CJ is a 49 year-old transgender male and has been on hormone therapy for over 11 years. CJ’s diet or physical activity level has not changed over the years in relation to his transition. He comments, “I don’t think transitioning has changed anything about the way I eat, really.” Rather, his diet fluctuates more so in relation to his income and employment benefits.
CJ has a BMI of 31 kg/m2, body fat percentage of 30% and waist circumference of 42 in., indicating obesity class I and central adiposity. He has a low risk of eating disorders (2/26 on the EAT-26) and yet a low degree of eating competence (26/48 on the EAT-26). CJ’s dietary pattern includes 3–4 eating instances per day at home, restaurants, or in his car. He consumes 0–3 servings of fruits and vegetables per day and added sugars in the form of candy, pastries, cookies, and coffee drinks. His beverage intake also includes low carbohydrate energy drinks.
CJ’s diet analysis was characterized by marginally high energy (112% kcal needs), high saturated fat (18% total kcals), low fiber (49% AI) and high sodium (205% DGAs limit). His macronutrient intake was 38% carbohydrate, 50% fat and 12% protein, or lower in carbohydrate and higher in fat than the AMDR ranges. CJ’s micronutrient intake reflected marginally high calcium (111% RDA), low vitamin D (3% RDA), low potassium (18% AI) and high iron (158% RDA).


GJ is a 51 year-old transgender male and has been on hormone therapy for 7 years. His diet has not changed much throughout his transition. He notes, “It’s pretty much been the same throughout.” GJ points out that much of the LGBT social community is centered around bars and that “you end up having a lot of calories of alcohol … if you center around a bar, you know, your eating habits and drinking habits are not the greatest.”
He has a BMI of 39 kg/m2, body fat percentage of 34% and waist circumference of 44 in., indicating obesity class II and central adiposity. He has a low risk of eating disorders (8/26 on the EAT-26) and yet a low degree of eating competence (23/48 on the EAT-26). GJ’s dietary pattern includes 3–4 eating instances per day. He consumes 0–2 servings of vegetables per day and sugar-sweetened foods and beverages in the form of soda and cookies. His beverage intake also includes 0–3 alcoholic drinks per day.
GJ’s diet analysis was characterized by adequate energy (109% kcal needs), appropriate saturated fat (7% total kcals), low fiber (39% AI) and high sodium (155% DGAs limit). GJ’s macronutrient intake was 64% carbohydrate, 24% fat and 8% protein, or slightly lower in protein than the AMDR ranges. Additionally, 4% of his kcals were derived from alcohol. GJ’s micronutrient intake reflected low calcium (22% RDA), low vitamin D (0% RDA), low potassium (9% AI) and low iron (70% RDA).


A 56-year-old woman presented with a dimpling breast lump for 6 months. She had no family history of breast and other cancers. Physical examination revealed a discrete mass at the middle inner quadrant of the right breast. Mammography showed a high-density mass of 2.3 cm in diameter with segmental microcalcifications and specular borders that caused slight skin retraction (). Ultrasound demonstrated an ill-circumscribed and hypoechoic mass of 2.2 × 2.1 cm in size with decreased posterior echo (). Enhanced computed tomography suggested multiple metastases to the right axillary lymph nodes. No metastasis to the other organs was noted. Core needle biopsy revealed an IC-NST with IMPC components. Furthermore, fine needle aspiration cytology from the right axillary lymph node detected adenocarcinoma, indicating metastasis. Radical mastectomy with lymph node dissection was performed about 1.5 months after her first visit. Postoperatively, the patient received various chemotherapy treatment for 9 months, such as 4 cycles of epirubicin and cyclophosphamide, 4 cycles of docetaxel, and 25 cycles of radiation. Then, antihormonal therapy with letrozole has been administered to date, without signs of recurrence during the follow-up period of 14 months.
To examine reverse polarization, the histopathology of the background IC-NST that is regarded as the origin of IMPC components was examined. Immunohistochemistry was performed with serial tissue sections, using Leica Bond-Max (Leica Biosystems, Australia). The characterization and staining protocol of each antibody for ANX A2 (catalogue number, 610068) and MUC-1 (catalogue number, NCL-MUC-1) have been described previously [, ]. Mouse anti-human EMA antibody (clone, GP 1.4; catalogue number, NCL-EMA; Leica Microsystems, UK) was used at a dilution ratio of 1 : 500, after a 10 min heat antigen retrieval with a citrate-based solution (pH 6.0). To detect apoptosis, the mouse monoclonal antibody M30 CytoDEATH (clone, M30; catalogue number, 12 140 322 001; Roche Diagnostics, Germany) was used at a 1 : 100 dilution ratio, after a 20 min heat antigen retrieval with an EDTA-based solution (pH 9.0). This antibody detects caspase cleavage products of cytokeratin subtype 18 in apoptotic glandular epithelial cells, including adenocarcinoma cells, and is considered to be more specific and reliable than the TUNEL assay [].


A 40-year-old female patient was admitted to our hospital for conspicuous vaginal sero-hematic secretions. Anamnestic information asserted that the patient previously received three endometrial curettage after a surgical abortion procedure. Histological examination after each endometrial curettage showed regression of chorionic villi and decidualization of the endometrium and the diagnosis of placental rests retention was made. After being admitted for conspicuous vaginal sero-hematic secretions, the patient received a further curettage in order to assess the possible retention of placental rests. The histological evaluation did not show any retention of chorionic rests, but demonstrated an endometrial and myometrial diffuse chronic inflammatory infiltration, with an extensive background of hyaline stroma. The inflammatory infiltrate showed a variegate composition, being made of lymphocytes, plasma cells and occasional polymorphonuclear leukocytes, but the majority of the cellular elements was represented by histiocytes with abundant granular cytoplasm and basophilic inclusions, morphologically relatable to the so called von Hansemann cells (Fig. ). Periodic acid-schiff (PAS) reaction highlighted a diffuse cytoplasmic staining in von Hansemann cells (Fig. ). The immunohistochemical analysis revealed that those elements were strongly positive for CD68 (Fig. ) and negative for CK-pool (Fig. ). On the basis of morphological, histochemical and immunophenotypical evidence, the histological diagnosis of malacoplakia was made, excluding uterine neoplasms and other differential diagnoses. In the following months, due to relapse of clinical manifestations, nonetheless administration of antibiotic drugs, the patient underwent two further uterine curettage, with the diagnosis of recurrent endometrial malacoplakia.


After obtaining written informed consent from the participant for the publication of this case report, we here describe a 38-year-old female patient presenting with a high incidence of polymorphic VEBs on a 24-hour rhythm monitoring (Holter) referred to our Cardiology Service. At the time of presentation, the patient was complaining of fatigue in response to minor and medium efforts and not tolerating any physical activity, and episodes of tachycardia associated with dyspnoea, pre-syncope, and syncope. This was associated with LV hypertrophy on her echocardiogram. She was hospitalized twice due to events of syncope. The episodes started ∼1.5 years ago. She was on bisoprolol 10 mg/d since the beginning of her VEBs. However, her attending physician tried to prescribe metoprolol which she did not tolerate because of her low blood pressure (BP) (111/73 mm Hg, measured in our office) mm Hg, also occurring when she was prescribed sotalol or verapamil. Subsequently, amiodarone was started, but she presented with ophthalmological side effects (perception of colored halos and blurred vision), and the antiarrhythmic medication was discontinued.
Her cardiac magnetic resonance imaging showed an average thickness of the LV inferior-lateral segment, a mild increase in the LV diastolic diameter (5.4 cm, standard range 3.9–5.3 cm), the right ventricle (RV) end-diastolic volume index and the RV end-systolic volume index were reduced (55.1 mL/mm3, standard range between 62 and 88 mL/mm3; and 33.1 mL/mm3, standard range varying between 19 and 30 mL/mm3, respectively). Her RV ejection fraction was 40% (normal range: 40%–60%), while her LV ejection fraction was 58.8% (normal range: 50%–70%). No signs of myocarditis, fibrosis, or myocardial necrosis were detected. A 24-hour Holter on bisoprolol 10 mg/d was performed at baseline (Table ).
In a joint decision with the patient and her attending physician, we decided to perform a 2-staged catheter ablation procedure. Electrocardiographically, one type of ectopic morphologies, suggested the RVOT as the site of origin. We; therefore, started from the RVOT ectopic beats ablation. In summary, through the Velocity-Ensite 3D mapping system (St. Jude Medical, St. Paul, MN) we detected the highest precocity point at the RVOT (intracavitary electrogram 30 ms earlier than VEBs). We performed thermo-controlled radiofrequency (RF) applications in the region (Fig. ), and 30 minutes post the last RF application, even in the presence of adrenergic medications, no ectopic activity from the RVOT was observed. No complications occurred, and the patient could be discharged the next day. One month post-procedure, the 24-hour Holter on bisoprolol 10 mg/d was repeated (Table ).
After 4 months post-ablation, we scheduled the second procedure. The patient underwent general anesthesia by the anesthesiologist and presented sinus rhythm with frequent VEBs originating from LV. Electrocardiographically, VEBs morphology suggested the free lateral wall of the LV as their site of origin. We performed a transseptal puncture, and positioned the decapolar catheter in the LV, performing the electro-anatomical mapping and reconstruction of this cavity using the aforementioned mapping system. We mapped the LV and found the point of highest precocity on its free lateral wall (Fig. ). Subsequently, the ablation catheter replaced the mapper catheter into the LV, and RF applications were performed on the free lateral wall of the LV. This resulted in activation of the sites at these moments (NSVT on the ablated sites) and substantially reduced the VEBs from this region. As a final step, we chose to perform percutaneous RDN using the EnligHTN system (St. Jude Medical), aiming to achieve blunting of the sympathetic drive and try to reduce the patient‘s baseline HR and frequency of remaining left VEBs (Fig. ). Neither cardiac nor vascular complications resulted from the procedures. The patient was discharged 24 hours post-procedures, presenting clinically stable and walking without difficulty.
Three months post-procedure, she underwent another 24-hour Holter off all concurrent medication (Table ). Also, her mean blood pressure (BP) value taken in our office remained stable at 109/76 mm Hg. Thus far, 18-months follow-up, she has been asymptomatic and doing physical exercises.


A 33-year-old man was hospitalized on October 10, 2018 for progressive fever lasting for 7 months. He presented with a temperature of 38°C to 40°C; swelling and pain in the wrists, knees, and ankles; and the purpura in the skin of the lower extremities. He had a previous medical history of congenital heart disease with a congenital ventricular septal defect (VSD). During examination, grade 3/6 systolic murmurs were heard in the mitral valve area, and skin petechia was noted in the lower limbs.
Blood tests revealed an increase in creatinine level from a baseline of 0.86 mg/dL (76 μmol/L) to 3.92 mg/dL (347 μmol/L) (reference range [RR] 57–97 μmol/L) over 10 days. Blood and protein appeared to be positive from urinalysis, and cytoplasmic ANCA (C-ANCA) 1:10 (RR < 1:10), PR3 level of 176.32 AU/mL (RR, 0–15 AU/mL). The measured anti-beta 2 glycoprotein I (β2GPI) level was 73 RU/mL (RR, 0–20 RU/mL). The antinuclear antibody test results were negative. The erythrocyte sedimentation rate and C-reactive protein level were elevated at 49 mm/h (RR < 10 mm/h) and 72.8 mg/L (RR < 20 mg/L), respectively. Virologic and fungal test results were negative. The complement C3 level was low at 0.67 g/L (RR, 0.9–1.8 g/L). A full blood count showed a hemoglobin level of 80 g/L, a white blood cell count of 7.26 × 109/L, and a platelet count of 62 × 109/L. Multiple blood cultures were positive for viridans streptococcus.
Splenomegaly was confirmed by ultrasound. Computed tomography of the chest revealed multiple nodules in each lobe of both lungs, about 0.5 to 1.5 cm in size, with a small amount of pleural effusion on both sides. Doppler echocardiography showed no valve vegetations. However, the continuity of the periventricular septal membrane was interrupted, and a 5.7-mm-wide defect had formed, reflecting the patient's congenital heart disease-ventricular septal defect. Kidney biopsy showed necrotizing glomerulonephritis with crescentic glomerulonephritis and interstitial nephritis. Immunofluorescence staining showed the tissue was IgA (+/−), IgG (−), C3 (−), C4 (−), C1q (−), and Flb (−), and electron microscopy showed no deposits (Fig. ).
The patient was treated initially with antibiotics, followed by moxifloxacin 3 days later, based on the drug sensitivity test result. The patient's fever subsided soon after initiation of antibiotics, but his platelet count, erythrocyte count, and ANCA index did not improve. Furthermore, progressive renal insufficiency developed, and his serum creatinine level increased to 417 μmol/L after 7 days. A subsequent renal biopsy revealed crescentic glomerulonephritis and interstitial nephritis with negative immunofluorescence (IgA (+/−), IgG (−), C3 (−), C4 (−), C1q (−), and Flb (−)), which is consistent with ANCA-associated pauci-immune glomerulonephritis.
The possibility of pursuing aggressive treatments was discussed with the patient's family based on the discovery of the ANCA-mediated disease (glomerulonephritis). In addition to antibiotics, he received intravenous corticosteroids (methylprednisolone, 40 mg/d) and intravenous immunoglobulin therapy. On this regime, his purpura, joint pain, and renal failure reversed rapidly, and his strength and nutrition recovered. Repeated cardiac ultrasound showed no valve vegetations. Subsequently, the corticosteroid dose was rapidly reduced to 30 mg/d given the patient's rapid improvement. And the patient received oral prednisolone first at 20 mg daily for 5 days and then at 10 mg daily for 5 days consecutively.
However, 4 months later, the patient experienced disease relapse, with the return of fever, purpura rash, weakness, and edema of the lower limbs. The patient was rehospitalized. Re-examination of cardiac ultrasound showed several patchy strong echoes at the right ventricular part of the septal defect in the heart, which swayed slightly with the cardiac cycle, indicating the formation of vegetations at the septal defect. Abdominal ultrasonography suggested that the spleen was greatly enlarged. Subsequent investigations revealed that the C-reactive protein level was elevated to 74.7 mg/L. C3 was low at 0.17 g/L, C4 was 0.04 g/L (RR, 0.1–0.4). A full blood count showed a hemoglobin level of 44 g/L, a white blood cell count of 2.4 × 109/L, and a platelet count of 99 × 109/L; as well as a serum creatinine level of 729 μmol/L, an ANCA-PR3 concentration of 62 AU/mL, and a C-ANCA ratio of 1:10. The blood culture was also positive for viridans streptococcus.
The patient was treated with antibiotics and intravenous immunoglobulin again. And after the fever had improved, he received a moderate dose of methylprednisolone (60 mg/d) intravenously for 3 days and a low dose of cyclophosphamide (0.2 g/wk), with gradual dose reduction, along with regular dialysis. One month later, after the short-term treatment with the low-dose glucocorticoid combining with continuous antibiotics, the patient's fever and renal insufficiency dramatically improved. We discontinued the intermittent hemodialysis when his creatinine level had reached 276 μmol/L. Then, he received VSD repair and debridement. After the surgery and a series of maintenance treatments, his renal function gradually recovered, with no presentation of edema. The glucocorticoid therapy was gradually reduced until it was stopped. After approximately 6 months without any medications, he remained asymptomatic and was able to live normally. His repeated echocardiogram at the 6-month follow-up was consistent with his postsurgery ultrasound.


A 43-year-old Hispanic male with active smoking history presented with new-onset right-sided scapular pain. Past medical history was negative for cardiopulmonary disease. Physical examination revealed expiratory and inspiratory wheezing over the right upper lung zone. Routine laboratory studies were unremarkable. Chest x-ray (CXR) showed a right middle lobe pleural-based mass with stippled calcification, measuring 12 x 7 cm (Figure ).
This was followed by CT of the chest showing a large irregularly shaped mass in the posterior right hemithorax, which appeared to involve the middle and lower lobes of the lung, abutting the intercostal space between ribs 5 through 8 (Figure ). Additionally, significant intrinsic calcifications were noted within the mass (Figure ).
CT-guided core needle biopsy revealed tumor fragments with partial translucent and opaque white flecks and pink areas in a rubbery to firm consistency. Histopathological examination showed dense collagenous matrix scattered with areas of psammomatous calcifications, nests of plasma cells, few mast cells, eosinophils, and lymphocytes (Figures , ). No atypia or mitotic activity was seen. Immunohistochemistry showed positive expression of cluster of differentiation (CD) 34, B-cell lymphoma 2 (Bcl-2), and patchy staining for CD 99. It was negative for factor XIII a, smooth muscle actin, myosin, desmin, CD 117, anaplastic lymphoma kinase 1 (ALK-1), S-100, cytokeratin (CK) 8/18, or beta-catenin. The proliferative index (Ki-67) was less than 1%. These findings were consistent with CFT. Oncological and thoracic surgery consultations were obtained. Given persistent pain, a large size, the possible involvement of lung causing obstructive symptoms due to compression, and anticipated tumor progression, surgical resection was planned.
The patient underwent thoracotomy. The tumor was firmly attached to the medial aspect of the aforementioned ribs in close proximity to the vertebral transverse process, almost completely decompressing adjoining lung. A 15 x 15 x 10 cm lobulated unencapsulated mass with a smooth, hard white surface was removed along with wedge resection of the involved portion of right upper and lower lobes and ribs 5 through 8 followed by chest wall reconstruction. Microscopically, the tumor was adherent to pulmonary tissue in an intimate relationship with ribs, but without local invasion. The benign tumor cells were notably intermingled with normal rib tissue structures; however, no evidence of cellular invasion was seen (Figure ). Immunohistochemistry of the piecemeal mass confirmed the above findings, with CD 138 positivity in the collection of plasma cells. Postoperatively, the patient’s pain improved; however, he developed hypoxia secondary to recurrent right-sided pleural effusions. Pleural fluid studies revealed a nucleated cell count of 102,880/μL, with 100% neutrophils, 20,000/μL red blood cells, and two out of three positive light’s criteria (lactate dehydrogenase 2,788 U/L and a fluid protein [4.8 g/dL] to serum protein [7.7 g/dL] ratio greater than 0.5) with positive cultures for methicillin-sensitive Staphylococcus aureus.
CT chest showed a large empyema in the right lower lobe requiring multiple invasive procedures for intercostal drainage (Figure ). The patient was started on a six-week course of antibiotics and was discharged with improvement in pleural effusions. Over one year of follow-up, he did not show any signs of recurrence of the tumor.


On March 10, 2020, a 50-year-old man, positive for SARS-CoV-2, was admitted to Wuhan Huoshenshan Hospital (Wuhan, China) after 47 days of cough and fever (). On February 15, nucleic acid results for SARS-CoV-2 were positive. Previous treatments included arbidol (0.2 g, thrice daily) and lianhua qingwen granules (6 g, thrice daily). On admission, peripheral oxygen saturation was 96% in ambient air and respiratory rate was 18 breaths/minute. Immunoglobulin M (IgM) and Immunoglobulin G (IgG) levels for SARS-CoV-2 were, respectively, 53.12 g/L and 173.69 g/L (normal range for both: <10 g/L; Shenzhen YHLO Biotech Co., Ltd., Shenzhen, China). Computed tomography (CT) findings showed a bilateral, scattered, high-density shadow and fiber- and spine-like opacities. From March 10 to 22, convalescent plasma from COVID-19 patients (200 mL, March 17 and 18), recombinant human interferon (0.3 mL, atomized inhalation, once daily), lianhua qingwen granules (6 g, thrice daily), and arbidol (2 tablets, thrice daily) were administered as treatment; on March 23, chloroquine phosphate (2 tablets, twice daily) was administered instead of arbidol. On March 23, SARS-CoV-2 RNA were positive. A CT scan showed substantial improvement, with no obvious pulmonary lesions, on March 24. He was treated with ritonavir-boosted danoprevir (DNVr) alone (100/100 mg, one tablet twice daily). From April 3 to 5, nucleic acid test results for SARS-CoV-2 were all negative. SARS-CoV-2 IgM and IgG levels were markedly reduced (5.38 g/L and 108.68 g/L, respectively). On April 7, he was discharged from the hospital after three consecutively negative SARS-CoV-2 RNA. The duration from positive SARS-CoV-2 RNA to three consecutive negative results was 55 days.


On March 12, 2020, an 81-year-old man diagnosed with COVID-19 was admitted to Huoshenshan Hospital following 50 days of intermittent fever and 40 days of chest distress and shortness of breath (). Type 2 diabetes mellitus, hypertension, and aortic dissection were associated comorbidities. On February 1, nucleic acid results for SARS-CoV-2 were positive. During prior hospitalization, digestive tract bleeding with black stool were observed; a CT scan showed bilateral patch shadow, a small amount of pleural effusion on the right lung, and aortic dissection. On admission, SARS-CoV-2 IgM and IgG levels were, respectively, 20.89 g/L and 187.92 g/L. Treatment included chloroquine phosphate (2 tablets, twice daily) and/or convalescent plasma from COVID-19 patients (400 mL) from March 15 to 26. On March 23, nucleic acid test results were positive for swab. On March 25, the patient’s feces were positive for SARS-CoV-2 RNA. A CT scan showed substantial improvement, with marked reduction of pulmonary lesions, on March 24. On March 27, he received DNVr treatment alone (100/100 mg, one tablet twice daily). On April 5, after three consecutive negative nucleic acid test results, he was discharged and transferred to another hospital for further treatment of comorbidities. The duration from positive SARS-CoV-2 RNA to three consecutive negative results was 65 days.


On March 13, 2020, a 42-year-old male with COVID-19 was admitted to Huoshenshan Hospital with 1 month of cough and fatigue and 10 days of fever (). Prior history included a diagnosis of chronic hepatitis C in 2015 that was successfully cured, with sustained negative results of hepatitis C virus (HCV) RNA. On February 14, nucleic acid results for SARS-CoV-2 were positive. Previous treatments consisted of lianhua qingwen granules (6 g, thrice daily) and ribavirin (900-1200 mg, thrice daily). On admission, CT results showed bilateral, multiple, scattered, and flaky high-density shadows and ground-glass opacities. On March 27, nucleic acid test results were positive. On March 31, a CT scan showed substantial improvement, with marked reduction of pulmonary lesions. On April 3, he was treated with DNVr (100/100 mg, one tablet twice daily). On April 14, he was discharged from the hospital following two consecutive negative SARS-CoV-2 test results. The duration from positive SARS-CoV-2 RNA to two consecutive negative results was 58 days.


On March 29, 2020, a 33-year-old male with COVID-19 was admitted to Huoshenshan Hospital with 64 days of cough, chest distress, and shortness of breath as well as 7 days of backache (). On January 31, CT results showed bilateral ground glass opacities. On February 6, nucleic acid results for SARS-CoV-2 were positive. On March 30, CT results showed bilateral small flocculent densities, ground glass opacities, and a solitary pulmonary nodule in the middle lobe of right lung. Previous treatments included lianhua qingwen granules (6 g, thrice daily), arbidol (0.2 g, thrice daily), and ritonavir-boosted lopinavir (2 tablets, once every 12 hours). On April 2, nucleic acid test results were positive. On April 4, he was treated with DNVr (100/100 mg, one tablet twice daily). On April 14, he was discharged from the hospital following two consecutive negative SARS-CoV-2 test results. The duration from positive SARS-CoV-2 RNA to two consecutive negative results was 66 days.


A 66-year-old male patient with a HeartMate II model LVAD (Abbott Laboratories, Abbott Park, IL) 4 months postoperative from implant was planned for robotic prostatectomy for prostate cancer after multidisciplinary oncologic case discussion, with a goal for a surgical cure in order to obtain candidacy for heart transplantation. His past medical history included viral cardiomyopathy with severe left ventricular dysfunction (EF 20%), ventricular tachycardia status post-implanted cardiac defibrillator (ICD), stage 2 chronic kidney disease, and hypertension.
Preoperative evaluation with a ramp transthoracic echocardiogram (TTE) demonstrated an optimal pump speed of 5300 revolutions per minute (RPM). This type of TTE is a protocolized assessment of LVAD operation during which continuous evaluation of the heart is used to determine an optimal RPM at which the patient’s ventricular function, aortic opening, and cardiac output are optimal []. The TTE showed minimal left ventricular contraction, mild aortic insufficiency with preserved valve opening approximately every 2–3 beats, moderate right ventricular dysfunction, mild tricuspid regurgitation, and no mitral regurgitation. He was admitted to the hospital the night prior to the procedure for LVAD interrogation, which showed flow rate 4.2 L/min, speed 5300 RPM, pulsatility index (PI) 4.5, and power 3.9 W. Pulsatility index is a dimensionless measure of left ventricle (LV) contribution to cardiac output as it describes how pulsatile flow through the pump is at a given time. PI is dependent on the relationship between the pressure generated by the LV and the pressure generated by the LVAD. In a state with low pulsatility index, the left ventricle does not generate a pressure sufficient to exceed aortic root pressure and therefore results in the aortic valve not opening during systole with low PI. ICD interrogation showed no recent VT events, VT threshold at 170 beats per minute with anti-tachycardia pacing available, 10 years battery life, and less than 0.1% ventricular pacing. Anticoagulation was managed with warfarin, physical exam was unremarkable given his past medical history, and electrocardiogram showed normal sinus rhythm.
Warfarin was held the night prior to the surgery. On the morning of prostatectomy, prothrombin international normalized ratio (INR) resulted as 3.2. He was given prothrombin complex concentrate (PCC; CSL Behring, King of Prussia, PA). PT-INR was again drawn upon arrival in the operating room and resulted at 1.4.
The intraoperative team included the urologic surgeon, general anesthesiologist, pharmacist, and a cardiac perfusionist. After placement of ASA standard monitors, a 20-gage right radial arterial line was placed under ultrasound guidance. Central venous access was obtained via the right internal jugular vein. Additional variables monitored included near-infrared cerebral oximetry (INVOS, Medtronic Inc., Minneapolis, MN), bispectral index monitor (Medtronic Inc, Minneapolis, MN), and LVAD power index and rotation speed communicated to the anesthesia team by the cardiac perfusionist.
Anesthesia was induced using fentanyl 1.5 mcg/kg, propofol 1 mg/kg, and rocuronium 1.2 mg/kg, which resulted in relative hypotension that responded to a bolus of 250 ml of 5% albumin. Rapid sequence induction was chosen to rapidly secure the airway and reach a stable plane of anesthesia using a volatile anesthetic (sevoflurane). Albumin was chosen as it is our institutional colloid of choice. Full details of the anesthetic record are provided in Fig. .
Surgical insufflation of the abdomen resulted in an acute rise in blood pressure, which was associated with the decrease in LVAD flow rate and increased power requirement presumed due to high afterload. This was treated with 0.75 mg/kg bolus of propofol and initiation of dobutamine and nicardipine infusions with good effect. The patient was placed in a Trendelenburg position in a stepwise manner while monitoring hemodynamics and LVAD indices. Trendelenburg positioning was associated with a rise in the central venous pressure (CVP), though this was tolerated. The LVAD showed the following parameters: pulsatility index 3.9, flow 4.5 L/min, rpm 5300, and power 3.8 W.
Approximately midway through the procedure, the pulsatility index began to decrease and central venous pressure (CVP) increased by 50%. This generated concern for worsening right ventricular function creating decreased left ventricular and LVAD preload. Cardiac anesthesia was called for intraoperative transesophageal echocardiogram (TEE). TEE demonstrated mild bowing of the intraventricular septum into the right ventricle and moderate right ventricular dysfunction (see Fig. ). Inhaled epoprostenol was initiated to further optimize the right ventricular function. Vasoactive medications (nicardipine; dobutamine) were continued. The LVAD pulsatility index, flow, and RPM returned to their prior values (Table ).
Robotic prostatectomy was completed in the standard fashion. Ten minutes prior to abdominal desufflation, nicardipine infusion was paused and dobutamine infusion rate was reduced. At the time of desufflation, there was an acute drop in arterial blood pressure which required initiation of phenylephrine and epinephrine infusions as well as a crystalloid bolus of 250 ml. Neuromuscular blockade was reversed using sugammadex (Merck, Kenilworth, NJ), and the patient was extubated. All vasoactive medications were able to be discontinued at this time, and the patient was transported to the cardiac surgery intermediate care unit in stable condition.
Postoperatively, he did not require vasoactive infusions. PT-INR was drawn postoperatively at 5 h after administration of prothrombin concentrate and resulted at 1.5. His preoperative dose of warfarin was resumed on the evening of postoperative day 0, and INR on postoperative day 1 was 2.0. The remainder of his postoperative laboratory studies was stable from preoperative values. He was discharged home on postoperative day 2. Subsequent evaluation by urologic surgery has determined that the procedure was curative. He is currently undergoing evaluation for cardiac transplant.


A 69-year-old Hispanic male with a history of type II diabetes mellitus presented to the emergency department with a two-month history of worsening abdominal pain. A computed tomography (CT) scan was ordered, which revealed a 4.3 cm ill-defined, low-density mass in segment 5 of the liver with nonspecific soft tissue encasing the superior mesenteric artery. As per the radiologist's impression, the mass was adjacent to, but did not originate from, the pancreas. No additional sites of disease were seen on a subsequent positron emission tomography (PET) scan. The patient was referred for a liver mass biopsy. At low magnification, the biopsy revealed almost complete destruction of the hepatic parenchyma by irregular glands surrounded by fibrous tissue (). Medium power showed dense pale eosinophilic material separating angulated glands lined by cells with a moderate amount of deeply eosinophilic cytoplasm with round to ovoid hyperchromatic nuclei (). The pale eosinophilic material was also present within the sinusoids of uninvolved hepatocytes (). A Congo red stain was performed, which showed salmon-orange areas around the glands and within the sinusoids and vasculature, some of which showed a globular appearance (). These areas displayed apple-green birefringence under polarized light and surrounded the glands and involved vessel walls (). These findings were consistent with amyloidosis, and the biopsy was sent for mass spectrometry analysis, which revealed a peptide profile consistent with ALECT2- (leukocyte chemotactic factor-2-) type amyloid. The glands were positive for CK7, while negative for CK20, CDX-2, and TTF-1. Given the tumor morphology and CK7 positivity, hepatocellular carcinoma was excluded and no mucin stain was performed. The patient was diagnosed with intrahepatic cholangiocarcinoma (ICC) with hepatic LECT2 amyloidosis.
One month after diagnosis, the patient was started on palliative gemcitabine and cisplatin. After three months of treatment, his CA19-9 decreased from 284 to 103 and the size of the mass decreased from 4.2 cm to 3 cm; however, the degree of vascular encasement worsened. No treatment was given for the amyloidosis. Currently, the patient is alive and tolerating treatment.


A full-term infant weighing 3.11 kg was born at 39 weeks and 4 days gestation age via normal spontaneous vaginal delivery, to a healthy 20-year-old G2P1011 mother. Maternal fever of 38.8°C (101.9°F) was noted 3 hours prior to delivery, with associated fetal tachycardia. However, no other symptoms were noted and maternal history and prenatal labs, including Group B streptococcus, were unremarkable. Spontaneous rupture of membranes with clear amniotic fluid was noted 8 hours prior to delivery. A neonatal team attended the delivery, and routine newborn care was given with Apgar score 9 at both 1 and 5 minutes, respectively.
Our institutional policy at the time was to have a low threshold for maternal SARS-CoV-2 testing in pregnant mothers, including any who developed an isolated fever. Although a clinical diagnosis of Triple I was made by the obstetrics team, given maternal fever, testing for SARS-CoV-2 was included as well. Appropriate personal protective equipment (PPE) was donned and doffed before and after delivery. Additionally, the newborn was admitted to the NICU and was placed in appropriate isolation as a person under investigation (PUI) for COVID-19 and for presumed infection due to maternal Triple I. Even though the mother had a clinical diagnosis of Triple I and no other symptoms except for fever, she later tested positive for SARS-CoV-2.
In the NICU, a partial sepsis workup was initiated, as per our guidelines for the management of asymptomatic neonates born to mothers with suspected chorioamnionitis. The neonate was treated with broad-spectrum antibiotics, ampicillin and gentamicin, after drawing a blood culture. A complete blood count test with manual differential at six hours of life was sent as per protocol. A white cell count of 16,000 per mm3 and platelets of 168,000 per mm3 were found, and on manual differential, there were 72 neutrophils and an immature to total neutrophil ratio of 0.04. The results of the physical exam and vitals were normal throughout the admission. Antibiotics were discontinued after the blood culture was negative for 48 hours. The neonate was tested for SARS-CoV-2 by nasopharyngeal swab using a real-time reverse transcriptase polymerase chain reaction at birth, and before discharge, as per local institutional policy for testing SARS-CoV-2 in neonates born to mothers with COVID-19. The results were negative at both occasions. Due to the maternal SARS-CoV-2 status, the patient was discharged home to his father with anticipatory guidance for routine care and infection prevention.


A 71-year-old woman presented to the emergency department with symptoms of dizziness, fatigue, and bright red bleeding per rectum. She has a past medical history of atrial fibrillation and hypertension. She started having six to seven bright red colored stools for about one week, unassociated with mucus. She reported concerns of constant right upper quadrant pain that started approximately two days before the presentation. She denied any nausea, vomiting, or subjective fever, and she had no recent travel or exposure to sick contacts and no history of hemorrhoids.
On examination, she was found to be tachycardic with a heart rate of 130 beats per minute. Her blood pressure was 98/50 mmHg, and her body temperature was 100.2°F. Her oxygen saturation was 93% on room air. She appeared thin, cachectic, and had no scleral icterus. Her lungs were clear on auscultation, and her cardiovascular examination revealed no significant murmurs.
Her laboratory investigation showed leukocytosis with white blood cell count of 29,000 per microliter (neutrophils, 88%; lymphocytes, 3.5%; monocytes, 3.7%; eosinophils, 1.2%; basophils, 0.3%). Her hemoglobin was 9 g/dl (reference range: 11.2-15.7 g/dl), and her mean corpuscular volume was 77. Urine analysis was negative for infection. Chest X-ray did not show any active consolidation (Figure ).
Her Clostridium difficile screening was negative. Right upper quadrant ultrasound showed several indeterminate hypoechoic solid masses, and both lobes of the liver had several indeterminate hypoechoic solid masses. A slight gall bladder wall thickening with no surrounding inflammatory signs was noted. MRI of the abdomen showed multiple circumscribed lesions throughout the liver compatible with metastasis (Figure ).
The patient was started on empiric antibiotics with vancomycin and cefepime for possible infection. Her blood cultures grew S. anginosus, and her antibiotic regimen was changed to ceftriaxone.
As the source of the bacteremia was unknown, and because of her microcytic anemia with a recent change in bowel habits, she underwent a colonoscopy and transthoracic echocardiogram (TTE). The colonoscopy revealed a fungating infiltrative, ulcerated, partially obstructing mass in the sigmoid colon. The biopsy results are positive for moderately differentiated adenocarcinoma of the colon (Figure ).
TTE showed thickening and possible vegetation involving the aortic and mitral valves. Subsequent transesophageal echocardiogram revealed vegetation (approximately 0.2 cm) on the aortic and mitral valves (Figures , ).
She had no signs of a perivalvular abscess, and her ejection fraction was within reference range at 55% to 60%. Her care team decided to continue treatment with antibiotics for at least six weeks. Her anticoagulation for atrial fibrillation was halted due to active gastrointestinal (GI) bleeding. The patient died several days later as her family focused on comfort care measures based on the patient's wishes.


A 17-month-old male boy of northern African origin presented to our hospital. At that time, he was in established renal failure, having been commenced on peritoneal dialysis (PD) at the age of 9 months in his home country. Diagnosis of PH1 has been confirmed within the first year of life by genetic analysis revealing a homozygous mutation in the AGXT gene (Ile244Thr). We measured free plasma oxalate (POx) concentrations following a protocol previously established in our laboratory. Using this protocol, POx concentrations between 20 and 40 μmol/L are commonly obtained in general ESRD patients []. In our patient, POx concentration was 128.9 μmol/L at presentation. In the further course, samples for control of POx concentration were taken after nocturnal peritoneal dialysis and pre-hemodialysis. The patient demonstrated slight pancytopenia, but no signs of retinopathy, echocardiography, and Speckle tracking echocardiography were unremarkable. He was initially anuric, and during the course of his hospitalization, urine output slightly improved (less than 0.1 ml/kg BW/h). The patient had already received pyridoxine (9 mg/kg BW per day) for several months prior to admission as responsiveness to this medication has been described in patients with the Ile244Thr genotype []. As his PD program has been insufficient to effectively lower POx concentration, we first introduced a daily program (10 dwells of 80 min with 300 mL each, Glc 1.5%; Ca2+ 1.25%) according to GPN standard. In addition to PD, we placed a tunneled catheter via the right vena jugularis interna and started our patient on continuous venovenous hemodiafiltration (CVVHDF, 5 sessions of 2–3 h per week; dialysate flow 5-7 L/h; blood flow 50–60 mL/min). Following initiation of this regimen, POx concentration dropped to 80.8 μmol/L (Fig. ). For the compassionate use of Stiripentol, the parents gave written informed consent. Subsequently, Stiripentol was introduced with a starting dosage of 4.7 mg/kg/d and increased stepwise up to 61 mg/kg/d for the duration of 2 months. At the end of the trial, we administered a dosage slightly above the recommended dosage; however, Stiripentol plasma measurements by high-performance liquid chromatography showed values within a non-toxic range. The manufacturer’s recommendations were followed specifically concerning dietary precautions. Most frequent side effects (≥ 1/100) of Stiripentol are loss of appetite and weight, dizziness, insomnia, irritability, hyperkinesia, nausea and vomiting, elevated GGT, and neutropenia. Adverse reactions were not observed in our patient. During the whole 3.5-month period of Stiripentol administration, we did not observe a decrease in POx concentration and, therefore, stopped administration. Four weeks after discontinuation, POx concentrations were found to remain within the same range, suggesting that the withdrawal did not increase oxalate load further.


Our patient is a 66-year-old Caucasian woman with a complicated medical history of third-degree atrioventricular block (3° AV block) status post implantation of a Boston Scientific dual chamber internal cardioverter-defibrillator (ICD) with subpectoral pocket placement in Sep 2017, upgraded to dual-chamber ICD with right ventricular (RV) pacing lead extraction in Jan 2018, nonobstructive coronary artery disease (CAD) (50% mid-left anterior descending artery (LAD) stenosis; 20% mid-right coronary artery (RCA) stenosis), ventricular tachycardia, severe aortic valve (AV) stenosis status post minimally-invasive #21 On-X mechanical aortic valve replacement (AVR) in Sep 2017, thoracic aortic mycotic pseudoaneurysm status post repair in Oct 2017, hypertension, heart failure with preserved ejection fraction (HFpEF), chronic obstructive pulmonary disease (COPD) requiring 3 L/min O2, mild chronic normocytic anemia, chronic anxiety, and chronic depression. On Jul 23, 2019, the patient presented to our hospital with a 2-day history of decreased oral (PO) intake, myalgias, nausea, bilious vomiting, night sweats, chills, diarrhea, lightheadedness, stool incontinence, and headache, as well as a 1-day history of chest pressure. Initial examination was positive for ventricular tachycardia, ill appearance, loud S1, and jugular venous distention (JVD). Pertinent findings in social history included a pet cat that sleeps in her bed at night but no known scratches or bites, a former smoking history of 50 pack-years, 1-2 cans of beer per night, and no illicit substance use. Initial labs indicated hyponatremia of 129 mEq/L, a white blood cell count (WBC) of 11.8 cells/mm3, negative serum troponins, a serum lactate of 2.4 U/L, and a subtherapeutic international normalized ratio (INR) of 1.7. Chest X-ray (CXR) and computed tomography angiography (CTA) of the chest were negative for pathologic findings. She was started on an enoxaparin to warfarin bridge with a goal INR of 2-3, given intravenous (IV) fluid boluses, and had blood cultures drawn. On Jul 24, she was started on IV piperacillin-tazobactam 3.375 g every 8 hours (q8h). On Jul 26, she had increased work of breathing requiring bilevel positive airway pressure (BiPAP) for a few hours, and blood culture results indicated Pasteurella multocida, Staphylococcus epidermidis, and Staphylococcus warneri bacteremia. A transthoracic echocardiogram (TTE) was positive only for left atrial (LA) and left ventricular (LV) hypertrophy, aortic stenosis without regurgitation, moderate mitral regurgitation, mildly dilated ascending aorta, and moderately elevated pulmonary artery pressure, but no vegetations. On Jul 28, her piperacillin-tazobactam was discontinued and she was started on PO moxifloxacin 400 mg daily. She was discharged on Jul 30 with continued moxifloxacin, the last dose of which was planned for Aug 6 to complete a total of 14 days of antibiotic treatment. The patient improved as an outpatient until the end of her antibiotic course, and an outpatient visit on Aug 19 revealed only occasional chills and fatigue, which resolved later that month. By Sep 9, however, she had developed aortic valve insufficiency, and on Sep 28, she developed shaking chills and altered mental status (AMS). On Sep 30, she presented to her primary care provider (PCP), who sent her to our emergency department (ED) for suspected sepsis.
On presentation to the ED, the patient displayed AMS, dyspnea with orthopnea, headache, and rigors, and was febrile to 38.5°C, hypotensive at 80/57 mmHg, tachycardic at 114 BPM, and hypoxic to 75% oxygen saturation (SpO2) on room air. Her CXR showed bilateral pulmonary edema, and labs were notable for a brain natriuretic peptide (BNP) of 12,000 pg/mL, lactate of 3.8 U/L, and serum Na of 123 mEq/L. In the ED, she was placed on IV piperacillin-tazobactam 4.5 g, decreased to 3.375 g q6h after the first dose, IV azithromycin 500 mg daily, IV doxycycline 100 mg once, and IV linezolid 600 mg once, as well as BiPAP with a positive end-expiratory pressure (PEEP) of 6 cm H2O until her shortness of breath (SOB) improved. Azithromycin was discontinued on Oct 1 when blood cultures drawn on Sep 30 indicated Gram-negative bacteremia. Transesophageal echocardiogram (TEE) on Oct 2 indicated an aortic valve vegetation, as well as a paravalvular aneurysm on the aortic-mitral septum. By Oct 3, her bacteremia was identified as Pasteurella multocida. Repeat cultures were negative, and the patient clinically improved; she was discharged on Oct 8 with a continued course of IV piperacillin-tazobactam to be taken at home until Nov 5. She continued to improve, and at an outpatient visit on Oct 21, she reported no chills, fever, chest pain, chest discomfort, or presyncope. At an outpatient visit on Oct 28, however, she was found to be severely dyspneic with an SpO2 of 81% on room air, with rales, wheezing, peripheral edema, and a diastolic murmur on exam. A TTE performed at that time indicated severe aortic regurgitation and a dilated right heart with severe tricuspid regurgitation, and she was readmitted.
On this admission, our patient described a gradual increase in SOB and home oxygen requirement, anorexia, and increased peripheral edema for 1 week, in addition to recent urinary hesitancy with oliguria. Exam indicated volume overload, and the patient was afebrile. Labs were notable for serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) of 195/161 U/L, alkaline phosphatase of 208 U/L, and a normal WBC count. She was continued on piperacillin-tazobactam, home torsemide, and 3 L/min O2. Her condition improved, and she remained stable until surgery on Nov 7, which found prosthetic aortic valve endocarditis with an aortic root abscess extending into the RA and associated tricuspid annulus destruction. Bovine pericardium was used to repair the atrial perforation, cadaver allograft for a Bentall procedure, and a 33 Epic bioprosthetic valve for tricuspid replacement. Epicardial pacing wires were placed with the intent of replacement with dual-chamber ICD after resolution of her infection, and her chest was left open (due to difficulty mobilizing the chest wall) and packed and sealed with an iodine-impregnated incision drape (Ioban™). Postoperatively, she required epinephrine, milrinone, vasopressin, and mechanical ventilation. Her WBC and temperature waxed and waned between elevated and normal for several days postoperatively, and hypoxia and hypercapnia required an increasing fraction of inspired oxygen (FiO2). On Nov 9, she received a chest washout and primary chest closure. On Nov 10, initial culture from the tricuspid valve was positive for Staphylococcus warneri in addition to another organism later identified as a Curtobacterium sp.; in addition to her continued piperacillin-tazobactam, she was placed on IV daptomycin 8 mg/kg daily due to a questionable history of drug reaction with eosinophilia and systemic symptoms (DRESS) to vancomycin and contraindications (thrombocytopenia and anemia) to linezolid. She also was noted to have increasing abdominal distention at this time, and an abdominal CT showed dilated bowel with pneumobilia, which resolved over the next few days. On Nov 13, her S. warneri sensitivities indicated resistance to gentamicin and one colony to gentamicin and clindamycin but resistance in all colonies to cefazolin, erythromycin, linezolid, methicillin, oxacillin, penicillin G, tetracycline, and vancomycin; her daptomycin was discontinued at this time. She had return of bowel function on Nov 15. A possible infection of the right knee joint at this time resulted in the reinitiation of daptomycin for empiric methicillin-resistant Staphylococcus aureus (MRSA) coverage, discontinued on Nov 18 for lack of signs or symptoms concerning for joint infection. She was able to be weaned off vasopressor and inotrope support on Nov 16, and because of her development of ARDS and an expectation of prolonged intubation, she was given a tracheostomy and endotracheal tube on Nov 19. Her WBC had been slowly declining over this period, and by Nov 20, she was no longer leukocytotic.
On Nov 21, she had return of abdominal pain and worsening distension, both of which had previously been resolving, and an abdominal XR indicated evolving ileus. Abdominal CT on Nov 22 found pneumatosis intestinalis and significant free air concerning for bowel perforation, and she was given a single dose of metronidazole before emergent exploratory laparotomy and small bowel resection for distal ileal obstruction. Postoperatively, she required norepinephrine for 1 day. She developed worsening abdominal pain and distension on Nov 24, and blood cultures drawn on Nov 21 were found to be positive for Gram-negative rods later identified as Klebsiella aerogenes; ciprofloxacin 400 mg IV daily was started at this time, due to the patient's history of allergies to ceftriaxone and ertapenem. By Nov 27, return of bowel function was noted, repeat blood cultures had failed to grow any bacteria, and Klebsiella sensitivities indicated resistance to ampicillin, ampicillin-sulbactam, cefazolin, ceftriaxone, and piperacillin-tazobactam, dose-dependent susceptibility to cefepime, and sensitivity to trimethoprim-sulfamethoxizole, tobramycin, meropenem, amikacin, and most importantly, ciprofloxacin, her last dose of which was planned for Nov 30. However, her WBC elevated from 6.4 to 12.9 cells/mm3 overnight, and by Nov 28, it was at 14.7 cells/mm3 in addition to the development of abdominal distention and an abdominal XR indicating a dilated small bowel concerning for ileus and possible ischemia. A CT that day indicated free air and was concerning for an anastomotic leak; emergent surgery confirmed bowel contents in the peritoneum due to dehiscence of the anastomosis, which was resected prior to an ileostomy. Her piperacillin-tazobactam and ciprofloxacin were discontinued, and she was started on meropenem 2000 mg q8h.
On Nov 30, she became febrile and leukocytotic to 21.1 cells/mm3, and her antibiotic regimen was adjusted to meropenem 500 mg q6h, daptomycin 8 mg/kg daily, and fluconazole 400 mg daily. She was afebrile by the following day, but her WBC count lowered only slightly over the next few days, and her fever had returned by Dec 6. A CT on Dec 6 indicated two abdominal rim-enhancing loculated fluid collections concerning for abscesses. Her daptomycin was discontinued, and she received an abscess drainage of 9 mL of purulent fluid, drain placement, and paracentesis of 40 mL clear yellow to red fluid on Dec 7. She became afebrile, and her WBC decreased to 14.9 cells/mm3, which continued to decrease over Dec 8 into the normal range. On Dec 10, surgical pathology of the resected bowel anastomosis was found to be consistent with cytomegalovirus (CMV) enteritis, and she was started on ganciclovir 5 mg/kg q12h on Dec 11 after a positive CMV quantitative polymerase chain reaction (qPCR) of 9419 IU/mL. By Dec 11, her abscess fluid had also cultured Enterococcus faecium. Her meropenem was discontinued, and she was started on linezolid 600 mg q12h and piperacillin-tazobactam 4.5 g q8h. Her WBC count continued to decrease and by Dec 15, she was leukocytopenic to 3.8 cells/mm3. By Dec 17, her leukocytopenia had worsened to 2.8 cells/mm3, and her ganciclovir was discontinued in favor of foscarnet 3500 mg q12h. On Dec 19, her piperacillin-tazobactam was discontinued to complete her endocarditis treatment. An abdominal CT on Dec 23 showed complete resolution of her prior abscesses, and her linezolid was discontinued. Her abscess drains were removed on Dec 24, and her foscarnet was discontinued, as she had also completed her 14-day course of treatment for CMV enteritis.
Despite her recurrent infections, over the course of December our patient continued to slowly improve in respiratory and hemodynamic status. By Dec 22, she was ambulatory and could tolerate unassisted ventilation with tracheostomy trials of 3.5 hours, which improved rapidly over the next week to complete freedom from mechanical ventilation on Dec 28. On Dec 30, after over 48 hours off mechanical ventilation, she was given a Metronic automatic ICD, and her epicardial pacing wires were removed. By Jan 10, 2020, she was able to tolerate endotracheal tube capping of over 24 hours with good oxygenation, and her endotracheal tube was removed.
Our patient was discharged on Jan 13, 2020 to a skilled nursing facility (SNF) for rehabilitation. At the time of discharge, she had a well-functioning ileostomy requiring PO NaCl supplementation due to ileostomy losses, but otherwise enjoyed a regular diet. She was oxygenating well on room air after removal of her endotracheal tube, and her heart was well-paced by her ICD. After less than one week in her SNF, she was released home. In follow-up, she was seen by cardiothoracic surgery (Jan 23) and cardiology (Jan 29 and Feb 4). Over this time, paroxysmal atrial flutter was noticed in addition to one 15-second episode of ventricular tachycardia. On Feb 9, she was admitted to an out-of-network hospital for pneumonia which resolved after a short stay in the ICU; she was discharged home on Feb 18. She was seen again by cardiology on Mar 2 and cardiothoracic surgery on Mar 4 and showed improvement from her Feb 4 and Jan 29 cardiology appointments, with resolution of her atrial flutter. She had no further episodes of ventricular tachycardia, and her low appetite, low weight, fatigue, anxiety, and depression, which had worsened over the course of her most recent hospital stay, were all improving. As of Mar 30, 2020, she was continuing to improve and had no new health concerns.


The patient is a 65-year-old woman who has a brother and a sister. Her brother and a nephew were diagnosed with AMN and CALD, respectively. Her nephew died at 31 years of age. Her sister had a gait disturbance. Since her forties, the patient has also noticed walking difficulty, pollakisuria, and spasticity of both legs. Later, her gait disturbance slowly progressed. She attributed her symptoms to age, despite her family history. At age 60, she visited our hospital for the first time. At that time, she was able to walk with assistance. As the pollakisuria got worse, she experienced incontinence and noticed difficulty in urination, but she had no sensation of residual urine. Referring to her family history, we tested her ABCD1 gene and identified a G298S hemizygous mutation. Hence, we diagnosed her illness as female ALD carrier. Three days before admission, she had a low-grade fever, a dull ache in the suprapubic region, and malaise. On physical examination, her temperature was 37.4°C. Her suprapubic region was soft, but there was mild tenderness. Knocking pain was not provoked in the costovertebral angle area. On neurologic examination, spasticity with contracture of hip joints, muscle weakness (MMT 2/5), and moderate hypesthesia were observed in bilateral lower limbs. She could stand with assistance. The tendon reflexes of the upper and lower extremities were symmetrically hyperactive except for the Achilles reflex, which was absent, and bilateral Babinski signs were elicited. There were no meningeal signs. Laboratory studies on admission yielded the following values: white blood cell count 9740/mm with 80% neutrophils, C-reactive protein (CRP) 3.92 mg/dL, and serum creatinine 0.74 mg/dL. The urine was turbid, the sediment of which was loaded with white cells and bacteria. The urine culture grew Escherichia coli. Abdominal computed tomography (CT) images showed trabeculated bladder and dilation of the left renal pelvis and ureter (Figure ). These findings indicated the presence of urinary stasis due to residual urine and vesicoureteral reflux. She was treated with 500 mg/day of levofloxacin, and her symptoms improved quickly. To decrease her residual urine volume, we introduced clean intermittent catheterization (CIC) three times a day. Even after urination, around 400 mL of urine was sometimes still obtained with a catheter. Follow-up CT on day 15 of admission showed reduction of the dilated urinary tract (Figure ). CIC was continued after discharge.


A 31-year-old active male with no prior medical history presented to the clinic with a one-month history of chronic, intermittent, throbbing, anterior-inferior right knee pain with severity rated 2/10 on average. The pain was aggravated by squatting and lunging and relieved with rest and icing. The patient reported no family history of musculoskeletal disorders and no history of substance abuse. On physical examination, the patient had a general athletic appearance and muscle tone was normal and symmetric bilaterally throughout both lower extremities. The right knee was observed to have a decreased range of motion to knee extension. Standard US of the right quadriceps tendon revealed hypoechogenicity and evidence of a partial tendon intrasubstance tear (Figure ). Conservative management (rest, ice, compression, elevation) and physical therapy were recommended.
At three-month follow-up, the patient reported significant improvement of the right anterior-inferior knee pain but reported new right suprapatellar pain. This pain was sharp and intermittent with no associated swelling and exacerbated with running. Repeat standard US of the right knee in the anterior approach with a longitudinal view revealed a new suprapatellar effusion, hypoechoic intrasubstance tendinopathy, and calcific enthesopathy of the quadriceps tendon (Figure ). MRI corroborated these findings but demonstrated nothing additionally. However, dynamic US revealed an anterior capsular tear with a suprapatellar effusion communicating into the vastus intermedius fibers of the quadriceps tendon when the knee was positioned in extension (Figure ). A plain film radiograph demonstrated patella alta, confirmed using the Blackburne-Peel Index []. We recommended continued conservative management, and at the final follow-up one month later, the patient expressed significant resolution of symptoms [].


A 24-year-old Haitian female with no known past medical history or smoking history was in her usual state of health until three weeks prior to presentation when she started to experience right arm pain, numbness, and tingling sensation. She did not report a history of cancer in her family. She initially presented to an urgent care facility where she was prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants without any improvement of her symptoms. She also had two episodes of pre-syncope over the past two months which she attributed to poor diet; she did not seek any medical attention. On the day of presentation to the emergency department (ED), the patient was returning from the Bahamas via airplane when she felt progressively worsening right-sided chest discomfort radiating to the right flank and back. She reported right upper extremity pain and numbness. She did not report cough, fever, shortness of breath, cold symptoms or recent changes in the weight and appetite. Her vitals in ED were a heart rate of 120 beats per minute, oxygen saturation of 98% on room air, blood pressure of 110/78 mm Hg, and temperature of 98.2 F. Her physical examination was unremarkable. Initial laboratory investigation was normal including complete blood count (CBC) and comprehensive metabolic panel (CMP). A preliminary chest X-ray was done (Figure ).
Due to tachycardia and positive travel history, a computed tomography angiogram (CTA) was performed which was negative for a pulmonary embolism. However, CTA revealed a heterogeneous superior right mediastinal mass, measuring about 10 cm. The trachea was noted to be severely deviated to the left and markedly stenosed. Multiple pleural-based lung masses and nodules were also present on imaging, which are classical imaging signs of adenocarcinoma (Figure ).
The patient underwent a mediastinal biopsy and was diagnosed with metastatic poorly differentiated non-small cell adenocarcinoma (Figure ). She later underwent a bronchoscopy with tracheal stent placement. Her right arm pain, numbness, and tingling eventually resolved after treatment with systemic steroids. She is now undergoing systemic chemoimmunotherapy with carboplatin/pemetrexed although she has recurrent admissions to the hospital for chronic malignant pleural effusions and chest pain, requiring tunneled pleural catheter placement.


A 44-year-old previously healthy female, who presented with generalized body weakness, was found to have severe anemia (hemoglobin 5.7 gm/dl; normal value is 12-15 gm/dl). She denied other symptoms. On examination, she showed a severe pallor and no hepatosplenomegaly (Tables -).
The patient received one dose of iron ferric carboxymaltose (Ferinject) 1000 mg. Her symptoms, anemia, and neutropenia improved after therapy (Table ).


A 74-year-old woman, with a history of treatment-refractory Crohn’s disease on budesonide therapy (6 mg daily), psoriasis, and pernicious anemia developed abdominal pain, cramping, and non-bloody diarrhea 8 weeks prior to her current hospital admission. Colonoscopy was performed at onset of these flare of symptoms and demonstrated edema, erythema, and erosions at the ileocolic anastomosis (Fig. ) with biopsies revealing severe active ileocolitis (Fig. ). Standard dose of ustekinumab was added to her chronic budesonide regimen with moderate improvement in her symptoms. Approximately 6 weeks after ustekinumab was started and 2 weeks prior to her current admission, she was evaluated in urgent care with complaints of low-grade fever and a tender, non-pruritic bilateral lower extremity rash. At that time she began treatment with oral levofloxacin for presumed cellulitis. Her rash subsequently progressed, spreading to the abdomen and upper extremities. Her subjective fevers persisted, and she developed headache, fatigue, arthralgias, and generalized weakness along with worsening of abdominal pain and diarrhea. Given worsening of her symptoms despite antibiotic therapy, she presented to the emergency department for further evaluation and was admitted for presumed ineffective outpatient treatment of cellulitis and intravenous vancomycin therapy.
She was a retired factory worker from Wisconsin, USA who had been diagnosed with Crohn’s ileitis 30 years prior (A1, L3, B1) and maintained on budesonide. Prior therapies ineffective for her CD included mesalamine, prednisone, and adalimumab. Methotrexate trial was not tolerated due to allergic reaction (hives), and both infliximab and vedolizumab led to worsening of her psoriasis. Following the latest CD flare up standard dose of ustekinumab had been added to budesonide with the plan to continue the regimen with 8 week dosing intervals.
The patient was a former smoker who did not drink alcohol or use illicit drugs. Her medications included ustekinumab, budesonide, vitamin B12 injections and a multivitamin. Her psoriasis had been quiescent, and had required no recent treatment.
On physical exam she appeared well-developed in mild distress due headache, abdominal pain, and painful rash. Patient was febrile to 38.2 °C; other vital signs were normal. Oral mucosa was moist and without ulcerations. Lungs were clear to auscultation bilaterally and heart sounds were regular, and without murmur. Abdominal exam revealed tenderness to deep palpation in the right lower quadrant without peritoneal signs. Rectal exam was negative for perianal fistulas. Neurologic exam was normal. Skin exam was remarkable for a tender, petechial rash involving her abdomen and extremities (Fig. ).
A complete blood cell count demonstrated hemoglobin of 13.0 g/dL, white blood cell count of 5.7 x × 109/L, and platelet count of 133 × 109/L. A comprehensive metabolic panel demonstrated normal electrolytes, renal and liver function. Tick-borne panel including testing for Lyme disease, Anaplasma spp, Ehrlichia spp and Babesia microti was negative as well as blood cultures. Inflammatory markers were elevated with sedimentation rate (ESR) 42 mm/h, and C-reactive protein (CRP) 15.2 mg/L. Rheumatoid factor, cryoglobulins, and anti-nuclear antibody (ANA) were negative. Serum protein electrophoresis (SPEP) was negative for monoclonal protein spikes. Complement C3 and C4 levels were within normal range. Testing for viral hepatitis including Hepatitis A, B, and C were negative for both acute and chronic infection, and showed immunity against Hepatitis B virus. Cerebrospinal fluid (CSF) demonstrated a nucleated cell count of 0 with normal glucose and protein. A non-contrast head CT was negative for intracranial lesions. Recent mammogram and cervical cancer screening were normal.
In the absence of leukocytosis and coupled with the symmetric distribution of the rash, cellulitis seemed unlikely, leading to discontinuation of antibiotics. Evaluation of rash with skin biopsy demonstrated findings consistent with leukocytoclastic vasculitis, including: 1) neutrophilic infiltration of the blood vessels with necrosis and perivascular fibrinoid deposition, 2) disruption of some small caliber blood vessels walls with hints of fibrin deposition, 3) bits of nuclear dust in and around blood vessel walls, and 4) extravasated erythrocytes (Fig. ). A Periodic acid–Schiff stain (with appropriate positive control) did not demonstrate spore or hyphal form. Bacterial cultures of skin and blood remained negative.
High dose intravenous steroids were recommended as treatment of choice, but patient declined. Budesonide dose was subsequently increased from 6 mg to 9 mg daily, and within 48 h her rash began to subside, and patient noted improvement in abdominal pain and constitutional symptoms. Prior to discharge, she received another dose of ustekinumab without exacerbation of her rash, and with continued improvement in her gastrointestinal and constitutional symptoms. Eight months following her episode of CD flare associated with LCV she continued to do well on ustekinumab and budesonide has been gradually tapered off.


A 29-year-old Hispanic female presented to the emergency room in the first week of April 2020 with sudden onset of severe vertigo, nausea, and vomiting two days prior to arrival. The only other symptom was generalized fatigue without any focal weakness in the extremities, fever, chills, and cough and phlegm or chest pain. She denied any diarrhea, abdominal pain, anosmia, or dysgeusia. She denied any accompanying symptoms such as tinnitus, hearing loss, feeling of unsteadiness, veering to one side when walking. She denied any prior history or prior episodes of vertigo, recent upper respiratory symptoms, or recent trauma. She complained of vertigo at rest and it worsened with any type of movement. She described it as "persistent" vertigo in every position, though she was not able to explain the direction in which movement made it worse.
She was working at a chicken plant in the local rural community, which had a huge cluster of COVID-19 infections.
On arrival at the emergency room, she had stable hemodynamics, was afebrile, had a blood pressure of 139/72 mmHg, and was saturating 100% on room air. She looked in severe distress from nausea, non-bilious vomiting, and severe vertigo. Neurologically, her cognition was intact, and the cranial nerve exam did not show defects. Fine finger movement and rapid alternating movements of the extremities were intact as well. It was difficult to identify nystagmus in her initial presentation due to the acuity of illness from the other symptoms. Further positioning maneuvers like Dix Hallpike could not be attempted for the same reason. Gait examination was deferred for the same reason.
Her urine toxicology was negative while white cell and platelet counts were within normal limits. Computed tomography (CT) scan of the head without contrast showed no acute pathology. With the presentation of nausea, abdominal pain, and non-bilious vomiting, a CT chest/abdomen and pelvis without contrast was done in the emergency room, which showed multifocal, bilateral, peripheral, ill-defined, rounded, ground-glass opacifications, features that could be consistent with acute COVID-19 pneumonitis (Figure ).
Acute thromboembolic stroke was a differential that had to be ruled out at the time of admission, and MRI/MRA of the brain was checked. They did not show any acute findings.
Acute vestibular neuritis was the initial admission diagnosis and she was managed symptomatically with anti-emetics, meclizine, and benzodiazepines as needed.
In the emergency room itself, the COVID-19 polymerase chain reaction (PCR) test was requested due to the CT chest findings. Upon testing positive, she was started on hydroxychloroquine and azithromycin, which at the time was thought to be a promising treatment for COVID-19 infection []. Interestingly, she never had a fever or any respiration symptom all through her hospital course. All the inflammatory markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and ferritin, were within normal limits and so were the coagulation parameters, including d-dimer, fibrinogen, and platelet count.
Her symptoms were refractory to the then considered "traditional" management of a COVID-19 infection, and she was subsequently treated with intravenous steroids along with supportive care. She also received vestibular rehabilitation from physical and occupational therapy for a brief period.
Her symptoms gradually improved, and she was able to tolerate a diet and eventually discharged home after an eight-day stay in the hospital. The symptoms were quite refractory to the above-mentioned treatment and it took more than a week for her to recover and become asymptomatic. After discharge, she was advised to quarantine herself for seven more days.


A 2 year old Afro-Caribbean girl was referred to a pediatric ophthalmologist with unilateral resting ptosis of 30%. Her parents reported it had been present for 3 months and varied from day to day. There was evidence of fatigueability on prolonged upgaze but eye movements appeared full. She was unable to tolerate electrodiagnostic testing but AChR-Ab was positive. She was started on pyridostigmine with a good symptomatic response. She was reviewed by her ophthalmologist 6 months later and her eye exam was noted to be normal. Her parents still reported intermittent ptosis, especially when tired and at times though her left eye “drifted out.” Due to the normal exam, a decision was made to wean her pyridostigmine, however, upon discontinuation, she experienced an acute worsening of her symptoms, with new onset double vision and bilateral ptosis. At this point she was prescribed 20 mg of prednisolone daily, which was stopped at her 3 month review as she was felt to be in remission. Once off steroids, her symptoms quickly returned. She was referred to the pediatric neurology service and on exam, she was also noted to have features of generalized MG with difficulty getting up from the floor and lifting her arms above her head.
This case highlights a number of issues in managing JMG: the importance of not weaning treatment too early, especially when the history suggested breakthrough disease; the need for an adequate course of steroids and gradual tapering of the dose prior to discontinuation; the need for combined neurology and ophthalmology input as subtle signs of more generalized disease may have been missed at earlier assessments; and patients with ocular JMG are at greatest risk of converting to generalized disease within the first 2 years and need regular review over this time.


A 13 year old Caucasian girl was referred to the neurology service with slurred speech, generalized weakness and fatigue, that had worsened over 6 weeks. She now became breathless on minimal exertion. Examination showed mild bilateral ptosis, normal eye movements, dysarthria (unable to count aloud to 10), and weakness of neck flexion and shoulder abduction. Her forced vital capacity was 50% normal. Her symptoms and exam were felt to be consistent with generalized MG and the severity raised concern for an impending myasthenic crisis. She was admitted to the neurology ward and anesthetic review was arranged. She was commenced on PLEX and concomitant pyridostigmine and oral steroids. She had a good symptomatic response to treatment and was discharged on a slow oral steroid taper, reducing by 10 mg every month to an initial maintenance of 20 mg on alternate days. Subsequent investigations showed she was AChR-Ab positive, her neurophysiology was consistent with a neuromuscular junction disorder and CT thorax was reported as showing no evidence of a thymoma.
Her first relapse occurred when her prednisolone was reduced to 30 mg alternate days, necessitating an increase in medication. She had developed a number of side-effects including weight gain and low mood. A decision was made to commence Azathioprine as a steroid-sparing agent. Her TPMT levels were normal. While her dosage was being uptitrated, her liver function became deranged, leading to discontinuation. She had another significant flare of symptoms requiring a further cycle of PLEX and her steroids were again increased. At this point she was 12 months into her diagnosis, while higher-dose steroids induced remission she was developing intolerable side-effects and was becoming depressed and withdrawn. A decision was made to refer her for thymectomy and continue intermittent PLEX prior to surgery.
This is a challenging case. While not treatment-refractory, our patient is steroid-dependent and was intolerant of first-line immunosuppression. We considered the addition of mycophenolate at this point, but were concerned about teratogenicity, now that she was of child-bearing age. She responded well to PLEX and given she was AChR-Ab positive with generalized disease, we felt thymectomy was the appropriate next step in management.


An 8 year old Caucasian boy presented acutely with generalized weakness, shortness of breath on minimal exertion, marked dysarthria and difficulty swallowing with nasal regurgitation of fluids. His symptoms has progressed rapidly over a few weeks. Clinically his symptoms were felt to be consistent with MG. He was admitted to the pediatric ward and reviewed by the anesthetic service. He was maintained under close surveillance but a decision was made to hold off invasive ventilation. He was commenced on ChE-I, oral prednisolone and IVIG. He made good progress and was discharged home with a plan for a further course of IVIG in 4 weeks in his local hospital due the severity of his initial symptoms, and lag time for steroids to take effect. He was seen in clinic 12 months later and at this time was on maximum alternate day steroids. He was also receiving 4-weekly IVIG infusions at his local hospital. Both him and his parents reported a dramatic response to the IVIG but felt the effect wore off after about 3 weeks and his symptoms particularly fatigue became “as bad as ever.” On examination he had no weakness. Prior to his diagnosis he was said to be an outgoing boy and very involved in sports. His parents now reported he was refusing to go to school most days and no longer engaging in any extra-curricular activities. They felt the slightest thing could have him in tears. A decision was made to assess him neurologically at the time of his next infusion. While on the ward strength was noted to be normal and on further questioning he said that he kept reliving his initial hospital admission and felt that the “only reason he didn't die was because of the special protein drip.” He was felt to have evidence of post-traumatic stress disorder and appropriate psychological supports were put in place. IVIG was withheld and a gradual improvement was seen.
This case highlights the importance of the multidisciplinary team in managing young patients with JMG. Psychological issues need to be addressed early and the necessary supports put in place. It is not uncommon for young patients to report fatigue rather than true muscle weakness, and this is often a manifestation of an underlying mood disorder rather than their MG. Careful assessment needs to be carried out in all patients prior to using IVIG to ensure that it is being used in the appropriate setting.


A ninety-year-old gentleman with underlying dementia and hypertension was presented with a sudden onset of central chest pain while watching television. Upon arrival at the emergency department, he was in severe pain and sweaty. Initial blood pressure was 90/50 mmHg with a heart rate of 110 beats per minute. ECG showed acute inferolateral myocardial infarction. On cardiovascular examination, there was no clinical sign of cardiac tamponade, and the auscultation of the lung was clear. Bedsides, echocardiography was performed showing pericardial effusion with a maximum diameter of 1.3 cm over the apex with no features of cardiac tamponade. The inferior lateral wall was hypokinesia, and the right ventricle wall was akinetic. Given the ECG and echocardiographic findings, and the patient was in severe pain, we decided to proceed with CT aortogram to rule out aortic dissection. The CT scan showed no evidence of aortic dissection; however, there was a presence of hemopericardium (). We decided to proceed with a primary percutaneous coronary angiogram ().
The patient was persistently hypotensive and did not respond to fluid resuscitation and inotropic support. We decided to abundant the angioplasty procedure and proceeded with emergency pericardial tapping (). 350 ml of blood was drained from the pericardium. The hypotension resolved after the procedure, and we were able to off the inotropic infusion. The pericardial drainage was in situ for three days and drained haemoserous fluid. After removal of the pericardial drainage, there was a reaccumulation of pericardial effusion. We referred the patient to the cardiothoracic surgeon, but the patient and family opted for conservative treatment and refused for any invasive or surgical intervention. The patient was not given heparin throughout the hospital stay and discharged home with a single antiplatelet. The proximal right coronary artery was stented three months later. He was last seen in our clinic in December 2019 and is currently doing well. The echocardiogram was repeated, and it illustrates mild left ventricular dysfunction with an ejection fraction of 47%. There was no significant residual pericardial effusion. The right ventricular function was normal.


A 96-year-old female body was received through the Saint Louis University Gift of Body Program of the Center for Anatomical Science and Education (CASE) with the signed informed consent from the donor. The CASE gift body program abides by all rules set forth by the Uniform Anatomical Gift Act (UAGA). Information obtained through the CASE program did not specify a cause of death but did mention a history of Alzheimer's disease, COPD, and atrial fibrillation in this donor. During dissection in 2018, it was observed that the donor was status post hysterectomy and status post ventral hernia repair with mesh.
During routine dissection, a markedly dilated left ureter was noticed and further explored (). The left renal pelvis was located outside of the kidney sitting medially, inferiorly, and slightly posteriorly from the kidney. The path of the ureter curved slightly posteriorly and medially before turning laterally. The ureter then turned sharply medially and anteriorly before continuing over the psoas major muscle. The ureter was most dilated as it passed anteriorly to the left psoas minor muscle, where its diameter measured at 1.70 cm. The ureter then passed posterior to the EIA and anterior to the IIA, about 0.50 cm away from the bifurcation of the AA.
Upon further dissection, it was found that what was initially identified as the left CIA was in fact the left EIA. The donor had three terminal arterial branches off the AA: the right CIA, left IIA, and left EIA. The left IIA branched off the posterior side of the AA. As a result, the median sacral artery was shifted and was observed branching off the right CIA (). After passing beneath the left EIA, the left ureter returned to a normal size (0.45 cm) and position following a normal path to the bladder ().
The three major calyces of the left kidney were found to join together outside of the kidney (). All arteries and veins of the left kidney were normal, and no evidence of hydronephrosis was observed (). Constriction of the ureteropelvic junction (UPJ) was noted, though this slight constriction did not result in any gross renal pathology ().
Finally, the subject exhibited extensive surgical sutures, likely from the hysterectomy, along the lateral paravertebral muscles as well as near the left IIA, inferolateral to the ureter.


This is the index case of a previously healthy 13-month-old male infant born in a nonconsanguineous Caucasian family. The child was admitted to hospital because of a fever and rash; the parents attributed the rash to the anti-inflammatory drugs administered to reduce the boy's temperature. The boy was born at term with a weight of 3,470 g and a height of 51 cm. At the time of admission, the patient's general condition was fair and his initial diagnosis was acute viral respiratory infection and rash of unknown aetiology, probably allergic. Blood analysis did not reveal any remarkable changes in total blood cell count or biochemical parameters.
During the first few days of hospitalization, the child had a moderate fever, diarrhoea, and maculopapular rash. On the fourth day of hospitalization, as the child's general condition had not improved, antibacterial drugs were administered; however, no significant improvement was observed. On the seventh day of hospitalization, the child's health suddenly deteriorated. He exhibited a high degree of fever, his rash was progressing, and he had hepatosplenomegaly. Laboratory analyses revealed the following: thrombocytopenia 34,000 (reference range 229,000–553,000); total leukocyte count was 8.26 × 106, 84% were lymphocytes; moderately increased liver transaminases Alt 225 U/L (reference range < 33 U/L), and Ast 520 U/L (reference range < 33 U/L); and C reactive protein was 34.26 mg/dL (reference range 0–5 mg/dL); coagulation tests revealed decreased clotting. Polyserositis was diagnosed by ultrasound investigation. Extra fluid and a therapeutic dosage of prednisolone were introduced, resulting in stabilization of the child's condition. After two days, the child's condition started to deteriorate again; he was lethargic, he did not display diuresis, and his feet were oedematous. His glucose level was 0.6 mmol/L (reference range 2.8–5.4 mmol/L), Alt 2,213 U/L, and Ast 2,989 U/L. At this point, he was transferred to the intensive care unit where a consulting haematologist suspected EBV infection, which was subsequently confirmed serologically. A bone marrow aspirate sample was collected for diagnostic purposes, and severe dishaematopoiesis without any traces of haematopoiesis and signs of macrophage activation syndrome was found. A final diagnosis of HLH was made ex consilio based on the clinical picture and laboratory analyses (thrombocytopenia, anaemia, neutropenia, decreased clotting, hypertriglyceridaemia, hyperimmunoglobulinaemia M, liver cytolysis, increased cell count (liquid portion), hyperferritinaemia, and hypoproteinaemia). Therapy comprising dexamethasone, etoposide, cyclosporine, and methotrexate was prescribed.
Two weeks after hospitalization, the child died from multiple organ failure. The autopsy reported haemorrhagic changes in the lungs, liver, spleen, and gastrointestinal tract, subtotal liver necrosis, kidney necrosis, ascites, and total bone marrow suppression.
One and a half years later, the deceased child's previously healthy 13-month-old brother was hospitalized with a low-grade temperature and rash covering his legs. The boy was born at 40/41 weeks with a weight of 3,470 g and a height of 52 cm; the mother's pregnancy was uneventful. During the hospitalization of their first child, it was noted that the parents had limited education and did not always fully understand the situation after several explanations; however, it was viewed that they provided adequate care for their children.
Over the next few days, the child slowly deteriorated; he had a febrile temperature and his rash progressed. On the third day of hospitalization, the child was transferred to the intensive care unit due to massive oedema, hepatosplenomegaly, thrombocytopenia 69,000, hypoproteinaemia, elevated levels of liver transaminases, and decreased clotting. He was found to have EBV infection. Based on the clinical picture, laboratory analyses, and medical history of his deceased brother, HLH treatment was initiated, although due to severe liver injury, his prognosis was poor. After 12 days of hospitalization and following unsuccessful cardiopulmonary resuscitation, the patient died. As XLP was suspected, DNA was isolated from both siblings and their mother. Immunoglobulin levels and lymphocyte subsets of second brother at time of hospitalization are shown in .
The Sanger sequencing analysis for the coding exons of the SH2D1A gene was conducted. For both of the siblings, it was not possible to amplify exons 1, 2, and 3 of the SH2D1A gene; exon 4 generated an amplification product, but no pathogenic variants were detected. In addition, integrity and quality of the extracted DNA samples were tested and evaluated as sufficient for the sequencing analysis. This suggested that the inability to amplify exons 1, 2, and 3 may have arisen from a large deletion within the SH2D1A gene. The possible presence of the large deletion within the SH2D1A was suggested but not confirmed.
In order to verify large rearrangements within the SH2D1A gene, we performed a genomewide analysis of genomic variants with the arraySNP HumanCytoSNP-12 v2.1 BeadChip Kit (Illumina) according to the manufacturer's instructions. Data analysis was performed with the BlueFuse Multi v4.4 and Genome Studio (with CNV Partition plug-in) software (Illumina). DNA samples of the two patients and their mother were evaluated for the presence of a large deletion within the SH2D1A gene. The patients' microarray analysis revealed a male hybridization pattern with approximately 192,000 bp deletion of chromosome X at band q25: arr [GRCh37]Xq25(123479999_123672135)x0. The lost region contained the SH2D1A gene and part of the STAG2 and TENM1 gene (DECIPHER). To confirm precise deletion breakpoints, primers corresponding to the breakpoint regions were designed and a 261 bp fragment containing breakpoint was amplified from the aberrant X chromosome by PCR. Sanger sequencing of this amplicon confirmed deletion of 197,730 bp. The maternal DNA sample revealed the same deletion found in the patients' DNA samples.


The second case is a 7-year-old boy with right-sided submandibular lymphadenopathy who was transferred from a regional hospital to the Children's University Hospital where he remained for approximately two weeks. His body temperature during this period was normal; however, his parents reported that he had occasional fatigue and poor appetite. It was noted that he had signs of dysmorphism and mild growth delay. He was born at 40 weeks (mother's 5th pregnancy, 5th birth) with a weight of 3,680 g and a height of 53 cm; there were no complications during pregnancy/birth. He had had some mild viral infections after starting kindergarten and had received all his immunizations according to the immunization schedule. His parents did not detail any chronic diseases. He had two healthy brothers, one sister with a double kidney, and one sister that had died at 11 years of age due to some type of congenital pathology, possibly microcephaly (not enough information was available)—family tree shown in .
Ultrasound examination of the boy's cervical lymph nodes and abdominal cavity, thoracic CT scan, and abdominal MRI were performed, and they showed suspicions of lymphoproliferative disease. Consequently, lymph node biopsy, bone marrow aspiration, and trephine biopsy were performed; however, no evidence of lymphoproliferative disease was found, and the boy was discharged in a stable condition. At a follow-up visit, two months later, it was observed that the lymph node conglomerate in his neck area had increased in size. An MRI of the head and neck area was subsequently performed, and the following was reported: large abnormal formation in the cervical soft tissues on the right side, with extracranial parapharyngeal, carotid space with internal carotid artery (ACI), ACE overgrowth, intracranial proliferation through the foramen jugulare in the cerebral cortex with peripheral oedema, and 4th ventricle compression with initial 3rd and lateral ventricle extension. Trepanation, extirpation, and biopsy of the mass were performed, and high-grade B-cell lymphoproliferation with Burkitt lymphoma-specific morphology and immunophenotype was confirmed. Chemotherapy was initiated according to B-NHL-2004 protocol for the R3 treatment group (Burkitt lymphoma IV, CNS +) with prophase + chemotherapy blocks. During chemotherapy, the boy had several very serious episodes of infection with sepsis and bilateral polysegmental lung damage. He was also found to be EBV DNA and IgG and IgM positive.
After chemotherapy, the boy reached complete remission. However, persistent hypogammaglobulinaemia was noted (shown in ), and consequently intravenous immunoglobulin was started.
As primary immunodeficiency was suspected, the boy was consulted by a geneticist. The Sanger sequencing analysis for the coding exons of the SH2D1A gene (NM_002351.5) was conducted. A hemizygous mutation was detected in the SH2D1A gene, NM_002351.4:c.5A > G, p.Asp2Gly, rs1556619319. It was classified as likely pathogenic, thus confirming a diagnosis of XLP. The classification was based on ACMG guidelines, fulfilling criteria PM1 (variant located in the functional domain); PM2 (variant not found in gnomAD exomes or genomes); PP2 (missense variant is the pathogenic mechanism in the SH2D1A gene); PP3 (multiple in silico tools suggesting pathogenicity); PP5 (reputable source, ClinVar classifies the variant as likely pathogenic) []. At present, the boy receives intravenous immunoglobulin regularly, and his condition is stable. Genetic testing for other family members were not performed.


The patient was a healthy 46-year-old female with no significant medical history (patient weight: 90.1 kg and height: 67 inches) who presented with a lateral malleolus fracture after a fall. She underwent an ORIF ankle, and surgery lasted about an hour and half. Her baseline preoperative pain score was 0, and she had no sensory or motor deficits. Preoperative nerve block placement was uneventful, and the patient received 20 mL of EXPAREL® 1.3% 20 ml (266 mg). On arrival to the PACU, she reported no cold sensation in the targeted dermatome areas; however, she reported 10/10 pain on VAS. In addition, the patient complained of pruritis, and she received 0.5 mg hydromorphone IV and diphenhydramine 50 mg IV. Her followed-up pain scores were 3/10 and 0/10 at 60 minutes and 120 minutes, respectively. On POD #1, the patient recorded a highest pain score of 8/10 and required 2 doses of Percocet 5/325 total for the day. On POD #2, the patient recorded a highest pain score of 10/10, so she took Advil for breakthrough pain as she reported pruritus after taking Percocet. On POD #3, her highest pain score was 4/10, and she continued to take Advil for breakthrough with two doses total for the day. The patient reported a 4/5 overall satisfaction score.


This patient was a 48-year-old female with a history of diabetes mellitus (type 2) (patient weight: 95 kg and height: 64 inches) who presented with a bimalleolar ankle fracture after a fall. The patient underwent an ORIF ankle, and her surgery lasted one hour and 15 minutes. Her preoperative pain score was 0/10, and she had no sensory or motor deficits. Preoperative nerve block placement was uneventful, and the patient received a single dose of EXPAREL® 1.3% 20 ml (266 mg). On arrival to the PACU, she reported no cold sensation in the targeted dermatome areas, 0/10 pain on VAS, and had a Ramsay sedation score of 3/6. Her pain score remained 0/10 for the entire PACU stay, while her sedation score improved to 2/6. On POD #1, the patient recorded a highest pain score of 8/10; however, she took no pain medication. On POD #2 and #3, the patient recorded pain scores of 0/10 for both days and had no oral pain medication requirements. For overall satisfaction, that patient recorded 5/5 and reported that her block lasted about three and half days (approximately 84 hours).


This patient was a 54-year-old female with no significant medical history (patient weight: 70.3 kg and patient height: 47 inches) who presented with a left bimalleolar fracture status after a fall. The patient underwent an ORIF ankle, and her surgery lasted 1 hour. Her preoperative pain score was 1/10, and she had no sensory or motor deficit. Nerve block placement was uneventful in the PACU where the patient received 20 mL of EXPAREL® 1.3% 20 ml (266 mg). The patient reported cold sensation in the targeted dermatome areas, with 3/10 pain. At 60 minutes of assessment, she had no cold sensation in the targeted dermatome and had a pain score of 5/10. At 120 minutes, her pain score was 0/10, and she did not require any pain medication while in the PACU. Postoperatively, the patient recorded 0/10 pain scores for POD #1–3 and took no breakthrough pain medication. She recorded an overall satisfaction score of 5/5 and reported that the block lasted about 72 hours.


The subject was a 49 year-old female with a history of hypertension, depression, and chronic low back pain (patient weight: 104 kg and height: 68 inches) who presented with a right bimalleolar fracture status after a fall. The patient underwent an ORIF ankle, and her surgery lasted 1 hours and 20 minutes. Her home medications included hydralazine-hydrochlorothiazide, metoprolol, and Percocet. Her preoperative pain score was 8/10, and she had no sensory or motor deficits. Nerve block placement was uneventful, and the patient received 20 mL of EXPAREL® 1.3% 20 ml (266 mg). In the PACU, she was sedated, not oriented, and had a Ramsay sedation score of 3. At 60 minutes, her sedation score had declined to 2/6, and she reported no cold sensation in the targeted dermatome with a pain score 0/10. At 120 minutes, her sensory and pain status were unchanged. On POD #1, the patient recorded 2/10 pain scores and took 5 doses of Percocet 5/325 for breakthrough pain. The record kept by the patient reported that the block wore off about 12 hours after placement. She was evaluated in the outpatient podiatry clinic and confirmed to have no sensory or motor deficits. When the patient woke up on the morning of POD #2, she reported a return of numbness to her foot and was unable to move her toes. Despite the return of numbness, the patient recorded a highest pain score of 10/10 and took 7 doses of Percocet and three doses of Motrin 600 mg throughout the day. On POD #3, the patient recorded a highest pain score of 4/10 and took three doses of Percocet for breakthrough pain. She reported that numbness continued up to the level of her calf. She recorded an overall satisfaction score of 4/5. After POD #3, the numbness in the foot resolved except a portion of her lateral foot in the sural nerve distribution. In this area, she had continuous numbness and developed hyperesthesia that lasted for 3 months (Tables –).