Clinical Research in Chronic Lymphocytic Leukemia in Pakistan; A Systematic Review.

Background: Significant advances have been made in the treatment of chronic lymphocytic leukemia (CLL) since the turn of the new millennium. However, most clinical trials were done in developed countries where minority ethnicities were underrepresented. Materials and Methods: To gauge the quality of research in CLL being done in Pakistan, we conducted a comprehensive literature search using PubMed, Clinicaltrials.gov, and Google Scholar on 14 January 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Results: A total of 16 studies met the inclusion criteria. The most common study design was cross-sectional. Eight studies evaluated the clinicohematological profile of CLL patients and the effect of various cytogenic abnormalities through fluorescence in situ hybridization (FISH) technique on disease progression and prognosis. Five studies discussed the prevalence of abnormalities such as autoimmune cytopenias and other serum chemistry derangements. Only two studies evaluated treatment outcomes, among which one study reported a 2-year overall survival of 65% among patients with 17p deletion. None of the studies had patients on novel targeted agents. No pharmaceutical sponsored or funded clinical trials were found. Conclusions: Our review suggests that although small clinical studies continue to be performed across the country, multiple financial and logistical barriers need to be addressed for larger, more impactful clinical trials to be conducted that will help answer demographic-specific questions and decrease reliance on foreign studies.

Uncovering the Uncommon: An 81-Year-Old Woman With Elevated Carcinoembryonic Antigen (CEA) but Normal Calcitonin Levels Diagnosed With Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor. However, non-elevated calcitonin levels have been reported in the literature. We present the case of an 81-year-old woman with chronic elevations in carcinoembryonic antigen (CEA) levels for the past 15 years, despite normal calcitonin levels, who was ultimately diagnosed with MTC. The patient had a remote history of breast cancer and presented with symptoms of unintentional weight loss, fatigue, and joint pain. A positron emission tomography (PET) scan revealed low fluorodeoxyglucose (FDG) uptake in partially calcified thyroid nodules, and fine needle aspiration cytology was consistent with medullary carcinoma. The patient underwent total thyroidectomy, with pathology revealing a pT1aN0M0 medullary thyroid microcarcinoma with negative margins. After thyroidectomy, CEA levels decreased to within the normal range, and calcitonin levels remained normal. This case highlights the importance of considering MTC in patients with unexplained chronic elevations in CEA levels, even with normal calcitonin levels.

Recurrent ST-Elevation Myocardial Infarction (STEMI) in Coronary Artery Aneurysm Secondary to Atherosclerosis.

We describe a rare case of coronary artery aneurysm (CAA) with recurrent ST-elevation myocardial infarction (STEMI) despite being on standard dual antiplatelet therapy (DAPT). A 47-year-old male presented with chest pain and was found to have inferior wall STEMI along with diffuse right coronary artery (RCA) ectasia and proximal RCA aneurysm, thrombotic occlusion, and dissection. He was managed with extensive thrombectomy, angioplasty, prolonged Heparinization, and DAPT. The patient went on to have a similar presentation nine months later with a recurrent inferior wall STEMI with proximal RCA aneurysm and thrombotic occlusion managed with thrombectomy and bare metal stent placement. He was placed on long-term anticoagulation and DAPT with no further recurrence of MI reported on follow-up.

Copper deficiency, a rare but correctable cause of pancytopenia: a review of literature.

INTRODUCTION: Copper is increasingly being recognized as a vital mineral required by both animals and humans. It plays a vital role in many metabolic processes such as cellular respiration, iron oxidation, and hemoglobin synthesis. Copper deficiency, which can be hereditary or acquired, can lead to a wide spectrum of disease processes such as ringed sideroblastic anemia, myelodysplasia, and pancytopenia. Timely identification and management of copper deficiency is necessary to prevent irreversible complications. AREAS COVERED: Our study focuses on prevalence, etiology, pathophysiology, complications, and treatment of copper deficiency. EXPERT OPINION: Copper deficiency is frequently underrecognized as the cause of anemia, neutropenia, and bone marrow dysplasia. As it is potentially treatable, it should always be kept in the differentials when patients present with neurological and hematological abnormalities.

A Peculiar Case of Fentanyl-Induced Cardiomyopathy.

An alarming rise in prescription and non-prescription misuse of opioids has been observed recently, leading to potentially devastating consequences. Opioid misuse contributes to cardiac risk burden and can cause diseases such as acute coronary syndrome, congestive heart failure, arrhythmias, QTc prolongation, and endocarditis. Here, we describe the case of a 35-year-old male with recreational fentanyl use who was found to have a cardiogenic shock on point-of-care ultrasound (POCUS), likely due to fentanyl-induced cardiomyopathy. Opioid-induced cardiomyopathy without any underlying cardiac disease in an adult appears to be a rare case. Our case highlights the importance of promptly recognizing fentanyl toxicity, screening for possible cardiomyopathy secondary to its use, and emergent resuscitation with the maintenance of ventilation, diuretics, and vasopressor support. The use of the reversal agent, naloxone, is a crucial part of management.

Septic shock from multiple intra-abdominal Streptococcus constellatus abscesses unamenable to percutaneous drainage.

Streptococcus constellatus are gram-positive cocci belonging to the Streptococcus milleri group that have a propensity to cause bacteremia and abscesses, especially in immunocompromised patients. Here, we report the case of a 39-year-old male who was initially admitted to the hospital for diabetic ketoacidosis. During the hospitalization, he developed sepsis and blood cultures grew Streptococcus constellatus. CT imaging revealed multiple hepatic abscesses. A periapical abscess of the left mandibular central incisor found on CT Scan of face was identified as the likely source of infection. IR-guided drainage was performed however the patient went on to develop septic shock despite attempted source control and IV antibiotic therapy. Repeat imaging showed persistent hepatic abscesses in addition to new intraperitoneal abscesses necessitating exploratory laparotomy, drainage and abdominal washout. Fluid cultures grew Streptococcus constellatus and common enteric flora. Our report highlights the need for high clinical suspicion in cases of Streptococcus constellatus bacteremia to obtain diagnostic imaging for any abscess formation. Prolonged antibiotic therapy is a must and imaging guided or surgical drainage may be needed.

Diagnosing and Managing Clinically Silent Lupus Nephritis and Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Syndrome: A Clinical Challange.

Lupus nephritis is typically associated with anti-nuclear antibodies and anti-double-stranded DNA antibodies resulting in the intrarenal immune complex deposition. Levels of anti-double-stranded DNA antibodies reflect disease activity in these patients. With negative anti-double-stranded DNA antibodies, establishing a diagnosis of lupus nephritis is difficult. Lupus nephritis overlapped with anti-neutrophil cytoplasmic antibody-associated vasculitis is both a diagnostic and therapeutic dilemma. Herein, we describe a case of an asymptomatic 41-year-old female who had incidental findings of low hemoglobin and elevated serum creatinine. Making a clinical diagnosis of lupus nephritis and anti-neutrophil cytoplasmic antibody-associated vasculitis in an asymptomatic patient can be challenging and must be made based on the interpretation of evolving serology, imaging studies, and histopathology. Based on extensive workup, the patient was diagnosed with concurrent lupus nephritis and anti-neutrophil cytoplasmic antibody-associated vasculitis overlap syndrome warranting immediate immunosuppressive therapy.

Anagrelide-Induced Supraventricular Tachycardia: A Case Report.

Anagrelide is an inhibitor of the phosphodiesterase-3 (PDE-3) enzyme that suppresses megakaryocytes; hence it is used in the treatment of essential thrombocythemia. Anagrelide can cause positive inotropic and chronotropic effects on the cardiovascular system. Its cardiovascular side effects are rare and include palpitations, tachyarrhythmias, cardiomyopathy, angina, and heart failure. We report the case of a 71-year-old female who presented with sudden onset chest pain. Her only outpatient medications included anagrelide and aspirin. She was found to have supraventricular tachycardia (SVT) with aberrancy that responded to beta-blockers. The chest X-ray, computed tomography angiogram (CTA), and echocardiogram were unremarkable. Her arrhythmia may be attributed to the anagrelide in the absence of any cardiovascular findings.

Emerging Role of Antibody-Drug Conjugates and Bispecific Antibodies for the Treatment of Multiple Myeloma.

Multiple myeloma (MM) is characterized by malignant proliferation of malignant plasma cells; it is the second most common hematological malignancy associated with significant morbidity. Genetic intricacy, instability, and diverse clinical presentations remain a barrier to cure. The treatment of MM is modernized with the introduction of newer therapeutics agents, i.e., target-specific monoclonal antibodies. The currently available literature lacks the benefits of newer targeted therapy being developed with an aim to reduce side effects and increase effectiveness, compared to conventional chemotherapy regimens. This article aims to review literature about the current available monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies for the treatment of MM.

Acute Myopericarditis in the Setting of Crohn's Colitis: Challenging Management Decisions.

Myopericarditis is a rare extraintestinal manifestation of Crohn's disease (CD). Myopericarditis has also been attributed to treatment with mesalamine and heart failure to tumor necrosis factor inhibitor (TNFi) use. When a patient with CD, controlled on these medications, presents with myopericarditis and/or heart failure, it can confound both the differential diagnosis and management of such patients. Our case is acute myopericarditis in a 34-year-old male, with a history of CD controlled with mesalamine and infliximab, who had been off TNFi therapy for over six months due to loss of insurance coverage and had been intermittently using leftover mesalamine. He presented to the ED complaining of a one-day history of abdominal pain with bloody diarrheal stools, chest discomfort, and fever. A colonoscopy performed two days back had demonstrated active colonic CD. Findings included ECG evidence of pericarditis, elevated cardiac biomarkers, and reduced left ventricular function on ventriculography consistent with myopericarditis. We present the differential, diagnostic and management challenges encountered in this situation, review the pertinent literature, and discuss decision making in what appears to be myopericarditis attributed to an extraintestinal manifestation of active GI Crohn's.

Novel Targeted Therapies for Chronic Lymphocytic Leukemia in Elderly Patients: A Systematic Review.

Chronic lymphocytic leukemia (CLL) typically affects older patients; administration of traditional cytotoxic therapies in old patients has very modest benefit with no survival improvement. With better understanding of CLL biology, trends are shifting towards the use of targeted therapies. The objective of this article is to review the safety and efficacy of various novel agents that specifically target the dysregulated pathways, with particular attention to elderly patients. Agents like B-cell receptor (BCR) inhibitors (Bruton's tyrosine kinase inhibitors [ibrutinib]), phosphatidylinositol 3-kinase inhibitors (idelalisib), spleen tyrosine kinase inhibitors (entospletinib), Bcl-2 inhibitors (venetoclax), immunomodulators (lenalidomide), and monoclonal antibodies (obinutuzumab, ofatumumab) have shown activity in CLL with a very favorable toxicity profile. Newer agents have improved clinical outcomes, and have tolerable toxicity profiles in elderly patients, resulting in the treatment with individualized therapy approach for CLL.

Chronic Kidney Disease and Calciphylaxis: A Literature Review.

Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a rare complication of chronic kidney disease (CKD). Its incidence is increasing due to a better understanding and diagnosis by physicians. Calciphylaxis is a fatal complication of many metabolic disorders. If not managed properly, it can lead to death within a year. This review is an effort to highlight the importance of research on prompt diagnosis and treatment guidelines for calciphylaxis, as it poses a challenge due to its diverse clinical presentation and high mortality rate.