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.

Tirzepatide: A Promising Drug for Type 2 Diabetes and Beyond.

Tirzepatide is a promising drug with dual-acting glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor activation that has revolutionized the treatment of type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise. In phase 3 clinical trials (SURPASS 1-5), the dose-dependent efficacy and safety of tirzepatide were assessed by once-weekly subcutaneous injection (5 mg, 10 mg, and 15 mg), as monotherapy or combination therapy, in individuals with T2DM. Tirzepatide has been shown to achieve better glycemic control in terms of glycosylated hemoglobin reduction and improved fasting and postprandial glucose levels as compared to other diabetic medications. Moreover, the studies demonstrate a reduction in body weight (-6.2 to -12.9 kg), and other cardiovascular benefits by altering the lipid profile, reducing blood pressure, and visceral adiposity. Tirzepatide has acceptable side effects and is well tolerated, with a low risk of hypoglycemia. The SURPASS 4 clinical trial has shown positive cardiovascular outcomes in people with T2DM and elevated cardiovascular risk. Additionally, encouraging results from SURMOUNT trials and ongoing SURPASS-CVOT studies will shed more light on cardiovascular safety in the future. In this review, we have summarized the clinical trials and their respective outcomes and highlighted the potential future indications for tirzepatide in the management of obesity, heart failure, and nonalcoholic steatohepatitis.

A Case of a Constricted Vessel: The Impact of Acute Myeloid Leukemia on the Superior Vena Cava.

Acute myeloid leukemia (AML) is the most prevalent form of leukemia in adults, with rising global incidence rates. AML usually presents with non-specific clinical features such as pallor, fever, and bleeding. This case report discusses a unique presentation of AML, where a 25-year-old female with a history of hypertension presented with unilateral facial swelling, chest pain, and shortness of breath. Radiologic investigations revealed a mediastinal mass encasing the superior vena cava (SVC), confirming the suspicion of SVC syndrome. Upon testing with a biopsy, the mass was found to be composed of immature myeloid cells confirming the diagnosis of myeloid sarcoma-associated AML. The patient's treatment involved a combination of surgical debridement, induction chemotherapy, supportive care, and management of complications. This case highlights that despite its common occurrence, AML may present with atypical clinical manifestations such as SVC syndrome, posing challenges in its diagnosis and timely management.

Treating Deep Venous Thrombosis in a Background of Crohn's Disease: A Clinical Conundrum.

Deep venous thrombosis (DVT) commonly affects the lower extremities, often as a result of prolonged immobilization. However, upper limb DVT is an atypical presentation, typically associated with risk factors such as the use of a peripherally inserted central catheter (PICC) line. This case report describes an uncommon case of DVT management in a patient with Crohn's disease, a condition more frequently characterized by painful lower gastrointestinal symptoms and chronic diarrhea. A 22-year-old male with a history of Crohn's disease developed swelling and purplish discoloration at the brachial site of a PICC line site. Laboratory results indicated anemia with a hemoglobin level of 9.9 g/dL and a hematocrit of 31.9%. Doppler ultrasound confirmed the DVT in the left long axillary, left subclavian, and left long basilic veins. Given the patient's concurrent lower gastrointestinal bleeding, a cautious approach was required to balance the risks and benefits of anticoagulation. Upon recommendation by Hematology, a prophylactic dose of enoxaparin was initiated and subsequently escalated to a therapeutic dose as tolerated. The patient's condition was closely monitored, and he successfully reached the full therapeutic regimen without complications. This case underscores the importance of individualized DVT treatment strategies in the context of concurrent Crohn's disease, offering insights into managing anticoagulation in the presence of bleeding risks.

Vemurafenib in the Treatment of Erdheim Chester Disease: A Systematic Review.

Erdheim Chester disease (ECD) is a type of histiocytosis characterized by a variable clinical presentation. The treatment of ECD is complex and mainly unknown. We aim to conduct a literature review of the treatment of ECD and consolidate the knowledge about the most recent and updated treatment for ECD. To conduct the systematic review, we used the preferred reporting items for systematic reviews and meta-analysis (PRISMA) protocol.  To analyze the bias, we used the Cochrane collaboration risk-of-bias tool to assess the bias. We included observational studies and clinical trials on humans, which were written in English. Papers not fulfilling the objective of our study were excluded. Overall, the drug showed efficacy in the clinical trials, showing prolonged improvement and high rates of response rate. Overall, the drug was not well tolerated, and patients had a long list of side effects. Nevertheless, the drug seems to be a good option for second-line treatment for patients with ECD and BRAFV600 mutation.