Bilateral myelomatous pleural effusions: an unusual presentation in newly diagnosed multiple myeloma.

Multiple myeloma is a rare haematological malignancy characterised by the clonal proliferation of plasma cells within the bone marrow. Typical manifestations include bone pain, fatigue and monoclonal protein elevation in serum and urine. Less than 1% of cases develop myelomatous pleural effusion, a severe complication indicative of advanced disease and a very poor prognosis.Here, we present a case of a woman with a new diagnosis of multiple myeloma complicated by bilateral myelomatous pleural effusions as the initial presentation. This case underscores the diverse clinical spectrum of multiple myeloma, the significance of timely diagnosis and the threatening implications associated with myelomatous pleural effusions.

Prior Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers and Clinical Outcomes of Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

ABSTRACT: Sepsis and septic shock are life-threatening conditions that are associated with high mortality and considerable health care costs. The association between prior angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) use and outcomes after sepsis is elusive. The aim of this study was to evaluate the role of the prior use of ACEi or ARBs and outcomes after sepsis and septic shock. A relevant literature review was performed in 4 databases from inception until July 2022. Independent reviewers first screened the title, abstract, and full text, and then, data extraction and analysis were performed. One post hoc analysis of a trial and 6 retrospective cohort studies were included in this review. There were 22% lower odds of in-hospital/30-day mortality among patients who have used ACEi/ARBs in the past [23.83% vs. 37.20%; odds ratio (OR), 0.78, 95% confidence interval (CI), 0.64-0.96], and reduced 90-day mortality (OR, 0.80, 95% CI, 0.69-0.92). ACEi/ARBs users were found to have 31% lesser odds of developing acute kidney injury as compared with nonusers (OR, 0.69, 95% CI, 0.63-0.76). There was no significant difference in the length of hospital stay (MD 1.26, 95% CI, ‒7.89 to 10.42), need for renal replacement therapy (OR, 0.71, 95% CI, 0.13-3.92), mechanical ventilation (OR, 1.10, 95% CI, 0.88-1.37) or use of vasopressors (OR, 1.21, 95% CI, 0.91-1.61). Based on this analysis, prior use of ACEi/ARBs lowers the risk of mortality and adverse renal events in patients with sepsis and septic shock.

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.

Novel Pharmacological Treatment Options of Steroid-Refractory Graft-versus-Host Disease.

Background: Graft-versus-host disease (GVHD) is a potentially fatal complication of allogeneic hematopoietic stem cell transplant. The mainstay of treatment is corticosteroids, which are ineffective in 30-50% of cases. Steroid-refractory GVHD (SR-GVHD) confers a poor prognosis, with high mortality rates despite appropriate therapy. While there is no reliable treatment for SR-GVHD, a variety of novel therapeutic options are slowly emerging and have yet to be examined simultaneously. Objectives: This review evaluates the potential of novel therapeutic options, as well as their efficacy and safety, for the treatment of SR-GVHD. Study Design. The literature search was conducted in PubMed, Cochrane, and Embase, employing MeSH terms and keywords. The studies had to be prospective phases 1, 2, or 3. We excluded retrospective and nonoriginal studies. Results: While the only approved drug for acute GVHD is ruxolitinib with an impressive overall response rate of 73.2% and a complete response of 56.3%, several monoclonal antibodies and other agents are currently under investigation, offering promising results. These include anti-CD2, anti-CD147, IL-2 antagonist, a mixture of anti-CD3 and anti-CD7 antibodies, anti-CD25, monoclonal antibody to a4b7 on T-cells, anti-CD26, pentostatin, sirolimus, denileukin diftitox, infliximab, itacitinib, and alpha-1 antitripsin. However, the toxicities associated with these novel drugs need further investigation. For chronic GVHD, approved options include ruxolitinib with an ORR of up to 62%, ibrutinib with an ORR of up to 77%, and belumosudil with an ORR of up to 77%. Meanwhile, emerging treatments include tyrosine kinase inhibitors such as nilotinib, rituximab, and low-dose IL-2, as well as axatilimab and pomalidomide. Conclusion: While their efficacy needs to be better evaluated through large-scale, multicenter, randomized clinical trials, these novel agents show potential and could provide a better alternative for SR-GVHD treatment in the future.

Partially Reversible Bilateral Papilledema in a Patient Using Anastrozole: A Case Study.

Anastrozole is an endocrine-modifying agent used in the treatment of estrogen-sensitive breast cancer in the postmenopausal breast cancer population. Anastrozole is known for its side effect profile which includes an increased risk of osteoporosis. However, emerging evidence in the literature in the form of case studies demonstrates several potential ocular side effects due to the use of the medication. In our study, a 66-year-old female using anastrozole suffered severe bilateral papilledema that resolved after cessation of the medication. There is a growing body of evidence demonstrating the use of anastrozole and its impact on ocular health leading to deleterious side effects, such as papilledema.

Effect of fibrinolytic therapy on ST-elevation myocardial infarction clinical outcomes during the COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: ST-elevation myocardial infarction (STEMI) is the result of transmural ischemia of the myocardium and is associated with a high mortality rate. Primary percutaneous coronary intervention (PPCI) is the recommended first-line treatment strategy for patients with STEMI. The timely delivery of PPCI became extremely challenging for STEMI patients during the coronavirus disease 2019 (COVID-19) pandemic, leading to a projected steep rise in mortality. These delays were overcome by the shift from first-line therapy and the development of modern fibrinolytic-based reperfusion. It is unclear whether fibrinolytic-based reperfusion therapy is effective in improving STEMI endpoints. AIM: To determine the incidence of fibrinolytic therapy during the COVID-19 pandemic and its effects on STEMI clinical outcomes. METHODS: PubMed, Google Scholar, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were queried from January 2020 up to February 2022 to identify studies investigating the effect of fibrinolytic therapy on the prognostic outcome of STEMI patients during the pandemic. Primary outcomes were the incidence of fibrinolysis and the risk of all-cause mortality. Data were meta-analyzed using the random effects model to derive odds ratios (OR) and 95% confidence intervals. Quality assessment was carried out using the Newcastle-Ottawa scale. RESULTS: Fourteen studies including 50136 STEMI patients (n = 15142 in the pandemic arm; n = 34994 in the pre-pandemic arm) were included. The mean age was 61 years; 79% were male, 27% had type 2 diabetes, and 47% were smokers. Compared with the pre-pandemic period, there was a significantly increased overall incidence of fibrinolysis during the pandemic period [OR: 1.80 (1.18 to 2.75); I2= 78%; P = 0.00; GRADE: Very low]. The incidence of fibrinolysis was not associated with the risk of all-cause mortality in any setting. The countries with a low-and middle-income status reported a higher incidence of fibrinolysis [OR: 5.16 (2.18 to 12.22); I2 = 81%; P = 0.00; GRADE: Very low] and an increased risk of all-cause mortality in STEMI patients [OR: 1.16 (1.03 to 1.30); I2 = 0%; P = 0.01; GRADE: Very low]. Meta-regression analysis showed a positive correlation of hyperlipidemia (P = 0.001) and hypertension (P < 0.001) with all-cause mortality. CONCLUSION: There is an increased incidence of fibrinolysis during the pandemic period, but it has no effect on the risk of all-cause mortality. The low- and middle-income status has a significant impact on the all-cause mortality rate and the incidence of fibrinolysis.

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.

Atraumatic Splenic Rupture as an Unusual Presentation of Hairy Cell Leukemia: A Case Report.

Hairy cell leukemia (HCL) represents a rare B-cell malignancy with 2% of all leukemias and should be differentiated from HCL-like conditions, including HCL-variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL). HCL gets its name from the short, thin projections that look like hair on its cells. It is associated with a specific immunophenotypic profile, cytopenia, and splenomegaly. Spontaneous splenic rupture can be a symptom of hematological malignancy such as HCL and is a life-threatening acute emergency. Here, we present a case of a 37-year-old man who presented to the hospital with signs of acute peritonitis and acute anemia and was found to have atraumatic splenic rupture secondary to splenomegaly. He underwent emergent angiography, where the bleeding splenic vessel was identified, and the patient was successfully treated with embolization. Immunophenotypic profile revealed that B-cells were positive for CD11c, CD103, CD25, and CD5, for which he received five days of cladribine and achieved complete clinical remission.

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.

Navigating the Storm: Managing Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) in a High-Risk Pregnancy.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare, life-threatening condition causing significant thrombocytopenia and bleeding with the risk of developing intracerebral hemorrhage (ICH). It results from maternal immunizations against fetal platelet antigens. Here, we report a case of a pregnant patient at 30 weeks gestation who presented to the hospital with a low platelet count of 90 th/mm3 and was found to have anti-human platelet antigen (HPA) 1a, 2b antibodies. She was treated with a weekly infusion of IV immunoglobulins. However, her condition was complicated by the development of hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, which was treated promptly with a platelet transfusion and intravenous magnesium. Even though the child had severe thrombocytopenia and its associated complications, there were no signs of post-delivery thrombocytopenia or any other adverse effects. This case report highlights the importance of the antenatal management of the FNAIT to prevent severe fetal complications, such as ICH.

Current Targeted Therapy Options in the Treatment of Cholangiocarcinoma: A Literature Review.

Biliary cancer (BC) is a rare disease. It is formed from the biliary epithelium of the small ducts in the liver periphery (intrahepatic) and the main ducts of the hilum (extrahepatic). The incidence of intrahepatic carcinoma is rising in the western world, and the incidence of gallbladder cancer is declining. Surgical treatment is the primary treatment option for localized forms of these tumors, but only a small group of patients is eligible for it. Palliative therapy is the standard treatment option for those with advanced cases, and it mainly relies on chemotherapy. The advanced form's five-year survival of BC does not exceed 5%. However, targeted therapy aimed at tumors with fusion mutations of the fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase (IDH) 1 and 2, the genes encoding the B-Raf protein (BRAF), breast cancer (BRCA1/2), epidermal growth factor receptor 2 (HER2), and the neurotrophic receptor tyrosine kinase gene (NTRK), is gradually changing the paradigm in the treatment of this disease. This can be seen especially in approaches to treating intrahepatic cholangiocarcinoma, which is associated with a high incidence of mutations. This literature review aims to provide the latest scientific evidence regarding targeted therapy in treating cholangiocarcinoma.

Food Allergy Prevention: Early Versus Late Introduction of Food Allergens in Children.

The emergence of food allergies in children is crucial for various medical fields seeking a viable strategy for allergy prevention. The most well-recognized approach adopted by numerous health care and government institutions hinges on the delay in the introduction of food allergens, which supposedly protects infants from sensitization and decreases the possibility of allergy development. However, recent experimental findings indicate that the benefits of this approach might be overestimated, as early exposure to allergenic foods has been shown to yield more advantageous outcomes. Multiple investigations on the causes of allergic diseases report that avoiding food allergies might be related to early consumption of these allergens. Alternatively, delaying the contact with allergenic nourishments, explored in contemporary research, has been proven to result in a higher prevalence of allergies among children, originating such conditions as atopic diseases and extreme sensitization to foods. The current paper compares the two prominent strategies of allergenic food introduction, gathering the most pertinent modern evidence to distinguish whether exposure to food allergens should be delayed or advanced.

Pharmacologic Management of Coronary Artery Ectasia.

Coronary artery ectasia (CAE) is a rare form of aneurysmal coronary heart disease. It is defined as a dilatation of the coronary artery by more than one-third of its length and with a diameter 1.5 times of a normal coronary artery adjacent to it. This condition increases the risk of angina pectoris and acute coronary syndrome. Hence, we discuss the pharmacologic options for primary and secondary prevention of CAE complications. Antiplatelets such as aspirin are considered the mainstay of treatment in patients with CAE. Anticoagulants such as warfarin are warranted on a case-by-case basis to prevent thrombus formation depending on the presence of concomitant obstructive coronary artery disease and the patient's risk of bleeding. Since atherosclerosis is the most common cause of CAE, statins are indicated in all patients for primary prevention. Angiotensin-converting enzyme (ACE) inhibitors may be indicated, especially in hypertensive patients, due to their anti-inflammatory properties. Beta-blockers may be indicated due to their antihypertensive and anti-ischemic effects. Calcium (Ca) channel blockers may be needed to prevent coronary vasospasm. Nitrates are generally contraindicated as they may lead to worsening of symptoms. Other antianginal medications such as trimetazidine can improve exercise tolerance with no reported adverse events in these patients.

Mechanisms and Potential Treatment Options of Heart Failure in Patients With Multiple Myeloma.

Multiple myeloma is a pathology of plasma cells, with one of the most common side effects of its treatment is heart failure. In addition, cardiac amyloidosis could cause heart failure by itself. Even though mechanisms of cardiac amyloidosis are known, and they involve lysosomal dysfunction, reactive oxygen species (ROS) accumulation, and infiltrative effect by fibrils, there is no specific agent that could protect from these effects. While the molecular mechanism of doxorubicin cardiotoxicity via topoisomerase II ß is established, the only FDA-approved agent for treatment is dexrazoxane. Liposomal doxorubicin can potentially improve response and decrease the development of heart failure due to microscopic liposomes that can accumulate and penetrate only tumor vasculature. Supplements that enhance mitochondrial biogenesis are also shown to improve doxorubicin-induced cardiotoxicity. Other agents, such as JR-311, ICRF-193, and ursolic acid, could potentially become new treatment options. Proteasome inhibitors, novel agents, have significantly improved survival rates among multiple myeloma patients. They act on a proteasome system that is highly active in cardiomyocytes and activates various molecular cascades in malignant cells, as well as in the heart, through nuclear factor kappa B (NF-kB), endoplasmic reticulum (ER), calcineurin-nuclear factor of activated T-cells (NFAT), and adenosine monophosphate-activated protein kinase (AMPKa)/autophagy pathways. Metformin, apremilast, and rutin have shown positive results in animal studies and may become a promising therapy as cardioprotective agents. This article aims to highlight the main molecular mechanisms of heart failure among patients with multiple myeloma and potential treatment options to facilitate the development and research of new preventive strategies. Hence, this will have a positive impact on life expectancy in patients with multiple myeloma.

The Pathophysiology of Anorexia Nervosa in Hypothalamic Endocrine Function and Bone Metabolism.

Anorexia nervosa (AN) is a persistent psychiatric disorder that is marked by abnormal reduced weight and amenorrhea, which may be primary or secondary. AN affects multiple endocrine axes such as gonadal, thyroid, and adrenal axis, growth hormone, and insulin-like growth factor-1, adipokines such as leptin, gut peptides like ghrelin, peptide YY, and amylin. As a result of these changes bone mineral density is reduced, which increases the risk of bone fracture in patients. In this review, we focus on substantial endocrine alterations in AN with a particular emphasis on the severe bone loss associated with this condition and current bone therapies. The disorder primarily affects girls and women, who are the focus of this review. Although the majority of AN-related endocrinopathies improve over time, long-term consequences such as short stature, osteoporosis, and infertility may occur. To avoid serious consequences, nutrition therapy in these patients requires a full understanding of bone complications, and new therapeutic options for treatment should be researched.