Secondary Prevention of Cryptogenic Stroke and Outcomes Following Surgical Patent Foramen Ovale Closure Plus Medical Therapy vs. Medical Therapy Alone: An Umbrella Meta-Analysis of Eight Meta-Analyses Covering Seventeen Countries.

Background: Cryptogenic stroke (CS) is an exclusion diagnosis that accounts for 10-40% of all ischemic strokes. Patent foramen ovale (PFO) is found in 66% of patients with CS, while having a prevalence of 25-30% in the general population. The primary aim was to evaluate the risk of recurrent stroke following surgical PFO closure plus medical therapy vs. medical therapy alone amongst CS, an embolic stroke of undetermined source (ESUS), or transient ischemic attack (TIA). The secondary aim was to evaluate new-onset non-valvular atrial fibrillation, mortality, and major bleeding. Methods: We conducted an umbrella meta-analysis using PRISMA guidelines on English studies comparing surgical PFO closure plus medical therapy versus medical therapy alone for managing CS. We extracted data on interventions and outcomes and used random-effects models with generic inverse variance to calculate relative risks (RRs) with 95% confidence intervals for outcome calculations. Results: A comprehensive search yielded 54,729 articles on CS and 65,001 on surgical PFO closure, with 1,591 studies focusing on PFO closure and medical therapy for secondary CS, ESUS, or TIA prevention. After excluding non-meta-analyses, 52 eligible meta-analyses were identified, and eight studies were selected for outcome evaluation, excluding non-English, non-human, and studies before January 2019 as of August 31, 2021. Among a total of 41,880 patients, 14,942 received PFO closure + medical therapy, while 26,938 patients received medical therapy alone. Our umbrella meta-analysis showed that PFO closure plus medical therapy had a 64% lower risk of recurrent strokes than medical therapy alone (pooled RR: 0.36). PFO closure plus medical therapy was associated with 4.94 times higher risk of atrial fibrillation. There was no difference in the risk of death or bleeding between both groups. Conclusion: In patients with CS, PFO closure, in addition to medical therapy, reduces the risk of recurrence. More research is needed to assess the efficacy of early closure as well as specific risk profiles that would benefit from early intervention to reduce the burden of stroke.

COVID-19 Coronavirus-Induced Atypical Pneumonia: Efficacy of the Monoclonal Antibody Bevacizumab in Moderate to Severe Cases.

COVID-19 novel coronavirus has created a global pandemic. Affected patients may develop acute lung injury and its more severe form - acute respiratory distress syndrome. Hypoxia and severe inflammation increase the production of vascular endothelial growth factor (VEGF), which induces vascular endothelial proliferation. Administration of the anti-VEGF monoclonal antibody bevacizumab is proposed for usage in moderate to severe pneumonia. We aim to present two cases of COVID-19 induced atypical pneumonia, which were treated with the anti-VEGF monoclonal antibody bevacizumab.

Non-uremic Calciphylaxis: A Rare and Late Adverse Reaction of Warfarin.

BACKGROUND: Calciphylaxis is a complex dermatological lesion of micro vascular calcification that is typically presented as panniculitis with gangrenous painful lesions having uremic and non-uremic causes. CASE REPORT: We present a case of a 48-year old male with a history of paroxysmal atrial fibrillation and hypertension taking amlodipine 5 mg and warfarin 5 mg daily for the last 26 months. The patient had a 6- months history of painful swelling followed by necrotic skin ulcer over the right leg. His remarkable examination findings were right leg tender ulcer with surrounding erythema and secondary sepsis. His hemogram, metabolic profile and connective tissue diseases work up were unremarkable except leucocytosis and raised inflammatory markers. His local part radiological and skin biopsy findings were suggestive of calciphylaxis. RESULTS AND CONCLUSION: In our case, warfarin and amlodipine were culprit drugs for the lesion, but Naranjo score (warfarin 7and amlodipine 1) speculate warfarin as a probable adverse reaction of warfarin. The lesion was cured with local wound treatment after discontinuation of warfarin. The physician should be aware of this rare cutaneous disorder of systemic origin for proper management.

Post Chikungunya Chronic Arthritis: Systemic Inflammatory Status Triggering Acute Coronary Syndrome.

BACKGROUND: Atherosclerosis, inflammation and coronary plaque destabilization are linked to each other. Infections due to various microbes may trigger Acute Coronary Syndrome (ACS) by systemic inflammation cascade. METHODS: We have evaluated the prevalence of Post Chikungunya Chronic Arthritis (PCCA) among 400 consecutive ACS patients (Case group) and compared with control group subjected to elective surgery by the prospective case-control observational study. Cases were excluded if standard criteria of ACS were not satisfied and in the control group if the patient suffered a Myocardial Infarction (MI) within 28 days of elective surgery. PCCA duration more than two years or serum IgM anti-CCP positive patients were also excluded from the case as well as a control group. RESULTS: The case and control groups were similar except, less number of heart failure (O.R.7.3, 95% C.I. 3.3-15.9) and chronic kidney injury patients (O.R. 0.5, 95% C.I. 0.3-0.9) in the elective surgery (control) group. PCCA was present in 24 out of 400 ACS cases and 8 out of 400 control group. Among ACS case-patients, those suffering from PCCA tended to be younger and more often women, with more diabetes, hypertension, chronic kidney injury and high mean CRP. In unadjusted analysis PCCA was three times more common in the case versus control (O.R. 3.0, 95% C.I. 1.4- 6.4); results were indistinguishable after multidiscipline adjustment (O.R. 3.0, 95% C.I. 1.3-6.8). CONCLUSION: PCCA is common among patients with ACS and post-infective systemic inflammation of PCCA may trigger plaque destabilization.

Phenytoin Induced Chorea: A Rare Adverse Effect of the Drug.

BACKGROUND: Dyskinetic neurological diseases are common presentations of adverse reaction to many therapeutic agents. Phenytoin, a widely used age-old antiepileptic drug has been reported to cause dyskinesias, a rare Adverse Drug Reaction (ADR) in adults with toxic therapeutic serum level. When the drug is used in combination with other drugs which augments free drug level of phenytoin or in patients of organic brain lesion, this side effect is very occasionally reported with even normal therapeutic drug level. CLINICAL CASE: We report a case of young male presented with chorea after two months of starting phenytoin for primary generalised epilepsy with normal therapeutic serum drug level. After excluding other differentials, drug-induced chorea was the final diagnosis. Despite phenytoin level was in therapeutic range, we have a trial of stopping Phenytoin with complete disappearance of chorea in 3 days. On reintroduction of phenytoin in the same dose, there was the reappearance of chorea in onemonth re-emphasising the diagnosis as "phenytoin-induced chorea". CONCLUSION: If any patient on phenytoin develops any new neurological feature including dyskinesias, it should be considered as an ADR despite drug serum level within the normal therapeutic range.