An 80-year-old man was referred to our clinic due to a 6-year history of PV. He previously received treatments with systemic corticosteroids and immunosuppressants, including azathioprine and mycophenolate mofetil, both pre-maturely interrupted after 6 and 4 months, respectively, due to inefficacy. A cycle of rituximab, followed by two maintenance administrations 6 and 12 months later, had revealed effective in establishing a prolonged remission off-therapy for about 2 years. He had an episode of thrombophlebitis of the lower limbs 2 years earlier, for which he was on treatment with rivaroxaban. At the time of the first dermatological visit, the physical examination showed erosions mainly affecting the trunk and scalp. The Pemphigus Disease Activity Index (PDAI) was 7. Because of the low disease activity, a treatment with topical steroids was attempted.
After 4 weeks, the patient returned because of a significant worsening of his cutaneous lesions, which were enlarging and increasing in number, located in the head and neck, trunk, and limbs, with no mucosal sites involved. Pemphigus exacerbation was associated with the onset of other symptoms, including a progressive dysphagia, weight loss, and melena. A periodic re-assessment of serum autoantibody concentration also indicated a significant increase in both anti-Dsg1 and anti-Dsg3 antibody titers. An endoscopic examination of the distal esophagus indeed revealed a stenosing esophageal mass; a PET/CT scan confirmed the presence of a lesion 3 cm in diameter, highlighting metabolic activity areas corresponding only to tumor location, without nodal or distant metastasis (). Previously, the chest RX and abdominal ultrasound conducted as screening for immunosuppressive treatments 2 years before were unremarkable, as well as the routine blood tests performed at that time.
The Gastrointestinal Surgery Unit opted for endoscopic resection of the tumor. In order to rule out paraneoplastic pemphigus (PNP), blood samples were collected for indirect immunofluorescence (IIF) on rat bladder and normal human skin and immunoblot for anti-plakin and anti-desmocollin autoantibodies, which resulted negative (; –).
Before the surgical intervention, delayed due to the COVID-19 outbreak, PV was managed with two cycles of intravenous immunoglobulins (IVIg, 2 g/kg per cycle) 4 weeks apart. The prolonged treatment with systemic steroids before major surgical interventions is associated with a significant risk of surgical complications; thereby, systemic steroids were not administered. After two cycles of IVIg treatment, the PDAI score remained stable.
The patient underwent robot-assisted Ivor–Lewis esophagectomy with latero-lateral anastomosis and jejunostomy feeding tube (J-tube) placement. Tissue perfusion and esophagogastric anastomosis evaluation with the indocyanine green method were performed. After the surgery, the patient achieved early mobilization, with no signs of anastomotic leak at endoscopies and CT scan. The post-operative course was uneventful, except for an episode of atrial fibrillation, which was managed with two subsequent doses of verapamil according to the advice of the cardiologist. The patient was then discharged on post-operative day 11, with no dysphagia nor nausea reported. The histopathologic examination of the esophageal mass confirmed the diagnosis of gastric cardia adenocarcinoma.
Despite the successful surgical management of the tumor, PV continued to worsen, with blisters and erosions affecting the entire body, except for mucosal sites and feet ().
Considering the recommendation to avoid high-dose systemic steroids also after surgery, due to the risk of anastomotic leakage, the patient was managed with 4 weekly infusions of rituximab at a dose of 500 mg (lymphoma protocol). A moderate-dose systemic steroid therapy (prednisone 0.6 mg/kg/day) was started only 2 weeks later in concomitance with the end of the national lockdown.
The skin of the patient started improving progressively, with complete resolution of the lesions. The anti-DSG1 and anti-DSG3 titers likewise decreased progressively ().
At the 4-month dermatologic follow-up, only post-inflammatory hyperpigmentation or hypopigmentation was detectable, with no active lesions (), while the last enzyme-linked immunosorbent assay (ELISA) performed resulted in lower anti-desmoglein autoantibody concentrations. No surgery-related criticalities or tumor recurrences were highlighted during this period.


A 75-year-old woman, past smoker (10 pack years), with a known history of hypertension and hyperlipidemia, no asbestos exposure, who was diagnosed in June 2017 with biphasic MPM in the right hemithorax. A fluorodeoxyglucose (FDG)-positron emission tomography–computed tomography (PET/CT) showed high FDG uptake in the parietal, visceral, and mediastinal pleura, as well as focal involvement of the right chest wall, T3N0M0, stage IB. The patient was determined to be inoperable by a multidisciplinary team and was referred for definitive radiotherapy. The patient was treated to 60 Gray (Gy) between August and September 2017. During RT, the patient developed grade 2 nausea and vomiting, grade 3 thrombocytopenia due to suspected immune thrombocytopenia (ITP), and improved after completion of RT and maintenance prednisone. Following RT, the patient developed persistent grade 3 pneumonitis. Disease remained stable until a PET/CT in March 2018 demonstrated high FDG uptake in suspected liver metastases. A biopsy was positive for metastatic MPM. The patient received systemic treatment and died in November 2018. The pleural disease remained stable until August 2018.


A 62-year-old man, past smoker (35 pack years), known history of diabetes type II and hyperlipidemia, who worked in asbestos production, was diagnosed in May 2017 with epitheloid type MPM in the left hemithorax. A PET/CT showed high FDG uptake in the parietal, viscera, and mediastinal pleura, as well as in mediastinal and internal mammary nodes, T2N2M0, stage IIIB. The patient refused surgery and was treated with definitive RT to dose of 54 Gy between September and October 2017. The patient did not experience any adverse events. A PET/CT in December 2017 demonstrated a partial response. The patient progressed clinically, as well as in a PET/CT, in August 2018 and began treatment with carboplatin-pemetrexed in November 2018. At the time of preparation of this manuscript, the patient is alive and continues palliative systemic treatment.


A 65-year-old man, non-smoker, known history of type II diabetes, hypertension, hyperlipidemia and ischemic heart disease, no history of asbestos exposure, diagnosed in May 2017 with epitheloid type MPM of the right hemithorax. A PET/CT showed high FDG uptake in pleural masses, as well as in mediastinal, supra and infraclavicular nodes T2N2M0, stage IIIB. The patient enrolled in a clinical trial investigating the addition of a tyrosine kinase inhibitor to standard chemotherapy in May 2017. Disease progressed in December 2017. The patient was then referred for RT and treated to 54 Gy between January and February 2018 and remained without progression until July 2018—with the appearance of distant nodal involvement and peritoneal spread. The thoracic disease remained stable until late September 2018—when one of the pleural masses increased in size. At the time of preparation of this manuscript, the patient is alive and continues palliative systemic treatment.
A comparison of dosimetry between IMRT step and shoot and 4 ARC VMAT is presented in . In addition shows a representation of the planning.
One can see a comparison of the effects of CPAP on the planning of the radiotherapy in these patients as is shown in .
These anatomic changes provided with CPAP inflation lead to improved dose distributions as seen in .


Patient 023: Patient 023 has been examined in the eye clinic since he was 50 years old. Initial BCVA was OD (right eye) 20/20 and OS (left eye) 20/25 without indication of amblyopia. The patient suffered from metamorphopsia and increased photophobia. Color vision impairment was negated, family history was unremarkable. Fundus examination showed bilateral yellowish alterations of the retinal pigment epithelium (RPE) and circumscribed areas of paracentral retinal atrophy. While spared in the left eye, atrophy partly covered the fovea in the right eye. STGD could not be confirmed by standard genetic diagnostics at the time. Furthermore, there was no genetic evidence for the differential diagnoses central areolar choroidal dystrophy (CACD) and pattern dystrophy. In the course of the disease, the patient reported gradual bilateral visual deterioration, reduced contrast perception and a paracentral visual field impairment in the left eye. BCVA was reduced to 20/40 OU (both eyes), perimetry showed deep central and paracentral scotomas. Retinal imaging revealed progressive complete RPE and outer retinal atrophy (cRORA) and, consequently, regression of the former spared “foveal islands” of cones in the left eye. Multifocal electroretinogram (mERG) detected reduced amplitudes in the central area in both eyes (described in ). Color vision testing results were unspecific. In spite of the rather mild clinical appearance, STGD was still suspected.


Patient 024: Patient 024 has been presented at the eye clinic since he was 53 years old. Initial best corrected visual acuity (BCVA) was OD 20/20 and OS 20/25 without indication of amblyopia. The patient suffered from bilateral paracentral visual field impairment since he was 50 years old. Color vision impairment and increased photophobia were negated, the family history was unremarkable. Fundus examination showed bilateral bright spots and yellowish lipofuscin deposits. Due to their pattern in the corresponding infrared image and hyperautofluorescence, pattern dystrophy was suspected at first and genetic testing was renounced. The differential diagnosis was STGD. Over time, the patient developed progressive bilateral symptoms including metamorphopsia and visual field impairment. BCVA was moderately reduced (OD 20/25, OS 20/32), perimetry showed partly deep paracentral scotomas. Retinal imaging (OCT, fundus autofluorescence) revealed progression by detecting new, partly confluent lesions and spots of cRORA (). Interestingly, foveal sparing could be observed. Though clinical appearance was comparably mild, STGD was suspected in the course of the disease.


A 38-year-old woman with pre-existing hypertension on her 18th postpartum day was admitted to the emergency department (ED) after sudden onset of severe (8/10) headache for two days, followed by moderate weakness of the right limbs several hours before the ambulance was called. She was also unable to understand orders and to speak properly, although at the same time she could repeat words and sentences. She has no history of fever or trauma, although the details of her obstetrical history were of great concern. This was her third pregnancy; the two earlier pregnancies had ended in first trimester miscarriages, with the last one ended in a preterm cesarean delivery at 30 weeks gestation for early severe preeclampsia 18 days before she was admitted to our hospital.
In the general clinical examination, the patient was shown to be obese (BMI = 30), with moderate hypertension and tachycardia (BP = 150/100 mmHg, HR = 94 bpm) but without fever.
In the ophthalmological exam, she had visual acuity of 20/20 without transient visual impairment, normal visual fields, and with normal anterior segment examination results in both eyes. The fundus of both eyes presented papilledema.
In the neurological examination, the patient was conscious (Glasgow Coma Scale Score of 15) but agitated, without nausea or vomiting; both pupils were normal in size and reactive and she showed no signs of sixth nerve palsy, meningeal irritation, or seizures. Our patient showed moderate (MRC = 4/5) right hemiparesis and right central facial paresis associated with a peculiar type of aphasia.
Language was evaluated using the Romanian version of the Western Aphasia Battery (WAB) [,].
The basic language characteristics were as follows. Initially, at the level of conversational language, the patient presented a transitory mutism, followed in the next few hours by non-fluent reduced verbal output and echolalia. Practically, the spontaneous language was absent and speech production was limited to repetition, which was relatively sparse, even for the words without meaning. The repetition was achieved with so much ease that it was best described as echolalia (the immediate, involuntary, and rather accurate repetition of any words spoken by the examiner). When asked a question, she repeated the question verbatim instead of providing an answer. Articulation was good and automatic language was relatively preserved. Pointing and naming were both defective (severe anomia). We observed that auditory and reading language comprehension was severely affected, showing difficulty with passive and complex grammar associated with severely impaired reading (alexia) and agraphia (written expression was severely affected).
Consequently, we noted that she had a severe dual deficit in language comprehension and intentional language formulation, combined with a normal capacity for oral repetition of even long sentences, devoid of any proper comprehension of sentence meaning. We concluded that she presented mixed transcortical aphasia (isolation aphasia).
The hyperdense appearance of the straight sinus, Galen vein, and lateral mesencephalic vein on the left revealed of the CT scan performed in ED was considered as a possible sign of cerebral venous thrombosis (A,B), as well as venous infarction in the left thalamus, left basal ganglia, left external and internal capsules, and corona radiata, with hemorrhagic transformation in the head and corpus of the left caudate nucleus (A,B).
A further CT venography scan was scheduled for a time when the patient was no longer agitated. After admission, the deficit became worse (MRC = 3/5), with stiff neck, anisocoria (right pupil > left pupil), and inability to speak or comprehend others when they spoke, although with preserved repetition (echolalia).
MRI of the brain revealed a left hydrocephalus and the presence of brain edema with compression of the ventricles to the right, as well as a slight hemorrhagic transformation located in the left basal nuclei and thalamus (A,B).
Magnetic resonance venography (MRV) of the brain showed almost complete occlusion of the superior sagittal sinus, the straight sinus, the vein of Galen, and in the deep venous system on the left, and only partial occlusion of the lateral sinus and internal jugular vein on the left (A–D).
Because of the patient’s medical history (onset on the 18th day after a cesarean section for preeclampsia with severe features), clinical spectrum, and the MRI-MRV images, the genetic profiling of thrombophilia was requested and performed, showing severe inherited thrombophilia (with combined thrombophilia represented by the association between homozygous MTHFR C667T, heterozygous Factor V-H1299R, and heterozygous PAI-1 4G/5G).
In addition, serologic measures of thrombophilia were used, including measurement of the anticardiolipin antibodies immunoglobulin G (IgG) and IgM, antigenic protein C, total and free protein S, antithrombin III, lupus anticoagulant, and homocysteine (which were all negative).
The lipid profile showed total cholesterol = 233 mg/dL, LDL = 170 mg/dL, HDL = 37 mg/dL, triglyceride = 102 mg/dL.
In conclusion, the patient presented focal neurological deficits (consisting of a mixed transcortical aphasia and right hemiparesis) and intracranial hypertension (headache and papilledema), both clinical syndromes due to the postpartum period and to severe inherited thrombophilia affecting multiple cerebral venous and dural sinus thrombosis.
The patient was treated with low-molecular-weight heparin (LMWH) in therapeutic dosages (180 anti-factor Xa U/kg/24 h) administered by two daily subcutaneous injections; the appropriate LMWH anticoagulation doses were adjusted based on the blood plasma antifactor Xa level.
She was also treated with osmotic diuretics (mannitol) and hypertonic NaCl 3% sol. for increased intracranial pressure and cerebral edema, along with hydroelectrolytic rebalancing solutions, antihypertensive drugs, painkillers, and prolactin inhibitors.
The patient recovered well and was discharged after 15 days with mild weakness of the upper limb (+4/5MRC) on the right side and anomic plus aphasia (the patient presented the hallmark feature of anomia, i.e., word-finding difficulty, which was noted in spontaneous speech and naming and was associated with circumlocutions and mild impairment of oral comprehension). Circumlocutions consisted of the use of generic terms (e.g., “thing” instead of an intended noun or “boy” instead of a specific boy’s name) and production of fillers such as “like” or “you know”.
In order to prevent recurrent CVT and other types of venous thrombosis (deep vein thrombosis or pulmonary embolism), in the patient’s case of severe inherited thrombophilia, we recommended that oral anticoagulation (with apixaban) should be continued after the acute phase of CVT for an indefinite duration.
Clinical and neuroimaging follow-up was performed at 6 months after discharge; the patient presented mild right central facial paresis and no symptoms of aphasia, with partial recanalization of dural sinuses (A,B) and hemosiderin deposition in the chronic hemorrhagic area in the head and corpus of the left caudate nucleus and in the left thalamus ().


A 36-year-old female with CCA and pectus excavatum underwent two pediatric Ravitch procedures and as a 30-year-old she underwent a modified Ravitch procedure with excision of bilateral second rib cartilages. She initially had improvement in shortness of breath, but presented six years later with worsening dyspnea, exertional chest pain, and significant structural deformity. Preoperative evaluation included pulmonary function testing (PFTs), chest computed tomography (CT), transthoracic echocardiography (TTE), and scoliosis radiographs. PFTs revealed moderate restrictive lung impairment while chest CT was significant for a Haller index greater than 6, external cardiac compression, and leftward cardiac displacement within the thoracic cavity (Figure ). TTE demonstrated left ventricle (LV) ejection fraction (EF) of 50-55% with external compression of the right atrium and basal right ventricle (RV) noted and trace tricuspid regurgitation, and scoliosis radiographs were significant for 40° thoracolumbar dextroscoliosis (Figure ). She underwent neurosurgical evaluation of her scoliosis, and no curvature progression was noted. As a result, she was deemed to not require surgical correction of her scoliosis.
Given her symptoms and imaging findings, she was scheduled for reoperation. The surgery was thoroughly planned with detailed evaluations and imaging used to determine incision selection, areas for reconstruction, and cartilage excision. The thoracic surgeons determined that an open reconstruction of the chest wall using a Nuss Strut would be most appropriate. Preoperatively, bilateral erector spinae plane catheters were placed. Due to concern for potential cardiopulmonary compromise from cardiac compression or mediastinal shift, defibrillator pads were placed on the patient prior to induction of anesthesia. General anesthesia was gradually induced using a combination of midazolam, lidocaine, ketamine, and propofol with preservation of spontaneous ventilation until it was observed that the patient had preserved hemodynamic and respiratory stability. Paralysis was subsequently achieved with succinylcholine to facilitate intubation, followed by rocuronium for continued paralysis. Because the surgical team performed the procedure via an open approach, two-lung ventilation throughout the procedure was considered to be acceptable, so endotracheal intubation was performed utilizing a single-lumen endotracheal tube. Following endotracheal intubation, a volume-controlled mode of ventilation was selected in an effort to minimize airway pressures while simultaneously achieving adequate tidal volume. Peak inspiratory pressures were consistently <20 cmH2O throughout the procedure while continually achieving tidal volumes of approximately 7-8 mL/kg ideal body weight. An 8-French double-lumen central venous catheter and an arterial line were placed in addition to transesophageal echocardiography (TEE) to guide intraoperative management. Baseline intraoperative TEE noted LV EF of 60-65%, redemonstration of external compression of the right atrium and basal right ventricle, no tricuspid regurgitation while the pulmonic valve was not well-visualized. She underwent an open reconstruction of the chest wall using a Nuss Strut, partial vertical splitting of the lower sternum, resection of left lower cartilages, and reconstruction with Gore-Tex mesh. The patient remained hemodynamically stable throughout the duration of the procedure, with an episode of mild hypotension upon insertion of the Nuss bar which responded to fluid administration. Both intraoperative TEE and postoperative TTE noted interval increase in right atrial and ventricular cavity sizes with normal RV function (Figure ). Left ventricular function improved slightly from 50-55% to 68%. Despite the notable changes observed on the TEE, no significant changes involving the patient’s pulmonary status were seen, as peak inspiratory pressures remained consistently <20 cmH2O both pre- and post- procedure.
The goal of extubation in the operating room following the case was set preoperatively. Therefore, a heavy emphasis was placed on multi-modal analgesia in an effort to minimize opioid-induced respiratory depression, placing this patient at risk for requiring reintubation. In addition to the preoperatively placed erector spinae plane blocks, intraoperative multimodal analgesia was provided by utilizing a combination of acetaminophen, diazepam, dexmedetomidine, ketamine, hydromorphone, and fentanyl. The patient was successfully extubated in the operating room at the end of the case and taken to recovery in stable condition. Postoperative pain control was achieved by continuing the patient’s pregabalin, bilateral erector spinae plane catheters running lidocaine infusions which were continued for five days, a ketamine infusion, and hydromorphone patient-controlled analgesia (PCA) that was subsequently converted to oral hydromorphone and scheduled acetaminophen. Postoperative chest radiograph revealed postoperative changes for treatment of pectus excavatum with fluid and airspace opacity of the left lung base compared to preoperative evaluation (Figure ).
The patient’s postoperative course was initially complicated by pain and discomfort lasting nearly six weeks after surgery, however, this improved significantly with the aforementioned management and time. Two months postoperatively, the patient was able to appreciate the marked improvement in her exertional chest pain and dyspnea. Approximately three months after surgery, the patient presented to the emergency department with complaints of a painful, pruritic rash overlying the insertion site of the metal bar. This was concerning for an allergic reaction to the metal implant, an event that has been reported to occur in approximately 2.7% of patients following a Nuss procedure []. Skin biopsy was significant for spongiotic dermatitis, confirming the diagnosis of an allergic reaction to the metal bar. At this time, the surgical team is working with the biomedical engineering department at our institution to potentially develop a bar developed from non-metallic material if the patient’s allergy becomes unforgiving.


A 28-year-old pregnant woman received her first dose of BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech, Mainz, Germany) at 25 weeks of gestation. The second was administered at 30 weeks. No problem was reported during the antenatal period, and no severe adverse events were reported after the vaccination. The patient only complained headache and tiredness the day after the second dose, which resolved with the administration of paracetamol twice a day. The delivery was planned to be on the 4th of July but occurred 8 days earlier, on the 26th of June at the Centre Hospitalier Régional (CHR) of Huy (Liège, Belgium), 90 days after the administration of the first vaccine dose. No delivery complications were reported, and all of the parameters of the newborn were normal. At 4 weeks, the newborn was still doing well. On the day of delivery, umbilical cord blood was collected as well as maternal blood to permit comparison of the level of SARS-CoV-2 neutralizing antibodies.
To compare the results obtained with the umbilical cord and maternal blood samples, 13 non-pregnant women of a similar age (i.e., 25 to 35 years of age) with no history of previous SARS-CoV-2 infection (i.e., no documented positive RT-PCR and the absence of anti-nucleocapsid antibodies), were included. These vaccinated controls were recruited at the Clinique Saint-Luc Bouge (Namur, Belgium) due to their participation in the CRO-VAX HCP study, a study which has already been described in detail elsewhere [,,]. All of the participants provided informed consent prior to specimen and data collection. The study was approved by a central ethical committee (EudraCT registration number: 2020-006149-21).
Blood samples were collected in SST™ II advanced tubes (BD Vacutainer, Plymouth, UK) and were processed according to the manufacturer recommendations to obtain serum. Serum samples were then aliquoted and were stored at −20 °C until analysis. Antibodies against the SARS-CoV-2 nucleocapsid (anti-NCP; Elecsys Anti-SARS-CoV-2 NCP total qualitative ECLIA, Roche Diagnostics, Machelen, Belgium) and the receptor binding domain of the S1 subunit of the spike protein (anti-S; Elecsys anti-SARS-CoV-2 spike total quantitative ECLIA, Roche Diagnostics) were measured at each time point. Results above 0.8 U/mL (manufacturer’s cut-off) or 0.165 COI (cut-off index as found previously []) for anti-S and anti-NCP antibodies, respectively, were considered positives.
Neutralizing capacity was estimated by performing a surrogate virus neutralization test (sVNT) []. The iFlash-2019-nCoV NAbs assay (performed on an iFlash1800 analyzer from Shenzhen YHLO Biotech Co., Ltd. (Shenzhen, China)) is a one-step competitive paramagnetic particle chemiluminescent immunoassay (CLIA) for the quantitative determination of 2019-nCoV NAbs in human serum and plasma. The assay detects NAbs that block the binding of RBD and ACE2. First, NAbs (if present) react with the RBD antigen coated on paramagnetic microparticles to form a complex. Second, the acridinium-ester-labeled ACE2 conjugate is added to competitively bind to the RBD-coated particles that were not neutralized by the NAbs (if present) from the sample, and these form another reaction mixture. Under a magnetic field, magnetic particles are adsorbed to the wall of the reaction tube, and unbound materials are washed away by the wash buffer. The resulting chemiluminescent reaction is measured in relative light units (RLUs), with an inverse relationship between the amount of NAbs and the RLU value being detected. A result <10.0 arbitrary unit (AU)/mL is considered negative, and a result >10.0 AU/mL is considered positive (according to the manufacturer’s information). The neutralizing capacity was also confirmed using a pseudovirus neutralization test, as previously described []. Samples are considered to be neutralizing if the dilution factor provides a 50% diminution of the relative infectivity that is superior to 1:20. The agreement of the sVNT assay with the pVNT was found to be 97.2% [].


The female patient was diagnosed as uterus didelphys at 28 years old when she was doing the transvaginal ultra-sound because of long-term abnormal uterine bleeding as 10–15 days/30 days. The gynecological physical and imaging examination confirmed the diagnosis as “double uterus, double cervix, double vagina”. She was operated hysteroscopy with endometrial polyp removal and segmental curettage in October 2018 for the first time. During the operation, it was found that there was a single polyp in the right cavity and multiple polyps in the left cavity. Postoperative paraffin pathology and immunohistochemistry showed that there was endometrial complex atypical hyperplasia and focal carcinoma (moderately differentiated endometrioid carcinoma) in the left cavity. IHC: ER 90% strong positive, PR 90% strong positive, p53+, Pax8+++, PTEN-, p16-, Ki67 10–30%. No lesion was found in the right uterine endometrium. The patient of childbearing age required conservative treatment which was taking oral megestrol acetate after surgery. In March 2019, hysteroscopy and curettage were reexamined. The postoperative pathology reported that there was mucinous metaplasia of endometrial glands in the left uterine cavity which can be explained because of the medication.
After the operation, the patient continued to take megestrol acetate. In June 2019, the hysteroscopy and segmental curettage were reexamined. Postoperative pathology showed that the endometrium of left uterus was moderately differentiated endometrioid carcinoma. With strong needs for child-bearing, our patient continuously chose to take megestrol acetate and reviewed hysteroscopy and curettage again in October 2019. Postoperative pathology result of left uterine endometrium was still in accordance with endometrioid carcinoma (moderately differentiated). Doctors recommended surgical treatment due to the unsatisfied outcome of conservative drug treatment. However, the patient refused and continued to take megestrol acetate for outpatient follow-up. Things changed in April 2020 when the pelvic enhanced MRI of our patient showed abnormal enhancement of left endometrium which was more obvious than before. In May 2020, she finally underwent the abdominal surgery with the left uterus and left fallopian tube resection. There were two spindle shaped uterus and accessories in bilateral iliac fossa. During the surgery, we opened the left ureteral tunnel, pushed down the bladder to 3 cm below the external orifice of the cervix and blocked the left uterine artery above it. The left utero-sacral ligament was cut and sewed 2 cm beside the uterus. The vaginal septum was cut open. We removed the left uterus along the space between the two cervixes. The left uterine endometrium was thick and crisp according to the postoperatively dissected specimen. The pathological findings were consistent with moderately differentiated endometrioid carcinoma with changes after treatment in the left uterus. The molecular and gene detection of the specimen showed that it may belong to the molecular type of MMR deficiency type which belongs to sporadic endometrial carcinoma and does not belong to Lynch syndrome.
The patient recovered well after operation. Combined with postoperative pathology, the patient was diagnosed as stage IA of moderately differentiated endometrial carcinoma in the left uterus. No abnormalities were found in the postoperative reexamination during which she has been trying to get pregnant in fertility center.


A 59-year-old female was presented to the dermatology clinic at King Khaled University Hospital, Riyadh, with a one-year history of few slightly pruritic skin eruptions over arms and thighs. She is known to have diabetes mellitus controlled on metformin for the last nine years, hypertension controlled on nifedipine and irbesartan for the last seven years, and allergic rhinitis on mometasone furoate nasal inhaler and on-off desloratadine. She started to take desloratadine in February 2020 and she only takes it when her rhinitis symptoms flare up. The patient noticed that whenever she takes desloratadine she starts to develop these lesions at the same locations and they clear up in few days leaving post-inflammatory hyperpigmentation. On examination, she has five, well-defined, round, variable in size, erythematous to violaceous patches and plaques over the left thigh and both arms as shown in Figure . Mucous membranes were free.
A skin biopsy was obtained from the lesion at the right arm. Histologic examination revealed a normal basket weave stratum corneum, interface dermatitis, scattered necrotic keratinocyte, perivascular lymphocytes, dermal eosinophils, and melanophages consistent with the diagnosis of FDE, as shown in Figure .
The patient was referred to an allergy clinic for patch testing of the involved site which was provoked by the application of desloratadine. The patient was given topical mometasone furoate 0.1% ointment and advised to stop desloratadine. Two months later, her skin examination showed only post-inflammatory hyperpigmentation as shown in Figure , for which she was given hydroquinone 4% cream.


A 77-year-old male nursing home resident presented with hypercalcemia. He had various medical conditions including type 2 diabetes, hypertension, peripheral artery disease, a history of above-the-knee amputation, coronary artery disease, and a renal mass suspicious for renal cell carcinoma (RCC) that was discovered during a prior hospitalization.
The patient was noted to have suffered a progressive decline in mental status in the nursing home for the past two weeks. The initial serum calcium levels were 13 mg/dL. Intravenous fluids were initiated at the nursing home. Repeat laboratory testing over one week showed worsening hypercalcemia, with serum calcium levels of 16.8 mg/dL, and the patient was sent to the emergency room for further evaluation.
In the emergency room, he was found to be mildly tachycardic (heart rate of 101 beats per minute), and his other vital signs were within the normal range. Physical examination revealed dry mucous membranes and decreased responsiveness to painful stimuli. Laboratory findings revealed elevated serum calcium levels of 18 mg/dL (corrected for albumin: 18.7 mg/dL) and acute kidney injury with serum creatinine levels of 2.4 mg/dL (baseline creatinine: 0.8 mg/dL) three months prior to the presentation.
The patient’s medications included losartan-hydrochlorothiazide, insulin glargine, carvedilol, and aspirin. A review of his nursing home records revealed a prescription of 2,000 IU cholecalciferol daily three months prior for 25-hydroxyvitamin D [25(OH)D] deficiency (17.0 ng/mL) which was discontinued after the initial increase in serum calcium levels. His calcium levels had last been measured three months prior to admission to the emergency room and were normal (9 mg/dL).
Further investigations revealed normal PTH levels of 36.5 pg/mL (reference range: 10-65 pg/mL), low PTHrP levels of 10 pg/mL (reference range: 14-27 pg/mL), elevated 25(OH)D levels of 200 ng/mL (reference range: 30-50 ng/mL), and elevated 1,25(OH)2D levels of 86 pg/mL (reference range: 18 -72 pg/mL).
Thyroid function test, angiotensin-converting enzyme levels, and serum and urine protein electrophoresis showed normal results. A whole-body bone scan was unremarkable, but a CT scan of the abdomen and pelvis revealed a hyperattenuating lesion of 3.1 × 3.0 cm deforming the contour of the right kidney, with a similar finding on MRI (Figures , ). The patient was treated with intravenous hydration, calcitonin, and pamidronate, and his calcium levels decreased to 12 mg/dL by day three. Prednisone was initiated due to an incomplete response to pamidronate and elevated levels of 25(OH)D and 1,25-(OH)2D resulting in a further reduction of serum calcium levels to 10.4 mg/dL (Figure and Table ).
However, the patient’s clinical condition remained poor, and his family decided not to pursue any further investigations, including a kidney biopsy. The patient was discharged to hospice care, where he died 20 days later.


A 64-year-old woman with hypertension, diabetes mellitus, hyperlipidemia, and history of cholecystectomy presented to the hospital for the evaluation of 4-day history of diffuse abdominal pain. Her home medications were lisinopril, metformin, and liraglutide. She denied alcohol use, illicit drug use, and use of over-the-counter supplements and herbal preparations. On examination, she had epigastric tenderness. She did not exhibit features of liver failure. Her laboratory tests were remarkable for alanine aminotransferase (ALT): 1359 U/L; aspartate aminotransferase (AST): 565 U/L; alkaline phosphatase (ALP): 405 U/L; total bilirubin (TB): 2.9 mg/dL; and INR: 0.9. R factor was consistent with hepatocellular injury. Hepatitis A IgM, hepatitis B surface antigen, hepatitis B surface antibodies, hepatitis B core antibodies and hepatitis C RNA, CMV viral load, and EBV viral load were negative. Immunoglobulin G, antinuclear antibodies, anti-smooth muscle antibodies, antimitochondrial antibodies, anti-liver-kidney microsomal antibodies, ferritin, iron saturation, alpha-1 antitrypsin, ceruloplasmin, and 24-hour urinary copper were normal. Abdominal ultrasound demonstrated fatty changes of the liver, without evidence of biliary obstruction. Her liver tests were normal 6 months prior to presentation, when the patient was started on liraglutide. Due to concern for DILI, liraglutide was discontinued and N-acetylcysteine was administered. On the third day of hospitalization, the patient's symptoms resolved, and her liver tests demonstrated gradual improvement. On the day of discharge, her liver tests were ALT: 335 U/L; AST: 58 U/L; ALP: 286 U/L; and TB: 1.3 mg/dL. 2 months after discharge, her liver tests normalized.


A 15-year-old female presented with a 8 cm x 7 cm, ovoid-shaped, hairy GCMN on the left side of her face on a medical mission trip in Mexico. The palm-sized solitary lesion was present since birth and enlarged as she grew (Figure ). An interview confirmed no personal or family medical history of melanoma or any form of cancer. The patient denied pain, pruritis, functional problems, or limitations in facial expression due to the lesion. Excision of the GCMN was performed due to the esthetic impact and lack of resources to continue monitoring the lesion.
GCMN excisional surgery aims to remove the pigmented area as much as possible without sacrificing other functional structures in non-malignant cases. Nests of melanin deposits were embedded in the subcutaneous fat deep to the nevus (Figure ). These were left in place to preserve the facial nerve branches, as the patient had no previous diagnosis of melanoma, and injuring her facial nerve would worsen outcome. Typically, the lesion would be biopsied to determine malignant patterns. In this global health setting, pathologic evaluation was not available; therefore, we provided the lesion in a specimen cup to the patient to have it evaluated separately.
Primary closure was not feasible due to the defect’s size and depth. We chose a pedicled submental flap to achieve the best esthetic outcome. The submental flap is indicated in defects of the oral cavity and the lower two-thirds of the face []. The flap was elevated distal to proximal in the submental plane across the midline until the contralateral anterior belly of the digastric muscle was encountered. The skin paddle was tailored to cover the defect adequately. An incision posterior to the mandibular angle was made, and a swatch of tissue was taken with the flap so the donor site would close primarily. The dissection was elevated beneath the platysma and carried to the defect. The submental cutaneous flap was rotated upward on the submental artery’s axis. The submental artery can be dissected backward to its origin at the facial artery to achieve flap advancement of another 1-2 cm to cover defects extending past the zygomatic arch; however, this was not necessary in this case (Figure ).
Follow-up after short-term mission trips is typically available only for a short period, leading to uncertain long-term outcomes if the patient cannot follow up with a local provider. Luckily, this patient was re-encountered on a subsequent mission six months later, as partial tip necrosis of the flap occurred (Figure ), leading to healing with a widened scar (Figure ). The flap edge was recontoured (Figure ).


A 59-year-old caucasian woman with a past medical history of chronic obstructive pulmonary disease, morbid obesity presented to the emergency department complaining of fevers, dry cough, and loss of taste and smell for about ten days prior to presentation. The woman tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) approximately nine days before admission.
Upon admission, vital signs included temperature 35.8° C (96.4° F), heart rate 116 beats per minute, respiratory rate of 22 breaths per minute, non-invasive blood pressure 138/67 mm Hg, and SpO2 67% on room air. An arterial blood gas analysis showed pH 7.4, PaCO2 36.9 mm Hg, PaO2 53 mm Hg; pertinent laboratory data upon admission included white blood cells 15,200 cells per microL, blood urea nitrogen 18 gm/dL, creatinine 1.32 gm/dL, aspartate transaminase 48 U/L. Inflammatory markers were: D-dimer 1.58 mg/L, ferritin 465 nanogram/mL, C-reactive protein 34.4 mg/dL, lactate dehydrogenase 619 U/L. Portable chest radiography at the time of admission showed bibasilar airspace disease. Pulmonary embolus protocol- computerized tomographic angiography showed severe, widespread bilateral ground glass (alveolar) airspace disease consistent with COVID19 pneumonia; no pulmonary embolism was noted.
The patient was initially placed on Bimodal Positive Airway Pressure (BiPAP) for hypoxia and was admitted to our step-down unit. She was treated with the then prevailing regimen of anti-viral remdesivir, high-titer anti-SARS-CoV-2 convalescent plasma, dexamethasone, and empiric therapeutic anticoagulation (shared decision making with the patient). Despite therapy and supportive care, she deteriorated and needed to be transferred to the ICU 12 days after admission.
On day #13 of this admission, the patient was endotracheally intubated and the ETT secured with a commercially available fastener {Hollister AnchorFast oral endotracheal tube fastener (Part # 9799), Libertyville, IL}. During the ICU course, she required vasopressors intermittently and daily prone sessions for severe ARDS. As she could not be weaned off from the ventilator, percutaneous tracheostomy (Cook Medical, Blue Rhino percutaneous tracheostomy, Bloomington, IN) was performed on day 21 of intubation.
After the tracheostomy had been inserted and was affixed in place, the Hollister AnchorFast oral endotracheal tube holder was gently removed, revealing - under the skin barrier pads - bilateral stage 2 pressure ulcers on her face; these had not been present prior to placement of the affixation device when the patient was endotracheally intubated (Figures , ).
While the pressure ulcers were managed with frequent (two times a day) cleaning with saline and the application of mupirocin our patient’s medical condition continued to deteriorate and, on day #31 post-intubation, her family (surrogate decision-maker) chose to withdraw life-sustaining treatment.


A 46-year-old male presented with recurrent abdominal pain and vomiting for six months with recent exacerbation of symptoms. Clinical examination was unremarkable and blood investigations revealed microcytic hypochromic anaemia with normal tumour markers.
Contrast enhanced CT scan of the abdomen revealed a large, ill-defined heterogeneously enhancing, hypodense mass within 2nd part of the duodenum which appeared resectable (, ). Upper Gastrointestinal (UGI) endoscopy revealed a large, ulcerated lesion at D1 - D2 junction projecting further into the duodenum. The ampullary area was not identified separately from the lesion (). The endoscopic biopsy of the lesion showed tubulo-villous adenoma. The patient was optimized and taken as an elective case for an open surgical procedure.
Intra-operatively, a large mass (8 × 4x3 cm with a very wide stalk) arising from the mesenteric border of the junction of the first and second part of the duodenum was found, which was causing luminal obstruction. Ampullary area could not be identified separately so a small catheter was introduced from cystic duct to ampulla (after cholecystectomy) () and an ampulla preserving duodenal resection with gastrojejunostomy and feeding jejunostomy was done. Frozen section showed tubulovillous adenoma. The patient had an uneventful post-operative course and was discharged on day 5 of surgery. The final biopsy showed tubular adenoma. 6 years follow up showed no long-term complications including recurrence.


A 26-year-old male presented with pain abdomen and vomitings for 4–5 months. Ultrasound abdomen suggested agenesis of left kidney with transient duodenal intussusception. CT scan showed a circumferential pyloroduodenal thickening, intussuscepting into duodenum with? neoplastic mass as a lead point. UGI Endoscopy showed a polypoidal growth at D1-D2 junction causing luminal narrowing and scope negotiated beyond with mild resistance. Endosonography (EUS) showed 38 × 32 mm lesion at D1-D2 junction, arising from 3rd layer of the duodenal wall. Biopsy and EUS guided trans-duodenal FNAC were inflammatory only.
Intra-operatively, posterior wall of second part of the duodenum had a 6x5x1.5 cm sized polypoidal friable mass. Ampulla was not separately visualised, so the ampullary area was spared after passage of a small catheter via cystic duct to ampulla. Wedge resection of the duodenum with retro colic gastrojejunostomy and feeding jejunostomy were done. Post-operative period was uneventful, and he was discharged on 6th post-operative day. Biopsy was suggestive of adenomatous polyp with low grade dysplasia.
The patient had no complications or recurrence in the one-year follow-up till the article was submitted for publication.


A 53-year-old woman came to our observation for persistent cough and dyspnea, increasing over the last 12 months. On physical examination, swelling and venous distention in the left side of the neck were noted, together with dilated vein collaterals in the upper left hemithorax. Chest x-ray detected a mass in the upper anterior mediastinum, causing narrowing and right-side deviation of the trachea. Blood tests were normal, including thyroid function tests. The patient medical history was unremarkable. Contrast-enhanced CT-scan of the neck and thorax showed a mass in contiguity with the left thyroid lobe and extending in the upper mediastinum, consistent with an intrathoracic ectopic goiter (A, B). An ultrasound-guided needle biopsy of the mass was performed through the neck, but histological examination found red blood cells. The echographic appearance of the mass was also consistent with a goiter.
Surgical resection was indicated. Prior to surgery, arteriography was performed which showed a predominant blood supply from the neck and no significant feeding arteries coming from the mediastinum (A, B). Therefore, a cervical approach was preferred instead of a thoracic approach. UM and AS performed the procedure. A low transverse collar incision was performed. The mass appeared to be encapsulated, adherent to the surrounding structures but without signs of tissue infiltration. The thyroid gland was normal and the lesion appeared to be separated from the left thyroid lobe. The superior pole of the mass was clearly visible but the rest of the lesion extended deeply into the upper mediastinum. After ligation of the feeding vessels in the neck, gentle blunt dissection by finger and pledget was accomplished within the capsule, to achieve an adequate mobilization of the mass. Finally, the mass was delivered from the mediastinum and completely removed through the cervical incision. No significant bleeding occurred from the mediastinum. The left recurrent nerve was identified and preserved throughout the procedure. Frozen section examination found a mesenchymal tumor. The thyroid gland was not removed.
The post-operative course was uneventful and the patient was discharged on the fourth postoperative day. Histological examination showed a paraganglioma with a low mitotic index <5% (). The resection was complete. The patient is alive without recurrence 30 months after surgery.


A 70-year-old female patient without a history of smoking presented with a subcutaneous tumor in the left thigh. Positron emission tomography (PET)-computed tomography (CT) scans revealed a 4.0 × 4.2-cm mass in the upper left lung lobe and multiple muscular and bone metastatic lesions (Figure ). She was diagnosed with stage IVB cancer (T2bN0M1c). Her performance status was 1 and serum carcinoembryonic antigen (CEA) level was 18.6 (normal range, 0–5.0) ng/ml.
Pathological examination of the resected subcutaneous tumor in the left thigh revealed moderately differentiated SCC with cornification (Figure ). Immunohistochemical analysis revealed diffuse and strongly positive staining for pan-cytokeratin, cytokeratin 5/6, and p40, although the cells were negative for thyroid transcription factor-1, CK7, napsin A, and CD56 (Figure ). The tumor expressed wild-type epidermal growth factor receptor (EGFR) based on the molecular analysis of exons 18–21 and was diffusely and strongly positive (3+) for ALK by intercalated antibody-enhanced immunohistochemistry with an ALK detection kit (Nichirei Bioscience; Figure ). Based on fluorescence in situ hybridization (FISH) using break-apart probes for ALK (Figure ), the patient was diagnosed with SCC harboring EML4-ALK rearrangement and treated with alectinib (300 mg twice daily). Two months later, PET-CT images revealed dramatic shrinkage in the size of primary tumor in the left upper lung lobe and reduction in the size of multiple muscular, bone, and skin metastases (Figure ); therefore, the patient was considered to have achieved partial response to alectinib according to the Response Evaluation Criteria in Solid Tumors guidelines (version 1.1). Although she experienced recurrence after a durable response of 9.5 months, there were no severe alectinib-related adverse events.


A 78-year-old man with end-stage renal disease presented to the ED with altered mental status. His daughter reported that he had two nights of hallucinations that progressed to whole-body shaking that morning. The patient’s baseline was alert and oriented to person, place, and time. He missed hemodialysis on the date of admission, but there were no other recent changes to his health.
The patient presented with a heart rate of 75 beats per minute, blood pressure of 131/95 millimeters of mercury, respiratory rate of 18 breaths per minute, oral temperature of 36.4 degrees centigrade, and an oxygen saturation of 99% on room air. A right-sided facial droop was noted. No other significant findings were recorded from the physical or neurological exams. His speech was unaffected, and he had no other focal neurological findings.
A CT of the head without intravenous (IV) contrast was performed 30 minutes after arrival in the ED. The exam was normal, with no intracranial hemorrhage, midline shift, herniation, or hydrocephalus. There was mild to moderate atrophy and white matter attenuation, as well as intracranial vascular calcifications and trace fluid in the left mastoid air cells. The paranasal sinuses were clear, with a normal appearance of the surrounding bone and soft tissue.
After consultation with neurology, a portable MRI brain scan was ordered without IV contrast and performed 6 hours after arrival. The scan revealed scattered subcortical and deep T2/fluid-attenuated inversion recovery (FLAIR) hyperintense foci, along with prominent sulci and ventricles (Figure ). Periventricular white matter changes were also evident on representative FLAIR and T2-weighted slices (Figures , ). The bony structures were intact, and the paranasal sinuses and mastoid air cells were clear. There was no significant change between the scan and a previous MRI from two years earlier. The diffusion-weighted imaging sequence was repeated twice, due to involuntary motion of the patient. After consultation with the radiologist, the patient was sedated and a 3T MRI brain without IV contrast was done 13.5 hours following arrival for higher imaging resolution.
The 3T scan was negative for acute infarction, midline shift, herniation, and hydrocephalus. T2/FLAIR hyperintensities in the central pons and white matter were noted, along with prominent ventricles (Figure ). Multiple foci (predominantly lobar punctate microhemorrhages) were evident in the right cerebral hemisphere and left basal ganglia. The major vascular flow voids were present, along with a trace amount of fluid in the left mastoid air cells. The paranasal sinuses were clear, and the surrounding osseous and soft tissues were unremarkable. There was no evidence of intracranial abnormalities or significant changes compared to the low-strength MRI exam.
After the CT and MRI results were negative for structural causes, the patient was admitted to a neurology stepdown unit the same night for encephalopathy.


A 63-year-old female presented initially with a history of seven days diarrhea, three days of shortness of breath, and pleurisy. Her past medical history was significant of remote stage 1 breast carcinoma status post-mastectomy, COPD, and ex-smoker. Physical examination was significant only for decreased air entry bilaterally with coarse crackles. Chest x-ray (CXR) and computed tomography angiogram (CT-A) of the chest confirmed bilateral ground-glass opacities of mid to lower lung fields without evidence of pulmonary embolism (PE) (Figure ). SARS-COV-2 PCR test was positive. On presentation, her oxygen saturation (SpO2) was 88% on room air but improved on nasal cannula. D-dimer was normal at 483 ng/mL (ref range ≤500 ng/mL), troponin was 0.01, and procalcitonin was negative. She was started on dexamethasone 6 mg PO daily for 10 days, remdesivir 100 mg/250 mL intravenous infusion daily for five days, enoxaparin 40 mg subcutaneously daily for deep venous thrombosis (DVT) prophylaxis. On the 10th day of her symptoms, the D-dimer suddenly spiked to 2,080 ng/mL and her enoxaparin dose was increased to 40 mg subcutaneously every 12 hours. At that point, the patient finished five days of remdesivir, she was ambulating without shortness of breath, and her SpO2 was >90% on room air. She was discharged home on dexamethasone 6 mg PO daily for five more days and started rivaroxaban 10 mg PO daily for 30 days. A follow-up visit was scheduled in one week with her primary care physician.
In less than 24 hours of discharge, the patient presented to the emergency department complaining of severe right foot pain and cramping that started two hours prior. She also reported chest tightness and shortness of breath. The sharp/shooting pain was severe enough in nature that it would limit ambulation. Her SpO on room air was 84% but improved to 94% when placed on OptiFlow with a flow rate of 50 liters and FiO of 70%. Otherwise vitally stable and examination was unremarkable. Her blood work is illustrated in Table .
Meanwhile, the patient’s CXR was similar to previous studies without acute changes. Bilateral lower extremity duplex doppler ultrasound showed diminished velocity in the right popliteal artery and right posterior tibial artery suggesting diminished inflow. The anterior tibial artery was patent. Immediately the patient had a CT angiography of the abdominal aorta with bilateral iliofemoral runoff that showed a large free-floating thrombus in the ascending aorta with few scattered eccentric thrombi in the descending and infrarenal abdominal aorta. In addition, there was a large thrombus in the distal abdominal aorta that extended into the origin of the right common iliac artery resulting in short segment severe stenosis. The remainder of the iliofemoral and popliteal segments were patent without hemodynamically significant stenosis. There was also an abrupt cut-off in the posterior tibial and peroneal arteries in the mid-calf on delayed phase images suggesting distal embolization (Figures , ).
The general surgery, vascular surgery, and cardiothoracic teams recommended systemic anticoagulation without surgical intervention. The patient was started on high molecular weight heparin infusion at 14 units/kg/hr. and was closely monitored in the intensive care unit. After monitoring for 24 hours in the intensive care unit with serial neurological and vascular examination with Doppler ultrasound, the patient was downgraded to the telemetry unit. After three days, the patient remained clinically stable, and her oxygen requirement lowered gradually to room air. Repeat CT angiography of the abdominal aorta with bilateral iliofemoral runoff showed stable foci of thrombus compared to the previous study. The patient was continued on heparin infusion and was being transitioned to warfarin orally daily with an international normalized ratio (INR) goal of 2.5-3.5. After nine days, the patient was medically and surgically stable. Her INR was at goal (2.61) and discharged on warfarin 2.5 mg tablets orally daily with outpatient follow-up for INR monitoring.
The patient was being followed up as an outpatient and she remained clinically stable. After five months, repeat CT angiography of the chest, abdomen, and pelvis showed complete resolution of the ascending and descending thoracic and abdominal intraluminal aortic thrombi. No aortic aneurysm or dissection.


A 36-year-old male presented to the emergency department with one week of progressively worsening dyspnea at rest, fatigue, and non-productive cough. He has a past medical history significant for diffuse large B-cell lymphoma (DLBCL) of the stomach and pancreas treated with R-CHOP chemotherapy regimen in 2014, and currently in remission. Review of systems was negative for chest pain, syncope, palpitations, orthopnea, paroxysmal nocturnal dyspnea, lower extremity edema, flu-like symptoms, fever, sick contacts, recent travel, recent trauma or stressors, recent alcohol use, and positive only for recent cannabis use. Vitals were significant for tachycardia at 110 and diastolic hypertension at 138/107 mmHg. Physical examination revealed no murmurs, rubs, or gallops but was remarkable for diffuse crackles bilaterally on auscultation and jugular venous distension. Chest x-ray revealed cardiomegaly with interstitial pulmonary edema (Figure ) and EKG was significant for sinus tachycardia with signs of left ventricular hypertrophy (Figure ). Laboratory studies were significant for elevated D-dimer (2.48 ng/mL), elevated troponin (0.09 ng/mL), and significantly elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) (12,600 pg/mL). Computed tomography (CT) angiogram was performed, with no evidence of filling defects suggestive of pulmonary emboli. He was started on intravenous (IV) furosemide with rapid symptomatic relief and admitted to the medical floor for diagnostic workup of acute decompensated heart failure of unspecified etiology.
Transthoracic echocardiogram (TTE) was performed and revealed global left ventricular (LV) wall hypokinesis with LV ejection fraction (EF) of 10-15% as well as an LV thrombus (Figures -). For assessment of an ischemic etiology, cardiac catheterization was performed with coronary angiography which revealed non-ischemic cardiomyopathy (NICMP), non-obstructive coronary artery disease, and normal pulmonary pressures. Viral pathogen panels, including HIV, influenza A and B, and SARS-CoV-2, were negative for an infectious etiology. IgG titers for Trypanosoma cruzi were not detected. Thyroid-stimulating hormone (TSH) levels for evaluation of thyroid-induced cardiomyopathy were within normal limits (2.78 mIU/mL). Urinalysis was unremarkable and urine toxicology screen was positive only for cannabinoids which were confirmed by our patient. CT scan of the abdomen and pelvis was unremarkable and negative for recurrence of malignancy. Further review of our patient’s medical records confirmed his completion of seven cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treatment of DLBCL in 2014, and that his TTE prior to chemotherapy was within normal limits (EF 55-60%), without a repeat TTE until this time.
As a diagnosis of exclusion, our patient was diagnosed with acute decompensated heart failure secondary to a delayed doxorubicin-induced, non-ischemic cardiomyopathy. He was initiated on a heparin drip for treatment of his LV thrombus and guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) including sacubitril-valsartan and spironolactone with the addition of metoprolol succinate and dapagliflozin scheduled for discharge. On day four of hospitalization, our patient was euvolemic with significant symptomatic improvement. He was discharged home with his regimen of GDMT for HFrEF, oral furosemide, apixaban for anticoagulation, a LifeVest wearable cardioverter-defibrillator for sudden cardiac death prevention and was scheduled for outpatient cardiology follow-up.


A 50-year-old man with a history of heavy smoking visited another hospital due to gross hematuria and weight loss of about 10 kg for 3 months in January 2019. CT showed bilateral hydronephrosis and irregular thickening of the bladder wall (Fig. ). MRI showed a large irregular mass with significant extravesical invasion around the right wall, bladder trigone, and invasion of the prostate and right seminal vesicle (Fig. ). Laboratory data showed acute renal failure (creatinine, 7.01 mg/dL; eGFR, 7.51 mL/min/1.73 m2). Clinical stage T4aN0M0 bladder cancer and acute postrenal failure due to the mass were diagnosed. TURBT for diagnosis and left percutaneous nephrostomy were performed. Histopathology findings showed invasive UC, high-grade, T2. Therefore, the patient was referred to our hospital for cystectomy. Renal failure did not improve sufficiently despite nephrostomy, so we performed robotic radical cystectomy and ileal conduit without neoadjuvant chemotherapy in February 2019. Histological examination showed high-grade NVUC, T4a (Fig. ), and lymph nodes metastases (pathological stage N2). The nested variant represented more than 90% of the tumor. Since renal failure gradually improved after cystectomy (creatinine, 1.39 mg/dL; eGFR, 44.03 mL/min/1.73 m2), he received adjuvant chemotherapy with gemcitabine (1000 mg/m2) and carboplatin (area under the concentration–time curve, 4) for 3 cycles. However, para-aortic lymph node metastasis appeared 7 months after cystectomy on CT and FDG PET/CT (Fig. ). He received pembrolizumab (200 mg) as systemic chemotherapy. After 5 cycles of pembrolizumab therapy, the metastatic lesion had decreased in size (Fig. ). After 10 cycles, the lesion remained undetectable (Fig. ). We assessed complete response based on the RECIST version 1.1. During pembrolizumab therapy, he developed herpes zoster on the face (Common Terminology Criteria for Adverse Events version 4.0, grade 2). He received 18 cycles of pembrolizumab therapy and continues the treatment. No recurrences or metastases have been observed (Fig. ).


A 63-year-old Caucasian male with a background of arterial hypertension and mild obesity (BMI 30.5 kg/m2) was admitted to hospital with dyspnea under COVID-19. He initially tested positive for SARS-CoV-2 via a polymerase chain reaction swab conducted in the ambulatory setting. When he arrived at the primary care hospital, he displayed a reduced general condition. Admission observations revealed: blood pressure 100/40 mmHg, heart rate 115 beats/minute, peripheral oxygen saturation 71%, body temperature 40 °C. His breathing noises were reduced, and there were rattling noises over his lungs bilaterally. He was cooperative and orientated, and showed no focal neurological deficit. His renal function markers were elevated [creatinine 1.66 mg/dl, estimated glomerular filtration rate (eGFR) 45 ml/minute], and the liver function markers were in the normal range. He was admitted to intensive care unit (ICU) 5 days later owing to worsening of respiratory symptoms. After 1 day of noninvasive ventilation, the patient decompensated into global respiratory insufficiency, and endotracheal intubation was required. Because of persistent global respiratory insufficiency under exhausted conservative therapy, the patient was transferred to our university hospital for venovenous extracorporeal support (vvECMO) in severe acute respiratory distress syndrome (ARDS). Computed tomographic (CT) imaging before transferal showed diffuse bilateral ground-glass opacities. On admission at our hospital, his acute phase reactants were elevated: white blood cell count 20,400/µl (normal range 3600–10,000/µl), CRP 316.5 mg/l (normal range < 5 mg/l), IL-6 420 ng/l (normal range < 7 ng/l), soluble IL-2-receptor 1549 kU/l (normal range 223–710 kU/l), ferritin 916 µg/l (normal range 27–365 µg/l), and fibrinogen > 9 g/l (normal range 1.8–3.5 g/l). He showed lymphocytopenia with a cell count of 470/µl (2.3%). SARS-CoV-2-PCR diagnostic was repeated from tracheal aspirate on arrival at our hospital and remained positive (cycle threshold 25). His medical treatment taken at home included valsartan, bisoprolol, amlodipine, and chlorthalidone as well as atorvastatin and mirtazapine. The patient did not smoke or consume alcohol regularly. He is married and has been working as a specialist in internal medicine until his recent retirement.
He received therapeutic anticoagulation with unfractionated heparin (UFH). Monitoring of anticoagulation was done by measurement of activated partial thromboplastin time (aPTT) every 6 hours with a target of 50–60 seconds. Preexisting treatment with acetylsalicylic acid was continued. Sedation proved to be difficult even under a multimodal intravenous sedative regime. First signs of pulmonary hemorrhage were noticed on day 11. Because of a suspected hyperinflammatory syndrome [], dosage of dexamethasone was increased from 6 to 18 mg per day. For a detailed depiction of events, see timeline (Fig. and Additional file ).
Over the following days, the patient continuously produced extensive aqueous and slightly bloody discolored tracheal secretion. Chest x-ray on day 15 in supine position showed a progressive extensive opacity projecting to the right inferior lobe (Fig. ). This corresponded with a heavy decline in pulmonary gas exchange. A diagnostic bronchoscopy on the same day revealed hemorrhagic pneumonia with extremely vulnerable mucosa and plenty of viscous mucus as well as extensive coagulum in segment 9. After removal of the coagulum, gas exchange improved at first. Because pulmonary hemorrhage remained persistent and gas exchange declined yet again alarmingly, the patient underwent a second bronchoscopy on the following day. Here, another extensive coagulum in right lung segment nine was cautiously and, due to high risk of bleeding, incompletely recovered. Dependence of extracorporeal support remained very high, and the patient became increasingly unstable. On day 17, the patient developed profound hemorrhagic shock (Table ) without evident source of bleeding. The patient required extensive doses of norepinephrine, epinephrine, and vasopressin as well as a massive transfusion of red blood cells, plasma, and platelets for stabilization. At the same time, a severe acute decrease of pulmonary compliance was noticed.


A 63-year-old white female with a past medical history of hypertension and previous appendectomy presented after 2 months of progressive headaches, with magnetic resonance imaging (MRI) demonstrating a sellar and suprasellar mass that grew rapidly in 1 month’s time (Figs. and ). The patient originally reported holocephalic headaches, with blurry vision and diplopia (more apparent with left lateral gaze). She described the headaches as moderate to severe in intensity, and characterized the pain as varying between sharp and throbbing. In addition, she reported significant fatigue as well as polydipsia and polyuria (awakening five to six times per night to urinate and drink water). The patient was a retired banker and lived at home with her husband and therefore had no social or environmental exposures and had no family history of autoimmune or neurological diseases. She denied any changes in ring/shoe size, muscle weakness, weight gain/loss, abnormal hair growth, chest pain, shortness of breath, difficulty swallowing, language changes, focal weakness, numbness, tingling, or other neurologic or systemic symptoms. At the time of presentation, the patient was taking hydrochlorothiazide–triamterene and ramipril but was not on any immune-modulating medications. She was a former smoker and consumed three to four glasses of wine per week.
On presentation, the patient was afebrile with a normal pulse (69 beats per minute) and normal blood pressure (124/70 mmHg). On physical examination, she was alert, cooperative, and oriented to person, location, and date. She had a visual acuity of 20/25 in the right eye and 20/20 in the left with a partial left-sided cranial nerve VI palsy. She was otherwise neurologically intact. Her neck was supple and nontender, oral mucosa moist, lungs clear to auscultation, heart rate normal and with a regular rhythm, and her skin warm and dry.
Initial outpatient laboratory studies showed an elevated antinuclear antibody (ANA) of 1:160 (normal: negative) and normal inflammatory testing [erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP)]. Laboratory studies showed an 7 am serum cortisol 28.1 μg/dL (slightly elevated), concurrent plasma adrenocorticotropic hormone (ACTH) 29 pg/mL (normal), free triiodothyronine (T3) 2.0 pg/m (normal 2.3–4.2 pg/m), follicle-stimulating hormone (FSH) 12.3 mIU/mL, luteinizing hormone (LH) 0.4 IU/L (low), Insulin-like growth factor 1 (IGF-I) 154 ng/mL, prolactin of 33.3 ng/mL (normal less than 20.3 ng/mL for a menopausal woman), and IgG4 levels of 57.1 mg/dL (7–89 mg/dL normal). Lumbar puncture was obtained, which showed no organisms, white blood cell count (WBC) of 95 cells/cu mm, red blood cell count (RBC) of 4 cells/cu mm, 54% neutrophils, 42% lymphocytes, 55 mg/dL glucose, 154 mg/dL protein, and IgG 26.7 mg/dL. Repeat laboratory studies 1 month later showed a 7 am cortisol level of 2 ug/dL and free thyroxine (T4) level of 2.9 ug/dL (normal range is 5–12). ACTH, growth hormone (GH), LH, FSH, thyroid-stimulating hormone (TSH), and prolactin levels were within normal limits. Her serum sodium was within normal limits (value), pointing to compensated diabetes insipidus. A water deprivation test was deferred at this time.
An MRI of the brain with and without gadolinium was obtained at initial presentation and showed a 1.5 × 1.2 × 1.4 cm enhancing lesion involving the sella and adjacent structures, including the infundibulum, hypothalamus, and sphenoid sinus (Fig. A, B). T2 FLAIR also showed edema extending symmetrically along the bilateral hypothalami and fornices (Fig. C). At that time, the patient was managed conservatively with observation. Repeat MRI 1 month later after her symptoms continued to progress showed progression of the lesion, now measuring 3.2 × 2.2 × 2.0 cm with more extension into the bilateral hypothalami and fornices and sphenoid sinus as well as new extension into the clivus with anterior displacement of the optic chiasm (Fig. A, B). T2 FLAIR demonstrated more extensive edema into the hypothalami and fornices (Fig. C). Notably, there was also diffusion restricting content filling the sphenoid sinus with peripheral enhancement concerning for infection. CT of the chest, abdomen, and pelvis with contrast showed no evidence of malignancy. Due to the progression of disease, the patient was transferred to our institution for further workup.
An endoscopic endonasal biopsy was performed 6 weeks after initial presentation. Endoscopically, it was noted that the fluid filling the sphenoid sinus was inspissated. A biopsy of the sphenoid sinus mucosa was evaluated intraoperatively by frozen section, which demonstrated acute and chronic inflammation, necrosis, and possible poorly formed granulomas. This finding raised the possibility of an autoimmune process such as granulomatous vasculitis or a chronic infection. A biopsy of the sellar lesion, which was performed through an infrasellar approach, was also evaluated intraoperatively; cytologic preparations showed predominantly chronic inflammation with occasional multinucleated giant cells. Permanent sections demonstrated an intense chronic inflammatory infiltrate composed predominantly of plasma cells, histiocytes, and lymphocytes (Fig. A–B). Numerous eosinophils were present, but there were few, if any, neutrophils. Immunohistochemical stains demonstrated abundant IgG-positive plasma cells, more than 40% of which stained positively for IgG4, and a smaller mixed T- and B-cell lymphoid population (Fig. C–F). The endoscopically sampled tissue fragments did not show histologic evidence of classic storiform fibrosis or obliterative phlebitis. Additional studies were performed to exclude infectious and neoplastic processes. Together, the findings were consistent with a diagnosis of IgG4-related hypophysitis. Notably, the cultures from the inspissated contents of the sphenoid sinus grew normal sinus flora but predominantly Cutibacterium acnes, a microbe that is not normally part of local flora. Notably, the sellar floor was partially dehiscent, and the sellar inflammatory tissue was biopsied very focally just in that area to avoid spread of any infection intracranially. Final pathology did not reveal any organisms, so it is thought that the sinusitis was not due to an infection, but the patient did complete Augmentin 875 mg twice daily for 7 days while we awaited the pathology report.
The patient was treated with levothyroxine (88 μg oral tablet daily) for central hypothyroidism, high-dose prednisone (tapered over 1 year), and rituximab (1 g intravenously every 6 months, planned for 2 years) postoperatively. Repeat MRI 5 days after biopsy showed significant improvement in the sellar and suprasellar enhancing lesion (Fig. A, B). At the time of discharge 6 days later, her cranial nerve (CN) VI palsy persisted, but her headache and blurry vision had resolved. The patient was followed for 3 months while continuing her prednisone and rituximab, and on her outpatient clinic appointment, the CN VI palsy had resolved. At that time, the imaging showed complete resolution of the abnormal enhancement in and around the hypophysis with a return to normal size of the pituitary gland, and stalk had returned to normal size (Fig. A, B). She continues to have central hypothyroidism and diabetes insipidus for which she remains on levothyroxine (88 μg oral tablet daily) and desmopressin (0.05 mg in the morning and 0.1 mg in the evening by mouth). At 1 year follow-up, the patient remained asymptomatic and had no evidence of pituitary inflammation on her MRI at that time.


A 72-year-old woman presented to our medical center with an altered mental status having suffered a fall. She had a history of primary hypothyroidism for many years treated with a stable dose of levothyroxine 0.075 mg/d. She was clinically euthyroid without tremors, palpitations, tachycardia, or other findings suggesting thyrotoxicosis. A pathologic fracture of her right humerus eight years before had led to a diagnosis of multiple myeloma with an IgG kappa M spike paraprotein. She received chemotherapy and went into remission. However, a recent reexacerbation had occurred, and she was being considered for further therapy. Routine admission labs revealed hematocrit 20.9% (normal 38–47%), sodium 132 mmol/L (136–145), potassium 4.0 mmol/L (3.5–5.1), chloride 104 mmol/L (98–107), urea nitrogen 45 mmol/L (20–31), and creatinine 2.8 mg/dL (0.6–1.0). Oncologic studies were consistent with multiple myeloma with an M spike kappa IgG paraprotein: total protein 10.1 g/dL (5.7–8.2), albumin 1.8 g/dL (3.4–5.0), and serum albumin: globulin ratio: 0.22 (0.60–1.50). Serum protein electrophoresis revealed gamma globulin 5.8 g/dL (0.8–1.7), kappa chain 9270 mg/L (3.3–19.4), Lambda chain 9.3 mg/dL (5.7–26.3), K/L ratio 996.7 (0.26–1.65), and B2—macroglobulin: 17.9 mg/L (<or = 2.51).
Thyroid biochemistry () on presentation performed with the Siemens Atellica chemiluminescent immunoassay kit reported a slightly high TSH of 6.27 uIU/mL (normal 0.55–4.78) with normal total T4 of 4.5 μg/dL (3.2–12.6) and free T4 1.22 ng/dL (0.89–1.76). However, total T3 was markedly elevated at >600 ng/dL (60–181). Tests for anti-ThyroPerOxidase (AntiTPO), anti-ThyroGlobulin (antiTG), Thyroid-Stimulating Immunoglobulin (TSI), and Human Anti-Mouse Antibodies (HAMA) were within normal limits at <1 IU/mL (<9), <1 IU/mL (<1), <89% (<140), and <56 ng/mL (<74), respectively. Assay for anti-T3 antibodies was negative using a proprietary chemiluminescent competitive immunoassay procedure performed by Quest/Nichols Laboratories. Repeat testing on the Siemens Atellica platform again reported an elevated TT3 >600 ng/dL. Reverse T3 (Thermo Aria platform) was normal at 21 ng/dL (8–25), while results for TSH, total T4, and free T4 were similar to those reported previously. Free T3 was low at 1.7 (2.3–4.2 pg/ml (Siemens Advia kit) consistent with Euthyroid Sick Syndrome. 14 months earlier, her thyroid biochemistry was reported to be normal using the Roche Cobas chemiluminescent immunoassay kit with total T3 82 ng/dL (80–200). Thyroid Hormone-Binding Protein (THBP) electrophoresis was normal: TBG 14.3 mcg T4/dL (10.3–24.9), albumin 16.6 mcg T4/dL (11.5–34.1), and transthyretin (prealbumin) 69 mg T4/dL (48.8–70.4). Follow-up testing on the Roche Cobas platform again reported normal total T3 47.4 ng/dL (). Polyethylene glycol (PEG) precipitation was planned, but the patient expired before it could be accomplished.
We conclude that the factitious elevation in TT3 was most likely due to assay interference from the documented multiple myeloma paraprotein as well as differences between the test platforms used.


A 5-year-old boy was referred to our department with proteinuria, delayed motor milestones, hypotonia, congenital cataract, and failure to thrive. His past medical history indicated he was born at full term after a normal pregnancy, received surgery for congenital cataracts at the age of 3 months, and experienced several limb fractures. He was the first child of a nonconsanguineous marriage, and detailed pedigree analysis indicated no family history of congenital disorders. At birth, his weight was 3200 g (-1SD-Median) and length was 51 cm (Median- + 1SD). The boy lifted his head at 8 months, sat up at 12 months, walked unassisted at 30 months, and talked at 3 years.
The physical examination at presentation indicated his body weight was 13.3 kg (< -3SD) and length of 96 cm (< -3SD). He presented with slight frontal bossing, deep-set eyes, chubby cheeks, low-set ears, sparse hair, funnel chest, simian line, joint hypermobility, decreased muscle tone, and hyporeflexia. The laboratory findings indicated occasionally positive urine glucose, hypercalciuria, phosphaturia, mild proteinuria, β2-microglobulinuria, metabolic acidosis, and occasional elevations of creatinine kinase and lactate dehydrogenase (Table ). The estimated glomerular filtration rate (eGFR), calculated using the Schwartz formula, was 162.6 mL/min/1.73 m2. Renal size and shape were normal based on an ultrasound examination. Magnetic resonance imaging (MRI) of the brain indicated mild ventriculomegaly, lacunar lesions in the bilateral white matter consistent with periventricular leukomalacia, and multiple gliotic lesions, which were hypointense on T1-weighted and hyperintense on T2-weighted analyses (Fig. ). An electroencephalography examination indicated no abnormalities. He was attending a school for children with special needs because his IQ was 55 and he had serious sensory integrative dysfunction.
Whole-exome sequencing, with validation by Sanger sequencing, indicated a de novo hemizygous pathogenetic c.659_662delAGGG mutation in exon 8 of the OCRL gene (NM_000276.3; Fig. a), confirming the diagnosis. This deletion caused a frame shift from protein position 220 (between the PH and 5-phosphatase domains) leading to an insertion of 28 aberrant amino acids and a premature termination codon, resulting in a truncated protein of 247 out of 901 amino acids (p.E220Vfs*29; Fig. b) with an altered three-dimensional structure (Fig. c).
To date, he is receiving treatment with an angiotensin converting enzyme inhibitor (ACEI) for proteinuria, hydrochlorothiazide for hypercalciuria, a citrate mixture for metabolic acidosis, and rehabilitation training.


The boy, 7 months old, was the first baby of a healthy nonconsanguineous couple. The pregnancy was uneventful, the baby had spontaneous vaginal delivery, and his birth weight was 3450 g (Median- + 1SD). The boy had bilateral cataracts since birth, and underwent surgery at the age of 3 months, but his visual acuity remained poor. At the age of 7 months, he could not roll over or crawl, and could not sit without support. He was admitted to our hospital with proteinuria. At admission, physical examination indicated his weight was 11 kg (+ 2SD- + 3SD), height was 76 cm (+ 2SD- + 3SD), and that he had sparse hair, chubby cheeks, bilateral nystagmus, visual impairment, hypotonia, and absence of deep tendon reflexes. The laboratory findings indicated hypercalciuria, mild proteinuria, β2-microglobulinuria, metabolic acidosis, elevation of lactate dehydrogenase, and hypovitaminosis D (Table ). The eGFR (Schwartz formula) was 137 mL/min/1.73 m2. An ultrasound examination indicated the size and shape of the kidneys were normal (left kidney: 6.5 × 2.5 cm, right kidney: 6.0 × 2.5 cm). MRI of the brain indicated severe ventriculomegaly, white matter shrinkage, leukoaraiosis, cerebellar hypoplasia, and a large cistern magna cyst (Fig. a). The electroencephalography results were normal. He could not complete the evaluation of psychomotor development because of poor vision. Histological examination of a renal biopsy sample indicated mild mesangial proliferation, mild infiltration of focal mononuclear cells, and interstitial focal fibrosis (Fig. b). Tubular lesions, including atrophy, necrosis, dilatation, and protein casts, were not detected.
To confirm the clinical diagnosis of Lowe syndrome, we analyzed the OCRL gene. Whole-exome sequencing, with Sanger sequencing validation, indicated a hemizygous c.2257-2A > T DNA variant in OCRL intron 20 (NM_000276.3; Fig. a), a novel splicing variant. We then designed two pairs of primers for reverse transcription PCR of exon 8 and exon 12, but this yielded no transcriptional products. Therefore, we speculated that the mutated transcript was removed by nonsense mediated degradation (NMD) of the mRNA. We only detected the expression of OCRL-1 protein in renal tissues by immunohistochemistry using an anti-OCRL polyclonal antibody against the C-terminus of the human OCRL-1 protein (Proteintech Group, USA). This patient had a markedly reduced content of OCRL-1 in kidney tissue compared with a control patient with thin membrane basement disease (Fig. b). Thus, this splicing mutation in the OCRL gene led to almost no expression of the wild-type protein. The patient’s mother was heterozygous for the c.2257-2A > T mutation, but had no proximal tubulopathy, and refused an ophthalmologic examination.
We treated this patient with ACEI for proteinuria, a citrate mixture for metabolic acidosis, hydrochlorothiazide for hypercalciuria, intraocular lens implantation, and rehabilitation training to improve his motor and sensory integrative function.


A 22-year-old man presented with a history of recurrent hemoptysis of small volume for a duration of two years. He also experienced progressive dyspnea for three months. The patient had no other complaints, such as hoarseness, dysphagia, or any other symptoms. Following the development of stridor in April 2017, the patient underwent a tracheostomy in the emergency department at West China Hospital, with dyspnea relieved markedly. The physical examination didn’t reveal any special issues except for a scar on the neck. A review of the patient’s medical history revealed that 7 years prior, he had undergone left thyroid lobectomy without the neck dissection for a palpable 3-cm left thyroid mass in a local hospital. Moreover, the post-operative histopathology was unknown.
He was then hospitalized at the respiratory department after tracheostomy. Flexible fiberoptic bronchoscope revealed a smooth and sessile vascularized mass, located 0.5–1.5 cm below the glottis, causing lumen narrowing by approximately 80% (Fig. a). Pathological analysis of a biopsy from the mass described it as lobulated capillary hemangioma. Furthermore, enhanced CT scans confirmed a bulky and vascularized tumor located primarily in the cervical trachea, which may have originated from the left tracheoesophageal groove with intraluminal exophytic and extratracheal components (Fig. b). Upon reviewing CT scans before the thyroidectomy 7 years prior, images showed that the tumor was also hyper-vascularized, though limited to the thyroid region with ambiguous tracheoesophageal sulcus (Fig. c). Lab work, which included complete blood cell count, C-reactive protein, calcitonin and thyroid function (TSH, FT3 and FT4), were within normal limits, which help exclude from acute infection, medullary thyroid carcinoma (MTC) and thyroid dysfunction.
With the initial consideration of subglottic or cervical tracheal hemangioma based on the biopsy results, the patient was referred to the department of otolaryngology for sclerotherapy combined with CO2 laser using suspension laryngoscope under general anaesthesia. The transoral surgery was aborted due to the potential presence of an undefined solid mass and possible excessive bleeding. Then, intra-operative frozen biopsy was performed and subsequently indicated a vascularized tumor characterized by small vessels and atypical proliferative cells. Therefore, a lateral cervical approach was taken to remove the tumor. The tumor was located in the subglottis with involvement of the lower portion of the cricoid cartilage and bulged into the left perichondrium of the first three tracheal cartilages (Fig. a). The mass was complete en-bloc resected, including the left lateral part of the cricoid cartilage and the first six tracheal rings with negative margins on permanent pathology (Fig. b). Histologically, hematoxylin and eosin staining showed a characteristic “zellballen” pattern growth traversed by a delicate capillary network (Fig. c). Immunohistochemical studies determined the followings: The chief cells were positive for chromogranin A (abcam, ab52983, 1:250) (Fig. d) and synaptophysin (abcam, ab8049, 1:200) (Fig. e), and the sustentacular cells were stained positively for S-100 (abcam, ab136629, 1:200) (Fig. f). In addition, the tumor was negative for calcitonin, keratin, carcinoembryonic antigen (CEA), and thyroid transcription factor 1 (TTF-1). Finally, the tumor was diagnosed as paraganglioma. The defect, created by complete removal of tumors with six tracheal rings and partial cricoid cartilage resection, was challenging to reconstruct by end-to-end anastomosis. Simultaneously, a pedicled thoracoacromial artery perforator flap (PTAPF) was harvested to reconstruct the left lateral wall of the trachea and cricoid cartilage. The anterior wall of the defect was left to second-stage reconstruction (Fig. g).
The patient was uneventful post-operatively and discharged with tracheostomy cannula. Six months post-operatively, the second-stage tracheal reconstruction was conducted with a local flap and the patient decannulated successfully. In addition, no evidence of local recurrence or distant metastasis was noted during the 3-year follow-up (Fig. h).


A 23-year-old woman with a past medical history of asthma, eczema, and hypothyroidism developed malaise, vomiting, a fever of 104°F (40°C), axillary lymphadenopathy and acute kidney injury 1 week after receiving the second dose of the Moderna inactivated SARS-CoV-2 vaccine. She denied joint pain, abdominal pain, headache, or dysuria. She worked as a nurse, had no recent travel history, no pets, and no other recent incident exposures.
CT scans showed left axillary lymphadenopathy, up to 2.1 cm, and multiple enlarged lymph nodes in the abdomen. An extensive infectious work-up was unrevealing (blood, urine and stool cultures, C. dificile, EBV serology, monospot, HIV, bartonella, tuberculosis, typus [rickettsial typhi] testing). Cytokine panel showed elevations in TNF alpha, interferon gamma, interleukin-5, interleukin-10, interleukin-13, and interleukin-6. The initial clinical impression was hemophagocytic lymphohistiocytosis (HLH)/macrophage activating syndrome versus adult Still's disease.
An excisional biopsy of the left axillary lymph node was performed. The H&E sections of the enlarged lymph nodes show hyperplastic follicles and marked paracortical expansion with polymorphic lymphohistiocytic infiltrate and hypervascularity and sinus histiocytosis. Higher magnification reveals the expansion to be caused by numerous small- to medium-sized lymphocytes intermingled with many histiocytes and rare larger atypical cells. There are focal aggregates of LCs, dendritic cells, and histiocytes with rare hemophagocytosis (Figure ).
By immunohistochemistry, the lymphoid cells are mixed T-cells and B-cells with normal compartment. Marked perifollicular/interfollicular T cells hyperplasia are noted with intact T-cell antigens (positive for CD2, CD3, CD5, CD7, and mixed CD4 and CD8). There are scattered CD30+/CD20+/CD45+ immunoblasts. No Reed-Sternberg cells or variants are identified. There is no aberrant expression of bcl-2 in the B-cells or expansion PD1+ T-cells. Focal paracortical LCs proliferation is highlighted by S100 and CD1a stains. EBV in situ hybridization is negative.
Flow cytometry revealed no overt immunophenotypical aberrancy. The CD4:CD8 ratio was slightly increased (4.0:1). There was a small population (0.60%) of large CD30+ hematolymphoid cells, which included both T- and B- lineage cells, and a definite aberrant population was not identified. Notably, normal reactive immunoblasts show expression of CD30. T-cell clonality by T-cell receptor gene rearrangement was negative, and cytogenetics revealed a normal female karyotype (46,XX [20]). Overall, the findings are consistent with a florid reactive lymphoid proliferation.
A bone marrow biopsy was also performed and showed a normocellular marrow with active trilineage hematopoiesis. No atypical lymphoid infiltrate or hemophagocytosis was detected. No immunophenotypical abnormality was detected. After ruling out viral infections and hematolymphoid malignancy, a diagnosis of post-vaccination reactive lymphadenitis, with paracortical/interfollicular lymphoid, LC hyperplasia, and secondary hemophagocytosis was rendered. The patient recovered rapidly with dexamethasone and anakinra within 2 weeks.


A 37-year-old female with an 11 year history of inhalation of heroin vapers, tobacco use (unknown pack-year history), alcohol usage not consistent with alcohol abuse and history not significant for chemotherapeutic usage, presented with two weeks of progressively worsening weakness in all extremities, blurry vision, and slowed speech. The patient required the assistance of her mother to perform all activities of daily living including urination, defecation, sanitation, ambulation, and nourishment. Patient's initial neurological exam was remarkable for restlessness, decreased visual acuity, slowed movements on coordination testing, delayed response time, and slurred speech.
Two weeks after initial presentation, the patient demonstrated extensor posturing of the upper extremities, dysautonomia, inconsolable crying and rigidity. She was started on a course of antibiotics, dantrolene and high dose antioxidants including coenzyme Q10, vitamin C and vitamin E with minimal improvement. The patient was given 0.5 mg of clonazepam to help with her emotional lability likely secondary to frontal lobe involvement. Antipyretics such as acetaminophen were given in the setting of autonomic fevers. The patient became mute, areflexic, and started to experience central fevers and muscle cramps. She was briefly intubated for concerns for aspiration, but was eventually extubated. Patient also received a percutaneous endoscopic gastrostomy tube given poor overall neurological prognosis and poor deglutition.
Lumbar puncture studies, pancultures (blood, urine, sputum, CSF), heavy metal toxicity screening, computed tomography angiography and magnetic resonance imaging (MRI) of the spine were unremarkable. Cardiac enzymes including troponin and B-type natriuretic peptide were also unremarkable. MRI of the head demonstrated extensive, symmetric T2 hyperintense signaling in the white matter of the cerebellum, brainstem, cerebral hemispheres, and some aspects of the frontal lobes (). Electroencephalogram showed disorganization, diffuse slowing, and sharp waves with triphasic morphology without evidence of epileptiform activity. Transthoracic echocardiogram (TTE) demonstrated basal ventricular ballooning, indicating rTTC (). The patient eventually demonstrated minimal improvement in speech and was clinically stable without fevers, symptomatic tachycardia, hypertension or hypotension. She was discharged to a skilled nursing facility shortly after with close outpatient monitoring with neurology and cardiology.
During the hospital course the neurology and medicine team closely monitored the patient on the general medicine floors while the patient resumed antioxidant therapy. Since discharge she has demonstrated gradual improvement in motor function and now is able to talk more consistently. The patient still requires assistance with activities of daily living.


A 68-h-old girl presenting with lethargy and a poor nutritional state among other symptoms was transferred from a local hospital to our department. She was born at 37 + 3 weeks of gestation by cesarean section due to cephalopelvic disproportion from a gravida 1, parity 1 (G1P1) mother. She had a birth weight of 2,600 g, an Apgar score of 10, and did not present asphyxia. Her parents were healthy and non-consanguine. After birth, the child manifested with progressive lethargy, no crying, and poor sucking ability. She was admitted to a neonatal department in the local hospital at 40 h of life, where she showed low spirit, decreased spontaneous breathing, poor terminal circulation, and blood pressure of 39/22 mmHg. She was intubated and ventilated, and administered 0.9% sodium chloride and dopamine (12 μg·kg−1·min−1) intravenously, as well as cefoperazone. However, the patient's condition did not substantially improve, and she was therefore transferred to our department.
On admission, physical examination showed profound coma with intubation and ventilation, yellowish skin, no autonomic activity, no autonomic breathing, no response to orbital pressure stimulation, slow pupil response to light, soft limbs, and poor peripheral blood circulation. Blood gas analysis showed respiratory acidosis (pH = 7.197, PCO2 = 65.7 mmHg, PO2 = 93.4 mmHg, [HCO3] = 24.9 mM, [Be] = 4.1 mM, and O2 saturation of 97.4%). Electrolytes and lactic acid levels were normal, and blood glucose was slightly high (7.8 mM).


A 75-year-old elderly Caucasian female with end-stage renal disease (ESRD), who was on continuous ambulatory peritoneal dialysis (CAPD) for the past three years, was admitted to the hospital with the chief complaint of worsening diffuse abdominal pain, nausea, and low-grade fever of three days duration. The abdominal pain was diffuse; eight of 10 in intensity, dull aching in type. She was having pain with each peritoneal dialysis exchange at home. The patient denies any vomiting, diarrhea, constipation, chills, or rigors. Past medical history was significant for type 2 diabetes mellitus, essential hypertension, and hyperlipidemia. She had no history of prior peritonitis. Her home medications included glipizide 5 milligrams (mg) daily, lisinopril 40 mg daily, carvedilol 25 mg twice a day, aspirin 81 mg daily, atorvastatin 40 mg daily, calcitriol 0.5 μg daily, and daily renal vitamin. Her CAPD prescription was four exchanges during daytime with 2.5 % dextrose solution, with 2 L in each dialysate and for 4 hours each exchange. She was essentially anuric.
The vital signs on presentation were as follows: temperature of 99.5 degrees Fahrenheit (°F), pulse rate of 77 beats per minute, blood pressure of 130/70 mm Hg, and respiratory rate of 22 breaths per minute with oxygen saturation of 99% on room air. The physical examination revealed that the patient was in moderate painful distress. Abdominal examination revealed diffuse tenderness but no rigidity. There were no peritoneal signs or fluid thrill present. Bowel sounds were audible in all four quadrants. The Tenckhoff peritoneal dialysis catheter exit site in the left lower quadrant was clean with no tenderness or discharge visible. The rest of the systemic physical examination was insignificant.
The laboratory data showed white blood cell (WBC) count 9330/mm3, hemoglobin 9.1 g/dL, platelets 119,000/ mm3, sodium 127 mmol/L, potassium 3.9 mmol/L, blood urea nitrogen 44 mg/dL, and serum creatinine 6.61 mg/dL (Table ). The peritoneal dialysis (PD) fluid analysis revealed a WBC count of 595 cells/μL, with 76% predominant neutrophils. Peritoneal fluid Gram stain revealed >100 WBC, and no organisms were seen. Chest x-ray was unremarkable. Computed axial tomography of the abdomen didn’t reveal any other source of intra-abdominal pathology. The patient was started on empiric intra-peritoneal broad-spectrum antibiotics, namely vancomycin and ceftazidime in an outpatient setting for suspected peritonitis two days prior, because of moderate abdominal pain. She was also started on p.o fluconazole for fungal prophylaxis. The peritoneal dialysis (PD) fluid culture grew C. parapsilosis in the aerobic bottle after three days of incubation. Intraperitoneal vancomycin and ceftazidime were stopped after the culture results and the patient was continued on treatment with fluconazole 200 mg daily for a total of four weeks duration. The PD catheter was removed for unremitting abdominal pain and as per guidelines for removal of the catheter in cases with fungal peritonitis. The dialysis modality was changed to thrice weekly in-center hemodialysis. She was discharged by day five of admission with outpatient dialysis unit follow-up. By four weeks of antifungal treatment, her symptoms resolved with no further abdominal pain or discomfort. She was resumed on peritoneal dialysis after four months and thereafter she has been doing uninterrupted peritoneal dialysis at home with no recurrence of fungal infection.