Prevalence and clinical implication of thrombocytopenia and heparin-induced thrombocytopenia in patients who are critically ill with COVID-19.

As the COVID-19 pandemic continues to evolve, different clinical manifestations are better understood and studied. These include various haematologic disorders that have been shown to be associated with increased morbidity and mortality. We studied the prevalence of one unusual manifestation, heparin-induced thrombocytopenia (HIT) and its clinical implications in patients who are severely ill with COVID-19 in a single tertiary centre in Israel. The presence of thrombocytopenia, disseminated intravascular coagulation (DIC) and HIT, and their association with clinical course and outcomes were studied. One-hundred and seven patients with COVID-19 were included. Fifty-seven (53.2%) patients developed thrombocytopenia, which was associated with the worst outcomes (ventilation, DIC and increased mortality). Sixteen (28.0%) patients with thrombocytopenia were positive for HIT, all of which were supported by extracorporeal devices. HIT was independently associated with ventilation days, blood product transfusions, longer hospitalisation and mortality.Platelet abnormalities and HIT are common in patients who are critically ill with COVID-19 and are associated with the worst clinical outcomes. The mechanisms underlying HIT in COVID-19 are yet to be studied; HIT may contribute to the dysregulated immunologic response associated with COVID-19 critical illness and may play a significant part in the coagulopathy seen in these patients. As many patients with COVID-19 require aggressive thromboprophylaxis, further understanding of HIT and the implementation of appropriate protocols are important.

Management and outcome of patients with non-ST elevation myocardial infarction and intercurrent non-coronary precipitating events.

AIMS: To evaluate the effect of an intercurrent non-coronary illness on the management and outcome of patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS AND RESULTS: Consecutive hospitalized patients with a primary diagnosis of NSTEMI between August 2008 and December 2019 at Sheba Medical Center. All patients' records were reviewed for the presence of a non-coronary precipitating event (NCPE): a major intercurrent acute non-coronary illness or condition, either cardiac or non-cardiac. The primary outcome was all-cause mortality. Cox regression with interaction analysis was applied. Final study population comprised 6491 patients, of whom 2621 (40%) had NCPEs. Patients with NCPEs were older (77 vs. 69 years) and more likely to have comorbidities. The most prevalent event was infection (35%, n = 922). During a median follow-up of 30 months, 2529 patients died. Patients with NCPEs were 43% more likely to die during follow-up in a multivariable model (95% CI: 1.31-1.55). Invasive strategy was associated with a 55% lower mortality among patients without NCPE and only 44% among patients with NCPE (P for interaction < 0.001). Dual antiplatelet therapy (DAPT) was associated with a 20% lower mortality in patients without NCEP and a non-significant mortality difference among patients with NCPE (P for interaction = 0.014). Sub-analysis by the specific NCPE showed the highest mortality risk among patients with infectious precipitant. The lower mortality associated with invasive strategy was not observed in this subgroup. CONCLUSION: Among NSTEMI patients, the presence of an NCPE is associated with poor survival and modifies the effect of management strategies.

[ETHICAL CHALLENGES IN TREATING CRITICAL CORONAVIRUS PATIENTS: EXPERIENCE FROM THE SHEBA MEDICAL CENTER ON THE FIRST COVID-19 PANDEMIC OUTBREAK].

INTRODUCTION: As the coronavirus pandemic emerged in late 2019, a task force was founded in the Sheba Medical Center and began preparing for the arrival of the pandemic to Israel. Several wards were put in charge of isolated COVID-19 patients. A new intensive care unit was formed for the most critical COVID-19 patients, requiring mechanical ventilation and multi-organ treatment. The Corona ICU began operating in March 2020, with a multi-disciplinary team, gathered from ICU units, an internal medicine ward, an anesthesiology department, social workers and psychologists. Simultaneously, the routine medical center functions in non-corona sections were maintained, as much as possible. The coronavirus pandemic entails challenges of many aspects: an unfamiliar pathogen causing an unknown illness, a necessity for social distancing, ambiguity regarding the risk factors for contamination and illness severity, and medical crews put at risk. Consequently, the pandemic involves ethical, social, economic and moral aspects, affecting the medical crew members and system, the patients and their families, and our society as a whole. In this article we review our joint experience in the Sheba Medical Center Corona ICU, of the medical, ethical and moral dilemmas that emerged from the first COVID-19 wave.

Assessing the effects of beta-blockers on pancreatic cancer risk: A nested case-control study.

PURPOSE: Both ß1- and ß2-adrenoceptor proteins were detected on the cell surface of pancreatic ductal adenocarcinoma. The current study evaluated the association between beta-blocker use and pancreatic cancer risk. METHODS: We conducted a nested case-control study in a large population representative database. Each pancreatic cancer case was matched with four controls based on age, sex, practice site, and duration of follow-up using incidence density sampling. Beta-blocker use was defined as any prescription prior to index date and was stratified into non-selective and selective ß1 -blockers. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for pancreatic cancer risk associated with beta-blocker use was estimated using conditional logistic regression. RESULTS: The study included 4113 patients with pancreatic cancer and 16 072 matched controls. When compared to never users, there was no association between any beta-blocker use and pancreatic cancer risk (adjusted OR 1.06, 95% CI 0.97-1.16, P = .16). Analysis by receptor selectivity showed use of non-selective beta-blockers for more than 2 years was associated with a reduced pancreatic cancer risk (OR 0.75, 95% CI 0.57-1.00, P = .05). When compared to former users both users of selective ß1-blockers and non-selective beta-blockers had a reduced pancreatic cancer risk (OR 0.78, 95% CI 0.67-0.90, P = .001) and (OR 0.67, 95% CI 0.49-0.92, P = .01), respectively. CONCLUSION: Beta-blocker use was not associated with increased pancreatic cancer risk. However, long-term use of beta-blockers may be associated with decreased pancreatic cancer risk.

[ACUTE RENAL FAILURE INDUCED BY METAMIZOLE].

INTRODUCTION: Sodium metamizole (Optalgin) is one of the most prevalent analgesic and anti-pyretic medications used in Israel. We describe a case of acute kidney injury subsequent to the use of metamizole in a healthy young patient. Metamizole may cause kidney injury in a number of different mechanisms and it is vital that this fact will be emphasized due to the widespread use of this medication.

Polyneuropathy, Myocardial Dysfunction and Pericardial Effusion Following Duodenal Switch.

Duodenal Switch procedure is a type of bariatric surgery that was reserved for severely morbid obese people. Patients undergoing this procedure are at high risk for nutrient deficiencies. In this report we present a case of a patient who had developed polyneuropathy, generalized muscle weakness, Wernicke encephalopathy, myocardial dysfunction and pericardial effusion six years following this operation. He was treated by multivitamins and trace elements with a complete resolution of all of these disturbances. The patient was fully rehabilitated.

Clinical characteristics and risk factors for low dose methotrexate toxicity: a cohort of 28 patients.

OBJECTIVE: Low dose (10-25 mg/week) methotrexate is widely used for the management of systemic inflammatory diseases, and is considered to be relatively safe. Toxicity due to low dose MTX has been reported but is poorly characterized. We describe the clinical features, risk factors, and outcomes of low dose MTX toxicity in a large case series at our center. PATIENTS AND METHODS: We conducted a retrospective case series of all adult (>18 years) patients hospitalized at Sheba Medical Center, between 2005 and 2012 for low dose MTX toxicity. RESULTS: We identified 28 patients (age: 70.4±13.7 years, range: 33-88; 20 (71%) females) hospitalized for low dose MTX toxicity. Indications for MTX therapy included: rheumatoid arthritis (39.2%), psoriasis±arthritis (21.5%), polymyalgia rheumatica (10.8%) and other inflammatory conditions (28.5%). Pancytopenia was the most common manifestation of low dose MTX toxicity detected in 78.5% of the patients. Potential risk factors included acute renal failure, hypoalbuminemia, concurrent use of drugs known to interact with MTX, and dose errors. Serum MTX concentrations (n=20, mean 0.04±0.07 µg/mL range: 0-0.3) did not correlate with the degree of either neutropenia (r=-0.36; p=0.18) or thrombocytopenia (r=0.44; p=0.10). Seven (25%) patients died, all from pancytopenia followed by sepsis. Serum MTX concentrations did not differ between the patients who died from MTX toxicity (n=6; mean: 0.05±0.04 µg/mL) and those who survived the toxicity (n=14 mean 0.04±0.08; p=0.45). CONCLUSIONS: Low-dose MTX toxicity can be life threatening, mainly due to myelosuppression. There is no rationale for MTX therapeutic drug monitoring in the setting of low-dose toxicity.

[Peripheral arthritis in polymyalgia rheumatica].

Polymyalgia rheumatica is characterized by aching and stiffness of the shoulder, the pelvic girdles and the neck. Peripheral joint involvement is less recognized by the medical community as a sign of the disease. In this article we present two patients whose disease was manifested by peripheral symptoms. The frequency, manifestations and the pathogenesis of the disorder are discussed and the importance of recognition of these symptoms and signs of the disease is stressed.

Tumor lysis syndrome and malignant melanoma.

Tumor lysis syndrome (TLS) is an oncological emergency that results from massive cytolysis of malignant cells with a sudden release of their contents into the systemic circulation. TLS was rarely described in patients with malignant melanoma. In this article, we describe two patients with malignant melanoma who developed this syndrome. In one of them, the syndrome occurred spontaneously, and this is the second description of spontaneous tumor lysis in a patient with melanoma. We reviewed the previous patients with melanoma-induced TLS and discussed the manifestations and the pathophysiology of the syndrome in our patients.

[Allergic reaction induced by steroid therapy].

Glucocorticoids are widely used for the treatment of allergies and various inflammatory conditions. However, steroids can cause allergic reactions, even anaphylaxis. The incidence of adverse reactions induced by steroids is up to 0.3%. The most commonly reported steroids causing anaphylaxis are hydrocortisone, prednisone and methylprednisotone. In this report we describe an 86 years old patient who developed stridor and respiratory failure immediately after treatment with hydrocortisone. The risk factors and the management of these reactions are discussed. It is important that the medical community should recognize and be aware of such reactions.

Kikuchi-Fujimoto disease.

BACKGROUND: Kikuchi-Fujimoto disease is a benign and self-limited disease, first reported in Japan in 1972. The characteristic features of this disorder include lymphadenopathy and fever. OBJECTIVES: To summarize our experience with Kikuchi disease with regard to clinical manifestations and outcome. METHODS: The patients included in the study were those diagnosed with Kikuchi disease during the years 2005-2008 in two departments of internal medicine at Sheba Medical Center. RESULTS: We identified five patients with Kikuchi disease; four were women and the mean age was 22.6 years. All the patients had cervical lymphadenopathy; three had other sites of lymphadenopathy. Four of the patients had fever higher than 39 degrees C. Two of them had splenomegaly and three reported weight loss. Three of the five patients experienced a relapse of the disease and were treated with steroids or non-steroidal anti-inflammatory agents. The diagnosis was confirmed in all the patients by an excisional biopsy of lymph node. CONCLUSIONS: Kikuchi disease must be considered in every young patient with fever and lymphadenopathy. The disease usually has a benign course.

West Nile virus-induced pancreatitis.

West Nile Virus (WNV) infection is a fairly common infection in Israel, especially during the summer season. Common manifestations are fever, headaches, malaise and myalgia. Pancreatitis had been described only twice previously as a complication of WNV infection in the medical literature. In this report, an 88-year-old patient is described, who was admitted to hospital with fever, confusion and general deterioration in her condition, accompanied by severe abdominal pain. WNV infection was diagnosed by a lumbar puncture and serological tests. The laboratory results demonstrated elevated amylase and lipase levels. The patient was treated conservatively and the symptoms regressed slowly until full recovery. WNV infection and its complications are described, along with descriptions of previous reports of pancreatitis associated with WNV infection.

Flare-up of ulcerative colitis after systemic corticosteroids: a strong case for Strongyloides.

Super-imposed infection with intestinal organisms can mimic a flare-up of underlying disease in patients with inflammatory bowel disease (IBD). We report a case of patient with long standing ulcerative colitis (UC), who presented with abdominal pain, diarrhea and low-grade fever after receiving systemic corticosteroids for an unrelated disorder. Despite a negative stool examination, a peripheral eosinophilia reappeared upon tapering down of a corticosteroid dose. Subsequently, duodenal biopsies showed evidence for Strongyloides, presumably acquired 20 years ago when the patient was residing in Brazil. The patient fully recovered following anti-helmintic therapy. This case underscores the importance of considering Strongyloides in the work-up of flaring-up IBD patients, even if a history of residing or traveling to endemic areas is in the distant past.

Hyperglobulinemia in amiodarone-induced pneumonitis.

BACKGROUND: Amiodarone is a very effective antiarrhytmic drug. However its use may be accompanied by side effects. Hyperglobulinemia was not described in association with amiodarone treatment. MATERIALS AND METHODS: Fifteen patients, who developed hyperglobulinemia while on amiodarone therapy, were identified among the patients hospitalized in our hospital. Serum globulin concentration was measured prior to, during and after amiodarone therapy. RESULTS: In 11 of the 15 patients with amiodarone-associated hyperglobulinemia, amiodarone treatment had to be stopped because of amiodarone-induced complications, nine of them had pneumonitis. Mean serum globulin level rose during amiodarone therapy from 2.48 +/- 0.51 g/dL to 4.11 +/- 0.71 g/dL (p = 0.001), and declined after it was stopped to 2.80 +/- 0.49 g/dL (p = 0.001). In 50 patients treated by amiodarone, serum globulin was similar to that found in 50 patients with ischemic heart disease not treated by amiodarone [2.64 +/- 0.39 g/dL and 2.56 +/- 0.29 g/dL respectively (p = 0.21)]. CONCLUSIONS: In some patients amiodarone therapy may be associated with hyperglobulinemia. The incidence of this association is not known. Most of the patients with amiodarone-associated hyperglobulinemia have amiodarone-induced toxicity, mainly pneumonitis. Amiodarone therapy does not cause a general increase in serum globulins. Hyperglobulinemia may be a marker for a damaged organ, or it may have a pathogenetic role in the induction of pneumonitis.