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Prion diseases are fatal, infectious, and incurable neurodegenerative disorders caused by misfolding of the cellular prion protein (PrPC) into the infectious isoform (PrPSc). In humans, there are sporadic, genetic and infectious etiologies, with sporadic Creutzfeldt-Jakob disease (sCJD) being the most common form. Currently, no treatment is available for prion diseases. Cellular cholesterol is known to impact prion conversion, which in turn results in an accumulation of cholesterol in prion-infected neurons. The major elimination of brain cholesterol is achieved by the brain specific enzyme, cholesterol 24-hydroxylase (CYP46A1). Cyp46A1 converts cholesterol into 24(S)-hydroxycholesterol, a membrane-permeable molecule that exits the brain. We have demonstrated for the first time that Cyp46A1 levels are reduced in the brains of prion-infected mice at advanced disease stage, in prion-infected neuronal cells and in post-mortem brains of sCJD patients. We have employed the Cyp46A1 activator efavirenz (EFV) for treatment of prion-infected neuronal cells and mice. EFV is an FDA approved anti-HIV medication effectively crossing the blood brain barrier and has been used for decades to chronically treat HIV patients. EFV significantly mitigated PrPSc propagation in prion-infected cells while preserving physiological PrPC and lipid raft integrity. Notably, oral administration of EFV treatment chronically at very low dosage starting weeks to months after intracerebral prion inoculation of mice significantly prolonged the lifespan of animals. In summary, our results suggest that Cyp46A1 as a novel therapeutic target and that its activation through repurposing the anti-retroviral medication EFV might be valuable treatment approach for prion diseases.

Background Due to the current Coronavirus Disease 2019 (COVID-19) pandemic, there is a realization for innovation in procedures and protocols to minimize hospital stay and at the same time ensure continued evidence-based treatment delivered to the patients. We present a same-day discharge protocol for transcatheter mitral valve repair (TMVR) using MitraClip under general anaesthesia in a six-patient case series. This protocol aims to reduce the length of hospital stay, thereby minimizing potential for nosocomial COVID-19 infections and to promote safe discharge with cautious follow-up. Case summary Six patients with severe symptomatic mitral valve (MV) regurgitation underwent successful transfemoral MV repair using standard procedures. Following repair, patients were monitored on telemetry in the recovery area for 3 h, ambulated to assess vascular access stability and underwent post-procedural transthoracic echocardiogram to assess for any pericardial effusion or post-procedural prosthetic mitral stenosis. Conclusion Same-day discharge after TMVR is possible when done cautiously with close follow-up, can minimize hospital stay, improve resource utilization, and reduce risk of nosocomial COVID-19 infection.

Currently there is no recognized curative treatment for diabetic polyneuropathy (DPN). Strict glucose control and symptomatic pain relief are the first line management routes. DPN is a common complication of diabetes and has a major detrimental influence on the quality of life (QOL) for many patients. Due to the scope of the problem, it is imperative that treatment options which impede DPN's progression and restore sensorineural function should be researched comprehensively and made available to the masses at an economical cost. We reviewed a multitude of atypical treatment options for DPN including capsaicin, lidocaine, acupuncture, electrical nerve stimulation, alpha lipoic acid, benfotiamine, and acetyl-l-carnitine and explored the evidence to date regarding their safety and efficacy. Most of these options have been around for a long time and have promising pilot studies or small-scale trials focused on DPN treatment.

Recurrent gastrointestinal bleeding (GIB) is a common complication following left ventricular assist device (LVAD) implantation. Our study aimed to estimate the comparative efficacy of different pharmacologic interventions for the prevention of GIB, through a network meta-analysis (NMA). A total of 13 observational studies comparing six strategies. Among those, 4 were for primary, and 9 were for secondary prevention of GIB. On NMA, thalidomide (Hazard ratio [HR]: 0.016, Credible interval [CrI]I: 0.00053-0.12), omega-3-fatty acid (HR:0.088, CrI: 0.026-0.77), octreotide (HR: 0.17, CrI: 0.0589-0.41) and danazol (HR:0.17, CrI: 0.059-0.41) reduced the risk of GIB. The use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker (ACEi/ARB) and digoxin were not associated with any significant reduction. Based on NMA, combining indirect treatment comparisons, thalidomide, danazol, and octreotide treatments were associated with decreased risk of recurrent GIB. Additionally, Omega 3 fatty acids were associated with a lower risk of the primary episode of GIB in the LVAD patient population.

Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in drastic changes to the practice of medicine, requiring healthcare systems to find solutions to reduce the risk of infection. Using a case series, we propose a protocol for same-day discharge (SDD) for selected patients undergoing transcatheter aortic valve replacement (TAVR) using real-time remote cardiac monitoring. Six patients with severe symptomatic aortic stenosis underwent TAVR and were discharged on the same day. Case summary Six patients with symptomatic severe native or bioprosthetic aortic valve stenosis underwent a successful transfemoral TAVR using standard procedures, including the use of rapid atrial pacing to assess the need for permanent pacemaker implantation. Following TAVR, patients were monitored on telemetry in the recovery area for 3 h, ambulated to assess vascular access stability, and discharged with real-time remote cardiac monitoring if no new conduction abnormality was observed. The patients were seen by tele-visits within 2 days and 2 weeks after discharge. Discussion Amidst the COVID-19 pandemic, SDD following successful transfemoral TAVR may be feasible for selected patients and reduce potential COVID-19 exposure.

Background: Cardiac sarcoidosis (CS) affects 35% of patients with pulmonary sarcoidosis (PS). CS presentation varies from asymptomatic patients to sudden cardiac death. The current screening modalities like EKG and conventional echocardiography lack sensitivity for early detection of CS. Speckle tracking echocardiography (STE) has shown potential for early detection of subclinical myocardial damage in patients with PS. We aimed to investigate the role of STE in early detection of CS. Methods: We queried Medline, EmCare, CINAHL, Cochrane Database and Google Scholar for articles investigating the role of left ventricle global longitudinal strain (LVGLS) in asymptomatic patients with PS versus (vs) controls. Studies that included patients with suspected or proven CS, patients with cardiac symptoms, arrhythmias, coronary artery disease or valvular abnormalities were excluded. The standard mean difference (SMD) in GLS for both groups was pooled using random effects model. Results: Our search yielded a total of 9 studies with a total of 967 patients with PS undergoing screening for CS. In individual studies, the baseline characteristics were not significantly different between both groups. Overall, the studies had more females than males. All patients in our cohort had preserved ejection fraction (EF) and no cardiac symptoms. The LVGLS was significantly decreased in the PS group as compared to controls, SMD: -3.98, (95% CI: -5.32 to -2.64; p-value 2 = 94.70%, Figure 1. Conclusion: As compared to controls, patients with PS with no clinically suspected or proven CS, and normal EF, have impaired LVGLS. More studies are warranted to investigate the role of LVGLS in CS screening.

Background: Octogenarians and nonagenarians are under-represented in major clinical trials studying the role of anticoagulation (AC) in atrial fibrillation (AF). These patients are at an increased risk of bleeding owing to their frailty, their propensity for falls, and frequently impaired kidney function. We performed a meta-analysis of studies that investigated the role of AC in these patients. Methods: We queried Medline, EmCare, CINHAL, Cochrane Database, and Google Scholar for studies investigating the role of AC for AF in octogenarians and nonagenarians. Our primary efficacy outcome was major thromboembolism (TE), and secondary safety outcome was major bleeding (MB). We used the PM method with HKSJ adjustment to estimate risk ratio (RR) with a 95% confidence interval (CI). Heterogeneity was assessed using Higgin’s I 2 . R version 3.6.2 was used for statistical analysis. Heterogeneity was addressed using outlier analysis. dmetar() package in R was used, and the pooled estimate was re-calculated, excluding the outliers. Results: Ten observational studies, including a total of 34,697 patients were included. There was no difference in the risk of TE [RR: 0.82, 95% CI: 0.49-1.38, I 2 =74%] or MB [RR: 1.00, 95% CI: 0.55-1.83, I 2 =88%] between the AC and Non-AC group. However, the pooled estimates were associated with considerable heterogeneity. Outlier analysis identified two studies "Perera et al., 2009" and "Yamashita et al., 2016" as an outlier for pooled estimation of TE, while [1] "Siu et al., 2014", "Bertozzo et al., 2016", "Ekerstad et al., 2018" and "Alnsasra et al., 2018" were outliers in the pooled estimate of MB. Following exclusion of outliers for each endpoint, the reanalyzed RR for TE and MB were [RR: 0.94, 95% CI: 0.82- 1.09, I 2 =0%] and [RR: 1.57, 95% CI: 1.41- 1.74, I 2 =0%]. Conclusion: There was no difference in the risk of TE, while the risk of MB increased with the use of AC for AF in octogenarians and nonagenarians.

Background: Long term outcomes of culprit multi-vessel and left main patients who presented with Non-ST Elevation Acute Coronary Syndrome (NSTE-ACS) and underwent either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) are not well defined. Randomized trials comparing the two modalities constituted mainly of patients with stable coronary artery disease (SCAD). We performed a meta-analysis of studies that compared the long term outcomes of CABG vs. PCI in NSTE-ACS. Methods: Medline, EmCare, CINAHL, Cochrane databases were queried for relevant articles. Studies that included patients with SCAD and ST-elevation myocardial infarction were excluded. Our primary outcome was major adverse cardiac events (MACE) at 3-5 years, defined as a composite of all-cause mortality, stroke, re-infarction and repeat revascularization. The secondary outcome was re-infarction at 3 to 5 years. We used the Paule-Mandel method with Hartung-Knapp-Sidik-Jonkman adjustment to estimate risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed using Higgin’s I 2 statistics. All statistical analysis was carried out using R version 3.6.2 Results: Four observational studies met our inclusion criteria with a total number of 6695 patients. At 3 to 5 years, the PCI group was associated with a higher risk of MACE as compared to CABG, (RR): 1.52, 95% CI: 1.28 to 1.81, I 2 =0% (PANEL A). The PCI group also had a higher risk of re-infarctions during the period of follow up, RR: 1.88, 95% CI 1.49 to 2.38, I 2 =0% (PANEL B). Conclusion: In this meta-analysis, CABG was associated with a lower risk of MACE and re-infarctions as compared to PCI during 3 to 5 years follow up period.

Background: The optimum revascularization modality in multi-vessel and left main disease patients presenting with non-ST elevation acute coronary syndrome (non-STE-ACS) is not well studied. The current recommendations are based on studies that primarily included patients with stable angina. Patients with non-STE-ACS were under-represented in clinical trials. We performed a meta-analysis of studies comparing coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) in non-STE-ACS, and reporting 30 days major adverse cardiac events (MACE). Methods: We searched Medline, EmCare, CINAHL, Cochrane database, and Google Scholar for relevant articles. We excluded studies that included patients with stable coronary artery disease and ST elevation myocardial infarction. Our primary outcome was 30 days MACE defined as all-cause death, stroke, repeat revascularization and re-infarction. We used the Paule-Mandel method with the Hartung-Knapp-Sidik-Jonkman adjustment to estimate risk ratio (RR) with a 95% confidence interval (CI). Heterogeneity was assessed using Higgin’s I 2 statistics. To account for heterogeneity, a meta-regression analysis was performed. Results: Five observational studies met our inclusion criteria summing to a total number of 7161 patients. At 30 days, there was no difference between CABG vs. PCI in terms of MACE, RR: 0.96, 95% CI 0.38 to 2.39, I 2 = 81% (Panel A). A meta-regression analysis reported that a history of PCI was associated with a lower risk of MACE with CABG compared to PCI (Panel B). Conclusion: At 30 days, there was no difference in MACE between the CABG and PCI groups. However, a history of PCI was associated with a lower risk of MACE in patients who underwent CABG.

Background: Prevention of recurrent Clostridioides difficile infection (CDI) is a challenge in clinical practice, particularly in patients who need systemic antimicrobial therapy. We aimed to evaluate the role of oral vancomycin prophylaxis (OVP) in prevention of primary or future CDI in patients on systemic antimicrobial therapy. Methods: A systematic search of MEDLINE, Embase, and Web of Science was performed from 2000 to January 2020. We included case-control or cohort studies that included patients on systemic antimicrobial therapy who did or did not receive oral vancomycin prophylaxis (OVP) and were evaluated for development of CDI. Odds ratio (OR) estimates with 95% confidence intervals (CI) were calculated. Results: Four studies including 1352 patients evaluated OVP for primary CDI prevention, with CDI occurring in 29/402 patients on OVP (7.4%) compared with 10.4% (99/950) without OVP. Meta-analysis revealed no significant decrease in risk of CDI in patients who received OVP (OR, 0.18; 95% CI, 0.03–1.03; p = 0.06). There was significant heterogeneity with I2 = 76%. Ten studies including 9258 patients evaluated OVP for secondary CDI prevention. Future CDI occurred in 91/713 patients on OVP (13.3%) compared with 21.9% (1875/8545) who did not receive OVP. Meta-analysis revealed a statistically significant decreased risk of future CDI (OR, 0.34; 95% CI, 0.20–0.59; p 2 = 59%. Discussion: Based on observational data, OVP appears to decrease the risk of future CDI in patients with prior CDI who require systemic antimicrobial therapy. However, OVP was not effective for primary prevention of CDI.

Background:People with rheumatoid arthritis (RA) have a higher risk of serious infections. The most common nosocomial infection in the United States (US) is Clostridioides difficile infection (CDI) and yet, little is known regarding the impact of comorbid RA on outcomes in persons hospitalized with CDI.Objectives:To evaluate the trends over time and predictors of inpatient mortality in hospitalized patients with CDI comparing those with and without RA.Methods:We used the National Inpatient Sample (NIS) database, the largest available all-payer database of inpatient hospitalizations in the US. Patients aged ≥18 years admitted with CDI from 2006-2018 were included. Patients with RA were identified using the International Classification of Diseases (ICD) 9 and 10 codes. Categorical variables between CDI patients with and without RA were compared using Chi-squared test. Temporal trends of hospitalization charges, length of stay (LOS) and inpatient mortality were assessed using the Cochrane Armitage test. Predictors of inpatient mortality were assessed using multivariable logistic regression adjusting for: age ≥65, sex, race, presence of RA, and Elixhauser comorbidity index.Results:There were 4,396,945 hospitalizations with a discharge diagnosis of CDI in the study period, of which 111,336 (2.5%) had a coexisting diagnosis of RA. Over the study period, the proportion of CDI patients with a diagnosis of RA increased from 1.7% in 2006 to 3.3% in 2018 with a statistically significant trend of rise (p trendp The inflation-adjusted average charge for hospitalization for CDI without RA was significantly higher than for CDI with RA ($95,863 vs $73,025, pCDI patients without RA had a significantly higher mortality over the study period than those with RA (7.8% vs 6.1%, pThe multivariable analyses found age≥65 was associated with increased inpatient mortality (adjusted odds ratio [aOR], 1.77, 95% confidence interval [CI], 1.73-1.80), whereas a diagnosis of RA was associated with a decreased mortality (aOR 0.86, 95% CI, 0.81-0.91) (Table 1).Table 1.Predictors of inpatient mortalityaOR95% C.I. for aORP-valueLowerUpperAge ≥ 651.7651.7301.801Hospitalization years -Years 2006-2011Ref -Years 2011-20140.7070.6930.721 -Years 2015-20180.5820.5690.594Elixhauser Comorbidity Index1.0561.0551.056Rheumatoid Arthritis0.8590.8100.911Female0.8700.8550.885Race -WhiteRef -African American1.0711.0441.099 -Hispanic1.1441.1081.180 -Asian/Pacific Islander1.2671.2001.337 -Native American1.0220.9101.1470.716 -Other races1.2631.2011.329aOR = Adjusted Odds Ratio; C.I.= confidence intervalConclusion:In this nationwide study, among hospitalized patients with CDI, those with comorbid RA had significantly decreased odds of inpatient mortality than those without RA. Further studies are needed to understand this association.Figure 1.Disclosure of Interests:None declared

Introduction Veno-venous extracorporeal membrane oxygenation (VV-ECMO) as bridge to recovery in critically ill COVID-19 continues to be commonly utilized strategy in cases with persistent respiratory failure refractory to traditional ventilation support Case Report We report 5 cases of severe acute respiratory syndrome coronavirus-2 infection (SARS-CoV-2) who were treated with ECMO (Table 1). All 5 cases presented with fever, cough and shortness of breath and a positive nasopharyngeal swab for SARS-CoV-2 on admission. Case 1, 2, 3 and 5 patients were hypoxemic with saturation less than 90% on admission and decompensated rapidly, whereas Case 4 decompensated after day 14. Mechanical ventilation failed to provide adequate oxygenation in all 5 cases; case 2,3 and 5 were started on recruitment measures with proning while it was not possible for case 1 owing to morbid obesity. Proning was not possible in the case 4 as patient became severely hypoxemic while patient was undergoing mechanical thrombectomy. The case 1-4 remained on ECMO for 19, 17, 17 and 2 days respectively. All except case 2 had improvement in APACHEII and SOFA score after ECMO initiation. All 5 patients had elevated inflammatory markers of serum ferritin, D-dimer, Lactate dehydrogenase (LDH), C-reactive protein (CRP) which trended down after a few days of ECMO initiation All 5 patients received high dose steroids during their stay in the ICU. Case 4 and 5 passed away after compassionate extubation. Case 1-3 had prolonged hospital course with complication of hospital acquired pneumonia requiring multiple courses of broad-spectrum antibiotics. Summary Our observational report of 5 patients reports the use of ECMO in critically ill SARS-CoV-2 with ARDS and difficult to maintain saturation despite mechanical ventilation and proning with recovery for 3 patients. However, given the lack of ECMO centers; this is not a readily available option. Further studies are warranted to investigate the role of ECMO in SARRS-CoV-2 and careful identification of appropriate candidates.

Traditionally ST-elevation myocardial infarction (STEMI) with multivessel coronary artery disease is treated with percutaneous coronary intervention (PCI) to culprit lesion only. The benefit of multivessel (MV) PCI among STEMI patients without cardiogenic shock is unclear.PubMed, EMBASE, and Cochrane Database were searched from 1996 to 2019, for studies of patients with STEMI without cardiogenic shock, who underwent PCI. Only randomized controlled trials comparing culprit PCI to MV PCI vs culprit vessel PCI were included for pairwise meta-analysis. All-cause mortality, cardiac mortality, reinfarction, revascularization and major adverse cardiovascular events (MACE) were compared. Trial sequential analysis (TSA) was performed for outcome variables.Nine randomized controlled trials contributed 6930 patients meeting inclusion criteria. Three thousand three hundred seventy-six underwent MV PCI, and 3554 underwent culprit PCI. Our analysis demonstrated no significant difference in all-cause mortality. MV PCI had a lower risk of cardiac mortality, reinfarction, MACE and repeat revascularization compared to culprit PCI (P values0.05). TSA showed futility for further trials to detect all-cause mortality benefit and lack of firm evidence of benefit in cardiac mortality and re-infarction, but firm evidence of benefit in revascularization and MACE.In conclusion, MV PCI strategy was beneficial in reducing cardiac mortality, reinfarction, repeat revascularization, and MACE but there was no all-cause mortality benefit when compared to culprit only PCI strategy. Evidence for benefit in cardiac mortality and re-infarction is not robust per TSA.

Introduction We present a case of COVID-19 causing hypercoagulability and inflammatory stress leading to STEMI in a patient who went on to develop persistent cardiogenic shock requiring LVA) implantation. Case Report 57-year-old lady developed COVID-19 infection in May 2020. In June 2020, she presented with chest pain, was noted to have STEMI on EKG, complicated by cardiac arrest with ROSC in 14 minutes. She was in cardiogenic shock as well and was started on veno-arterial ECMO. She underwent left anterior descending artery stent placement. Further hospitalization was complicated by persistent cardiogenic shock and complete heart block and underwent pacemaker and cardiac-defibrillator implantation. She developed pulmonary edema, acute kidney injury requiring hemodialysis, shock liver, and persistent cardiogenic shock. She was weaned off VA-ECMO after 4 days but continued to have severely reduced cardiac function. RHC revealed severe volume overload, pulmonary venous hypertension, low cardiac output, and right heart dysfunction. Echo showed severe LV dysfunction with an EF of 15%. A femoral intra-aortic balloon pump(IABP) was placed on July 7, 2020. An attempt was made to wean her off of IABP on July 10th,however, it was unsuccessful and she was transitioned to axillary intra-aortic balloon pump. She remained IABP dependent thereafter and on July 15th, given persistent cardiogenic shock, decision was made to pursue advanced heart failure therapies. After multi-disciplinary discussion, the decision to pursue LVAD implantation was made. She underwent a successful LVAD implantation on July 20th . She failed an extubation trial and underwent tracheostomy on July 23rd . Post LVAD, she developed atrial fibrillation and was started on digoxin and amiodarone. Her symptoms improved and she was subsequently discharged to rehabilitation in late August on amiodarone, digoxin, metoprolol, prasugrel, warfarin, spironolactone and lisinopril. The detailed timeline is shown in figure 1. Summary Hypercoagulability and severe inflammatory stress leading to life-threatening illness is a significant complication of COVID-19 infection. A low threshold for suspecting and treating hypercoagulability and inflammatory induced myocardial ischemia and injury and cardiogenic shock is a reasonable strategy to decrease acute as well as chronic morbidity and mortality.

Introduction Heart failure patients with difficult to manage volume status and recurrent heart failure exacerbation benefit from CardioMemsTM placement. This helps in remote monitoring of pulmonary artery (PA) pressure and diuretic dosing can be changed on the basis of these readings preventing hospitalizations. During the COVID-19 pandemic, a stay-at-home order was issued by the state government, which may have led to heart failure deterioration secondary to poor follow up and change in dietary habits. Hypothesis We aim to evaluate changes in the mean PA pressure during stay-at-home order during COVID-19 pandemic as patients are not seen in clinic and there are presumed changes in dietary habits. Methods We identified 26 patients with a history of CardioMemsTM implant using our heart failure clinic database. We extracted their daily available PA pressure reading before the COVID-19 pandemic and during pandemic. Results The characteristics of the patients are described in Table 1. 26 cases with were identified with sufficient CardioMemsTM readings. Average age was 69.7 years with 38.5% females. There were 54% patients with systolic heart failure. Number of COVID-19 cases rose to almost 700 in 1 month. With regression analysis, we observed a trend towards increase in the mean PA pressure readings during the pandemic (R2 = 0.09, P-value

Streptobacillus moniliformis is a pleomorphic bacillus found in the oral cavity of rodents. Rat bite can transmit these bacteria to humans and can lead to bacteremia as well as infective endocarditis. We present an unusual case rat-bite endocarditis and septic emboli. 24 year-old-female presented

Transcatheter aortic valve replacement (TAVR) is an evolving treatment for symptomatic aortic stenosis (AS). We present a case of aorta to right ventricle (RV) fistula as a rare complication of TAVR. 90-year-old male with history of systolic heart failure and severe AS presented to hospital with

Amlodipine toxicity is commonly reported medication involved in overdose. Its management involves early action with aggressive measures. We describe such a case managed successfully. 64-year-old female was admitted to hospital with severe hypotension and junctional rhythm 36 hours following

Hydralazine-induced lupus syndrome (HILS) is an uncommon drug reaction that typically manifests as fever, myalgia, serositis, and arthralgia. This is a rare presentation of HILS with pericardial effusion. A 57-year-old male with hypertension and chronic kidney disease presented with a four-week

The correlation between masses identified on implantable cardiac devices and device related infective endocarditis (DRE) is not well established. This was a retrospective analysis including patients with prior implantable cardiac devices who underwent trans-esophageal echocardiograms (TEE) from