Safety and efficacy of antithrombotics in outpatients with symptomatic COVID-19: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease (COVID-19) is a global health emergency, with well over six hundred million infections and over six million deaths to date. Besides other ramifications, it is also associated with inflammation and an augmented risk of thromboembolic complications. Despite this, the risks and benefits of antithrombotic drugs in patients with mild to moderate COVID-19 have not been well-established and remain controversial. OBJECTIVES: To evaluate the safety and efficacy of antithrombotic drugs on mild to moderate symptomatic COVID-19 patients by performing an updated systematic review and meta-analysis. METHODS: We queried electronic databases (PubMed, Cochrane Central, Scopus, and Embase) from their inception up to September 2022 for randomized controlled trials comparing antithrombotic drugs against placebo. The outcomes of interest were the need for hospital care, mortality, and thromboembolic events in the enrolled participants. Dichotomous outcomes were presented as risk ratio (RR) with 95 % confidence intervals (CIs) and were consolidated using random-effects model. MAIN RESULTS: Five eligible studies (Rivaroxaban/Apixaban, two; enoxaparin, two; Sulodexide, one), consisting of 2,005 participants with mild to moderate COVID-19, were included. Pooled results show that antithrombotics, when compared to placebo, do not significantly reduce all-cause mortality (RR 0.51, 95 % CI 0.15-1.68; P = 0.27; I2 = 0), thromboembolic events (RR 0.78, 95 % CI 0.17-3.51; P = 0.74; I2 = 0), need for hospitalization (RR 0.73, 95 % CI 0.51-1.03; P = 0.08; I2 = 0), nor significantly increase clinically relevant non-major bleeding events (RR 2.36, 95 % CI 0.56-9.89; P = 0.24; I2 = 0). However, when Sulodexide was compared independently to other antithrombotics, it significantly reduced the need for hospitalization (RR 0.60, 95 % CI 0.37-0.95; P = 0.03). CONCLUSIONS: Our pooled analysis was not able to establish statistically significant benefits or risks of using antithrombotic drugs in mild to moderate COVID-19 patients. To further improve our understanding of the efficacy, safety and risk profile of such a therapy, large sample randomized clinical trials are required on a wide scale.

Efficacy of Allopurinol in Improving Endothelial Dysfunction: A Systematic Review and Meta-Analysis.

INTRODUCTION: Endothelial dysfunction has been implicated in various cardiovascular disorders as the initial pathology. Allopurinol has been shown to improve endothelial dysfunction in patients with gout, but its effect on cardiovascular patients is unclear. AIMS: We aim to assess allopurinol efficacy in improving endothelial dysfunction overall and in different disease states including but not limited to heart failure, chronic kidney disease, ischemic heart disease METHODS: We conducted a literature search of PubMed, Cochrane's Central Library, and Scopus until December 2022, including randomized controlled trials and double-arm observational studies. The primary outcome measure was endothelial function assessed by change in flow mediated dilation (FMD) RESULTS: Our meta-analysis included 22 studies with a total of 1472 patients. Our pooled analysis shows that allopurinol significantly improved FMD (WMD = 1.46%, 95% CI [0.70, 2.22], p < 0.01) compared to control. However, there was no significant difference between allopurinol and control for endothelial-independent vasodilation measured by forearm blood flow (WMD = 0.10%, 95% CI [- 0.89, 0.69], p = 0.80). Subgroup analysis indicated that the effect of allopurinol on FMD was more significant in diabetic and congestive heart failure patients. CONCLUSION: While allopurinol may improve endothelial function in various patient populations, further high-quality randomized controlled trials are needed to determine its efficacy in preventing cardiovascular disease exacerbation.

Folfirinox vs. Gemcitabine + Nab-Paclitaxel as the First-Line Treatment for Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Background: The efficacy and safety of Folfirinox (FFX) or gemcitabine + nab-paclitaxel (GnP) to be used as the first-line drugs for pancreatic cancer (PC) is yet to be established. We conducted an analysis of retrospective studies to assess the efficacy and safety of these two regimens by comparing their survival and safety outcomes in patients with PC. Methods: We conducted an extensive review of two electronic databases from inception till February 2023 to include all the relevant studies that compared FFX with GnP published and unpublished work. Retrospective studies were only included. Overall survival (OS) and progression-free survival (PFS) were pooled using hazard ratios (HRs), while objective response rate (ORR) and safety outcomes were pooled using odds ratios (ORs) with 95% confidence interval (CI) using the random effects model. Results: A total of 7,030 patients were identified in a total of 21 articles that were shortlisted. Pooled results concluded that neither FFX nor GnP was associated to increase the OS time (HR: 0.93, 95% CI: 0.83 - 1.04; P = 0.0001); however, FFX was more likely associated with increased PFS when compared to GnP (HR: 0.88, 95% CI: 0.81 - 0.97; P < 0.0001). ORR proved to be non-significant between the two regimens (OR: 0.90, 95% CI: 0.64 - 1.27; P = 0.15). Safety outcomes included neutropenia, anemia, thrombocytopenia and diarrhea. GnP was more associated with diarrhea (OR: 1.96, 95% CI: 1.22 - 3.15; P = 0.001), while FFX was seen to cause anemia (OR: 0.70, 95% CI: 0.51 - 0.98; P = 0.10) in PC patients. Neutropenia and thrombocytopenia were in-significant in the two drug regimens (OR: 1.10, 95% CI: 0.92 - 1.31; P = 0.33 and OR: 0.83, 95% CI: 0.60 - 1.13; P = 0.23, respectively). Conclusion: FFX and GnP showed a significant difference in increasing the PFS, while no difference was observed while measuring OS. Safety outcomes showed that FFX and GnP shared similar safety profiles as FFX was associated with hematological outcomes, while GnP was more associated with non-hematological outcomes.

Effectiveness of Emergency versus Nonemergent Coronary Angiography After Out-of-Hospital Cardiac Arrest without ST-Segment Elevation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The optimal timing of coronary angiography (CAG) in patients after out-of-hospital cardiac arrest (OHCA) without ST-segment elevation remains controversial. Therefore, we conducted a meta-analysis of randomized control trials to investigate the effectiveness of emergency CAG versus delayed CAG in OHCA patients with a non-ST-segment elevated rhythm. PubMed, Scopus, CINAHL, Cochrane CENTRAL, and JBI databases were searched from inception to September 7, 2022. Our primary end point was survival with a good neurological outcome, whereas the secondary outcomes included short-term survival, mid-term survival, recurrent arrhythmias, myocardial infarction after hospitalization, major bleeding, acute kidney injury, and left ventricular ejection fraction. Nine randomized control trials involving 2,569 patients were included in this analysis. Our meta-analysis showed no significant difference in the improvement of neurological outcome (RR 0.96, 95% Confidence Interval [CI] [0.87, 1.06]), short-term survival (risk ratio [RR] 0.98, 95% CI [0.89, 1.08]), mid-term survival (RR 0.98, 95% CI [0.87, 1.10]), recurrent arrhythmias (RR 1.02, 95% CI [0.50, 2.06]), myocardial infarction (RR 0.66, 95% CI [0.13, 3.30]), major bleeding (RR 0.96, 95% CI [0.55, 1.69]), acute kidney injury (RR 1.20, 95% CI [0.32, 4.49]) and left ventricular ejection fraction (RR 0.89, 95% CI [0.69, 1.15]) in patients who underwent emergency CAG compared with delayed CAG patients. In conclusion, our analysis revealed that emergency CAG had no prognostic superiority over delayed CAG in patients with OHCA without ST-segment elevation.

Duet of Death: Biventricular Thrombus in a Methamphetamine User.

We present the case of a 60-year-old male who developed an ischemic stroke due to left ventricular (LV) thrombus emboli as a complication of methamphetamine-induced cardiomyopathy. The patient had a history of methamphetamine abuse, hypertension, and ischemic stroke with no residual deficits presented with new onset slurred speech, left-sided weakness, and numbness for two hours. Computed tomography (CT) of the head showed no acute changes, and a tissue plasminogen activator was given in the emergency department within 30 minutes of arrival. Urine drug screen (UDS) was positive for methamphetamine, and magnetic resonance imaging (MRI) of the brain showed acute cortical infarcts in the right frontal lobe and parietal lobe and chronic infarct in the left occipital lobe. Transthoracic echocardiography showed bilateral ventricular thrombus and severely reduced ejection fraction of 20-25%. The patient had no evidence of thrombophilia and was started on a heparin drip for thrombus and goal-directed medical therapy for heart failure with reduced ejection fraction (HFrEF). Upon discharge, the patient was prescribed the oral anticoagulant rivaroxaban. The LV thrombus emboli were attributed to causing ischemic stroke. This case highlights the potential risk of ischemic stroke due to LV thrombus emboli in patients with methamphetamine-induced cardiomyopathy.

Fat Pulmonary Embolism With Crazy-Paving Pattern Opacities and Pneumothorax: A Rare Complication of Liposuction.

Fat embolism syndrome (FES) is a rare multiorgan disease caused by microvascular obstruction by fat globules and free fatty acid-mediated endothelial injury leading to pro-inflammatory cytokine release. We present a rare case of a 54-year-old woman who underwent elective aesthetic liposuction and developed FES and pneumothorax within 12 hours of the procedure.

An Individual Patient-Level Meta-Analysis of Ischemic Versus Nonischemic Cardiomyopathy and Trajectory of Decongestion in Patients With Acute Decompensated Heart Failure.

Data are limited regarding the impact of ischemic cardiomyopathy (ICM) or non-ICM (NICM) on the trajectory of in-hospital decongestion among patients with acute decompensated heart failure (ADHF). Therefore, we aimed to assess the course of decongestion among patients admitted for ADHF by history of ICM and NICM. Patients included in the DOSE (Diuretic strategies in patients with acute decompensated heart failure), ROSE (ROSE acute heart failure randomized trial), and Ultrafiltration in decompensated heart failure with cardiorenal syndrome (CARRESS-HF) trials of patients with ADHF were categorized into ICM and NICM based on history. Among 762 patients included in our meta-analysis, 433 (56.8%) had a history of ICM. Patients with ICM were older (70.8 vs 63.9 years; p ≤0.001) and had higher rates of co-morbidities. After covariate adjustment, there was no significant differences between NICM and ICM regarding net fluid loss (4,952 vs 4,384 ml, p = 0.81) or mean change in serum N-terminal pro-brain natriuretic peptide (-2,162 vs -1,809 pg/ml, p = 0.092). Mean change in weight showed modest improvement in favor of patients with NICM, but this did not meet statistical significance (-8.24 vs -7.70 pounds, p = 0.068). After adjustment, there was no significant difference in the risk of 60-day composite all-cause mortality or hospitalization for HF among those with ICM versus NICM. Among patients with left ventricular ejection fraction <40%, NICM was associated with higher scoring on global sense of well-being (global visual analog scale; +25.5 vs +19.1, p = 0.023) and improvement in serum creatinine (-0.031 mg/100 ml vs +0.042 mg/100 ml, p = 0.009) at 72 hours. Among patients with left ventricular ejection fraction >40%, NICM was associated with decreased scoring on global visual analog scale at 72 hours (+15.7 vs +21.2, p = 0.049). In conclusion, more than half of the patients admitted for ADHF had ICM. History of ICM was not independently associated with a difference in course of decongestion, self-assessment of well-being and dyspnea, or short-term clinical outcomes.

A Systematic Review and Meta-Analysis on Effectiveness of Mineralocorticoid Receptor Antagonists in Reducing the Risk of Atrial Fibrillation.

Mineralocorticoid receptor antagonists (MRAs) are known to improve clinical outcomes in heart failure, particularly heart failure with reduced ejection fraction. However, the effect of MRAs on the incidence of and recurrence of atrial fibrillation (AF) is not well established. Therefore, databases, such as PubMed, EMBASE, and Cochrane Central, were searched from inception to September 2021 for randomized controlled trials of MRAs with AF as an outcome. Risk ratios (RRs) with 95% confidence interval (CIs) were combined using the random-effects model. A total of 10 randomized controlled trials (n = 11,356) were included. Our pooled analysis demonstrates that MRAs reduce the risk of AF occurrence by 23% compared with the control therapy (RR 0.77, 95% CI 0.65 to 0.91, p = 0.003, I2 = 40%). Subgroup analysis demonstrated that MRAs reduced the risk of both new-onset AF (RR 0.84, 95% CI 0.61 to 1.16, p = 0.28, I2 = 43%) and recurrent AF (RR 0.73, 95% CI 0.59 to 0.90, p = 0.004, I2 = 26%) similarly; p interaction = 0.48. Our meta-analysis concludes that MRAs reduce the risk of development of AF overall, with consistent effects in new-onset and recurrent AF.

The Role of Vitamin D Supplementation Before Coronary Artery Bypass Grafting in Preventing Postoperative Atrial Fibrillation in Patients With Vitamin D Deficiency or Insufficiency: A Systematic Review and Meta-Analysis.

This study aims to evaluate the role of preoperative vitamin D supplementation before coronary artery bypass grafting (CABG) surgery in preventing postoperative atrial fibrillation (POAF) in vitamin D deficient or insufficient patients. Three randomized controlled trials (RCTs) comprising 448 subjects were selected after a detailed search was conducted on PubMed, Cochrane CENTRAL, Scopus, and Embase in December 2022. Analysis was run using RevMan (version 5.4.1; Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). The analysis collected risk ratio (RR) and 95% confidence interval (CI) data from the relevant studies, which were then pooled using a random effects model. A significance level of less than 0.05 (p<0.05) was considered significant. Our analysis showed that compared with the standard of care, preoperative vitamin D supplementation in vitamin D deficient and insufficient patients effectively reduced POAF after CABG surgery (RR=0.6, 95% CI=0.4-0.9, P=0.01). There was no significant difference in the duration of hospitalization between the vitamin D supplementation group compared with the control following CABG (mean difference -0.85, 95% CI -2.13 to 0.43, P = 0.19). This meta-analysis shows that preoperative vitamin D supplementation in vitamin D deficient and insufficient patients undergoing CABG can reduce the rate of POAF. As POAF is associated with many complications, providing vitamin D supplementation to individuals with a vitamin D deficiency undergoing CABG can improve long-term cardiovascular outcomes following surgery.

The Safety and Efficacy of GLP-1 Receptor Agonists in Heart Failure Patients: A Systematic Review and Meta-Analysis.

Evaluation of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) usage in heart failure (HF) patients with or without type 2 diabetes mellitus (T2DM) could be proven to be a critical breakthrough in treatment options available for these patients. Our study focuses on understanding the safety and efficacy of GLP-1 RAs in this patient population by pooling the data from 9 randomized controlled trials (RCTs) comprising 871 subjects. As compared with the placebo, GLP-1 RAs did not improve major adverse cardiovascular events (MACE) which include cardiovascular (CV) mortality and heart failure (HF) hospitalizations, our primary outcome. CV mortality (RR = 1.03, 95% CI = 0.56-1.88, P = 0.92) and HF hospitalizations (RR = 1.18, 95%CI = 0.93-1.51, P = 0.18). Similarly, GLP-1 RAs did not improve our secondary findings of left ventricular ejection fraction (LVEF) and 6-minute walk test (6MWT). LVEF (RR = 1.96, 95%CI = -0.16-4.07, P = 0.07) or 6 MWT (RR = 8.43, 95% CI = -2.69-19.56, P = 0.14). This meta-analysis shows that GLP-1 RAs do not improve cardiovascular outcomes in HF patients with or without T2DM.

COVID-19 and Bradyarrhythmias: A Case Report With Literature Review.

We report a case of a 51-year-old male with no past medical history who was admitted for acute hypoxic respiratory failure secondary to COVID-19. During his hospitalization, the patient developed sinus bradycardia and frequent sinus pauses were observed on telemetry. No other cause of his bradyarrhythmia was identified except for his COVID-19 infection. There has been numerous case reports and case series describing different arrhythmias seen in patients infected with COVID-19. We present a case of sinus arrest in a patient with COVID-19 and a review of other case reports describing bradyarrhythmia in COVID-19 patients.

Post-Paracentesis Hemoperitoneum From a Bleeding Mesenteric Varix: A Case Report on a Rare Presentation.

We report a case of a 53-year-old male with decompensated liver cirrhosis secondary to alcohol abuse and hepatitis C infection who was admitted for hemorrhagic shock secondary to upper GI bleed. He underwent a therapeutic paracentesis 17 days after admission with the removal of 6 L of ascitic fluid. The patient became hemodynamically unstable after paracentesis and an acute drop in his hemoglobin was noted. On imaging, he was found to have massive hemoperitoneum secondary to a bleeding mesenteric varix. This is a very rare complication of paracentesis in patients with advanced cirrhosis and should be recognized early in the post-procedure period to initiate prompt life-saving measures to minimize morbidity and mortality.

Resistant Polymorphic Ventricular Tachycardia in a Patient Taking Raspberry Ketones Weight Loss Supplement.

A 32-year-old female with no cardiac risk factors was admitted for treatment of a perianal abscess. During her hospital stay, she had a pulseless electrical activity arrest with a return of spontaneous circulation after one round of cardiopulmonary resuscitation (CPR). After transfer to the Intensive Care Unit (ICU), the patient had polymorphic ventricular tachycardia (PVT) requiring defibrillation shock. Her PVT was resistant to medical interventions. She was shocked a total of 33 times before her arrhythmia was terminated by passing a temporary transvenous pacemaker with overdrive pacing. After an extensive review of her history and presentation, no clear cause of her resistant arrhythmia was identified, however, she was found to have recently started taking over-the-counter weight loss supplements containing raspberry ketones which is a potentially cardiotoxic ingredient.

Development of Central Nervous System Vasculitis in a Patient with Waldenstrom Macroglobulinemia: A Rare Presentation with Poor Prognosis.

Waldenstrom macroglobulinemia (WM) is a rare lymphoproliferative disorder characterized by the presence of monoclonal immunoglobulin M in serum. WM may present with neurologic complications involving the peripheral and central nervous systems (CNS) though CNS complications associated with WM are rare. We present a case of a 72-year-old male with an 18-month history of WM who experienced neurologic and constitutional symptoms indicative of WM progression over a three-week period while on rituximab maintenance therapy. The patient's symptoms were initially attributed to rituximab-induced asthenia though his clinical condition did not improve with rituximab discontinuation. Due to progressively worsening neurologic symptoms, the patient was re-evaluated and found to have multiple cerebral infarcts and increased serum cryoglobulin levels indicative of cryoglobulinema. The patient was promptly initiated on a combination regimen of high dose steroids, intravenous immunoglobulin (IVIG), and plasmapheresis but had a poor response. Brain biopsy revealed necrotizing vasculitis with dense intra- and peri-vascular CD3 positive T-cell infiltrates with mural necrosis. This is a unique case of WM complicated by type 1 cryoglobulinemia associated with CNS vasculitis that was unresponsive to active rituximab therapy; this case illustrates a poor prognosis of patients with CNS involvement in WM.

Sternoclavicular Joint Septic Arthritis and Anterior Mediastinal Mass in a Young Athlete: Possible Immune-modulatory Effect of Growth Hormone.

Septic arthritis of sternoclavicular joint (SCJ) is a rare disease, however, not uncommon in patients who abuse intravenous drugs. It can present with a wide range of manifestations that can pose diagnostic challenges, which can result in a delay in diagnosis and treatment. Over the last few decades, there is a surge in the use of nonprescription recombinant human growth hormone (rhGH) by the young healthy population and athletes for its purported ergogenic effects. Furthermore, we lack quantitative information about the adverse effects of the chronic use of rhGH in a healthy population due to the scarcity of epidemiological data. We are reporting a case of a young male athlete who was chronically using the subcutaneous rhGH formulation to build lean body mass, and presented with septic arthritis of right SCJ due to methicillin-sensitive Staphylococcus aureus (MSSA) complicated by a necrotic inflammatory response involving the mediastinum which infiltrated the apical lung parenchyma. The clinical presentation masqueraded as the mediastinal mass raising the suspicion of mediastinal malignancy. Histological analysis of the tissue of SCJ and mediastinal area revealed no malignant cells but a lymphocyte-predominant inflammatory response with germinal centers was observed, which was an atypical response to MSSA bacterial infection. We have reviewed the literature to elucidate the immune-modulatory effect of rhGH, as the chronic use of rhGH by our patient probably has contributed to an atypical immune response to MSSA. The patient was treated with an extended duration of parenteral antibiotics and multiple incision and debridements to achieve complete resolution of infection over the next six months. This is a unique case of septic arthritis of right SCJ in a patient on chronic subcutaneous rhGH which masqueraded as a mediastinal mass raising concern of malignancy; moreover, it highlights the probable immune-modulatory role of rhGH which instigated an atypical immune response to MSSA infection.