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Few therapies exist to treat severe COVID-19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID-19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID-19 respiratory failure.A multicenter, retrospective, observational study of patients with confirmed COVID-19 and severe respiratory failure who received systemic tPA (alteplase) was performed. Seventy-nine adults from seven medical centers were included in the final analysis after institutional review boards' approval; 23 were excluded from analysis because tPA was administered for pulmonary macroembolism or deep venous thrombosis. The primary outcome was improvement in the PaOtPA was associated with significant PaOThese data suggest tPA is associated with significant improvement in pulmonary function in severe COVID-19 respiratory failure, especially in patients whose pulmonary function is in decline, and has an acceptable safety profile in this patient population.

The association between Diabetes and cancer has been known for decades with obesity and insulin resistance being postulated as the main underlying risk factors for both disorders. With rise of the epidemic of obesity in the USA and around the globe, there has been a rise in diabetes that is currently reaching epidemic proportions. Diabetes is known to be associated with increased risk of several types of malignancy including breast, cervical, pancreatic and colon cancer. In this review, we discuss the epidemic of obesity and its consequential epidemic of diabetes highlighting the pathophysiologic mechanisms of increased cancer in the diabetic population. We will then discuss the role of insulin therapy as well as, other antidiabetic medications, particularly metformin that has been to be associated with lower risk as well as better survival with GI malignancies based on several studies including a study that was recently published by our group.

Marijuana is the most common drug of abuse in the United States. Marijuana acts on cannabinoid receptors CB1, CB2 and another distinct endothelial receptor. Marijuana is known to cause tachycardia, hypotension and hypertension. Various arrhythmias including atrial fibrillation, atrial flutter, II degree AV block, ventricular fibrillation, ventricular tachycardia, asystole and brugada pattern associated with marijuana use have been reported. We here present an interesting case of Type I Brugada pattern in electrocardiography (ECG) in a 36 year old healthy African American male who presented after smoking four joints. Urine toxicology test proved marijuana use. Acute coronary syndrome was ruled out, coronary angiogram revealed normal coronaries, 2D echocardiogram showed no evidence of structural heart disease. Upon resolution of Brugada pattern in ECG, procainamide challenge performed in electrophysiology laboratory did not induce Brugada pattern. Patient was asked to return to hospital if he developed fever that did not resolve with antipyretics. Further studies are required to to understand the effect of marijuana on cardiac ion channels.

Despite advances in diagnostic and therapeutic interventions, coronary heart disease remains as one of the leading causes of death in developed countries. ST-segment elevation myocardial infarction is associated with the highest mortality and is an indication for emergent reperfusion therapy. Current guidelines for emergent reperfusion not only include ST segment elevations but also consider evidence of a new onset Left Bundle Branch Block (LBBB). However, accumulating evidence indicates that RBBB is also associated with poor outcome in coronary artery disease. To-date, guidelines do not comment on the urgency of reperfusion therapy with sole evidence of a new onset Right Bundle Branch Block (RBBB). Particularly we question whether clinicians should focus on new-onset RBBB as a ST-segment elevation equivalent. If so, appropriate management of patients with the new onset RBBB during cardiac ischemia can have a significant impact on cardiac function and outcomes. In this series, we present four cases of new-onset acute RBBB associated with chest pain in the setting of acute myocardial infarction with critical lesions of the left anterior descending artery. We also highlight the need to consider new RBBB as an additional indication for acute reperfusion therapy in acute myocardial infarction. This will call for revision in the current guidelines by American Heart Association following the initiative recently implemented by the European Society of Cardiology 2018.

Introduction: End-stage renal disease requiring renal transplantation comprises a growing patient population at risk for cardiovascular disease (CVD) morbidity and mortality in large part due to accelerated atherosclerosis. Consequently, these patients are at even higher risk of major surgical CVD mortality. A paucity of research has addressed the posttransplantation CVD outcomes related to different treatment strategies in this patient population and therefore, there are no specific preoperative guidelines regarding management of coronary artery disease in this high-risk population undergoing renal transplantation. Objective: Through meta-analysis we compare coronary revascularization to medical management prior to renal transplantation in patients who are found to have significant obstructive coronary artery disease. Results: A total of 6 studies were deemed suitable out of 777 articles reviewed. This included 260 patients who received medical management and 338 who received coronary revascularization. There were 36 events in the revascularization and 57 events in the medical management group. One study only reported hazard ratios but no CVD outcomes. Comprehensive Meta-Analysis software was used to calculate pooled odds ratio with 95% confidence intervals (CI) for the fixed effects. The data is presented as forest plots. The pooled odds ratio with 95% CI for the fixed effects was 1.415 (95% CI 0.885–2.263), p = 0.147, indicating that there is no difference in CVD outcomes between pretransplant treatment strategy. This observation suggests that the CVD outcomes posttransplantation are not affected when optimal medical therapy is used instead of coronary revascularization.

Cardiovascular disease (CVD) is the number one cause of death globally, accounting for 31% of all deaths in the world, and one out of every three deaths in the United States, in 2017 [1]. It is estimated that 90% of CVD is preventable, with traditional risk factors including tobacco use, excessive alcohol consumption, and unhealthy diet and physical inactivity, leading to hypertension, diabetes, dyslipidemia, and obesity. The epidemic of obesity has increased over the past decade, affecting an estimated 37.7% of adults, and 18% of children, in the US, and projected to rise to 51% of the population, a 130% increase, by 2030 [2]. This obesity epidemic has ushered in a new, highly prevalent, but largely underdiagnosed CVD risk factor: obstructive sleep apnea (OSA). OSA affects 34% of men, and 17% of women in the United States [3]. It is characterized by repetitive episodes of hypoventilation and complete apnea during sleep caused by total pharyngeal collapse and airway obstruction, despite normal breathing effort and drive. OSA’s impact on CVD appears to be due to recurrent cardio metabolic perturbations experienced when repetitively attempting to breath against an occluded airway, precipitating nightly episodes of hypoxia, sleep disturbance, and sympathetic nervous system surges, culminating in elevated blood pressure and heart rate, endothelial dysfunction, systemic inflammation and insulin resistance-all mechanisms involved in the pathogenesis of CVD (Figure 1) [4]. Accumulating evidence has linked OSA to multiple cardiovascular disorders including hypertension, type 2 DM, coronary artery disease, heart failure and cardiac arrhythmias (Figure 2). Open in a separate window Figure 1 Pathophysiological mechanisms linking obstructive sleep apnea to cardiovascular disease.

Despite underreporting and "dry" bites (bites by venomous snakes without envenoming), snake envenomation is a cause of high morbidity and mortality in the suburban and rural areas of tropical and subtropical world. In addition to local effects at the site of the bite, envenomation affects almost all the tissues in the body both primarily or secondarily. Envenomation is known to cause cardiotoxicity. Multiple case reports of myocardial infarction (MI) following snake bites have been reported. We hereby present the first systematic review of such cases. Our review revealed that MI following envenomation is mostly reported in young adult males from tropical and subtropical world with no history of coronary artery risk factors. Most of the cases presented 60 minutes after the bite. Among the cases that reported electrocardiography (EKG) findings, 63% had ST-segment elevation. 88% of the cases had elevated troponin levels. 75% of the reported echocardiograms had wall motion abnormality. All patients who had emergent coronary angiography were noted to have a "culprit" vessel. 25% of the cases suffered cardiac arrest and 25% subsequently passed away. The pathophysiology of MI following envenomation is multifactorial. When MI is suspected, coronary angiography should be considered after hemodynamic stability and anti-venom therapy is ensued.

Objectives: To conducted a meta-analysis assessing the relationship between Obstructive Sleep Apnea (OSA) and the risk of Atrial Fibrillation (AF).Methods: We searched PUBMED, Medline, and Cochrane Library using the keywords “atrial fibrillation”, “obstructive sleep apnea” and “sleep disordered breathing (SDB)”. All subjects included had established diagnosis of OSA/SDB. We then compared the occurrence of AF versus no AF. Analysis done with Comprehensive Meta- Analysis package V3 (Biostat, USA).Results: A total of 579 results were generated. Duplicates were removed and 372 records were excluded based on irrelevant abstracts, titles, study design not consistent with the stated outcome, or full-text unavailable. Twelve studies meeting the inclusion criteria were reviewed in full-text; 2 of these articles were eventually removed due to unconfirmed OSA diagnostic modality, and one was also removed based on a control group inconsistent with the other studies. Therefore, a total of 9 studies were included (n=19,837). Sample sizes ranged from n=160 patients to n=6841 patients. The risk of AF was found to be higher among OSA/SDB versus control group (OR; 2.120, C.I: 1.845- 2.436, Z; 10.598 p

Implantable cardioverter-defibrillators (ICDs) are the standard of care for preventing sudden cardiac death in patients who are predisposed to malignant ventricular arrhythmias. Causes of inappropriate ICD shock include equipment malfunction, improper arrhythmia evaluation, misinterpretation of myopotentials, and electromagnetic interference. As the number of implanted ICDs has increased, other contributors to inappropriate therapy have become known, such as minimal electrical current leaks that mimic ventricular fibrillation. We present the case of a 63-year-old man with a biventricular ICD who received 2 inappropriate shocks, probably attributable to alternating-current leaks in a swimming pool. In addition, we discuss ICD sensitivity and offer recommendations to avoid similar occurrences.

Ovarian cancers are highly heterogeneous and while chemotherapy is the preferred treatment many patients are intrinsically resistant or quickly develop resistance. Furthermore, all tumors that recur ultimately become resistant. Recent evidence suggests that epigenetic deregulation may be a key factor in the onset and maintenance of chemoresistance. We set out to identify epigenetically silenced genes that affect chemoresistance. The epigenomes of a total of 45 ovarian samples were analyzed to identify epigenetically altered genes that segregate with platinum response, and further filtered with expression data to identify genes that were suppressed. A tissue culture carboplatin resistance screen was utilized to functionally validate this set of candidate platinum resistance genes. Our screen correctly identified 19 genes that when suppressed altered the chemoresistance of the cells in culture. Of the genes identified in the screen we further characterized one gene, Glycogen Synthase Kinase 3 Beta (GSK3β), a proline-directed serine-threonine kinase, to determine if we could determine the mechanism by which it increased resistance. Preliminary results have indicated that the loss of GSK3b decreased the level of apoptosis in response to carboplatin. Furthermore, ovarian cell lines transcriptionally silenced for GSK3β are more invasive, have migratory ability, and display a transformed epithelial to mesenchymal (EMT) phenotype. Taken together, we provide the evidence of a role for GSK3β as an important epigenetic regulator of chemoresistance in ovarian cancer and hypothesize EMT as one of the underlying mechanisms. Citation Format: Noelle L. Cutter, Mena Yacoub, Robert D. Lucito, Nevenka Dimitrova, Elena Lum, Michael Vigliotti, Kazimierz Wrzeszczynski, Douglas A. Levine. A possible role for GSK3β in epithelial ovarian cancer chemoresistance by epigenetic regulation. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A24.