A 28-year-old healthy woman, with a family history of breast and ovarian cancer, was referred to our laboratory for multigene testing. Our proband was informed about the significance of molecular testing, provided information about her personal and family history and signed an informed consent form prior to molecular genetic testing and permission for the anonymous use of her data for research purposes and/or scientific publications.
Genomic DNA was extracted from peripheral blood leukocytes using MagCore® Genomic DNA Whole Blood Kit (RBC Bioscience) according to the manufacturer’s instructions.
The analysis of genes involved in hereditary cancer predisposition was performed using a solution-based capture approach. Targeted NGS was performed with a panel of 33 genes (Roche NimbleGen SeqCap EZ Choice) [APC (NM_000038.5), ATM (NM_000051.3), BARD1 (NM_000465.2), BMPR1A (NM_004329.2), BRCA1 (NM_007294.2), BRCA2 (NM_000059.3), BRIP1 (NM_032043.2), CDH1 (NM_004360.4), CDK4 (NM_000075.3), CDKN2A (NM_000077.4), CHEK1 (NM_001114121.2), CHEK2 (NM_007194.3), EPCAM (NM_002354.2), MEN1 (NM_000244.3), MLH1 (NM_000249.3), MRE11 (NM_005591.3), MSH2 (NM_000251.2), MSH6 (NM_000179.2), MUTYH (NM_001128425.1), NBN (NM_002485.4), NF1 (NM_000267.3), PALB2 (NM_024675.3), PMS2 (NM_000535.5), PTEN (NM_000314.4), RAD50 (NM_005732.3), RAD51B (NM_133509.3), RAD51C (NM_058216.2), RAD51D (NM_002878.3), RET (NM_020975.4), SMAD4 (NM_005359.5), STK11 (NM_000455.4), TP53 (NM_000546.5), VHL (NM_000551.3)]. The sample preparation was performed according to the manufacturer’s instructions in the SeqCap EZ Choice Library User’s Guide (Roche NimbleGen). Sequencing was carried out using the Miseq Illumina NGS technology and sequence changes were identified and interpreted in the context of a single clinically relevant transcript using the commercially available software suite SeqNext (JSI medical systems GmbH, Germany).
The clinical significance of variants was further examined using standards and guidelines for the interpretation of sequence variants recommended by the ACMG Laboratory Quality Assurance Committee and the Association for Molecular Pathology (AMP) []. The impact of missense substitutions on protein function or structure was analyzed using computational (in silico) predictive algorithms combined with the ensemble mutational impact score of MetaSVM []. The effect on splicing was computationally examined using Human Splicing Finder [].
Total RNA was extracted from peripheral blood lymphocytes using Trizol (Invitrogen, Paisley, UK) following standard protocol. cDNA was synthesized using SuperScript™ VILO™ cDNA Synthesis Kit (Thermo Fisher Scientific) as described by the supplier. The resulting cDNA was amplified with the CHEK2 specific primers CHEK2X5F_RNA:5′-ACATCATGTCAAAAACTCTTGGAA-3′ and CHEK2X8-9R_RNA: 5′-CCCCTTCCATCAATTCCAAAACAA-3′ and the PCR-products were purified using NucleoFast® 96 PCR Clean-up kit (Macherey-Nagel GmbH and Co., Düren, Germany). The purified PCR product were used for each sequencing reaction, which was performed using the BigDye® Terminator v1.1 Cycle Sequencing kit (Applied Biosystems, Foster City, CA, USA) and Sequencing reaction products were purified prior to electrophoresis using the Montage™ SEQ96 Sequencing Reaction kit (EMD Millipore Corp., Billerica, MA, USA) and sequenced using an Applied Biosystems 3130 Genetic Analyzer (Applied Biosystems).


A 39 year-old unmarried gravida 0 para 0 woman presented to the gynecology office complaining of a self-detected right pelvic mass noted 3 years ago which increased significantly in size during the last year. She complained only of mild pressure discomfort. She had no complaints of constitutional symptoms. She had no medical or surgical history. Physical examination showed a non-tender abdomen and a mobile solid hard mass of nearly 20 cm in diameter. Pelvic ultrasonography and MRI reported a 19 x 14 x 12 cm right-sided subserosal leiomyoma of the uterus, and normal bilateral ovaries. There was no sign of ascites, free fluid, or plural effusion and no preoperative tumor markers were obtained. Her pre-operative hemoglobin was 13.2 g/dL and hematocrit was 37.8%. The patient was scheduled for laparoscopic myomectomy and indicated procedures. On the day of surgery, she had no additional complaints.


A 57-year-old woman underwent bilateral total knee arthroplasty for treatment of severe degenerative joint disease 10 years prior to her current presentation. She presented to our hospital with progressively worsening pain and swelling of both prosthetic knee joints for six weeks. She also reported a history of indolent fever, night sweats, and malaise started one week prior to joint symptoms. She was recently diagnosed with deep vein thrombosis of the left femoral vein for which she is on rivaroxaban. She reported consumption of possibly unpasteurized milk four weeks prior to her illness.
Examination revealed a lethargic, febrile woman with bilateral swollen, warm, and tender knee joints with moderate effusions. Rest of examination was normal. Initial investigations showed a hypochromic microcytic anaemia with a haemoglobin of 9.4 g/dl, a normal total white cell count (5600 cells/mm3), and elevated inflammatory biomarkers with an erythrocyte sedimentation rate (ESR) of 109 mm/h and C-reactive protein (CRP) of 101 mg/dL. Single-photon emission computed tomography/computed tomography (SPECT/CT) of both knees is shown in .
Diagnostic aspiration of both knee joints was performed. Analysis of the synovial fluid revealed 8200 white cells/μL with predominance of lymphomononuclear cells. Lateral flow alpha-defensin (Synovasure AD test) was performed intraoperatively on fluids from both knee joints and was negative twice. Meanwhile, a blood culture that was sent on admission grew Brucella melitensis after 6 days of incubation. Subsequently, culture of the synovial fluid (from both joints) grew Brucella melitensis on day 8 of incubation. A diagnosis of bacteraemic brucellosis with brucellar bilateral prosthetic knee joint infection was established, targeted antimicrobial therapy was commenced with combination of intravenous gentamicin 5 mg/kg once daily (for one week) in addition to oral doxycycline 100 mg twice daily and oral rifampicin 600 mg once daily (both given for 24 weeks), and a rescue revision arthroplasty was planned contingent on the outcome of antimicrobial therapy. In view of the chronicity of symptoms and associated bacteraemia, the patient underwent a transthoracic echo which showed no vegetations. Subsequent follow-up sterility blood cultures were negative. By end of first week of antimicrobial therapy, the patient was able to walk unassisted, and at 3 months, she had complete resolution of symptoms with normalization of inflammatory biomarkers; hence, a revision surgery was not performed. The patient remained symptom-free three years later with no evidence of disease recurrence or relapse.


A 43-year-old female presented in the emergency department of the hospital with SE. Her previous medical and family history for epilepsy was unremarkable. However, she had a six-month history of migraines for which she was treated for by a neurologist. On clinical examination, she had tonic contractions and clonic jerks, her pulse was 55 beats per minute, Glasgow coma scale (GCS) was 4/15, blood pressure was 80/50 (supine), and she had brittle nails, alopecia, and mouth ulcers.
The initial laboratory investigation revealed white blood cell (WBC) count of 4.7 x 103/mm3, a platelet count of 241 x 103/mm3 and a hemoglobin level of 8.6g/dl. The serum electrolytes, metabolic screening of urine and blood, lactic acid, pyruvic acid were normal. Renal function tests and liver function tests were found to be in the normal range as well. A lumbar puncture performed revealed no WBCs or protein and glucose was within the normal range. Serological studies revealed positive anti-nuclear antibody (ANA). Whereas, anti-double stranded DNA (anti-dsDNA), antiphospholipid antibodies, anti N-methyl-D-aspartate (NMDA) were negative. There was no evidence of viral, bacterial, fungal infection found in the results from the cerebrospinal fluid (CSF) and blood. Toxicological studies were also negative. Brain MRI and brain magnetic resonance angiography (MRA) did not reveal any underlying pathology. Also, an electroencephalogram was performed, which showed generalized epileptic activity.
Conventional antiepileptic drugs failed to control the seizures and therefore intravenous midazolam infusion was started, which controlled the seizures successfully. The patient was intubated in order to prevent respiratory failure as her GCS was 4/15. She was further managed with IV fluids and a nasogastric tube was attached to maintain parenteral nutrition. There was no improvement in the GCS for six days. Therefore, she was given a continuous infusion of midazolam to control her subclinical seizures and she was monitored through an electroencephalogram. Methylprednisolone IV 1 gm was infused as autoimmune encephalitis was not initially ruled out. GCS of the patient improved to 15/15 on sixth day. As subclinical seizures subsided, respiratory support was removed and midazolam was discontinued. She was then discharged on antiepileptic drugs and advised to continue anti-migraine medications.
Shortly after discharge, she had episodes of muscle twitching, so her antiepileptic drugs were adjusted accordingly. She also developed a malar rash for which a rheumatologist was consulted. He established the diagnosis of SLE on the basis of refractory cytopenia, positive ANA, arthritis, mouth ulcers, malar rash, seizures, and migraine. She was treated with IV methylprednisolone 1 gm for five days. Rituximab was administered in the dosage of 2 gm (1 gm each one week apart), which improved her condition drastically. She was followed with oral prednisolone 45 mg, which was tapered gradually. The patient's cytopenia, arthritis, rash and migraine improved after treatment. The patient is now overall stable and the lupus flares secondary to any sort of infections are successfully managed with corticosteroids.


A 69-year-old woman presented with a long history of bilateral hearing loss and a 2-year history of left-sided pulsatile tinnitus. The patient also suffered from the itching of the left ear canal and mild vertigo; however, she had no recollection of middle ear infections, ear discharge, or ear pain. Otomicroscopy revealed the presence of a pulsatile purple-colored middle ear mass in the anterior inferior quadrant of the tympanic membrane of the left ear. The right ear had no visible abnormalities.
Due to the mild asymmetry in the pure-tone audiometry and the pulsatile tinnitus in the left ear, including the pulsating purple-colored mass, the patient was subjected to magnetic resonance imaging (MRI).
The MRI revealed a right-sided extrameatal vestibular schwannoma of 8 mm and a left-sided almost purely extracranial GJ tumor of 18 mm (). After the diagnosis, the patient went into watchful waiting with annual follow-up MRI.
Two years after diagnosis, the patient experienced the deterioration of hearing and vertigo symptoms. The pure-tone audiometry () showed a bilateral though asymmetric hearing loss with a pure-tone average (PTA) of 63 and 43 dB HL on the right and left sides, respectively. Speech audiometry demonstrated a discrimination score of 76/88 (%). Caloric irrigation was performed and revealed a unilateral weakness of 81% towards the side of VS ().
The patient was scanned independently of the standard MRI protocol. The MRI showed stationary dimensions of the GJ tumor; however, the extrameatal size of VS had increased from 8 mm to 12 mm. The patient underwent suboccipital retrosigmoid surgery with intended hearing preservation and the total removal of the VS.


A 50-year-old male patient initially presented with a 1-month history of 3 bouts of mucoid bloody diarrhea per day, lower abdominal pain and crissum discomfort. The ileocolonoscopic findings in the local hospital indicated the colorectal inflammation and bleeding, which was consistent with ulcerative colitis. Then, he was introduced with mesalamine slow release granules (Etiasa) at 4,000 mg/day in our gastroenterology clinic. Unfortunately, he started to develop fever over 40 °C, worse abdominal pain and bloody diarrhea with 10–20 stools movements per day 2 h after mesalamine treatment. He has no history of medications intolerance before Etiasa was considered as the most possible cause and was immediately discontinued at the emergency department. The symptoms subsided after 24 h and disappeared after 72 h.
Subsequently, the patient was admitted to our department for further management. Laboratory examinations revealed increases in C-reactive protein level (CRP) 46.30 mg/L (< 8 mg/L) and erythrocyte sedimentation rate (ESR) 26 mm/h (< 15 mm/h). EB virus DNA (PCR) was positive at 764 copies/mL (< 400 copies/mL) in plasma. Other infectious values were negative, including cytomegalovirus, tuberculin skin tests, T-SPOT.TB test, stool and blood tests for bacterial and fungal pathogens. An ileocolonoscopy was not performed immediately because of sinus bradycardia in the electrocardiogram. Thus, then he carried a Holter monitor for 24 h, and sick sinus syndrome was finally diagnosed. Three days later he was readministered with Etiasa at 500 mg/day with the similar anaphylactic symptoms that promptly disappeared after another suspension of Etiasa. Given an EB virus infection with the patient, oral corticosteroids were not used. Probiotics and glutamine entero-soluble capsule were ultimately prescribed, which attenuated his abdominal pain and bloody diarrhea.
However, the patient self-discontinued those medications and individually took mesalamine enteric-coated tablets (Salofalk) at 500 mg/day, leading to the similar adverse reactions again and readmission to our hospital. Laboratory examinations revealed: CRP 36.70 mg/L and ESR 26 mm/h. Other laboratory indexes were in the normal range. An ileocolonoscopy revealed diffuse hyperemia, swelling and effusion in the colorectal mucosa, with histological features of ulcerative colitis. In view of his intolerance to Etiasa and Salofalk, mesalamine slow release tablets (Pentasa) was subsequently given, which similarly induce the above-mentioned allergic symptoms 2 h later. Considering the hypersensitivity for 5-ASA, he was finally prescribed with rectal corticosteroids to control the symptoms.


A 52-year-old woman initially presented with a 2-month history of 4–5 bouts of bloody diarrhea per day, abdominal discomfort and tenesmus, with deteriorative hematochezia since half a month ago. She was subsequently diagnosed with ulcerative colitis by ileocolonoscopy. Therefore, she was initially prescribed with Salofalk at 2,000 mg/day, which, however, induced generalized maculopapular skin rashes over the trunk and limbs with pruritus.
Then, the patient was admitted to our hospital. Laboratory examinations were: hemoglobin level (Hb) 9.5 g/dl (11.5–15.0 g/dl), CRP 55.10 mg/L, ESR 38 mm/h and serum albumin level 2.59 g/dl (3.5–5.5 g/dl). EB virus and cytomegalovirus tests were negative, as well as stool tests for bacterial and fungal pathogens. An ileocolonoscopy showed moderate to severe inflammation from descending colon to rectum, with histological findings in favor of ulcerative colitis. According to her medical history, the rash was considered to be associated with mesalamine administration, which prompted the withdrawal of Salofalk. Rash and pruritus began to subside within the next 24 h. To further confirm whether the allergic skin reaction was due to Salofalk, the reintroduction was performed, and the similar symptoms emerged unsurprisingly which disappeared after the discontinuation of Salofalk. Thus, mesalamine suppositories (Pentasa) at a dosage of 1000 mg/day was then tried to control the symptoms after seven days, and unexpectedly found with an excellent response. Ten days later, mesalamine slow release tablets (Pentasa) at 1,000 mg/day was added. Subsequently, the dosage of mesalamine tablets increased to 2,000 mg/day for 7 days, next to 3,000 mg/day for one day and eventually maintained at 4,000 mg/day. The patient gradually got better and had no adverse reactions during the administration of Pentasa.
Three months later, an updated ileocolonoscopy demonstrated the remarkable improvement of colonic inflammation. Therefore, mesalamine tablets were reduced to a dose of 3,000 mg/day, still accompanied with mesalamine suppositories at 1,000 mg/day. Then one month after that, mesalamine suppositories were suspended and oral mesalamine was returned to 4,000 mg/day for maintenance treatment. The patient has been well-response with absolute resolution of symptoms.


A 29 year old male visited the fertility center of Sree Avittom Thirunal Hospital of Government Medical College, Thiruvananthapuram for fertility treatment. Consent was taken from the patient before the study. The present finding of unexpected association between DSD and infertility in Kerala population was observed on 1st March 2018 at Sree Avittom Thirunal Hospital of Government Medical College, Thiruvananthapuram, Kerala, India during karyotyping and molecular characterization of azoospermic male patients.
Physical examination and medical history showed that the patient having height of 170 cm and weight of 75 Kg had no history of smoking, alcohol consumption and tobacco chewing. He has been using modern electronic gadget (Mobile phone) for the last five years and did not have any history of orchitis, STDs, psychological and endocrine disorders. Clinical findings revealed that the subject did not have palpation of testis, cryptorchidism, testicular torsion and changes in his extremities. Family history of patient did not show any infertility related problems. The study subject showed normal male secondary sex characters, penile length and androgenic hair pattern and no erection problem, gynecomastia and hypospadias were observed. The testis volume was <2 ml and both testicles were soft and atrophic. Major noticeable changes observed during clinical evaluation were small sized testis and ejaculatory dysfunction. Semen analysis was done on sample collected after 3 days of abstinence and the results confirmed non obstructive azoospermia on repeated analysis. Volume was 2 ml, pH=7.4, liquefaction time 15 min, WBC 0–1 pc/ml and fructose was present. Percutaneous Epididymal Sperm Aspiration (PESA) was done on both sides and sperm could not be retrieved. The couples opted for artificial insemination by donor (AID). Ultrasonography (USG) of scrotum showed right testis to be 1.2 cm × 1.8 cm × 1.4 cm in size with normal echotexture. Epididymis was normal with dimensions of 1 cm × 0.7 cm. Left testis measured 1.3 cm × 1.7 cm × 0.9 cm in size with no indication of varicocele. Transrectal ultrasound (TRUS) showed prostate with 38 mm X 35 mm × 20 mm size. No lesions were observed in any of the transrectal components. Urinary bladder was normal with no dilation in the seminal vesicles and ejaculatory ducts. Hormonal analysis showed an increase in Follicle Stimulating Hormone (FSH) to 35 mIU/ml (1–12 mIU/ml) and Luteinizing Hormone (LH) to 19.9 mIU/ml (1.5–10 mIU/ml) whereas testosterone to 3.2 ng/ml (2.45–10 ng/ml) and prolactin to 6.7 ng/ml (3.1–16.5 ng/ml) which were within the limit of reference range.
Chromosomal analyses of peripheral lymphocytes were used for identifying the numerical and structural aberrations of chromosomes. GTG banding was done for karyotyping. A total of 30 metaphase chromosomes were analyzed and the results showed that the patient had 46 XX karyotype () known as de la Chapelle syndrome with no evidence of other structural/numerical chromosomal abnormalities including mosaicism.
Molecular analysis of the Y-chromosome specific STS region by real time PCR and Uniplex PCR amplification of Y chromosome specific six sequence tagged sites (STS) primers were used for identifying AZF gene microdeletion (). The primers were designed based on EMQN guidelines (). Primers against SRY gene and a unique fragment in X chromosomes and ZFX gene were used as internal controls. Real time PCR analysis showed absence of entire AZFa, AZFb and AZFc region but the presence of SRY gene was confirmed as shown in . All STS primers were amplified in the male positive control. The female genomic DNA failed to amplify in any of the STS primers and the SRY gene, however, showed amplification of the ZFX gene. These findings confirmed that the patient is 46 XX male with the presence of SRY gene.
Fluorescent in situ hybridization (FISH) analysis was performed on metaphase chromosomes from cultured peripheral lymphocytes to confirm the 46 XX male condition using LSI SRY/CEPX probe (Vysis Inc., USA) localized on Yp11.3 and p11.1-q11.1 of X chromosome. The probe hybridization showed two signals for CEPX (Green) at the centromeric region of both the X chromosome and one signal for SRY (Red) on terminal region of one X chromosome in all the metaphases analyzed (). This finding confirmed the 46 XX karyotype, a case of DSD.


A 70-year-old man presented to the emergency room of Shizuoka Cancer Center with a high-grade fever, headache, and nausea. He had a five-year history of unresectable thymoma (Masaoka stage IVa; Fig. ) treatment, including cisplatin and amrubicin, amrubicin monotherapy, and a phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor which was discontinued due to tumor progression 12 months prior. Two months prior, he had received thoracic radiotherapy (40 Gy with 20 fractions) for palliation of chest pains due to multiple pleural disseminated lesions. During the previous month, he had experienced multiple febrile episodes, dry cough, fatigue, weight loss, and watery diarrhea. Upon admission, he had a fever (≥40 °C), nausea, and immobility. Physical examination revealed indistinct consciousness, neck stiffness, and oropharyngeal candidiasis. The patient’s white blood cell count was 15,380 cells/μl with 91% granulocytes, and biochemical examination revealed elevated AST/ALT levels (81 and 153 IU/L, respectively). Both cerebrospinal fluid and blood cultures yielded multiple short chains of Gram-positive rods later identified as Listeria monocytogenes, so he was diagnosed with Listeria meningitis (Fig. ). Intravenous administration of vancomycin (1 g/12 h) and ceftriaxone (2 g/12 h) was initiated, followed by ampicillin (2 g/4 h) and gentamicin (80 mg/8 h) for three weeks. The patient fully recovered and was discharged.
Additional examination found normal levels of total IgG (1148 mg/dL), IgM (57 mg/dL), and IgA (156 mg/dL). Flowcytometric analysis of peripheral-blood cells disclosed 528 lymphocytes/μl (normal range, 1000–3100 lymphocytes/μl), 108 CD4+ cells/μl (normal range, 320–1900 cells/μl), 129 CD8+ cells/μl with a CD4+/CD8+ ratio of 0.84 (normal range, 0.40–2.30), and 2% B cells (11 cells/μl). Tests for antibodies to human immunodeficiency virus type 1 (HIV) and human T-lymphotropic virus type 1 were negative. The patient was diagnosed with cellular immunodeficiency due to thymoma. His CD4+ cell count has remained < 150 cells/μl during 15-month follow up after discharge (after 3 months, 79 cells/μl; 6 months, 107 cells/μl; 9 months, 146 cells/μl; 12 months, 132 cells/μl).


We report the case of a 36-year-old woman, who was 27.5 weeks pregnant and had no antecedents of interest or consanguinity with her partner. The patient was referred to us from a private clinic for ductus venosus agenesis (DVA), polyhydramnios and small fetal stomach with suspicion of oesophageal atresia. The patient was controlled outside of our unit until that moment; however, her first trimester combined screening results were low-risk. The study was reviewed and approved by the University Hospital of Salamanca Institutional Review Board (no. PI 201 8 03 205; date of approval 18 March 2018). The patient referred in the case report participant provided informed written consent.
Our exploration showed a bifurcation of the umbilical vein, giving rise to a normal hepatic-portal portion and another varicose portion of 5.2 mm, which ran intrahepatic, describing a curved path in the form of an intrahepatic "C" (A). This joined to the suprahepatic veins and drained into the inferior vena cava (IVC), giving rise to an umbilical-IVC portosystemic shunt. The fetal stomach was normal, though a slight polyhydramnios was present (27 Amniotic Fluid Index). Echocardiography showed a cardiac axis displaced to the left, with the wall of the right ventricle thickened, especially at the level of tricuspid valve implantation. The Tei-Index was 0.59 (>p95 for gestational age at the expense of isovolumetric relaxation time), which indicated mild diastolic dysfunction. Estimated fetal weight (EFW) was in the 77th percentile, with fetal biometry parameters as follows: Biparietal Diameter (BPD) = 70.8 mm (p63), Head Circumference (HC) = 287.7 mm (>p98), Abdominal Circumference (AC) = 241.4 mm (p64) and Femur Length (FL) = 53.8 mm (p59) (B). The rest of the examination was normal.
Amniocentesis was offered, requesting array-CGH and molecular study through a massive panel sequencing of 16 genes related to Noonan Spectrum Disorders (RASopathies), finding no pathogenic mutations in the sequences analyzed.
The analysis by array-CGH of the DNA extracted from uncultivated amniocytes obtained a result of arr (hg19) 12p13p11 (222,688-34,345,726) × 4 and male genomic pattern (A). A gain of chromosomal material was detected in the entire short arm of chromosome 12, compatible with Pallister–Killian Syndrome (PKS) (B). After obtaining the result, we proceeded to perform karyotype from a sample of amniotic fluid kept in culture in the Genetics Service to visualize the 12p isochromosome and confirm this finding. To our surprise, however, 3 weeks after its extraction, the result of the conventional cytogenetic showed a normal karyotype, probably due to clonal selection of normal diploid cells over the tetrasomal ones during the culturing process. The couple was informed of these results, deciding to terminate the pregnancy. Unfortunately, termination of pregnancy was carried out in a different center and no autopsy report was available.


A 60-year-old female with a medical history of unexplained prolonged hematuria for the last four years presented to the emergency department (ED) with complaints of hemoptysis, fever, myalgia, and night sweats that had persisted for at least one week. She had no other comorbidities, and her family history was unremarkable. Before coming to the ED, the patient experienced four episodes of hemoptysis and was referred from urgent care to the ED due to the concern of acute anemia and chronic kidney injury. The patient gave her informed consent for inclusion before participating in the study.
On admission, vital signs included blood pressure of 162/93 mmHg, heart rate of 98 beats/minute, respiratory rate of 24 breaths/minute, and oxygen saturation of 94%. A physical examination yielded non-significant findings except for pallor, blood around the nares, and prominent right-sided pulmonary crackles on auscultation.
The results of the initial laboratory tests, including hematology, metabolic panel, arterial blood gas, and culture and sensitivity, are shown below in .
Urine analysis and baseline antibody panel for diagnostic workup are shown in and respectively.
A baseline chest radiography finding is shown in . A high-resolution computed tomography (HRCT) of the chest is shown below in .
A flexible fiberoptic bronchoscope was introduced through the endotracheal tube and advanced to the tracheobronchial tree of both lungs under adequate sedation. Fresh blood was found throughout the tracheobronchial tree, with no focal bleeding focus. During serial aliquoting, the blood remained unchanged, as aliquots progressed with 60 mL saline flushes.
A bronchoscopy image showed blood in the right middle lobe in the tracheobronchial tree, failing to show the specific focal source, as shown in .
A microscopic evaluation of the broncho-alveolar lavage showed a red color aspirate with numerous pulmonary alveolar macrophages and red blood cells; bacterial and fungal cultures, as well as acid-fast staining of the broncho-alveolar aspirate were negative.
The auto-antibody panel indicated a very high level of C-ANCA. The initial laboratory tests revealed a low estimated glomerular filtration rate and a high creatinine level, as well as an increase in anion gap, metabolic acidosis, hyperphosphatemia, parathyroid hormone level, and a decrease of vitamin D level. The nephrology department was consulted, and a kidney biopsy was performed. The renal biopsy findings suggested pauci-immune (ANCA-associated), rapidly progressive glomerulonephritis. Specifically, light microscopy revealed a medullary segment with no cortex or glomeruli and intraluminal hyaline casts. Cortical sections contained three glomeruli containing fibro-cellular crescents. Electron microscopy revealed wrinkled glomerular basement membranes and capillary luminal compression with variable levels of endothelial cells and diffused effacement of the foot processes. Additionally, scattered electron-dense mesangial deposits and a loss of brush borders on adjacent tubules were observed. Immunofluorescence staining was inconclusive. A presumptive diagnosis of diffuse alveolar hemorrhage due to GPA was made based on the constellation of anemia, positive C-ANCA test, high proteinase-3 antibody titer, bronchoscopy findings of diffuse alveolar hemorrhage without a focal source, chronic kidney disease stage-5, and renal biopsy findings of rapidly progressive glomerulonephritis. Other differential diagnoses included:Microscopic polyangiitis—this was difficult to differentiate on the basis of the clinical background, but a negative myeloperoxidase titer helped us to rule this out. Eosinophilic granulomatosis with polyangiitis—this was difficult to differentiate on the basis of the clinical presentation, but this was ruled out considering the negative myeloperoxidase findings and a normal eosinophil count. Drug-induced vasculitis—although this can have a similar presentation, a thorough history-taking ruled out this disease.
We administered a seven-day course of plasmapheresis on alternate days together with a combination of pulse steroids (methylprednisolone 1000 mg twice daily) for seven days and cyclophosphamide 730 mg q3/week. Antibiotic coverage with vancomycin 1000 mg and ceftriaxone 1000 mg was also given during plasmapheresis and immunosuppressants. During treatment, the respiratory status was supported by low tidal volume minute ventilation followed by successful extubation. For chronic kidney disease (CKD) treatment, the patient underwent hemodialysis through a right subclavian permanent catheter with a transition to the arteriovenous fistula route for an outpatient dialysis route.
A multidisciplinary therapeutic approach including fluid support, ventilatory support, plasmapheresis, pulse steroids, and cyclophosphamide led to a remarkable symptomatic improvement of the pulmonary symptoms and to the resolution of the pulmonary imaging findings, as shown in part B of .
The patient was discharged with outpatient prednisone 40 mg with a taper over four weeks. For end-stage renal disease secondary to granulomatosis with polyangiitis, our patient received scheduled outpatient hemodialysis through an arteriovenous (AV) fistula.


An 18-year-old male who reported no past medical history presented to the pediatric emergency department (ED) complaining of mild substernal chest pain, intermittent palpitations, and dyspnea with minimal exertion over the prior week. He endorsed decreased oral intake of fluids and solids over the prior week and occasional non-productive cough. He endorsed some caffeine intake (1–2 caffeinated sodas per day), but no recent increase in caffeine consumption. He denied any fevers, drug use including cocaine, and reported no significant familial history of hyperthyroidism, cardiac disease, or sudden death. There was no history of recent upper respiratory infections, muscle pain, back pain, joint stiffness, nausea, vomiting, diarrhea, rash, dizziness, syncope, leg swelling, or history of trauma. There were no known ill contacts.
Initial exam revealed a very well-appearing young man in no distress, speaking in full sentences, and sitting on the stretcher playing with his 9-month-old child. Initial vital signs included a temperature of 96.7 degrees Fahrenheit, pulse of 116 beats per minute (bpm), blood pressure of 126/81 millimeters of mercury (mmHg), respiratory rate of 18 breaths per minute, and an oxygen saturation of 95% on room air. There were no murmurs on cardiac exam. His pulmonary exam was normal with no wheezes or accessory muscle use. The abdomen was soft with no tenderness, and his extremity and neurologic exams were unremarkable. No lower extremity edema, calf cords, or leg tenderness was noted.
The patient had an intravenous line placed, and initial labs included a complete blood count and electrolytes, which were normal. He was given one liter of normal saline and his heart rate improved to 92 bpm. A point-of-care cardiac ultrasound was performed. He had a normal ejection fraction on the parasternal long view with no pericardial effusion. However, the parasternal short-axis view demonstrated a “D-sign,” wherein bowing of the interventricular septum into the left ventricle (LV) caused it to take on the shape of a capital letter D, indicative of right ventricular (RV) strain ( and ). The apical four-chamber axis view demonstrated an enlarged RV, although the team did not observe akinesis of the mid-free wall of the RV (“McConnell’s sign”) ( and ). A D-dimer was sent, as the identification of RV strain on POCUS increased the team’s suspicion for pulmonary embolism (PE). Ultrasound of the lower extremity veins identified a non-compressible right popliteal vein, indicative of an occlusive thrombus.
On further questioning regarding family history, the patient called his mother and subsequently reported that he carried a diagnosis of factor V Leiden mutation, which had been identified after his mother developed an unprovoked PE several years prior. He also recalled twisting his right ankle one week prior to presentation, although he had no significant swelling or difficulty walking thereafter.
The patient’s D-dimer subsequently came back at greater than 6,000, with a N-terminal pro b-type natriuretic peptide (NT-proBNP) elevated at 1096. Troponin was negative. Computed tomography (CT) angiography of the chest identified a saddle PE, with near-occlusive clot in the right pulmonary artery, signs of right heart strain, and pulmonary arterial enlargement (). The patient was taken to the cardiac catheterization suite for ultrasound-assisted, catheter-directed, low-dose thrombolysis using the EkoSonic Endovascular System (EKOS catheters). He was admitted to the medical intensive care unit thereafter and recovered without complications. He was discharged two days later on rivaroxaban, with the plan for lifelong anticoagulation.


An 83-year-old Filipino female was referred to our clinic with a 3-year history of headaches. She also reported intermittent perioral paraesthesia but denied epistaxis, rhinorrhoea, anosmia, or facial pain. She had a past medical history of hypertension managed on perindopril and previous transient ischaemic attack (TIA). She was a lifelong nonsmoker and had no significant history of alcohol use.
On flexible nasendoscopic examination, a left posterior septal mucosal-covered, polypoid, pedunculated mass without ulceration was identified and found to extend into the nasopharynx. The right nasal passage was clear with no extension through the septum.
A high-resolution computed tomography (CT) of the paranasal sinuses demonstrated a left nasal mass measuring approximately 3.4 × 4.1 cm ().
Examination under anaesthesia (EUA) and biopsy were recommended. However, the patient was unwilling to proceed and declined further investigations or treatment. She was subsequently lost to follow-up. One year later, the patient re-presented to the emergency department with an acute onset of coughing and mild epistaxis. Clinical examination demonstrated that the lesion had marginally grown since previous review, now crossing the midline posterior to the septum.
Repeat CT of the paranasal sinuses demonstrated an irregular 4.8 × 5.2 cm polypoid mass originating from the posterior nasal septum and projecting into the left side of the nasopharynx. The mass had a central core of high-density material, with an outer soft-tissue layer, and did not enhance with contrast (). Magnetic resonance imaging (MRI) demonstrated a slightly heterogenous though predominantly T2 hyperintense and T1 hypointense mass. Gadolinium contrast demonstrated a heterogenous, cerebriform appearance ().
In view of the slow growth of the lesion and central high-density, a presumptive diagnosis of a rhinolith was made, while neoplasia was considered less likely.


A 31-year-old primigravida presented to a maternity unit with shoulder tip pain two days after an uncomplicated spontaneous vaginal delivery. She was born in Nigeria and moved to the United Kingdom when she was seven years old. She had a normal gestation and childhood. Her family’s medical history was unremarkable. She had a past medical history of gastro-oesophageal reflux disease and uterine fibroids. In the month prior to her presentation she had sustained a traumatic comminuted fracture of her right third metacarpophalangeal joint which was managed conservatively with splinting. Her first pregnancy was complicated by worsening of her fibroid-related pain in the first trimester and she was commenced on regular analgesia, antiemetics and aspirin (due to concerns of predicted low birth weight). Following delivery she was not on any regular medications. There was no history of drug allergies. Following assessment at the maternity day unit it was concluded that her shoulder tip pain was related to her fibroids and she was discharged with analgesia and safety-netting.
Two days later, she was admitted as a priority call to our emergency department with a working diagnosis of possible massive pulmonary embolism from the ambulance service. On arrival she was in extremis. Her airway was patent. She was unable to speak with a respiratory rate of 56 and oxygen saturations of 56% on non-rebreather mask (15L of oxygen). Her trachea was central and there was poor air entry bilaterally. She was in shock with a heart rate of 170 beats per minute and unrecordable blood pressure. Point-of-care echocardiography carried out by the emergency department team demonstrated good biventricular systolic function without right ventricular dilatation or pericardial effusion. There was absent pleural sliding bilaterally on thoracic ultrasound. Chest X-ray demonstrated large bilateral pneumothoraces (see Figure ). Fifty milligrams of intravenous ketamine was given to provide analgosedation for surgical thoracostomies and chest drain insertion. Both pneumothoraces were under tension with audible hiss and rapid physiologic improvement. Subsequent radiograph demonstrated substantial resolution with ex-vacuo pulmonary oedema and new subcutaneous emphysema.
Following stabilisation she underwent computed tomography which additionally demonstrated signs of interstitial lung disease (see Figure ). There was an 8.3 by 6 cm pedunculated uterine leiomyoma.
She was transferred to a tertiary cardiothoracic centre for further assessment and care. Due to persistent left-sided air leak she underwent unilateral video-assisted thoracoscopic surgery. Apical bullous disease was noted with normal appearances of the horizontal fissure and diaphragm and she underwent left apicectomy and parietal pleurectomy. Histopathological assessment found areas of subpleural fibrosis, patchy interstitial fibrosis and emphysematous changes with very occasional collections of bland spindle-shaped cells at the margins of dilated airspaces. These findings in conjunction with immunohistochemistry (Smooth Muscle Actin and Progesterone Receptor positivity with equivocal to negative Human Melanoma Black 45) suggested an underlying diagnosis of pulmonary lymphangioleiomyomatosis.
Serial imaging demonstrated persistent basal left-sided hydropneumothorax and on the sixth post-operative day she had a 12-French Seldinger chest drain inserted by interventional radiology to good effect. She was discharged with outpatient cardiothoracic surgical and respiratory medicine follow-up to evaluate the need for follow-on right-sided video-assisted thoracic surgery and further assessment of her interstitial lung disease.


A 59-year-old Chinese male presented with a 6-month history of intermittent dizziness. The dizziness occurred exclusively at meal times and was worst when swallowing large quantities of solid food, such as rice or bread. He initially was symptom free when consuming smaller quantities of solids or fluids, but his condition worsened progressively with presyncopal events occurring even while eating smaller quantities of solid food. The patient described a sensation of increasing difficulty in swallowing despite reducing the size of his meals. He denied any associated syncope or seizures. His past medical history and physical examination were unremarkable and blood investigations were within normal limits. Echocardiography revealed a structurally normal heart with normal systolic and diastolic function. 24-h electrocardiogram (ECG) monitoring recorded a sinus pause of 4.5 s at the time the patient had his meal (Fig. ). A provisional diagnosis of swallow syncope was made and a permanent pacemaker (PPM) implantation was scheduled.
Tilt table testing prior to pacemaker insertion resulted in a hypotensive response 5 min after provocation with 400 micrograms of sublingual glycerin trinitrate administered sublingually, with reproduction of symptoms of syncope. The minimal blood pressure was 32.9/29.2 mmHg and the heart rate 75.3 bpm. No asystole was observed during tilt table testing (Fig. ).
The patient’s symptoms resolved completely after implantation of a dual chamber PPM. A diagnostic workup to exclude gastrointestinal disease was performed. A barium swallow test was normal and effectively ruled out achalasia. The oesophagus appeared healthy with no structural disease on oesophagogastroduodenoscopy (OGD). The pacemaker was continuously interrogated during the OGD. Increased pacing requirements were noted when the endoscope was advanced into the esophagus (Fig. b). Subsequently, a 20 mm diameter TTS (through-the-scope), CRE™ (controlled radial expansion) balloon (Boston scientific) was sequentially inflated in the proximal, mid and distal esophagus while the pacemaker was programmed “OFF” to assess the physiologic response. Inflation in both distal and mid oesophagus resulted in significant sinus pauses of up to 5.6 s (Fig. c) confirming the cardio-inhibitory response to oesophageal distension as the underlying pathophysiological mechanism of this patient’s syncopal events.


A 13-year-old Oromo girl presented with a progressively increasing right-sided abdominal mass, low-grade intermittent fever, and a dull right upper abdominal pain of 3 years’ duration with no other associated symptoms. There were no known past illnesses and there was no family history of similar illness. She was given pain medications and antibiotics on various occasions but there was no improvement.
Her general appearance was not acutely sick looking. Her vital signs were within normal limits. The pertinent abnormal finding was right-sided abdominal mass with well-defined medial and inferior border extending to right subcostal region. Complete blood count (CBC), urine analysis, and organ function tests were all normal. Ultrasound and a computed tomography (CT) scan demonstrated a huge vascular suprarenal mass displacing her right kidney caudally; it measurements were 16 × 19 cm and it contained multiple internal calcifications. There were no enlarged regional nodes and no vascular invasion.
Laboratory tests for functional adrenal tumors including serum and 24-hour urine metanephrines were all normal.
A working diagnosis of huge nonfunctional adrenal tumor was made and our patient underwent exploratory surgery through a bilateral subcostal incision. The operative findings were a well-capsulated and highly vascularized mass arising from the superior aspect of her right kidney, which got a significant blood supply from the right lobe of the liver. The mass was successfully and completely resected and the specimen subjected to histopathology.
The histopathology report showed 18 × 15 × 12 cm white solid mass with necrotic center arising from right adrenal gland. There was a patternless proliferation of spindle cells and ovoid cells that had mild pleomorphic nuclei and focally hyalinized stroma containing blood vessels. Mitosis was seen infrequently. These findings were consistent with a SFT of the adrenal gland.
Our patient was followed-up for 3 months and is doing remarkable well and members of her family were very grateful.
This is the sixth or seventh case of its kind in the world to the best of our knowledge (Figs. , , , and ).


A 60-year-old male with history of Bronchial Asthma and Gastroesophageal reflux disease (GERD) first presented with an episode of small-volume hemoptysis. He denied history of smoking or carcinogen exposure. He also denies a family history of malignancy. Chest x-ray showed a small nodular density in the right lower zone. Chest CT revealed two benign-appearing sub-centimeter pulmonary nodules and multiple hepatic lesions. Abdominal MRI revealed multiple hypovascular hepatic lesions, largest 3.2 × 1.4cm in the left hepatic lobe. He declined liver biopsy and did not follow up. The patient presented a year later with abdominal pain, early satiety and unintentional weight loss. He denied any other symptoms. Follow-up CT abdomen demonstrated hepatomegaly, diffuse hepatic lesions with near replacement of the left hepatic lobe with metastases and new lesions in the right lobe (). Liver biopsy confirmed metastatic, well-differentiated intermediate grade neuroendocrine tumor. Ki-67 proliferative rate was 5–10%. Immunohistochemistry (IHC) staining was positive for synaptophysin and chromogranin and negative for CDX2 and TTF-1.
Due to bulky liver lesions, the patient was referred for left hepatic artery embolization after receiving 2 doses of octreotide. Two days following the procedure, he became disoriented, complained of worsening abdominal pain and vitals revealed tachycardia, hypotension, and fever (100.40F). Laboratory studies showed an increase in AST (86 to 1335mg/dl) and ALT (90 to 500 mg/dl), potassium of 6meq/dl, phosphate 5.5mg/dl, uric acid 10.5mg/dl and lactic acidosis. CT abdomen was negative for acute intra-abdominal pathology. Aggressive IVF resuscitation was initiated with allopurinol and rasburicase for TLS prophylaxis and treatment. The patient also received empiric antibiotic coverage with piperacillin/tazobactam, lactulose and rifaximin for presumed hepatic encephalopathy in setting of fulminant hepatitis. Blood cultures remained sterile.
He was admitted to the intensive care unit (ICU) for management of TLS and post embolization syndrome. His course was further complicated by oliguric renal failure requiring continuous renal replacement therapy and sterile ascites. The patient’s mental status gradually returned to baseline and by day 18 of admission, the TLS, post embolization syndrome and renal failure resolved with normalization of laboratory parameters. He was eventually discharged to subacute rehabilation and continued follow-up with primary oncologist.


It is a 13-year-old boy born as only child from healthy non-consanguineous parents. He was born at 38 weeks of gestational age. Maternal preeclampsia was detected in the last month. Growth parameters at birth were: weight 3,880 g (+2.5 Standard deviation (SD)), length 54 cm (+3 SD), and Occipital frontal circumference 38.5 cm (+4.5 SD). No facial dysmorphisms were evident at birth. He showed mild respiratory distress, treated with oxygen support in incubator for few hours, transient hypoglycemia, requiring early oral feeding, and jaundice, treated with phototherapy.
Normal acquisition of milestones was reported with exception of mild delay in independent walking. The patient hold up the head at 4 months, he sat unsupported at 7 months, and began walking independently at age 18 months. He started speech therapy at the age 3 years due to language delay. The first formal neuropsychological test was assessed at 11 years (WISC IV), showing a total IQ of 55, with language subitem being the worst skill. He attended the secondary school with support. He has fluent language, can read and write well. He is quiet and sociable, no behavioral problems and Autism spectrum disorder were reported. He never had seizures. As a child, at age 2 years, he suffered from viral infection with myocarditis and transient hepatosplenomegaly that spontaneously resolved after 6 months. Periodic ultrasound examination of heart, kidneys, and thyroid gave normal results. Endocrine evaluations, including Follicle-stimulating hormone, Luteinizing hormone, Thyroid-stimulating hormone, FT4-FT3, testosterone, and IGF1, gave normal results. Kidney and liver function were normal. Growth profile in term of weight and height was always harmonic and above normal ranges for Centers for Disease Control and Prevention's growth charts (respectively, weight at +3.5 SD and height at 4 SD), whereas Occipital frontal circumference measure progressively increased till +8 SD at the age of 10 years. A bone age study was performed at 7 years of age, showing mild advanced bone age (8 years). At age 12 years, weight was 80 kg (+3.6 SD), height 180 cm (+4 SD), Occipital frontal circumference 66.5 cm (+8 SD).
He was presented with trunk hypotonia and minor facial anomalies (Figure ). Pectus excavatum, mild joint hyperlaxity (Beighton score 3/9), and moderate scoliosis treated with corset, were also present. He underwent dermatological examination and dermoscopy because of multiple small acquired nevi. The only atypical lesion was surgically excised, and diagnosed as dysplastic Clark nevus. A small hyperkeratotic lesion on the foreskin of about 3 mm in diameter was present from birth. Brain CT scan performed at age 2 years, due to macrocephaly, showed hypodensity of the bilateral posterior periventricular white matter, and mild asymmetric lateral ventricle enlargement. Brain MRI at 12 years showed a Chiari malformation type I with right cerebellar tonsillar ectopia 12 mm below mcRae's line and mild lateral ventricular asymmetry without hydrocephalus. Symmetric megalencephaly without polymicrogyria was diagnosed.


A 39-year-old male patient was received at our emergency department due to unspecified abdominal complaints and fever in the last four days. The patient denied any kind of pre-existing conditions. During the physical examination, the abdomen was soft, without any focal painful site. Blood laboratory tests showed marked leukocytosis (17 x 109/L), as well as a high neutrophil (15.6 x 109/L) count. A computed tomography (CT) scan was requested by the emergency physician, which showed a rounded hypodense structure located at the end of the appendix, adjacent to the ascendent portion of the colon. This structure showed higher attenuation with intravenous contrast material and stranded circumferential fat (Figure ), which corresponded to an abscess. The appendix showed a diameter of 2 cm.
Antibiotic and analgesic treatment was initiated because of the potential risk of complications. The case was presented to the interventional radiology department, which decided that a conservative approach was the best option for the patient. An ultrasound-guided percutaneous drain was placed in the right flank without any complications (Figure ). After 11 days, the leukocyte count was normal (7000 x 109/L) and the patient was afebrile, therefore, the drain was taken out and the patient was discharged without any complications. An appendectomy was performed 14 days later, without any complications. The pathology report concluded inflammatory infiltrates secondary to appendicitis.


A 13-year, nine-month-old male neutered Yorkshire terrier presented with a peracute onset of left-sided circling, and a history of polyuria and polydipsia. The general physical examination identified a grade III/VI systolic heart murmur and obesity. On neurological examination, the dog was obtunded and was circling in small circles toward the left. The proprioceptive positioning was absent in the right thoracic and pelvic limbs. The remainder of the neurological examination was unremarkable, and a neurolocalization of left forebrain was determined.
Routine hematology was within normal limits, while serum biochemistry results included a moderately increased alkaline phosphatase activity (731 U/L; RI: 23-212 U/L). Noninvasive blood pressure (NIBP) assessment using Doppler identified a systolic pressure of 200–210 mmHg. An echocardiogram demonstrated mitral regurgitation consistent with presumed preclinical degenerative mitral valve disease. Urine-specific gravity was 1.020. Urine chemistry dipstick analysis was consistent with proteinuria (3+; RI: negative to trace), and a urine protein:creatinine (UPC) ratio was elevated (3.97; RI: 0-1). Urine sediment examination was normal, and urine culture was negative. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and D-dimer were all within normal limits. A shortened reaction time (R) and split point (SP) were seen on TEG analysis performed on citrated plasma ().
An MRI scan of the brain (VetMR Grande 0.35T, Esaote, Genova, Italy) was performed under general anesthesia and included T2-weighted (T2W) transverse images, fluid attenuated inversion recovery (FLAIR) dorsal images, and short-TI inversion recovery transverse images. Sagittal, transverse and dorsal T1-weighted (T1W) images were acquired before and after intravenous (IV) administration of gadolinium contrast (0.1 mmol/kg, gadolinium demeglumine). An intra-axial, focal, well-defined and sharply demarcated lesion was identified within the left thalamus (). The lesion was hypo- to isointense compared to normal gray matter on T1W images and hyperintense on T2W and FLAIR sequences. The lesion did not show enhancement after gadolinium administration, and there was no evidence of mass effect. These findings were suggestive of an extensive dorsal thalamic infarct.
Further investigations were performed to evaluate for evidence of predisposing causes for cerebrovascular disease and hypertension. Bilateral adrenomegaly was seen on abdominal ultrasound and a low-dose dexamethasone suppression test [basal cortisol: 204 nmol/L (RI: 27.5–125 nmol/L), 4 h post suppression: 34 nmol/L (RI: <40 nmol/L), 8 h post suppression: 168 nmol/L (RI: <40 nmol/L)] was consistent with pituitary dependent hyperadrenocorticism. Thoracic radiographs were unremarkable.
Treatment consisted of amlodipine (1 mg/kg PO q12 h; Istin 5 mg tablets, Pfizer Limited, Kent, UK), enalapril (0.5 mg/kg PO q24h; Enacard 2.5 mg tablets, Merial Animal Health, Harlow Essex, UK) and trilostane (5 mg/kg PO q24h; Vetoryl 30 mg tablets, Dechra, Shrewsbury, UK). The dog was hospitalized for seven days and during this time showed a gradual neurological improvement; the systolic blood pressure had stabilized around 170 mmHg at discharge. On reassessment 10 days after discharge, the dog was only showing mild proprioceptive deficits on the right side. The dog was lost to follow-up thereafter.


A 10-year, 10-month-old male neutered Shih Tzu presented for further investigation of a peracute onset of lethargy and left-sided circling. The general physical examination was normal. On neurological examination, the dog was circling to the left, had decreased proprioceptive positioning of the right thoracic and pelvic limbs and a decreased menace response on the right side. The remainder of the neurological examination was unremarkable, and the findings were considered consistent with a left forebrain neurolocalization.
Routine hematology and serum biochemistry was normal, and serum thyroxin and thyroid-stimulating hormone (TSH) concentrations were within normal limits. Urine-specific gravity was 1.018, urine chemistry dipstick analysis and sediment examination, UPC ratio and urine culture were all unremarkable. Assessment of NIBP using Doppler identified a systolic pressure of 170 mmHg. Fibrinogen, PT, aPTT, and D-dimer were all within normal limits. A shortened R time and SP were seen on TEG analysis on citrated plasma ().
An MRI scan of the brain using the same protocol and scanner as in case 1 was performed under general anesthesia. There was an extensive intra-axial, focal, well-demarcated lesion affecting the cerebral gray matter extending from the left frontal lobe to the rostral aspects of the left temporal lobe. The lesion was T2W and FLAIR hyperintense compared to normal gray matter and T1W hypointense. There was evidence of mild mass effect and there was no contrast enhancement. The findings were consistent with an ischemic stroke affecting the vascular territory of the left middle cerebral artery. CSF collected from the cerebellomedullary cistern was unremarkable. Abdominal ultrasound and thoracic radiographs were performed to evaluate for predisposing causes of the cerebrovascular event. No abnormalities were detected and accordingly no underlying cause for the ischemic stroke could be identified.
The dog improved with time and was discharged from hospital 72 h after admission. The dog made a near to full recovery within 14 days, and was neurologically normal at re-assessment five months later.


A seven-year, five-month-old male neutered Shih Tzu presented for further investigation of a peracute onset of a head tilt and loss of balance. The general physical examination was normal. On neurological examination, the dog was lethargic with a moderate left head tilt. The dog was non-ambulatory due to severe ataxia affecting all four limbs; with support the dog was dysmetric with hypermetria affecting the right thoracic and pelvic limbs. The remainder of the neurological examination was unremarkable, and a neurolocalization of right cerebellum was made, suspecting paradoxical vestibular disease.
Routine hematology, serum biochemistry, and standard urinalysis were normal. Serum thyroxin, TSH and an ACTH stimulation test were also within normal limits. Assessment of NIBP using Doppler identified a systolic pressure of 160–165 mmHg. Fibrinogen, PT, aPTT, and D-dimer were all within normal limits. A shortened R time and SP were seen on TEG analyses performed on citrated plasma ().
An MRI scan of the brain using the same protocol and scanner as in case 1 was performed under general anesthesia. An intra-axial, focal, well-defined and sharply demarcated lesion was identified within the right cerebellar hemisphere (). The lesion was hypointense compared to normal gray matter on T1W images, hyperintense on T2W, and FLAIR sequences and mainly affected the gray matter. The lesion did not show enhancement after gadolinium administration, and there was no evidence of mass effect. These findings were consistent with an ischemic stroke affecting the territory of the right rostral cerebellar artery. Supracollicular fluid accumulation was also evident, a finding that was considered to be incidental. CSF collected from the cerebellomedullary cistern was unremarkable. No underlying cause for the ischemic stroke could be identified.
The dog improved with time and was discharged from hospital after five days. On re-examination 14 days after discharge the dog was only showing mild hypermetria of the right thoracic limb, he was lost to follow-up thereafter.


A six-year, two-month-old female cavalier King Charles spaniel presented with a history of a peracute onset of lethargy and circling to the right. The dog presented to the hospital seven days after the onset of clinical signs, and had already improved clinically, according to the owner. The general physical examination was normal. On neurological examination, the dog showed delayed proprioceptive positioning on the left thoracic and pelvic limbs and an inconsistent menace response on the left side. Circling was not detected on presentation. The remainder of the neurological examination was normal, and the findings were considered consistent with a right forebrain neurolocalization.
Mild thrombocytopenia with the presence of macrothrombocytes was seen on routine hematology (). Serum biochemistry and standard urinalysis were unremarkable. Serum thyroxin and TSH were also within normal limits. Assessment of NIBP using oscillometry identified a systolic pressure of 170 mmHg. D-dimer, PT and aPTT were within normal limits whereas the fibrinogen level was mildly increased (). TEG analysis performed on citrated whole blood was considered hypercoagulable with a normal R time, shortened clotting time (K) time, and increased maximum amplitude (MA), angle (α), and global clot strength (G value) (). The TEG tracing is shown in .
An MRI scan of the brain (VetMR 0.2T, Esaote, Genova, Italy) was performed under general anesthesia and included T2W sagittal and transverse images and FLAIR transverse images. Sagittal and transverse T1W images were acquired before and after IV administration of gadolinium contrast (0.1 mmol/kg, gadolinium dimeglumine). In the right frontal and rostral aspects of the temporal lobe there was an intra-axial, focal, well-defined, and sharply demarcated lesion. The lesion was hyperintense on T2W and FLAIR sequences and hypointense on T1W images compared to normal gray matter. The changes were particularly evident within the cortical gray matter. The lesion was associated with mild mass effect and there was no contrast enhancement. These findings were suggestive of an ischemic stroke affecting the territory of the right middle cerebral artery. Changes consistent with Chiari-like malformation and a left-sided otitis media with effusion were also seen; both were considered incidental findings. Further investigations to evaluate for a predisposing cause for cerebrovascular disease was not undertaken based on the owner's decision.
The dog improved with time, and was considered neurologically normal at re-examination 49 days after discharge, with no recurrence of neurological deficits.


A six-year, 11-month-old male Weimaraner presented with a five-day history of a peracute onset of a right-sided head tilt and loss of balance. The signs were improving on presentation. The general physical examination was normal. On neurological examination, the dog had an alert mentation, a mild right-sided head tilt, cerebellovestibular ataxia, and a broad-based stance affecting all limbs. There was occasional falling to the right with delayed and dysmetric hopping affecting all limbs. The remainder of the neurological examination was unremarkable, and a neurolocalization of right cerebellum was made.
Routine hematology, serum biochemistry, and standard urinalysis were unremarkable. Serum thyroxin and TSH were also within normal limits. Assessment of NIBP using oscillometry identified a systolic pressure of 170–175 mmHg. Fibrinogen, PT, aPTT, and D-dimer were all within normal limits. TEG analysis on citrated whole blood was considered hypercoagulable with a shortened R and K time, and an increased MA, α, and G value ().
An MRI scan of the brain using the same protocol and scanner as in case 4 was performed under general anesthesia. There was an intra-axial, focal and sharply demarcated wedge-shaped lesion within the right paravermis and rostrodorsal aspect of the cerebellar cortex. The lesion was hyperintense on T2W and FLAIR images compared to normal gray matter, and T1W hypointense. There was no mass effect or evidence of enhancement after contrast medium administration. These findings were most consistent with an ischemic stroke affecting the territory of the right rostral cerebellar artery. CSF collected from the cerebellomedullary cistern was normal. No predisposing cause for the ischemic stroke could be identified in this case.
The dog improved with time and was considered neurologically normal on re-assessment two months after presentation.


A 59-year-old woman presented to an outside hospital with dysuria, weakness, and diarrhea for 10 days prior to presentation. Her pertinent medical history included hypertension, hyperlipidemia, coronary artery disease status post drug eluding stent to the right coronary artery with residual 60% disease in the left anterior descending artery, chronic obstructive pulmonary disease, and craniopharyngioma status post resection complicated by pan-hypopituitarism. She was an active smoker with a 40 pack-year history but denied alcohol or illicit substances.
Initial examination included a normal blood pressure, pulse of 46 beats per minute, temperature of 91.6 degrees Fahrenheit, and saturating 92% on room air. She had occasional scattered rhonchi on lung exam and no murmurs, rubs or gallops on cardiac exam. She did not have jugular venous distension, and no peripheral edema. Chest X-ray was without evidence of acute disease and electrocardiogram (ECG) revealed sinus bradycardia. The patient had leukopenia to 2.1 thou/uL and thrombocytopenia to 42 thou/uL. Electrolytes, lipase and lactic acid were normal. Urinalysis was supportive of a urinary tract infection and she was started on antibiotics.
On day three of hospitalization, the patient developed sudden onset of shortness of breath requiring bi-level positive airway pressure ventilation. A computed tomography angiography of the lungs was performed and ruled out pulmonary embolism. Troponins were drawn and were elevated. A repeat ECG was performed (Figure ) revealing a new left bundle branch block (LBBB).
Four hours later, the LBBB resolved. An echocardiogram was performed which demonstrated a new reduction in ejection fraction (EF) of 20% with the wall motion abnormality most prominently in the territory of the left anterior descending artery. There was no apical ballooning noted. At this point, the patient was transferred to our hospital for further management of the new cardiomyopathy with positive cardiac markers.
On arrival, influenza testing was performed and the patient was positive for influenza A infection for which she was started on oseltamivir. The patient then underwent angiography which revealed non-obstructive coronary artery disease. A repeat echocardiogram was then performed within 48 hours of prior with a demonstrated EF of 61%. The patient’s symptoms improved and she was discharged home with close follow-up with her primary care provider.


A 50-year-old Caucasian female with hypothyroidism presented to an outpatient clinic for evaluation after 1 year of fatigue, unplanned weight loss of 10 pounds, proximal hip, and shoulder girdle pain that had not improved with physical therapy and daily NSAID use. A clinical diagnosis of polymyalgia rheumatica was suspected based on findings of proximal hip and shoulder girdle bursitis and the presence of elevated inflammatory markers in the absence of specific antibodies or peripheral synovitis. She had near immediate response to 20 mg daily prednisone with subsequent normalization of her inflammatory markers.
During subsequent rheumatologic review of her medical history, she endorsed a chronic intermittently productive cough with an associated foul taste and smell. Due to this, additional laboratory work and chest imaging were performed (Table : Patient laboratory values).
She denied sick contacts, had no infectious exposures in travel and no previous exposures to tuberculosis. She was a lifelong non-smoker.
An initial chest X-ray revealed an incidental right upper lobe lung mass (Figure ). A malignant process was suspected after a CT scan of the chest revealed a 5.0 cm right pulmonary irregular, spiculated cavitary mass (Figure ) that subsequently showed a PET active right mediastinal lymph node.
The patient elected to undergo a right lung robot-assisted video-assisted thoracoscopic surgery (VATS) wedge resection after non-diagnostic trans-bronchial biopsies. The gross specimen was described as a nodule that measured 1.1 cm at widest dimension and crossed both upper and lower lobes of the lung. Staining of the lesion was negative for IgG and IgG-4 immunopositive plasma cells. Other features of IgG4-related disease such as sclerosis or obliterative vascular patterns were also not identified. Pleura over the mass was red-tan and roughened but did not appear adherent or puckered. Cut surface of the mass was tan-gray with a stellate appearance and had areas of calcification, identified by pathologic analysis as an inflammatory pseudotumor.
The patient recovered from surgery and tolerated a very slow taper of the low dose corticosteroid treatment without recurrence of her presenting symptoms of hip and shoulder girdle pain.


A 48-year-old male with AIDS presented to a community hospital with 3 weeks of increasingly painful oral and perianal lesions after a year of nonadherence with antiretroviral therapy. He was hypotensive and tachycardiac and therefore treated for sepsis with antibiotic therapy. A perianal ulcer and a small ulcer on the anterior midline of the tongue were noted. Intravenous (IV) acyclovir was initiated for presumed herpes simplex virus (HSV). The patient was discharged on oral acyclovir after clinical improvement. His CD4 lymphocyte count was 24 cells/mm3. Antiretroviral therapy (ART) consisting of lamivudine, dolutegravir, darunavir, and ritonavir was initiated during the admission.
Two days after discharge, he presented to our hospital with worsening rectal pain, fevers, and chills. He was restarted on acyclovir intravenously, and dermatology was consulted. A 4-cm shallow ulcer on the perianal buttock with fibrinous yellow exudate and raised margins was noted (Figure ) and biopsied. Histopathology revealed interface dermatitis with basal vacuolization as well as spongiosis and scattered dyskeratotic cells (Figure ). Periodic acid-Schiff, cytomegalovirus (CMV), Grocott's methenamine silver, and Treponema pallidum infectious stains were negative. Laboratory assessment including rapid plasma reagin, direct fluorescent antibody for HSV and varicella zoster virus, CMV DNA polymerase chain reaction (PCR), and HSV PCR and culture were all negative. A CT abdomen/pelvis performed due to abdominal discomfort did not reveal an etiology of his pain and fever.
Concern for gastrointestinal bleeding prompted an esophagogastroduodenoscopy, which revealed an esophageal ulcer. Colonoscopy revealed punched out ulcers with raised borders and complex bases exposing underlying muscular mucosa at the cecum, ascending colon, and hepatic flexure. Colonic biopsies were negative for CMV, cryptococcus, and histoplasmosis infection; histology revealed ulceration with surrounding inflammation.
His multifocal ulcerative disease was treated with methylprednisolone intravenously followed by an oral prednisone taper with subsequent clinical resolution.


In November 2014, a 53-year-old woman with a history of depression was admitted to a regional hospital after resuscitation as a result of a suicide attempt by strangulation, where hypoxia led to the development of a malignant brain oedema. She was afebrile on admission and showed a normal chest radiograph along with microbially negative urine and tracheal secretion. On the sixth day of hospitalisation, she showed clinical signs of bacterial infection (CRP 93.4 mg/l, leukocyte count 17.3 × 109/l), with a chest X-ray showing suspected infiltrate in the basal part of the right lung. A standard microbiological examination was then carried out in conjunction with empiric antibiotic therapy (amoxicillin clavulanate 1.2 g á 8 h i.v.). Forty-eight hours later, Klebsiella pneumoniae and Escherichia coli, susceptible to all tested antibiotics except ampicilin - i.e. strains which did not meet generally accepted multidrug-resistance criteria, without ESBL production - were detected in the sputum along with microbially negative urine. Not having any pre-existing diseases, after 10 days in the ICU on mechanical ventilation, she was identified as a potential brain-dead organ donor and transported to the TC for further examination (echocardiography, coronarography), instrumental confirmation of brain death and possible organ procurement.
On admission to the TC, the patient was mechanically ventilated, achieving adequate ventilation and oxygenation status (tidal volume 500 ml, respiratory rate 12/min, FiO2 0.4, SpO2 99%); perfusion pressure was maintained with norepinephrine at a maximum dose of 0.05 mcg/kg/min. Laboratory results indicated an increase in inflammatory parameters except for procalcitonin (CRP 227 mg/l, leukocyte count 17.3 × 109/l, PCT 0.35 ng/ml), requiring blood cultures to be sent for microbiological examination before organ procurement, no other samples were taken. However, since she was afebrile and her chest radiograph was normal, there was no clinical evidence of infection. Because organ procurement was initiated just 4 h after admission and the results of the new microbiological examination were not available at that stage, no changes were applied to the primary antimicrobial therapy given to the donor. ICU care of the donor and multi-organ procurement were performed in the standard manner according to current guidelines, with the heart, liver, kidneys and pancreas all procured for islet isolation.
The organs were transplanted to 5 different recipients. All transplantation procedures were performed in the same TC and in a routine manner using standard techniques. Antibiotic prophylaxis (3 doses of cefuroxime 1.5 g i.v. á 8 h for kidney transplantation, piperacillin-tazobactam 4.5 g á 8 h i.v. for 3 days for liver transplantation, piperacillin-tazobactam 4.5 g i.v. single dose before Langerhans islet transplantation, ceftriaxone 1 g á 12 h for 2 days for heart transplantation) and immunosuppressive therapy were applied for all recipients according to routinely used organ-specific protocols and appropriately modified based on the level of immunological risk in each individual patient.
The first kidney recipient was a 60-year-old male on haemodialysis with end-stage kidney disease (ESKD) caused by diabetic nephropathy and a history of tricuspid valve replacement and atrial fibrillation. Since it was his second kidney transplantation, his immunological risk was considered high. The immunosuppression protocol consisted of thymoglobulin, tacrolimus, mycophenolate mofetil and prednisone, with induction by thymoglobulin and methylprednisolone. Cefuroxime 1.5 g á 8 h i.v. was used for antibiotic prophylaxis. On the first postoperative day, the patient suddenly developed haemodynamic instability with signs of both left heart failure and severe sepsis. Immunosuppression therapy was withdrawn and antibiotics were changed to meropenem 2 g á 8 h i.v. and amikacin 1.5 g á 24 h i.v.. Septic shock treatment – inotropes, vasopressors, fluid management and renal replacement therapy – was initiated immediately. On the second postoperative day, surgical intervention was performed due to visceral ischaemia. The patient died on the second day after kidney transplantation secondary to severe septic shock and multi-organ failure (MOF). On the third day after transplantation, microbiology (surgical samples cultures and blood cultures) confirmed the presence of ESBL producing Klebsiella pneumonia and ESBL producing Escherichia coli in the kidney graft.
The second kidney recipient was a 32-year-old male on peritoneal dialysis with ESKD due to glomerulonephritis and a history of recurrent peritonitis requiring antibiotic treatment. Because this was his third kidney transplantation and his immunological risk was extremely high, plasmapheresis was performed prior to surgery. Immunosuppression was induced by thymoglobulin (3 doses in total according to protocol) and intravenous immunoglobulin, and maintained by tacrolimus, mycophenolate mofetil and prednisone. Cefuroxime 1.5 g á 8 h was initially used as prophylaxis, as in the first kidney recipient. On the first postoperative day, the patient showed signs of bleeding, and on the second postoperative day he suddenly developed both haemorrhagic and septic shock caused by a strangulated sigma loop via the peritoneal catheter. As with the first recipient, immunosuppression therapy was discontinued, meropenem 2 g á 8 h i.v. and metronidazole 500 mg á 8 h i.v. administered, and emergency surgery performed. Despite sepsis treatment, volume substitution including blood products, and renal replacement therapy, the patient died on the third day after transplantation secondary to MOF caused by hypovolemic and septic shock. Microbiological examination (surgical samples cultures, drain secretion cultures) showed the same results as those of the first kidney recipient.
The liver recipient was a 49-year-old male with hepatitis B virus-related cirrhosis with portal hypertension and a Model for End-Stage Liver Disease score of 19. He was admitted to hospital 10 days before transplantation because of a ruptured umbilical hernia resulting in peritonitis, which was treated by cefotaxime for 10 days. Immunosuppression consisted of methylprednisolone induction, tacrolimus, mycophenolate mofetil and prednisone. Antibiotic prophylaxis consisted of piperacillin-tazobactam 4.5 g á 8 h i.v. administered over 3 days. The patient exhibited no postoperative complications. On the second day after transplantation, ESBL-producing Klebsiella pneumoniae was found in the drain secretion. Antibiotics were therefore changed to meropenem 1 g á 8 h i.v. for 8 days. At the time of writing, the patient is still alive with good graft function.
Langerhans islets were transplanted to a 59-year-old female with type I diabetes mellitus complicated by daily episodes of hypoglycaemia and chronic kidney disease. Immunosuppression was induced by thymoglobulin and methylprednisolone and maintained by tacrolimus and rapamycin. The recipient was administered piperacillin-tazobactam 4.5 g i.v. single dose for prophylaxis. On the first day after transplantation, she developed severe haemorrhagic shock with extreme blood loss. This was followed by the development of sepsis due to pneumonia on the second day after transplantation, accompanied by acute kidney injury leading to MOF. The patient underwent several emergency surgeries. ICU treatment was based on immunosuppression withdrawal, antibiotic therapy (piperacilin-tazobactam 2.25 g á 6 h i.v. because of extracorporal renal replacement therapy and metronidazole 1 g á 8 h i.v., changed on the 4th day to meropenem 1 g á 6 h i.v. for 10 days and amikacin - dose adjusted according to serum level á 24 h i.v. for 10 days) and treatment of hypovolemic and septic shock, consisting of blood products, mechanical ventilation and haemodialysis. On the second day after transplantation, ESBL-producing Escherichia coli was detected in her sputum, and on the third day ESBL-producing Klebsiella pneumoniae was found in her blood cultures. After 81 days in-hospital, the patient was discharged despite the failure in function of the transplanted Langerhans islets. She subsequently underwent another, successful islet transplantation.
The heart allograft recipient was a 40-year-old male suffering from dilated cardiomyopathy and cardiorenal syndrome. Immunosuppression consisted of thymoglobulin and methylprednisolone as induction, with thymoglobulin, tacrolimus, mycophenolate mofetil and methylprednisolone for maintenance. Ceftriaxone 1 g á 12 h i.v. for 2 days was initially used for prophylaxis, but because of infectious complications to the other recipients, meropenem 1 g á 6 h was administered on the third post-transplant day, this treatment was maintained for 10 days. No complications or positive microbial findings were recorded for this patient. He is presently alive with good graft function (Table ).
In summary, 4 out of 5 recipients developed donor-derived infectious complications within 48 h post-transplant (Fig. ). While bacteria of good susceptibility were found during the primary microbiological examination of the donor on the sixth day in ICU, MDR strains (both ESBL Klebsiella pneumoniae and ESBL E. coli) were found in the transport medium in which the organs (kidney and Langerhans islets with duodenum) were stored during organ procurement, but not in the blood culture taken before procurement. In the samples of both kidney allograft recipients, the Langerhans islet recipient, and the liver recipient, the same MDR bacteria were detected on the third postoperative day. Pulsed field gel electrophoresis confirmed the identity of these bacterial strains. Using PCR the presence of extraintestinal virulence factors pap C, sfa/focCD (adhesins) and gimB (invasin) was detected in ESBL E. coli. The graft perfusion solution (Custodiol) was microbially negative. Secondary contamination during organ procurement/transplantation was ruled out (Tables and ).


A 50-year-old African-American male with no significant comorbidities and not on any medications presented to the emergency department with complaints of three days of worsening epigastric pain. The pain was dull, non-radiating and 10/10 in intensity, associated with nausea and three episodes of vomiting. There was no history of similar pain episodes in the past. He was a chronic smoker and consumed a bottle of beer a few days in a week with the last drink six days prior to presentation. On examination, the patient was found to have a BMI of 29. He was in distress due to pain (10/10) but was alert and oriented. The patient was tachycardic with a heart rate of 102 beats/minute; other vitals were stable. An abdominal examination revealed epigastric tenderness with no rebound tenderness and negative Murphy's sign. Bowel sounds were sluggish with no palpable organomegaly or lumps. Cardiovascular and respiratory system examination revealed no abnormalities.
The patient was kept nil by mouth, and aggressive intravenous fluids were administered. Morphine was given for pain. Investigations were ordered in the line of the acute abdomen. Lipase was high: 1796 U/L (normal range 0-160 U/L). Other significant lab findings were leukocytosis of 12,800 per cu mm (normal range:4500-1100 per cu mm), hematocrit of 47% (normal range 40-54%), and blood glucose of 300 mg/dl. Arterial blood gas (ABG) analysis showed anion gap metabolic acidosis with a pH of 7.1 (normal pH:7.35-7.45), HCO3 of 8.3 mEq/L (normal range 22-28 mEq/L), and PCO2 of 20 mm Hg on room air (normal range: 38-42 mm Hg). Besides sodium (Na) of 132 mEq/L (normal range 135- 145 mEq/L), all other electrolytes were normal. HBA1c was 10.7% (normal range: 4-5.6%). All these metabolic abnormalities were questionable given the mild presentation of acute pancreatitis. However, urinalysis showed ketonuria and glycosuria. Based on lab parameters and ABG analysis, a diagnosis of DKA was made. He was transferred to the ICU for closer monitoring. Insulin infusion and IV fluid were started. Meanwhile, imaging finding by ultrasonography (USG) abdomen showed inflamed pancreas and no gallstones. CT of the abdomen (Figures -) showed inflammation surrounding the pancreas compatible with acute pancreatitis. No focal fluid collection was seen. No other acute abnormalities were observed in the abdomen or pelvis. Lipid profile showed a high TG level of 1226 mg/dl and a high LDL cholesterol of 307 U/L. TG level declined from 1226 mg/dl to 193 mg/dl after treatment with IV insulin in two days. After the closure of the anion gap and when the patient was able to tolerate feeding, diet was started and gradually advanced as tolerated. Anti GAD 65 Ab was tested, which was negative, favoring type 2 diabetes. The patient was discharged on bolus and basal insulin and atorvastatin.


A 17 months old girl presented with trembling voice, opsoclonus, head tremor, unsteadiness and ataxia for one month (Table ). Routine laboratory results demonstrated a leukocytosis (22,850 cells per μl) while all other parameters were within normal limits. Abdominal ultrasound was unremarkable. Based on clinical presentation the patient was suspicious for a neuroblastic tumor and a WB-MRI was performed one day after the presentation (Fig. ). WB-MRI revealed a left-sided paravertebral mass at the level of thoracic vertebrae T 9/10 (2.6 × 1.1 × 2.2 cm), hyperintense in T1 and T2 weighted sequences with low ADC in in diffusion imaging, and strong diffuse enhancement after the administration of gadolinium compound. I-123-mIBG scintigraphy did not reveal any non-physiological tracer uptake. Following thoracoscopic resection of the paravertebral mass, histopathology showed matured neuroblastoma tumor cells with schwannian stroma, consistent with a thoracic ganglioneuroblastoma (Hughes classification: grade 1a). Consequently, treatment with immunoglobulins, steroids, cyclophosphamide and rituximab was initiated. Her regular follow-up examinations were unremarkable without any neurological sequelae.


A 13 months old boy was referred to the department with neurological conspicuities presenting multiple relapses, failure to walk and speak as well as intermittent opsoclonus for a few months (Table ). Abdominal ultrasound examination revealed no abnormal finding. Clinical examination confirmed OMS, laboratory testing showed a slightly increase of lymphocytes (48,000 cells per μl). Urinary catecholamine excretion revealed no pathological increase. In order to rule out neuroblastic neoplasia, an I-123 MIBG scintigraphy was performed, which was negative. Given the persistent clinical suspicion, a WB-MRI was performed (Fig. ), showing a triangular T2-hyperintense mass (1.0 × 1.1 cm) adjacent to the upper pole of the left kidney with mild enhancement in the post-contrast sequences and partially restricted diffusion in the diffusion weighted MRI consistent with a neuroblastic tumor to the left adrenal gland. Following an adrenalectomy, histopathology revealed fibro-muscular tissue infiltrated by neuroblastic tumor nests with focal ganglionic differentiation and adjoining differentiated ganglioneuroma-like schwannian stroma, consistent with an intermixed ganglioneuroblastoma of the left adrenal gland (Shimada system: schwannian stroma-rich ganglioneuroblastoma, intermixed type). Steroid therapy, immunoglobulins, corticotropin and rituximab were initiated for approximately 2 years. In regular follow-up examinations including whole body MRI, no recurrence was detected and urinary tests were negative. Furthermore, neurological anomalies and OMS completely regressed.


A 2 year old boy presented with steroidresponsible OMS and progressive resting and postural tremor and ataxia (Table ). Laboratory testing was within normal range. A 99 m-Tc-Anti-GD2 immunoscintigraphy, performed at the time of diagnosis, was negative. Annual follow-up examinations including recurring clinical examinations, laboratory tests, abdominal ultrasound and urinary catecholamine excretion tests were negative. Due to the persistent neurological symptoms, a WB-MRI was performed at the age of 13 years to preclude a paraneoplastic genesis associated with OMS (Fig. ). The WB-MRI demonstrated a paravertebral right-sided retroperitoneal mass at the level of T11 to L1 (2.9 × 1.5 × 5.4 cm), remarkable hyperintensity in T2 and vigorous contrast enhancement. Complementing I-123-mIBG scintigraphy revealed no abnormality. Following laparoscopic resection, the histopathology demonstrated mature ganglion cells and fibrillary stroma with spindle-shaped cells, consistent with benign ganglioneuroma (Shimada system: schwannian stroma-dominant ganglioneuroma, mature subtype). Intermittent steroid therapy was continued for treatment of residual OMS. In regular follow-up examinations, the patient still presented neurological features and residual OMS, which responded well to steroid therapy.


A 47-year-old male presented to our institution with persistent, progressive low back pain, without any dermatomal radiculopathy, lower extremity weakness or paresthesias, and without point tenderness. The patient failed several weeks of conservative treatment with analgesics and physical therapy, and was then considered for further workup. He then underwent thoracic MRI and was found to have a positive “Scalpel Sign” on T2 weighted sequencing at the T7-T8 level suggesting an intradural extramedullary band of arachnoid tissue causing dorsal thoracic cord indentation, consistent with symptomatic dorsal arachnoid web (Figure ).
Given the persistent, progressive nature of his back pain and an identified surgical target, the patient was offered surgery to excise the dorsal arachnoid web and relieve the locoregional mass effect that this band of tissue was exerting upon the spinal cord.
Operative report
The patient was positioned prone, using a regular table. Neuromonitoring was available for the entirety of the case, and fluoroscopy was utilized to confirm localization of the T7-T8 level. The spinous processes and lamina of T7-T8 were exposed, and a laminectomy was performed. The dura was then opened sharply, exposing the dorsal spinal cord and revealing the arachnoid web (Figure ).
The arachnoid web was then carefully microdisected away from the dorsal spinal cord and was removed in entirety. There was an immediate improvement in dorsal column SSEP after the dorsal web was lysed. The dura was then approximated with watertight closure and a post-surgical drain was placed.
Post-operative course
The patient remained at his neurologic baseline post-operatively, having full strength in his upper and lower extremities. There was no loss of sensation postoperatively; however, the patient had immediate relief from his low back pain. The drain was then removed, and the patient underwent a routine postoperative course with physical therapy and occupational therapy, prior to successful discharge to home. With the improvement in his low back pain, the patient no longer required the use of oral analgesia to rectify his pain as of clinic follow-up one month after surgery.


The patient was a 41-year-old male with a past medical history of unspecified congenital heart disease, hypothyroidism, and hypogonadism (taking intramuscular testosterone injections twice weekly), who presented with a chief complaint of chest pain during exertion of 1-month duration. The pain was described as 10 out of 10 in intensity, burning with a band-like tightness in nature, and located in the epigastric area with radiation toward the substernal region. His initial cardiac enzymes were significant for a troponin level of 0.62 ng/mL. His B-type natriuretic peptide (BNP) level was 1,190. An electrocardiogram (ECG) revealed a sinus rhythm with right superior axis deviation, biatrial enlargement, and right ventricular hypertrophy. Further evaluation with a TTE revealed that the patient had a LVEF of 20-29% with a markedly dilated left atrium and left ventricle. Subsequently, a cardiac catheterization did not reveal evidence of obstructive coronary artery disease. Given the trivial history of congenital heart disease and nonischemic cardiomyopathy, a cardiac MRI was then conducted and revealed a noncompacted to compacted myocardium ratio of greater than 2.3 in the left ventricle, global hypokinesis with severely depressed left and right ventricle ejection fractions of 27% and 26%, biatrial enlargement, and no evidence of a left ventricular thrombus (Figures and ). His hospital course was complicated by an episode of nonsustained ventricular tachycardia, which given his LVNC and low ejection fraction, placed him at an elevated risk for SCD. The patient subsequently received an internal cardiac defibrillator (ICD) and was discharged home with aspirin, beta blocker, angiotensin-receptor blocker, and anticoagulation therapy with warfarin.


A 2-month, 24-day-old girl was referred to our department presenting with recurrent vomiting. The birth and medical history were uneventful. The patient had metabolic acidosis (pH 7.267, bicarbonate 17.6 mmol/L), alkaline urine (pH 7.5), and hypokalemia (serum potassium 2.4 mmol/L). An ultrasound of the kidneys demonstrated increased echo reflectance at the bilateral medulla. The patient was initially given common treatments to replace fluids and to correct the acidosis and hypokalemia. However, the metabolic acidosis and hypokalemia remained during for 4 days (Table ). Meanwhile, the hearing, liver function, renal function, count of blood cell, C-reactive protein, and erect abdominal x-ray results were normal. Because hereditary dRTA was suspected, the patient was treated with potassium citrate on day 5 after admission. Since treatment initiation, the patient has shown normal pH and potassium levels.
Genomic deoxyribonucleic acid (DNA) was extracted from whole blood using the QIAamp DNA Mini Kit (Qiagen, Shanghai, China) per the manufacturer's instructions. A minimum of 3 μg DNA was used for the indexed Illumina libraries according to the manufacturer's protocol (MyGenostics, Inc., Beijing, China). DNA fragments with sizes ranging from 350 bp to 450 bp and those including the adapter sequences were selected for the DNA libraries. Next, the genes associated with the endocrine system were selected using a gene capture strategy and the GenCap custom enrichment kit (MyGenostics, Inc., Beijing, China) following the manufacturer's protocol. The biotinylated capture probes (80–120-mer), were designed to tile all of the exons with non-repeated regions.
The patient was found to have a homozygous deletion in exons 13 and 14 of the ATP6V0A4 gene, which confirmed the diagnosis (Fig. ). Moreover, quantitative real-time polymerase chain reaction (PCR) (qRT-PCR) of exons 13 and 14 from the ATP6V0A4 gene using 3 primer pairs was performed on both the patient and her parents using a SYBR@Premix Ex TaqTM (TAKARA, Japan). The Applied Biosystems 7500 real-time PCR system was applied to amplify and quantify the ribonucleic acid (RNA). The relative RNA quantity was calculated based on the comparative Ct and analyzed by the Sequence Detection System software package version 2.0 (PE Applied Biosystems, Carlsbad, CA). The patient's father was found to have a heterozygous deletion of the same regions whereas the mother was found to be normal (Fig. ).
The parents of the patient have permitted and provided written consent for the publication of this medical data.


A 52-year-old man was admitted to the hospital on emergency basis due to symptoms of chest tightness for 5 years and palpitation aggravated for 5 days. The patient reported a history of chest tightness, shortness of a breath, and occasional headache persist for 5 years after fast walking, climbing stairs, fatigue, anger, and the symptoms could be alleviated 1 or 2 minutes later. In November 2011, he came to the hospital for a recurrent and unknown chest tightness. Coronary angiography examination observed that both left anterior descending coronary artery (LAD) and left circumflex branch (LCX) morphed into mild stenosis (Fig. ). The coronary atherosclerotic heart disease was diagnosed, and no change of blood was found in the routine exam (white blood cell count, 9.1 × 109/L; hemoglobin, 165 g/L; and platelets, 272/ × 109/L). After discharging from the hospital, the doctor prescribed him aspirin (100 mg QD), clopidogrel (75 mg QD), atorvastatin (20 mg QD), and metoprolol (12.5 mg BID) for secondary prevention of CHD, but he did not take the medicine as directed.
In July 2012, the patient came back to the emergency department because of chest pain and the other symptoms significantly worsened than ever. Physical examination of normal vital signs revealed there was no obvious petechiae or blood spots found on his skin. Then the patient underwent coronary angiography examination, and the result showed an aggravation of stenosis (Fig. ), so did percutaneous transluminal coronary angioplasty and placement of 1 drug-eluting stents in the LAD (Fig. ). His chest pain and pathological changes quickly resolved by PCI procedure, and on a regimen of aspirin (100 mg QD), clopidogrel (75 mg QD).
One day later, he was found to have unknown pancytopenia (hemoglobin, 6.9 mg/dL; white blood cell count, 3.4 × 109/L; and platelets, 12 × 109/L), for which no explanation was found and suspected to have hematological diseases. A bone marrow aspirate and biopsy were performed to evaluate thrombocytopenia and it showed the abundance of immature myeloid cells with coalescent granules. Histochemical staining showed the myeloid cells stained positive with myeloperoxidase, so the patient was diagnosed with AML, and the AML was identified as AML-M2 (World Health Organization classification M2; Fig. ). Cytogenetic karyotypes revealed 88 to 91,XX,YY,2 × t(8;21)(q22;q22)[20], immunophenotype suggested myeloid expression with HLA-DR, CD13, CD15, CD19, CD33, CD34, CD38, CD56, CD64, CD117, CD123, MPO (Fig. ). Notably, PML/RARa fusion genes were no expression, but ETO fusion genes were expressed as 4.59 × 104. Besides, the mutation testing of C-KIT, FLT-3, and NPM1 was negative. The patient received 7 cycles of IA (idarubicin 10 mg D1-3, cytarabine 200 mg D1-7) and HD-Ara-C (high dose cytarabine, 2000 mg D1,3,5) scheme chemotherapy, and he was in complete remission after chemotherapy (Figs. and ). To prevent stent thrombosis, the patient received clopidogrel (75 mg QD) monotherapy when the platelet counts between 60 and 100 × 109/L, and combined aspirin (100 mg QD) when the platelet counts greater than 100 × 109/L, wherever stopped all the antiplatelets when the platelet counts less than 60 × 109/L. The disease-free survival in the patient has been over 6 years, and the patient is still being followed up in clinic.