Maternal exposure to folate antagonists and susceptibility to congenital heart disease in offspring: A systematic review and meta-analysis.

AIMS: The objective of this meta-analysis was to determine whether maternal exposure to folate antagonists is associated with increased rates of congenital heart disease in offspring. METHODS: A comprehensive search for articles in the MEDLINE (PubMed) and EMBASE databases published up to 21 August 2023 was performed. The search strategy was not limited by study design but only for articles in the English language. RESULTS: Analysis of 6 cohort studies and 5 cross-sectional studies, published between 1976 and 2020, showed significant increase in rate of congenital heart disease (odds ratio 1.55, 95% confidence interval, 1.28-1.87) when exposed to folate antagonists compared with the control. Further subgroup analysis showed the increased rate for exposure to both dihydrofolate reductase inhibitors and antiepileptic drugs separately. No differences were observed when analyses were stratified by timing of study. CONCLUSION: Administration of folate antagonists within the 12-week period preceding conception and throughout the second and third months of gestation exhibited a statistically significant elevation in the susceptibility to congenital heart diseases. Notably, the protective effect of folic acid supplementation was reported in cases of congenital heart disease linked to dihydrofolate reductase inhibitors but not that associated with antiepileptic drugs.

Danazol for the Treatment of Myelodysplastic Syndromes: A Systematic Review.

Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched for relevant publications from inception June 1, 1950, until June 28, 2022. The studies were screened by title and abstract, followed by full-text screening. The quality of the included studies was assessed via a prespecified set of questionnaires. Data on the efficacy measures and adverse outcomes were extracted and included in a descriptive summary. Results Nine studies consisting of 246 participants were included in our review. The overall quality of the included studies was fair. The age of the participants ranged from 61 to 78 years. In all 9 studies, more male patients had been enrolled than female patients. Overall, a proportion of patients in all the studies reported a desired major response to a danazol dose of 400 to 800 mg/day. Few studies did not observe any improvement in the platelet count. Elevated liver enzyme levels, weight gain, headache, dermatitis, and weakness were the most common AEs observed. One study reported a fatal intracerebral hemorrhage in 1 participant. Conclusions Danazol has been effective in increasing platelet count and hemoglobin level. Despite a few AEs, danazol is a safe drug for the treatment of patients with myelodysplastic syndromes.

Safety and efficacy of danazol in immune thrombocytopenia: a systematic review.

Background: The treatment landscape for relapsed or refractory immune thrombocytopenia (ITP) after corticosteroids is complex. Objectives: We aimed to assess the efficacy of danazol in treating ITP and evaluate the safety and adverse events following its administration. Methods: We searched the databases PubMed, EMBASE, and ClinicalTrials.gov for all published studies assessing danazol's efficacy and safety in treating ITP. The retrieved studies were screened by title and abstract, followed by full-text screening based on the eligibility requirements. The quality assessment was performed using a set of questionnaires. The data were extracted on the descriptive characteristics of the studies and participants, drug dosage, efficacy measures, and adverse effects, and the data were synthesized. Results: A total of 17 studies consisting of 901 participants were included. The overall response rate is around 61% in this analysis. Among the participants, 315 (34.9%) were men. The age of participants ranged from 16 to 86 years. Danazol combined with other pharmacologic interventions, including all-trans-retinoic acid or glucocorticoids, generated better results. The most common side effects appear to be liver injury and elevation of liver enzymes, weight gain, oligomenorrhea, amenorrhea, and myalgia. Conclusion: Danazol at low-to-medium doses was well tolerated and succeeded in improving ITP. Danazol therapy may be helpful in the treatment of chronic ITP that is corticosteroid refractory and when corticosteroids or splenectomy (or both) is contraindicated. Danazol can be considered for further research and development in treating primary immune thrombocytopenia.

Diagnostic and prognostic role of elafin in skin acute graft versus host disease: a systematic review.

BACKGROUND AND OBJECTIVE: Graft versus host disease (GVHD) is the common complication seen after allogeneic hematopoietic stem cell transplantation (HSCT) and a pleomorphic syndrome that resembles autoimmune and other immunologic disorders, leading to profound immune dysregulation and organ dysfunction. The most common targets of GVHD are skin, gastrointestinal tract and liver. GVHD is classified as acute graft versus host disease (aGvHD) if it occurs within the first 100 days after HSCT and chronic graft versus host disease(cGVHD) if it occurs after day 100. The skin is most frequently and earliest affected by aGvHD, followed by the gastrointestinal tract and liver. An ideal biomarker would predict the onset and severity of clinical acute GVHD and help to direct management, and this is an area of active research regarding the use of biomarkers for diagnosis and prognosis of acute GVHD. Recently, elafin has been identified as a potential plasma biomarker for aGVHD. METHOD: We searched the databases PubMed, Cochrane library, and medRxiv for all studies investigating the Diagnostic or prognostic role of elafin in GVHD. We set the search strategy incorporating the search terms, 'elafin', 'graft versus host', and 'GVHD', and operated using the Boolean operators 'AND', and 'OR'. Thus, retrieved articles were then exported on an Excel® sheet, and duplicates were removed. The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After selecting the study based on inclusion criteria, data on study characteristics and biomarker description was extracted on a pre-determined data extraction table on the Microsoft Excel version. The quality assessment of the included studies was determined using the QUIPS tool. RESULT: The search revealed 547 studies and 6 studies that met the eligibility criteria of this review have been included. The major finding of our study is the significant elevation of elafin in skin aGVHD. CONCLUSION: Elafin is a significant biomarker for diagnosis and prognosis of skin aGVHD and should be assessed within 2 weeks of the onset of the disease.

Anisodamine for the prevention of contrast-induced nephropathy in patients with acute coronary syndrome: a pilot systematic review and meta-analysis of randomized controlled trials.

Introduction: Contrast-induced nephropathy (CIN) is a common post-procedural complication of percutaneous coronary intervention for acute myocardial infarction (AMI). Anisodamine hydrobromide is an alkaloid that has demonstrated efficacy in improving microcirculation. This meta-analysis aims to evaluate the reno-protective effects of Anisodamine in patients undergoing percutaneous coronary intervention (PCI) for AMI. Methods: PubMed, Embase, Cochrane Library, Scopus, and clinicaltrials.gov were searched from inception to January 2024 for randomized controlled trials (RCTs) comparing the efficacy of Anisodamine in preventing the development of CIN. Outcomes of interest included the incidence of CIN, serum creatinine levels, and estimated glomerular filtration rate (eGFR). A random-effects model was used for pooling standard mean differences (SMDs) and odds ratios (ORs) with a 95% CI. Statistical significance was considered at a P less than 0.05. Results: Three RCTs involving 563 patients were included. Anisodamine was associated with a reduction in the incidence of CIN [OR: 0.44; 95% CI: 0.28, 0.69; P=0.0003], a reduction in serum creatinine levels at 48 [SMD: -6.78; 95% CI: -10.54,-3.02; P=0.0004] and 72 h [SMD: -6.74; 95% CI: -13.33,-0.15; P=0.03], and a higher eGFR at 24 [SMD: 5.77; 95% CI: 0.39, 11.14; P=0.03], and 48 h [SMD: 4.70; 95% CI: 2.03,7.38; P=0.0006]. The levels of serum creatinine at 24 h and eGFR value at 72 h were comparable between both groups. Conclusions: Anisodamine has demonstrated clinical efficacy in ameliorating the development of CIN post-PCI in AMI patients. Large, multi-centric RCTs are warranted to evaluate the robustness of these findings.

Exploring Transthyretin Amyloid Cardiomyopathy: A Comprehensive Review of the Disease and Upcoming Treatments.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a mutation-based genetic disorder due to the accumulation of unstable transthyretin protein and presents with symptoms of congestive heart failure (CHF) and numerous extracardiac symptoms like carpal tunnel syndrome and neuropathy. Two subtypes of ATTR-CM are hereditary and wild-type, both of which have different risk factors, gender prevalence and major clinical symptoms. Timely usage of imaging modalities like echocardiography, cardiac magnetic imaging resonance, and cardiac scintigraphy has made it possible to suspect ATTR-CM in patients presenting with CHF. Management of ATTR-CM includes appropriate treatment for heart failure for symptomatic relief, prevention of arrhythmias and heart transplantation for nonresponders. With the recent approval of tafamidis in the successful management of ATTR-CM, numerous potential therapeutic points have been identified to stop or delay the progression of ATTR-CM. This article aims to provide a comprehensive review of ATTR-CM and insights into its novel therapeutics and upcoming treatments.

Comparison of recent updates in genetics, immunology, biomarkers, and neuroimaging of primary-progressive and relapsing-remitting multiple sclerosis and the role of ocrelizumab in the management of their refractory cases.

Background: Primary-progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS) are two frequent multiple sclerosis (MS) subtypes that involve 10%-15% of patients. PPMS progresses slowly and is diagnosed later in life. Both subtypes are influenced by genetic and environmental factors such as smoking, obesity, and vitamin D insufficiency. Although there is no cure, ocrelizumab can reduce symptoms and delay disease development. RRMS is an autoimmune disease that causes inflammation, demyelination, and disability. Early detection, therapy, and lifestyle changes are critical. This study delves into genetics, immunology, biomarkers, neuroimaging, and the usefulness of ocrelizumab in the treatment of refractory patients of PPMS. Method: In search of published literature providing up-to-date information on PPMS and RRMS, this review conducted numerous searches in databases such as PubMed, Google Scholar, MEDLINE, and Scopus. We looked into genetics, immunology, biomarkers, current breakthroughs in neuroimaging, and the role of ocrelizumab in refractory cases. Results: Our comprehensive analysis found considerable advances in genetics, immunology, biomarkers, neuroimaging, and the efficacy of ocrelizumab in the treatment of refractory patients. Conclusion: Early detection, timely intervention, and the adoption of lifestyle modifications play pivotal roles in enhancing treatment outcomes. Notably, ocrelizumab has demonstrated potential in symptom control and mitigating the rate of disease advancement, further underscoring its clinical significance in the management of MS.

ANCA-associated vasculitis following Johnson and Johnson COVID-19 vaccine.

Introduction: Antineutrophil cytoplasmic autoantibodies associated vasculitis (AAV) is characterized by antibodies against antigens in cytoplasmic granules of neutrophils and predominantly affects small vessels. AAV after COVID-19 mRNA vaccination has been reported. Case presentation: We report a rare case of AAV in a patient who presented with rapidly progressive glomerulonephritis (RPGN) after Johnson & Johnson COVID-19 vaccine administration. Discussion: The temporal causal association between autoimmune manifestations like AAV and COVID-19 vaccines can be explained by hypothesized mechanisms like molecular mimicry, defective neutrophilic apoptosis, polyclonal activation, and systemic proinflammatory cytokine response. These mechanisms are likely to trigger autoimmune responses in genetically susceptible individuals. Still there are many research going on to fill the research gap on the development of ANCA associated with COVID-19 vaccines. Conclusion: Increasing reports of rare adverse effects like AAV following COVID-19 vaccination warrants the further study and evaluation of immune responses induced by those vaccines. Considering the potential severity of COVID-19 and the rarity of the above-mentioned adverse effects, COVID-19 vaccination should not be withheld.

A rare case of atrial and biventricular thrombi with dilated cardiomyopathy as a delayed presentation in a patient with COVID-19.

Introduction: Coronavirus 2019 (COVID-19) can cause cardiovascular manifestations including myocardial injury and thromboembolic events. Case presentation: Here, we report a case of a 27-year-old female with dilated cardiomyopathy, right atrial and biventricular thrombi infected with COVID-19. Discussion: There are several complex coagulation abnormalities in COVID-19 patients that have been suggested to create a hypercoagulable state. Evidence have shown that endothelial injury potentially leading to thromboembolic events is caused by direct invasion of endothelial cell by SARS-CoV-2 and complement activation contributed by the virus spike protein. Conclusion: DCM can be complicated by atrial and biventricular thrombi due to coagulation abnormalities that are likely to persist after recovery from COVID-19. Thus, long-term careful monitoring of cardiac function is necessary after recovery of COVID-19.

Patient with Dravet syndrome: A case report.

Dravet syndrome is rare genetic epilepsy syndrome and epileptic encephalopathy. The patient initially has normal developmental profile with plateau or regression that begins after seizure onset. We report a case of two-year-old child diagnosed as dravet syndrome with moderate cerebral atrophy and ventricular dilatation as rare MRI finding.

A case report on role of hypertonic saline solution in management of parotid fistula.

Introduction: Parotid fistula is an uncommon consequence of surgical or non-surgical trauma to the parotid gland or the area surrounding it. To treat it, a variety of pharmacological medicines and surgical techniques are used, each with their own set of benefits, drawbacks, and patient preferences. Case Presentation: We present the successful care of a young female with post-traumatic parotid fistula using hypertonic saline injections into the parotid substance, which is a simple yet efficient approach of treating this abnormality. Discussion: Thermodynamic and physicochemical calculations suggest that hypertonic saline solutions work to close parotid fistula by causing conformational denaturation of the cell membrane proteins in situ and saline can be diluted to a point where there will be no cellular toxicity. It is advised that temperature of the saline should be raised above body temperature to enhance the fibrosing property of physiologic saline. Conclusion: The use of hypertonic hot saline injections combined with compression dressing is a cost-effective, patient-friendly, and almost complication-free approach of treating parotid fistulas with promising results.

Bronchopleural fistula and bilateral pneumothorax in a patient with COVID-19.

COVID-19 pneumonia causes several complications that include pneumothorax, hydropneumothorax, empyema, and rarely leads to bronchopleural fistula (BPF). BPF is a communication between the pleural space and the bronchial tree. We report a case of 24 years man with pneumothorax, hydropneumothorax, and BPF that appeared after COVID-19 infection.

Acute Lower Limb Ischemia in COVID-19 Patient with Delayed Presentation.

Thromboembolism is a common complication of SARS-CoV-2, which generally involves venous thromboembolism, although there have been reported cases of arterial thrombosis affecting cerebral, coronary, and visceral arteries, as well as arteries in the extremities. We discuss a case of a 45-year-old diabetic man with COVID-19 who developed late-onset acute lower limb ischemia.