Evaluating the efficacy and safety of mavacamten in hypertrophic cardiomyopathy: A systematic review and meta-analysis focusing on qualitative assessment, biomarkers, and cardiac imaging.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is a complex cardiac condition characterized by hypercontractility of cardiac muscle leading to a dynamic obstruction of left ventricular outlet tract (LVOT). Mavacamten, a first-in-class cardiac myosin inhibitor, is increasingly being studied in randomized controlled trials. In this meta-analysis, we aimed to analyse the efficacy and safety profile of Mavacamten compared to placebo in patients of HCM. METHOD: We carried out a comprehensive search in PubMed, Cochrane, and clinicaltrials.gov to analyze the efficacy and safety of mavacamten compared to placebo from 2010 to 2023. To calculate pooled odds ratio (OR) or risk ratio (RR) at 95% confidence interval (CI), the Mantel-Haenszel formula with random effect was used and Generic Inverse Variance method assessed pooled mean difference value at a 95% CI. RevMan was used for analysis. P<0.05 was considered significant. RESULTS: We analyzed five phase 3 RCTs including 609 patients to compare mavacamten with a placebo. New York Heart Association (NYHA) grade improvement and KCCQ score showed the odds ratio as 4.94 and 7.93 with p<0.00001 at random effect, respectively. Cardiac imaging which included LAVI, LVOT at rest, LVOT post valsalva, LVOT post-exercise, and reduction in LVEF showed the pooled mean differences for change as -5.29, -49.72, -57.45, -36.11, and -3.00 respectively. Changes in LVEDV and LVMI were not statistically significant. The pooled mean difference for change in NT-proBNP and Cardiac troponin-I showed 0.20 and 0.57 with p<0.00001. The efficacy was evaluated in 1) A composite score, which was defined as either 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction, or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening and 2) changes in pVO2, which was not statistically significant. Similarly, any treatment-associated emergent adverse effects (TEAE), treatment-associated serious adverse effects (TSAE), and cardiac-related adverse effects were not statistically significant. CONCLUSION: Mavacamten influences diverse facets of HCM comprehensively. Notably, our study delved into the drug's impact on the heart's structural and functional aspects, providing insights that complement prior findings. Further large-scale trials are needed to evaluate the safety profile of Mavacamten.

Novel anti-psoriasis agent-associated cardiotoxicity, analysis of the FDA adverse event reporting system (FAERS).

INTRODUCTION: Psoriasis is a chronic skin condition characterized by hyperproliferation of epidermal keratinocytes, resulting in erythematous and scaling lesions. The US Food and Drug Administration (FDA) has approved nine biologic agents to address the burden of psoriasis, but their cardiovascular risks remain poorly studied. METHODS: This retrospective pharmacovigilance study utilized the FDA Adverse Event Reporting System (FAERS) database to analyze adverse events associated with newly approved therapeutic agents for psoriasis. We employed disproportionally signal analysis, calculating the reporting odds ratio (ROR) with a 95% confidence interval. RESULTS: Among the vast FAERS database, which contained >25 million adverse events, a total of 334,399 events were associated with newly approved therapeutic agents for psoriasis. Cardiac adverse events accounted for 3852 cases, including pericarditis, atrial fibrillation, and coronary artery disease. Secukinumab had the highest number of reported adverse events, followed by brodalumab, while tildrakizumab had the lowest. Coronary artery disease was the most reported adverse event (1438 cases), followed by pericarditis (572 cases) and atrial fibrillation (384 cases). Secukinumab had the highest incidence of coronary artery disease, pericarditis, and atrial fibrillation. Risankizumab was significantly associated with an increased risk of coronary artery disease and atrial fibrillation, while tildrakizumab and Ixekizumab were associated with atrial fibrillation. Secukinumab was associated with an elevated risk of pericarditis. CONCLUSIONS: The study uncovers the cardiovascular adverse effects related to biologic agents used in psoriasis treatment. These findings emphasize the importance of monitoring and evaluating the cardiovascular safety profiles of biological agents used in psoriasis treatment.

Lung infection or inflammation-a puzzling case of MDA-5 associated juvenile dermatomyositis.

BACKGROUND: Juvenile dermatomyositis (JDM) is an uncommon inflammatory myopathy predominantly affecting children under 18 years of age. Diagnosis relies on identifying specific clinical features, such as muscle weakness, skin rash, elevated muscle enzymes, and MRI and muscle biopsy findings. Autoantibodies associated with inflammatory myopathy offer valuable prognostic insights and can indicate the risk of internal organ involvement, though they are relatively rare in childhood myopathies. JDM can progress to interstitial lung disease (ILD) if associated with MDA5 antibodies, and immunosuppressive therapy constitutes the primary treatment approach. CASE PRESENTATION: We present a unique case of JDM complicated by disseminated histoplasmosis in a 12-year-old African American male cross-country runner with no prior medical history. He presented with unintentional weight loss and a rash on his hands, genitals, and fingertips, which persisted despite previous treatments. Diagnosis of JDM was confirmed through clinical and laboratory evaluations. Over time, the patient developed recurrent fevers, thrombocytopenia, and signs of ILD, leading to the identification of disseminated histoplasmosis as a complicating factor. Appropriate antifungal treatment resolved the infectious condition, while continued immunosuppression aided in managing JDM and ILD. CONCLUSIONS: Juvenile dermatomyositis (JDM) remains a rare and intricate autoimmune disorder affecting young individuals. The presence of MDA5 antibodies in JDM patients can lead to severe complications like ILD, necessitating vigilant monitoring. Management includes immunosuppressive therapy, with glucocorticoids and mycophenolate mofetil proving effective, particularly in Clinically Amyopathic Dermatomyositis (CADM) cases. In cases of refractory disease, intravenous immunoglobulin (IVIG) plays a crucial role, offering a safe and beneficial adjunct to treatment. We emphasize the importance of recognizing atypical presentations of JDM, as it can lead to delays in diagnosis and treatment. Our case highlights the complexities of managing dual lung pathology, where a secondary infection exacerbated lung nodules and thrombocytopenia, while ILD was a consequence of atypical myopathy. Combining antifungal treatment with immunosuppression effectively managed both conditions and follow-up evaluations demonstrated improvement in ILD. Awareness of potential fungal infections in immunosuppressed JDM patients is crucial for successful treatment and patient outcomes.

Novel Approach in Cardiac Sarcoidosis: A Case Report Highlighting Abatacept as a Promising Treatment Option.

Cardiac sarcoidosis (CS) is a rare auto-immune disorder where immune cells form granulomas in the heart that may lead to potential arrhythmias and heart failure. Due to the low prevalence of CS, the management remains challenging, requiring a multidisciplinary approach. In addition to the management of the resulting arrhythmias and heart failure, corticosteroids and immunosuppressants are used as anti-inflammatories to prevent disease progression. Immunosuppressive regimens for the treatment of CS are not yet well established. Abatacept has been approved for rheumatoid arthritis and psoriatic arthritis and both are mainly Th1-driven autoimmune diseases. Even though there are several different drugs used to treat corticosteroid-dependent sarcoidosis, abatacept may represent a unique option as its side effects differ from other drugs like methotrexate, azathioprine, or mycophenolate, especially bone marrow and liver toxicity. We present the case of a 52-year-old CS patient treated with abatacept after the failure of methotrexate and mycophenolate mofetil. Our patient had a history of stage D heart failure with reduced ejection fraction (HFrEF) with ejection fraction (EF) of 15-20%, nonischemic cardiomyopathy (NICM) s/p left heart catheterization (LHC), CS diagnosed by positron emission tomography (PET), status post implantable cardioverter-defibrillator (ICD) implantation, lung sarcoid, paroxysmal atrial fibrillation, and aflutter, who followed with cardiology, rheumatology, and pulmonology. He had multiple admissions for heart failure exacerbations. The patient was initially diagnosed with pulmonary sarcoidosis after which he completed a small course of steroids. CT chest showed lymphadenopathy; however, endobronchial ultrasound (EBUS) did not show evidence of pulmonary sarcoidosis. During an admission for heart failure about four years later, cardiac PET CT showed CS, and rheumatology was brought on board. The patient initially refused steroids and steroid-sparing agents. At subsequent visits, the patient was amenable to medication and was started on methotrexate 10mg weekly. However, given worsening chronic kidney disorder, methotrexate was discontinued and mycophenolate 200mg daily was started. A couple of weeks after mycophenolate was started, the patient felt like "his throat was closing up" and his stomach was cramping, which was thought to be an allergic response to the mycophenolate so it was discontinued. He then received an abatacept infusion which he tolerated well. Currently, our patient has been referred for heart transplantation.

Beyond the Acne.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) is a relatively rare and often underdiagnosed disorder characterized by chronic inflammation affecting the bones, joints, and skin. While the precise cause of SAPHO syndrome remains elusive, multiple factors such as genetics, immunological dysregulation, and bacterial influences have been implicated in its pathogenesis. One notable aspect of SAPHO syndrome is the wide variability of symptoms experienced by afflicted individuals. A diverse array of osteoarticular manifestations may be observed, with common sites of involvement including the anterior chest wall, sacroiliac joints, and peripheral joints. Concurrently, patients often present with various skin disorders, such as palmoplantar pustulosis or acne, further adding to the complexity of the syndrome's clinical presentation. Treatment strategies for SAPHO syndrome primarily focus on managing symptoms and improving the quality of life for affected individuals. Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, methotrexate (MTX), and tumor necrosis factor (TNF) inhibitors are considered to modulate the immune response and provide relief. One of the challenges encountered in diagnosing SAPHO syndrome is its potential overlap with other related conditions, leading to diagnostic confusion and difficulties. Distinguishing SAPHO syndrome from similar entities can be complex, requiring a comprehensive evaluation of clinical features, imaging studies, and laboratory investigations. We would like to share an intriguing case involving a 28-year-old woman who arrived with perplexing symptoms of pain in her bilateral hands and feet, her lower back, and acne in the bilateral upper arms and thighs. Through a comprehensive workup, the underlying SAPHO syndrome was uncovered, and it was effectively managed using adalimumab.

Crimean-Congo haemorrhagic fever-induced liver injury: A systematic review and meta-analysis.

BACKGROUND: Crimean-Congo haemorrhagic fever (CCHF) is a fatal acute tick-borne viral infection and substantial emerging global public health threat. This illness has a high case fatality rate of up to 40%. The liver is one of the important target organs of the CCHF virus. OBJECTIVE: The aim of this meta-analysis to evaluate the correlation between CCHF and liver injury and draw more generalised inferences about the abnormal serum markers of liver injury such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) in CCHF patients. METHODS: A literature search was accomplished for published eligible articles with MEDLINE/PubMed and Embase databases. All eligible observational studies and case series were included from around the world. The inclusion criteria were articles describing liver injury biomarkers amongst patients diagnosed with CCHF. RESULTS: Data from 18 studies, consisting of 1238 patients with CCHF were included in this meta-analysis. Overall pooled incidence of at least one raised liver injury biomarker was 77.95% (95% CI, I2  =  88.50%, P < .0001). Similarly, pooled incidence of elevated AST and ALT was 85.92% (95% CI, I2  = 85.27%, P < .0001) and 64.30% (95% CI, I2  =  88.32%, P < .0001), respectively. Both Egger and Begg-Mazumdar's tests detected no apparent publication bias in all three meta-analyses (P > .05). CONCLUSION: Our study shows that CCHF has a very detrimental effect on liver function. Abnormal liver function may lead to poor prognosis and increased morbidity and mortality in CCHF patients. Hence, Physicians must recognise and continuously monitor these biomarkers, since these markers may aid in early stratification of prognosis and the prevention of severe outcomes in infection with such a high case fatality rate.

Myocarditis associated with Covid-19 disease: A systematic review of published case reports and case series.

BACKGROUND: Covid-19 is an extremely contagious illness caused by the severe acute respiratory syndrome (SARS-CoV-2) virus. The cardiac involvement in such a public health emergency disease has not been well studied and a conflicting evidence exists on this issue. OBJECTIVE: This systematic review article aimed to compile and illustrate clinical characteristics, diagnostic findings, management, and outcomes manifesting in myocarditis linked with Covid-19. METHODS: A literature search was accomplished for published eligible articles with MEDLINE/PubMed and Embase databases. All eligible case reports and case series were included from around the world without any language restrictions. For this review, inclusion criteria were laboratory-confirmed SARS-CoV-2 infection cases reporting a diagnosis of acute myocarditis. RESULTS: Data from 41 studies describing myocarditis in 42 Covid-19 patients was obtained. The median age of these patients was 43.4 years, with 71.4% of them being men. Fever was the most prevalent presenting symptoms seen in 57% of patients. Hypertension was the most pervasive comorbidity accompanying these patients. Cardiac biomarkers troponin and brain natriuretic peptide (BNP) were raised in almost 90% and 87% of patients, respectively. Electrocardiogram findings were nonspecific and included ST-segment and T-wave changes. Echocardiogram commonly showed left ventricular systolic dysfunction with increased heart size. Cardiac magnetic resonance imaging (CMRI) exhibited myocardial edema and injury. The most prevalent histopathological feature appreciated was diffuse lymphocytic inflammatory infiltrates. Antivirals and corticosteroids were the most frequently used medications. About 38% of patients also needed vasopressor assistance. Out of 42 patients, 67% recovered, and eight died. CONCLUSION: Because of the risk of a sudden worsening of patients conditions and myocarditis association with considerable mortality and morbidity, a knowledge of this cardiac complication of Covid-19 disease is crucial for healthcare professionals.

Association of Gastrointestinal System With Severity and Mortality of COVID-19: A Systematic Review and Meta-Analysis.

At present, the novel coronavirus disease (COVID-19) is causing a major pandemic. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In COVID-19, the patient usually presents with fever, dry cough, and respiratory manifestations. However, the involvement of other systems has also been reported in the literature. Abdominal pain, diarrhea, vomiting, and nausea are the predominant gastrointestinal (GI) manifestations underlined in the literature. We conducted a literature search using four databases (PubMed, Web of Science, Google Scholar, and Clinicaltrials.gov). Our search strategy included Medical Subject Headings (MeSH) terms and keywords for COVID-19, SARS-CoV-2, and GI system from inception to October 2020. After excluding duplicates, review articles, and non-relevant articles, we included 20 studies out of 842 articles reporting GI manifestations in COVID-19 patients. Using Cochrane RevMan version 5.4 (Cochrane, London, UK), a compute pooled analysis using a random-effect model was performed. Our study included 6,022 patients with a median age of 49.5 years. Pooled analysis via random effect model revealed an increased risk of severe COVID-19 in patients manifesting GI symptoms with an odds ratio (OR) of 2.07 (95% Confidence Interval [CI]: 1.34-3.18) with I2=41%). Odds of mortality in COVID-19 with GI manifestation and hepatic abnormalities included 0.92 (95% CI: 0.50-1.69) (I2=57%) and 1.26 (95% CI: 0.67-2.37) (I2=0%), respectively. Severe COVID-19 may have a strong association with GI manifestations and have a significant impact on GI practice. Holistic knowledge of the spectrum of the GI consequences in COVID-19 is crucial to get a hold of virus spread. In this article, we have summarized the association of GI manifestations in severe COVID-19 patients.

Maculopapular skin eruptions associated with Covid-19: A systematic review.

In this systematic review, we anticipated in summarizing clinical features, histopathological hallmarks, and possible pathology behind the maculopapular skin eruptions occurring in Covid-19 patients. A literature search was executed using MEDLINE/PubMed and Embase databases for articles published till 20 November 2020. All eligible articles including observational studies, case reports, and case series reporting the maculopapular skin lesion in Covid-19 patients were included. Data were obtained for 354 Covid-19 patients presenting with maculopapular lesions from 40 studies. The mean age of these patients was 53 years, and with 42% of them being male. These maculopapular lesions differed considerably in terms of distribution and appearance, ranging from diffuse erythematous maculopapular lesions to scattered erythematous macules coalescing into papules to maculopapular lesions in plaques. The mean duration of the lesion was 8 days. These lesions were frequently localized on trunks and extremities. Superficial perivascular dermatitis with lymphocytic infiltrate was a histopathological hallmark of these lesions. As these skin lesions may have a possible association with diagnosis, management, prognosis, and severity of the disease, all health practitioners need to be well acquainted with these Covid-19 skin lesions. Also, in the middle of this worldwide pandemic, early identification of this eruption may help manage this infection's further spread.