Antithrombotic Therapy for Heart Failure in Sinus Rhythm - A Concise Review.

Heart failure (HF) is a common disorder associated with significant morbidity and mortality. It can increase the risk of thromboembolic events, which subsequently lead to increased risk of stroke, ischemic heart disease, thromboembolism, and death. Antithrombotic therapy has been investigated as a potential management strategy for HF patients in sinus rhythm, but its efficacy remains uncertain. Current guidelines do not recommend the routine use of antithrombotics in patients with HF in sinus rhythm without any other indication for their use. Several randomized controlled trials have investigated the efficacy of antithrombotics in HF patients in sinus rhythm. This article provides a concise review of the existing literature to assess the evidence supporting the use of antithrombotics in HF patients in sinus rhythm. The use of warfarin or other anticoagulants has demonstrated a lower risk of stroke but an increased risk of bleeding. The studies demonstrate that anticoagulant therapy in HF patients in sinus rhythm does not provide significant benefits in terms of overall ischemic events or death.

Stroke in a Young Patient Due to Moyamoya Disease.

Moyamoya is an uncommon, chronic vasocclusive disease of brain which affects the terminal portion of the internal carotid artery. Moyamoya disease is a disease of young with peak incidence of around 10-40 years. It can present as a transient ischemic attack (TIA), stroke or intracerebral hemorrhage in the pediatric or young adults. Treatment usually includes medical therapy or surgery. Surgical treatment generally involves use of external carotid system for blood supply which are spared in this disease process. We present a case of a young male patient with stroke from Moyamoya disease, who underwent successful EDAS (encephaloduroateriosynangiosis) procedure with complete resolution of his stroke symptoms.

Application of Genetic Testing in Unveiling the Diagnosis of Fabry Disease in a Patient with Hypertrophic Cardiomyopathy.

Fabry disease (FD) is a lysosomal storage disorder with an X-linked genetic pattern. It is caused by the genetic mutations in the galactosidase alpha gene on the long arm of the X-chromosome, resulting in the deficiency of the alpha-galactosidase A enzyme activity. This leads to an accumulation of globotriaosylceramide in a variety of cells, including cells in the heart. Left ventricular hypertrophy is one of the most common manifestations of FD involving the heart. Further cardiac disease progression portends significant morbidity and mortality. The early initiation of enzyme replacement therapy is associated with reversal or halting of the disease's progression and an improved clinical outcome. Here, we present the case of a 40-year-old male patient with left ventricular hypertrophy based on the results of a transthoracic echocardiogram and advanced cardiac imaging. He was later diagnosed with FD with the assistance of genetic testing. We also briefly outline the diagnostic challenges and treatment of FD.

Diagnosing missed cases of spinal muscular atrophy in genome, exome, and panel sequencing datasets.

Spinal muscular atrophy (SMA) is a genetic disorder that causes progressive degeneration of lower motor neurons and the subsequent loss of muscle function throughout the body. It is the second most common recessive disorder in individuals of European descent and is present in all populations. Accurate tools exist for diagnosing SMA from genome sequencing data. However, there are no publicly available tools for GRCh38-aligned data from panel or exome sequencing assays which continue to be used as first line tests for neuromuscular disorders. This deficiency creates a critical gap in our ability to diagnose SMA in large existing rare disease cohorts, as well as newly sequenced exome and panel datasets. We therefore developed and extensively validated a new tool - SMA Finder - that can diagnose SMA not only in genome, but also exome and panel sequencing samples aligned to GRCh37, GRCh38, or T2T-CHM13. It works by evaluating aligned reads that overlap the c.840 position of SMN1 and SMN2 in order to detect the most common molecular causes of SMA. We applied SMA Finder to 16,626 exomes and 3,911 genomes from heterogeneous rare disease cohorts sequenced at the Broad Institute Center for Mendelian Genomics as well as 1,157 exomes and 8,762 panel sequencing samples from Tartu University Hospital. SMA Finder correctly identified all 16 known SMA cases and reported nine novel diagnoses which have since been confirmed by clinical testing, with another four novel diagnoses undergoing validation. Notably, out of the 29 total SMA positive cases, 23 had an initial clinical diagnosis of muscular dystrophy, congenital myasthenic syndrome, or myopathy. This underscored the frequency with which SMA can be misdiagnosed as other neuromuscular disorders and confirmed the utility of using SMA Finder to reanalyze phenotypically diverse neuromuscular disease cohorts. Finally, we evaluated SMA Finder on 198,868 individuals that had both exome and genome sequencing data within the UK Biobank (UKBB) and found that SMA Finder's overall false positive rate was less than 1 / 200,000 exome samples, and its positive predictive value (PPV) was 97%. We also observed 100% concordance between UKBB exome and genome calls. This analysis showed that, even though it is located within a segmental duplication, the most common causal variant for SMA can be detected with comparable accuracy to monogenic disease variants in non-repetitive regions. Additionally, the high PPV demonstrated by SMA Finder, the existence of treatment options for SMA in which early diagnosis is imperative for therapeutic benefit, as well as widespread availability of clinical confirmatory testing for SMA, warrants the addition of SMN1 to the ACMG list of genes with reportable secondary findings after genome and exome sequencing.

Intimate partner violence during pregnancy among married women in Putalibajar municipality, Nepal.

Introduction: Intimate partner violence during pregnancy (IPVDP) is increasingly being recognized as a significant problem in the developing world due to its adverse health consequences on both pregnant women and children. The objective of the study is to measure the magnitude of intimate partner violence during pregnancy and the factors associated with IPVDP. Methods: A community-based cross-sectional study was conducted among 263 married women in their extended postpartum period between October 2019 and March 2020 in Putalibajar municipality, Nepal. A face-to-face interview was conducted and data were collected using an interview schedule. A Chi-square test and logistic regression analysis were performed to examine the association between IPVDP and the independent variables. Results: Among the 263 women interviewed, 30% experienced IPV during pregnancy, the most common type of violence was controlling behavior (20.2%) followed by emotional (18.6%), sexual (10.6%), economic (6.1%), and physical violence (5.3%). It was observed that IPV was more likely to occur among women whose husbands consumed alcohol (AOR = 3.171; CI 95%: 1.588-9.167), women whose husbands consumed tobacco (AOR =3.815; CI 95%: 2.157-7.265), women who sometimes received family support during pregnancy (AOR =2.948; CI 95%: 1.115-7.793) and women who did not decide on marriage timing (AOR =2.777; CI 95%: 1.331-5.792). Conclusion: Three out of ten pregnant women experienced IPVDP. To prevent violence, and ensure women's empowerment, formulating strict laws and discouraging the element of a violent milieu is important.

Intravenous Immunoglobulin-Associated Severe Hemolytic Anemia.

Intravenous immunoglobulin (IVIG) is used to treat immunodeficiency conditions, neuro-immunological, infection-related, autoimmune, and inflammatory disorders and is typically well tolerated. A hematological adverse reaction such as hemolytic anemia and neutropenia is known to occur with IVIG, which is usually transient and subclinical. However, severe hemolytic anemia is known to occur in some cases. We present a case of a 66-year-old man who developed severe symptomatic hemolytic anemia after receiving IVIG for acute inflammatory demyelinating polyneuropathy (AIDP). The patient had known risk factors such as non-O blood group, high cumulative dose of IVIG, and underlying autoimmune condition, which would have put him at high risk for developing hemolytic anemia after IVIG. Therefore, it is prudent for clinicians to have increased awareness regarding the potential for severe hemolysis and closely monitor these patients with risk factors after treatments to identify this adverse reaction before more severe complications occur.

A Retrospective Study Comparing the Effect of Conventional Coagulation Parameters Vs. Thromboelastography-Guided Blood Product Utilization in Patients With Major Gastrointestinal Bleeding.

Background: The use of thromboelastography (TEG) has demonstrated decreased blood product utilization in patients with specific etiologies of major gastrointestinal bleeding (GIB), such as variceal and non-variceal bleeding in cirrhosis patients; however, in a non-cirrhosis patient with GIB, there is far less evidence in the literature. Our retrospective study compares the effect of TEG-guided blood product utilization in patients with major GIB with all etiologies, including cirrhosis, admitted to medical intensive care unit (MICU). Methods: A retrospective chart review was conducted on patients admitted to the MICU of a tertiary academic medical center diagnosed with GIB using ICD-9/10 codes from 2014 to 2018. A total of 1,889 patients were identified, and validation criteria such as "GI or hepatology consult note", type and screen, pantoprazole, or octreotide drip" were used, which resulted in 997 patients, out of which 369 had a diagnosis of cirrhosis. Propensity score matching was done for baseline variables (age, sex, and race), ICU length of stay, hospital length of stay, ventilator days, and vasopressor use. As a result, 88 patients were included in the final analysis, with 44 in TEG and 44 in non-TEG group. A sub-group analysis was done in 46 patients with cirrhosis, 23 in TEG group and 23 in non-TEG group after propensity score matching. Results: There was significantly higher total blood volume (4,207 mL vs. 2,568 mL, P = 0.04) in the TEG group as compared to the non-TEG group, including total volume of cryoprecipitate (80 mL vs. 55 mL, P = 0.03) and total volume of platelet (543 mL vs. 327 mL, P = 0.03). In the cirrhosis sub-group, there was no significant difference in the amount of blood products transfused between the two groups. Conclusion: This study revealed that TEG is not superior to conventional coagulation parameters in limiting the volume of blood product transfusion in major GIB patients in ICU settings.

An Unusual Presentation of Tuberculosis With Dysphagia.

About a quarter of the world's population is infected with tuberculosis (TB). It is one of the leading causes of death worldwide. However, the prevalence of TB in the United States is rare. Pulmonary TB is the commonest form of TB. Most patients with TB present with pulmonary symptoms. Extrapulmonary TB usually presents with symptoms related to the organ system involved and can present with very unusual symptoms. TB presenting with dysphagia is uncommon, and spinal TB presenting with dysphagia is very unusual. A 57-year-old woman presented to the emergency department with a four-month history of dysphagia and chest pain. She was undergoing an outpatient workup of her symptoms that included esophagogastroduodenoscopy, gastric emptying study, and computed tomography (CT) scan of the chest, which showed incidental findings of a focus in the thoracic spine. It was followed by a bone scan, and the results were concerning for malignancy. She was awaiting an oncology appointment when she presented to us. A basic workup after her presentation that includes complete blood count, comprehensive metabolic panel, troponin, chest x-ray, and electrocardiogram was unrevealing. Magnetic resonance imaging (MRI) of the thoracic spine showed findings suggestive of tuberculous spondylitis, tuberculous paraspinal, and prevertebral abscesses. Chest CT was repeated, which showed mass effect and erosion on the posterior esophageal wall with anterior displacement of the esophagus. Tissue biopsy revealed acid-fast bacilli (AFB) on AFB stain, and the culture grew Mycobacterium tuberculosis. She was successfully treated with the antitubercular regimen of rifampin, isoniazid, ethambutol, and pyrazinamide. TB can present with a myriad of symptoms, and although rare, it can present with symptoms like dysphagia. In patients with a history of travel to or immigration from an endemic region, previous infection, and immunosuppression, TB should be considered as one of the differential diagnoses even for unusual symptoms like dysphagia.

Experience With Dexmedetomidine Use in the Treatment of Dysautonomic Crisis in Familial Dysautonomia: An Off-Label Use.

Familial dysautonomia is a rare genetic neurodevelopmental disorder characterized by episodes of hyperautonomic state known as dysautonomic crises. The features of dysautonomic crises are hypertension, tachycardia, vomiting, sweating, flushing, and behavioral changes. The etiology of such crises is supposed to be a consequence of the inability to control sympathetic overflow due to damage to the afferent neurons carrying baroreceptor inputs to the central nervous system. A 19-year-old male with a known history of familial dysautonomia and frequent dysautonomic crises presented to the Emergency Department with intractable nausea and vomiting for six hours. He was hypertensive and tachycardic on presentation. The patient had tried oral labetalol and clonidine at home with no improvement. In the emergency room, the patient received intravenous labetalol, diazepam, and clonidine which were ineffective. He was then treated with intravenous dexmedetomidine, and his symptoms resolved within a few hours. The patient was discharged home on the same day. The mainstay of treatment for dysautonomic crises is benzodiazepines and clonidine. The use of these treatment modalities has its challenges. Here, we present a case of a dysautonomic crisis that was resistant to the conventional treatment, treated safely and successfully with dexmedetomidine.

Interesting case of incidental diagnosis of pulmonary embolism by endobronchial ultrasonography.

Pulmonary embolism (PE) is the obstruction of the pulmonary artery or its branches, usually by a thrombus that originates in the lower extremity veins. PE is associated with high mortality risk. Here, we present the case of a patient who initially presented with dysphagia. Chest radiography revealed a lung nodule. Endobronchial ultrasonography (EBUS) was performed to evaluate the nodule, which revealed a pulmonary embolus. Subsequently, CT angiography of the chest was performed to confirm the diagnosis of PE. Anticoagulation therapy was initiated. The biopsy results were positive for lung adenocarcinoma. There are only few reported cases of PE diagnosed using EBUS. Here, the patient had not presented with the signs and symptoms of PE. Had PE not been diagnosed by EBUS, our patient could have potentially had a disastrous outcome. Moreover, this case shows that EBUS may be used for diagnosing PE.

A Case of Severe Hypoxia Caused by Phenazopyridine-Induced Methemoglobinemia: A near Fatal Event from Over-the-Counter Medication Use.

Methemoglobinemia is a rare blood disorder characterized by the oxidation of heme iron from ferrous (Fe2+) to ferric (Fe3+) state, which increases oxygen affinity and impairs oxygen release to the tissue causing hypoxia. It can be congenital or acquired; however, most cases are acquired and caused by exogenous substances such as medications, chemicals, and environmental substances. Phenazopyridine is an over-the-counter urinary analgesic medication commonly used for symptomatic relief of dysuria and has been reported to cause methemoglobinemia. However, only a handful of cases of phenazopyridine-induced methemoglobinemia have been reported. We present a case of an 89-year-old female who presented with severe hypoxia, shortness of breath, headache, nausea, and dizziness caused by phenazopyridine-induced methemoglobinemia. She was found to have a methemoglobin level of 21.5% and was treated with methylene blue, leading to a rapid improvement of her symptoms. She was taking one over-the-counter phenazopyridine 200 mg tablet three times daily for two weeks for her chronic dysuria. This case highlights the need to have a high index of suspicion of phenazopyridine-induced methemoglobinemia in a patient presenting with unexplained shortness of breath with a history of phenazopyridine use as it could lead to severe methemoglobinemia with hypoxia that could potentially be fatal if not promptly diagnosed.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Presenting as Chronic Diarrhea; An Unusual Presentation of a Common Lymphoproliferative Disorder.

Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the United States. It has a variable presentation with most patients having asymptomatic lymphocytosis. Many other patients present with lymphadenopathy or enlargement of other organs of the reticuloendothelial system. However, CLL can present with extramedullary involvement. Most commonly, this is in the form of skin or central nervous system involvement, though rarely it can present with gastrointestinal involvement. Here, we present the case of a 70-year-old Caucasian male who presented with chronic diarrhea for over 4 months. After failing conservative treatment, a colonoscopy was performed which showed diffuse mucosal nodularities with a biopsy revealing CLL. The patient was treated successfully with chemotherapy and his diarrhea improved. This is a differential to keep in mind in patients with chronic diarrhea, once the more common causes have been ruled out.

Extremely Hyperdominant LAD Supplying the Anterior, Inferior, and Lateral Walls of the Left Ventricle.

Hyperdominant left anterior descending artery (LAD) is a rare anomaly in which the LAD gives rise to the posterior descending artery. Our case report describes an extreme case of hyperdominant LAD supplying the anterior, inferior, and partially the lateral walls of the left ventricle. It is crucial that physicians be aware of the possibility of extreme LAD dominance. A proximal occlusion of such a vessel might have catastrophic consequences with atypical presentation on electrocardiogram.

The Sudden Development of Multi-Organ Lesions in a Patient With Pulmonary Sarcoidosis: A Case Report.

INTRODUCTION: Sarcoidosis is a systemic granulomatous inflammatory disease that can involve almost any organ system in the human body. It most frequently presents with pulmonary infiltrates, hilar lymphadenopathy, and skin lesions. Clinical and subclinical involvement of other organ systems is not uncommon. However, the simultaneous development of clinically apparent multisystem sarcoidosis is very rare. CASE DESCRIPTION: This 44-year-old Caucasian man presented to an outpatient clinic with a 2-month history of fatigue, night sweats, weight loss, loss of appetite, and mild abdominal discomfort. Initial laboratory finding showed elevated liver enzymes. Imaging studies revealed cirrhotic liver with steatosis, few enhancing hepatic masses, and multiple enlarged periaortic and portocaval lymph nodes. Liver biopsy revealed scattered necrotizing granulomatous hepatitis. Positron emission tomography scan showed extensive hepatic uptake, diffuse lymphadenopathy, as well as numerous fluorodeoxyglucose-avid osseous lesions. After extensive workup to rule out malignancy and infectious etiologies, a diagnosis of diffuse multi-organ sarcoidosis was made. He was ultimately treated with methotrexate and steroids, resulting in marked improvement in symptoms and liver function, with stable disease on repeat imaging. CONCLUSION: Diffuse multi-organ sarcoidosis is often associated with widespread lymphadenopathy and osseous lesions, which appear indistinguishable from malignancy on imaging. The angiotensin converting enzyme levels and inflammatory markers may be normal. Clinicians should be aware of the possibility of diffuse systemic sarcoidosis in any patient with a remote sarcoidosis history and the simultaneous development of multi-organ-related symptoms.