Efficacy and Safety of Mavacamten in the Treatment of Hypertrophic Cardiomyopathy: A Systematic Review.

BACKGROUND: Current pharmacological options for hypertrophic cardiomyopathy (HCM) are not disease-specific; while it treats symptoms, mavacamten targets the underlying pathology. We aim to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive HCM. METHODS: This systematic review of the literature followed the PRISMA guidelines. Title/abstract and topics were searched using the following term: "mavacamten". The electronic research literature databases included the Cochrane Library, MedLine, and clinicaltrials.gov from July to August 2022. Primary efficacy endpoint was to assess clinical response at the end of treatment compared with baseline, defined as, at least one New York Heart Association (NYHA) class reduction. Two secondary endpoints from baseline were determined. The first was defined as improvement in mixed venous oxygen pressure (pVO2). The second was defined as reduction of the post-exercise left ventricular outflow tract (LVOT) gradient. RESULTS: We included in our analyses data from four studies that met our review eligibility criteria. There were three randomised placebo-controlled clinical trials and one non-randomised open-label clinical trial. All four studies showed a reduction in NYHA class from mavacamten use. Three out of four studies demonstrated >1 NYHA functional class improvement ranging from 34% to 80%, while only one study showed a smaller percentage of patients remaining at class 3. Three out of four studies measured pVO2 as an outcome, and all three studies noticed an increase in peak oxygen consumption after mavacamten treatment. Additionally, three out of four studies measured post-exercise LVOT gradient reduction as an outcome and all three found significant reduction in the post-exercise LVOT gradient after treatment. The most commonly observed adverse side effects were atrial fibrillation and decreased left ventricular ejection fraction, but all participants recovered without long-term sequelae and only one patient dropped out of the trial. CONCLUSIONS: Mavacamten has a greater efficacy than placebo in the treatment of HCM. It also showed promising tolerability and efficacy profiles in the treatment of HCM in adults. The three endpoints used in the evaluation of studies were reduction in NYHA class, increase in pVO2, and post-exercise LVOT gradient reduction. Mavacamten showed greater reduction in NYHA, larger effects on increase of pVO2, and significant reduction of the LVOT gradient. Mavacamten was also found to be well tolerated, like the placebo. The side effect profile was limited for the majority of individuals taking mavacamten. In the future, authors recommended dose-optimisation studies, and studies that evaluate mavacamten both in comparison to, and in conjunction with other current treatments.

Septic Shock and Bacteremia Secondary to Herbaspirillum huttiense: A Case Report and Review of Literature.

The Herbaspirillum species are gram-negative bacteria that inhabit soil and water. Infections caused by this pathogen are an uncommon clinical entity. We describe a rare case of septic shock and bacteremia caused by Herbaspirillum huttiense in an immunocompetent adult female. The patient, a 59-year-old female, presented to the hospital with circulatory shock, fever, chills, and cough. Chest x-ray revealed right lower lobe lung consolidation consistent with pneumonia, and blood cultures with a positive concerning gram-negative curved rod which was later identified as H. huttiense. The patient was treated in the ICU for three days with cefepime and vasoactive agents. After improvement and an additional seven days of hospitalization, the patient was discharged home with a five-day course of oral levofloxacin. Although our patient responded well to cefepime and levofloxacin, meropenem and piperacillin-tazobactam were found to be the most commonly used and the most effective antibiotics to treat H. huttiense infections in other reported cases. This is amongst the few reported cases of H. huttiense bacteremia in an immunocompetent individual with pneumonia.

Uncommon presentations of common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder that causes decreased immunity and increased susceptibility to infections. It affects B lymphocyte differentiation, resulting in predominantly bacterial and less frequently viral, fungal, and protozoal infections. The respiratory and gastrointestinal tracts where antibody defences are essential are usually affected. Individuals with CVID are also predisposed to developing lymphoid and gastrointestinal malignancies. We present two cases with rare infectious and oncological complications of CVID, including a patient with Mycobacterium avium complex-intracellular infection and ovarian cancer, and another patient with group B Streptococcus empyema of the lung with acute myeloid leukaemia. The main objective of this study is to highlight how CVID-induced hypogammaglobulinaemia can lead to rare infections and malignancies. The management of these complications can vary according to severity, but an awareness of their existence is crucial to diagnose them promptly in an already immunocompromised CVID patient.

Vaccine hesitancy with a history of Guillain Barre Syndrome: Weighing the risks and benefits of SARS-CoV-2 vaccination.

Since the beginning of the COVID-19 pandemic, great hesitancies regarding the COVID-19 immunization have existed. The most striking adverse events reported include thrombosis with thrombocytopenia syndrome (TTS), myocarditis, and Guillain Barre Syndrome (GBS). Post-vaccination GBS is known since the time of Influenza vaccination, but several cases of GBS have also been reported in the current COVID-19 vaccination era. As a result, our patient with a history of GBS post-Influenza vaccination, went unvaccinated for SARS-CoV-2, due to fear of GBS re-activation. Consequently, he contracted COVID-19 pneumonitis complicated with deep venous thrombosis, requiring a prolonged hospitalization. Weighing the risks and benefits of vaccination to COVID-19 is difficult, especially for people with a previous history of GBS related to Influenza vaccination. We reviewed and analyzed the reported cases of GBS temporary related to COVID-19 vaccination to determine the safety of their administration in those with a history of GBS.

Necrotizing Cellulitis and Myositis in a Neutropenic Leukemic Patient.

In this article, we review a case of necrotizing cellulitis and myositis in a neutropenic leukemic patient. He underwent a series of investigations to reach the diagnosis of pyoderma gangrenosum (PG). The lesion improved dramatically after pertinent identification and initiation of appropriate treatment. The management of PG is exceedingly challenging due to a lack of proper clinical criteria for detection and guidelines for treatment. PG must be considered as a differential in patients with enlarging, sterile, necrotic lesions, unresponsive to prolonged broad-spectrum antibiotics. Prompt recognition can prevent deeper infections and the formation of a chronic open wound causing cosmetic disfigurement along with other catastrophic complications.