Cardiovascular Adverse Events Associated With Second-generation Bruton Tyrosine Kinase Inhibitor Therapy: A Systematic Review and Meta-analysis.

PURPOSE: Cardiovascular adverse events (CVAEs) are common adverse effects of first-generation Bruton tyrosine kinase inhibitors (BTKis) and limit their use considerably. This led to the development of second-generation BTKis-acalabrutinib and zanubrutinib-which are more selective, potent, and presumed to have better safety profiles than the previous group of medications. However, there have been sporadic reports of CVAEs associated with second-generation BTKis in clinical practice. To address this issue, a comprehensive meta-analysis to pool the documented CVAEs was performed, including major hemorrhage, any bleeding, atrioventricular block, atrial fibrillation/flutter, pericardial effusion, pericarditis, heart failure, cardiac arrest, myocardial infarction, hypertension, hypotension, and stroke. This meta-analysis incorporated 8 studies. Among these, 6 were Phase III trials and 2 were Phase II trials. These studies collectively enrolled a total of 2938 patients. METHODS: Multiple databases, including PubMed, MEDLINE, Cochrane Library, Scopus, and EMBASE, were systematically searched for relevant clinical trials from inception through January 14, 2023. The effect measure used was odds ratio (OR) and 95% CI. FINDINGS: Of a total of 1774 studies identified during the initial database search, 8 were included in the meta-analysis. The incidence of overall and cardiovascular mortality was comparable between the 2 groups. There were no significant differences observed for cardiovascular mortality (OR = 0.36; 95% CI, 0.08-1.65; n = 2588; I2 = 45%; P = 0.19). Similar results were found for all-cause mortality (OR = 0.85; 95% CI, 0.67-1.07), any bleeding (OR = 1.90; 95% CI, 0.88-4.09), major bleeding (OR = 1.07; 95% CI, 0.65-1.76), atrioventricular block (OR = 0.74; 95% CI, 0.15-3.68), atrial fibrillation/flutter (OR = 0.74; 95% CI, 0.37-1.50), and other CVAEs associated with second-generation BTKis. IMPLICATIONS: Based on the available evidence, there is no indication of worse cardiovascular outcomes or superiority of second-generation BTKis compared with standard treatments in terms of safety profile. However, additional large-scale controlled trials are needed to provide robust support for the superior tolerability of new-generation BTKis.

An Uncommon Side Effect of Rivaroxaban: A Drug-Induced Liver Injury.

Rivaroxaban is rarely associated with drug-induced liver injury (DILI). A 57-year-old male was sent to the emergency room from an endocrine clinic for a presyncope evaluation. His exam was non-focal, and his laboratory work was remarkable for the hepatocellular pattern of liver injury. Upon detailed assessment, he was found to have DILI due to rivaroxaban. The liver function tests improved after its discontinuation. This case emphasizes the need for early recognition and timely intervention to prevent further hepatotoxicity from the culprit drug.

A Rare Case of Elevated Transaminases With Incomplete Abortion Due to Cytomegalovirus Infection: An Experience From a Resource-Limited Setting.

Cytomegalovirus (CMV) infection during pregnancy may cause spontaneous abortion, stillbirth, and death of newborns. CMV is the most common congenital infection in newborns. It generally has a benign course in immunocompetent individuals, while the severe disease is usually seen in immunocompromised patients. Most of the published studies about CMV infection describe congenital abnormalities in newborns. Only a handful of case reports mention CMV infection associated with elevated transaminases during pregnancy. Here, we present a case of incomplete abortion with elevated liver enzymes in a 26-year-old female caused by CMV infection. Our case report illustrates the importance of considering CMV infection as a differential in an incomplete abortion associated with elevated liver enzymes.

A Case of Severe Aplastic Anemia in a 35-Year-Old Male With a Good Response to Immunosuppressive Therapy.

Aplastic anemia (AA) is a severe but rare hematologic condition associated with hematopoietic failure leading to decreased or total absent hematopoietic precursor cells in the bone marrow. AA presents at any age with equal distribution among gender and race. There are three known mechanisms of AA: direct injuries, immune-mediated disease, and bone marrow failure. The most common etiology of AA is considered to be idiopathic. Patients usually present with non-specific findings, such as easy fatigability, dyspnea on exertion, pallor, and mucosal bleeding. The primary treatment of AA is to remove the offending agent. In patients in whom the reversible cause was not found, patient management depends on age, disease severity, and donor availability. Here, we present a case of a 35-year-old male who presented to the emergency room with profuse bleeding after a deep dental cleaning. He was found to have pancytopenia on his laboratory panel and had an excellent response to immunosuppressive therapy.

Acute Portal Vein Thrombosis as an Initial Presentation of Protein C Deficiency: A Case Report.

Protein C (PC) is an essential vitamin K-dependent protein that regulates thrombosis and hemostasis in the body. A mutation in the PROC gene on chromosome 2q14.3 results in PC deficiency. The clinical presentation of PC deficiency can vary, ranging from a single vein thrombosis to disseminated intravascular coagulation, purpura fulminans, or even life-threatening complications such as sepsis. Here, we present a case of a 37-year-old female who was found to have acute portal vein thrombosis as an initial presentation of PC deficiency. She presented to the hospital with acute onset of abdominal pain associated with nausea, blood-streaked emesis, and bloody bowel movement.

Thrombophilia Testing in Stroke: A Case Report and Review of Evidence.

Thrombophilia is commonly associated with venous thromboembolism, but its relationship with arterial thrombosis, specifically stroke, is not as clearly established. Several large studies have failed to establish a significant connection between inherited thrombophilia and stroke. While tests for Factor V Leiden mutation, prothrombin mutation, protein C deficiency, protein S deficiency, antithrombin deficiency, and antiphospholipid antibodies are typically done for thrombophilia diagnosis, there appears to be little or no correlation between these markers and stroke. In this article, we discuss a case of a 26-year-old male admitted with right neck pain that developed after playing basketball; he was found to have a right cerebellar infarction. He underwent extensive tests for hypercoagulable disorders, which were negative. We also review current evidence and reassess the value of thrombophilia testing in stroke patients.

Vasopressin versus norepinephrine as the first-line vasopressor in septic shock: A systematic review and meta-analysis.

Background and Aim: Norepinephrine is currently the first-line vasopressor for septic shock. We conducted this meta-analysis to examine the outcomes of adult patients with septic shock who received vasopressin instead of norepinephrine. Methods: We selected studies in adults with septic shock that compared the outcomes of patients treated with vasopressin versus norepinephrine. Cochrane ROB 2.0 and the Joanna Briggs Institute quality assessment tools were used to assess the risk of bias in RCTs and observational studies. Meta-analysis was conducted using RevMan 5.4. Results: Eight studies were included in this meta-analysis. There were no significant differences in 28-day mortality rates (OR, 1.07; CI, 0.80-1.44) and intensive care unit (ICU) mortality (OR, 0.74; CI, 0.21-2.67) between the two groups. Similarly, length of ICU stay, length of hospital stay, mean arterial pressure at 24 h, urine output at 24 h, and serious adverse events also did not differ significantly. However, the odds of renal replacement therapy (RRT) requirement in the vasopressin group were substantially lower than in the norepinephrine group (OR, 0.68; CI, 0.47-0.98). Conclusion: There were no differences in mortality, duration of hospitalization, and adverse effects in adults with septic shock across the two groups. However, the patients treated with vasopressin had lower chances of requiring RRT. Relevance for Patients: Vasopressin use as the first-line vasopressor in septic shock showed a significant reduction in RRT, though there were no significant differences in terms of mortality and other adverse events. Therefore, vasopressin can be considered as a first-line vasopressor in septic shock patients with other risk factors which may contribute to renal failure requiring RRT.

A Diagnostic Enigma of Central Versus Nephrogenic Diabetes Insipidus: What Does the Value of Copeptin Signify?

Diabetes insipidus (DI) is a rare disease characterized by hypotonic urine output and polydipsia. We report the case of a 50-year-old male admitted for diabetic ketoacidosis (DKA) in an intensive care unit with sepsis and alcoholic pancreatitis who later developed DI. He had a high copeptin level of >21.4 pmol/L, suggesting DI of nephrogenic origin. At presentation, he had DKA-associated osmotic diuresis. His later finding of elevated copeptin suggesting partial nephrogenic DI created a diagnostic enigma.

Immune Thrombocytopenic Purpura Following Pfizer-BioNTech COVID-19 Vaccine in an Elderly Female.

Mass vaccination campaigns are being run all over the globe to combat the ongoing COVID-19 pandemic. There have been several reports of immune thrombocytopenic purpura (ITP) occurrence following COVID-19 vaccination. However, ITP due to the Pfizer-BioNTech vaccine has been rarely reported, and a causal link has not been identified. The pathophysiology behind immune thrombocytopenia is similar to heparin-induced thrombocytopenia. The management is also similar to other secondary immune thrombocytopenia. We present a case of a 67-year old female diagnosed with immune thrombocytopenia following Pfizer-BioNTech vaccination. The treatment was resistant to high-dose steroids, intravenous immunoglobulin (IVIG), and rituximab and eventually responded to a thrombopoietin-stimulating agent.

Tubercular Pericardial Effusion Presenting as Cardiac Tamponade.

Pericardial effusion is an uncommon extra-pulmonary manifestation of tuberculosis, tamponade being even rarer. Here, a 14-year female presented with cough, chest pain and fever. She had raised jugular venous pressure, hypotension, and muffled heart sound, suggestive of cardiac tamponade, confirmed by echocardiogram. She underwent pericardiocentesis with continuous pericardial fluid drainage. Her jugular venous pressure normalized after the aspiration. The high adenosine deaminase level in pericardial fluid analysis was suggestive of tuberculosis for which she was treated with antitubercular therapy and steroid. This case highlights the importance of adenosine deaminase for diagnosing the etiology of a rare presentation. Keywords: Adenosine deaminase; echocardiography; pericardial effusion; tamponade; tuberculosis.