. On a surveillance cystoscopy performed by the patient's urologist in December 2016, a lesion was seen in the bladder, for which a biopsy was subsequently done which showed papillary hyperplasia and inflammation with no cancer. For this recurrence, the patient was planned for a cystoscopic transurethral bladder tumor resection and instillation of 40 mg of mitomycin C in the bladder, which she underwent three days before her current hospital presentation. The patient was intubated during this procedure which was uneventful, and was subsequently extubated without difficulty. The patient's oral temperature on presentation was 98.0 F, heart rate of 107/min, respiratory rate of 25/min, and blood pressure of 152/63 mmHg (right arm, supine position). On examination, the patient was in no acute distress and appeared comfortable, although was complaining of having mild chest pain, alleviated by leaning forward. Her laboratory data were as follows: cardiac troponins on the day of presentation, 0.57 ng/ml at 12:30 pm; D-dimer, 257 ng/ml; and white blood cell count, 12.2 K/ml with 67.3% neutrophils. 12-lead electrocardiogram (Figure 1) showed diffuse concave ST elevations with PR depressions in all leads, except in aVR which showed ST depression and PR elevation. The patient was treated with aspirin 325 mg orally and nebulized albuterol. An echocardiogram was performed which showed normal left ventricular ejection fraction of 61-65%, mid and apical inferior wall motion abnormality, mild to moderate left ventricular diastolic dysfunction, and trivial pericardial effusion. Although the patient's clinical presentation and electrocardiogram findings were consistent with pericarditis, an urgent coronary angiogram was planned due to the possibility of the patient having an acute coronary syndrome, considering her continuing chest pain, elevated cardiac troponin level, echocardiogram findings of mid and apical inferior wall motion abnormality, and the presence of multiple risk factors of ischemic heart disease. The coronary angiogram, performed through right radial artery access, showed a normal left main stem artery, proximal left anterior descending luminal irregularities, a 95% stenotic focal lesion of the mid left anterior descending artery, 40% stenosis of distal left circumflex artery, 30% stenosis of the ostial right coronary artery, 40% stenosis of proximal right coronary artery, 50% stenosis of mid right coronary artery, and 99% stenosis of right posterior descending artery. Left ventricular diastolic pressure was recorded to be 24 mmHg. A single 2.5 x 20 mm synergy monorail drug-eluting stent was placed in the stenosed segment of the mid left anterior descending artery. The patient received 60 mg of prasugrel orally during the procedure, a bolus dose of intravenous tirofiban followed by a maintenance dose intravenous tirofiban drip, and was admitted to the telemetry floor. Dual antiplatelet therapy with aspirin 81 mg daily and prasugrel 10 mg daily was initiated, and the patient was also started on colchicine 0.6 mg every 12 hours for pericarditis. The remainder of the hospitalization was uneventful, and the patient was discharged on the third hospital day, with a plan for a staged percutaneous coronary intervention for the 99% stenotic lesion in the right posterior descending artery in a few weeks.
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PMC4857360_01
Female
21
A 21-year-old Caucasian lady presented to the psychiatric ward with anxiety, agitation and an erratic speech pattern. She was treated for 'acute psychosis' with haloperidol. Two days later, she developed twitching of the eyelids with gaze fixed to the right upper quadrant. This was treated as oculogyric crisis secondary to haloperidol and treated with procyclidine. She was also commenced on olanzapine and sodium valproate. Apart from eating disorder, there was no past psychiatric illness or any family history. For 2 weeks, she continued with pure psychiatric manifestations before developing pyrexia, tachycardia and cough. She was noted to have slow telegraphic speech and gegenhalten, but the rest of the neurological examination was normal. Soon after her conscious level dropped (Glasgow Coma Scale (GCS) 9), she was transferred to the high dependency unit with a diagnosis of aspiration pneumonia and Type 1 respiratory failure. Blood tests showed raised white blood cell (WBC) with neutrophilia and raised C-reactive protein (CRP). Chest X-radiograph was normal. Computed tomography (CT) of the head showed no abnormality, and a lumbar puncture showed a cerebrospinal fluid (CSF) WBC count of 38 (100% lymphocytes) with three red blood cells (RBCs), normal glucose and protein. Magnetic resonance imaging (MRI) of the brain was unremarkable. A transthoracic echocardiogram was normal. CT pulmonary arteriogram was suggestive of aspiration pneumonitis and features of mediastinal emphysema. Her breathing deteriorated requiring ventilation. She was given intravenous (IV) acyclovir and broad-spectrum antibiotics. Three days later, she developed abnormal eye movements with divergence of both eyes, although pupils were equal and reactive. She had generalised hypertonia and hyper-reflexia with flexor plantar response bilaterally. Further tests showed a weakly positive CSF polymerase chain reaction (PCR) for enterovirus but negative for herpes simplex virus, varicella zoster virus and cytomegalovirus. CSF angiotensin-converting enzyme, lactate, lactate dehydrogenase, virology and tests for tuberculosis, fungi and syphilis were negative. Monospot test for EBV was weakly positive. Thyroid functions, B12, ferritin, folic acid, autoimmune profile, HIV, antithyroid antibodies, T spot for tuberculosis, toxoplasma antibody, anti-voltage-gated potassium channel antibodies, antineuronal antibodies, anti-Purkinje antibody, cerebellar antibody and serological tests for syphilis were negative. Tumour markers were negative apart from Cancer Antigen (CA) 19-9 which was non-specifically raised at 62.8. Repeat CT and MRI of the head were normal. Electroencephalogram (EEG) showed runs of slow wave activity over both frontal areas consistent with encephalitis. A diagnosis of a neuroinflammatory disorder was considered for which a 5-day course of IV 1 g methylprednisolone followed by oral prednisolone 60 mg once daily was given. She showed some improvement, and by the end of the third week of admission, she was alert but not following commands and had developed generalised rigidity and catatonia. She had a generalised tonic-clonic seizure following which she was treated with phenytoin. She had a tracheotomy as she remained ventilated. The results for anti-NMDA receptor antibody in the serum returned positive, and a diagnosis of 'Anti-NMDA receptor antibody-positive encephalitis' was made. Her CT of the abdomen and pelvis was normal, and fluorodeoxyglucose positron emission tomography (FDG-PET) of whole body showed no signs of malignancy. She was given intravenous immunoglobulins (IVIGs) 0.4 mg/kg for 5 days and continued with oral steroids in a tapering dose through nasogastric tube, to which she responded slowly. Phenytoin was later changed to sodium valproate for its mood-stabilizing effect. The patient continued to improve. One week later, psychiatrist review documented delusional beliefs with persecutory paranoid ideation. She was given another dose of IVIG, IV methylprednisolone for 5 days. She continued to improve in the rehabilitation unit with regular input from the multidisciplinary team of neurologist, psychiatrist, oncologist, dietician, physiotherapist and occupational therapists and was discharged home after 3 months. She made a full recovery, and all medications were successfully withdrawn. No malignancy was found in the 2-year follow-up. We confirm that patient's consent to report the case has been obtained. Institutional approval is not required for reporting this case.
autoimmune encephalitis, anti-n-methyl-d-aspartate receptor encephalitis, neuropsychiatric encephalitis
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PMC3016786_01
Female
60
To the Editor: Severe acute respiratory syndrome (SARS) is an emerging infectious disease worldwide, and relapsing SARS is a major concern. We encountered a 60-year-old woman who was admitted to the Princess Margaret Hospital in Hong Kong on March 29, 2003, with a fever of 39 C, chills, cough, malaise, and sore throat for 2 days before admission. She had no history of travel within 2 weeks of admission. She also had no close contact with patients who had a diagnosis of suspected or confirmed SARS. Chest radiograph on admission indicated consolidation over the right middle zone. In accordance with the diagnostic criteria proposed by the World Health Organization (WHO), this patient's condition was diagnosed as SARS in view of her symptoms, temperature, and chest radiograph findings (1). Standard microbiologic investigations to exclude common respiratory virus and bacterium for community-acquired pneumonia, including Mycobacterium tuberculosis, were negative in our patient. Reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal aspirate samples was negative for coronavirus twice. The coronavirus antibody titer was less than 1/25. The patient was initially treated with oral clarithromycin (500 mg twice a day) and intravenous amoxycillin-clavulanate combination (1.2 g three times a day). Despite the negative evidence for coronavirus infection, she was treated with intravenous ribavirin (24 mg/kg once a day) and hydrocortisone (10 mg/kg once a day) after 48 hours of antibiotics therapy (2). The patient's symptoms were relieved, and she remained afebrile 3 days after admission. Tolerance for medication was good except for a moderate degree of hemolytic anemia (her hemoglobin level dropped to 9.1 g/dL) and hypokalemia that developed during treatment. On day 15, the chest radiography was clear. The patient was discharged after 3 weeks of hospital stay. The patient attended outpatient clinic on day 35, complaining of exertional dyspnea, low-grade fever, and malaise since her discharge. Her chest radiography showed extensive shadowing. Computer tomographic scan of the thorax indicated widespread ground-glass shadowing in both lung fields, which was especially prominent at left lower and lingular lobes. Her hemoglobin level had dropped further to 8.4 g/dL. Sputum culture yielded substantial growth of methicillin-sensitive Staphylococcus aureus and Pseudomonas aeruginosa. RT-PCR results of throat and nasal swabs were positive twice for coronavirus, but coronavirus cultures from these areas were negative. One month after onset, her coronavirus antibody titer was 200. In view of possible relapse of SARS, she was treated with oral ribavirin (1,200 mg a day) and lopinavir (133.3 mg a day)/ritonavir (33.3 mg) combination (3 capsules twice a day) in addition to intravenous piperacillin/tazobactam combination. The patient was afebrile, and symptoms improved 3 days after admission. Serial chest radiograph showed gradual resolution of shadowing. Subsequent RT-PCR and sputum culture were negative. This case illustrates several important issues regarding problems of infection control, diagnosis, and management of SARS. As the definition of SARS is nonspecific, patients with upper respiratory infection or community-acquired pneumonia could be mislabeled as having SARS. Accommodating confirmed SARS patients and patients mislabeled as having SARS in the same facility may be disastrous. Unfortunately, isolating every single case is impossible, particularly when a large number of patients are admitted. Our patient may have acquired the disease after admission since she was placed in the same ward with other patients confirmed to have SARS. For this reason, special cohorting of SARS patients with closely related signs and symptoms should be strictly implemented at admission. Since fever is the most common feature of SARS, isolating febrile cases with respiratory or gastrointestinal symptoms may be appropriate. Even patients with fever alone should be quarantined since the other symptoms of SARS may not be clinically obvious. Secondly, the sensitivity of diagnosing a coronavirus infection on admission is only 32% to 50% by nasopharyngeal RT-PCR test (3,4). Many infected cases will be missed as a result. Our patient may have had a relapse of disease during her second admission, although she had positive RT-PCR and antibody surge only 1 month after onset. However, we could not conclude whether the first RT-PCR on admission was a false negative or whether the patient acquired coronavirus infection in the hospital. Our study showed that sensitivity for diagnosing coronavirus infection could be increased by performing RT-PCR on samples from different parts of the body (4). Unfortunately, these samples were not taken from our patient. Furthermore, the chest infection with organisms recovered from her sputum could be the sole reason for her second admission, especially when her immune system was weakened by the administration of a high-dose steroid. The presence of genetic material for coronavirus from her nasal cavity and throat might not suggest that the virus is active. The absence of coronavirus growth in this patient might indicate that the virus is no longer viable, although the culture technique itself might not be sensitive enough to justify this claim. Therefore, further refinement of the diagnostic techniques for SARS is essential, especially for diagnosis during early onset. Thirdly, giving treatment to a patient without a legitimate diagnosis may be inappropriate, especially when the treatment carries substantial adverse effects, as illustrated in our patient, and a universally accepted therapy has not been available. Whether lopinavir/ritonavir combination is the key to a cure remains to be clarified, despite the satisfactory response that we observed, since the clinical and radiologic improvement in our patient might be the natural course of the disease.
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PMC7509409_01
Male
23
The subject was a 23-year-old White non-Latino male with no family history of neuropsychiatric disorders and a favorable psychosocial background. His medical history included seasonal allergies, anisocoria, a condition where the pupils of the eyes differ in size, a fractured vertebra, a broken wrist, and six "documented" concussions. The subject was a professional hockey player, and all his injuries were hockey-related. Table 1 summarizes the timeline of the subject's history of concussion. The subject had never been diagnosed with mild TBI (mTBI). His clinical head computed tomography (CT) and magnetic resonance imaging (MRI) exams had been negative (see Figure 1 for representative baseline MRIs). The subject had experienced concussion-related memory gaps and feeling dazed; however, he had never lost consciousness. Thus, he was classified as a "possible TBI" by the Ohio State University TBI screen. The subject approached Vielight, Inc., in Toronto, Canada about their PBM devices after his last concussion left him with a desire to "improve his mental sharpness." Prior to starting treatment, the subject's symptoms included headaches [six-item Headache Impact Test (HIT-6) score = 76], mild anxiety, difficulty concentrating, and an inability to maintain attention. The subject reported previously trying acupuncture, nutritional supplements, and hyperbaric oxygen treatments for his condition. This report was undertaken as an exercise to observe potential improvements in the subject's cognitive and brain function after PBM treatments. Vielight provided the subject with two non-thermal, non-laser light-emitting diode (LED) devices as wellness devices for his mental acuity. Vielight requested the subject to undergo neuroimaging and cognitive assessment by the first author so that observations could be made on whether objective neuroimaging data can support changes in cognition. The subject consented to this. The PBM devices used are considered non-regulated under "General Wellness: Policy for Low Risk" published by the Food and Drug Administration in September 2019. The Vielight Neuro Alpha delivers 810-nm light pulsing at 10 Hz, 50% duty cycle; the Vielight Neuro Gamma delivers 810-nm light pulsing at 40 Hz, 50% duty cycle. Both devices have four transcranial and one intranasal LED modules designed to target nodes of the default mode network (DMN), a group of strongly interconnected brain regions that include the medial prefrontal/anterior cingulate cortex (targeted by the anterior transcranial LED), posterior cingulate cortex/precuneus (targeted by the central posterior transcranial LED), lateral parietal cortex (targeted by two lateral posterior transcranial LEDs), ventromedial prefrontal and entorhinal cortex, and hippocampus (targeted by the intranasal LED). The posterior transcranial LEDs have a power of 100 milliwatts (mW) each; the anterior transcranial LED, 75 mW; and the intranasal LED, 25 mW. Each posterior transcranial LED has a power density of 100 mW/cm2; the anterior transcranial LED, 75 mW/cm2; and the intranasal LED, 25 mW/cm2. The beam spot size of each LED is about 1 cm2. The energy delivered by posterior transcranial LEDs is 60 joules (J); anterior transcranial LED, 45 J; and intranasal LED, 15 J. The energy density of the posterior transcranial LEDs is 60 J/cm2; anterior transcranial LED, 45 J/cm2; and intranasal LED, 15 J/cm2. Both the PBM devices, programmed to shut off automatically after 20 min, deliver 240 J per 20-min treatment session. Table 1 summarizes the timeline of the subject's assessments and PBM treatments. After baseline assessments, the subject began home PBM treatments every other day with the Vielight Neuro Gamma device (pulsing 810 nm at 40 Hz). This recommendation was based on a report of cognitive improvements after participants had used the Vielight Neuro Gamma device. However, the subject developed mild headaches after 1 week of using the Neuro Gamma device. Consequently, Vielight advised him to switch to the Neuro Alpha device (pulsing 810 nm at 10 Hz). When the subject's headaches resolved after 10 days, Vielight advised him to alternate between using the Neuro Alpha and Neuro Gamma devices, while keeping the every-other-day schedule of treatments. After 3 weeks, Vielight advised the subject to continue PBM treatments every other day using just the Neuro Alpha device. This decision was based on a report that PBM treatments pulsed at 10 Hz produced the most beneficial effects in an animal model of TBI. Although he remained in training during the PBM treatments, the subject did not play any hockey games and did not suffer any further blows to the head. The following neuropsychological tests were administered pre- and post-treatment: California Verbal Learning Test II (CVLT-II), D-KEFS Color Word Interference test, Trail Making Test (TMT), Digit Span subtest of the Wechsler Adult Intelligence Scale-III (WAIS-III), and verbal and category (semantic) fluency. The following scans were acquired on a Siemens 3-Tesla Trio scanner with a 32-channel receiver head coil pre- and post-treatment: structural T1-weighted 3D Magnetization Prepared Rapid Gradient Echo image [repetition time (TR)/echo/time (TE)/inversion time (TI) = 2,500/2.98/1,100 ms, 1 x 1 x 1 mm3 resolution], arterial spin-labeled (ASL) magnetic resonance images (MRI) acquired with echo-planar imaging (EPI) sequence (700 ms inversion of arterial spins, 1,900 ms total transit time of spins, 100 ms tag thickness; 13 ms echo time; field of view: 256 mm, 64 x 64 matrix, 24 4-mm tick axial slices; 52 tag + control image pairs with 22.5 ms time lag between slices), and resting-state functional MRI (RS-fMRI) (8-min 12-s EPI sequence with 140 time points, 3,000 ms TR, 30 ms TE, 80 flip angle, 48 3.3-mm-thick slices, 3.3 x 3.3 x 3.3 mm3 resolution; 64 x 64 matrix). FreeSurfer 6.0 and FreeSurfer's longitudinal stream were used to process the structural MR images and to extract volumes from anatomical regions of interest (ROIs). Total cortical gray matter (GM) volume was derived by summing the Desikan-Killiany atlas cortical ROIs bilaterally. Total subcortical GM, thalamic, and hippocampal volumes were derived from FreeSurfer's automatic subcortical segmentation. Hippocampal subfield volumes were derived from the FreeSurfer's hippocampal subfield segmentation. The volumes from right and left hemisphere ROIs were combined. Statistical Parametric Mapping (SPM, version 8) was used to process the ASL-MRI data, which included motion correction, aligning each ASL frame to the first frame using a rigid body transformation, and least squares fitting. Perfusion-weighted images were computed as the difference between the mean of tagged and untagged ASL data sets. To account for signal decay during acquisition and to allow for intensities in meaningful physiological units, the perfusion-weighted images were intensity scaled. After geometric distortion correction, the ASL images were aligned to structural T1-weighted images. To estimate GM perfusion and to minimize the effects of the lower perfusion in white matter on the perfusion estimates, a partial volume correction was performed using the assumption that GM perfusion is 2.5 times greater than white matter perfusion. The FreeSurfer generated anatomical ROIs were used to analyze the ASL MRI perfusion data. Mean ASL perfusion values from the cerebellum were used as a control for the meta-ROIs. Total cortical GM perfusion was derived by averaging ASL perfusion values across all the Desikan-Killiany atlas cortical ROIs bilaterally. Frontal, parietal, temporal, and occipital lobe perfusion were derived by averaging CBF values across the Desikan-Killiany ROIs that corresponded to each lobe bilaterally. Hippocampal perfusion was derived by averaging ASL perfusion values from the right and left FreeSurfer hippocampal ROIs. CONN-fMRI Functional Connectivity toolbox version 17 was used to analyze the functional connectivity data. Blood oxygen level-dependent (BOLD) signal noise from the white matter and cerebral spinal fluid was characterized with the principal component-based noise-correction "CompCor" method utilized in the CONN toolbox. Band-pass filtering was performed with a frequency window of 0.008-0.09 Hz and each scan was Hanning weighted. The ACC was chosen as a seed region to examine ROI-to-ROI functional connectivity with other brain regions. Bivariate-regression analyses were used to determine the linear association of the BOLD time series between each pair of sources in first-level analyses.
cognition, home treatment, neuroimaging, photobiomodulation, traumatic brain injury (tbi)
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PMC3362964_01
Female
66
A 66-year-old African American woman with osteoporosis, osteoarthritis, and impaired glucose tolerance presented to the emergency department with a 5-day history of left groin pain, nausea, vomiting, and fatigue. Five days prior to admission, she had noted an abscess on her inner left thigh that progressively ruptured and drained purulent, bloody material. On evaluation, she was tachycardic (HR: 111-136) and febrile to 103.2 F. The left thigh wound drained a thin serous and dishwater-type fluid. Labs revealed leukocytosis and hyperglycemia (WBCs = 23.8 x 103: 86.4% neutrophils, 5.4% lymph, 8.1% monocyte; glucose: 239 g/dL; BUN 13 mg/dL, creatinine 0.6 mg/dL, chloride 92 mmol/L, total CO2 24 mmol/dL, total creatinine kinase = 67 mg/dL). CT scan showed a 4.6 x 1.4 x 5 cm fluid collection proximal to the left gracilis muscles with presence of gas bubbles, edema, and fat stranding in the subcutaneous tissues. The patient was taken emergently to the operating room to undergo radical debridement, washout, packing, and subsequently admitted for IV antibiotic therapy. Microscopic analysis of the debrided specimen revealed areas of necrosis and acute and chronic inflammation, consistent with a diagnosis of necrotizing fasciitis. Gram stain of the initial intraoperative specimen showed "few gram positive cocci in pairs and chains," and final bacterial culture showed many GBS, moderate S. lugdunensis, and moderate Corynebacterium (see Figure 1). Subsequent additional debridement grew many GBS and many S. lugdunensis. Blood cultures were negative. Blood tests for HIV 1, HIV 2, hepatitis B, and hepatitis C were negative. QuantiFERON gold tuberculosis test was negative. During the course of hospitalization, the patient was empirically treated with IV antibiotics including vancomycin, clindamycin, and aztreonam. After multiple debridements, the patient underwent plastic surgery reconstruction of her left groin. She was discharged home in stable condition after a 67-day hospital course and is doing well at followup 18 months later.
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PMC3189692_01
Male
60
Philip, a White 60-year-old British man, had a road traffic accident on the motorway 3 months before presenting for assessment. The driver of an adjacent car fell asleep and drove into Philip's car from the side. His daughter and grandson were sitting in the back seat. Philip's car spun twice. He tried to look around to see if his daughter and grandson were safe, but he was trapped and could not see them. He thought they were flying about in the car like everything else and that they had died. The car eventually landed on its four wheels. Philip described excruciating pain in his back. He thought that he had broken his back. He could not hear his daughter or grandson and believed they must be dead. However, they had survived. His daughter had a broken arm and his grandson was without injury. When Philip presented for assessment he was having intrusive memories of the accident every day in which he saw the car spinning. He also had intrusive images of what could have happened and pictured his daughter and grandson dead in the backseat. Philip had flashbacks when he drove his car, which happened several times per week, and he felt hot and sweaty in these situations. He also often woke up with nightmares about the accident. Philip pushed memories of the accident out of his mind, especially at bedtime. He avoided places that reminded him of the trauma, especially motorways and where it happened on the motorway. Whilst he could remember the trauma, he could not remember that the car had rolled twice until he was told by his daughter. Philip had many hyperarousal symptoms. He had difficulty sleeping, felt irritable, had trouble concentrating, and was overly alert. Philip also developed depression after the accident. He was low in mood, tearful, unmotivated, and preferred to stay indoors rather than engage in his previous activities, such as meeting friends for a drink and going out with his wife once a week for a meal. Philip met the criteria for PTSD and major depression as set out in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV; American Psychiatric Association,) and assessed with the Structured Clinical Interview for DSM-IV (SCID; First, Spitzer, Gibbon, & Williams,). In addition, Philip had chronic back pain from the accident. The pain was a constant reminder of the accident and could trigger intrusive memories and rumination. In terms of personal meanings of the trauma, objectively Philip knew the accident was not his fault but he felt as though it was. He believed this 60%. He concluded from the accident that he was incapable of keeping his daughter and grandson safe, especially because another (small) accident had happened when his grandson was in his care. He believed this 80%. Philip's primary symptoms were upsetting, recurrent memories of seeing the car spinning. His memory was unclear about some details, for example, he had only learned from his daughter about the car spinning twice. When the intrusive memories popped up, he imagined his daughter and grandson being dead, and then tried to push thoughts of the accident out of his mind. Thought suppression made his images pop-up more frequently. Pushing them out of his mind at the worst moments also prevented him from updating these moments in memory with the information that in fact his daughter and grandson were alive. In addition to the suppression of trauma memories, Philip used a range of other behaviours that maintained his PTSD. Philip still drove but he avoided going on motorways. When he was required to drive on the motorway, he checked the position and speed of other cars very closely and imagined accidents happening. This maintained his conviction that he had to be especially careful to prevent further accidents and, thus, his anxiety about driving. He ruminated about the accident being his fault and his inability to keep his family safe, which maintained these appraisals and caused him to feel sad. He also avoided seeing his grandson to limit the chances of further accidents and limited how often he saw his daughter because he felt guilty about what had happened. The withdrawal from his family prevented him from finding out that they were safe with him. It also contributed to his low mood and because he felt low, he stopped going out and doing the things he used to enjoy such as eating out once a week with his wife. This further maintained his low mood. According to the case formulation, the main treatment goals according to the Ehlers and Clark model were: To reduce Philip's sense that he was responsible for the accident. To change his appraisal that he was incapable of keeping his daughter and grandson safe. To reduce intrusive re-experiencing and nightmares by (1) identifying information that puts the threatening meanings of the moments represented in re-experiencing into perspective, and (2) updating these moments in memory with this information. Suppression of intrusive memories. Rumination about his perceived inability to keep his daughter and grandson safe. Avoidance of his daughter and grandson. Avoidance of motorways. Excessive checking of other traffic when driving. Activities that were important to Philip before the accident. Daily activity, including physical activity, to help with depression and pain. To reduce:To build up: Updating the memory for the worst moments of the trauma. Reclaiming your life assignments. Behavioural experiments to reduce thought suppression, avoidance, and excessive checking. Cognitive restructuring of appraisals of being responsible for the accident and incapable of keeping his family safe. According to the initial formulation, the following treatment procedures described in Appendix A appeared especially relevant for Philip: On the Post-traumatic Stress Diagnostic Scale (PDS; Foa, Cashman, Jaycox, & Perry,) Philip scored 29 in the moderate-to-severe range of PTSD symptom severity. On the Impact of Events Scale-Revised (IES-R; Weiss & Marmar,), Philip scored 71 in the severe range. On the 9-item Patient Health Questionnaire (PHQ-9; Kroenke, Spitzer, & Williams,), Philip scored 15 in the severe range for depression. On a 7-item measure of generalised anxiety (GAD-7; Spitzer, Kroenke, Williams, & Lowe,), Philip scored 16 in the severe range. Philip completed these questionnaires at assessment and prior to every weekly treatment session. Two weeks prior to session 1, Philip was assessed by an independent assessor who administered the Clinician-Administered PTSD Scale (CAPS; Blake et al.,). The total CAPS severity score was 76. The therapist met briefly with Philip after the independent CAPS assessment to give him the first two core modules (It All Makes Sense and Reclaiming Your Life) and asked him to complete them before the first session. The It All Makes Sense module focuses on normalising the symptoms of PTSD and obtaining information that will help the case formulation and develop treatment goals. It includes patient testimonies of their experience of CT-PTSD. It asks clients to describe their flashbacks as well as feelings and physical responses to reminders of their trauma. It encourages them to note any triggers of their trauma memories and the key emotions linked to their trauma, such as fear and shame, and the thoughts linked to these emotions. It then helps patients to identify their safety-seeking behaviours (Salkovskis,). The module explains why PTSD is linked to physiological arousal and guides the patient to elicit the ways in which they cope with their trauma memories, such as through distraction, alcohol, rumination, or suppression. The module includes an example of another client's treatment goals and space for the client to write out their goals for treatment. The Reclaiming Your Life module educates the patient as to how PTSD can cause patients to stop doing activities they used to do. It then encourages patients to identify what they would like to do again in different areas of their life, such as in their free time and in their home and social life. The module then encourages them to complete a weekly plan in which they identify activities they would like to do and aim to try at least one of these before they meet with their therapist. The module includes a troubleshooting section, which normalises and problem solves potential obstacles to completing the planned activities, such as "I don't have any energy for doing anything" and "It will be too traumatic:I won't be able to cope." In addition, the therapist gave Philip the Chronic Pain and PTSD module that describes the effects of chronic pain on feelings and behaviours and guides the patient to identify the effects of chronic pain in their life, as well as the effects of PTSD on chronic pain, such as continually reminding the patient of their trauma. The module also explains why it is important to not give up physical activity in response to chronic pain. Philip arrived at the session having completed all three modules. The therapist reviewed these prior to commencing the 90-min session. Philip had spent 55 min over 2 days completing the It All Makes Sense module. He had spent 200 min over 2 days completing the Reclaiming Your Life module, and this included the time he spent on an activity he had conducted as part of his weekly plan to reclaim his life. He had spent 85 min over 3 days completing Chronic Pain and PTSD. The therapist's aims for the session were to operationalise Philip's treatment goals in a concrete way, provide a treatment rationale, and to conduct an imaginal reliving of the accident (Foa & Rothbaum,) to identify Philip's emotional hot spots; that is, the worst moments of the trauma, their linked emotions, and personal meanings. The client's operationalised goals were to: First, to feel happy, which would mean that he could go out more, go shopping with his wife, and feel comfortable driving on the motorway. His second goal was to reduce his nightmares so he could sleep through the night and no longer wake up in a cold sweat. His third goal was to think about his accident without getting upset. The therapist was able to weave the client's goals into the rationale for revisiting and updating his memory of the accident, since it was hypothesised that his sleep would improve and he would come to terms with his trauma following the process of updating his trauma memory. When presenting the rationale, the therapist drew on information the client provided in the module It All Makes Sense, specifically that he pushed the trauma out of his mind. The client was guided to discover that going over his trauma memory in detail would help him to emotionally process it, and transform it into a regular autobiographical memory without unexpected intrusions. The session contained 30 min of imaginal reliving. Philip rated his distress at 90% and the "nowness" (impression that it is happening now rather than being a memory from the past) as 80%. This was followed by asking the client to identify his worst moments, and what went through his mind in these moments during the trauma. Philip identified two hot spots: The car spinning after the impact and then the car landing on its wheels from what appeared like a great height. Both hot spots meant at the time to him that his daughter and grandson may die or had died. This filled him with fear, sadness, and feelings of guilt. The second also meant to him that he may have broken his back. To conclude the session, the therapist drew out a weekly plan of Reclaiming Your Life homework with Philip and asked him to note his level of satisfaction out of 100% for each activity. This aimed to target inactivity, which maintained his low mood and contributed to his pain. The client was also given a module, Working on Your Memories, which addresses the consequences of suppressing unwanted memories, how to cope with them, clients are asked to write out a narrative of the trauma in the first person present tense, and write out questions to help identify hot spots. The module also includes a patient's example of their written narrative and hot spots. Philip had spent 65 min completing Working on Your Memories over 3 days. He had also completed his weekly Reclaiming Your Life plan and had rated most activities as being 70% satisfying. The therapist's plan for this session was to review the client's homework, reinforce what he had learned from being active, and elicit new information to update the meanings of his hot spots. Philip had learned that when he was active his mood improved, and this encouraged him to plan more activities. The therapist then focused on one belief linked to both hot spots: that his daughter and grandson had been harmed or died in the accident. The therapist encouraged Philip to think about what he knew now in relation to his daughter and grandson being alive. Philip was asked to think about the times he had seen them since the accident. He recalled that he had seen them a few times and that on one occasion this had been a happy experience. They had surprised him on Father's Day. Philip could visualise their smiling faces, recall their conversations, and could vividly picture his grandson playing with his mini-football. To update the hot spots in memory, Philip was then asked to close his eyes and recall the moment of impact of his accident, recalling what went through his mind and what he knew now. He ran the worst moment on to include the information that this daughter and grandson were safe and he pictured them at his recent Father's Day celebration. Again, in conclusion to this session, the therapist and Philip agreed on a weekly plan of Reclaiming Your Life activities for him to complete and to note his level of satisfaction for each activity. As Philip had been avoiding seeing his daughter and grandson because he believed they would be unsafe with him, one of his reclaiming his life activities was set up as a behavioural experiment. This experiment had two purposes: to test his belief that they would be harmed in his presence and to encourage him to re-engage in significant activities he had given up since the trauma, which was to see his family more often. The client was also given the Updating Your Memories module to further focus on information to update his worst moments. This module includes a rationale for looking at hot spots in detail to update them and examples of how other patients have done this. A space is provided for the patient to describe the situation linked to their hot spot, the thoughts that went through their mind, and their meaning at the time (then), what they know now, and how they can remind themselves of what they know now. Philip had spent 70 min completing the Updating Your Memories module. Table 1 shows his hot spots and how he had updated them in the module. Philip had also completed his weekly Reclaiming Your Life plan and had rated most activities as being 80% satisfying. The therapist planned to review the client's homework; address his rumination about what could have happened and about his inability to keep his daughter and grandson safe, which were maintaining Philip's anxiety; and to address his appraisal that he was responsible for the accident. Philip was continuing to learn from his homework that being active helped to lift his mood. In comparison to his level of activity before therapy, he was also able to see that being inactive kept him feeling low. Philip had completed his behavioural experiment to test his belief that his daughter and grandson were unsafe with him. He had asked them to come over for lunch on the weekend. Nothing had happened to them in his presence and he re-rated his belief that they would be harmed with him from 80 to 20%. In the session, the therapist guided Philip to discover that ruminating about his inability to keep his daughter and grandson safe triggered intrusive memories of his accident and made him feel anxious. He discovered that when he was ruminating, he was not taking in new information that they were in fact well and that there were many times he had been with them and no danger had occurred. Philip now planned to visualise his daughter and grandson at his Father's Day celebration when he noticed he was ruminating, and to focus on the information that they were well and had survived the accident. Philip was then asked to generate reasons for why the accident had happened. He recalled that the main one was that the driver who had hit their car had fallen asleep. This information did not fit with his belief that he was responsible for the accident, which dropped from 60 to 40% with this information. In addition, the session started to address Philip's checking behaviours when driving. Philip understood that constantly checking the position, speed, and so on of other cars may contribute to his concerns about the dangers of driving and he was willing to do a behavioural experiment that involved (1) driving on the motorway while checking, and (2) driving while dropping the checking behaviour to observe the effect on his levels of anxiety/relaxation and his sense that an accident was going to happen. To conclude the session, the therapist again drew out a weekly plan of Reclaiming Your Life activities with Philip to complete in the following week. The behavioural experiment to drive with and without checking behaviour was also noted on this plan. The module Guilt and Self-Blame was given to the client. This module helps clients to understand why they feel guilty, what thoughts and thinking errors guilt is linked to, and how to let go of guilt. The client is encouraged to consider all possible causes of their trauma and to rate the contribution of these factors to the occurrence of their trauma in a responsibility pie chart. The module has examples of how other patients have completed specific questions. The client had conducted his behavioural experiment and rated that he felt 80% relaxed when driving without checking compared to 80% anxious when he drove and checked. He agreed to build on this experience and do more driving without checking until the following session. He had also completed his Reclaiming Your Life tasks. He had spent 90 minutes over 4 days working on the Guilt and Self-Blame module. Philip's self-blame about the accident had dropped from 60 to 40% in the previous session and following this module, it dropped to 0%. The main plan for this session was to continue updating Philip's hot spots by simultaneously bringing the hot spots and the information gathered in therapy to mind that were relevant to their meanings. First, this was that Philip's daughter and grandson had not died as he had feared. A moment when he had seen them just after the accident sitting on a bench talking and smiling reinforced the updated meaning that they were alive, as did the image of them smiling at his Father's Day celebration. Second, the accident was not Philip's fault as it was the other car that had hit theirs. Third, Philip did not break his back and could walk again after the accident. One problem that made it difficult for Philip to update his hot spots was that he had not been able to see his daughter and grandson during these moments. To facilitate access to his knowledge about what had actually happened while focusing on the trauma, the therapist had the client imagine the trauma from a third-person perspective, watching what was happening to him and his family. The client rated this as 75% distressing with a nowness rating of 80%, but this came down to 0% distressing and 10% for nowness when he also visualised his daughter and grandson in imagery first sitting on the bench smiling and then smiling at his Father's Day celebration. Homework included driving without checking, teaching his other daughter how to drive, and pleasurable activities. The client was asked to read through the Guilt and Self-Blame module again to consolidate learning about being responsible for the accident. The client felt much improved and his intrusive memories and nightmares had ceased. He had spent 30 min reviewing the Guilt and Self-Blame module, had continued to drive without checking, and reported he had felt 85% relaxed. This session addressed his belief that he was incapable of looking after his grandson because the car accident was the second time there had been an accident of some sort while Jake had been in his care. Another time, he had held Jake and had fallen. Philip realised that he had been with his grandson many times without any accidents happening and that he thus overestimated the likelihood of accidents. He further realised that the car accident had not been his fault and thus was not good evidence for his ability to look after his family. Furthermore, in both cases Jake had not been seriously hurt. Homework was again to conduct daily activities, which included seeing his daughter and grandson and rate his satisfaction, to continue with his driving, and to complete the module Blueprint. The Blueprint module reviews what the client has learned in treatment to help with the prevention of any setbacks or relapse. It asks the client to answer key questions about how their problem started, what kept it going, what they learned in therapy, what their unhelpful and now updated thoughts were, how they could build on what they have learned, and how they could address setbacks if they occurred. This session focused on reviewing and adding to the client's blueprint and troubleshooting any problems that could arise in the 1-month follow-up period. Philip had spent 60 min completing his Blueprint module. For homework, the client was asked to continue driving, doing activities regularly, and to review his blueprint once per month. Philip attended a brief follow-up session 1 month after treatment ended. This session contained a probe reliving the accident. Philip's distress and nowness levels were 0%. Philip's treatment spanned 6 weeks. In his sixth and final session, he scored in the non-clinical range on all symptom measures, PDS: 2, IES-R: 8, PHQ-9: 1, GAD-7: 1. He no longer met criteria for PTSD on the CAPS as assessed by an independent assessor, with a CAPS total score of 4. He no longer met criteria for major depression as assessed by the SCID. At the 1-month follow-up session, he scored 0 on the PDS, IES-R, PHQ-9, and GAD-7. Philip was contacted again 2 months after treatment ended. He maintained his gains and scored in the non-clinical range on all measures, PDS: 4, IES-R: 5, PHQ-9: 4, and GAD-7: 0.
ptsd, cognitive behavioural therapy, cognitive therapy, road traffic accident, self-help, self-study assisted treatment
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PMC7646501_01
Male
23
In May 2020, during the outbreak of SARS-CoV-2 in Italy, a 23-year-old male, non-smoker, with no remote clinical history, presented to the Emergency Department; he had suffered from fever (up to 38 C), cough, and worsening shortness of breath for 3 days. At clinical examination, the most important clinical feature was bilateral wheezing; nevertheless, the patient did not have a history of asthma nor chronic sinusitis with nasal polyposis. During the visit, the patient did not refer to new smoking or second hand smoke habit, nor drugs or new antigen exposures. Blood test showed an increase in peripheral blood eosinophilia (1.8x1,000/muL, 12.5% of the total leukocyte number) with leukocytosis (14.45x1,000/muL); in particular, neutrophils were 61.6% (8.91x1,000/muL), lymphocytes were 17.7 (2.56x1,000/muL), monocytes 7.6% (1.1x1,000/muL), and basophils were 0.6% (1.8x1,000/muL). A mild elevated C-reactive protein (CRP=1.53 mg/dL) was found, with negative procalcitonin, mild elevated Lactate dehydrogenase (LDH 384 U/L), mild elevated Interleukin-6 (IL-6=12.4 pg/mL), and negative D-dimer (230 ng/mL). Arterial blood gases showed: pH=7.39; pO2=59 mmHg; pCO2=40 mmHg; HCO3=25 mmol/l with a fraction of inspired oxygen of 35% in Venturi mask and arterial oxygen pressure on fraction of inspired oxygen ratio (PaO2/FiO2) of 168. Due to the persistence of respiratory symptoms and respiratory failure, the patient underwent a chest high-resolution CT scan, which reveal bilateral GGO localized in the upper left lobe (in particular in lingular segment) and in the right lower lobe (Figure 1). For these reasons, he was hospitalized with suspected COVID-19 in the Infectious Diseases Unit in Santa Maria Nuova Hospital of Reggio Emilia. As of the chest CT, the suspicious of COVID-19 was high, but we had to consider other possibilities in differential diagnosis, such as eosinophilic granulomatosis with polyangiitis (EGPA), alveolar hemorrhage, AEP, parasitic pneumonia, drug toxicity, or toxic inhalants. In the Infectious Diseases Unit, on day one the patient was tested negative with nasopharyngeal swab for SARS-CoV-2, and the result was confirmed after 24 hours with a second nasopharyngeal swab that was negative as well. Moreover, serology test for SARS-CoV-2 was also negative. In order to exclude a vasculitis, antineutrophil cytoplasmic antibodies (ANCA) were searched, and resulted asnegative. After 24 hours from admission in hospital, patient's respiratory conditions worsened with symptoms such as dyspnea and increase in respiratory rate (25 breaths per minute), so high flow oxygen therapy with a fraction of inspired oxygen of 60% was needed. A therapy with two daily inhalations formoterol/beclomethasone metered-dose inhaler 100/6 mug was introduced to improve respiratory symptoms, with only partial improvement of symptoms. In consideration of the increase in peripheral blood eosinophilia and bilateral GGO on chest CT, a flexible bronchoscopy with bronchoalveolar lavage (BAL) was performed; an amount of 150 mL of physiological liquid was introduced to perform BAL and 70 mL of clear liquid was collected, with no traces of blood in it. BAL revealed eosinophils alveolitis (40%) and mucous secretion with no evidence of bacteria or viruses, SARS-CoV-2 included. These findings were compatible with AEP (Figure 2). For this reason, we started a therapy with oral corticosteroid (prednisone 50 mg daily), with a rapid clinical improvement and no more fever. After 1 week of therapy, the initial respiratory failure was resolved and blood tests revealed a lower peripheral blood eosinophilia. The prednisone dose was halved in 14 days, and the patient was discharged with the dose of 25 mg. Before the discharging we obtained the informed consent for the publication of this case report.
covid-19, acute eosinophilic pneumonia, bronchoalveolar lavage, ground glass opacities
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PMC9343201_01
Female
25
Sarazin and colleagues reported the case of a 25-year-old female with a history of recent travel to Madagascar, presenting with fever for a week, rapidly progressive headache, limb ataxia, and memory impairment. She was diagnosed with watershed bilateral infarction. Stool positivity and seroconversion occurred only 3 weeks after neurological presentation. The case was complicated by progressive cardiomyopathy requiring surgery. No neurological recurrence occurred. Sonneville and co-workers described a case of a 56-year-old woman with sudden onset of hemiplegia due to watershed infarction. Acute pericarditis and myocarditis complicated the case. The outcome was favorable with steroidal therapy, and neurological recovery was reported after 6 months. Two case reports were published by Jaureguiberry. A 54-year-old man living in Mali for several years, where he had been repeatedly exposed to fresh groundwater, was medically examined due to a history of fever for 10 days, followed by acute cerebellar syndrome, hemiparesis, and confusion, with multiple cortical and subcortical infarcts caused by cerebral vasculitis. Serology and urinary positivity for the presence of schistosoma eggs was observed 4 months after the acute event when the patient still showed psychomotor slowing and insomnia. The second case reported a 21-year-old male patient who bathed 1 month earlier in a lake in Mali. Four days after starting therapy with praziquantel due to a maculopapular rash and fever, he presented with confusion and anosognosia, and he was diagnosed with cerebral vasculitis. The patient had a positive serology at hospitalization, but schistosoma eggs could be detected in urine only 4 months later. The neurological features resolved after 48 hours of steroid therapy. In the report by Camuset and coworkers, a 28-year-old female patient went on a mission in Burkina Faso for 1 year, where she bathed in a lake. She had a 6-month history of headaches. She was hospitalized for hemiplegia associated with an unspecified language disorder. Serology and rectal biopsy showed positivity for schistosoma. One month later, the patient presented with headache, diplopia, and VI cranial nerve palsy, with stenosis of carotid syphon. The exacerbation of vasculitis was considered due to the adverse effects of praziquantel. Minor improvement of carotid stenosis was reported at 6 months, but no details on hemiplegia were provided. The case reported by Wu and colleagues lacked anagraphic details. The patient presented with acute headache and walking impairment, and multiple low densities in the alba were observed on imaging. Exposure history suggested chronic schistosomiasis. Grandier-Perez and coworkers reported the case of a 19-year-old girl back from Kenya, where she had bathed in lake Victoria 2 weeks earlier. She presented with a 15-day history of fever and urticaria. Neurological features occurred on day 12, with the appearance of ataxia, confusion, and unilateral dysmetria. Imaging showed features of watershed infarction. Serology was positive at hospitalization, while stool and urine became positive for the presence of schistosoma eggs 4 months later. A full neurological recovery was reported 5 days after starting steroidal therapy. Lastly, in the report by Nyein and colleagues, a 52-year-old patient had visited Myanmar during a schistosomiasis outbreak 1 year earlier, had swum in ponds and had eaten snails, and was hospitalized because of cognitive impairment, memory deficits, and behavioral changes, with multiple cerebral infarcts on imaging. This picture was followed, 3 weeks later, by dysarthria, hemiplegia, and facial palsy, with frontal lesions on imaging, bilateral terminal internal carotid artery narrowing, and beaded anterior cerebral artery. New frontal lesions appeared at week 9 after hospitalization. The patient had a positive serology, but no eggs were detected by optical microscopy assessment of stool. On follow-up, neurologic recovery was partial, and the patient could walk with the aid. The cases are summarized in Table 1; for clarity, each case was assigned with a number, which will be used further in the text to refer to single patients. Tables 2 and 3 reports the incidence of specific neurological symptoms.
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PMC3320427_01
Male
35
A 35-year-old man with an unremarkable medical history sought treatment for headaches, hearing loss, and night sweats. The headaches were occipital and bilateral and had started 3 months earlier. They came on as the day progressed and were neither positional nor associated with nausea, vomiting, or visual changes. Three weeks before arriving at the hospital, he noted a sense of "fullness" in his ears; he said that spoken voices sounded muffled, and he had difficulty hearing telephone conversations. When someone at the restaurant where he worked dropped a dish, he heard that sound clearly and reported that it was almost painful, causing him to become dizzy. He otherwise denied ear pain or recent trauma. His appetite was good, and he had not lost weight. Although he reported no fever, he did report night sweats for several weeks. He had no rash, diarrhea, abdominal pain, chest pain, shortness of breath, joint complaints, or dysuria. The patient attributed his headaches to stress. He also said that he was exposed to dust at his workplace because of remodeling. The patient was taking no regular medications and had no drug allergies. He had quit smoking 7 months earlier and drank 10-12 beers per week. He reported no history of intravenous drug use. He lived in New Hampshire, had no pets, and worked as part owner of a restaurant. Exposures included multiple male and female sexual partners with inconsistent condom use, and he had acquired several tattoos 8 months earlier while traveling in Spain and Italy. He had no known tuberculosis exposure. An HIV antibody test had been negative 18 months earlier. On physical examination, he appeared healthy but anxious. Temperature was 36.7 C, blood pressure 128/84 mm Hg, pulse 80, respirations 16/minute. Sclerae were anicteric, and his pupils reacted to direct and consensual testing and responded normally to accommodation. Funduscopic examination showed no retinal abnormalities. The left tympanic membrane was retracted; both sides demonstrated a small effusion. No vesicles were seen. Bedside testing showed that his hearing was diminished to low volume sounds, but he was able to hear loud sounds, which he found painful. When the examiner clapped his hands loudly a few feet from the patient's ear, the patient exhibited nystagmus. His sinuses were not tender, and the oral mucosa had no lesions. The patient's neck was supple; a 1.5-cm, nontender lymph node was palpated in the left upper anterior cervical chain. No other lymphadenopathy was noted. The remainder of the examination was unremarkable, with negative Romberg test; normal gait; and normal motor, sensory, and reflex performance. Laboratory evaluation (Table) showed low hematocrit and normal renal and liver function. HIV enzyme-linked immunosorbent assay and confirmatory test were positive. Rapid plasma reagin (RPR) was positive at a titer of 1:128 and was confirmed by a fluorescent treponemal antibody test. Subsequent studies showed a CD4 receptor-positive T-cell (CD4) count of 899/mL and an HIV viral load of 878 copies/mL. A lumbar puncture showed protein 33 mg/dL, glucose 78 mg/dL, 9 erythrocytes/microL, and 8 leukocytes/microL (100% lymphocytes). Cerebrospinal fluid venereal disease research laboratory test (CSF-VDRL) results were negative.
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PMC6000763_01
Male
71
A 71-year-old male patient of Asian Origin referred by a general physician, without significant comorbidities, family, and personal history presented with a one-month history of regurgitation of acid, retrosternal burning and vomiting after eating. Physical examination revealed bowel sounds upon chest auscultation and decreased breath sounds in the base of the right lung. Clinical findings were as follows: blood pressure, 110/76 mm Hg; pulse rate, 88/min; his body temperature, 36.3 C; and oxygen saturation, 94%. Upper GI esophagogastroduodenoscopy revealed an upward migration of Z line with Grade III Hiatus Hernia (Fig. 1A). Chest X-ray showed an air-fluid level with obscuration of right heart border (Fig. 1B). A manometric examination revealed the average pressure of lower esophageal sphincter was ten mmHg. CT demonstrated a significant 3.4 cm defect in the anterior diaphragmatic wall, with herniation of bowel on the right side of the chest. The stomach is present on the left side with the anterosuperior displacement of the gastric antrum along with a grade III Para-esophageal hernia (Fig. 2). The Diagnosis of Morgagni Hernia, Para-esophageal Hernia (Grade III) with Organo-Axial Gastric volvulus was made based on the patient symptoms, clinical findings, imaging, and endoscopy results. Because of the patient's symptoms and possible severe complications caused by the two hernias, the decision was taken to go for mesh reinforcement, laparoscopic Hiatal reconstruction with fundoplication. Before the elective surgery, the patient was started on Incentive Spirometry and administered antibiotic and VTE prophylaxis. Under general anesthesia in the Fowler position, with the surgeon (specializing in minimal access surgery) standing between the patient's legs, a laparoscopic approach was achieved. A Morgagni Hernia containing omentum, stomach and transverse colon was noticed (Fig. 3A, B). The contents were removed from the hernia sac relatively easily using two atraumatic graspers (Fig. 3C). We also found the gastric fundus herniated into the thoracic cavity at a diameter of about 5 cm (Fig. 4A). The stomach is pulled back into the abdominal cavity, and then the hiatus was reconstructed with interruptedly tied 2/0 Prolene sutures behind the esophagus after ensuring that the lower esophagus was at least 3 cm in length in the abdominal cavity (Fig. 4B). Mesh Reinforcement of the Hiatus defect with the bioabsorbable composite mesh. The gastrophrenic ligament mobilized, short gastric vessels ligated, and gastro-splenic ligament was cut to have an adequate Fundic wrap. The vagus nerves were recognized and preserved. Intra-operative esophagogastroduodenoscopy was performed to confirm that the dentate line was 3 cm below the hiatus. A 360 Nissen's fundoplication was then performed to complete the Hiatal closure (Fig. 4C). The 3.4 cm Subcosto-sternal defect was too large to approximate using the trans-abdominal trans-fixation suture. Hence, the decision was taken to close the anterior diaphragmatic defect with the Polypropylene mesh. The mesh was fastened to the diaphragm with the help of tackers and interrupted sutures using Prolene 2/0, taking special precaution to avoid damage to the pericardium (Fig. 4D). The patient was kept Nil by mouth for three days after which he was resumed on a liquid diet advancing to soft food one week after the surgery. The patient reported a single port site infection, which required removal of the skin suture without any need of an antibiotic [Clavien-Dindo classification Grade I]. The patient returned home eight days post operation on proton pump inhibitors medication. At one-month follow-up, the patient did not report any dysphagia, heartburn or symptoms related to reflux. The scars were normal without any pain. Follow-Up CT showed adequate repair of a diaphragmatic and Para-esophageal hernia without any evidence of herniation of Greater Omentum, stomach, and bowel (Fig. 5). There were no gastric complaints at follow-up six months after discharge.
case report, diaphragmatic hernia, fundoplication, minimally invasive surgery, morgagni, para-esophageal hernia
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PMC9035915_01
Female
70
A 70-year-old female developed a sudden onset of slurring of speech and dryness of mouth after snake bite. During presentation in local hospital after 2 h of the event, the patient was unconscious and needed intubation. Anti-snake venom (ASV) was given immediately according to the local protocol. She regained her consciousness the next day and was extubated. There was no limb weakness, blurring of vision, diplopia, or other neurological symptoms. The patient did not recall any specific character of the snake; however, the geographic region suggested the snake was most likely to be a cobra snake. She was discharged after 3 days of admission; slurring of speech completely improved during discharge. After 16 days of the episode, the patient presented to our center with a complaint of blurring of vision for 10 days followed by bilateral loss of vision. The detailed timeline of events is shown in Figure 1. Loss of vision was painless and progressive. The vision loss was diffuse, and no postural variation was present. There was no redness of the eye, photophobia, increased lacrimation, or pain in eye movement. There was no headache, vomiting, limb weakness, slurring of speech, nasal intonation of voice, or nasal regurgitation. She did not complain of any tingling sensation, numbness, paresthesia, abnormal body movement, and weakness of the limbs. She was a diabetic under regular oral antidiabetic drugs for 16 years. She was also diagnosed with hypertension 10 years back for which she has been under regular antihypertensive medication. There is no history of cigarette smoking or consumption of alcohol. On examination, her vitals were stable with the pulse rate of 72 beats/min, 120/80 mm of Hg blood pressure, respiratory rate of 20 breaths/min, and temperature of 98 F. Visual acuity was assessed using the Snellen Chart, but as the patient could not read the largest letter, could not count finger or see hand movement, and only see the light shined in bilateral eyes, visual acuity of <<perception of light>> in both eyes was recorded. The cup to disc ratio was 0.1:1 in the right eye and 0.2:1 in the left eye, and the disc was hyperemic. On neurological examination, higher mental function was intact with normal cranial nerves except CN II where visual acuity was limited to perception of light. Pupils were regular and round while both direct and consensual light reflex were sluggish. Examination of the anterior and posterior segments, ocular motility, and intraocular pressures were normal. Motor and sensory system examinations were normal. There were no signs of cerebellar dysfunction and meningeal irritation. Routine blood investigations such as complete blood count and renal and hepatic function tests were normal. CSF examination for total protein, albumin, IgG, IgA, IgM, glucose, lactate, cell count, microbiological/virological analysis, and the oligoclonal band was normal. With this history and examination findings, a provisional diagnosis of ON was made. and visual-evoked potential (VEP) and MRI of the brain were planned but were not done due to patient uncooperativeness. On the basis of our provisional diagnosis, 1 g intravenous methylprednisolone (MP) was given for 5 days along with oral thiamine and methyl cyanocobalamin supplements. Chest X-ray was performed before administrating the steroid to rule out pulmonary tuberculosis, and it was normal. On the 2nd day of treatment, the patient was able to perceive hand movements. The patient's visual symptoms gradually improved to bilateral visual acuity of 6/60 on the fifth day of admission. Pinhole correction further did not show any visual acuity correction. There was abnormal color vision assessed by the Ishihara chart. MRI of the brain was also done which showed no abnormal findings (shown in Fig. 2). Intraocular pressure, VEP, and visual perimetry test were normal. Examination of the fundus showed a bilateral normal optic disc (shown in Fig. 3). The patient was given oral steroids at an initial dose of 1 mg/kg and tapering over 4 weeks after completion of intravenous MP. On the ninth day, the patient was discharged with improved visual acuity to 6/36 on left and 6/12 on right. On 2 months' follow-up, the patient's visual acuity improved to 6/9 on the left side and 6/6 on the right. Blood sugar monitoring was done throughout the course of treatment, and it did not rise to the level that warranted possible discontinuation of steroids or other treatments.
anti-snake venom, optic neuritis, snake bite, visual loss
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PMC9238204_01
Male
49
A 49-year-old male was admitted to the local emergency room (ER) with right upper abdominal pain that occurred after excessive drinking a day earlier. He was a heavy alcoholic. There was no family history. Enhanced abdominal CT scan showed a distal CBD stone and acute cholecystitis with multiple gallbladder stones. Endoscopic biliary sphincterotomy was performed followed by stone removal (Fig. 1A). After that, his jaundice persisted. His serum bilirubin and alkaline phosphatase levels continued to increase. Follow-up CT scan showed persist dilated CBD, dilated both intrahepatic bile ducts, and thrombus in the left portal vein (Fig. 1B). After 3 days, percutaneous transhepatic biliary drainage (PTBD) was performed and drainage catheter interposition was performed. Follow-up cholangiography revealed a long intraluminal filling defect (Fig. 1C). A large amount of stone debris was removed using a stone basket. After that, about a month after the initial symptom, the patient was transferred to the emergency center of our hospital. At the time of the visit to the ER, vital signs were normal and jaundice was observed in the sclera and skin. Laboratory data showed bilirubin of 6.22 mg/dL (reference range: 0.2-1.3 mg/dL), alanine aminotransferase of 107 IU/L (reference range: 13-69 IU/L), aspartate aminotransferase of 101 IU/L (reference range: 15-46 IU/L), alkaline phosphatase of 613 IU/L (reference range: 42-140 IU/L), gamma-glutamyl transferase of 261 IU/L (reference range: 5-55 IU/L). Hepatitis c was confirmed in the patient with viral test and hepatitis C virus RNA positive were 4462906 IU/mL in quantitative tests (real-time quantitative polymerase chain reaction). Three days after hospitalization, a follow-up cholangiography was performed through an 8F drainage catheter that was previously inserted. On cholangiography, a smooth cast like material, filling of the extrahepatic duct extending into both intrahepatic ducts, and marked ductal irregularity were identified. The patient was diagnosed with biliary cast syndrome and the cast was extracted using a basket through the PTBD catheter (Fig. 1D). The cast was composed of inflammatory exudates with pigmented material (Fig. 1E). The pathology report was negative for malignancy. The patient was discharged with PTBD after conservative treatment. After a month, the patient visited the emergency center again for abdominal pain and melena. He was diagnosed with cholecystitis and cystic artery pseudoaneurysm (Fig. 1F). He was discharged after cholecystectomy and CBD repair. Over the next two years, there had been intermittent episodes of abdominal pain and general weakness. Each time he was admitted, he received ERCP or PTBD for recurrent biliary cast. Finally, he received liver transplantation. The patient was symptom-free at one-month follow-up. This case report was exempt from the institutional review board standards (IRB No. KUGH 2021-06-017).
bile ducts, choledocholithiasis, ercp, ptbd
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PMC6787143_01
Female
16
A 16 year and 7-month-old African American female, who participates in multiple sports including cheer, softball, and competitive volleyball, presents with 5 months of worsening atraumatic bilateral anterior leg pain. She normally trains 6 h per day and 4 days per week. Initially, her pain only occurred with sports-related activities; however, after a recent 3-day volleyball tournament, her pain acutely worsened, yet improved with rest. She denied prior history of stress fractures, multiple previous fractures, and a family history of bone diseases, such as osteogenesis imperfecta. She is otherwise healthy with menarche at age 11 and reported normal cycles. The mother reported the patient had no dietary concerns but could be eating healthier. The patient had a normal BMI, with no concerning signs of metabolic or hormonal abnormalities. After obtaining radiographs and a physical exam, the patient was found to have bilateral multiple anterior cortex mid-tibial diaphyseal stress fractures. Three focal lucencies were noted over the anterior cortex of the right mid-tibial diaphysis and one over the left with bilateral cortical thickening and periosteal reaction (Figure 1). Bone metabolic labs and bilateral lower extremity CT scans were obtained. The patient's serum calcium was normal at 9.4 mg/dL, but her 25-hydroxy vitamin D resulted low at 17 ng/mL, and she was diagnosed with vitamin D deficiency. All other labs were noted to be within normal limits. She was started on high-dose vitamin D at 50,000 IU weekly for 8 weeks, and was referred to a registered dietician for consultation. CT scan of the bilateral lower extremities demonstrated additional smaller lucent defect in the left anterior cortex proximal to the stress fracture noted on x-ray. The atypical nature of multiple stress fractures and a low vitamin D level were concerning for possible prolonged healing. After extensive discussion with the patient and parents regarding activity level and risks of operative management, they wished to proceed with surgery for a potentially faster return to competitive volleyball in hopes of obtaining collegiate scholarships. She first underwent a transpatellar tendon reamed intramedullary nailing of the more symptomatic left tibia with proximal and distal locking screws. She underwent IM nailing of the contralateral tibia 6 weeks later. She attended physical therapy shortly after the right tibial procedure, focusing on a sport-specific return to play. Three and a half months after surgery, she reported the pain had dramatically improved and was cleared to gradually return to sports. Improvement in radiographic appearance of the linear lucencies was appreciated. At the 1-year post-operative follow-up, the patient had returned to full sports (HSS Pedi-FABS = 23) and reported minimal anterior knee pain with impact-related activities. She transitioned her vitamin D supplements to 1,000 IU QD, and her most recent 25-hydroxy vitamin D level was noted to be normal at 41 ng/mL (Figure 2).
adolescent athlete, anterior tibial diaphyseal stress fractures, bone health, high risk stress fractures, intramedullary nailing, vitamin d deficiency
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PMC10351041_01
Male
18
An 18-year-old male presented to our hospital with worsening fatigue. His past medical history was negative for any pathologies. He progressively developed pericardial and pleural effusions; subsequently, polyserositis was diagnosed. Therapy with ibuprofen, corticosteroids, and colchicine was started without any significant improvements; therefore, the patient was started on anakinra, which also did not contribute to any substantial improvement in the condition. Broad serological tests of infectious and collagen diseases were performed, including hepatitis viruses, toxoplasma, mycoplasma, venereal disease research laboratory (VDRL), cytomegalovirus, human herpes 6 (HH6), human herpes 8 (HH8), Epstein-Barr virus (EBV), human immunodeficiency virus, Coxsackie viruses, and antinuclear and rheumatic factors. All results were negative except for immunoglobulin M (IgM) antiviral capsid antigen (VCA) for EBV. Our patient was not related to a tuberculosis-endemic area; however, PCR for tuberculosis was performed in blood samples, sputum, and pericardial fluid, and the results were negative. Blood tests were found weakly positive for IgM VCA, and the extended autoantibody panel (ANA, ENA, ANCA, ASCA, and FR) was negative. Screening for celiac disease was also negative, and thyroid function tests were within normal limits. We also found tamponade pericardial effusion. It was, therefore, necessary to perform the first pericardiocentesis. Pericardial fluid was negative for malignant cells yet positive for inflammatory cells, and the polymerase chain reaction (PCR) test was positive only for EBV. Examinations for all other infectious agents (HH6, HH8, TB, CMV, Enterovirus) were negative. A chest computed tomography (CT) scan was performed, identifying lymph node conglobate in the right lung hilum, bilaterally in the supraclavicular and mesenteric areas. A bone marrow biopsy was also performed and was negative for lymphoproliferative disease. The transthoracic echocardiography showed moderate dysfunction of the left ventricle (LV) (with an ejection fraction of 46%), severe desynchrony of the ventricular septum, a global longitudinal strain (GLS) of -12.9%, the right ventricle (RV) with a normal function, and no significant regurgitation of the atrioventricular valve (Figure 1A). Cardiac magnetic resonance imaging (MRI) showed mild global biventricular systolic dysfunction [left ventricular ejection fraction (LVEF) 46%, right ventricular ejection fraction (RVEF) 47%] and circumferential pericardial effusion (maximum thickness 15-16 mm); right pleural effusion was identified (maximum thickness 3.5 cm), and there were no signs of pericardial constriction. Several days after pericardiocentesis with the extraction of about 400 ccs of blood serum liquid, a positron emission tomography (PET) CT scan and whole-body MRI scan were performed to exclude any underlying neoplastic processes. Once clinical and hemodynamic improvements were achieved, the patient was discharged with indications for close follow-up. One and two months after the patient was discharged, the echocardiography showed a stable condition with the persistence of a slight amount of pericardial effusion in the apical site and along the lateral wall of the left ventricle. After 3 months and mainly after 4 months, the echocardiogram showed worsening of the condition toward effusive-constrictive pericarditis, with enlargement of atrial sizes, alterations of diastolic function, dilation of the hepatic veins and inferior vena cava, and thickening and hyper-reflection of the pericardial leaflets. Abdominal ultrasound revealed effusion in all quadrants. A cardiac MRI was performed also 6 months after the first one and confirmed constriction with diffuse fibrotic thickening of the pericardial sac and signs of ventricular interdependence evident in the dynamic sequences (flattening of the interventricular septum in maximal inspiration), suggestive of constrictive physiology (Figure 2). The persistence of pericardial effusion along the mid-apical lateral wall of the LV was also identified (maximal thickness 10 mm). Finally, to confirm a restrictive picture, cardiac catheterization was performed, highlighting multiple elements suggestive of constrictive physiology with equalization of the diastolic filling pressure of the cardiac chambers and left and right ventricular diastolic "dip and plateau" appearance. Marked ventricular interdependence during the respiratory cycle and post-capillary pulmonary hypertension was noted. A diagnosis of constrictive effusive pericarditis was made (Figure 3, Table 1). The pre-operative cardiac catheterization showed pressure in the pulmonary artery of 35/21-25 mmHg and pulmonary wedge pressure of 22 mmHg (Table 1). At this point, the patient underwent anterior and posterior pericardiectomy surgery with preservation of the phrenic nerves, a procedure performed in normothermic cardiopulmonary bypass with a beating heart (Figure 4). Both intraoperative and postoperative periods were uncomplicated. The histological sample confirmed marked fibrous thickening with extreme rarefaction and fragmentation of the elastic fibers and mild lymphoplasmacytic inflammatory infiltrate (CD3+, CD20+, and CD38+), as well as neutrophilic granulocytes with numerous hemosiderin deposits and neovascularization. The in situ hybridization investigation with the Epstein-Barr-encoded small RNA (EBER) probe for the detection of EBV was positive, confirming the clinical suspicion of chronic pericarditis caused by EBV. Transesophageal echocardiography performed immediately after surgical excision of the fibrous pericardium showed complete recovery and normalization of ventricular septal motion. A few weeks after surgery, abdominal ultrasound showed a complete absence of peritoneal effusion. One week after surgery, transthoracic echocardiography was repeated and showed normalization of left ventricular function (3D ejection fraction 55%), and the GLS improved (-18.3%) (Figure 1B). The follow-up at 3, 6, and 12 months revealed no signs and symptoms related to diastolic heart failure, and echocardiogram findings were normal.
epstein–barr virus, constrictive pericarditis, effusive-constrictive pericarditis, mononucleosis, ventricular mechanics
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PMC3398492_01
Female
37
To find differences in the expression of transforming growth factor-beta-induced protein (TGFBIp), a major component of GCD2 corneal deposits, western blot analysis of primary cultured corneal fibroblasts was performed on ten different donated normal corneas. Corneas were collected from a 37 year-old man (normal corneal fibroblasts (NCF-1), a 62 year-old man (NCF-2), a 20 year-old woman (NCF-3), a 46 year-old man (NCF-4), a 29 year-old man (NCF-5), a 60 year-old man (NCF-6), a man with unknown-age (NCF-7), a woman with unknown-age (NCF-8), a 69 year-old woman (NCF-9), and an 81 year-old man (NCF-10). We first performed western blot analysis of four corneas (Figure 1A) to find out the variable expression level of TGFBIp from NCF-1, 2, 3, and 4 and the expression level was very low in NCF-3. We performed western blot analysis of another six corneas from normal donors (Figure 1B). Western blot analysis of NCF-4 was repeated in the second experiment to allow comparison between the two separate experiments. To measure the level of TGFBIp expression, total cellular protein was electrophoresed on Tris-glycine SDS polyacrylamide gels. Equal amounts of proteins were then transferred onto polyvinylidene difluoride membranes (Millipore Corp., Bedford, MA), blocked in 5% dry milk in Tris-buffered saline containing Tween-20 (TBS-T) at room temperature for one hour, and then incubated with primary antibodies to TGFBIp (0.2 microg/ml; Cat. No. AF2935; R&D Systems, Minneapolis, MN) and beta-actin (1:5,000 dilution; Cat. No. A-5441; Sigma, St Louis, MO) overnight at 4 C. After three washes with TBS-T, blots were incubated with secondary antibodies conjugated to horseradish peroxidase at room temperature for 1 h. Horseradish peroxidase-linked anti-mouse IgG (1:5,000 dilution; Cat. No. 31460) or anti-goat IgG (1:5,000 dilution; Cat. No. 31430) were used as a secondary antibody (Pierce, Rockford, IL). Western blots were visualized using the enhanced chemiluminescence system (Pierce). This study was approved by the Severance Hospital Institutional Review Board and informed consent was obtained from all subjects participating in this study.
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PMC3420437_01
Male
17
Our patient is a 17-year-old male who was diagnosed with FA at 13 years of age when he presented with bruising, fatigue, and pancytopenia. Physical stigmata of FA included hypopigmented skin lesions, short stature (below 3rd percentile), micrognathia, and hearing loss. Diepoxybutane (DEB) testing revealed increased chromosomal breakage. FA complementation grouping was not performed. Two years later, at the age of 15, the patient experienced bruising, epistaxis, and fatigue and was diagnosed with T-cell ALL. T-cell ALL markers included CD1+, TdT+, CD2+, CD3+, CD4+, CD5+, CD7+ and CD 8+; however, cytogenetic markers were not available. He was treated with standard 4-drug induction therapy and received vincristine, prednisone, PEG-asparaginase, and 2/4 doses of daunorubicin at an outlying hospital as per Children's Oncology Group Protocol AALL0434. His clinical course was complicated by prolonged neutropenia (ANC < 500) lasting greater than 2 months and bacterial sepsis. He developed grade IV vincristine-related neuropathy by the Balis scale grading system. Within weeks of initiating vincristine dosed at 1.5 mg/m2/dose, the patient became immobile and wheel-chair bound. He remained immobile for 12 months after vincristine therapy was terminated. He received cytarabine dosed at 125 mg/m2/dose via continuous infusion for 3 consecutive days after which the patient developed fever and profound myelosuppression. Because of new onset respiratory symptoms, a chest X-ray was obtained that revealed a right middle lobe infiltrate. CT scan of the chest showed a cavitary lesion consistent with fungal infection and he was placed on voriconazole. Five months after the diagnosis of T-cell ALL, the patient was referred to our center for evaluation for bone marrow transplant. Pretransplant bone marrow aspiration and cerebral spinal fluid showed no evidence of malignant cells. MRI of the brain revealed a left parietooccipital abscess and CT scan of the chest showed enlargement of the right middle lobe cavitary lesion and small bilateral nodules consistent with fungal infection (Figures 1 and 2). CT scan of abdomen and pelvis showed multiple soft tissue abscesses of the upper thighs which were drained and found to be sterile. Antifungal therapy was initiated. The patient underwent complete surgical resection of the left parietooccipital lesion and partial resection of the lung lesion. Hyphae consistent with Aspergillus were identified on histopathologic studies from lung and brain lesions. Aspergillus species was cultured from brain tissue. Hematologic remission was sustained with modified dosing of cytarabine and intrathecal methotrexate. Our patient received an approximately 50% dose reduction of cytarabine (60 mg/m2/dose) from the initial 125 mg/m2/dose he had received previously. Cytarabine was administered over 15 minutes for 3 consecutive days instead of a 24 hour infusion in order to reduce cell exposure to chemotherapy. Reduced dose of intrathecal methotrexate (50% reduction of age-based dosing) was given followed by leucovorin rescue. Twenty-four hours after the completion of chemotherapy, filgrastim (5 mcg/kg) was started. The patient tolerated these agents well, neutrophils recovered within 12 days, and there was no progression of aspergillosis or leukemia. One month after partial pulmonary aspergilloma resection and 4 months after complete parietooccipital aspergilloma resection, the patient underwent a 10/10 matched unrelated donor bone marrow transplant using a modified reduced-intensity preparative regimen. The patient received voriconazole 200 mg orally daily and micafungin 100 mg IV daily for 4 months prior to BMT. Galactomanman levels remained negative, and radiographic studies of the brain and chest showed improvement and no new fungal foci. The BMT preparative regimen included fludarabine 140 mg/m2, cyclophosphamide 40 mg/kg, thymoglobulin 6 mg/kg (total doses), and 450 cGy TBI. 3 x 106 CD34+ stems cells were obtained from the donor's bone marrow. T-cell depletion was achieved using rabbit ATG. GVHD prophylaxis included tacrolimus and mycophenolate. Neutrophils engrafted by day 14. There were no acute transplant-related complications. He received voriconazole for 6 months after BMT. At the time of this writing, 30 months after BMT the patient is without evidence of recurrent aspergillosis or leukemia, and continues to do well.
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PMC8177992_01
Male
28
A 28-year-old male with no significant medical history presented to our emergency room five days after sustaining a right-hand injury from a fall on an outstretched hand while playing basketball. On examination, there was swelling and tenderness on palpation at the base of the right thumb. Right hand radiographs (Figure 1) and CT with 3D reconstruction (Figure 2) showed a comminuted trapezium fracture. The patient was taken to the operating room seven days after his initial injury. A dorsal radial approach was used to expose the trapezium protecting the radial sensory nerves, radial arteries and EPL and EPB tendons. After exposing the trapezium, we reduced the fracture with a dental pick and provisional Kirschner wires. C arm was utilized throughout the procedure to confirm fracture and joint reduction as well as to appropriately size the screw. A 2 mm headless compression screw (HCS, Synthes Inc, West Chester, PA, USA) was utilized to definitively fix the fracture (Figure 3). Intraoperatively, there was excellent stability of the fracture and restoration of the articular surface. The patient's joint was immobilized with a thumb spica splint for two weeks. Unrestricted range of motion exercises as well as occupational therapy were initiated two weeks following surgery. Three months after surgery, repeated X-rays showed a healed trapezium fracture (Figure 4). During this time, his DASH score was 10 and his SANE score was 95. The patient demonstrated full range of motion of the thumb (Figure 5) and returned to all previous activities.
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PMC9218179_01
Male
78
On March 21st, 2022, the patient, a 78-year-old man, who had four negative nucleic acid tests and a fifth positive, was transferred to our hospital. He has been isolated in the designed hotel since March 17th, 2022, due to close contact with his daughter, a laboratory-confirmed COVID-19 patient. His daughter had worked with other laboratory-confirmed COVID-19 patients, who had close contact with the COVID-19 cases from other provinces. This patient described that he only had a mild cough and denied other symptoms, including fever, chills, sore throat, runny nose, chest pain, shortness of breath, muscle soreness, and fatigue. Chest computed tomography (CT) in the local hospital didn't show typical signs of COVID-19, like glass opacity, bilateral multifocal ground, peripheral distribution, and multilobe involvement. This patient had a 20-year history of primary hypertension and paroxysmal atrial fibrillation. His daily medication included one 40 mg telmisartan, one 5 mg amlodipine, and one 2.5 mg warfarin, all taken orally. He had a history of tuberculous pleurisy, which had already been cured for many years (details unknown). He also had a history of gallstone surgery about 26 years ago (details unknown). He had received inactivated COVID-19 vaccine (Sinovac Coronavac) two times (August 19th, 2021 and September 9th, 2021). This patient and his wife did not have a significant personal history. They had one son and one daughter, and the family medical history was unremarkable for any significant disorders. Upon admission, the detected temperature, pulse, respiratory rate, blood pressure, and oxygen saturation of the patient were within normal range. The auscultation of the heart revealed an irregular heartbeat and the varied intensity of the first heart sound. At the same time, there were no apparent abnormalities observed in the examination of the lungs, abdomen, and limbs. The baseline laboratory findings of this patient showed no obvious abnormalities (Table 1). Moreover, he tested negative for both anti-SARS-CoV-2 immunoglobulin (Ig) G and IgM antibodies. This patient had multiple positive reverse-transcription polymerase chain reaction (RT-PCR) results of SARS-CoV-2 nucleic acid during hospitalization [a cycle threshold (Ct) value <40 was defined as SARS-CoV-2 viral positive; Ct value of ORF1ab/N gene: March 21st, 10.22/7.46; March 22nd, 29.20/33.72; March 26th, 21.31/23.53; March 27th, 20.79/22.73]. The genome sequencing test confirmed the infection of the SARS-CoV-2 Omicron BA.2 variant. Based on the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia" (9th Trial Version) and the discussion of our COVID-19 expert group, this patient was diagnosed with a confirmed case of COVID-19. Then this patient received traditional Chinses medicine for 15 days (starting on March 23rd) and appropriate treatment for primary hypertension and paroxysmal atrial fibrillation. On March 25th, 2022, this patient developed a low-grade fever, with a maximum body temperature of 37.9 C. Chest CT revealed few pulmonary ground-glass opacities (Figure 1A). Later, on March 27th, this patient's body temperature rose to 38.5 C, and he presented with shortness of breath. The oxygenation index greatly decreased, with a minimum number of 115 mmHg. Re-examination of chest CT showed the pulmonary lesions increased significantly (Figure 1B). According to the Berlin definition, this patient was diagnosed with moderate ARDS. Meanwhile, the interleukin (IL)-6 dramatically rose to 1,137 pg/mL, and other inflammatory parameters:including white blood cell, percentage of neutrophils and C-reactive protein:were all increased than at admission. The number of lymphocytes decreased gradually, with the lowest value of 0.36 x 109/L. The coagulation parameters:including platelet, D-dimer, activated partial thromboplastin time, prothrombin time, and thrombin time:didn't change a lot over time. And the laboratory parameters of heart, liver, and kidney function didn't show signs of organ failure. Table 1 presents detailed results of laboratory parameters. Considering this patient's condition deteriorated rapidly, he was soon transferred into the intensive care unit. Our COVID-19 expert group conducted an urgent consultation, and a series of interventions were taken: (1) this patient had rapidly escalating oxygen requirements, therefore the high flow nasal cannula (HFNC) oxygen therapy (flow rate 50 L/min, oxygen concentration 50%) was administered. However, after several hours, his oxygenation index tended to decrease (oxygenation index = 115 mmHg), therefore we switched it to non-invasive ventilation (spontaneous/timed model, inspiratory positive airway pressure 10 cm H2O, expiratory positive airway pressure 6 cm H2O, fraction of inspired O2 40%); (2) this patient had a persistent fever, increased inflammatory parameters and radiographically observed pulmonary lesions, therefore co-infected with bacterial should be considered. This patient received piperacillin-tazobactam intravenously (4.5 g thrice daily); (3) methylprednisolone (40 mg once daily) was used to suppress cytokine storm for 3 days; (4) thymalfasin (1.6 mg once daily) and immunoglobulin (20 g once daily) were used to modulate immunity for 3 days; and (5) anti-hypertension (adalat, 30 mg once daily), anticoagulation (edoxaban, 60 mg once daily), stabilizing ventricular rate (digoxin, 0.125 mg once daily), and nutritional supplementation were used and adjusted according to the actual situations. After treatment, this patient's temperature fell to normal on March 28th, 2022. Although his temperature fluctuated in the following days, values were lower than 38.5 C. We observed a trend toward a reduced respiratory rate, and this patient had an improved symptom of shortness of breath. The oxygen index increased to 200-300 mmHg, and this patient was weaned from non-invasive ventilation on March 31st, 2022. Follow-up chest CT on March 30th and April 3rd showed the pulmonary lesions were further reduced (Figures 1C,D). Until April 3rd, this patient recovered well with no complications. Figure 2 presents the timeline of essential clinical parameters and management of this patient. On April 7th, this patient achieved two negative results of nucleic acid tests (Ct value of ORF1ab/N gene: April 6, 39.45/39.48; April 7, 35.36/39.68), and his oxygen index was 348 mmHg without fever and shortness of breath. Then, he was monitored for disease progress and continued the treatment program of the underlying diseases.
ards, covid-19, omicron ba2, clinical characteristics, therapy
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PMC5348461_01
Male
23
A 23-year-old man with a history of severe aplastic anemia (SAA) underwent bone marrow transplantation from his HLA-haploidentical mother in January 2014. The conditioning regimens consisted of busulphan cyclophosphamide and antithymocyte globulin (BUCY+ATG). Cyclosporine A (CsA) and short-term methotrexate (MTX) plus mycophenolate mofetil (MMF) were used as prophylaxis against graft-versus-host disease (GVHD). Standard measures were adopted for the prevention of infectious complications, which included fluconazole for antifungal prophylaxis and acyclovir to prevent herpes-related infections. A hemogram revealed the reconstruction of granulocytes (ANC>0.5x109/L) on day +12 post-transplantation. The patient developed grade II acute GVHD of the skin on day +42 post-transplantation. This was treated by treatment with a standard-dose of methyl-prednisolone, which achieved a complete response (CR). The patient's chronic GVHD (cGVHD) of the skin gradually progressed from day +100 post-transplantation and he was treated with prednisolone and CsA. On day 120 post-transplantation, he complained of a cough and antibiotics were administered. A blood analysis revealed the following: WBC, 2.34x109/L; ANC, 1.72x109/L; hemoglobin, 85 g/L; and platelets, 72x109/L. Although both a chest computed tomography (CT) scan and tests for pathogens via routine culturing, including blood tests for Beta-D glucan (G-test) and Galactomannan (GM-test) were all negative, the patient's cough did not respond to antibiotics and we empirically initiated treatment with voriconazole (6 mg/kg/12h for the first day, followed by 4 mg/kg/12h). Liver toxicity occurred during voriconazole treatment, thus the anti-fungal regimen was changed to micafungin (100 mg/d). However, the persistent cough did not improve and hoarseness developed after two weeks of treatment - ulcers were then observed in the throat by laryngoscopy (Fig. 1a). The patient developed severe dyspnea in the following week when anti-infection and topical treatments were applied. Fiberoptic bronchoscopy revealed an irregular, nodular material with white moss, which nearly obstructed the bronchus; however, chest CT imaging was negative (Fig. 1b and c). The histopathological examination of biopsy specimens revealed an Aspergillus species (Fig. 1d). The patient was diagnosed with pseudomembranous Aspergillus tracheobronchitis type ITBA based on the results of bronchoscopy and a pathological examination. The antibiotic and micafungin treatments were ceased and liposomal amphotericin B (liposomal AmB) was administered daily at a target dose of 3 mg/kg. The patient's serum creatinine level rose from 60.4 mumol/L to 168 mumol/L during the first 7 days of liposomal AmB treatment. Due to progressive renal dysfunction, the anti-fungal regimen was switched to a combination of posaconazole (400 mg/12 h) and caspofungin [50 mg, daily (70 mg for the first dose)]. The combination therapy continued for 2 weeks, until the previous nodules in the throat completely disappeared under bronchoscopy (Fig. 2a); however, a repeat chest CT scan showed progression (Fig. 2b). The symptom of dyspnea gradually progressed, thus fiberoptic bronchoscopy was performed to remove the obstructive material from the patient's airways once a week for two weeks. All of the symptoms were relieved and the final chest CT scan showed negative results before the discontinuation of anti-fungal therapy, and all of the tests were negative for Aspergillus. Posaconazole was administered as a secondary prophylactic treatment and the patient was discharged from hospital. The patient is still being followed and remains free of any recurrence of invasive fungal infection.
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PMC8581772_01
Male
31
A 31-year-old Caucasian man presented to our clinic with a 4-month history of a solitary mass on the left mandibular area believed to be an abscess. It was slightly tender and exuded pus from several openings within the mass. He had a history of being HIV positive for 7 years. His HIV was well controlled on once daily oral Biktarvy containing bictegravir, emtricitabine, tenofovir, and alafenamide, and he had a normal CD4+ count and an undetectable viral load. Clinical examination showed a 5 by 5 cm erythematous mass with a rough surface and a few draining sinuses over the right mandibular area (Figure 1). A previous X-ray showed no evidence of periostitis or bone destruction and he had previously seen a dentist and a dental sinus was ruled out. The differential diagnosis when seen included infectious causes such as actinomycosis, a deep fungus, tuberculosis (TB), and atypical mycobacteria. Two 4-mm punch biopsies were done, one for histology and one for cultures. Skin biopsy showed a squamous-lined cystic structure at the deep biopsy edge compatible with a sinus tract (Figure 2). Periodic acid-Schiff (PAS), Grocott's methenamine silver (GMS), Ziehl-Neelsen (ZN), and Fite stains were all negative. Cultures sent for aerobic and anaerobic cultures grew a few Staphylococcus aureus but were negative for Actinomyces species. Tissue culture for deep fungus, TB, and atypical mycobacteria were all negative. He was treated with oral doxycycline 100 mg PO BID for 2 months, and when reassessed, the morphology of the lesion had markedly changed (Figure 3) to a flesh-colored indurated plaque with marked cribriform scarring. A full skin examination at this time showed no lesions in the axillae, groin, and buttocks except for a 5-mm depressed scar in the left lower abdomen which the patient attributed to an "ingrown hair." At this time, the clinical appearance suggested HS localized to the face. An incisional biopsy from the plaque including an area of cribriform scarring was submitted for pathology and showed an acute folliculitis with deep dermal fibrosis and a lymphoplasmacytic infiltrate. All repeated cultures were negative. He was put on a course of oral isotretinoin and the plaque was injected with intralesional triamcinolone acetonide 10 mg/cc and he has a good response to this treatment.
hidradenitis suppurativa, face, human immunodeficiency virus
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PMC8523264_01
Male
30
A 30-year-old male with no previous medical history presented to the endocrinology department in 2013 with loss of body hair. The clinical examination showed a loss of axillary and facial hair (beard). The general examination of the patient was unremarkable. In particular, the neurological exam was normal. The endocrine workup showed decreased testosterone levels with inappropriate gonadotropin levels (testosterone: 0.18 ng/mL [3-12 ng/mL], FSH: 0.63 mUI/mL [1.3-11 mUI/mL], and LH: 0.59 mUI/mL [1.1-10 mUI/mL]) and a slightly elevated prolactin level (20.3 ng/mL [2-10 ng/mL]) concluding to an isolated hypogonadotropic hypogonadism (TSH: 0.99 muUI/mL [0.25-4.5 muUI/mL] and FT4: 16.11 pmol/L [9-24 pmol/L]). The 1 mug synacthen test revealed appropriate cortisol levels in response to the stimulation test. The ophthalmologic examination showed preserved visual acuity and a normal fundus examination. MRI of the brain and sella showed a large suprasellar mass with cerebral and spinal leptomeningeal spread (Figures 1-3). A lumbar puncture revealed no pathological findings. Polymerase Chain Reaction (PCR) evaluation for Mycobacterium tuberculosis in the cerebrospinal fluid (CSF) was negative. Tumor markers in the blood and the CSF were also negative. The converting enzyme dosage revealed normal levels, making the diagnosis of sarcoidosis unlikely. A thoracoabdominal-pelvic CT scan did not show any associated lesions. The patient was referred to the neurosurgery department, and a biopsy of the arachnoid leaflet and the dura mater was taken. On exploration, the arachnoid was thick and blackish. The histopathological examination was suggestive of a grade I meningeal pigmented melanocytoma. An androgen replacement therapy was instaured, and then, a dopaminergic agonist (bromocriptine) was added due to the increase in prolactin levels reaching 50-60 ng/mL. Total resection of the tumor, as well as the meningeal spread, was not possible. The patient refused any radiotherapy. Owing to the benign nature of the lesion and the absence of neurological or ophthalmological impairment, we opted for clinical and radiological monitoring. The patient was then lost to follow-up. He consulted in 2020 for a sudden drop in visual acuity. The fundoscopy showed stage 3 papillary edema. The neurological exam of the patient was normal. An MRI was urgently done to reveal an increase in the size and number of leptomeningeal seeding complicated by obstructive hydrocephalus (Figure 4). The CT scan showed no abnormalities other than well-defined intraspinal masses (Figure 5). The patient was urgently rereferred to neurosurgery, and treatment with radiotherapy is currently being discussed.
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PMC7102419_01
Male
5
A 5-year-old boy with a history of uncontrolled, moderate-persistent asthma presented to the pulmonology clinic for asthma management. The patient had a previously normal developmental history, up-to-date immunization record including Streptococcus pneumoniae and Haemophilus influenzae, and notable past medical history significant for recurrent otitis media due to poor compliance to oral antibiotics, which were subsequently successfully treated with parenteral antibiotics. Upon presentation, the patient recently had a left lower lobe community-acquired pneumonia that was treated with one dose of intramuscular ceftriaxone in the emergency department followed by a standard 10-day course of amoxicillin. The patient's family was instructed to open the capsule and mix the powder with food to improve compliance due to known history of poor palatability with previously prescribed antibiotics. The patient returned to the emergency department two weeks later with worsening of symptoms and was treated with oral cefdinir for unresolved pneumonia. He was subsequently seen in the pulmonology clinic four days later to establish care without acute complaint. He was started on fluticasone/salmeterol and a five-day course of oral prednisolone for management of an acute asthma exacerbation. One month later, the patient presented to the emergency department with fever and increased cough and was diagnosed with right middle lobe pneumonia. He was treated with intramuscular ceftriaxone to be followed with a home course of oral antibiotics, which was reportedly completed. Two weeks later, the patient again presented to the emergency department with recurrent symptoms and diagnosed with right lower lobe pneumonia that failed outpatient treatment. The patient was subsequently admitted to the medical floor and managed with a single dose of intravenous ceftriaxone. He was discharged the following day in stable condition on cefdinir and azithromycin. The patient was to follow-up as an outpatient with his pulmonologist and primary care physician. Hospital laboratory work including CBC with differential, peripheral blood cultures, sweat chloride test, immunoglobulin assay, T cell count, and Aspergillus antibody was unremarkable. At the two-week follow-up, he had persistent fever, wheezing, daytime and nighttime cough, shortness of breath, exercise intolerance, and difficulty breathing. The patient was scheduled for further evaluation with high-resolution chest CT without contrast and flexible bronchoscopy with bronchoalveolar lavage and nasal cilia biopsy to evaluate for Primary Ciliary Dyskinesia (PCD). Repeat chest X-ray at that time revealed an improved right lower lobe consolidation without complete resolution, as expected. CT scan revealed a mild degree of bronchiectasis in the lower lobes, bilaterally, associated with consolidation on the right and linear atelectasis and scarring on the left with other nonspecific evidence of chronic inflammatory versus infectious process. Bronchoscopy identified multiple mucus plugs in the right bronchus intermedius (Figures 1-3), right middle lobe (Figures 4 and 5), and right lower lobe (Figure 6). Gross inspection of the bronchoscopy sample revealed a solid, rock-like mucus plug (Figure 7). Airway clearance via a high-frequency chest wall oscillation vest along with nebulized therapies was initiated. The patient did not tolerate postoperative oral azithromycin and required mixing with grape juice. One week following the procedure, he was readmitted for recurrent fever and a new rounded lucency on chest X-ray in the right lung base, suspicious for cavitation or pneumatocele. Chest CT demonstrated a 2.5 x 3.2 x 3.7 cm area of cavitation within a region of consolidation or bronchiectasis in the posterior aspect of the right lower lobe with mediastinal and right hilar adenopathy, suspicious for cavitary bacterial pneumonia or fungal disease (Figure 8). Home treatment continued with the addition of intravenous ceftriaxone. Bronchoalveolar lavage culture from the previous week grew beta lactamase negative Haemophilus influenza and Moraxella catarrhalis. Fungal culture, mycobacterial culture, bronchial aspirate cell count, cytology, gastrin pepsin assay, and pathology report were all unremarkable. A PICC line was placed for 3 weeks of home antibiotics as a management for complicated cavitary pneumonia. Further workup included QuantiFERON-TB Gold, HIV assay, complement assay, tetanus antibody, diphtheria antibody, and pneumococcal antibody which were all unremarkable. At 3-week follow-up post hospitalization, the patient was symptomatically improved without coughing or fever and he was reported to be back to his baseline. The mother reported adherence to antibiotic regimen through the PICC line. He continues maintenance therapy with fluticasone/salmeterol, montelukast, and vest therapy. He was started on oral azithromycin three times weekly. At the two-month follow-up, the patient remained asymptomatic, and repeat imaging at the nine-month follow-up revealed complete resolution of cavitating consolidation with residual bilateral mild bronchiectasis (Figure 9).
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PMC7717955_01
Male
29
The subject of this report is a 29 year old male, US citizen of Palestinian descent, who works full-time as a biomedical research technician. His health history is unremarkable, except for the fact that at age 16 he was diagnosed with ulcerative colitis and primary sclerosing cholangitis. Since then, he has been treated successfully with mesalamine (1.2 g, 2 times per day), azathioprine (50 mg, 3 times per day), and ursidiol (300 mg, 2 times per day). The subject has been able to live an active lifestyle and participate in a variety of sports including running, weightlifting, basketball, and baseball. The subject denies any history of smoking or use of alcohol, opioids, or illicit drugs. On April 22, 2020, the subject's father, who lives in the same house as the subject, and works for a major shipping company, was diagnosed with COVID-19. This was about 2 months after the first case of COVID had been confirmed in his state of residence, which was one of the early active zones of COVID-19 transmission in the US. On April 25, the patient began to experience general malaise and fatigue. Over the next 24 h, the symptoms worsened to include severe fatigue and weakness, loss of appetite, tiredness, slight dry cough, body aches, muscle pain, loss of taste and smell, sore throat and fever. The patient was then seen by his general practice physician. Vital signs at the time of examination were BP 110/72, pulse 97 BPM, respiration 14 per minute, oxygen saturation 98%, and body temperature 101.7 F. The patient was given a naso-pharyngeal swab, real-time RT-PCR test [COBAS (R) SARS-COV-@ test, Labcorp Laboratories, South Bend, IN] that confirmed a diagnosis of COVID-19. In compliance with standard medical practice standards, the patient was ordered to self-isolate and to start a 5-day course of azithromycin (250 mg, daily), and to also take 1 g of paracetamol (acetaminophen) every 6 h for treatment of pain and fever. Despite good adherence to the recommended treatment, the symptoms other than fever, did not improve, and he also started to feel depressed, demotivated, and spend long periods in bed. During this period, the patient experienced ongoing generalized myalgia and musculoskeletal pain. He described the pain as persistent and relatively severe (rated 7 on a scale of 1-10). Because of this discomfort, after 4 days the patient decided to consume kratom to relieve his symptoms. According to the patient, he had first used kratom 14 months earlier before his COVID-19 infection. He used kratom sporadically (no more than 4-5 times in total) as a cognitive enhancer and not to self-treat pain. The patient decided to take 2.5 gms (or grams) of green kratom (as ground leaf powder suspended in water). The product was purchased at a local shop in April 2020 sold under the name "Green Bali." After 30 min, he noticed a significant improvement in the intensity of the physical symptoms (mainly pain and fatigue), and within 60 min he felt a sensation of mild euphoria and well-being that lasted for about 5 h. After 6 h following consumption the effects of kratom wore off, and the patient administered another dose. He used kratom three times a day continuously for 3 days (for a total of 9 doses of 2.75 g each) with significant benefit. When asked to score from 0 to 100% the improvement that kratom had on COVID-19 symptoms: fatigue and weakness (80% improvement), tiredness (70% improvement), body aches (80% improvement), muscle pain (90% improvement, "much better than paracetamol/acetaminophen"). The kratom did not seem to have an impact on: fever, cough, or sore throat. The patient also stated: "I didn't have anxiety or any psychological symptoms. For me, kratom mainly gave improvement in physical reaction." "It also elevated my mood and made me feel less miserable, to the point where I was able to get out of bed, shower, look at work emails without feeling completely exhausted and drained"; "Kratom helped me more than antibiotic"; "I slept better, I essentially fell asleep immediately. Without kratom, sleep was not nice, with kratom less wake ups, about 6 h." Over the next 2 weeks the patient's symptoms gradually subsided and on May 13 he had a televisit with his physician and a follow-up swab test that was negative for COVID-19. The subject was able to end his quarantine and return to work in early June. In a follow-up interview with us, the patient reported that he did not experience any side effects from using kratom, except for a very bad taste when swallowing it. The patient was also able to discontinue kratom use immediately without any evidence of physical or psychological withdrawal symptoms. The patient also informed us that he still had some of the kratom product that he had taken and he agreed to provide us with a sample for chemical analysis. An established quantitative liquid chromatography mass spectrometry method was conducted and found that the sample obtained from the patient is kratom due to the presence of mitragynine (102 mg/g kratom powder) and 7-hydroxymitragynine (0.8 mg/g kratom powder). The extracted kratom sample was analyzed for the presence of 13 opioids and 8 benzodiazepines by comparing the chromatograms to those of the reference mixtures Pain Management Multi-component Opiate Mixture-13 solution and Benzodiazepine Multi-component Mixture-8 solution. These data suggest the sample was not fortified with 7-hydroxymitragynine and there was also no evidence of adulteration with opioids or common benzodiazepines in the sample.
covid-19, kratom, long covid, new psychoactive substances, new treatments, opioid, stimulants
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PMC5844233_01
Male
42
A 42 years old male teacher referred to our hospital complaining of the 15-day history of progressive back pain radiating to both thighs. He subsequently developed weakness affecting both lower limbs, but mainly on the left side, with urinary incontinence and constipation. It was associated with low-grade fever, loss of appetite and ended with the inability to walk. On examination, he looked pale and uncomfortable. He had a pulse rate of 95 beats per minute, blood pressure 110/70, temperature 38.3 C, and a respiratory rate of 19 cycles per minute. Inability to walk, severe tenderness in the back around the midline and paraspinal region, and severe limitation of spinal motion. Sensation: paresthesia below the inguinal ligaments in both lower limbs. grade 2 knee extension; grade 1 knee flexion; grade 1 ankle dorsiflexion; grade 1 ankle plantar flexion. Left side: grade 3 knee extension and flexion; grade 2 ankle plantar flexion and dorsiflexion. Right side: diminished knee and ankle jerk; equivocal Babiniski sign. urinary incontinence; constipation. Hemoglobin 11.1 g/dL, white blood cell count 11 x 109 with lymphocytosis (60%), essential sedimentation rate 95 mm/hour, C-reactive protein 90, random blood sugar 114 g/dL, blood urea 78 mg/dL, and serum creatinine 1.3. Plain X-ray of the lumbosacral spine in both Antero-posterior and lateral view revealed no abnormality. MRI of lumbosacral spine in both T1, T2, and STIR showed a localized collection of pus in the canal compressing the dural sac at L3, L4 and L5 levels with a small collection of pus at L2-L3 level. Also, there were multiple pockets of pus in the paraspinal muscles (Figures 1-3). After discussing the treatment options with the patients, we decided to proceed with surgery. Using a posterior midline approach, in a prone position and under general anesthesia, the paraspinal muscles were dissected. We noticed multiple pockets of pus imbedded in the paraspinal muscles, mainly on the left side, which were evacuated. Then a laminectomy of L3-L4 was done with hemilaminectomy at L2-L3 and L4-L5. Pus was draining from these levels through the spinal canal. Samples were taken from pus, laminae bone, and soft tissue and sent for histopathological and microbiological studies. Thorough irrigation and debridement were done, a drain was applied, and the wound was closed in layers. The patient was kept on broad-spectrum antibiotics for 14 days pending microbiological laboratory results. Microbiological results showed no growth of bacteria, Acid Fast Bacilli was negative, but Polymerase chain reaction (PCR) was positive. Histopathological study: sections showing calcified mature bony trabeculae and degenerative cartilaginous tissues component in between marked hematopoietic depletion, dense chronically inflamed fibrous replacement including heavy mixed chronic inflammatory cells which include foamy histiocytic and mature lymphocytic cells infiltrate. Multiple ill-defined granulomas were seen with obvious extra bony inflammatory extension to the surrounding soft tissue and skeletal, muscular tissues. The final impression was a chronic specific tuberculous granulomatous spinal cold abscess. Anti TB antibiotics were started after the above results became available. Postoperatively, gradual neurological recovery occurred in both lower limbs. At one month follow up, the right lower limb had full motor recovery (grade 5), while the left lower limb was weaker on knee flexion and ankle dorsiflexion (grade 4). The patient was still incontinent to urine and constipated. At two months after surgery, the left lower limb showed further neurological improvement (grade 4+), and though the patient reported some improvement of his sphincter control, he was still complaining of nocturnal incontinence and constipation. A follow-up MRI at two months of index surgery showed complete abscess resolution with good decompression of the cauda equina region (Figure 4). Surprisingly, The images also showed signs of spondylitis of L5. Because the clinical condition of the patient was improving, there were no signs of discitis nor vertebral collapse, the patient was further treated conservatively. Five months later, he recovered both lower limbs motor strength and full control of his sphincters.
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PMC7563086_01
Male
57
A 57-year-old man was received in our department with a long acting fever, which had been developing for 3 months, weight loss, and profuse night sweats. He was a smoker (pack years were 10) and had neither regular medication nor a particular medical antecedent. Physical examination showed a poor performance status (PS = 4/5), clinical anemia, and diffuse lymphadenopathies at different sites: cervical, axillary, and inguinal. Pain and inflammatory swelling were also found particularly on knees, elbows, and interphalangeal joints. Pulmonary examination showed a diminution of vocal fremitus and the presence of coarse precipitations on the left side. Physical examination also revealed a 7 cm subcutaneous nodule, located in the anterior face of the right arm. Blood count results showed hyperleukocytosis associated with anemia and thrombocytopenia (HB: 9.1 g/dl, MCV: 94 fl, WBC: 22600/mm3 with neutrophils: 53% and lymphocytes: 36%, and PLQ: 34400/mm3). Antinuclear autoantibodies were positive, and rheumatoid factors were high: 62 IU/ml. No bone marrow involvement was found after cytological examination. A thoraco-abdominopelvic CT scan was performed and showed the presence of mediastinal and abdominal lymphadenopathies with necrotic centers and bilateral basal pneumopathy (Figure 1). Diagnosis of multifocal tuberculosis was retained based on clinical symptoms and cytological examination of lymph node sample obtained by fine needle aspiration showing aspect of tuberculous adenitis and CT imaging. Antituberculosis (TB) treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol) was administered for two months, but it did not reduce clinical signs. A lymph node biopsy was then performed, and pathological analysis revealed a diffuse lymphomatous proliferation consisting of large atypical cells with clarified nuclei and immunostaining showed a lymphoid proliferation consistent with the diagnosis of AITL : EBV+, CD3+, CD5+, CD2+, CD4+, CD278+, CXCL13+, PD1a+/-, CD10+, and Ki67+. The time from the onset of signs to definitive diagnosis of AITL was 5 months. The patient was diagnosed at an advanced stage and was classified as IPI3 (Ann Arbor: IIIBb, PS: 4, and lactate dehydrogenase: 680 U/L). Pretherapeutic evaluation revealed hyperuricemia and polyclonal gammaglobulinemia; all other results were normal (serology of HIV, hepatitis B and C, ionogram, urea, creatininemia, 24 hours proteinuria, alanine aminotransferase, aspartate aminotransferase, bilirubinemia, C-reactive protein, prothrombin time, activated partial thromboplastin time, fibrinemia, fasting blood glucose, and cardiac ultrasound). Chemotherapy according to CHOP protocol (cyclophosphamide: 750 mg/m2, hydroxydaunorubicin: 50 mg/m2, vincristine: 1.4 mg/m2, and prednisone: 40 mg/m2), applied every 21 days, was performed. After 8 cycles of CHOP, complete remission was achieved with normalization of clinical and biological anomalies. A relapse occurred 5 months later, and treatment consisted of 2 additional CHOP cures followed by 2 COP cures. A complete clinical and radiological remission was achieved again. Currently, one year after stopping treatment, the patient remains with no clinical symptoms; biological and morphological explorations are normal. Considering complications during treatment, febrile neutropenia was noted after the first treatment, and the patient was treated with G-CSF and antibiotics (3rd generation cephalosporin + gentamicin) for a duration of 10 days. Other complications were alopecia and nail hyperchromy.
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PMC3336222_01
Male
53
Our patient was a 53-year old previously healthy, nonsmoker with no reported unusual recent exposures, male who presented to an outside hospital with severe respiratory distress. He was started on empiric broad-spectrum antibiotics and oseltamivir phosphate (150 mg PO BID, Tamiflu, Genentech, Inc., San Francisco, Calif, USA) and Methylprednisolone (60 mg intravenous, Q6H for 3 days). Initial bacterial blood and respiratory cultures were negative, but had a positive nasal swab for Influenza H1N1. Initial chest X-ray showed severe diffuse pulmonary infiltrates and edema consistent with adult respiratory distress syndrome (ARDS, Figure 1). Five days later, due to failure of maximal mechanical ventilation and worsening hypoxemia with hypercarbia he was placed on percutaneous veno-veno ECMO and transferred to our Institution. Upon arrival, bacterial and fungal blood, urine, and respiratory cultures from a bronchial alveolar lavage were obtained and were negative. Real-time polymerase chain reaction assay was positive for H1N1-2009. Other viral cultures, including HIV-1/-2 and a hepatitis panel, were negative. A transthoracic echocardiogram was unremarkable. Over several days, antibiotic therapy was deescalated, and he completed a 10-day course of oseltamivir. After 7 days of ECMO support, he was successfully weaned and decannulated. His ventilator requirements slowly improved, and despite an Enterobacter aerogenes ventilator-associated pneumonia that developed post-ECMO decannulation, the remainder of his hospital course was unremarkable. He was discharged for rehabilitation 22 days after ECMO decannulation (hospital day 31). At followup, 4 months following-discharge, he was doing well, repeat chest X-ray showed no evidence of acute or chronic disease, and pulmonary function testing showed normal spirometry, a mild restrictive ventilatory defect, a mildly impaired diffusing capacity (23.6 ml/min/mmHg, 74% predicted), and a normal 6-minute walk (515 meters, normal: 365 meters). In discussion with the patient, he recalled having been vaccinated against "the flu". Following appropriate release of medical records, it was confirmed that 2 months prior to the onset of symptoms he received 0.5 ml of inactivated trivalent influenza vaccine in the left deltoid (Fluzone, Sanofi-Pasteur Inc., Swiftwater, Pa, USA). Vaccination was provided by a local Pharmacy run vaccination clinic with established policies and procedures conforming to State and Federal regulations regarding the storage and administration of vaccines. No postvaccination problems were reported. Influenza H1N1-2009 was a formidable challenge worldwide during 2009 in terms of severity of illness and ease of transmission, particularly in otherwise young and healthy patients. The Australian experience estimated 1.6-2.6 cases per million required ECMO following infection with H1N1. In the 68 patients who required ECMO the mortality was 21%:a rate much greater than expected with recent seasonal Influenza outbreaks. Large-scale vaccination efforts were undertaken to minimize the spread and impact of the evolving pandemic. While the immunogenicity of the vaccine has been documented, the incidence of seroconversion is variable. In one study, only 75% of adults seroconverted while another study demonstrated a 95% seroconversation rate within 21 days in those adults who received a single 15 ug dose of a trivalent, unadjuvanted, inactivated, split-virus vaccine. Regardless, given inherent variability in antigenicities and immune responses, with such a large population at risk, even a small percentage of vaccine failure can have a significant epidemiologic impact. Furthermore, considering the virulence of H1N1-2009 the risk of developing catastrophic respiratory failure requiring high-intensity ventilator or even ECMO support is not negligible.
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PMC4283393_01
Male
14
A 14-year-old previously healthy boy presented with left periorbital swelling and redness for 1 year and muscle weakness and joint pain for 4 months. On examination he had purple discoloration and swelling around the left eye (Figure 1(a) before therapy and Figure 1(b) after therapy), Gottron's papules over the metacarpophalangeal (MCP) joints bilaterally, and muscle weakness with a grade of 3/5 in the proximal group and 4/5 in the distal group. Workup revealed a normal CBC, ESR 33 mm/hr, and CRP 0.383 mg/L. Liver function test showed the following abnormalities: AST 281 U/L, ALT 95 U/L, GGT 24 U/L, ALP 149 U/L, and CK 4585 U/L. Antinuclear antibodies negative with ENA are all negative. Renal function test and thyroid function test were normal. MRI muscle revealed diffuse muscle edema involving the muscles of the pelvis, thighs, legs, and upper extremities as well as the muscle of back suggestive of inflammatory myopathy. CT orbital shows soft tissue swelling in the anteromedial and superior aspects of the left orbit which shows minimal enhancement in the postcontrast, there was an appearance of a left-sided preseptal periorbital cellulitis with no evidence of abscess formation. Biopsy from the lower lid revealed no malignant cells or acid fast bacilli with subsequent negative culture for tuberculosis after 8 weeks. Muscle biopsy was performed and revealed mildly and focally increased endomysial and perimysial connective tissues. There was perivascular chronic inflammatory cells infiltration in the perimysial areas with few mononuclear inflammatory cells that were scattered in-between the muscle fibers. The muscle fibers showed mild to focally moderate variation of size and shapes and the majority had peripheral nuclei. Scattered foci of myofiber necrosis and regeneration were evident. Perifascicular atrophy was not a prominent feature, but it could be focally appreciated (Figure 1(c)). Ultrastructural examination revealed findings that were in keeping with light microscopy, including prominent myofibrillar disarray (Figure 1(d)). In addition, scattered rod-like structures and cytoplasmic bodies were detected. The overall features were in keeping with an inflammatory myopathy, with features suggestive of dermatomyositis. Skin biopsy of the left lower lid showed evidence of mild hyperkeratosis in the epidermis. The dermis showed heavy chronic inflammation cell infiltration that consists mainly of lymphocytes and plasma cells, infiltrating the hair follicles. Adjacent mild dermal fibrosis, focal solar elastosis, and pigment incontinence are noted. The patient was started on prednisolone 50 mg daily with an increasing dose of methotrexate 15 mg reaching 20 mg per week. At 6 months, the patient showed a dramatic improvement with normalization of muscle power, fading of the skin rashes, and reduction of muscle enzymes. As of April 2014, he is back to school with a normal performance on prednisolone 5 mg daily and methotrexate 20 mg weekly.
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PMC5828086_01
Female
66
A 66-year-old female patient without medical history or professional exposures was diagnosed with ankylosing spondylitis 12 years ago. She had formerly responded to nonsteroidal inflammatory drugs. In 2006, she started treatment with infliximab, due to poor therapeutic response to various NSAIDs. After eight years of remission, the patient had repeated flares of ankylosing spondylitis symptoms with increased inflammatory back pain. In August 2015, due to persistent clinical activity with increased acute-phase reactant levels (C-reactive protein level of 16 mg/l), the treatment with etanercept at 25 mg twice weekly was started. Following national guidelines to exclude latent tuberculosis, mycobacterium tuberculosis research in sputum and interferon-gamma test were negative and a chest radiograph was normal. Two months after etanercept therapy onset, the patient developed persistent dry cough and dyspnea without fever or night sweating. Physical examination was unremarkable apart from tachypnea and severe spinal stiffness. High-resolution computed tomography (HRCT) scanning showed mediastinal lymphadenopathy and multiple nodules in both lung fields (Figure 1). Echocardiography was normal. The blood analysis demonstrated ESR 35 mm/h, CRP 14 mg/l, and normal renal and hepatic function tests. Sputum culture and polymerase chain reaction and interferon-gamma release assays were negative. Viral serology (human immunodeficiency virus, hepatitis B virus, and hepatitis C virus) and syphilis serology were negative. Serum angiotensin-converting enzyme was very elevated at 147 UI/ml (reference range 8-52 UI/ml). Calcemia and calciuria tests were normal. The pulmonary function test showed restrictive ventilatory alteration. It was not possible to perform neither bronchoscopy nor thoracoscopy because of respiratory failure and severe ankylosis of the cervical spine. Histopathological examination of minor salivary gland biopsy revealed a chronic granulomatous sialadenitis without caseous necrosis (Figure 2). Diseases showing similar histologic changes were excluded, and a diagnosis of sarcoidosis was made. Etanercept was discontinued plus a course of corticosteroids with 40 mg/day of prednisone for two months. An evident improvement of cough and dyspnea was seen. Follow-up HRCT 4 months later showed regression of mediastinal lymph nodes and pulmonary nodules (Figure 3).
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PMC5822822_01
Male
44
Our patient is a 44-year-old male who was brought in by ambulance for altered mental status. As per the patient's wife, the week prior to admission he began staring off in space and responding to internal stimuli. His mentation deteriorated, and he began hallucinating and became aggressive, at which point she brought him to the emergency department. Six months prior to admission, he was diagnosed with metastatic renal cell carcinoma and underwent primary cancer removal with subsequent right nephrectomy. He was found to have multiple leiomyomas and was referred to the National Cancer Institute in Maryland. Genetic testing showed autosomal dominant Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC). Follow-up L-spine MRI for back pain showed extensive metastasis to the lumbar spine, sacrum, and right and left ilium. He was started on targeted immunotherapy of nivolumab and given a single dose of 240 mg two weeks prior to admission. On presentation, he was febrile and unable to communicate. He was acutely encephalopathic and responding to internal stimuli. During the interview, he was experiencing and responding to auditory, visual, and tactile hallucinations. On admission, his blood pressure was 122/86 with a pulse of 118 and temperature of 100.8 F. Chest X-ray showed no signs of pneumonia or metastases. Brain MRI showed no evidence of metastases or lymphoreticular disorder. Blood work showed an elevated white blood cell count of 16.61, unchanged from a previous admission due to home medication of Decadron. Serum Na was 132 with AST/ALT 36/72, TBili 0.5, alkaline phosphatase 246, and a creatinine of 2.0 at his baseline. Urinalysis performed in the ED showed packed hyaline casts without superimposed urinary tract infection. Blood cultures were drawn, and he was started on normal saline and oxygen. His home medications included methadone, naproxen, omeprazole, oxycodone, risperidone, hydromorphone, trazodone, benzonate, dexamethasone, buproprion, cyclobenzaprine, and ondansetron. Given the nature of the patient's pain and the severity of his illness, all of his home medications were continued. He was started on Haldol for agitation and transferred to the medical intensive care unit for treatment of encephalopathy. On examination, he exhibited garbled speech and continued encephalopathy. Initial attempts to sedate the patient using ketamine were effective and resulted in increased lucidity. He eventually became hypertensive and required treatment with Precedex while in the MICU. After 5 days in the MICU, the patient was found to be speaking in short sentences and was alert, awake, and oriented to person, place, and time with no signs of encephalopathy. Blood cultures throughout the stay showed no growth. Given the patient's lack of metabolic abnormalities, acute infection, continuation of all home medication throughout the hospital stay, and temporal resolution of symptoms after removal of nivolumab, he was diagnosed with nivolumab-induced encephalitis. The patient was discharged home on his home medications and scheduled for outpatient radiation therapy with discontinuation of nivolumab. After a short stay at home, patient was advanced to hospice and soon after passed away from metastatic renal cell carcinoma.
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PMC6560998_01
Male
58
A 58-year-old man presented to our hepatogastroenterology clinic with non-colicky pain in right hypochondrium and vomiting for 1 month. The pain was mild in intensity, dull, aching in nature, gradual in onset and progressive in course. It was non-radiating and not associated with meals. There was history of weight loss of 3 kg over a period of 1 month. There was no history of jaundice and tuberculosis or exposure to tuberculosis in the past. The general physical examination was unremarkable. There was no lymphadenopathy or abdominal visceromegaly. The laboratory investigations revealed raised ALP, 111 IU/L, Gamma-glutamyl transpeptidase (GGT), 61 IU/L and erythrocyte sedimentation rate (ESR), 70 mm/1sth; while complete blood count (CBC), renal function tests, coagulation profile and CA 19-9, 18.9u/ml (normal: 0-31u/ml) were within normal limits. Ultrasonography (US) of the abdomen revealed distended and irregular thick walled GB. Computed tomography (CT) of the abdomen revealed GB with irregularly thickened wall in the region of the fundus. There was an illness defined hypodense area extending from the body of GB to adjacent hepatic parenchyma measuring 3.0x1.5 cm and an enlarged lymph node at porta hepatis measuring 2.0x1.5 cm. The above constellation of findings raised a radiological suspicion of malignant lesion of GB (Figure 1). Bone scintigraphy and CT chest were negative for metastatic deposits. Based on the clinicoradiological diagnosis of GB carcinoma, extended cholecystectomy was planned. Diagnostic laparoscopy was done to get tissue diagnosis prior to the definitive procedure. It revealed adhesions around liver with multiple small whitish spots on its surface. Liver lesion biopsy was taken as well as two lymph nodes removed and sent for frozen section. The histopathological evaluation of frozen section of liver tissue revealed numerous caseating epithelioid granuloma containing Langhan's giant cells, consistent with tuberculosis (Figure 2). The sections examined from lymph nodes revealed benign reactive changes. Based on these findings, exploratory laparotomy was not done and the wound was closed. Patient was prescribed anti-tuberculous treatment (ATT) for one year. After 4 months of starting ATT, the patient improved markedly. His clinical symptoms completely disappeared. Repeated laboratory investigations revealed ESR 10 mm/1sth, and liver function tests (LFTs) also returned to normal levels. He is still on treatment and on regular follow-up.
carcinoma, frozen section, gall bladder, liver biopsy, tuberculosis
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PMC3600993_01
Male
42
A 42-yr old man initially presented with exertional dyspnoea and cough. He had no previous medical history of significance and was a non-smoker. The clinical examination and biochemistry were unremarkable, except for elevated serum angiotensin converting enzyme (ACE). Chest x-ray showed bulky hilar lymphadenopathy with extensive reticulonodular and mass like opacities in both lungs with a middle zone predominance (Figure 1). A non-contrast computed tomography (CT) scan of the thorax demonstrated numerous nodules in a perilymphatic distribution (subpleural and peribronchovascular) together with perihilar conglomerate masses (Figure 2). Several enlarged partly calcified hilar, paratracheal and subcarinal mediastinal lymph nodes were evident. Histopathology of a transbronchial lung biopsy showed numerous well-formed, non-necrotising epithelioid granulomas (Figure 3), but tests for bacilli, fungi and tuberculosis were negative. Based on clinical, radiological and pathological findings the diagnosis of pulmonary sarcoidosis was made. Five years after initial presentation the patient represented with dyspnoea and peripheral edema. ACE was within normal limits and electrocardiogram (EKG) was normal. Findings on chest x-ray and CT scan showed minimal change compared to previous imaging. Transthoracic echocardiography showed normal LV function, and a severely dilated RV with moderately impaired contractile function. Pulmonary pressures were only mildly elevated as measured by both echocardiography and right-heart catheterisation. A cardiac magnetic resonance (CMR) scan confirmed a dilated RV with impaired systolic function (Figure 4), RV ejection fraction (EF) was 34% (normal 44-63%). Extensive, patchy delayed gadolinium enhancement was observed in the RV free wall, as well as subtle mid-wall delayed enhancement in the interventricular and the interatrial septum (Figure 5). The CMR findings led to a diagnosis of right heart failure secondary to sarcoidosis infiltration of the RV wall. The evidence of RV infiltration by sarcoidosis led to immediate immunosuppressive therapy in accordance with general recommendations for cardiac sarcoidosis, and insertion of an implantable cardioverter-defibrillator (AICD). Follow-up interrogation of the AICD revealed an episode of non-sustained fast ventricular tachycardia.
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high resolution coronal. reformats from a non-contrast helical CT shows striking bilateral bulky hilar and mediastinal adenopathy. Mass-like fibrosis is encasing the hila and central bronchi causing traction bronchiectasis. There are several partially calcified hilar lymph nodes. There are also extensive perivascular and perilymphatic nodules throughout both lobes with relative sparing of the lower zones and right upper lobe bullae.
PMC3899174_01
Male
23
In November 2009 a 23-year-old Chinese man presented to the emergency department with a 7-day history of helmet headache radiating to the nuchal region and associated with vomiting, confusion, and fever. Physical examination showed modest neck stiffness, lateral decubitus position, and hyper-excitable tendon reflexes. Babinski and Lasegue signs were negative bilaterally. The patient underwent brain and cervical spine CT scan, which was unremarkable. LP revealed CSF with increased pressure, lymphocytic pleocytosis, decreased glucose, and increased protein levels. Bacterial antigen detection test on CSF was negative, as were CSF bacterial and fungal cultures. CSF acid-fast bacilli smear and culture were negative. Broad-spectrum parenteral therapy with acyclovir, cefotaxime, chloramphenicol, mannitol, and dexamethasone was started. In the following days the patient still complained of insomnia, diplopia, headache, neck stiffness, and pain in the sacral region. Eye and ENT exams were unremarkable. Therefore, a second LP was performed. CSF had the same characteristics as the first LP. The following blood test results were all negative: antibodies against Herpes simplex virus types 1 and 2, HIV, hepatitis A, B, and C viruses, Widal's and Wright's serodiagnosis, VDRL and TPHA, QuantiFERON-TB, Western blot test for Lyme disease, and parasitological stool exam. A brain and spinal cord MRI was performed (Figure 1), revealing widespread arachnoiditis and small septated cysts with CSF-like signal in the cisterna magna, within the fourth ventricle, and at the level of L3-L4. These findings were likely due to arachnoiditic adhesions. Differential diagnosis included toxoplasmosis, fungal abscess, primary or metastatic brain tumour, vasculitis, tuberculoma, and neurocysticercosis. However, the patient had no evidence of immunodeficiency and no predisposing factors for immunocompromise. CSF cultures for Mycobacterium tuberculosis and QuantiFERON-TB were negative. Cysticercus-specific immunoglobin G antibodies were detected by ELISA in the CSF. The patient received albendazole (15 mg/kg/day) and dexamethasone (5 mg/day) for 4 weeks, with progressive resolution of neurological symptoms. A second MRI performed 6 months later confirmed the regression of the lesions.
meningitis, neurocysticercosis – diagnosis, neurocysticercosis – physiopathology, taenia solium
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PMC7446552_01
Female
66
A 66-year-old Japanese woman with complaint of chest dullness was referred to Chiba University Hospital. She was a housewife with no history of smoking or any other complications. She had not been exposed to asbestos in her life, not even for a short period of exposure. Her residential area has not been contaminated with asbestos and her family had not been engaged to any works dealing with asbestos. These suggest the para-exposure or environmental exposure to asbestos was quite unlikely. Until the first visit to our hospital, she had no previous medical history of pneumonia, tuberculosis, or thoracic trauma that may cause pleural effusion. At the first visit, she complained left-sided dull pain, extending from lateral chest to back (grade 2 of the Numerical Rating Scale) and slight dyspnea on effort (grade 1 of the MRC dyspnea scale). These complaints continued thereafter for 11 years without any deterioration. Weight loss, continuous fever, and nocturnal sweat were not observed. Chest X-ray showed left-sided pleural thickening and pleural effusion. The mild pleural effusion of unknown etiology was already detected 7 years ago before her visit to the hospital. Chest computed tomography (CT) on admission demonstrated left-sided thickened pleural of 13 mm at the lower thorax with some pleural effusion. Pleura thickening was not extended to the mediastinal side and there was no finding of fissure thickening or lung parenchyma involvement. Pleural plaques, pleural implantation, and thoracic wall invasion were not detected. Typical radiological finding of malignant pleural mesothelioma was therefore absent. Nevertheless, it is sometimes difficult to make differential diagnosis between malignant pleural mesothelioma and non-mesothelioma diseases, since mesothelioma does not demonstrate these typical features, especially in the earlier stage. Even though she had no history of asbestos exposure, malignant pleural mesothelioma was suspected based on CT scan findings and an abnormally high concentration of hyaluronic acid (2,030,000 ng/mL) in the pleural fluids. A pleural biopsy was performed with video-assisted thoracoscopic surgery (VATS) under local anesthesia and the pathological diagnosis with the specimens was epithelioid malignant pleural mesothelioma. The patient refused to take surgery and chemotherapy and was carefully monitored in the outpatient clinic. Four months after the VATS biopsy, the pleural effusion increased (Figure 1) and the CT scan detected a nodule with 4 cm in size (Figure 2(a)), which were compatible with mesothelioma or dissemination of lung cancer into the thoracic cavity. The patient then consented to a surgical pleural biopsy under general anesthesia in order to obtain an additional tissue for further analysis, and we conducted several examinations as described below. A positron emission tomography (PET) scan did not show fludeoxyglucose (FDG) accumulation in the nodule, but detected a round-shaped atelectasis (Figure 2(b)). The patient survived 3 years after the last biopsy without any respiratory symptoms and more than 11 years from the first manifestation of pleural effusion. In summary, we presented a rare case of diffuse pleural thickening that was indistinguishable from mesothelioma with routine immunohistochemical examinations. Number of this type of marginal case will increase in the future according to expansion of asbestos-related disease. We presume that large biopsied samples by open surgery and p16 FISH analysis and BAP1 immunohistochemistry are crucial for differential diagnosis between mesothelioma and the benign diseases, in order to avoid misdiagnosis which leads to highly invasive medical interventions.
diffuse pleural thickening, homozygous deletion of p16, malignant pleural mesothelioma
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PMC4840424_01
Male
22
A 22 year-old Asian male smoker presented with ten days of non-productive cough, subjective fevers, night sweats, right-sided pleuritic chest pain and increasing dyspnea. One week prior to presentation, he was empirically treated for pneumonia with levofloxacin without improvement. The patient was an exchange student from China whose last visit home was two months prior to presentation to our facility. Both of the patient's parents had been diagnosed with TB before his birth with unclear treatment status. The patient's physical exam was remarkable for decreased right-sided breath sounds. Vital signs were: temperature, 98.4 F; heart rate, 102/min, regular; BP, 102/58 mm Hg; respiratory rate, 28/min; oxygen saturation, 95% on room air. Chest radiograph (CXR) showed a large right hydropneumothorax and right upper lobe infiltrate with scarring (Fig. 1). A right-sided 32 French chest tube (CT) was placed in the emergency department (Fig. 2A). A chest computed tomography scan showed tree-in-bud nodularity in the right upper lobe, possible consolidation in the right lower lobe and calcified hilar lymphadenopathy. Additionally, there were foci of gas in the right-sided hydropneumothorax which could have represented a loculated component. Due to imaging findings suggesting prior granulomatous infection and patient history, there was high suspicion for TB and on airborne precautions were instituted. A pleural drainage catheter was placed into the hydropneumothorax. Analysis of the pleural fluid obtained from this procedure revealed: pH, 7.70; glucose, 11 mg/dL; protein, 4.5 g/L; LDH, 1458 units/L; WBC, 1340 cells/muL (64% lymphocytes); RBC, 4000 cells/muL; adenosine deaminase (ADA), 57.5 units/L. Additionally, serum protein was 5.6 g/L. Throughout his hospitalization, the patient had multiple AFB smears and cultures performed (2 concentrated sputum, 2 pleural fluid, 1 bronchoalveolar lavage), which were negative. A pleural biopsy demonstrated 1+ AFB on smear and necrotizing granulomatous inflammation. The patient was started on an anti-tuberculosis regimen (isoniazid (INH) 300 mg, ethambutol (EMB) 800 mg, rifampin (RIF) 450 mg and pyrazinamide (PZA) 1000 mg) because of his findings of a lymphocyte predominant exudative pleural effusion, AFB positive pleural biopsy with necrotizing granulomatous inflammation and history of exposure to TB. Given the persistent pleural effusion, he was given four doses of tissue plasminogen activator (tPA) and dornase alfa (DNase) instilled via the chest tube over a period of 6 days resulting in improved drainage and clinical and radiologic improvement (Table 1, Fig. 2B). Fibrinolytic therapy was terminated at the point of near complete resolution of the pleural effusion as evidenced by CXR. The chest tube was removed and the patient was discharged on hospital day 13. Two weeks after discharge, a follow-up CXR demonstrated a persistent small right-sided effusion, however; the patient was asymptomatic (Fig. 3). Ultimately, the pleural fluid and biopsy cultures were positive for Mycobacterium tuberculosis.
ada, adenosine deaminase, afb, acid fast bacilli, ct, chest tube, cxr, chest radiograph, emb, ethambutol, fibrinolytic therapy, hd, hospital day, inh, isoniazid, pza, pyrazinamide, pleural effusion, pleural tuberculosis, rif, rifampin, tb, tuberculosis, tuberculosis
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PMC2732535_01
Male
25
To the Editor: On October 21, 2000, a previously healthy 25-year-old male farmer was admitted to a mission hospital in western Kenya with an acute hemorrhagic illness. Four days before admission, the patient had rapid onset of fever, headache, nausea, vomiting, severe muscle pains, and diarrhea, which became bloody. On admission his temperature was 36.4 C, pulse was 60/minute, respiratory rate was 20/minute, and blood pressure was 90/40 mm Hg. In addition to the signs and symptoms listed above, the only other abnormal finding on admission was neck stiffness. The differential diagnoses included bacterial dysentery and meningitis. Results of a blood smear for malaria parasites and Widal test for typhoid were negative, and cerebrospinal fluid and urine examinations were normal. The patient was treated with doxycycline, cotrimoxazole, metronidazole, and intravenous fluids. On the day after admission, the patient's vomitus became blood stained and blood was passed rectally. The patient was isolated and strict barrier nursing implemented on the suspicion of viral hemorrhagic fever (VHF). Progressive hypotension developed, resistant to resuscitation efforts with intravenous fluids and corticosteroids, and later massive bleeding from the nose, mouth, and upper and lower gastrointestinal tract occurred. The patient died on the second day of admission, 6 days after onset of illness. A serum sample was sent to the Arbovirus and Viral Hemorrhagic Fever Reference Laboratory in Nairobi for diagnostic screening. Serologic tests in Nairobi were negative for yellow fever, dengue, West Nile, Chikungunya, and Rift Valley fever (immunoglobulin [Ig] M-capture enzyme-linked immunosorbent assay) and reverse transcriptase-polymerase chain reaction (RT-PCR) tests for flaviviruses, alphaviruses, and Bunyamwera serogroup bunyaviruses were also negative. RT-PCR for Crimean-Congo hemorrhagic fever virus (C-CHFV) was positive. Tests for anti-C-CHFV-specific IgM antibody by indirect immunofluorescence were negative. Virus isolation attempts were then terminated because the cultivation of C-CHFV (the presumptive cause) requires biosafety level 4 facilities. The specimen was submitted to the Special Pathogens Unit in Johannesburg for confirmation of the result. The sample was positive by RT-PCR for C-CHFV and was IgM and IgG antibody negative. No isolation of the virus could be made from the serum sample, possibly because it was received by the Johannesburg laboratory 8 days after initial collection and following freeze-thaw conditions. The specimen was was insufficient to attempt C-CHVF antigen detection assays. Sequencing of the RT-PCR amplicon confirmed C-CHFV. C-CHFV is a tick-borne virus of the genus Nairovirus, family Bunyaviridae, and is widely distributed throughout eastern Europe and the Crimea, to the Middle East and western China, Pakistan, and Africa. Natural hosts for this virus are varied (including wild and domestic animals and birds) and may reflect the feeding preferences of the host tick. While C-CHFV infections are rare in humans, the virus is notorious for nosocomial outbreaks of VHF, typically following admission of an index case to a health-care facility where VHF was not suspected, with mortality rates up to 40%. Previous evidence for C-CHFV in Kenya is limited and based on serology (human and bovine) and two isolations of C-CHFV from non-human sources. This report represents the first documented case of acute human C-CHFV infection in Kenya. The hospital concerned belongs to a VHF surveillance network serving to increase awareness and preparedness within Kenyan health-care facilities. In this case suspicion of VHF was raised, and the patient was immediately isolated, noninvasive procedures were instigated, and barrier nursing was implemented to prevent nosocomial transmission. No family or hospital staff member who had close contact with the patient became ill. Although VHFs are rare, this report stresses the need for health facilities in Kenya and East/Central Africa to include VHFs in their differential diagnosis of unexplained fever with hemorrhagic tendencies, as well as the utility of the surveillance network. The causative agents of Ebola hemorrhagic fever, Marburg hemorrhagic fever, C-CHFV, Rift Valley fever, and yellow fever are all endemic in East and Central Africa, and sporadic cases, as well as outbreaks, are likely to continue to occur in this region.
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PMC10081906_01
Female
58
A 58-year-old white woman with diabetes type 2 (5-year duration) taking metformin 1 g/day came for evaluation due to progressive visual loss associated with visual field constriction and bilateral scotomas. Visual acuity was 20/40 bilateral (Snellen chart). Ishihara plates, ocular motility, applanation tonometry, pupillary reflex, and anterior biomicroscopy were normal. Retinal mapping showed light arterial narrowing, optic disc pallor, and focal RPE alterations. FA showed few microaneurysms in the left eye (LE). VF (Goldmann perimeter) showed bilateral and concentric visual field loss. OCT showed thinning of the photoreceptor layer and sparse disruption of the ellipsoid zone. ERG showed an accentuated reduction in photopic and scotopic responses and in implicit time. Serologic investigations (including syphilis, tuberculosis, and toxoplasmosis) were nonreactive. Cardiovascular, hematologic, and neurologic investigations were normal. Thorax tomography showed a tumoral lesion in the right pulmonary lobe. The patient was submitted for lobectomy. Antirecoverin became positive. Treatment was initiated with oral and subtenonian triamcinolone, without response. Systemic immunosuppression was not tolerated. Ozurdex has been injected at 6/6-month intervals (last 2 years), and no more changes were observed in comparative examinations. The patient has remained functionally stable (Figure 1).
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PMC9608540_01
Male
29
A 29-year-old male salesman complained of hip pain and limited range of motion (ROM) for 4 months in both hips. On July 10, 2019, insidious pain began in his left hip after walking, and the pain gradually subsided over 1 week without any treatment. At left hip pain relief after 1 month, the pain gradually started in both hips. The pain was alleviated after rest and aggravated with walking. No infectious contacts, such as tuberculosis, were found at his presentation. On primary physical examination, no warmth or swelling was noted in the patient's hip, nor was there any inguinal lymphadenopathy. X-rays of the pelvis showed osteoporosis of the femoral head on both sides (Figure 1A). The blood draw result was normal. He had an 11-year history of liquor intake in excess of 130 g per day and no history of glucocorticoid intake or trauma. No history of hereditary disease was found in his family. He was diagnosed with a synovitis of the hip and was managed with conservative methods such as the administration of non-steroidal anti-inflammatory drugs (NSAIDs), physical therapy, and functional exercises. Bilateral hip pain and loss of ROM were gradually exacerbated by non-operative measures. Subsequently, he was admitted to the Department of Orthopedic Surgery of the Affiliated Hospital of Zunyi Medical University. Physical examinations showed limitations in weight-bearing during walking, and pain was noted in all planes of the hip by 15 . Preoperative Harris hip scores (HHSs) were 58 and 61 for the left and right hip, respectively. The Visual Analogue Scores (VAS) were 8 and 7 for the left and right hip, respectively. The patient showed limited ability to perform daily activities (Table 1). Magnetic resonance imaging (MRI) revealed geographically aberrant signal intensity impairments with typical appearances of bilateral ONFH (Figures 2A,B). Computed tomography (CT) (Figures 2C-E) showed a mixed appearance, including sclerosis and cysts on the bilateral femoral heads without flattening or crescent signs. The preoperative x-ray showed cystic and sclerotic changes in the bilateral femoral heads (Figure 1A). Laboratory test results were normal. He was diagnosed with bilateral ONFH (stage II) according to the Ficat classification. An all-arthroscopic light bulb technique through outside-in fashion without distraction was recommended because no concomitant central compartment pathologies such as a labral tear, femoroacetabular impingement, and loose bodies were found on x-ray, CT, and MRI examinations. Arthroscopy was performed on the patient's left hip under general anesthesia through the anterolateral (AL) portal, distal anterolateral accessory (DALA) portal, and mid-anterior (MA) portal in the supine position on the traction table without applying distraction. The all-arthroscopic light bulb technique to the hip was applied according to outside-in fashion and "touch method". The AL portal was made after making a vertical stab incision, and the subcutaneous and muscular layers were split by using a straight clamp. The straight clamp was directed medially, pointing in the direction of the femoral neck. When the tip of the straight clamp touched the bone, it was replaced with a blunt trocar and the femoral neck could be felt, and the tip of the trocar was situated extra-articularly at the femoral neck of the hip joint. The DALA portal was made after making the skin incision, and a straight clamp was introduced and directed toward the arthroscope trocar. When the straight clamp touched the trocar of the arthroscope, the trocar was used as a guide to travel medially in the direction of the femoral neck. The straight clamp must touch the arthroscope trocar until the straight clamp touches the bone, and an ablator or shaver was introduced. After the fatty tissue of the precapsule was removed with the shaver, the white structure of the joint capsule was shown. Then, an extra-articular longitudinal capsulotomy was performed from outside to inside. The necrotic site was located using a Kirschner pin under arthroscopic (Figure 3A) and radiographic (Figures 3B,C) visualization before managing ONFH. Then, the MA portal was established under direct visualization. After the fluoroscopic image of the Kirschner pin location was obtained to find the center of the necrotic site at the femoral head, a cortical bone window with a diameter of approximately 1.5 cm was established at the femoral head-neck junction with a cannulated drill through the DALA portal, and the necrotic bone (Figure 3D) was removed using a rongeur and curette until bleeding or healthy bone (Figure 3E) was found. Then, an arthroscopic check was performed to ensure that the necrotic bone was removed. Furthermore, the femoral head and neck were percutaneously penetrated for improving blood circulation using a 2.0 mm Kirschner pin. Finally, the ipsilateral auto-iliac cancellous bone was harvested and was used to fill the cavity of the femoral head (Figure 3F) through the cannula after necrotic bone removal. The surgery lasted 136 min. Two weeks postoperatively, the same procedure was performed on his right hip. The patient was followed up at 1, 3, 6, and 12 months and annually thereafter. Early core-strengthening exercises and closed-chain hip stabilization were carried out to optimize the joint ROM. Relative to the literature, in our institution, weight-bearing to prevent femoral head collapse is implemented with caution. For example, in the case under study, the patient was not allowed weight-bearing for the initial 3 months. Toe-touch weight-bearing using crutches was allowed for the second 3-month phase. The patient began full weight-bearing to prevent femoral head collapse when the grafted bone site fully healed. Three months after the procedure, the patient experienced no pain and had an improved VAS of 0. The VAS, HHSs, Hip Outcome Score Activities of Daily Living subscale (HOS ADL), International Hip Outcome Tool-12 (iHOT-12), and active ROM of the left hip and right side demonstrated consistent improvement at the 2-year postoperative follow-up (Table 1). This consistent improvement in outcomes showed that an all-arthroscopic light bulb technique through outside-in fashion without distraction could be a feasible method for the treatment of ONFH. The MRI (Figure 2I,J), CT (Figure 2F-H), and x-ray (Figures 1B-F) revealed a well-healed area of previous bone graft in the bilateral femoral heads, but there was radiological progress (slight collapse) on the left hip (Figures 1A-D). The patient was followed regularly and was strictly required to comply with the therapeutic plan. The patient presented that he was very satisfied at a follow-up visit 2 years after surgery. "As far as I know, ONFH is not always successful in hip-preserving procedure. The bilateral necrotic areas are healed, I am very lucky. The arthroscopic procedure is minimally invasive and aesthetically pleasing," the patient said. Also, he did not have any complications. The timeline for ONFH course and management response was presented in Figure 4.
arthroscopy, case report, distraction, femoral head, osteonecrosis, treatment
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PMC4629765_05
Male
63
A 63-year-old man was diagnosed with Mantle-cell lymphoma in 2009. He was treated with high doses of chemotherapy, followed by stem-cell transplantation with complete remission until January 2013, where the disease recurred in retroperitoneal and mediastinal lymph nodes. The patient was switched to weekly RTX for 4 weeks, followed by a combination of RTX and bendamustin. Prior to the initiation of RTX, his spirometry was normal and PET-CT revealed no lung parenchymal abnormalities. The patient developed severe cough and exertional dyspnea immediately after treatment with the second series of RTX. Sputum cultures were negative. The patient completed the treatment regimen with four series. Body plethysmography showed restrictive reduction in lung function and low diffusion capacity (DLco 45%). HRCT of the lungs revealed diffuse GGO and nodular changes. BAL fluid analysis and transbronchial biopsies (TBB) revealed signs of eosinophilic inflammation with drug-induced pneumonitis as the possible underlying etiology. The diagnosis of RTX-ILD was made on clinical, radiological, and histological bases. The patient was treated with prednisolone and follow-up revealed stability of symptoms and lung function parameters.
interstitial pneumonitis, lymphoma, rituximab
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PMC5759803_01
Female
90
Despite M. simiae being one of the most relevant NTM due to its emergence as a human pathogen, the genomic features and genetic potential of this species remain poorly described. In collaboration with the State Laboratory of Public Health of Guanajuat, located in central Mexico, we had access to a clinical isolate of M. simiae, termed MsiGto. The sample was isolated from a 90 years old female patient from Leon, the largest and most industrialized city of the State of Guanajuato, Mexico, in 2011 (Table 2). This sample was selected for genomic sequencing due to the emerging clinical importance of strains from the M. simiae complex worldwide, combined with a lack of representative genomic sequences from Mexico to this date. The available genome sequences could allow comparative analyses in order to increase our understanding of this opportunistic bacterium. MsiGto was isolated from a sputum specimen. Briefly, 2 mL sample were transferred to a sterile tube and decontaminated by adding an equal volume of 4% NaOH with phenol red. The mix was immediately vortexed and incubated at 37 C for 15 min. The liquefied sample was centrifuged at 3000 g at 4 C for 15 min, the supernatant was discarded and pH was adjusted between the 6.5 and 7.2 range using 1 N HCL. Finally, 0.2 mL of sample were inoculated into Lowenstein-Jenssen slants (Difco) and incubated at 37 C for three weeks. Biomass was collected and suspended in phosphate buffered saline solution, pH 7.4, and inactivated by heating at 80 C for 45 min. After centrifugation, genomic DNA was extracted from the pellet using the FastDNA SPIN Kit for Soil (MP Biomedicals) according to manufacturer's instructions. Extracted gDNA was assessed for quantity and quality using a NanoDrop Spectrophotometer (Thermo Fisher Scientific). The MsiGto genome was sequenced on a HiSeq 2000 platform with a 100 bp paired-end cycle according to standard Illumina protocols, at Macrogen facilities. Quality of the generated sequencing reads (13,676,836 reads, total read length: 1,381,360,436 bp) was checked with FastQC. Reads were filtered before assembly, such that both sequences in paired-end reads exhibited more than 90% bases of quality greater than or equal to Q20. Post-filtering Q20% was 97.69 and Q30% was 88.6 at the base level. The filtered reads were assembled using SOAP de novo aligner, yielding 50 contigs. Scaffolding was performed with SSPACE Standard and resulted in 12 scaffolds, generating a genome size of 6.7 Mb with a coverage of 216X (Table 3). Gene prediction and functional annotation were performed using the Rapid Annotation using Subsystem Technology platform. A prophage region prediction was completed using PHAST. CRISPRs were searched using the CRISPR finder, and antibiotic resistance genes were investigated using Resistance Gene Identifier from the Comprehensive Antibiotic Resistance Database. Genome-to-genome comparisons were performed using multiple approaches, including conservation analysis of protein families across genomes with the Protein Family Sorter from the PATRIC Platform, and comparing functionally related clusters using the function-based comparison of the RAST server. MsiGto and related genomes were also aligned using a genome-wide BLAST comparison, and visualized through the Artemis Comparative Tool for manual inspection. Genomic assembly yielded a total length of 6,684,413 bp fragmented in 50 contigs, the largest M. simiae genome reported to date. The MsiGto genome consists of a unique chromosome, as no plasmid DNA was found. The GC content of the genome was 66.08%, consistent with other reported M. simiae strains. Gene prediction analysis documented 3 rRNAs, 49 tRNAs and 6409 coding sequences. Out of these, 4462 genes (69.62%) were assigned to putative functions, and 3669 genes (approximately 62.57%) were assigned to clusters of orthologous groups functional categories. Sequence searches using RGI evidenced resistance genes to amynoglycosides, ethambutol and beta lactams, which is a concern as to date standard antibiotic regimes for this species include the use of ethambutol, the aminoglycoside amikacin, as well as the macrolides azithromycin and clarithromycin. The genome properties and statistics are summarized in Tables 4 and 5. Gene distribution among the COG functional categories is shown in Table 6. A circular map of MsiGto chromosome is provided in Fig. 2. We report here the third genome sequence of M. simiae. MsiGto was isolated from a clinical sample obtained from an elderly woman, and is the largest M. simiae genome reported to date with an approximate 745 Kbp additional to the next largest genome (strain MO323). As pathogenic mycobacteria tend to undergo genome decay, the large genomic size of MsiGto speaks out of an organism capable of thriving in both environmental conditions and in the human host. Indeed, by comparison, the genome of M. tuberculosis, an obligate pathogen, is significantly smaller with 4.41 Mb. Meanwhile, with 6406 genes, the genome size of MsiGto is similar to that of the opportunistic pathogen Pseudomona aeruginosa (5570 predicted ORFs), which thrives in a variety of environments including soil, water, as well as the multiple human tissues it infects. Analysis of the P. aeruginosa genome evidenced its large size arose from genetic expansion to enhance functional diversity rather than from gene duplication. Interestingly, investigating protein families in MsiGto, in comparison with MO323 and DSM 44165, evidenced a larger proportion of proteins uniquely found in MsiGto (1.17 times more than DSM 44165 and 4.7 times more than MO323), suggestive of a relatively increased versatility in accordance with the multiple niches it can thrive in (Fig. 3). The genome of MsiGto is rich in virulence factors, genes conferring infective mechanisms, and host immune response evasion systems. Some of these proteins are common to other pathogenic mycobacteria, and shared by the two previously sequenced M. simiae genomes, such as ESAT-6, known to modulate host immune responses by affecting human T-cell responses. Interestingly, all M. simiae strains including MsiGto have three of the four antigen 85 complex genes (fbpA, fbpC, and fbpD) responsible for cell wall synthesis. The enzyme products of these genes are responsible for the conversion of trehalose monomycolate (TMM) into the Cord Factor trehalose dimycolate (TDM), which is considered one of the most important virulence factors of mycobacteria. Other genera belonging to the Mycobacteriaceae family that include both pathogenic and environmental species, such as Rhodococcus, Corynebacterium and Nocardia, also produce TDM. Mammalian Cell Entry proteins are cell surface exposed proteins that play a crucial role in M. tuberculosis virulence by permitting the bacteria to enter mammalian cells and survive inside the macrophage, modulating the immune response. Mce clusters consist of 4 homologous operons in M. tuberculosis (mce1, mce2, mce3, mce4) with a similar arrangement: two genes encoding integral membrane proteins followed by six mce genes (A, B, C D, E and F). Mce proteins are also involved in lipid metabolism, acting as transporters and allowing cholesterol degradation to free carbon and energy for use by M. tuberculosis. In the genome of MsiGto we found that the cluster mce3 is overrepresented. While the DSM 44165 and MO323 genomes present none and a single copy of mce3, respectively, two complete copies of the mce3 cluster were found in MsiGto. As the transition from an environmental organism to a pathogen has been associated with the acquisition of Mce genes in actinobacteria, and Mce3 proteins are expressed by M. tuberculosis during the infection phase, it is tempting to speculate the increased number of Mce3 copies found in MsiGto provided the strain with human infection potential. The presence of multiple copies of these potential lipid transporters in mycobacterial genomes is consistent with the finding that pathogenic mycobacteria switch from carbohydrates to lipids as their main carbon and energy source inside cells. The evolution of this locus, through duplication and divergence, has almost certainly contributed to virulence in mycobacteria, and even in other distantly related actinobacteria, such as Streptomyces. Given that the ability to acquire cholesterol from the host is crucial to maintain a chronic infection, we postulate that cells having a large mce copy number, such as that found in MsiGto, may potentially evolve pathogenicity relatively faster when compared with other environmental mycobacteria. A total of 493 protein families were found exclusively present in MsiGto when compared to the other two available M. simiae genomes (MO323 and DSM 44165). Consistent with findings in the Pseudomonas aeruginosa genome, it seems that MsiGto has undergone genome expansion. Within the gene pool unique to MsiGto we found the arginine/ornithine antiporter gene arcD, which is involved in the persistence of the zoonotic pathogen Streptococcus suis in host cells. Additional unique genes found in the MsiGto genome participate in aromatic amino acid metabolic pathways. For instance, 2-oxo-hepta-3-ene-1,7-dioic acid hydratase (hpcG gene, EC 4.2.1.80) participates in the degradation of tyrosine and the 2-keto-3-deoxy-D-arabino-heptulosonate-7-phosphate synthase I alpha participates in the synthesis of chorismate (aroG gene, EC 2.5.1.54). The latter is an interesting observation as tyrosine is a key nutrient source during infectious growth within macrophages of some pathogenic fungus. At this stage, however, it would be risky to rule out the involvement of these specific genes in important environmental functions that allow MsiGto to survive outside the host, or during both lifestyles.
mycobacterium simiae, nontuberculous mycobacteria, opportunistic pathogen
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PMC6495004_01
Male
44
A 44-year-old man was referred to our interdisciplinary center for vertigo and balance disorders at the University Hospital Zurich (tertiary referral center) with recurrent spontaneous attacks of spinning vertigo, which started several months prior to his first visit. The attacks usually lasted for 3-12 h and were accompanied by fluctuating hearing loss and tinnitus in the right ear. According to the patient's medical history, he had suffered a left-sided longitudinal TB fracture caused by a car accident at 10 years of age (the original neuroradiology report but not the CT images were available for this study). Pure-tone audiometry (PTA) 4 months after the accident showed a pronounced high-frequency shift in bone conduction thresholds at 6 kHz on the left side (PTA not shown here), consistent with acoustic trauma and probably caused by the impact noise in the car. No further accident-related injuries or audiovestibular symptoms occurred, according to the available clinical records from that time. A synopsis of relevant events in the patient's medical history is given in Figure 1A. In the initial neurotological work-up at age 44, vestibular-evoked myogenic potentials (VEMPs) indicated left-sided saccular dysfunction (absent cervical VEMPs). Other vestibular test results (ocular VEMPs, subjective visual vertical, video-oculography with caloric stimulation, and video head impulse test) were within the normal range (data not shown). PTA showed that the left ear had mixed, predominantly sensorineural, downward-sloping hearing loss (HL) up to 100 dB HL at 6 kHz (Figure 1B), while the right ear had moderate to severe presbyacusis (Figure 1C). Speech discrimination scores were 35 % on the left side and 100 % on the right side, and stapedial reflex responses were normal on both sides (data not shown). Two months later, the patient presented in our emergency department immediately after an acute, hours-long vertigo attack accompanied by nausea and emesis. The HL and tinnitus in the left ear temporally worsened. Clinical examination showed a spontaneous nystagmus to the right side, a positive head impulse test to the left, and a positive Romberg test with a tendency to fall to the left side. Finally, a diagnosis of left-sided Meniere's syndrome was made, and a possible traumatic etiology was considered based on the patient's history. The patient subsequently received repeated intratympanic dexamethasone (6.6 mg)/hyaluronate (2 mg/ml) injections over the course of several days, and in the following years, he undertook sequential trials of different vestibular suppressants [cinnageron, 75 mg, two times daily for 8 weeks, betahistine, 24 mg, two times daily for 16 weeks; prior to publication of ]. Although the vertigo episodes continued with an average frequency of two attacks per month, the patient was coping well with the symptoms, and no vestibular ablative treatment was considered. In the 4 years following the onset of MD symptoms, hearing function in the left ear fluctuated in the low and middle frequencies and progressively declined to a level of 50-80 dB HL (Figure 1B). Finally, the patient was fitted with a contralateral routing of signals (CROS) hearing aid. He was then lost to further follow-up. During initial neurotological evaluation (age 44), high-resolution CT (HRCT) imaging of the TBs was performed to rule out retrocochlear pathologies (e.g., vestibular schwannoma), posttraumatic inclusion cholesteatoma, and otosclerosis. HRCT imaging showed no evidence for the previously mentioned pathologies but demonstrated an old fracture sign in the posterior wall of the external ear canal. Four years later (age 48), gadolinium-enhanced MRI (Gd-MRI) of the inner ear fluid spaces with a 4-h delayed 3D inversion recovery (3D IR) sequence detected moderate [grade I, ] vestibular and moderate-to-severe [grade I-II, ] cochlear hydrops in the left inner ear, consistent with the previously assigned clinical diagnosis. No radiological (Gd-MRI) signs of endolymphatic hydrops were found in the right inner ear. In the present study, we reassessed the available imaging data with regard to potential pathologies of the VA and ES on the clinically affected left side. On HRCT imaging, the left VA appeared to be almost completely obliterated by bone along its course between the isthmus and the operculum (Figure 2A). In contrast, the right VA exhibited a patent lumen throughout its entire course (Figure 2B). Correspondingly, on Gd-MRI (3D IR sequence), a segment of total T2 signal loss was observed in the partially obliterated left VA (Figure 2C) but not in the right VA (Figure 2D). In the left VA, a delineated T2 signal was seen distal (posterior) to the segment with total signal loss (Figure 2C, blue arrows). Fusion of HRCT and Gd-MRI (color-coded) data in the focal plane of the operculum clearly localized this T2 signal distal (posterior) to the operculum (Figures 2E-H). Therefore, the signal most likely originated from the eES, as proposed previously. In summary, the HRCT and Gd-MRI data indicated that the left eES was structurally preserved but anatomically separated from the labyrinth due to bony obliteration of the VA. Upon reassessment of the imaging data for the present study, no radiological signs for bony labyrinthine dehiscence, nor for cerebellopontine angle tumors were found that could account for the fluctuating otological symptoms.
endolymphatic hydrops, endolymphatic sac, gadolinium-enhanced magnetic resonance imaging, otic capsule, temporal bone fracture
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PMC7896536_02
Male
83
Scenario 2: an 83 year old elderly man presented to our hospital with low grade fever and productive cough of one-week duration and shortness of breath of 3 days duration. He also reported an episode of streaky hemoptysis and a background history of treatment for a sputum-confirmed pulmonary tuberculosis, 19 years previously. There was a recent history of a self-limiting sore throat and generalized body weakness. He was hypertensive and diabetic but reported good drug compliance. He had presented at the early stage of community transmission of COVID-19 infection within the country with strong consideration given to its likelihood. However, he had been screened for COVID-19 through RT-PCR test from nasopharyngeal and throat swabs obtained at an accredited outside laboratory which returned negative; the result of which he made available at the time of admission to our facility. The remarkable findings on clinical examination were tachypnoea (respiratory rate of 36/minute), poor room air oxygen saturation of 90%, tachycardia (pulse rate of 100/minute) and systemic hypertension (blood pressure of 165/96mmHg). All initial laboratory blood panels were within normal limits except for borderline elevation in serum creatinine of 1.6mg/ml (normal: <1.5mg/dl) and low estimated glomerular filtration rate of 45.5ml/min/1.73m2 (normal: >90ml/min/1.73m2) indicating low renal reserve. The chest radiograph done on admission revealed dextrocardia with features of multiple consolidations in both lung fields demonstrating peripheral disposition. There was no evidence of pleural or pericardial effusion (Figure 5). A 12-lead electrocardiogram revealed features of left ventricular hypertrophy and left axis deviation with sinus tachycardia. Two-dimensional trans-thoracic echocardiography revealed concentric left ventricular hypertrophy with good biventricular systolic function (left ventricular ejection fraction {EF} of 65% and Tricuspid Annular Plane Systolic Excursion {TAPSE} of 2.5cm). Given the negative COVID-19 test, the clinical diagnosis of community-acquired bacterial pneumonia was made with a differential diagnosis of reactivated pulmonary tuberculosis. He was commenced on broad-spectrum antibiotic therapy according to hospital infectious disease protocol for community-acquired pneumonia as well as other supportive therapy, including corticosteroids and anticoagulants. Consideration was also given to commencement of a trial of empirical anti-tuberculous therapy because of his past medical history. However, his clinical condition remained poor, necessitating further imaging evaluation with chest computed tomographic (CT) scan on the 5th day of admission (12th day from the onset of illness) which revealed diffuse ill-defined ground glass densities in both lungs with multiple peripherally-distributed non-enhancing peri-bronchovascular consolidations especially in the lower lobes. There was bilateral pleural thickening with mild cardiomegaly (CTR=54%), rightward cardiac apex, and bovine branching pattern of a rightward aortic arch consistent with dextrocardia. The liver was located on the left and the spleen on the right, in keeping with a situs inversus (Figure 6). These imaging findings heightened suspicion of COVID-19 viral pneumonia, especially as there was a prevailing surge in community-transmitted cases at the time. The patient was transferred to the hospital isolation facility with repeat throat and nasal swabs sent for the COVID-19 test, which returned positive after five days. The patient made a full recovery from the infection and was discharged home after 16 days in the isolation centre after two subsequent consecutive COVID-19 RT-PCR tests had returned negative. No hospital staff among the primary contacts of this patient was reported to be infected with COVID-19 after contact tracing and isolation.
covid-19, diagnostic challenges, surge, thoracic imaging, viral pcr testing
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PMC7231992_01
Female
53
A 53-year-old female patient has got burned when handling a propane-butane gas cartridge that exploded at her kitchen. The patient sustained 16% TBSAB (Total Body Surface Area Burned) to face, neck, trunk, both hands and right thigh associated with severe inhalation trauma. The burn depth was diagnosed clinically as mixed deep dermal/third degree of 12% TBSAB (third-degree burns at hands, neck and lower part of the face, total 6%) and superficial burns of 4% TBSAB (Fig. 1). Because of inhalation injury, the patient was intubated immediately at admission. There was an extensive edema of the epiglottis and a huge mass of carbon blacks in examined airways. Shortly after admission, despite adequate fluid replacement therapy, the patient s circulation became unstable. High doses of circulatory support drug (norepinephrine) were needed for the restoration of normal blood pressure although there were not any cardiac or other internal diseases in the patient s medical history. In that condition early surgical intervention was risky and it was replaced by enzymatic debridement. The enzymatic debridement of the deep burn areas at the face, neck, both hands and trunk (total 8% TBSA), was performed 17 h post-injury using bromelain-derived proteolytic enzymes mixture gel. The procedure was accomplished according to the manufacturer s instructions. We added just one more step, protection of the orbital area and outer ear canal with medical-grade sterile vaseline. Single debridement efficacy was 95% on the face, neck and trunk and 90% on both hands. (Fig. 2) In the high-risk patient with unstable circulation enzymatic debridement proved to be safe and effective. All the debrided wounds were covered temporarily by cryopreserved porcine xenografts. The porcine xenografts were standardly processed in the Central Tissue Bank at Department of Burns and Reconstructive Surgery, University Hospital, Bratislava. Healing by epithelization under the xenografts of most of the wounds including face area was achieved within 5 weeks. Only 2,5% TBSA of the debrided areas on both hands and neck were full-thickness deep burns. Full-thickness burns were closed by split-thickness autografts after patient stabilization, fifteen days after the debridement. The patient was discharged from our department 5 weeks after injury with all burned areas healed. We followed-up the patient for 20 months after the injury (Fig. 3). The quality of scars after spontaneous healing at the patient s face and neck was satisfying with good aesthetical and functional outcome. Only a few sebaceous cysts formed at the patient s chin. The scars after skin grafting at the patient s left hand were also satisfying with full function of the hand. Only one scar contracture formed in the grafted area at the patient s right hand, which limited the flexion of the little finger and the index finger. The patient was readmitted 20 months post-injury for the contracting scars revision. Scar contractures of the 2 above-mentioned fingers of her right hand have been released using Z-plasties. Sebaceous cysts from the chin have been removed as well. The patient was discharged after 2 days and did not come back for follow-up anymore.
case report, deep burns, enzymatic debridement, facial burns, inhalation injury
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PMC9727639_01
Male
29
A 29-year-old man presented to the emergency department at Sultan Qaboos University Hospital (SQUH) with a 3-day history of fever, productive cough and shortness of breath. 10 days prior to current presentation, he had runny nose and tested positive for SARS-CoV-2 PCR from nasopharyngeal and throat swab. His medical background comorbids include severe anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) manifesting as pulmonary hemorrhage and biopsy proven necrotizing glomerulonephritis, as well as Hemophilia A. His regular medications were amlodipine 10 mg once daily, carvedilol 6.25 mg twice daily, metformin XR 500 mg once daily, factor VIII replacement (2500 units) three times a week, prednisolone tapering dose and co-trimoxazole 480 mg once daily for PJP prophylaxis. On physical examination he was alert and oriented but in moderate respiratory distress. His vitals were as follows: temperature 36, blood pressure 101/60 mmHg, heart rate 90 bpm, respiratory rate 26 bpm and oxygen saturation 93% on 6 liters of face mask oxygen (75% in room air). Chest auscultation revealed bilateral crackles. Other systematic examination was unremarkable. Laboratory findings are presented in Table 1. Results of full blood count showed hemoglobin of 7.6 g which is at his baseline as well as normal platelets counts. However, He had neutrophilic leukocytosis, and his CRP was elevated at 122 mg/l. His coagulation profile showed isolated prolongation of APTT of 65.5 s, consistent with his hemophilia A. Renal parameters were remarkable for acute deterioration in comparison with his baseline (Baseline eGFR 40 s). His chest radiograph (not shown) showed bilateral air space opacities. At this point he was admitted with impression of COVI-19 pneumonia. Patient was started on piperacillin-tazobactam at dose of 2.25 g IV every 8 h, azithromycin 500 mg PO once daily, dexamethasone 10 mg IV once daily along with esomeprazole 20 mg once daily. During the same day of admission, the patient started having episodes of painless fresh bleeding per rectum estimated to be around 200 ml and hemoglobin dropped to 5.6 g/dl.In view of his background of hemophilia and difficulty in performing endoscopic evaluation due to his oxygen requirements, it was decided to manage him conservatively with packed red blood cell transfusions and factor VIII replacement, in liaison with the hematology team. Despite daily factor VIII replacement, the lower GI bleeding persisted over the subsequent days. His oxygen requirements by then were minimal. Therefore, the gastro-enterology team was consulted for endoscopic evaluation of the colon. His colonoscopy showed a caecal circumscribed ulceration with central small polypoid lesion with no signs of active bleeding. The remaining segments of the colon were normal as shown in Fig. 1. Multiple biopsies were taken from the described lesions for histopathology evaluation. In view of ongoing lower GI bleeding requiring multiple blood transfusions, a Computed Tomography (CT) angiogram of the abdomen was also performed which showed evidence of a large ill-defined, eccentrically placed, heterogeneously enhancing soft tissue mass occupying the cecum. The mass extends across the serosal surface with multi-lobulated extra luminal component having broad area of contact with anterior peritoneum, concerning for malignancy. Fig. 2A, B. During his hospital stay the patient's COVID-19 pneumonia recovered gradually and by the second week he was maintaining saturation of 94% and above in ambient air. However, fresh bleeding per rectum persisted, albeit smaller in volume, and his hemoglobin eventually stabilized at his baseline of 7 g/dl. The caecal lesion histopathology report showed ulcerated colonic mucosa accompanied by fragments of granulation tissue and hemorrhagic necro-inflammatory debris. Several trophozoites of amoeba -were highlighted by PAS stain- within necrosis shown in Fig. 3. There was no dysplasia or malignancy. No fungi are demonstrated by GMS and PAS. Immunohistochemistry stain for CMV was negative. Entamoeba histolytica serology was sent. It came positive with IgG titer of 15.66 NovaTecUnits (NTU). Infectious Diseases team was consulted for the caecal ameboma and he was started on Intravenous metronidazole 750 mg every 8 h for total of 10 days. Patient's general status and rectal bleeding episodes improved after that course and his vitals stabilized. Therefore he was discharged to complete 21-day course of oral Metronidazole 800 mg every 8 h followed by cysticidal treatment with paromomycin for 7 days. Our patient was seen in the outpatient clinic after 3 weeks from the discharge. He was doing well without any further episodes of lower GI bleeding. His follow up labs shown in Table 2 demonstrated stability of his blood counts, improvement in his inflammatory markers as well renal parameters. Follow up CT (Fig. 2 C, D) showed near-total interval resolution of previously visualized exophytic caecal mass as well as significant interval resolution of previously visualized ill-defined eccentric heterogeneously enhancing soft tissue caecal wall thickening. Follow up colonoscopy was done (images not shown) and showed distal caecal annular ulcer of 3 cm length by 1 cm width which was biopsied for histopathological evaluation, mycobacterial tuberculosis, and cytomegalovirus evaluation. The follow up histopathology report (Fig. 4) showed no residual amoeba histolytica trophozoites and unremarkable for any other pathogens.
anca vasculitis, ameboma, case report
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PMC4530232_01
Male
21
A 21-year-old Tarahumara male was transferred from his community hospital with a 4-month history of cough, hemoptysis, progressive dyspnea, intermittent fever, and significant weight loss. On admission, he presented with a bad general condition, with the following vital signs: blood pressure of 90/60 mmHg, heart rate of 140 bpm, respiratory rate of 35 breaths per minute, and core body temperature of 99.5 F. The physical examination revealed a cachectic young man with evident signs of ARF including tachypnea, breathy speech, and accessory muscle use. Chest auscultation evidenced fine inspiratory crackles, mainly in the right apex. Arterial blood-gas (ABG) analysis while he breathed supplemental oxygen via a mask showed a pH of 7.37, PaO2 of 98 mmHg, PaCO2 of 36.5 mmHg, and HCO3 - of 20.8 mEq/L. Laboratory admission tests showed Hb of 11.1 g/dL, white blood count (WBC) of 11.6 cells/muL, neutrophils count of 10.9/muL, lymphocytes count of 0.2/muL, Na+ of 136 mmol/L, Cl- of 98 mmol/L, K+ of 4.02 mmol/L, Ca2+ of 7.6 mg/dL, glucose of 77 mg/dL, Cr of 0.36 mg/dL, blood urea nitrogen (BUN) of 6.1 mg/dL, uric acid of 3.7 mg/dL, cholesterol of 91 mg/dL, triglycerides of 98 mg/dL, and albumin of 2.1 g/dL. The HIV and hepatitis B and C tests were all negative. Sputum acid-fast stains were positive since his previous hospitalization and a real-time polymerase chain reaction (PCR) assay performed with another sputum sample confirmed the presence of Mycobacterium tuberculosis DNA. A chest X-ray showed diffuse alveolar and nodular opacities, as well an extensive right upper lobe cavitary disease (Figure 1). Based on the above findings, we calculated an APACHE II score of 13. The patient was treated with hydrocortisone 100 to 250 mg intravenously for 8 hours, and a daily regimen of intravenous amikacin 750 mg, and moxifloxacin 400 mg, along with antituberculosis treatment of 3 tablets of a fixed-dose combination (DoTBal, SILANES Laboratories) of rifampicin 150 mg, isoniazid 75 mg, pyrazinamide 400 mg, and ethambutol 300 mg. The patient was admitted to the intensive care unit but on day 4 in the hospital, the increased work of breathing required the initiation of NIPSV with a single-limb-circuit bilevel ventilator (VPAP III, ResMed) through an oronasal interface at pressures of 8-12/4 cm H2O. The DoTBal dose was increased to 4 tablets per day; however, the characteristic red color of the urine produced by rifampicin was no longer observed and the serum levels in a random sample were undetectable. Over the next 4 days despite slight improvement in PaCO2, it was not possible to wean the patient from NIPSV due to the persistent tachypnea. After a discussion regarding alternative therapies and under the respective observations of the local board of pharmacovigilance, the medical team decided as an extraordinary measure to administer etanercept (Enbrel, Wyeth Laboratories) 25 mg subcutaneously. The following day the patient showed a general improvement and an improved respiratory condition (Figure 2). After 2 days, he could finally be separated from NIPSV and undergo continued care in an isolated hospital ward breathing supplemental oxygen via nasal prongs. Three days after the first dose of etanercept, a second dose was administered without significant changes in the clinical condition of the patient. However, 4 days after the second dose of etanercept, the patient experienced exacerbation of respiratory symptoms, malaise, and fever of 100.5 F (Figure 2). Due to the short half-life of etanercept, this scenario was attributed to a paradoxical reaction and resolved promptly with the administration of a final third dose of etanercept along with hydrocortisone 200 mg intravenously. Within a few days, the clinical condition of the patient allowed his transfer to a unit with long-term care facilities, and after a month with negative smears for acid-fast bacilli he was finally discharged to their community under a directly observed therapy (DOT) program.
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PMC4532053_01
Female
52
A 52-year-old woman was admitted due to intermittent abdominal pain for 10 days. The pain was postprandial, periumbilical, migrating and colicky and was accompanied by occasional nausea and vomiting. She also had weight loss of 8 kg for 1 month. There was no history of pulmonary tuberculosis, hypertension or diabetes mellitus. She never smoked or drank alcohol. On admission, her body temperature was 36.4 C, the pulse 72/min and respiration 20/min. Her blood pressure was 100/70 mmHg. She had a chronically ill-looking appearance. The conjunctivae were not pale and the sclerae were not icteric. Her abdomen was flat and mildly tender on the epigastrium without rebound tenderness. Bowel sound was slightly increased. No mass or organomegaly could be noted. There was no abnormal finding on digital rectal examination. Hemoglobin was 11.5gm/dl, hematocrit 34.2%, and WBC 9,000/mm3 (60% segmented neutrophils, 7% band neutrophils and 32% lymphocytes). Total serum bilirubin was 0.9 mg%, AST 40 IU/L, ALT 20 IU/L and albumin 3.7 gm%. Serum electrolytes, CEA and alpha fetoprotein were normal. There was no abnormal finding on the chest X-ray. The upright plain abdominal film revealed a mild ileus of the small bowel. Broad spectrum antibiotics were started and she was forced to take nothing by mouth, but no improvement was noted. On the 3rd hospital day, abdominal ultrasonogram demonstrated an echogenic lesion located in the supravesical space (Fig. 1), and abdominal CT scan disclosed a dilated small bowel loop filled with fluid and a round solid mass in the right anterior supravesical space (Fig. 2). On the 4th hospital day, she underwent an exploratory laparotomy with an impression of small bowel obstruction by a tumor. During the operation, a jejunojejunal intussusception was noted with an intraluminal obstructing mass. The small bowel was dilated proximally and lymphadenopathy on the surrounding mesentery was noted. Grossly, it was a well-established polypoid mass (2.3x2.1x2 cm) located perpendicular to the plane of mucosa on the edge of the mesenteric line of the jejunum (Fig. 3). The cut surface of the polyp was homogeneously pinkish-yellow with smooth glistening surface (Fig. 4). Grossly, the serosa and the mucosa of the jejunum were unremarkable. Microscopically, the lesion consisted mainly of a mass of loose connective tissue developed in the submucosa. Loose fibrous stroma infiltrated the muscularis propria, and the variably sized small vessels were observed with diffuse inflammatory infiltrates, mostly eosinophils (Fig. 5, 6). Resected mesenteric lymph nodes showed reactive hyperplasia. All these findings were well compatible with an inflammatory fibroid polyp. The patient's postoperative course was uneventful with prompt resolution of periumbilical pain and vomiting.
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PMC7303448_01
Male
56
A 56-year-old, healthy man who was a current smoker required emergency admission at Asakura Medical Hospital with chief complaints of a fever, cough, sputum, and dyspnea for 10 days. He had no history of medications or circumstances indicative of inhaled hyphal exposure before the onset of respiratory symptoms. His respiratory rate was 30 beats per min, and his oxygen saturation was 92% (87% at room air) with 4 L/min of nasal oxygen therapy. His blood test showed values almost within the normal range: neutrophil count (4,940x103 cells/mL), fasting glucose (10.8 mg/L), and hemoglobin A1c (6.2% of the value recommended by the National Glycohemoglobin Standardization Program). The 1-3-beta-D glucan level in blood was 488 pg/mL (cut-off value, 20 pg/mL). The serum galactomannan antigen level for Aspergillus, assessed by an enzyme-linked immunosorbent assay, was 3.8 according to the cut-off index. A complement fixation test (BML, Tokyo, Japan) indicated a less than four-fold increased level of anti-Aspergillus antibodies (negative results). Serum human immunodeficiency virus (HIV)-1 and HIV-2 antibodies and HIVp24 antigen were not detected by a chemiluminescent enzyme immunoassay (BML). Chest computed tomography (CT) revealed multiple regions of bronchial wall thickening with peribronchial infiltrations before treatment (Fig. 1). No evidence of rhinosinusitis was found on facial CT. Fiberoptic bronchoscopy showed multiple areas of ulceration and swelling, with geographical, moss-like white coats on the tracheobronchial mucosa (Fig. 2A). Treatment with a combination of empirical intravenous anti-fungal agents [250 mg twice daily (total 500 mg/body/day) of voriconazole and 150 mg twice daily (total 300 mg/boy/day) of micafungin] was initiated after confirming the presence of fungal hyphae in bronchial lavage samples (eighth day of hospitalization). Evidence of bacterial and mycobacterial infections in the sputum, bronchial lavage, and blood and tests for urinary antigens of Legionella and pneumococcus were negative; nevertheless, intravenous administration of 500 mg thrice daily (total 1,500 mg/body/day) of doripenem and 200 mg twice daily (total 400 mg/body/day) of minocycline was added to the treatment regimen for suspected mixed typical and/or atypical pneumonia with fungal infections from day 1 to 10 after hospitalization. Pneumocystis jirovecii DNA was not detected in the bronchial lavage samples by a polymerase chain reaction assay. Transbronchial lung biopsies (TBLBs) of the right B1, B3, B5, and B8 lung segments were performed. Each TBLB specimen stained with hematoxylin and eosin showed similar findings of the presence of extensive fungal hyphae, although the presence of hyphal invasion into the lung parenchyma and surrounding blood vessels could not be verified (Fig. 2B). Grocott staining revealed multiple septate hyphae, branched at acute angles, and the hyphae were grouped in typical Aspergillus conidial heads (Fig. 2C). Chest CT 14 days after treatment initiation revealed cylindrical bronchiectatic changes with peribronchial infiltration (Fig. 3). The patient died on the 29th day of hospitalization due to multiple organ failure with disseminated intravascular coagulation despite being transferred from the intensive-care unit to the high-care unit of Kurume University Hospital (16th day of hospitalization). Aspergillus fumigatus was repeatedly isolated from the bronchial washings and sputum, and the minimum inhibitory concentration (MIC) for micafungin and voriconazole, calculated based on the isolated strains by the modified broth dilution method (BML), were found to be <=0.015 and 0.25 mug/mL, respectively.
fulminant, healthy individual, tracheobronchial aspergillosis
Chest CT findings before treatment. lower lobe. revealed bronchial wall thickening with para-bronchi infiltration in almost all large bronchi. CT: computed tomography.
PMC7303448_01
Male
56
A 56-year-old, healthy man who was a current smoker required emergency admission at Asakura Medical Hospital with chief complaints of a fever, cough, sputum, and dyspnea for 10 days. He had no history of medications or circumstances indicative of inhaled hyphal exposure before the onset of respiratory symptoms. His respiratory rate was 30 beats per min, and his oxygen saturation was 92% (87% at room air) with 4 L/min of nasal oxygen therapy. His blood test showed values almost within the normal range: neutrophil count (4,940x103 cells/mL), fasting glucose (10.8 mg/L), and hemoglobin A1c (6.2% of the value recommended by the National Glycohemoglobin Standardization Program). The 1-3-beta-D glucan level in blood was 488 pg/mL (cut-off value, 20 pg/mL). The serum galactomannan antigen level for Aspergillus, assessed by an enzyme-linked immunosorbent assay, was 3.8 according to the cut-off index. A complement fixation test (BML, Tokyo, Japan) indicated a less than four-fold increased level of anti-Aspergillus antibodies (negative results). Serum human immunodeficiency virus (HIV)-1 and HIV-2 antibodies and HIVp24 antigen were not detected by a chemiluminescent enzyme immunoassay (BML). Chest computed tomography (CT) revealed multiple regions of bronchial wall thickening with peribronchial infiltrations before treatment (Fig. 1). No evidence of rhinosinusitis was found on facial CT. Fiberoptic bronchoscopy showed multiple areas of ulceration and swelling, with geographical, moss-like white coats on the tracheobronchial mucosa (Fig. 2A). Treatment with a combination of empirical intravenous anti-fungal agents [250 mg twice daily (total 500 mg/body/day) of voriconazole and 150 mg twice daily (total 300 mg/boy/day) of micafungin] was initiated after confirming the presence of fungal hyphae in bronchial lavage samples (eighth day of hospitalization). Evidence of bacterial and mycobacterial infections in the sputum, bronchial lavage, and blood and tests for urinary antigens of Legionella and pneumococcus were negative; nevertheless, intravenous administration of 500 mg thrice daily (total 1,500 mg/body/day) of doripenem and 200 mg twice daily (total 400 mg/body/day) of minocycline was added to the treatment regimen for suspected mixed typical and/or atypical pneumonia with fungal infections from day 1 to 10 after hospitalization. Pneumocystis jirovecii DNA was not detected in the bronchial lavage samples by a polymerase chain reaction assay. Transbronchial lung biopsies (TBLBs) of the right B1, B3, B5, and B8 lung segments were performed. Each TBLB specimen stained with hematoxylin and eosin showed similar findings of the presence of extensive fungal hyphae, although the presence of hyphal invasion into the lung parenchyma and surrounding blood vessels could not be verified (Fig. 2B). Grocott staining revealed multiple septate hyphae, branched at acute angles, and the hyphae were grouped in typical Aspergillus conidial heads (Fig. 2C). Chest CT 14 days after treatment initiation revealed cylindrical bronchiectatic changes with peribronchial infiltration (Fig. 3). The patient died on the 29th day of hospitalization due to multiple organ failure with disseminated intravascular coagulation despite being transferred from the intensive-care unit to the high-care unit of Kurume University Hospital (16th day of hospitalization). Aspergillus fumigatus was repeatedly isolated from the bronchial washings and sputum, and the minimum inhibitory concentration (MIC) for micafungin and voriconazole, calculated based on the isolated strains by the modified broth dilution method (BML), were found to be <=0.015 and 0.25 mug/mL, respectively.
fulminant, healthy individual, tracheobronchial aspergillosis
Chest CT findings 14 days after initiation of anti-fungal treatment. lower lobe. revealed cylindrical bronchiectatic changes in almost all large bronchi. CT: computed tomography.
PMC4306077_01
Female
45
A 45-year-old previously well Sri Lankan lady was admitted to the Teaching Hospital, Kandy, Sri Lanka with severe shortness of breath and respiratory distress for a duration of 24 h. She had experienced sore throat and mild fever 10 days back followed by left-sided neck pain for the last 5 days. Pain was not radiating but aggravated by neck movements. There was no associated trauma to the neck. Subsequently, the patient had noted progressive facial and left upper limb swelling without any color changes and motor or sensory disturbances. For the past 24 h, she had experienced progressive shortness of breath. There was no odynophagia, pleuritic chest pain, cough or hemoptysis. She denied constitutional symptoms, features suggestive of connective tissue disorder and past history of miscarriages or thromboembolic diseases. She had no recent travel history or sexual risk behaviors. Drug and allergic history were nil of note. On examination, she was obese with a body mass index (BMI) of 28.4 kg/m2. Her axillary temperature was 100 F. Symmetrical facial swelling and left upper limb swelling were noted but had no color changes in the swollen areas. Ear and throat examinations were unremarkable. There was no cervical lymphadenopathy. Cord sign (an induration of the internal jugular vein beneath the anterior border of the sternocleidomastoid muscle) was positive. Her pulse rate was 130 beats per minute, low volume pulse noted with pulsus paradoxus, blood pressure was 80/50 mmHg, and had soft heart sounds. Respiratory rate was 48 cycles per minute; oxygen saturation was 93% on air and had bi-basal reduced air entry with stony dull percussion note. Abdominal and neurological system examinations were unremarkable. Urgent investigations revealed sinus tachycardia with electrical alternans in the electrocardiogram and cardiomegaly with bilateral pleural effusions on chest roentgenogram. Echocardiogram showed evidence of pericardial tamponade with right atrial and right ventricular collapse. Pericardial fluid aspiration was performed under sterile conditions, removing 450 ml of straw color fluid. Subsequently, her respiratory distress settled and blood pressure normalized. Further investigations revealed the following: hemoglobin - 11 g/dL, white cell count - 17.7 x 103/muL (neutrophils - 86.2%, lymphocytes - 6.9%, monocytes - 6.1%, eosinophils - 0.7%, basophils - 0.1%), and platelets - 486 x 103/muL. Blood picture was suggestive of bacterial infection (polymophonuclear leucocytes with left shift up to band forms and mild thrombocytosis). Her erythrocyte sedimentation rate was 52 mm in the first hour (normal <20) and C-reactive protein level was 162 units (normal <5 units). Two blood cultures were positive for MRSA species. Pericardial fluid analysis showed the following: protein - 4 g/dL, white cells - 156/muL (neutrophils - 90%, lymphocytes - 9%), acid fast bacilli - not seen, liquid culture for mycobacterium tuberculosis - no growth, adenosine-deaminase level - 35 units/L, cytology - negative for malignant cells. Pericardial fluid culture revealed a growth of MRSA in 26 h of incubation. Ultrasound scan and venous duplex scan of the neck showed thrombosis of left internal jugular, left external jugular, and left subclavian and left axillary veins with preserved flow in superior vena cava. Computed tomography (CT) scan of the neck and the chest showed similar findings to the venous duplex with additional moderate pericardial effusion (following first pericardiocentesis), bilateral pleural effusion, and left-sided consolidation of the lung (Figure 1). No lymphadenopathy or retropharyngeal abscess formation was noted in CT scan. Abdominal ultrasound scan was normal. Her urine analysis, lactase dehydrogenase level and renal and liver function tests were normal. Nebulized samples for sputum acid fast bacilli staining and Mantoux test were negative. Serology for infectious mononucleosis, Epstein-barr virus, hepatitis B and C, and human immunodeficiency virus showed negative results. Thrombophilia screening was normal (anti-nuclear antibodies, anti-cardiolipin antibodies, homocysteine level, sickling test and factor V Leiden mutation). The diagnosis of Lemierre's syndrome secondary to community-acquired MRSA was made with the evidence of history of sore throat, left internal jugular vein thrombosis, MRSA septicemia and distant metastatic infection involving pleura and pericardium, resulting in pleural and pericardial effusions. Pericardiocentesis was performed three times on day 0, day 1, and day 3 due to repeated tamponade effect. Patient was treated initially with intravenous meropenem and subsequently changed over to intravenous vancomycin (according to the antibiotic sensitivity of MRSA) and clindamycin. She showed dramatic response with complete resolution of symptoms and normal follow-up echocardiogram findings. Intravenous antibiotics were continued for 2 weeks and oral clindamycin was continued for further 4 weeks. Patient was initially given intravenous heparin followed by warfarin for a duration of 3 months. On further follow-up after 2 months, patient was completely asymptomatic without residual effects and repeat venous duplex of the neck veins showed recanalization and restoration of the blood flow in the previously thrombosed veins.
cardiac tamponade, community acquired methicillin resistant staphylococcus aureus, fusobacterium necrophorum, lemierre’s syndrome, pericardiocentesis, thrombophlebitis
Contrast-enhanced CT of chest showing pericardial effusion (white arrow), bilateral pleural effusions and left-sided lung consolidation (red arrow).
PMC10423562_01
Male
53
A previously healthy 53-year-old male was admitted to our emergency department on 2022-10-10 at 12:00 p.m. with fever, thrombocytopenia, and abnormal liver function. The patient is a cook. In the past 20 years, he has smoked approximately 10 cigarettes a day and consumed approximately 80 grams of alcohol once a week. Before the onset of this disease, he had no underlying diseases, his annual check-ups had never indicated thrombocytopenia or abnormal liver function, he had never had any hepatitis or any surgery or any history of blood transfusion before and had not used any drugs or herbs recently. Eight days prior, the patient displayed weakness and severe nausea without a clear cause. He started experiencing muscle aches all over his body, a 39 C body temperature, a gradual darkening of his urine to a coffee colour, yellow skin, and sclera staining 5 days prior. He visited the neighbourhood hospital. The results of the tests at that time revealed severe thrombocytopenia, abnormal liver function, and inflammation. His symptoms grew worse after 4 days of treatment with piperacillin sodium and tazobactam sodium for injection 4.5 g q8h, compound glycyrrhizin, reduced glutathione, transmetil, ursodeoxycholic acid, and interleukin-11, and he visited our emergency room. At admission, he was conscious, able to answer questions clearly, his body skin and sclera depth yellow staining, and had no obvious haemorrhagic points or purpura on his body. He also had no obvious cardiopulmonary abnormalities, light tenderness in his xiphoid process, no enlargement of his liver or spleen, Murphy's sign (+), and no abnormalities in the nervous system physical examination. Urgent laboratory testing were as follows: PLT count 13 K/UL, Hb 104 g/L, Ret 52.4 K/UL, RBC count 3.47*10^6/UL, WBC count 10.94 K/UL, CRP 84.9 mg/L, ALT 288 U/L, AST 580 U/L, GGT 130 U/L, ALP 217 U/L, TB 15.76 mg/dL, DB 12.89 mg/dL, PT 14s, INR 1.22, and Cr 1.68 mg/dL. The direct Coombs test was negative, and the COVID-19 nucleic acid test was negative. Therapies were initiated empirically with intravenous fluids. Glucocorticoids were given intravenously at a dose of 80 mg q12h and were combined with high-dose gamma globulin, meropenem 1 g q8h of anti-infection, ornithine aspartate and adenosine methionine for liver protection, and interleukin-11 to produce platelets. He also received 20 units of platelets and 300 mL of plasma. On 2022-10-11 at 02:30, the patient suddenly displayed unconsciousness, an elevated heart rate, and limb convulsions, then developed decreased blood pressure and heart rate, and the carotid pulse was unreachable. Cardiopulmonary resuscitation was immediately performed. Approximately 1 minute later, the patient returned to sinus heart rate. After the rescue, we immediately performed blood tests on the patient, and the results showed that the levels of myocardial injury markers and blood potassium were normal. An urgent CT scan showed no obvious brain abnormalities, scattered cholecystitis or inflammation in the two lungs. Ten hours later, laboratory test results were returned as follows: anti-HEV-IgM antibodies (1.3 S/CO) and anti-HEV-IgG antibodies (5.9 S/CO) were positive, whole blood metagenomics for pathogen detection failed to find any pathogens' DNA or RNA, anti-endothelial cell antibodies (AECA) +1:100. His laboratory tests did not support the diagnosis of hepatitis A or B or C, toxoplasmosis, Treponema pallidum, rubella, cytomegalovirus, herpesvirus and HIV. After a multidisciplinary discussion among doctors in the infectious, haematology and emergency departments, the preliminary diagnosis was 1. Acute hepatitis E; 2. Non-exclusion of haematological diseases; 3. Possibility of autoimmune liver disease; and 4. Cholecystitis. Considering the haematological diseases, we immediately performed bone marrow aspiration and biopsy and peripheral blood smear cell morphology analysis. We found more than 1% schistocytes on the peripheral blood smear (shown in Figure 1). On that day, his haemoglobin level was 8.3 g/dL, and schistocytes on the bone marrow smear were also found, suggesting microangiopathy haemolytic anaemia (MAHA). Laboratory results on 2022-10-10 were used to evaluate the patient via the PLASMIC score: peripheral blood platelet counts 13 K/UL (1 score), indirect bilirubin 2.87 mumol/L (1 score), no advanced cancer (1 score), no history of solid organ transplantation or stem cell transplantation (1 score), International Normalized Ratio (INR) 1.22 (1 score), and Cr 1.68 mg/dL (1 score), with 6 scores in total. It was suggested that the patient had a high risk of TTP. The patient's peripheral blood was sent for testing on 2022-10-12 to determine ADAMTS-13 activity and its inhibitor. The test results came back the following day, showing that ADAMTS-13 activity was 0% and ADAMTS-13 inhibitor was positive. The diagnosis of iTTP was clear. We started the primary treatment plan immediately, which included intravenous administration of rituximab 0.6 g once a week, 80 mg of glucocorticoids every 12 hours, and daily plasma exchange. The time between plasmapheresis was gradually increased throughout the course of the treatment, and the dosage of glucocorticoids was decreased from 80 mg q12h (for 6 days) to 40 mg q12h (for 5 days) to 20 mg q12h (for 7 days) to 30 mg qd (for 5 days) to 20 mg qd (at discharge). The patient gradually became conscious, his platelet counts gradually increased, while bilirubin, AST, ALT, and Cr gradually decreased, ADAMTS-13 activity recovered to 100%, and the ADAMTS-13 inhibitor returned negative on 2022-10-18. The patient's platelet counts reached 254 K/UL on 2022-11-04 following the final plasma exchange and rituximab treatment on 2022-11-03, with a total of 12 plasma exchanges and 4 doses of rituximab. Liver function indicators were also much better than they were previously (shown in Figure 2). Schistocytes were still visible in peripheral blood smears that day, but they were considerably fewer than they had been earlier in the course of treatment. The patient was eligible for discharge and was discharged on 2022-11-05 with oral glucocorticoids (20 mg qd) and ursodeoxycholic acid. The patient underwent routine follow-up exams at the hospital over the course of the following five months, which revealed no anomalies.
abnormal liver function, case report, extrahepatic manifestations related to hepatitis e, thrombocytopenia
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PMC5992945_01
Male
30
A 30-year-old teacher presented to the outpatient department with the complaints of swelling of the right index finger for the past 2 years. This swelling was slowly progressive in size and was associated with dull pain and difficulty in flexing the affected digit. There was no history of trauma or drug abuse. He had no history of TB or other systemic diseases. On evaluation, the swelling was found to involve the flexor aspect of the index finger extending onto the palm [Figures 1 and 2]. Fine-needle aspiration cytology of the swelling revealed giant cells suggesting the possibility of giant cell tumour (GCT) of the tendon sheath. A plain radiograph [Figure 3] of the finger was done, and the phalanges and the second metacarpal were found to be free from any visible lesions. The patient was not affordable for any further workup, and hence, MRI was not included in the pre-operative planning. A provisional diagnosis of GCT of flexor tendon sheath and a differential diagnosis of compound palmar ganglion and tendinous xanthoma was kept, and the patient was planned for exploration/excision after taking consent for amputation of the digit. The exploration was done under brachial block and tourniquet control. Brunner's zig-zag incision was used to expose the tumour over the flexor aspect of the digit and palm. A lobulated swelling was found extending from the distal interphalangeal joint to the proximal palm of the concerned digit. The swelling was covered by a tough, thickened, fascia-like structure. This covering was gingerly opened at several places to reveal a synovial sac full of small, shiny rice-bodies, which spilled out from the sac due to the excessive pressure inside the sac [Figure 4]. All the rice bodies were evacuated, and the sac was excised. We were unable to differentiate the synovial sheath of the flexor tendon as separate from this thickened sac-like structure, and hence concluded that this sac-like structure was indeed the synovial sheath of the tendon. The rice bodies along with the excised thickened synovial sheath were sent for the histopathological examination. Flexor tendon pulley was reconstructed by palmar fascia. The wound was closed in layers over a suction drain. The limb was dressed with mild compressive bandage and splinted with a plaster of paris dorsal slab. On histopathological examination, sections from the intra-lesional content showed acellular, proteinaceous material with mild inflammatory infiltrate [Figure 5] and sections from the cyst wall showed fibrocollagenous tissue diffusely infiltrated by confluent granulomas [Figures 6 and 7] comprising of epithelioid cells, lymphocytes, plasma cells and Langhan's type giant cells suggesting TB. After the histopathology report suggested the possibility of TB, the patient was investigated and found to have elevated erythrocyte sedimentation rate (ESR) of 32 (Normal range in males below 50 years of age is <15) and a positive Mantoux test (>10 mm). Polymerase chain reaction for Mycobacterium tuberculosis (PCR-Tb) was negative. Chest radiography showed minimal pleural effusion on the left side, and pulmonary physician opinion was sought for the same. Sputum examination by Ziehl-Neelsen staining was positive for acid-fast bacilli (reported 1+). The patient was started on empirical anti-tuberculosis therapy (ATT) and showed improvement of pleural effusion and hand swelling. After regular follow-up, at the end of 9 months of ATT, the patient had no clinical or radiological evidence of the disease.
flexor, tendon, tenosynovitis, tuberculosis osteoarticular
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PMC5457660_01
Male
73
Clostridium perfringens CBA7123 (=KCCM 43242) was isolated from the feces of a 73-year-old man, and a pure culture was obtained using serial dilution. The colony was cultured anaerobically in ATCC medium no. 2840, modified Eggerth-Gagnon medium (10 g peptone, 4 g Na2HPO4 2H2O, 2 g porcine gastric mucin, 50 ml sheep blood, and 15 g agar per liter) at 37 C for 24 h. The total genomic DNA of strain CBA7123 was extracted using QuickGene DNA tissue kit S (Kurabo, Japan) and the G-spin total DNA extraction kit (iNtRON Biotechnology, Korea). The purity, quality, and quantity of genomic DNA were measured using Agilent 2100 Bioanalyzer (Agilent Technologies, USA) as described the manufacturer's instruction. Detailed genome sequencing was performed as described previously. Briefly, the genomic DNA of strain CBA7123 was sheared according to the PacBio 20-kb Template Preparation using BluePippin Size-Selection System protocol, and SMRTbell library was prepared using P6-C4 chemistry (Pacific Biosciences, USA). The sequences were obtained using PacBio RS II system (Pacific Biosciences) as following an instruction of the manufacturer. The 150,292 reads were generated with 7090 bp of average read length by the PacBio RS II system from one SMRT cell. De novo assembly of the genome sequence was performed using Hierarchical Genome Assembly Process (HGAP) version 2 software, with default parameters supported by PacBio SMRT Analysis ver. 2.3.0. rRNA and tRNA of the assembled sequence were identified using RNAmmer 1.2 and tRNAscan-SE 1.21, respectively. Genes were predicted using Glimmer3 of Rapid Annotation using Subsystem Technology (RAST) server (http://rast.nmpdr.org), and functional gene annotations were performed using the SEED, Clusters of Orthologous Groups (COG, http://www.ncbi.nlm.nih.gov/COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG, http://www.genome.jp/kegg/) databases. PathogenFinder 1.1 and ResFinder 2.1 were used to estimate the pathogenicity and antimicrobial resistance genes, respectively. The virulence factors were searched using the Basic Local Alignment Search Tool (BLAST) in the virulence factors of pathogenic bacteria database with default parameters and predicted with zero e-value. The C. perfringens strains for comparative genomic analysis were selected using Microbial Nucleotide BLAST in the NCBI complete genome database. The four strains with BLAST total scores over 5.5e+06 were selected: strains FORC 003, JP55, FORC 025, and JP838. To compare the genomic structures between strain CBA7123 and these four strains, the progressive alignment algorithm in MAUVE multiple genome alignment software 2.4.0 was used. The OrthoANI algorithm was used to analyze genomic relatedness between strain CBA7123 and other C. perfringens species. OrthoANI percentages were calculated and a phylogenetic tree was constructed, as described by Lee et al.. Orthologs between strain CBA7123 and the reference strains were predicted and mapped using the reciprocal best hit method in UBLAST. Pan-genome orthologous groups (POGs) were estimated using the EzBioCloud Comparative Genomics Database (http://cg.ezbiocloud.net/), and their presence was calculated using the Jaccard coefficient. UPGMA clustering was then used to show clustering between strain CBA7123 and the reference strains as a dendrogram, based on the presence or absence of gene content. The intersections and differences of POG sets of the different strains were visualized as a Venn diagram, using the jvenn program. The single colony of strain CBA7123 was transferred more than three times to obtain a pure culture and confirmed using a variable pressure field emission scanning electron microscope (Chuncheon Center, Korea Basic Science Institute, Korea) (Additional file 1: Figure S1) and a PCR-sequencing approach targeting 16S rRNA gene as described by Min et al..
antimicrobial resistant, clostridium perfringens, comparative genomic analysis, complete genome sequence, pathogenesis, virulence factor
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PMC7098350_01
Male
24
A 24-year-old previously healthy male soldier experienced an upper respiratory tract infection (URI) 2 weeks prior to his presentation. One week after the infection subsided, he had dysphagia, truncal and limb ataxia, and symmetrical proximal muscles weakness. On the third day of his neurological illness, total ophthalmoplegia, cerebellar dysarthria, and generalized hyporeflexia were evidenced at a primary hospital, and then, he was immediately transferred to our hospital. He had never been exposed to food or substances containing neurological toxins. On admission to our center, the weakness of limbs and respiratory muscles progressed rapidly to flaccid quadriparesis, which was dominant in the upper limbs, and respiratory muscle paralysis so that mechanical ventilation was indicated. All deep tendon reflexes were absent. Nevertheless, his consciousness, pinprick sensation, and proprioception were absolutely intact. MFS and GBS overlap syndrome was a provisional diagnosis at initial evaluation. The GBS disability score at that time was 5. Medical Research Council sum score was 44; the muscle strength was symmetrical as follows: both shoulders abduction 3; elbow flexion 3; wrist extension 4; hip flexion 4; knee flexion 4, and ankle dorsiflexion 4. The results of routine blood chemistry tests, anti-HIV, anti-HBV, anti-HCV, as well as a panel of serology tests of autoimmune disorders were unremarkable. The cerebrospinal fluid (CSF) analysis revealed clear CSF, normal pressure, and no blood cells. The CSF/serum glucose ratio was 83/110 mg/dL. CSF protein was 74.9 mg/dL. CSF culture and polymerase chain reaction for possible organisms, such as bacteria, mycobacterium tuberculosis, herpes viruses, Japanese B virus, and Dengue viruses, yielded negative results. The electroneuromyographic (ENMG) study showed symmetrical sensorimotor axonal polyneuropathy, which was dominant in both upper limbs. Left facial axonal neuropathy was detected as well (Fig. 1). A panel of AGAbs, including anti-GM1, -GM2, -GM3, -GD1a, -GD1b, -GT1b, and -GQ1b, was negative. Based on the clinical presentation and ENMG results, MFS/AMSAN-GBS overlap syndrome was the final diagnosis, and intravenous immunoglobulin (IVIG) therapy was immediately initiated. The neurological symptoms dramatically resolved 4 days after the treatment. GBS disability score became 2 eventually.
demyelinating disease, guillain-barré syndrome
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PMC4865634_01
Male
33
A 33-year old man was admitted to our hospital because of a 5-day history of continuous fever up to 39 C, and diffuse headache. He was unmarried and lived with his parents in Thirasia Island near Santorini, working as a builder, was sexually active and consistently used condoms. He did not smoke, use illicit drugs, or misuse alcohol, had no pets or exposures to animals, and had never traveled abroad. The man reported no recent tick or mosquito bites, no ingestion of unpasteurized milk or milk products, and no sick contacts and had received all routine childhood vaccinations, had no known medical problems, and did not take any medications. His family history was negative for tuberculosis, cancer or autoimmune disease. On physical examination, the patient appeared well and was in no acute distress; he was alert and communicative. His temperature was 39 C, heart rate 73 beats per minute, blood pressure 120/80 mmHg, respiratory rate 16 breaths per minute, and oxygen saturation 99% while breathing ambient air. He had no synovitis, rash, photophobia, or nuchal rigidity. His abdomen was soft, with mild tenderness in the left upper quadrant on deep palpation. There was no hepatomegaly or splenomegaly, and no cervical, axillary, or femoral lymphadenopathy. Heart murmurs were not detected. Laboratory analyses revealed normocytic, normochromic anemia (hemoglobin level, 12 g per deciliter), with a low reticulocyte count (0.3%), leukopenia (white-cell count, 3420 per cubic millimeter, with 68% neutrophils, 25% lymphocytes, 7% monocytes, and no eosinophils or band forms), thrombocytopenia (platelet count, 87,000 per cubic millimeter), and elevated levels of hepatic aminotransferases (aspartate transaminase 138 U per liter, alanine transaminase 111 U per liter), lactate dehydrogenase (1383 U per liter), creatine phosphokinase (1019 U per liter), and C-reactive protein (112 mg per liter). Clotting times (dilute prothrombin time and activated partial-thromboplastin time) were not prolonged. Urinalysis was normal. Multiple blood cultures were sterile. An abdominal ultrasound examination revealed a mildly enlarged spleen, with two peripheral wedge-shaped hypoechoic lesions, which were characteristic of splenic infarcts. A computed tomography (CT) scan of the abdomen (Fig. 1), obtained after the administration of intravenous and oral contrast material, confirmed the results of ultrasonography, demonstrating splenomegaly (with the spleen measuring 15.4 cm in the craniocaudal dimension), and two wedge-shaped areas of hypoenhancement in the periphery of the spleen, features that were consistent with splenic infarcts. No other organ abnormality was observed. An electrocardiogram showed sinus rhythm. Transesophageal echocardiography showed no valvular vegetations. Hepatitis A immunoglobulin M (IgM) antibody, hepatitis B surface antigen and core IgM antibody, a polymerase chain reaction (PCR) assay for hepatitis C viral RNA, and serologic tests for cytomegalovirus (CMV), herpes simplex virus, coxsackie A virus, echovirus, human immunodeficiency virus, Rickettsia species, Coxiella burnetii, Brucella melitensis, and Leishmania were negative, as was real-time reverse transcriptase PCR for H1N1 influenza A virus. Antibody tests for Epstein-Barr virus (EBV), coxsackie B virus, and Toxoplasma gondii showed evidence of past infection. Parvovirus B19 IgM antibodies were positive, while parvovirus B19 immunoglobulin G (IgG) antibodies were negative, indicating an acute infection. Titers of anticardiolipin and anti-beta2-glycoprotein I antibodies were within normal limits. The patient received symptomatic treatment with antipyretic and analgesic agents. Over the following few days, his clinical and laboratory status gradually improved. On the fifth hospital day, his fever resolved. He was discharged home on the tenth hospital day. Whether he developed parvovirus B19-specific IgG antibodies during the convalescent phase remained unknown, because the relevant test could not be performed in his island.
parvovirus b19, splenic infarcts
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PMC6744768_01
Female
37
A 37-year-old female presented with the sudden onset of abdominal pain rapidly accompanied by numbness and weakness in both lower extremities. On examination, she was paraparetic (right 3/5 and left 4/5 proximally/distally) and exhibited decreased pin, temperature, vibration, and position perception below the T8 level. The thoracic magnetic resonance image (MRI) revealed a dorsal intradural extramedullary cyst at the T7 level, compressing, and displacing the cord anteriorly. The T2-weighted image is showed a high-intensity uniform cyst (filled with cerebral spinal) [Figure 1]. The myelogram further demonstrated a near complete block at the T7 level (e.g., intrathecal contrast only slowly passed the T7 level extending cephalad). The thoracic computed tomography myelography confirmed the presence of a uniformly filling arachnoid cyst [Figure 2a-c]. Initially, the patient was treated conservatively with steroid therapy; indeed, she exhibited some gradual spontaneous improvement (e.g., able to walk without any support within 1 day). However, her ataxia and proprioceptive deficits in both legs persisted, and the spinal arachnoid cyst did not regress on the follow-up MRI. Surgery consisting of a T6-T8 hemilaminectomy, therefore, was performed 2 weeks after the onset of symptoms. Upon opening the dura mater, we found an arachnoid cyst with a thick whitened wall compressing the spinal cord. Notably, the cyst pulsated with each heartbeat and contained clear CSF fluid. There was, however, no documented communication between the cyst and the subarachnoid space. After removing the cyst, the histological examination confirmed the diagnosis of an arachnoid cyst. Two weeks postoperatively, the patient fully recovered.
paraparesis, spinal arachnoid cyst, sudden onset, valsalva-like maneuver
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PMC7575779_01
Female
62
A 62-year-old female patient, who resides in Caracas, Venezuela, and had no previous relevant medical history was seen in January 2019, because of a lower back pain and a sciatica leg pain affecting both lower limbs. The straight leg raise test (Lasegue test) was positive, producing a radiating pain in both extremities. Other physical examinations, including a neurological examination, biochemical and cellular blood examinations, a chest X-ray and an electrocardiogram, were normal. An MRI (Magnetic Resonance Imaging) scan of the lumbar spine showed evidence of a fracture and pseudoarthrosis of L2-L3-L4 and lysis of discs L2-L3 and L3-L4. The patient was hospitalized with a differential diagnosis of infectious spondylodiscitis versus a space-occupying lesion (Fig. 1). A percutaneous transpedicular biopsy of the spine was cultivated on egg-based solid Lowenstein-Jensen and Stonebrink media. On Stonebrink medium, a confluent growth of smooth colonies was observed after 3 weeks of incubation. After 7 weeks of incubation (one week longer than the regular incubation time for cultures in most TB laboratories), dysgonic growth of a few small colonies of acid-fast bacilli were observed in l-J medium. Due to this dysgonic growth on said medium and the appearance of smooth colonies and atypical rough colonies of M. tuberculosis, the laboratory further characterized the Mtb-complex strain for the presence of regions of difference (RD), a molecular technique used to differentiate between the members of the MTBC based on variable regions among the genomes of the MTBC, which are results of insertion-deletion events. This genetic analysis revealed an RD9 and RD4 deletion and the presence of the region RD1, characteristic for a M. bovis strain. Given that M. bovis is naturally resistant to pyrazinamide, the patient was treated with a standard TB treatment replacing pyrazinamide with moxifloxacin. A control MRI scan was performed after six months of treatment and showed a radiological improvement compared to the earlier imaging studies. The patient is now on the waiting list for a bilateral laminectomy of the L3, L4, and L5.
glycerol, growth inhibition, lowenstein-jensen medium, mycobacterium bovis, pott, sodium pyruvate, stonebrink medium, tuberculosis, zoonosis
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PMC6675865_01
Female
36
The patient was a 36-year-old woman, married, with no children; having completed a higher education, she is a lawyer by profession. In October 2013, the patient sought psychiatric help in an outpatient clinic due to depressed mood, decreased interest, insomnia, feelings of worthlessness, and significant weight change (-10%). MDD, 296.22 [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)] was diagnosed, and the patient received escitalopram 20 mg/d, with no improvement after 5 weeks' treatment. Thus, the treatment changed to paroxetine 60 mg/d and trazodone 150 mg/d, which resulted in a marked improvement within 6 weeks (difficulties in starting activities remained). In January 2014, the patient was diagnosed with Hashimoto autoimmune thyroiditis. Introduction of levothyroxine 75 mg/d was temporally connected to remission of depressive symptoms. The diagnosis was updated to mood disorder due to hypothyroidism with major depressive-like episode, 293.83 (DSM-IV-TR). In March 2015, psychiatric treatment was concluded. In May 2015, the patient became pregnant. Ultrasound examination revealed multiple birth defects of the fetus, which led to its death in week 16 of the pregnancy. The patient was hospitalized in the Department of Gynaecology and Obstetrics, where she gave birth to a dead fetus. During the event, she experienced intense fear and helplessness. Following the incident, the patient sought psychiatric help, again due to symptoms she had experienced earlier and which had returned, that is, depressed mood, decreased interest, insomnia, and feelings of worthlessness. Additional symptoms of PTSD, unreported previously, ensued: recurrent distressing dreams of the event, the sensation that the traumatic event was recurring, and the inability to recall an important aspect of the trauma (the patient did not remember a part of her stay at the gynecological ward). Attempts at broaching the subject of losing her child were met with defiance and emotional withdrawal. Her general state was characterized by an increased arousal typical of PTSD cases (irritability, outbursts of anger, difficulty concentrating, hypervigilance). The patient no longer managed to function normally in social contexts (workplace, home). MDD, 296.22, was diagnosed with the co-occurrence of acute PTSD, 309.81. Given that selective serotonin reuptake inhibitor (SSRI) medications such as sertraline and paroxetine are approved by the FDA for the treatment of PTSD and with her previous treatment response, we decided to start with paroxetine 20 mg/d and trazodone 75 mg/d. However, no marked improvement was noted following 5 weeks of treatment. Paroxetine was increased up to 60 mg/d and trazodone up to 150 mg/d, the same dose prescribed previously, which has resulted in marked improvement of her MDD. Due to a massive sleep dysfunction consisting in troubles with falling asleep, frequent waking periods during the night, and a very high level of irritability, as well as multiple outbursts of anger and anxiety, it was necessary to increase the trazodone dose to 200 mg/d and to introduce diazepam in the dose of 5 mg/tds. Moreover, the patient's somatic health condition was deteriorating rapidly. The patient lost weight [-10% within a month; body mass index (BMI) = 19 kg/m2]; she complained of general weakness, dizziness and fainting, as well as of episodes of hyperventilation and paresthesia. Physical examination revealed dehydration and low blood pressure (100/60 mmHg), which plummeted even further when standing (orthostatic hypotension). Assessments of both morning adrenocorticotropin (ACTH) and morning cortisol levels in the blood performed on an outpatient basis revealed slightly decreased results (ACTH = 6.00 pg/ml; cortisol = 4.90 ng/ml). Therefore, in April 2016, the patient was admitted to the Department of Endocrinology with suspicion of adrenal insufficiency. During the patient's stay at the ward, examination revealed correct circadian rhythm in serum cortisol (6:00, 5.60 mug/dl; 8:00, 11.30 mug/dl; 20:00, 4.40 mug/dl; 24:00, 4.20 mug/dl), as well as correct levels of the hormone in a 24-h sample of urine: 28.2 mug/24. Also, the ACTH concentration in the daily profile of the serum was correct (6:00, 6.12 pg/ml; 8:00, 10.20 pg/ml; 20:00, <5.40 pg/ml; 24:00, 7.07 pg/ml). Thyrotropin concentration (TSH) with both free thyroxine (fT4) and free triiodothyronine (fT3) were within normal range, with elevated anti-thyroid peroxidase (TPO) antibodies, 253 IU/ml (reference range < 35 IU/ml). In order to assess the ACTH/cortisol axis for detecting secondary adrenal insufficiency, a standard ITT was performed. Symptomatic hypoglycemia, with blood glucose values below 40 mg/dl, was required to evoke a reliable central stress response with the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Intravenous insulin was administered (0.1 units/kg; 6j aspart insulin). Symptomatic hypoglycemia, with blood glucose values of 29 mg/dl within 30 min of the test, was achieved. The patient experienced mild palpitations, massive hot flushes, and sweating, which disappeared within several minutes of the procedure. The results of the test excluded any abnormalities of the ACTH/cortisol and growth hormone secretion ( Table 1 ). Four days after hospitalization, the patient had a consultation with her psychiatrist (the first author of this manuscript). During the examination, a marked improvement of the patient's mental state was noted. Symptoms of PTSD were reduced: increased arousal diminished, sleep was normalized, and bouts of anxiety became much less frequent and less severe. The patient was able to recall an important aspect of the trauma, and recurrent distressing dreams of the event disappeared. MDD symptoms persisted in the clinical picture, including depressed mood, decreased interest, and feelings of worthlessness. Such results enabled the psychiatrist to take the patient off diazepam (in the course of 10 days). Over the following month, MDD symptoms gradually became less intense; consequently, trazodone was reduced from 200 to 100 mg/d, and paroxetine from 60 to 40 mg/d. In July 2017, 14 months after the ITT, pharmacological treatment was concluded, and presently, the patient remains in remission and is planning a pregnancy.
acute hypoglycemia, insulin tolerance test, major depressive disorder, posttraumatic stress disorder, psychoneuroendocrinology
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PMC7566203_01
Male
19
A 19-year-old male came to the hospital presented with back pain and weakness of both lower limbs of three months duration. It initially started in the left lower limb and subsequently involved the right lower limb. The patient also complained of urine hesitancy and a feeling of incomplete voiding of urine, but normal defecation. He came from primary health facility with acid-fast bacilli (AFB) smear-positive sputum. He was on anti-tubercular treatment for last two months with non-reactive HIV status, but there was no significant past medical history such as cough, night sweat, or decreased body weight. He denied any recent exposure from people who had tuberculosis. On examination, his mental functions and cranial nerve were normal. All of his reflexes are brisk and had a Babinsky sign for both of the lower limbs. Both of the upper limbs power were 5/5, whereas both of the lower limbs were 2/5. He had sensory impairment below T6 corresponding to vertebrae level and altered sensation with hypoesthesia. Laboratory findings revealed negative sputum examination for tuberculosis. Plain chest X-Ray, thoracolumbal, and lateral radiographs revealed normal finding (Fig. 1). Magnetic Resonance Imaging (MRI) on T1-weighted image exhibited hypointense portion, which appeared to surround the intermediate intensity lesion. The hypointense part represented the inflammatory reaction that occured around the lesion, whereas the isointensity in the middle reflected the presence of necrosis. Axial T1- weighted image showed an intradural hypointensity at T6 level (Fig. 5). T2-weighted image also showed low signal intensity at the vertebral level of thoracal VI, VII, and VIII. The hypointense portion reflected necrosis and also hypocellularity with increased macrophages and gliosis. The pathological layers were indistinguishable on T2-weighted image (Fig. 2). The patient suspected with intramedullary mass spinal tumour. With the above imaging characteristics of intramedullary lesion, differential diagnosis of tuberculous granuloma, ependymoma and glioma were suggested. Surgical resection was performed through posterior approach from T6 to T8 Level. Midline durotomy was perfomed and showed a thick mass intramedullary tumour at the vertebral level of thoracal VI, VII, and VIII (Fig. 3). The patient underwent posterior decompression of spinal cord and vertebral laminectomy with open biopsy. The tuberculoma was a brown greyish, multilobulated, irregular, but well-circumscribed mass. Excisional biopsy resulted as granulomatous chronic inflammation process, which was seen by the formation of epitheloid histiocytes (multinucleated langerhans type giant cells), with peripheral lymphocytes and plasma cells, and a central area of caseous necrosis. These pictures below were suggestive for tuberculoma of the spinal cord (Fig. 4). The patient's lower limbs power gradually improved throughout one month after the surgery. Clinically, there was an improvement in neurological deficits and bladder dysfunction, but he still had mild hesitancy while passing urine. The patient was able to ambulate independently and resume productive activities.
case report, mimicking, spinal cord tumour, tuberculoma
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PMC4868942_01
Female
80
The medical records of our patient with ARN were retrospectively reviewed. An 80-year-old woman developed blurred vision in both eyes 1 month before presenting to JR Sapporo Hospital. Upon entering, an examination found evidence of iritis, vitreous opacity, a mild vitreous hemorrhage and extensive multifocal exudation around the optic disc in her right eye (fig. 1a), as well as mild vitreous opacity, an optic disc hemorrhage and peripheral white granulomatous exudation in her left eye (fig. 1b). A fluorescein fundus angiography demonstrated hyperfluorescence of the optic disc and a wide range of occlusive vasculitis in her right eye (fig. 1c), and retinal vasculitis in the nasal area in her left eye (fig. 1d). The aqueous humor of the right eye was subsequently collected for pathogen analysis by the PCR system. Since the serological analysis was positive for cytomegalovirus (CMV) IgG, she was presumed to have CMV retinitis. She received ganciclovir (75 mg/day) orally, but this triggered no effective response. The uveoretinitis in her right eye deteriorated, and after 1 week, she was transferred to our hospital. Upon admittance, she disclosed that she had been taking oral methotrexate for over 10 years for rheumatoid arthritis. The initial ophthalmic examination showed a best-corrected visual acuity of light perception in the right eye and 20/25 in the left eye. The intraocular pressure was 13 mm Hg in the right eye and 10 mm Hg in the left eye. A slit-lamp examination demonstrated moderate cell infiltration in the anterior chamber, severe vitreous infiltration, an inferior vitreous hemorrhage and massive exudation in the posterior pole in her right eye. There was no sign of apparent progression in her left eye (fig. 1f). Both eyes showed substantial anterior chamber depth without goniosynechia, and mild senile cataracts. Results of the laboratory investigations of serum including antinuclear antibodies, anti-double stranded DNA antibodies, an adult T-cell leukemia antigen and antineutrophil cytoplasmic antibodies were unremarkable except for a high rheumatoid factor value. Serological analyses indicated that there was no active infection of syphilis, tuberculosis, human T-cell lymphoma virus 1 or toxoplasma gondii. The virus antibody titer screen was negative for IgM and positive for IgG for HSV, VZV, and CMV. The EBV antibody test showed negative for either IgG against an early antigen or IgM against a viral capsid antigen and positive for both IgG against a viral capsid antigen and IgG against a nuclear antigen. The patient received continuous administration of topical betamethasone and intravenous aciclovir (700 mg/day) upon admission. Due to the progressive symptoms in her right eye, vitrectomy, retinal photocoagulation and silicone oil tamponade were applied, and phacoemulsification surgery was conducted 5 days after admission. The fundus findings during surgery showed the occlusive vasculopathy of the entire retina, retinal fibrosis and retinal detachment with retinal breaks and vitreous traction (fig. 1e). The vitreous fluid was collected for cytology and pathogen screening. The cytological examination of infiltrated cells in vitreous fluid showed lymphocytes and a few neutrophils but no atypical cells. The culture examination using vitreous fluid was negative for bacteria or fungus. The genomic DNA in vitreous fluid was analyzed by comprehensive PCR to screen infectious pathogens including bacteria, parasites and viruses. The PCR analysis was performed in the laboratory for retinal regeneration at Riken's Center for Developmental Biology (Kobe, Japan), as previously described. Both the aqueous humor that was collected at the former hospital and vitreous fluid that was collected during surgery showed high copies of EBV but were negative to HSV, VZV, CMV and other pathogens (table 1). Two days after surgery, the patient received oral valaciclovir (1,500 mg/day) and predonisolone (30 mg/day). The dosage of valaciclovir and predonisolone administration was reduced gradually without recurrence of retinitis or development of side effects. Retinal atrophy occurred in her right eye in the necrosis area, and optic nerve atrophy also developed. This resulted in a loss of light perception in the eye. The lesion in her left eye was diminished by the drug treatment. No relapse was observed in 1 year.
acute retinal necrosis, epstein-barr virus, methotrexate, polymerase chain reaction
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PMC8274706_01
Female
57
A 57-year-old woman presented to our hospital because of dry cough, intermittent chest wall and back pain for 3 weeks. She complained the pain gradually aggravated but did not influence the length of sleep bouts. Simultaneously, the level of daily physical activity was significantly decreased, with a 3kg unintentional weight loss over the past month. She denied tobacco and tuberculosis exposure history. Physical examination suggests obvious swollen bilateral supraclavicular lymph nodes. A chest enhanced computed tomography (CT) scan revealed over 200 uniform size pulmonary nodules in an evenly dispersed pattern at bilateral lungs with a 38x45mm new creature at the dorsal segment of the lower lobe of the left lung (Figure 1A-C), in addition to a small amount of left-sided pleural and pericardial effusion. Interestingly, the artificial intelligence (AI) system (The AI software supported by Yitu CT, YITU Healthcare Technology Co., Ltd., China. The AI system of deep learning-based quantification was performed using a novel established lung nodule net based on one automatic segmentation software. This module was developed as a combination of U-net and fully convolutional networks. Approaches for lung nodule segmentation involved the detection of a volume of interest (VOI) covering the nodule area and segmentation inside this VOI. These methods can be generally classified into machine-learning methods based on China big date, which covered more than 10 provinces and more than 50 hospitals), only identified 18 pulmonary nodules (Figure 2), which are lower than 10% of the real data. Besides, all of these were judged as low-risk nodules. Another enhanced CT scans showed multiple liver and adrenal metastases, multiple bone metastases (including thoracic spine, sternum, ribs and left scapula), as well as apparent lymphadenopathy in the left hilar, bilateral mediastinal and retroperitoneal area. Magnetic resonance imaging (MRI) revealed multiple osteolytic bone destruction in thoracic vertebrae and a T7 vertebral body's compression fracture. T-SPOT was negative while a significant elevation of the serum tumor markers (including CEA 839.30 ng/mL , NSE 60.38 ng/mL , Cyfra 21-1 20.11 ng/mL , CA125 466.70 U/mL , CA153 181.00 U/mL , CA199 74.16 U/mL and CA724 151.40 U/mL ). Biopsy of the left supraclavicular node confirmed metastatic adenocarcinoma (Figure 3A) with supportive immunohistochemical staining reaction: positive for TTF-1 (Figure 3B), PCK (Figure 3C), CK7, but negative for P40, Syn, and the Ki 67 index was reported in 70% (Figure 3D). The peripheral blood gene detection showed wild-type epidermal growth factor receptor (EGFR) with no gene mutation sites. In light of clinical and instrumental examinations, the diagnosis of lung adenocarcinoma (T4N3M1 stage IV), EGFR-negative, was made. This patient lost the chance of surgical treatment due to the extensive metastatic transfer of primary tumors to distant organs. The negative gene detection result indicated that she could not benefit from target therapy. We recommended a combination therapy regimen, the subsequent imaging revealed a significant decrease in the size and number of primary tumors and metastases (Figure 4).
artificial intelligence, lung adenocarcinomas, metastases, miliary nodules
After combined therapy, the primary tumor size significantly decreased and the miliary lung metastasis almost wholly disappeared on 16-slice computed tomography.
PMC6637434_01
Male
57
A 57-year-old man, who has been blind in the left eye secondary to blunt trauma for the past ten years, presented with a three-day history of left eye pain associated with purulent discharge after a foreign body entry. The patient had no known medical illness and he was a heroin chaser. On examination, he had no light perception in the left eye with positive relative afferent pupillary light defect. There was a melting central corneal ulcer, associated with proptosis, periorbital swelling, diffuse conjunctival chemosis, and injection (Figure 1 (Fig. 1), Figure 2 (Fig. 2)). His intraocular pressure, measured gently with a tonopen, was elevated to 24 mmHg. The iris and fundus details were not visible due to the opaque cornea. B-scan ultrasonography showed a hyperechoic mass with surrounding exudative retinal detachment, resembling a choroidal tumour (Figure 3 (Fig. 3)). Systemic examination showed multiple non-tender cervical lymphadenopathies with rubbery consistency, measuring 0.5 cm by 0.5 cm. Otherwise, his cardiovascular, respiratory, and abdominal examinations were normal with no evidence of malignancy or systemic infection. The patient was initially diagnosed with left bacterial keratitis secondary to a foreign body entry with possibly an underlying choroidal tumour. Our differential diagnosis was left bacterial keratitis resulting from a ruptured bullous keratopathy secondary to chronically raised IOP due to the tumour. However, the MRI imaging showed left choroidal detachment with lens displacement, surrounding inflammatory changes and no evidence of tumour. There was no increase in vascularity within the mass as well (Figure 4 (Fig. 4)). Blood investigations showed a markedly elevated erythrocyte sedimentation rate (ESR) of 105 mm/hour (reference range: 1-10 mm/hour), raised C-reactive protein of 69.6 mg/L (reference range: <5 mg/dL) with positive HIV and Hepatitis C status. His corneal scraping grew Pseudomonas Aeruginosa. Due to the patient's immunocompromised status, markedly elevated ESR, lymphadenopathy, and inflammatory changes of the mass, a possible diagnosis of intraocular tuberculosis (TB) was made. However, TB work-up, which included chest X-ray, Mantoux test and sputum to look for acid-fast bacilli were normal. The patient was started on Ceftazidime 5% and fortified Gentamicin 0.9% eye drops which was sensitive for the Pseudomonas Aeruginosa species and two IOP lowering agents. Despite the initial targeted treatment, the patient's condition worsened. His cornea perforated within two days of presentation and the patient was in intractable pain, not responding to analgesics. After an elaborated discussion and counselling, we proceeded with evisceration of the affected eye. The corneal tissue and vitreous humour was sent for TB polymerase chain reaction (PCR). The PCR result came back positive for M. Fortuitum. The patient was not started on any systemic antibiotics as there was no evidence of systemic dissemination of the infection.
mycobacterium fortuitum, atypical, choroidal tumour, non-tuberculous mycobacteria
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PMC3114544_01
Female
52
A 52-year-old female patient was referred to the Infectious Diseases Department of the Faculty of Medicine Ankara University with complaints of fatigue, arthralgias, fever, and 10 kg weight loss over two months before admission. At the time of hospitalization, her vital parameters were body temperature: 38.0 C, blood pressure: 100/80mm/Hg, heart rate: 88 bpm, and respiratory rate: 22 bpm. Lung auscultation revealed decreased respiratory sounds in both lower lobes. Chest radiography showed bilateral pleural effusions and diffuse infiltrative opacities in the bases of both lungs. Her physical examination showed a palpable mass in the liver 4 cm below the right costal margin, along the midclavicular line. The spleen was not palpable but with percussion splenomegaly could be determined. No abnormal physical examination finding was present in the other systems. On laboratory findings serum transaminase levels were two times higher than the upper limits of normal; she had a mild leucopenia and an elevated CRP level (see Table 1). After blood cultures were performed from both arms, empiric 2 g ceftriaxone twice daily intravenously and clarithromycin 1 gm twice daily orally was started because of a suspected respiratory tract infection. In the following days the patient's fever had subsided. Abdominal ultrasound revealed hepatosplenomegaly, sludge in the gallbladder, intrahepatic venous congestion, and multiple hypodense splenic lesions (the largest one was 1 cm in diameter). Thoracic CT scan showed bilateral pleural effusions and atelectasis in adjacent lung zones. A subpleural nodular opacity was detected in the right apical segment, and peribronchovascular interstitial thickening was seen in the right lower lobe. On the basis of these findings, ultrasound-guided thoracentesis was planned, but the patient refused any invasive procedure. Brucella melitensis was isolated from the blood cultures obtained at the time of hospitalization, on the fourth day of incubation. The antibiotic therapy was switched from ceftriaxone and clarithromycin to oral rifampicin 600 mg/day and doxycycline 200 mg/day. The Brucella isolate was sent to a reference laboratory, and it was reported as Brucella melitensis biotype 3. The titers of brucellosis antibodies were measured as 1 : 640 (seropositive) using the standard tube agglutination test. The patient had no history of contact with animals, consuming fresh cheese or milk, but she had a history of eating raw meatballs (a traditional Turkish food which is made with raw meat and pounded wheat) two months before admission. The patient was reevaluated for a suspected brucella endocarditis, but her cardiac examination and transthoracic echocardiography was normal. Because she also had a complaint of mild back pain, thoracolumbar MRI was performed without pathology seen. Fifteen days after the initial course of brucellosis treatment, no pleural effusion or pulmonary consolidation was seen on the follow-up chest radiography and ultrasonography. At the end of the 24th day abdominal ultrasonography was repeated. Splenic lesions and hepatosplenomegaly were totally regressed, and a normal gallbladder was seen. Brucellosis was expected to be the cause of all pathological signs that were previously seen in the lungs and abdomen, and the regression of these was assumed as a response to the therapy. The patient was discharged in good health after a 32-day hospital stay. She completed a 6-week drug regimen at home. During this time all her complaints have resolved. She has been followed for 3 months after the end of therapy without recurrence.
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PMC5227132_01
Female
65
A 65-year-old farming lady admitted to the hospital having three-month history of on and off dysuria and renal colic. She was continuously afebrile. While being in hospital, she has developed sudden onset bilateral lower limb weakness and severe backache. There were no history of trauma and fall and no recent weight loss. Her apatite was good. There was no past or contact history of tuberculosis. Physical examination revealed tenderness to palpation over the tenth and eleventh thoracic vertebrae. The neurologic examination reveals spastic paraparesis with hyperreflexia. Her cranial neuron examination was normal and she is well oriented (Glasgow Coma Scale 15/15). Her total white cell count was 16,900/cmm (normal: 4.400-11,300/cmm) with 90.45% granulocytes, 5.6% lymphocytes, and 1.0% monocytes. Erythrocyte sedimentation rate (ESR) was 120 mm/hr. (normal: 0-10 mm/hr.). C-reactive protein (CRP) was 42 mg/dL (normal: <0.6 mg/dL). Magnetic resonance imaging (MRI) and CT of the thoracic spine revealed severe thoracic (T10-T11) discitis with minimal soft-tissue component and vertebral body destruction (Figures 1 and 2). Features are suggestive of Asian variety of tuberculous spondylodiscitis rather than pyogenic spondylodiscitis. No contiguous spread and no epidural and psoas muscle abscesses were found. So, we were in doubt to use the trial of antituberculous therapy or empiric antibiotic to cover common microbes causing pyogenic spondylodiscitis. Blood culture revealed Enterobacter agglomerans with 41-hour incubation in 99.9% probability from Ramel identification system. Isolate was susceptible to ciprofloxacin, carbapenems, and aminoglycosides and resistant to ceftazidime and aztreonam. We have started intravenous ciprofloxacin 400 mg 12 hourly with weekly monitoring of ESR and the clinical response (Table 1). Computed topography- (CT-) guided biopsy culture was negative for bacteria, fungi, and tuberculosis. Histology shows possible bacterial infection. Chest X-ray radiography is normal and Mantoux test was negative. Imaging study of genitourinary system shows calculus over right renal pelvis. Urine culture was negative for bacteria. Patient was successfully treated with intravenous ciprofloxacin, 400 mg 12 hourly for 3 weeks followed with 3 weeks of oral ciprofloxacin. Follow-up examination on 6th week on completion of treatment showed mild residual bilateral lower limb weakness and ability to walk with aid. Follow-up CT in 6 weeks shows T10-T11 vertebral body and disc regeneration (Figure 3).
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PMC7569429_01
Male
65
A previously healthy 65-year-old man presented to an outside hospital with fatigue, folliculitis, easy bruising, vision changes, and decreased hearing. He had a normal coagulation screen; however, he was found to have cytopenias with a white blood cell count of 5.5 K/microL that included approximately 50% blast forms, hemoglobin of 10.0 g/dL, and platelet count of 78 K/microL. Marrow showed 70-80% blasts positive for CD34, terminal deoxynucleotidyl transferase (TdT), CD3, myeloperoxidase (MPO), and CD5, and negative for PAX-5 and c-Kit (Figure 1). Flow cytometry (FC) demonstrated the blasts to express markers specific for myeloid (cytoplasmic MPO) and T-lymphoid (cytoplasmic CD3) lineages. Blasts were also positive for CD5, CD7, CD10, CD34, CD11b, CD33, and TdT on FC. Cytogenetics were normal, and no abnormalities were identified on 200 interphase cells examined by fluorescence in-situ hybridization: specifically, analysis showed no evidence of 3q21.3q26.2 translocation or inversion, deletion 5q31, monosomy 7, deletion 7q31, RUNX1T1-RUNX1 translocation, KMT2A rearrangement, CBFB rearrangement, or PML/RARA translocation. Next generation sequencing identified the following mutations: DNMT3A c.2206C > T (variant allele frequency (VAF) 43.9%); DNMT3A c.1755dup (VAF 36.5%); IDH1 c.394C > T (VAF 44.0%); CBL c.1227 + 2T > C (VAF 51.6%); and NOTCH 1 c.5023_5025del (VAF 13.9%). Together, findings established the diagnosis of T/myeloid MPAL. Cerebrospinal fluid was negative by cytology and FC. Induction treatment was given with 3 half cycles (1A, 1B, and 2A) of cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine (hyper-CVAD) and intrathecal (IT) prophylaxis. This achieved a complete remission (CR), with bone marrow biopsy after cycle 1A, showing no evidence of disease by morphology or FC and no circulating blasts in the peripheral blood. He was transferred to our facility for consideration of consolidation stem cell transplantation. A repeat bone marrow exam was performed and demonstrated continued remission. The patient proceeded to a matched related donor allogeneic stem cell transplantation (allo-SCT) from his brother with reduced intensity conditioning (RIC) (fludarabine 30 mg/m2 daily for 3 consecutive days (Flu) and 200 cGy total body irradiation (TBI)) with tacrolimus and mycophenolate mofetil graft versus host disease (GvHD) prophylaxis. Marrow on day 28 posttransplant showed morphologic remission with 0.06% blasts by FC. Markers used to detect MRD by FC included CD45, CD34, CD38, CD48, CD56, CD71, CD117, CD123, CD5, CD7, CD33, cCD3, sCD3, CD4, CD8, CD13, CD14, CD15, CD16, CD19, CD64, and HLA-DR. A repeat marrow one week later showed an increase in blasts to 0.1% by FC, and chimerism analysis showed donor CD3 of 40%, CD33 of 85%, and CD56 of 71%. His immunosuppression was tapered and completely discontinued on day 47, and he received donor-lymphocyte infusion with pentostatin on day 50 posttransplant. At day 18 post DLI blasts had increased to 6% by FC; by morphology, a population of 5% TDT + CD34+ blasts were shown. The patient was next treated with one cycle of intensive reinduction using cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M) plus vincristine and dexamethasone. This was complicated by neutropenic sepsis requiring prolonged intensive care, but the patient made a full recovery, and restaging bone marrow biopsy showed a CR by morphology and FC. A second allogeneic stem cell transplant was planned, but shortly beforehand, the patient developed grade 2 GvHD of the skin and was treated successfully with oral corticosteroids. Given that he was still in CR by FC and hoping the GvHD would correspond to increased graft versus leukemia, the 2nd transplant was postponed. Unfortunately, repeat bone marrow exam approximately 3 months later confirmed low-level relapse detectable by FC. Reinduction with 2 cycles of CLAG-M plus vincristine and dexamethasone (with mitoxantrone omitted from the 2nd cycle) was again administered but associated with substantially increased toxicity to the patient's functional status and a prolonged length of recovery. CR by morphology and FC was briefly achieved before disease was identified at a level of 0.9% by FC on day 441 posttransplant. At this juncture, the patient was >1-year post-allo-SCT with relapsed T/myeloid MPAL despite several rounds of high-intensity chemotherapy. He was reasonably fit, evidenced by his regular exercise bicycling regimen, but had shown declining tolerance of successive cytotoxic chemotherapy regimens. He had no clinically active GvHD. Given the paucity of published data to inform this clinical scenario, we presented 3 options for management that included (1) directly pursuing a 2nd allo-SCT using a different donor; (2) additional conventional multiagent chemotherapy; or (3) venetoclax plus HMA. He began venetoclax 400 mg by mouth daily and decitabine 20 mg/m2 intravenous daily on days 1-5 in 28 day cycles. No dose ramp-up of venetoclax was given in the setting of low disease burden. Because of grade 4 neutropenia and grade 4 thrombocytopenia, venetoclax was stopped on day 25. Both cell lines recovered by day 35, and a bone marrow exam at that time showed CR by morphology and FC. A 2nd cycle was given, with venetoclax dose-reduced to 100 mg daily. A full 28 days of venetoclax was administered with recovery of neutrophils and platelets on day 37. Other than cytopenias, the regimen was well tolerated. He proceeded to a 2nd SCT from a matched unrelated donor allograft with Flu/TBI RIC and cyclosporine, mycophenolate mofetil, and sirolimus GvHD prophylaxis. Engraftment of neutrophils occurred on day 19 after transplantation, and no grade >1 GvHD has been observed to date. At his most recent follow-up 1 year after his 2nd allo-SCT he remains in CR by morphology and FC with CD3, CD33, and CD56 compartments entirely of donor origin.
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PMC9053539_01
Male
50
A 50-year-old man with a history of alcohol and tobacco abuse presented with chronic and recurrent epigastric pain, weight loss, and weakness. The patient was known to receive antituberculous therapy for active pulmonary tuberculosis. A contrast-enhanced abdominal computed tomography was performed. Axial images of portal phase demonstrated multiple wedge-shaped non-enhancing areas at the periphery of the spleen suggestive of splenic infarcts (Figure 1a). Splenic vein was permeable (Figure 1b). Axial and sagittal images of arterial phase revealed a small splenic artery related to severe stenosis and angulation of celiac axis caused by a thick soft tissue band (5 mm) anterior to the abdominal aorta creating a hooked appearance (Figure 2a, b). Coronal maximum intensity projection CT showed a prominent gastroduodenal artery with large collateral vessels around the pancreatic head (Figure 3). Median arcuate ligament syndrome causing splenic infarcts was retained and the patient was referred to vascular surgery service.
celiac artery compression, median arcuate ligament syndrome, splenic infarcts
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PMC4734679_01
Male
31
In 1996, a 31-years-old previously healthy man presented with right hemiparesis, unsteadiness and dysarthria. After a more detailed physical examination horizontal nystagmus while looking to the right and both right arm and leg ataxia were patent. A demyelinating disease of the central nervous system was initially suspected. Extensive laboratory tests were completed, all of them normal or negative. Erythrocyte sedimentation rate (ESR) was normal, as well as autoimmune screening including serum tests for antinuclear antibodies, antineutrophil cytoplasmic antibody, HLA-B27, HLA-DR2, anti-double stranded DNA antibodies, antithyroglobulin, and serum angiotensin-converting enzyme. Several infectious diseases were ruled out by serological and spinal cerebral fluid (CSF) tests, including Lyme disease, syphilis, HIV, herpes simplex virus, human herpes virus 6 and 8, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, and Mycobacterium tuberculosis complex. On CSF analysis, the level of proteins, glucose, and cells were normal. Neither was there evidence of intrathecal immunoglobulin synthesis, as 8 identical oligoclonal bands (OCB) were found in blood and CSF. Somatosensory-evoked potentials showed a prolongation of latencies in the right hemisphere and in brainstem auditory-evoked potentials, bilateral central conduction time prolongation was found. Visual-evoked potentials were normal. A brain MRI showed hyperintense patchy lesions without mass effect in the brainstem, mostly affecting the pons and the cerebellar peduncles; these lesions were confluent and undefined, unlike the typical lesions described in multiple sclerosis (MS). No intravenous contrast was administered on this occasion. However, the inflammatory appearance of the lesions in the absence of proven infection or malignant cells on CSF testing prompted the decision to start treatment with intravenous methylprednisolone at high doses. After 5 of daily 1-gram doses, a significant improvement of the symptoms was observed, leaving only a minimal right arm paresis and mild gait ataxia. Due to the remaining neurological deficits, a tapering dose of 70 mg of oral prednisone after discharge was prescribed. Unfortunately, only 2 months after stopping treatment with oral glucocorticoids, our patient presented again with symptoms similar to those in the first admission, in addition to diplopia. A second MRI with gadolinium contrast was requested then, which showed the same patchy lesions in the brainstem (Figure 1A) but with no gadolinium enhancement. However, this new imaging was obtained after initiating intravenous treatment with methylprednisolone 5 days prior, which probably altered the final results. Over the next 4 years, despite long-term therapy with oral corticosteroids, our patient had several relapses, always involving the brainstem, with a frequency of at least 1 exacerbation per year. Each relapse was treated with intravenous glucocorticoids, but the improvement achieved was only partial and residual ataxia was more severe each time. It was clear that maintaining a low dose of oral corticosteroids was the only way to reduce the time between relapses. On May 2000, a control MRI between relapses showed a patchy and curvilinear gadolinium enhancement on T1-weighted images, peppering the cerebellum (Figure 1B). By then, several data suggested that our patient did not have MS: he did not meet the dissemination-in-space criteria because lesions were always restricted to the cerebellum and the pons; their appearance on T2-weighted-MRI was atypical for MS; the presence of a mirror pattern on OCB testing did not fit the pattern; and the ultimate dependence on daily steroids to avoid worsening was inconsistent with the diagnosis. On the other hand, an autoimmune origin was suspected, as the infectious or tumor etiologies were safely ruled-out after 4 years of follow-up. A vasculitis of the central nervous system was considered, but the ESR and other analytical features were normal, CSF showed no pleocytosis, and there was no proof on MRI of vascular-related lesions such as microbleeds. However, after 4 years of treatment, the deleterious effects of chronic corticoid therapy caused concern and the need for a glucocorticoid-sparing therapy was evident. After careful consideration, on July 2000, immunomodulatory treatment with subcutaneous IFNbeta-1a (Rebif 22 3 times a week) was decided on. The choice was based on the uncertainty of the diagnosis and the search for a treatment with a more secure profile than classic immunosuppressants. From that moment on, relapses occurred further apart, with a frequency of 1 exacerbation every 4-5 years, and they were no longer associated to increasing disability. The patient had a good tolerance to the treatment; he reported no significant flu-like syndrome or injection-site reactions and consecutive laboratory studies showed no alteration in leucocytes, liver, or thyroid function. However, low doses of oral Deflazacort (30 mg every 2 days, equivalent to 25 mg of Prednisone every 2 days) were sustained, in fear of further exacerbations. Suspension of corticosteroids was achieved during 11 months in 2001, but after a new relapse, we chose not to insist on total withdrawal. When Pittock et al. published their research in 2010 and the diagnosis was evident, a modification of the treatment was considered, but, taking into account both the patient s clinical stability and the excellent tolerance to immunomodulatory treatment, watchful waiting was decided on.
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PMC3785352_01
Female
63
A 63-year-old female visited Toho University Omori Hospital with complaints of heartburn and persistent laryngeal discomfort. She received an endoscopic examination two years ago as a further examination of gastric cancer screening. At that time, atrophic gastritis was pointed out and Helicobacter pylori (H.pylori) infection was positive. Although H.pylori was successfully treated with a PPI-based triple therapy, laryngeal discomfort had not been disappeared. First, an upper endoscopic examination was performed, but abnormal findings of the esophagus, including a mucosal break, hiatal hernia, and whitish mucosa, were not detected (Fig. 1). Therefore, saliva scintigraphy was performed to evaluate the salivary function. In our previous study, we defined the optimal cutoff point for determining the decreased salivary secretion as 51% in parotid glands and 36% in submandibular glands. After an overnight fasting, saliva scintigraphy was performed with the patient in the supine position under a gamma camera with high-resolution collimators. No oral stimulus was permitted before and during imaging. Following intravenous injection of 180 to 200 Mbq 99 mTc-pertechnetate, anterior sequential imaging was performed every minute for 40 minutes. At 20 minutes after injection of radio-nuclide, a lemon candy was administrated intraorally to stimulate salivary secretion. Regions of Interests (ROI) were selected on the individual submandibular and parotid glands, oral cavity, and thyroid gland. Time activity curves were drawn for each of these. Washout ratio (peak count before lemon candy administration-lowest count after administration/peak count before administration) was examined. Washout ratio was 40% in the right parotid gland, 25% in the left parotid gland, 25% in the right submandibular gland, and 30% in the left submandibular gland (Fig. 1). After the first scintigraphy was performed, the patient received 300 mg of nizatidine per day for 2 months based on the treatment for peptic ulcer in Japan. During the two months course of the nizatidine treatment, the patients has not taken any other drugs and there have no possible confounding factors that would also change salivary flow. After the treatment, salivary scintigraphy was done and demonstrated the increased washout ratios in all four major glands (Fig. 2). The value of right parotid gland increased from 40% to 80% and that of left one did from 25% to 78% after treatment with nizatidine. Likewise, the washout ratio of right submandibular gland increased from 25% to 45% and that of left one did from 30% to 51%. GERD symptoms, including heartburn and laryngeal discomfort disappeared completely after treatment. The patient has been followed up for 10 months after nizatidine treatment and GERD symptoms have not reappeared.
gerd, laryngeal discomfort, nizatidine, salivary scintigraphy
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PMC9894286_01
Male
28
A 28-year-old male with no previous comorbidities and no interstate travel history was admitted with complaints of fever, dry cough and breathlessness on exertion for a duration of 3 days. General physical examination of the patient was normal except fever of 100 F. He was maintaining saturation of 95% on room air at rest and post exercise, there was no dip in saturation. A nasopharyngeal and throat swab was taken for SARS-COV-2 and it tested positive. Hematological parameters showed pancytopenia with a Total Leucocyte Count of 3800/mm3, Hemoglobin of 9 gm% and mild thrombocytopenia of 1,30,000/mm3. Chest Radiograph was normal. Electrocardiography was normal sinus rhythm with QTc interval of 380 ms. He was diagnosed with Coronavirus disease 19 (COVID-19). His fever subsided after 5 days of symptomatic treatment. However, after 3 days of an afebrile period, he again started mounting fever. There was a generalised erythematous rash with papules over the extremities and face along with mucosal involvement [Figure 1a]. Oral mucosa was involved in the form of painless ulcers. Work up for fever including Dengue Ns1Ag, Dengue serology and Blood for Malarial Parasite was negative. Serology for Scrub Typhus and Leptospira was negative. Urine Routine and microscopic examination were normal. Blood culture and urine culture showed no growth. His repeat nasal and throat swab test for SARS-COV-2 was negative. Viral markers including HIV, HBsAg and Hepatitis C were negative. CRP levels were 25 mg/L and IL6 levels were 15 pg/mL. His pattern of fever was continuous in nature with a maximum spike of 102.8 F. He underwent CECT Chest and Abdomen to look for secondary infections. It revealed Ground glass haziness involving bilateral lower lobes and patchy areas of consolidation involving bilateral upper lobes [Figure 2a, b]. Sputum examination for Gram stain, Acid Fast Bacilli, and Fungal stains were negative. Sputum culture for bacteria and fungi yielded no growth. He was empirically treated with broad spectrum intravenous antibiotics and it was de-escalated as serum procalcitonin levels were normal. During examination, lymph node enlargement was found in axillary and cervical regions. Lymphadenopathy was soft, non-tender, discrete and non-matted. In view of pancytopenia and persistence of fever, he was worked up for Secondary hemophagocytic lymphhistiocytosis (sHLH). Levels of Serum ferritin and Serum triglyceride were 680 ng/ml and 118 mg/dl, respectively. Bone marrow examination showed reactive marrow without any features of hemophagocytosis. No granulomas or blast cells were seen. He underwent a Fine needle aspiration of the Cervical lymph node. It tested negative for GeneXpert MTB. Cervical lymph node biopsy showed follicular hyperplasia with no evidence of granuloma/malignancy and no features of hemophagocytosis. Based on the HS score probability of him suffering from HLH was less than <1%. As a part of the work up for PUO, testing of Antinuclear antibody (ANA), Rheumatoid arthritis (RA) factor was done. ANA titres by Enzyme immunoassay (EIA) were significantly high 208.79 units (>60: Strongly positive). RA factor was negative. Extractable nuclear antigen antibody profile by EIA showed positivity to Smith (Sm), anti-double standard DNA. C3 and C4 complement levels were low. Immunological work up at tertiary care center revealed positive ANA by Indirect immunofluorescence (IIF) method (4+ Speckled). Based on EULAR 2019 criteria, he was diagnosed to be suffering from SLE, triggered by COVID-19. He was started on a daily dose of Tab HCQS 300 mg once daily (OD), Tab Prednisolone 10 mg OD and Tab Azathioprine 75 mg OD. He showed a favourable response to treatment. Fever subsided and skin rash resolved [Figure 1b]. Repeat CECT Chest showed normal scan with complete resolution of ground glass haziness [Figure 2c, d] and there was a significant decrease in cervical and axillary lymph nodes. His pancytopenia resolved and weakness subsided. During follow-up visit at the completion of 1 year, ANA positivity was persistent by IIF and he was asymptomatic on immunomodulatory therapy.
autoimmunity, covid-19, coronavirus triggered, lupus erythematous
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PMC3591261_01
Female
45
A 45 year old Caucasian female with HIV infection, CDC-A3 and HCV, genotype 1b co-infection, Child-Pugh score 5, non-active IV drug habit, on 35 mg day of methadone, smoking habit of 20 cigarettes per day, nutritional disorder that had led recently to a loss of weight >10 kilos and on HIV treatment including tenofovir/emtricitabina and lopinavir/ritonavir was admitted to a local hospital complaining of fever which began a week prior as well as cough over the last 2 days. The patient was taking levofloxacin 500 mg day during the last week. Three months before admission immune-viral assays resulted being: HIV-RNA 71 copies ml, CD4 T 144 mm3. HCV-RNA resulted 780.000 copies ml. On admission, the liver was 5 cm below the costal margin, the erythrocyte sedimentation rate (ERS) was 78 mm 1 hour, hemoglobin 10.8 mg dl, white blood cells 4400 mm3, neutrophils 79.6%, coagulation, liver and renal functional tests were normal. A chest radiograph depicted micro nodular shadowing consistent with miliary TB. This finding was confirmed with a chest computed tomography (CT). A bronchoscopy did not show lesions. Bronco-alveolar lavage (BAL) fluid was negative for acid fast bacilli (AFB) and M. tuberculosis complex strand displacement amplification (SDA) was non-reactive. Culture subsequently identified multi-susceptible Mycobacterium tuberculosis. On the same day, in the absence of neurologic symptoms, cerebrospinal fluid (CSF) was examined leading to the diagnosis of a probable TB meningitis: glucose CSF 25 mg dl (blood glucose 99 mg dl), white cells 150 mm3 and proteins 273 mg dl, Ziehl-Neelsen (ZN), SDA and culture for M. tuberculosis resulted negative. CSF cultures for bacteria and fungi were also negative. Latex agglutination test for Cryptococcus resulted negative both on CSF and blood. Isoniazid 300 mg day, ethambutol 1200 mg day, pyrazinamide 1500 mg day, rifabutin 150 mg day and dexamethasone 4 mg per day were added to anti-retroviral therapy and levofloxacin. Four days later, the patient developed a right side stroke. A brain CT depicted a left frontal parietal cortical sub-cortical post ischemic high density lesion. On admission to our Infectious Disease Clinic (IDC), 72 hours later, the patient was aphasic with right hemiplegia (Glasgow coma score non-applicable). Tuberculosis skin (TST) and gamma-interferon assay (IGRA) tests resulted negative. The repeated CD4 T cells count showed 72 cells mm3. The rapid plasma reagin treponemal test for syphilis was negative. Ultrasound of carotid arteries, EKG, trans-thoracic heart ultrasound, antinuclear antibodies, anti neutrophil cytoplasm antibodies, lupus anticoagulant factor and factor V Leiden were negative. Protein S, protein C, anti-thrombin III, homocysteine values were in the normal ranges. A repeated brain CT confirmed the fronto-parietal cortical sub-cortical ischemic lesion with minimal hemorrhagic transformation. Magnetic resonance (MRI) and angio-MRI (Figure 1) also depicted recent ischemic cortical sub-cortical lesion with minimal hemorrhagic transformation, absence of flow through the left middle cerebral artery and thickening as well as contrast enhancement on the left Sylvian fissure surrounding the artery. Thus, the patient was diagnosed with TBM complicated with stroke. The patient continued with tenofovir/emtricitabine and lopinavir/ritonavir plus isoniazid 300 mg day, ethambutol 1200 mg day, pyrazinamide 1500 mg day and rifabutin 150 mg day plus meropenem for the first 7 days, whereas corticosteroids and levofloxacin were suspended. Moreover, due to the presence of multiple risk factors for stroke and the absence of an absolute contraindication, aspirin100 mg day was administered. This was done despite the radiological findings evidenced microbleeds in the ischemic lesion. A percutaneus gastrostomy was performed as a nasal gastric tube was not tolerated. General and neurologic conditions improved while on anti-TB, anti-HIV and aspirin treatments. Two weeks later, CFS findings also improved: glucose 41 mg dl (blood glucose 93 mg dl), white cells 32 mm3, all lymphocytes, and proteins 174 mg dl, microscopic and culture for M. tuberculosis, bacteria and fungi were negative. Latex agglutination test for Cryptococcus test resulted once again negative. Real time polymerase reaction (PCR) for Toxoplasma gondii, Human poliomavirus JC-V, Herpes simplex virus type I and type II, Herpes virus type 8, Varicella Zoster virus, Cytomegalovirus resulted negative on CSF. The test for Cytomegalovirus antigen pp65 (Indirect Immunofluorescence, anti-CMV pp-UL83, Argene, Verniolle, France) in blood was also reported being negative. Five weeks later, the patient was transferred to another hospital where the prescribed treatments and rehabilitation were continued with further improvement.
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PMC3310108_01
Male
43
The second case of infection was in a 43-year-old man who was admitted to Awali Hospital, Awali, Bahrain, in November 2006. The patient reported malaise, insomnia, cough, weight loss, and anorexia. Radiographs showed features suggestive of tuberculosis (left upper lobe consolidation with focal cavitation). Sputum specimens collected on 3 consecutive days were positive for AFB and mycobacterial growth. To identify the pathogen(s), we used the same 4 mutiplex line-probe assays as used for case-patient 1, and results were similar. The identified strain was considered to be the pathogen responsible for the respiratory disease. The patient was treated with a combination of clarithromycin (CLR) and ciprofloxacin (CIP) for 12 months; however, he had a clinical and microbiological (i.e., positive for AFB and culture results with the same NTM) relapse during this treatment. In November 2007, 3 sputum specimens from the patient were positive for AFB, and cultures yielded a mycobacterial strain identical to that identified by the assays. The patient was treated with antituberculous drugs (INH, RIF, EMB, PZA, plus CLR and CIP) for 6 months, and then INH, RIF, CLR, CIP were continued for 2 additional months (Table), after which the patient showed clinical improvement. In the 2 cases, molecular identification of the isolates as M. riyadhense was achieved by using partial hsp65 and rpoB gene sequencing, which was based on the high level of sequence identities with the type strain of M. riyadhense and a distance score of 3.5 and 4.6, respectively, to the next species, "M. simulans" (Table). Broth microdilution panels (SLOMYCO Sensititer; Trek Diagnosis Systems, Cleveland, OH, USA) were used to determine drug susceptibility (Table). Commercial probes are frequently used for rapid identification of mycobacterial species; however, M. riyadhense and other recently proposed NTMs (e.g., M. kumamotonense and "M. simulans") cross-react with MTBC DNA probes and may be missed by line-probe assays (,). With the emergence of new NTM species, commercial probes could fail to discriminate between species, leaving clinical isolates either unidentified or misidentified. Because of its ease of use, accuracy, and discriminatory power, multilocus sequence analysis may soon become the standard for routine NTM species identification. We have shown evidence for the pathogenic role of M. riyadhense in pulmonary diseases, a pathogen that has previously been reported to have extrapulmonary pathogenicity. Clinical and radiologic signs and symptoms of pulmonary infection caused by M. riyadhense, including cough, weight loss, fever, and cavitating lung lesions, were similar to those in typical cases caused by MTBC strains. van Ingen et al. suggested that the region of difference 1 (RD1) virulence locus identified in MTBC members may also play a crucial role in virulence of some NTM species. These authors found RD1 genes in NTMs that were causing human disease, including M. kansasii, M. szulgai, M. marinum, and the type strain of M. riyadhense. We confirmed the presence of RD1 esat-6 and cfp-10 genes in the M. riyadhense isolates reported here (GenBank accession nos. JF896090-JF896093). Because M. riyadhense is an emerging pathogen with, to our knowledge, only 1 previously reported extrapulmonary case of infection, the optimal treatment for infected patients is unknown. Our results and drug susceptibility testing indicate that antituberculous drugs, including INH, RMP, and EMB, are effective against M. riyadhense infection (Table), but the combination of CLR plus CIP was not effective in 1 case-patient reported here, despite in vitro susceptibility to both drugs.
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PMC3015621_01
Male
48
A 48-year-old Caucasian male with a history of hypertension and poorly controlled type II diabetes mellitus presented with 4 months of early satiety, epigastric pain, heartburn, nausea, and daily emesis. An upper gastrointestinal endoscopy did not reveal any anatomic abnormalities. Scintigraphy demonstrated greater than 50% gastric content retention after 2 hours (Figure 1). Neither dietary changes nor Metoclopromide administration provided symptomatic relief. A diagnosis of drug-refractory diabetic gastroparesis was made and a laparoscopic gastric electrical stimulator implantation was planned. The procedure requires 4 ports (Figure 2). Ten-mm ports are placed in the left upper quadrant (lateral gastric retraction) and umbilicus (camera) and 5-mm ports (working ports) are placed in the left lower and right upper quadrants. The surgeon stands on the patient's right side. The pylorus is identified, and a ruler is used to identify a point 10 cm proximal to it along the greater curvature, which is in the region of the pacemaker area. Marks are made with electrocautery 1 cm apart on the gastric serosa. The lead is prepared by tying 2 silk sutures to its anchor. After the lead is inserted through the left upper quadrant port, the Prolene suture, which comes attached to the electrode, is placed through the seromuscular layers of the stomach. An upper gastrointestinal endoscopy assures that the gastric mucosa has not been violated. The Prolene suture is used to pull the electrode into the gastric muscularis propria. The electrode is secured to the gastric wall by using the silk suture, which had been previously tied to the anchor with the intracorporeal knot tying technique. The above procedure is repeated for a second lead with its electrode placed 1cm from the first. The leads are brought out through the left upper quadrant port. An external programming device is used to confirm that the impedance between the 2 electrodes is between 200 and 800 Ohms. The electrodes are then further secured by placing a disc and 2 clips on the Prolene suture adjacent to the electrode (Figure 3). An abdominal wall subcutaneous pocket is made for the stimulator 4 fingerbreadths below the left inferior costal margin. The leads are tunneled from the left upper quadrant port site to the subcutaneous pocket, where they are connected to the stimulator. Two sutures are used to secure the stimulator to the abdominal wall fascia. The pocket is closed in layers, and the stimulator parameters are set by using the external programming device. The voltage is calculated by multiplying the measured impedance by a current of 5 mA. The other parameters include a frequency of 14 Hz, a pulse width of 330 micros and a cycling time of 0.1 seconds on and 5 seconds off. One month following surgery, the patient no longer required Metoclopramide. Two months later, he was symptom free, on an unrestricted diet with significantly improved glycemic control, and hemoglobin A1C within the normal range. At 6 months following surgery, a gastric scintigraphy demonstrated a normal pattern of gastric emptying with 22% gastric content retention at 2 hours (Figure 4).
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PMC9751188_01
Female
68
The study was completed by seven older Australians, each a member of the University of the Third Age (U3A), recruited via a posting about the cultural probe study in their local chapter's newsletter. As part of a larger research partnership between RMIT University and U3A Network Victoria, Shaping Connections, invitations to express interest in the study were sent to members in the South-east of Melbourne, Victoria, from Kingston, Cranbourne, Frankston, Glen Eira, and Bayside local chapters. Based on a member profile survey conducted by the Victorian Network, we note 75% of members are women, predominately from 71 to 75 (27%) and 66-70 (24%) age groups, with 48% having obtained a degree or higher compared to 24% for the general population, and 31% of survey respondents living alone (Szwed,). Regarding the cultural probe study, the demographics of the member profile reflected participants well, with an average age of 68 years old (M = 76.29, SD = 8.50), respondents were primarily women (6 women, one man), while education and living conditions were not evaluated, all resided in the south-east of Melbourne and were members of one of the local chapters engaged. As the study focused on technology use, hobbies, social; habits, and preferences for social connection, participants were invited to discuss these aspects. For example, almost all respondents noted a "regular" level of technology use and skill, with only one suggesting they were at a "beginner" level. All owned a mobile phone, with at least three a table or laptop. All completed the TechPH scale (Anderberg et al.,) showing a reasonable overall level of interest and appreciation of technology across the respondents, with low anxiety. When discussing their interests and hobbies, many indicated their involvement in classes with their responding U3A chapters, such as Genealogy, Book club, social studies, archaeology, or photography, alongside traveling around Australia or spending time with family. Regarding how this time with others was spent, almost all preferred regular, in-person catch-ups, whether for a meal, coffee, or walking, as long as it was focused on talking and listening. Using the Lubben Social Network Scale (Lubben and Gironda,) to determine their social engagement, respondents indicated similar levels of social engagement with family and friends across the board. The following backgrounds serve to contextualize each participant: Sally: With her son moving in with his family during the pandemic, Sally spends her days helping to look after her grandchildren, preparing meals and watching television together. Most mornings, she plays Pokemon Go on a walk before breakfast, alongside hip exercises to reduce her ongoing bursitis. Joan: As a retiree who volunteers at the local visitor information center, Joan lives with her husband on the coast. Her days during the study were spent taking daily walks, completing gardening tasks, and supporting friends and family through in-person chats and online calls. Olivia: Due to an immune system badly impaired from the Guillain Barre syndrome, Olivia is housebound and requires daily support from her carers. During the study, she noted how much more accessible her interests had become, such as weekly church and football games. Emma: A retiree at 66, Emma enjoys working part-time as a local golf clubhouse gardener and lives in a share house. While looking after her garden and spending time with friends; she also writes short children's books and helps look after neighbors' children. Mary: Continuing to work into her late seventies, Mary has set up a home office during the lockdowns but prefers to go into the office to see the other accountants in her unit. At home, with her husband, she enjoys learning and using new devices while also regularly walking their puppy. Claire: With her partners separated from her in Canada during the Australian lockdowns, she keeps in contact with him and her family primarily online and in calls. As an avid traveler, she spent her days learning Spanish while preparing to sell her house in Australia. Robert: Previously an IT worker, Robert remains engaged with technology through his passion for cameras, though he also provides technical support at his U3A. Outside this, he enjoys spending his time following creative pursuits such as photography and painting, being with his partner and like-minded individuals that join the photography class he teaches. The cultural probe kit contained three main components:a social activity diary, an accompanying workbook, and a collection of photovoice task prompts with an instant-digital camera:alongside supporting documentation and instructions (Figure 1). Intended for remote and self-sufficient use by participants, all components were printed and sent to participants. In addition, the kit included necessary stationery such as pens and pencils, spare photo papers for the instant-digital camera, and a charging cable in case the camera did not last the week. The optional exit interview was conducted via online conferencing software, such as Zoom, or via a phone call, per participants' requests. As this article discusses the analysis of the photovoice responses, social diary entries, and exit interview transcript, the development and resultant materials from these elements will be discussed. It is also important to note that as part of the development process, the probe kit was iterated multiple times and tested with a volunteer U3A officer. Reflecting the approach of Mikus et al., this independent project advisor was consulted to ensure the kit's components, terminology, and distribution were appropriate, potentially increasing engagement and connection. In particular, this involved making changes to language and the text size and replacing activities foreseen not to resonate with this audience, with the tester refining the probe into a more accessible, intuitive, and helpful format. Developed initially by health promotion researchers (Wang and Burris,), Photovoice is a technique that involves placing cameras into participants' hands to help them record, reflect upon, and communicate issues of concern (Budig et al.,). Serving as a powerful medium for capturing everyday life, the photovoice component of the cultural probe kit prompted participants to consider and reflect on Social Technology, Social Networks, Wellbeing, and Social Practices. The camera provided to participants, a Kodak Printomatic Instant Print Camera, was intended to provide a novel and interactive platform for capturing imagery, chosen due to its ability to automatically print photos with point-and-shoot ease, as well as record them digitally via an SD card. The cue cards were developed to support participants in considering the context of the study:the ongoing lockdowns in Victoria and social interactivity:posing questions and examples that sought to resonate with the situations facing respondents. Each topic responded to their established concepts, such as social technology that captures any technology that facilitates social interaction and has some form of communication capability. This saw a participant respond to a prompting statement (i.e., "COVID-19 has changed our experience and reliance on technologies to keep social") and question (i.e., "Find and capture examples of technologies you use to socialize around you"), with additional prompting statements for the images taken (i.e., "You might use a device to play games or talk with others...", or "Perhaps you make use of assistive equipment to access the community..."). Meanwhile, a social network can best be understood as a network of individuals (such as friends, acquaintances, and co-workers) connected in relationships. Participants were prompted with cue card questions (i.e., What do you do with others? Try to capture hobbies, groups or communities that you engage with) that focused on both common interests (i.e., Maybe you have a common interest with others, a hobby or sport, that you do with others?) and online connectivity prompts (i.e., Do you have a digital, online place you talk or meet with others, a regular Zoom call?). Alongside these, the topic of social practices centered on how everyday actions are typically and habitually performed and are meaningful parts of everyday life. This saw typical photovoice questions focus on representation (i.e., How do you represent yourself to others? Find and capture examples of your social identity, what makes it up, or what you like others to see in you) and sources of support. The final topic of wellbeing not only focused on happiness and life satisfaction (i.e., What might make you happy or proud?) but also on mood change across days (Figure 2). These cue cards were printed double-sided for participants to review the prompts and capture their photographic and written responses, forming a collection of eight activities. Diaries studies form a frequent component and common item in a probe kit, often as a blank book to be filled with observations or a templated format to guide input (Wherton et al.,; Thoring et al.,). Here, the diary provides a template for recording day-to-to events, relevant imagery, and reflections on daily interactions: with technology, social activities, and wellbeing-related events. Intended to capture actions, events, and reflections over a 7-day week, the diary formed around a "Daily Schedule" template, with simple instructions to follow, allowing participants to record what they wanted (Figure 3). As a way of capturing specific events or determining routine tasks, the diary provides information that might otherwise be absent or forgotten in an interview setting. The additional "Today's Interactions" elements provided a separate section for reflections and review on the day, breaking away from the chronological schedule element to focus on discreet technological, social, and wellbeing experiences. After completing the cultural probe, participants were invited to complete a semi-structured, post-survey interview. As an opportunity to provide feedback on the cultural probe experience and further explore the study's themes, these interviews varied from 30 min to 1.5 h in length. An interview guide was provided before participants to prepare participants and structure the interviews. It focused first on general and component-specific feedback, then discussed how they understood and perceived social technology, networks, practices, and their wellbeing (Table 1). Alongside addressing these topics, participants were also asked to clarify any images, wording or response they wished to have removed from the data set. These discussions were all conducted via the Zoom video conferencing platform, except one via a phone call, and were recorded and transcribed for use in the later analysis. Approval for the study was obtained through our institution's human research ethics board, which established that participants' data would be personal and re-identifiable (coded) in nature, before we collected consent from all participants. The study was conducted from August to October 2021, with potential participants required to review the consent information and associated materials before engaging with the study. Once permissions and postage were organized, a parcel containing the study materials was mailed to them. In line with sanitation requirements due to the COVID-19 pandemic, mailed components were handled safely, with all elements sealed or cleaned thoroughly before provision. Participants were given 10 days to complete the kit. Seven days after the kit arrived, participants were sent a reminder to complete the tasks and an invitation to participate in an optional semi-structured interview. Of the seven provided with the mail-out kit, all kits were completed and returned within 2 weeks, and all respondents participated in an exit interview. During the exit interview, participants were invited to review their submitted materials and determine if they wanted anything removed from the data set (i.e., the faces of grandchildren or family members, etc.). This also saw participants provide permission for imagery, written responses, and interview transcripts to be used for publication and dissemination purposes. In conducting this study, we acknowledge there are limitations and drawbacks to this work. Foremost, we note the small number of participants and single recruitment source:U3A Network Victoria:suggesting that this research might provide a rich and engaging dataset but that the results should not be considered definitive and are reflective of a small sample. Like other cultural probe studies, we also note that these studies often see limited interaction between researchers and participants, which reduces the support and engagement respondents may desire, as an issue only worsened by the conditions of the COVID-19 pandemic and health-related lockdowns (Wherton et al.,; Celikoglu et al.,). This saw participants being limited to being able to seek technical support or, in the interviews, to express themselves via phone call, email, or videoconference, which did reduce the potential for capturing non-verbal communication and other benefits from face-to-face interactions. After the probes were returned and post-study interviews conducted, the resulting written, photographic, and audio datasets were transcribed into a format beneficial for use with the qualitative data analysis computer software NVIVO. From the 35 individual probe tasks, we reviewed 76 images, 93 captions, 49 diary entries, and 322 min of interview transcription. To effectively analyse these materials, we employed Braun and Clarke's reflexive approach to thematic analysis, which we found offered a level of theoretically flexible as well as the critical reflection necessary to interrogate the characteristics of resolution in imagery of aging. Used widely across the social, behavioral, and applied sciences, this format of thematic analysis has been effective in responding to (a) people's experiences, views or perceptions; (b) understandings or representations; (c) factors or social processes that engage with phenomena; (d) rules or norms that deal with human behavior or practices, as well as this behavior or practices themselves; and (e) the construction of meaning (Braun and Clarke,). Further, as we seek to engage with methods that support a disciplined practice of critically interrogating what we do:the how and why:the reflexivity central to this approach engages with the role and actions of the designer, valuing their subjectiveness, situatedness, and awareness, questioning them and their work. Following Braun and Clarke's six phases of thematic analysis, the photovoice, social diary, and semi-structured interview datasets were reviewed individually and then coded by the author to develop themes that spoke to the topics of the study. Encompassing the stages of thematic analysis refined by Braun and Clarke, the author undertook a process of (1) dataset familiarization through a combination of transcription and digitizing of the response, (2) data coding on the NVIVO software then took place; (3) where initial themes were generated and sorted into the overarching topics; (4) these themes were developed and reviewed; (5) which led to further theme refining, defining, and naming; and (6) resulted in the write up of this analysis in a narrated form. Specific to this study, we took a deductive orientation to code the data and sorting themes, with the first exercise in coding for social technology, networks, practices, and wellbeing (Section Social interactivity in later life). This was supplemented by a second exercise sorting themes around the conceptual idea we sought to understand through the dataset:image resolution (Section Perspectives on producing imagery of aging). Pseudonyms have been used for participants, with identifying features such as faces, names, etc., obscured. In analyzing older adults' responses across the topics of social technology, networks, practices, and wellbeing, we documented both technology-dependent and more general forms of interaction, suggesting that social interactivity captures concerns for interpersonal human interaction that we found. While technologies may form a key (and growing) role in social interaction, respondents were more likely to describe its utility or friction in relation to other aspects of their everyday. This point, and other insights, were determined as the author systematically coded an initial fifteen to twenty codes for each topic (n = 67), which was reviewed and sorted into thirteen initial sub-themes, developed and refined into three overarching themes. These resulting themes are explained below through a short descriptor supported by responding photography and illustrative quotes. As foremost a comment on how an individual's social network and personal identity can change over time, the theme of adapting to the shifting, and in many ways reducing, groups an older adult has around them resonated strongly with respondents. As Joan framed it, as a senior, "your social networks do change because people retire and ... quite a lot of people are moving into lifestyle communities or retirement villages". Other respondents also captured this perspective in their own lives, as Mary discussed how an annual camping trip with friends needed to be adapted to a holiday house as the group's interests and accessibility needs changed, with the group itself having dwindled as many passed away. Meanwhile, as a retiree, Claire had tried to join groups with other retirees in their 70s and 80s, which she found "a bit challenging because that's not very stimulating. For me, it's not just trying to find that set of people in my own age group".
cultural probes, design for aging, imagery resolution, images of aging, interaction design
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PMC5519229_01
Female
80
A woman aged 80 years was admitted to hospital with dyspnea, cough, and fatigue, which she had had for 2 years. She reported having pulmonary tuberculosis when she was aged 15 years. The patient had no smoking history. She was using bronchodilator drugs for asthma and levothyroxine for hypothyroidism. In the physical examination, decreased breath sounds on the right side and mild wheeze were found. Her complete blood count and biochemistry parameters were normal. Lung function tests revealed a mild obstructive pattern: forced vital capacity (FVC) 1.60 L (92.7% predicted), forced vital capacity in one second (FEV1) 1.22 L (88.7% predicted), and the FEV1/FVC ratio was 0.76.
adult, geriatric, pulmonary artery hypoplasia
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PMC6831874_01
Female
14
A 14-year-old female with a 1- week history of intermittent right-sided chest and back pain and shortness of breath presents to the Emergency Department. She describes the pain as dull in quality, diffuse but non-radiating, and lasts approximately 1 hour before subsiding. The pain is pleuritic in nature and the only alleviating factor identifiable is ibuprofen. The shortness of breath is not related to any exertion or activity and was constant. There is no past medical history of a specific or relevant medical problem and the patient specifically denies a history of asthma, pneumonia, gastro-esophageal reflux, or broncho-pulmonary dysplasia. The patient was a full term baby born via spontaneous vaginal delivery without any complications. Menarche occurred at 12 years of age. Cycles are regular, occurring every 31 days and lasting for 4 days. The patient received all of her recommended immunizations for age. She lives with her mother, father, and brother in a house. There are no pets or smokers in the home. There is no history of recent sick contacts, no recent illnesses, and no recent travel. She denies sexual activity and denies alcohol, tobacco, or other illicit substance use. Family history is significant for asthma in her maternal grandfather but negative specifically for tuberculosis, Connective tissue disease, pneumothorax, or Sarcoidosis. Vitals signs are within normal limits. She is breathing at a rate of 20 breaths per minute and oxygen saturation is 100% on room air. Height and weight reveal a girl at the 90th and 10th percentiles respectively. Physical exam reveals an alert, awake female who appears her stated age and is in mild distress. All physical exam findings are within normal limits with the exception of the respiratory exam, which reveals diminished breath sounds in the right upper lung field, and the musculoskeletal exam that reveals a mild scoliosis and a Marfanoid body habitus. A complete blood count and basic metabolic panel are within normal limits. A chest x-ray demonstrates a 2.3cm apical pneumothorax in the right hemithorax. This was the patient's first of several presentations. During a 2-year period she developed 9 pneumothoraces both in the right and left hemithorax, all confirmed radiographically. After the first 5 were treated primarily with a non-rebreather mask and symptom management, she had a bilateral video-assisted thoracoscopic surgery (VATS) and a blebectomy of the most highly affected areas. The VATS did not reveal any lesions suggesting a definitive pathology for the pneumothoraces. For 9 months following this procedure, she continued to have recurrent pneumothoraces that occurred approximately every 3 months. Testing for cystic fibrosis, alpha-1 antitrypsin deficiency, and Fibrillin-1 (to evaluate for Marfan's and adolescent idiopathic scoliosis) was negative. A CT-Chest w/o contrast (see Fig. 1) performed on her 7th presentation displayed a left-sided 2.1cm pneumothorax but did not demonstrate any evidence of blebs or bronchiectasis. After her 9th presentation, the obstetrics and gynecology team was consulted. The pneumothoraces always presented within+-two days of her menses. She was placed on a trial of continuous combined oral contraceptive pills (COCs), specifically 90 mcg levonorgestrel and 20 mcg ethinyl estradiol tablets (Amethyst ). She achieved complete resolution of her symptoms after this and was thus clinically diagnosed with catamenial pneumothorax. Three years after starting the COC she has remained in total remission and has not experienced another episode of pneumothorax.
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Non-contrast CT scan demonstrating one of many right-sided pneumothoraxes in our patient. No bronchiectasis or blebs present on CT.
PMC10460171_01
Male
83
An 83-year-old male with an established diagnosis of psoriasis from 20 years before was referred to our clinic with a 3-month duration of pruritus followed by eruption of pruritic, erythematous and urticarial patches associated with polycyclic lesions on his limbs and trunk. His psoriasis, which had been treated in the past with topical corticosteroids and narrow band ultraviolet B phototherapy, began to quickly worsen in the meantime. Psoriasis Area Severity Index (PASI) was 12. He also had insulin-dependent diabetes mellitus and hypertension. Current medications included metformin, atenolol and chlorthalidone for many years. The patient was diagnosed with BP with typical histology, positive direct and indirect immunofluorescence findings with Bullous Pemphigoid Disease Area Index (BPDAI) 66. Oral prednisone, 25 mg/day was started. Due to a persistent corticosteroid-induced hyperglycemia, prednisone doses were gradually tapered until a 5 mg/day maintenance dose. While BP improved rapidly with BPDAI 16, psoriasis worsened (Figures 1 and Figure 2). Methotrexate was initiated at 15 mg/week (0.20 mg/kg), but BPDAI increased to 30. Due to ineffectiveness in both diseases, methotrexate was stopped after 12 weeks of therapy. Apremilast was then introduced and discontinued after 3 months due to inefficacy. In order to initiate a biological antipsoriatic therapy, the patient was screened for the presence of tuberculosis, hepatitis B, C and HIV. QuantiFERON-TB Gold resulted positive. The patient refused isoniazid therapy. DMF was then started at a dose of 30 mg/day for 7 days and gradually up-titrated over 8 weeks to a maximum of 150 mg/day. A maintenance dose of prednisone 5 mg on a day was also administered. Within 12 weeks of treatment with DMF 150 mg/day, marked improvement of both psoriasis and BP was observed and pruritus resolved. Complete remission of BP (BPDAI 0) and psoriasis (PASI 0) was finally achieved 6 months from treatment start. Prednisone was then tapered to 5 mg every 2 days without side effects. Over the following months, there was a persistent clinical remission of psoriasis and BP. Due to a progressive lymphopenia with a total lymphocyte count of less than 300/microL, DMF was discontinued after 15 months. The patient experienced relapse of his psoriasis, while clinical remission of BP was observed. Psoriasis was then treated with risankizumab subcutaneously, at a dose of 150 mg at week 0, week 4, and then 12-weekly thereafter, without tuberculosis prophylaxis. At his most recent follow-up visit, 12 months after the initiation of risankizumab therapy, no relapse of both diseases was seen (Figures 3 and Figure 4). Autoimmune blistering diseases of the skin may be observed in patients with psoriasis, BP being the most frequently reported. There is no standardised therapeutic approach to coexistent psoriasis and BP. Corticosteroids are the mainstay of treatment for BP. However, their use is limited in diabetic patients due to the risk of acute hyperglycemic complications, particularly in elderly patients. Recently, a successful treatment with dupilumab, a fully human monoclonal antibody targeting the IL-4 and IL-13 signaling pathways, was reported. However, cases of dupilumab-induced psoriasis are also described. A potential functional role of the proinflammatory cytokine IL17A has been shown leading to IL17A inhibition as a promising therapeutic strategy. Therefore, emerging, novel targeted therapeutic approaches in BP are being awaited with great interest. DMF was able to control both psoriasis and BP in our patient. However, treatment was discontinued due to grade 3 lymphopenia, which is a possible adverse effect of DMF, particularly among older patients. Also, Bilgic-Temel et al reported clearance of BP in a patient with multiple sclerosis following treatment with DMF. At the cellular level, DMF could act in ABDs through inhibition of neutrophil and monocyte recruitment into the skin. Considering its pleiotropic effects, DMF could be an effective treatment in psoriatic patients who develop BP. Additional observations are needed to confirm if DMF may be considered a possible therapeutic option in the clinical scenario of BP associated with psoriasis. Institutional approval was not required to publish the case details. The patient reportedly gave written consent to the Authors for the publication of his clinical history and photographs.
bullous pemphigoid, elderly, latent tbc, psoriasis, treatment
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PMC3930962_02
Male
56
A 56 year-old caucasian male was admitted due to fever of unknown origin. He had end stage renal disease due to a rapidly progressive IgA nephropathy treated with cyclophosphamide for 6 months (cumulative dose 21.6 g) plus prednisone. Was on hemodialysis since April 2005 (day - 2355). He also had a prior history of Polycythemia Vera diagnosed in 2001 (day - 3566), arterial hypertension, rickettsiosis diagnosed and treated on May 2010 (day - 441), and pulmonary tuberculosis infection, with clinical response to treatment. Patient was submitted to deceased-donor renal transplant on 1st of September 2011 (day - 0). Induction immunosuppression was performed with basiliximab, tacrolimus, MMF, and prednisolone. Post-surgery was complicated with infected retroperitoneal hematoma (treated with meropenem and vancomycin), surgical wound infection by Pseudomonas aeruginosa (treated with ciprofloxacin plus ceftazidime), and Candida albicans oropharyngitis (resolved with fluconazole). Allograft presented delayed graft function and later, acute vascular rejection (Banff IIA) for which ten doses of Anti-thymocyte globulin (ATG) were administered (day - 35). Due to persistent fever and sepsis with negative blood cultures, and failure to recover renal function, patient was submitted to transplantectomy 3 months later (day - 88). Cultured fluid collected from the abdominal drain placed in the area of the removed allograft was positive for C. neoformans. Allograft histology also revealed the presence cryptococcus. Normal opening pressure was found on lumbar puncture, with negative India-ink CSF. On day 89 patient was started on liposomal amphotericin B (1.0 mg/kg per day IV) for four weeks, with complete resolution of symptoms. He progressively recovered and was discharged under fluconazole (200 mg per day, oral).
cryptococcosis, immunosuppression, lupus, meningoencephalitis, transplant
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PMC4531673_01
Male
69
In April 2000, a 69-year-old man was admitted to Inha General Hospital due to productive cough with dark, brown-colored sputum. He complained of night sweat and weight loss of more than 9 killograms for 2 months. Nine years before entry, the patient experienced a cerebrovascular accident which left a sequelae of left side weakness, mild dysphagia and dysarthria. Because of poor oral hygiene, plaque and calculus, the patient had frequent visits to the dentist but no dental care was given within the previous 5 years. The patient had no past medical history of pulmonary tuberculosis, chronic lung disease or any other condition. On physical examination, the patient's blood pressure was 130/90 mmHg, pulse rate 80/min and body temperature 36.7 C. His mental status was alert but dysarthric feature and left side hemiparesis was shown. Oral examination by a dentist revealed gingivitis, dental decay, very poor hygienic state and moderate amount of plaque and calculus. On chest examination, abnormal breathing sounds, such as crackle and expiratory wheezing, were not audible. There were no other physical abnormalities noted. Laboratory examination showed the hemoglobin was 13.8 g/dL, hematocrit 40.4%, white blood cell 6,700/muL, platelet 177,000/muL. Erythrocyte sedimentation rate was 14 mm/h. C-reactive protein was 0.5 mg/dL. Cytologic examination of sputum was negative. Bacteriologic examination of sputum showed no evidence of mycobacterial tuberculosis or fungal infection. Chest radiographs revealed increased opacity and atelectatic change in the anterior segment of the left upper lobe, suggestive of obstructive pneumonitis or pulmonary tuberculosis (Figure 1A). A computed tomographic scan (CT) of the thorax showed consolidation and air bronchogram in the left upper lobe with partial atelectasis, but significant enlargement of mediastinal or hilar lymph node was not observed (Figure 1B). Bronchoscopic examination showed a pink and soft protruding mass obstructing the left upper lobar bronchus was suggestive of bronchogenic carcinoma (Figure 2A). The presumptive diagnosis by bronchoscopy was bronchogenic carcinoma. However, biopsy of the lung tissue obtained by bronchoscopy showed gram-positive sulfur granules and hyphe-like components within a granulomatous formation, which showed squamous metaplasia of bronchial mucosa with mixed inflammatory cellular infiltration and some colonies of actinomycosis (Figure 3). The final diagnosis was endobronchial actinomycosis. The patient was given 10 million units of intravenous penicillin-G daily for two weeks. The opacities and infiltration on chest radiographs gradually decreased. After two weeks of penicillin therapy, he was switched to 2 g amoxicillin daily. At discharge, more than 80% of his pulmonary infiltration had resolved and the remainder was markedly reduced in size. After discharge, oral antibiotics were administered for 4 weeks. Follow-up bronchoscopic examination revealed a complete resolution of the endobronchial mass lesion and, in place, a foreign body was exposed (Figure 2B). The removed foreign body was proven to be a very small-sized fish bone. This unfortunate accident is the first case of a foreign body-induced pulmonary actinomycosis in Korea. The patient was completely cured with no remaining symptoms.
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A chest CT scan obtained at the level of the aortic arch reveals consolidation with airbronchogram (arrow) in the left upper lobe. Fish bone was not identified in the CT scan.
PMC5757588_01
Male
46
A 46-year-old man consulted our department for the chief complaint of exacerbation of respiratory distress of 2-month duration, with accompanying night sweats, fever, and weight loss. He was an electrician and had no history of dust inhalation, drug use, or pet birds. He was previously healthy with unremarkable medical history. He had been smoking 20 cigarettes per day from age 20 years. He had quit paper cigarettes 3 months before, and smoked 20 cigarettes per day using an e-cig pen. He used the e-cigs until the day before examination. Physical findings at presentation revealed pallor, body temperature 37.1 C. Chest auscultation revealed mild fine crackles in both sides of the chest with normal heart sounds. Laboratory data at hospital arrival included white blood cell count 15,200/mm3 (77.5% neutrophils, 11.5% lymphocytes, and 4.0% eosinophils). C-reactive protein levels (11.81 mg/dL) were elevated and Krebs von den Lungen 6 (KL-6) was high at 1841 U/mL. Blood gas analysis findings in room air revealed pH 7.504, PaCO2 29.0 Torr, PaO2 52.6 Torr, HCO3 22.7 mmol/L, and base excess 0.7. Pulmonary function testing (PFT) revealed the %vital capacity of 50.6%, indicating restrictive impairment. Chest radiography revealed opacities in the bilateral upper lung fields with extensive bilateral ground-glass opacity (GGO) predominantly around the lateral segments of the lungs (Fig. 1A). Chest computed tomography (CT) revealed GGO and traction bronchiectasis throughout the entire bilateral upper lobes; non-segmental GGO with curvilinear shadow was also observed in the middle lobe, lingula, and bilateral lower lobes (Fig. 1B). Two days after the initial examination, BAL and TBLB were performed. Bronchoscopic examinations revealed normal airways. The BAL fluid findings included CD4/CD8 0.6, total cell count 4.0 x 105/mL, and cell fractionation of 18% macrophages, 57.5% neutrophils, 6.0% lymphocytes, and 18.5% eosinophils. Bacterial culture examination revealed normal flora. Abundant lipid-laden macrophages were observed upon Oil Red O staining of BAL fluid (Fig. 2A). Lung histological examination revealed lesions with acute changes, alveolar septum swelling, and eosinophil and neutrophil invasion, with intra-alveolar invasion of eosinophils and neutrophils; in addition, abundant macrophages containing blackish-brown pigment and multinucleated foreign-body giant cells and intra-alveolar organization (Fig. 2B-D). These changes were considered to be caused by inhalation of foreign bodies through the airways, which led to the histopathological diagnosis of acute alveolitis with intra-alveolar fibrosis caused by e-cig use. We diagnosed e-cig-induced ALI caused by inhalation. After bronchoscopy, methylprednisolone was administered at a dose of 1 g/day for 3 days. The patient received high-dose steroids, because at the time of treatment he had severe hypoxia. Thereafter, the patient received maintenance therapy of 1 mg/kg prednisolone. Antibiotics were not prescribed. After 2 weeks of treatment, chest radiography showed that the extensive GGO had markedly ameliorated (Fig. 1C). After 4 weeks, PFT results returned to normal range. The subject was tapered off gradually from steroid therapy with follow-up observation and discharged from the hospital on Day 30. He completely quitted e-cig smoking and no subsequent flare up of pneumonitis was observed on outpatient follow-up.
acute lung injury, bronchoalveolar lavage, electronic cigarette, lipid‐laden macrophages, transbronchial lung biopsy
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PMC8683165_01
Male
33
A 33-year-old male presented to our center with chief complaints of profuse per rectal bleed mixed with stool for three days that was associated with easy fatigability for one week prior to the initial presentation. He also had one episode of black tarry stool. However, he had no complaints of blood in vomit, purpuric rashes, or petechiae. He also had no hematuria, weight loss, night sweats, evening rise of temperature or loss of appetite, cough, chest pain, dyspnea, palpitation, limb edema, loose stools, jaundice, and abdominal distension. Bleeding was absent from other orifices. He had no history of diabetes mellitus, hypertension, cardiac diseases, and pulmonary tuberculosis in the past. He consumed 80 grams of alcohol per day for 15 years, but he did not smoke. On examination, he was ill looking, conscious, and was well oriented to time place and person. He had pallor and was dehydrated. However, he had no icterus, clubbing, cyanosis, or edema. His pulse rate was 110 beats/minute, blood pressure was 80/60 mm of Hg, body temperature was 98 F (36.6 C), respiratory rate was 19 breaths/minute, and oxygen saturation was 95% in room air. The digital rectal examination showed fresh blood over the examining finger and otherwise normal findings. Abdominal and cardiac examination was normal. Laboratory investigations showed hemoglobin 10.8 g/dl and hematocrit 31.6%. The total leukocyte count was 11510/mm3, neutrophils were 78%, and platelet count was 291000/mm3. The prothrombin time was 14 seconds, and the International normalized ratio was 1.08. The albumin level in the blood was 2.4 gm/dl, and total protein was 6.1 gm/dl, total and direct bilirubin were 0.7 and 0.1 mg/dl in the blood. Alanine aminotransferase and aspartate aminotransferase level was 97 U/L and 114 U/L, respectively. HbA1C level in the blood was 7.2. The level of urea (33 mg/dl), creatinine (1.1 mg/dl), sodium (132 mEq/l), and potassium (3.6 mEq/l) were within normal range. Traces of sugar and albumin (++) were present in the urine examination. The fecal occult blood was found in the stool. Mycobacterium tuberculosis was not detected in sputum in the acid-fast bacilli (AFB) stain. The chest X-ray was normal. Ultrasonography (USG) of the abdomen and pelvis and upper gastrointestinal endoscopy showed normal findings. A Computed Tomography (CT) scan of chest and abdomen showed asymmetric circumferential thickening in the ileocaecal region with lobulated thickened caecum, soft-tissue stranding and necrotic mesenteric lymphadenopathy, and indeterminate lobule in the lung (Figure 1). Colonoscopy showed multiple transverse ulcers with overlying exudates in terminal ileum and ascending and transverse colon. Histopathological examination of the ileum and colon showed patchy ulcers with exudates, granulation tissue, fibrosis, deep lymphoplasmocytic inflammation, and crypt regenerative changes with fibrinoid changes in scattered capillaries and venules and was inconclusive. However, gene XPERT was positive for Mycobacterium tuberculosis. He was diagnosed with ileocaecal tuberculosis. The hemoglobin level dropped to 6.1 g/dl after two days of admission, and he had an episode of weakness associated with profuse sweating and rigor. Fluid resuscitation followed by two pints of whole blood transfusion was performed. After that, his hemoglobin was increased to 10.2 mg/dl. He was managed with four antitubercular drugs and showed significant improvement. Following this, he was discharged on oral antitubercular medications (isoniazid, rifampicin, pyrazinamide, ethambutol, and pyridoxine) after 10 days of admission. On follow-up after two weeks, he was responding well to antitubercular medications with improved symptoms, i.e., no per rectal bleeding, and his liver function test was within the normal range.
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PMC9872202_01
Male
72
The patient was a 72-year-old male heavy smoker (50 pack-years). During a routine examination in December 2020, a space-occupying lesion (2.9 cm x 2.6 cm) near the lung hilum (Figures 1A, F) and mild fibrotic changes of unclear origin were detected (Figures 2A, F). He underwent EBUS-TBNA pathological examination and PET-CT to confirm the final diagnosis of squamous cell lung carcinoma (SqCLC; T1N1MO, stage IIb). Genomic sequencing test showed no driver mutation for targeted therapy (ALK(-), BRAF(-), BRCA1(-), BRCA2(-), EGFR(-), ERBB2(HER2)(-), FGFR2(-), FGFR3(-), KIT(-), KRAS(-), MET(-), NRAS(-), NTRK1(-), NTRK2 (-), NTRK3(-), PDGFRA(-), RET(-), ROS1(-), and IDH2(+)); however, the patient tested positive for PD-L1 (TPS=25%, IPS<1%, tested using a Ventana SP263 assay), with tumor mutation burden of 7.26 Muts/Mb (tested using a next-generation sequencing (NGS) panel and paired with peripheral blood sample sequencing). Other genetic mutations related to immunotherapy were also tested as follows: CD274(-), PDCD1LG2(-), MLH1(-), MSH2(-), MSH6(-), PMS2(-), POLD1(-), POLE(-), TP53(+), ATM(-), ATR(-), BRIP1(-), CHEK2(-), FANCA(-), RAD50(-), PALB2(-), CHEK1(-), MRE11(-), PBRM1(-), MDM2(-), MDM4(-), DNMT3A(-), JAK1(-), JAK2(+), PTEN(-), STK11(-), CCND1(-), FGF19(-), FGF3(-), FGF4(-). The patient had no history of cardiopulmonary or connective tissue disease, and the Eastern Cooperative Oncology Group (ECOG) performance status was rated as 2 points. Owing to the patient's age and tumor location, systemic chemotherapy combined with immunotherapy was administered: intravenous infusion of albumin-paclitaxel 160 mg (D1, D8) combined with camrelizumab 200 mg (D1). After two cycles of the above treatment, the patient developed fever after fatigue and colds on 13 February, 2021, with a maximum temperature of 39 C and shortness of breath. The patient was admitted immediately the next day. Bilateral bronchial breathing sounds and Velcro rales were detected. Laboratory examination revealed an inflammatory blood reaction (Figures 3A, B), decreased oxygen partial pressure (Figure 3C), decreased oxygen saturation (85% SaO2), and increased D-dimer levels (>=20 mug/ml) (Figure 3D). Images showed that the primary cancer foci shrank significantly and were surrounded by patchy ground-glass opacities (GGOs) and consolidation shadows (Figures 1B, G). Bilateral peribronchovascular and subpleural GGOs, reticulation, and consolidation were predominant in the middle to lower lungs (Figures 2B, G). Contrast-filling defects were also observed in the pulmonary artery branches of the upper and lower lobes of the left lung. The patient was preliminarily diagnosed with type I respiratory failure and interstitial pneumonia (CIP?), pulmonary embolism, and SqCLC (T1N1MO stage IIb, partial response [PR]). The patient was administered with mask oxygen inhalation therapy (8 L/min), systemic corticosteroid pulse therapy (methylprednisolone sodium succinate, 240 mg Q.D. for 2 days), and anticoagulation treatment (enoxaparin sodium, 4,000 U Q.D.) on February 16. Considering that infection could not be ruled out, empirical anti-inflammatory and antiviral treatments were administered, along with anti-asthmatic, gastric-protecting, calcium-supplementing, and other symptomatic support treatments. After 48 h, respiratory failure progressively aggravated, and the oxygenation index (PaO2/FiO2) was calculated as 125 mmHg. The patient was then transferred to the MICU for further treatment on February 18. The patient was intubated for mechanical ventilation. Bedside chest radiography revealed poor lung transparency (Figure 4A). As a diagnosis of exclusion, we considered that the pulmonary symptoms and signs were caused by ICI toxicity and responded inadequately to high-dose corticosteroids. The patient had no signs of other concurrent irAEs, such as dermatitis, hepatitis, nephritis, or myopericarditis. The final diagnosis was steroid-refractory CIP grade 4 (G4), defined as a life-threatening respiratory compromise. For steroid-refractory CIP G4, infliximab (500 mg for 1 day) was administered intravenously, and the ICIs were permanently discontinued. Oral corticosteroids were slowly tempered. Two days after immunomodulatory treatment, the inflammation indicators increased again (Figures 3A, B), and plenty of sticky sputum was collected from the patient. We performed sputum culture and sputum smear and found G+ cocci, G- bacillus, Acinetobacter baumannii, and Candida albicans. We then examined the bronchoalveolar lavage fluid (BALF) using NGS and found Acinetobacter baumannii, C. albicans, and Enterocooccusum faecium infection (Table 1). Considering severe comorbid infectious pneumonia due to compromised immune system, the patient was administered with tigecycline combined with meropenem as anti-inflammatory therapy, micafungin as antifungal therapy, and intravenous immunoglobulin pulse therapy for 3 days to enhance the self-immunological barrier. Enoxaparin sodium anticoagulant therapy was continued for pulmonary embolism. After 3 days, the temperature and laboratory indicators improved (Figure 3). Bedside chest radiography showed improved bilateral lung transmittance (Figure 4B). On March 2, endotracheal intubation was removed, and the patient was administered with nasal high-flow oxygen (45 L/min, oxygen concentration 50%). Figure 5 shows the management axis of CIP G4 and the critical complications in this patient. After sufficient medical care in the MICU, the patient's condition stabilized, and he was transferred to the general ward on March 9. To manage pulmonary interstitial fibrotic changes and potentially inhibit tumor growth, nintedanib 150 mg was prescribed orally twice daily during the subacute phase of CIP. With good tolerance, the dosage was increased to 200 mg orally twice daily 1 week later and has been maintained to date. On 2 April 2021, the patient's ECOG score was rated 4 before discharge; lung CT reexamination showed no new space-occupying lesions, and the original occupation was significantly smaller than the previous one in December 2020 (Figures 1C, H). The therapeutic efficacy of SqCLC was evaluated as PR. For CIP, pulmonary injury had evolved into an organizing and fibrotic stage. Multiple GGOs, reticulation, grid lesions, and traction bronchiectasis in a cryptogenic organizing pneumonia (OP) pattern were found in the dominant lobe around the primary tumor site, with patchy lesions in the opposite lobe (Figures 1C, H). The bilateral lower lungs were predominantly fibrotic with GGOs, reticulation, consolidation, honeycomb shadows, and thickened interlobular septa (Figures 2C, H). Owing to the patient's deteriorating physical status and COVID-19 public control policy, the patient had recuperated at home for 6 months and maintained oral nintedanib therapy (200 mg twice daily), with slow tapering of oral corticosteroid therapy. The patient visited the hospital for a review on 13 October 2021. The performance status improved, with an ECOG score of 2. The CT scan showed a lobulated mass with a size of 5.0 cm x 2.6 cm in the upper lobe of the right lung, surrounded by fine burrs and thick-walled cavities (Figures 1D, I). The interstitial changes in the bilateral lower lobes were significantly improved compared to the previous films (Figures 2D, I). There were swollen lymph nodes in the mediastinum, and the largest one was approximately 2.6 cm x 2.0 cm in size. Moreover, the levels of serum tumor markers increased (U/L): CEA, 16.6; AFP, 2.55; CA125, 102; CA153, 36.1; CYFRA, 9.43; NSE, 20.00; and SCCA, 13.6. The therapeutic efficacy of lung cancer was evaluated as progressive disease (PD), with T2bN2M0 stage IIIa. After consultation with the patient's family, the third chemotherapeutic cycle, comprising albumin-paclitaxel, was started at 200 mg (D1, D8/q3w), and oral nintedanib treatment was continued. In addition, afatinib 30 mg orally once daily was administered as second-line cancer therapy. The patient received four to seven cycles of albumin-paclitaxel treatment on 11 and 30 November 2021, 22 December 2021, and 21 February 2022. Lung CT examination showed that the former shadow was 4.2 cm x 4.3 cm in size (Figures 1E, J) and stable mild interstitial changes (Figures 2E, J). The largest lymph node in the mediastinum was approximately 2.4 cm x 1.8 cm in size. The remaining abdominal CT, brain MRI, and whole-body bone ECT scans showed no obvious abnormalities or metastasis. A response of stable disease was achieved. The patient showed mild adverse reactions: slightly increased levels of liver transaminase (72 U/L AST (15-40) and 69 U/L GGT (10-60). To date, the patient has maintained the current lung cancer treatment regimen. The process of antitumor therapy for the patient is shown in Figure 6.
checkpoint inhibitor-related pneumonitis, immunotherapy, nintedanib, non-small-cell lung cancer, pulmonary fibrosis
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PMC7124200_01
Male
44
A 44-year-old man with known compensated chronic hepatitis B was admitted on March 5, 2003, with a 1-week history of malaise, anorexia, and tea-colored urine. On examination, he had jaundice but no other signs of chronic liver disease. He was afebrile and his vital signs were normal. He had thrombocytopenia (platelet count, 124 x 109/L) and a deranged coagulation profile (international normalized ratio: 1.82). Liver function was grossly abnormal (total bilirubin, 6.7 mg/dL; albumin, 3.2 g/dL; alkaline phosphatase, 132 U/L; alanine transaminase, 2090 U/L). Serological tests confirmed hepatitis B surface antigen (HBsAg) positivity. He was hepatitis B e antigen (HBeAg) negative and anti-HBeAg positive. Both anti-hepatitis C virus and immunoglobulin M anti-hepatitis A virus antibodies were negative. His serum HBV-DNA was 5.1 MEq/mL. The diagnosis was acute reactivation of chronic hepatitis B. Treatment with lamivudine (100 mg daily) was started. He remained clinically stable with biochemical improvement until day 4, when he developed a fever of 39 C. No focal source of infection was found and his chest radiograph was normal. Despite empirical intravenous cefotaxime and levofloxacin, his fever persisted. A chest radiograph on day 7 showed bilateral air space consolidation. His condition deteriorated the next day, involving respiratory failure and shock, and he was admitted to the intensive care unit. By this time it was apparent that he had contracted severe acute respiratory syndrome (SARS) during the hospital outbreak of the disease. This was subsequently confirmed when SARS-coronavirus (SARS-CoV) was isolated from his nasopharyngeal aspirate. Despite mechanical ventilation and therapeutic intervention that included broad-spectrum antibiotics, ribavirin, and pulse methylprednisolone, his condition worsened and led to multiple system organ dysfunction. The patient died on day 16. Postmortem examination revealed extensive consolidation in the lungs with diffuse alveolar damage and hyaline membrane, features commonly found in patients who had died of SARS. His liver was cirrhotic and showed severe hepatocyte dropout with small islands of hepatocytes left in the parenchyma (Figure, A). Most of the portal tracts had minimal-to-mild chronic inflammatory cell infiltration with some portal tracts showing lymphocyte depletion (Figure, B and C). There was moderate periportal cholangiolar transformation (Figure, D). Furthermore, severe cholestasis was demonstrated with large bile plugs observed within the bile canaliculi (Figure, E). There was also mild macrovesicular steatosis without accompanying hyaline change (Figure, F). SARS-CoV could not be isolated from the liver tissue. Peiris et al found a higher percentage of patients with HBsAg positivity among SARS patients who developed acute respiratory distress syndrome. However, whether the worse pulmonary outcome was directly related to chronic hepatitis B is not known. In this patient, reactivation of chronic hepatitis B was probably not the major cause of death. The patient was improving until he developed symptoms of SARS. With lamivudine treatment and without SARS, he most likely would have recovered. Conversely, his impaired hepatic function might have aggravated the course of SARS and contributed to his death. The interval between the onset of fever and death was much shorter (16 days) than the mean admission-to-death time of 36 days in other SARS patients who had died. The postmortem finding sheds light on the effect of SARS on the patient's hepatitis. Lymphocyte depletion in the portal tracts was unusual because submassive necrosis of liver due to exacerbation of chronic hepatitis B is often associated with prominent lymphocytic infiltration. Peripheral lymphopenia is an important feature in SARS and appeared to have affected the liver even in the face of hepatitis. Interestingly, lymphocyte depletion in this patient is reminiscent of hepatic histology in patients with full blown AIDS. This may reflect the overwhelming effect of SARS on the immune system. As no SARS-CoV could be isolated from the liver tissue, a direct cytopathic effect of SARS-CoV on the liver was unlikely. Cytokine dysregulation probably is important in the pathogenesis of SARS, and hence steroid or other immunosuppressive agents have been used as first-line therapy. Because immunosuppression may predispose to flare up of chronic hepatitis B, we propose the use of prophylactic antiviral therapy, such as lamivudine, before beginning immunosuppressive treatment in SARS patients with chronic hepatitis B. By decreasing the viral load, the likelihood of reactivation of hepatitis B may be reduced. Meanwhile, further studies are warranted to investigate whether chronic hepatitis B has any effect on the prognosis of SARS.
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PMC9678122_01
Male
64
We report a case of a 64-year-old male patient, with a history of left nephrectomy due to lithiasis, chronic kidney disease (baseline serum creatinine levels: 1.7 mg/dl) and in situ papillary urothelial carcinoma (2017) treated with transurethral resections and six BCG instillations in 2019. He presented to our emergency department with a fever up to 39 C, with concomitant shudder and mild dysuria symptoms, a few hours after the last intravesical instillation of bacillus Calmette-Guerin (BCG), fifteen days prior. He was receiving ciprofloxacin for the previous two days, without remission of his symptoms. On admission he was oriented, febrile (38.5 C), normotensive, with sinus tachycardia (115 bpm) and normal pulse oximetry (SpO2:98%). He also showed a petechiae non-palpable rash on both legs, and his liver was mildly enlarged. Laboratory tests revealed neutropenia (neutrophils: 1,000 K/muL) and severe thrombocytopenia (platelets: 8 K/muL); normal haemoglobin levels; acute kidney injury (urea:59 mg/dL, serum creatinine:2.01 mg/dL); abnormal liver function tests (AST:177U/L, ALT:94U/L, ALP:201U/L, GGT:380U/L);high LDH levels (604U/L), triglycerides (282 mg/dl) and d-dimers (5.5 mug/ml). There were also significantly elevated inflammation markers (CRP: 229 mg/L, ferritin: 5,596 ng/ml), with normal erythrocyte sedimentation rate (12 mm/hr) and coagulation tests (PT and PTT). Serologic tests were negative for hepatitis B, C, HIV, parvovirus B19, EBV and CMV viruses, as well as for Leishmania and Brucella. Multiple urine and blood cultures with specific cultures for mycobacteria were sterile. Serum complement levels, serum immunoglobulins, antinuclear and antineutrophil cytoplasmic autoantibodies were also negative. A peripheral blood smear was evaluated suggesting platelets with characteristics of peripheral consumption. The chest radiography was normal, and the abdomen ultrasound revealed an enlarged liver (23 cm) and spleen (16.8 cm). Whole-body computed tomography (CT) also revealed hepatomegaly and splenomegaly, without focal lesions or lymphadenopathy and emphysematous lesions in the right upper lobe. The patient was immediately treated with broad-spectrum antibiotics (piperacillin-tazobactam and amikacin) and empiric anti-tuberculosis treatment with isoniazid 300 mg, rifampicin 600 mg and ethambutol 1,200 mg three times weekly, and levofloxacin 750 mg. Immune thrombocytopenic purpura (ITP) was also considered due to the peripheral blood smear analysis, so the patient also received prednisone 1 mg/kg and intravenous immunoglobulin (IVIG) 400 mg/kg/day for five days, without clinical or laboratory improvement. The patient remained febrile in the sixth day with a further decrease in neutrophils, platelets and haemoglobin levels. Antibiotic treatment was upgraded to meropenem, but the patient showed no signs of improvement, and as a result it was discontinued three days later. Haemophagocytic lymphohistiocytosis (HLH) was suspected due to cytopenia, organomegaly, high ferritin and triglycerides levels and persistent fever above 38.5 C. The patient underwent bone marrow aspiration, which confirmed the diagnosis showing marked phagocytosis of platelets by histiocytes (Fig. 1). Bone marrow PCR for TBC, Ziehl-Neelsen stain and TBC cultures all came back negative. Unfortunately, we were not able to measure NKcell activity and soluble IL-2 receptor levels. Dexamethasone 10 mg/m2 was immediately started and the patient showed gradual clinical and laboratory improvement. Etoposide was not administered because of the abnormal liver and kidney biochemistry, and the severe cytopenia the patient suffered. Finally, a liver biopsy was performed, showing multiple parenchymal non-necroticising granulomas, composed of epithelioid histiocytes (Fig. 2) and Ziehl-Neelsen histochemical staining revealed a small number of acid-fast bacilli (Fig. 3).
bcgitis, hlh syndrome, intravesical bcg instillation
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PMC5251324_01
Male
0
Fifty-four commercial 1-day-old male white Plymouth Rock broiler chickens (Bonnie's Chick Hatchery, Elmira, ON, Canada) were randomly divided into 4 experimental groups (n = 13-14 per group). The chickens were fed an antibiotic-free chicken starter containing 20% protein for 11 days followed by turkey starter containing 28% protein (Arkell Research Station, University of Guelph). For the experimental infection (challenge) of birds, wild type CP1, CP1DeltapCP1netB and CP1DeltapCP1netB(netB +) were grown in cooked meat medium (Difco) (CMM) for 24 h at 37 C under anaerobic conditions. FTG medium (Difco) was then inoculated 3% (v/v) with an overnight CMM culture and incubated aerobically at 37 C for 15 h. The growth at 15 h was approximately log10 8.45 +- 0.14 C. perfringens colony-forming units (CFUs) per ml. The FTG-grown culture was then mixed with feed at a ratio of 2:1 (v/w). The chickens were starved for 24 h before the C. perfringens contaminated feed was administered on day 13. Inoculated feed was prepared fresh twice daily and fed to chickens for 5 days. Chickens were euthanized with carbon dioxide on the day following a 5-day challenge, and at necropsy the small intestine was examined for grossly visible lesions. Necrotic enteritis lesions were scored blindly using the system described by Keyburn et al.. To determine if there were differences in the number of birds with lesions between two challenge groups, a two-tailed Fisher's exact test was used to assess the null hypothesis that the proportion of birds with lesions among the two groups was the same. The null hypothesis was rejected at p <= 0.05.
clostridium perfringens, neloc-1, necrotic enteritis, netb, plasmid-deficient mutant
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PMC4555913_01
Female
10
A 10-year-old female child seropositive for HIV (acquired perinatally) presented to our dermatology outpatient department with a swelling on left cheek, which had gradually increased in size over a period of 6 months. In addition, she also complained of multiple skin coloured to white lesions over face, neck, lower abdomen, both hands and lower extremities since 6 months. Patient didn't have any other systemic complaints. There was no history of tuberculosis, herpes zoster, diarrhoea, or any other opportunistic infections. One-year back, patient had been started on anti-retroviral therapy (ART) (zidovudine, lamivudine, nevirapine [ZLN]) in a government ART centre on account of her low CD4 count (222 cells/mm3 [normal: 448-1611 cells/mm3]). However she had poor compliance and her CD4 count was consistently low (ranging between 172 and 224 cells/mm3) during the year. On examination there was a single, well defined, lobulated, tumoral swelling 5 cm x 6 cm x 7 cm in size on the left cheek [Figure 1]. Skin overlying the swelling was thinned out with surface showing evidence of ulceration, haemorrhagic crust with slough. Swelling was freely mobile over underlying structures. Multiple, discrete, pearly white, umbilicated papules were present over cheek, forehead, upper eyelids, nose, lower extremities and buttocks. There was no lymphadenopathy. Systemic examination including central nervous system examination was normal. A differential diagnosis of giant molluscum contagiosum, keratoacanthoma, squamous cell carcinoma and cryptococcosis was considered. On investigations, she had anemia (Haemoglobin: 7.6 g/dl [Normal: 9-11 g/dl]) and CD4 count was 251 cells/mm3. Other investigations including total leukocyte count, liver function tests and renal function tests were normal. Viral load estimation could not be done as the patient's parent refused to do the same due to financial constraints at that time. A punch biopsy of the tumoral swelling on left cheek revealed acanthosis with keratinocytes showing intracytoplasmic eosinophilic inclusion bodies, which were becoming basophilic in the granular layer. Thus a diagnosis of giant molluscum contagiosum was made. After correction of anemia, complete excision of the giant molluscum contagiosum was done followed by split thickness skin grafting. The cut surface of the excised lesion showed multiple gyri like corrugations corresponding to the marked acanthosis seen on histopathology. At the base of the excised lesion, multiple pearly white papules could be seen [Figure 2]. On histopathological examination [Figure 3], there was marked acanthosis, keratinocytes showing intracytoplasmic eosinophilic to basophilic inclusions which were extruding out with keratinous debris. The epidermal ridges extended deep into the dermis surrounded by a dense lymphohistiocytic infiltrate with multiple giant cells and few plasma cells/neutrophils. Within the infiltrate, occasional degenerated molluscum bodies were seen. The infiltrate also extended into the subcutaneous fat resulting in septal panniculitis with extensive fibrosis. One-month later, there was complete healing at the site of skin grafting with minimal scarring [Figure 4]. Rest of the lesions were treated with topical 10% trichloroacetic acid (TCA) application resulting in gradual resolution. The patient was continued on ART (ZLN) with thorough counselling regarding compliance with medication. Her CD4 count improved to 676 cells/cmm after 10 months and had undetectable viral load. One-year later, on follow up, there has been no recurrence of lesions.
giant, hiv, granulomatous, molluscum contagiosum, panniculitis
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PMC5987074_01
Male
22
A 22-year-old male was admitted to Valiasr Hospital affiliated to Birjand University of Medical Sciences Iran, with complaints of painful swelling of the left lower limb for the last two days. His vital signs were stable (oral temperature 37.3oC, pulse rate = 67, respiratory rate = 16, systolic blood pressure = 120 and diastolic blood pressure = 80) and his physical examinations, except, the swallowed tender left leg (from ankle up to the thigh) were unremarkable. Chest-x-ray, abdominal sonography and echocardiography were normal. CBC revealed mild normocytic anemia (Hb: 11 gr/dl) with normal WBC and Plt count (6.4, 172*103 respectively). The erythrocyte sedimentation rate and the c reactive protein were elevated unexpectedly (ESR = 50 mm/h, CRP = >10mg/L). Routine biochemical investigations, thyroid function tests and tumor markers were normal. He had neither undergone any major surgeries in recent past nor history of prolonged immobilization, other diseases and smoking. Ultrasound Doppler study of the left lower limb revealed DVT in left popliteal up to external iliac veins. The patient was treated through catheter directed thrombolysis (CDT) with infusion of streptokinase 250.000 unit stat and 100.000 unit per hour infusion for 48 hours with concomitant 500 unit per hour of heparin and taking warfarin tablets 5mg/daily. During hospitalization he had severe pleuritic chest pain that we thought that is due to small distal pulmonary embolism which is a common finding in venous thromboembolism. The patient discharged from hospital with a good general condition after 10 days with international normalized ratios (INR = 2), partial thromboplastin time (PTT = 30) and Prothrombin Time (PT = 18.4). A high sedimentation rate (ESR: 50) was our question mark at the patient discharge time when all primary evaluations were normal. The day after discharge, the patient re-admitted with cough, haemoptysis and pleuritic chest pain. The patient had blood -streaked sputum 6 times a day which was not massive (10 cc/24h). Laboratory tests showed an elevated ESR (80 mm/h) and CRP (139 mg/l). There was hemoglobin decline (hgb = 10.5 gr/dl). Biochemical findings were within normal limits. CXR and pulmonary CT angiography showed minimal pleural effusion and massive PTE and pulmonary necrosis were ruled out (Figure 1, Figure 2). Along with His subjective and objective findings a clinical suspicion to TB was raised that a surprising positive result of the sputum for acid fast bacilli (3 samples) confirmed it. Since the patient's symptoms were in the context of pulmonary tuberculosis, not lung infarction, he was referred to infectious service for TB treatment.
deep vein thrombosis, haemoptysis, pulmonary tuberculosis
The patient's CT pulmonary angiography.
PMC8550988_01
Male
7
A fifty-seven-year-old male patient without previous history of heart disease presented to the hospital with worsening shortness of breath since one week before admission. He also complained of fever and weight loss for three months. Additionally, he also experienced back pain along with lower limb weakness for a month. The patient was diagnosed with pneumonia and was treated with moxifloxacin. His sputum examinations were sterile and negative for acid-fast bacilli staining and GeneXpert MTB/RIF. After one week of antibiotic therapy, at the day of illness (DOI)-14, there is no noticeably clinical improvement. The patient was then referred to the cardiology department and underwent transthoracic echocardiography (TTE), in which a large oscillating mass at the posterior mitral leaflet (PML) was detected. The patient was diagnosed with infective endocarditis (IE) and given Ampicillin/Sulbactam and Gentamycin. Three consecutive blood cultures were negative. On the third week of hospitalization (DOI-28), the patient's condition did not improve, and he was referred to our hospital. Upon our hospital admission (DOI-30), the patient looked lethargic; the blood pressure was 100/60 mmHg, with a heart rate of 88 bpm, respiratory rate of 30 times per minute, and the temperature was 36.8 C. Physical examination showed an enlarged heart with a 3/6 pansystolic murmur at the apex with paraparesis and paresthesia of the lower limb at the level of L3. However, no gibbous was observed on spine examination. The laboratory results showed a hemoglobin of 9.2 gr/dl, leukocytes of 15,230/mm3 with increased C-reactive protein (CRP) (6.01 mg/dL), and procalcitonin (10.20 ng/ml) level, and positive rheumatoid factor. The electrocardiogram showed left ventricular hypertrophy with first-degree AV block. The echocardiography evaluation revealed mitral regurgitation (MR) with ruptured chordae tendineae, perforated leaflet, and multiple vegetation attached to both leaflets (Fig. 1). Magnetic resonance imaging (MRI) for the spine revealed multiple small abscesses at L2-3, L5-S1 (Fig. 2). The patient was diagnosed with blood culture-negative infective endocarditis (BCNIE) and spondylodiscitis due to pyogenic infections. We resumed the antibiotic, performed blood culture assessments, and planned for early surgery. However, the subsequent five consecutive blood cultures were negative for aerobic, anaerobic, and fungal blood cultures. A multidisciplinary clinical meeting was performed, and it was decided that the patient would undergo discectomy first, followed by cardiac surgery afterward. An open discectomy was performed three weeks after admission to our hospital (DOI-48). Granuloma tissue was found without purulent or abscess tissue. Debridement and irrigation were conducted. The pathologic examination of the spinal tissue showed proliferation of epithelioid cells with multinucleated datia Langhans (Fig. 3a and b). Although these findings suggest tuberculous infection, the GeneXpert MTB/RIF test was negative. Cardiac surgery was performed one week later (DOI-57). The surgery was performed with the left atrial approach. Multiple vegetation in the anterior mitral leaflet (AML) and PML (Fig. 4) were detected. The mitral valve was replaced with a mechanical prosthetic valve. During the postoperative period, rebleeding occurred in the intensive care unit. We planned to perform a redo surgery; however, the patient's family refused, and the patient passed away. The pathologic examination of mitral valve tissue showed proliferation of epithelioid cells with caseous necrosis area and multinucleated datia Langhans (Fig. 3c and d). The vegetation was cultured and showed no bacterial, MTB, or fungal growth. The smear for Acid Fast Bacilli and GeneXpert MTB/RIF were also negative. The real-time polymerase chain reaction (RT-PCR) consisted of IS6110, an insertion gene corresponding to the detection of MTB complex, which was performed on the vegetation tissue. The RT-PCR result showed amplification for IS6110 and was confirmed with the pyrosequencing method. The summary of patient history can be seen in Fig. 5.
aml, anterior mitral leaflet, bcnie, blood culture-negative infective endocarditis, blood culture-negative infective endocarditis (bcnie), crp, c-reactive protein, dna, deoxyribonucleic acid, doi, day of illness, eptb, extrapulmonary tuberculosis, hiv, human immunodeficiency virus, ie, infective endocarditis, mr, mitral regurgitation, mri, magnetic resonance imaging, mtb, mycobacterium tuberculosis, pml, posterior mitral leaflet, rt-pcr, rt-pcr, real-time- polymerase chain reaction, tb, tuberculosis, tte, transthoracic echocardiography, extrapulmonary tuberculosis, pyrosequencing method, tuberculous endocarditis
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