Immunomodulatory Effect of Withania somnifera (Ashwagandha) Extract-A Randomized, Double-Blind, Placebo Controlled Trial with an Open Label Extension on Healthy Participants.

The immunomodulatory effect of Withania somnifera (WS) extract was tested in healthy adults. In this randomized placebo-controlled double-blinded study, subjects were allocated either 60 mg WS extract or placebo. It consists of a blinded 30-day period and an open-label extension study of another 30 days with crossover of only placebo to test. After the 30-day blinded study period, the WS test group reported significant increase (p < 0.05) in Ig's (IgA, IgM, IgG, IgG2, IgG3 and IgG4), Cytokines (IFN-γ, IL4), TBNK (CD45+, CD3+, CD4+, CD8+, CD19+, NK cells) whereas in the placebo group TBNK cells showed significant decrease (p < 0.05) and Ig's and cytokines showed no change (p > 0.05). In the extension period on day 60, the subjects on placebo who were crossed over to the WS test group showed significant increase (p < 0.05) in Ig's, cytokines and TBNK cells and the subjects who continued on the WS group showed a further significant improvement (p < 0.05) in Ig's, cytokines and TBNK cells. There were no adverse events reported in the study. WS extract significantly improved the immune profile of healthy subjects by modulating the innate and adaptive immune systems. Boosting the immune system of people at risk of infection and during widespread infections can be targeted with WS extract.

Fostering mesenchymal stem cell therapy to halt cytokine storm in COVID-19.

The coronavirus disease 2019 (COVID-19) has been threatening the globe since the end of November 2019. The disease revealed cracks in the health care system as health care providers across the world were left without guidelines on definitive usage of pharmaceutical agents or vaccines. The World Health Organization (WHO) declared COVID-19 as a pandemic on the 11th of March 2020. Individuals with underlying systemic disorders have reported complications, such as cytokine storms, when infected with the virus. As the number of positive cases and the death toll across the globe continue to rise, various researchers have turned to cell based therapy using stem cells to combat COVID-19. The field of stem cells and regenerative medicine has provided a paradigm shift in treating a disease with minimally invasive techniques that provides maximal clinical and functional outcome for patients. With the available evidence of immunomodulatory and immune-privilege actions, mesenchymal stem cells (MSCs) can repair, regenerate and remodulate the native homeostasis of pulmonary parenchyma with improved pulmonary compliance. This article revolves around the usage of novel MSCs therapy for combating COVID-19.

Clinical Outcomes of Warfarin Initiation in Advanced Chronic Kidney Disease Patients With Incident Atrial Fibrillation.

OBJECTIVES: The aim of this study was to examine the efficacy and safety of warfarin initiation following the diagnosis of atrial fibrillation (AF) in patients with late-stage chronic kidney disease (CKD) who transitioned to dialysis. BACKGROUND: The clinical benefit of warfarin therapy for thromboprophylaxis after incident AF diagnosis in patients with late-stage CKD who are transitioning to dialysis is unknown. METHODS: In this retrospective cohort analysis, the study population was a national cohort of 22,771 U.S. veterans with incident end-stage renal disease who developed incident AF before initiating renal replacement therapy. This study examined the association of warfarin therapy following the diagnosis of incident AF with ischemic cerebrovascular accidents (CVAs) (ischemic stroke or transient ischemic attack), ischemic CVA-related hospitalization, major bleeding events (gastrointestinal or intracranial bleeding), bleeding event-related hospitalizations, and post-dialysis, all-cause mortality in multivariable adjusted Cox regression analyses that adjusted for demographic characteristics and comorbidities. RESULTS: The mean ± SD age of the cohort was 73.5 ± 8.8 years, 13% were African American, and the mean CHA2DS2-VASc score was 5.7 ± 2.1. Of the overall cohort, 6,682 (29.3%) patients were started on warfarin during the follow-up period. The hazard ratios (95% confidence intervals) for ischemic CVA, bleeding events, and death for those started on warfarin were 1.23 (1.16 to 1.30), 1.36 (1.29 to 1.44), and 0.94 (0.90 to 0.97), respectively, compared with those who received no anticoagulation. Warfarin exposure was associated with higher risk for ischemic CVA and bleeding event-related hospitalizations. CONCLUSIONS: In patients with late-stage CKD who transitioned to dialysis, warfarin use was associated with higher risk of ischemic and bleeding events but a lower risk of mortality. Future studies such as those comparing warfarin with newer oral anticoagulant agents are needed to granularly define the net clinical benefit of anticoagulation therapy in patients with advanced CKD with incident AF.

Cost-effectiveness and Outcomes with Early or Same-Day Discharge After Elective Percutaneous Coronary Intervention.

PURPOSE OF REVIEW: Shorter hospital stay after percutaneous coronary intervention (PCI) can provide economic advantage. Same-day discharge (SDD) after transradial PCI is thought to reduce the cost of care while maintaining the quality and safety. This review summarizes the current knowledge of the benefits and safety of this concept. RECENT FINDINGS: Increase in rate of transradial PCI over the last two decades has resulted in recent growth in rate of acceptance of SDD after a successful procedure. SDD is shown to result in savings of $3500 to $5200 per procedure with comparable adverse event rate of traditional discharge processes. SDD after PCI is shown to be safe and results in cost advantage maintaining the safety profile. The acceptance rate of SDD is still not optimum, and further market penetration of SDD practice would be achieved only if the institutional and operator preference barriers are addressed.

Predialysis coronary revascularization and postdialysis mortality.

Objectives: Coronary artery bypass grafting (CABG) is associated with better survival than percutaneous coronary intervention (PCI) in patients with mild-to-moderate chronic kidney disease (CKD) and End-Stage Renal Disease (ESRD). However, the optimal strategy for coronary artery revascularization in advanced CKD patients who transition to ESRD is unclear. Methods: We examined a contemporary national cohort of 971 US veterans with incident ESRD, who underwent first CABG or PCI up to 5 years prior to dialysis initiation. We examined the association of a history of CABG versus PCI with all-cause mortality following transition to dialysis, using Cox proportional hazards models adjusted for time between procedure and dialysis initiation, socio-demographics, comorbidities and medications. Results: 582 patients underwent CABG and 389 patients underwent PCI. The mean age was 66±8 years, 99% of patients were male, 79% were white, 19% were African Americans, and 84% were diabetics. The all-cause post-dialysis mortality rates after CABG and PCI were 229/1000 patient-years (PY) [95% CI: 205-256] and 311/1000PY [95% CI: 272-356], respectively. Compared to PCI, patients who underwent CABG had 34% lower risk of death [multivariable adjusted Hazard Ratio (95% CI) 0.66 (0.51-0.86), p=0.002] after initiation of dialysis. Results were similar in all subgroups of patients stratified by age, race, type of intervention, presence/absence of myocardial infarction, congestive heart failure and diabetes. Conclusion: CABG in advanced CKD patients was associated lower risk of death after initiation of dialysis compared to PCI.

Acute kidney injury following coronary revascularization procedures in patients with advanced CKD.

BACKGROUND: Previous studies reported that compared with percutaneous coronary interventions (PCIs), coronary artery bypass grafting (CABG) is associated with a reduced risk of mortality and repeat revascularization in patients with mild to moderate chronic kidney disease (CKD) and end-stage renal disease (ESRD). Information about outcomes associated with CABG versus PCI in patients with advanced stages of CKD is limited. We evaluated the incidence and relative risk of acute kidney injury (AKI) associated with CABG versus PCI in patients with advanced CKD. METHODS: We examined 730 US veterans with incident ESRD who underwent a first CABG or PCI up to 5 years prior to dialysis initiation. The association of CABG versus PCI with AKI was examined in multivariable adjusted logistic regression analyses. RESULTS: A total of 466 patients underwent CABG and 264 patients underwent PCI. The mean age was 64 ± 8 years, 99% were male, 20% were African American and 84% were diabetic. The incidence of AKI in the CABG versus PCI group was 67% versus 31%, respectively (P < 0.001). The incidence of all stages of AKI were higher after CABG compared with PCI. CABG was associated with a 4.5-fold higher crude risk of AKI {odds ratio [OR] 4.53 [95% confidence interval (CI) 3.28-6.27]; P < 0.001}, which remained significant after multivariable adjustments [OR 3.50 (95% CI 2.03-6.02); P < 0.001]. CONCLUSION: CABG was associated with a 4.5-fold higher risk of AKI compared with PCI in patients with advanced CKD. Despite other benefits of CABG over PCI, the extremely high risk of AKI associated with CABG should be considered in this vulnerable population when deciding on the optimal revascularization strategy.

Outcomes of Percutaneous Antegrade Intraluminal Coronary Intervention of Chronic Total Occlusion With Remote Surgical Backup.

Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) is not favored in facilities without on-site surgical backup. We reviewed outcomes of patients who had CTO intervention with remote surgical backup in our institution. All patients who underwent attempted antegrade intraluminal CTO PCI from January 2013 to July 2017 were analyzed. Twenty cases (18 patients, 58.1 ± 7.0 years, 70% males) were identified. Procedure was successful in 85% (17 of 20). There were 2 nonflow limiting dissections and 1 wire perforation. Two patients had post-PCI myocardial infarction. There was no cardiac death, myocardial infarction, target vessel revascularization, or stroke at 30 days and at mean follow-up of 19.5 ± 13.7 months. There were 4 rehospitalizations for angina requiring repeat angiogram in 3 cases: 2 without intervention, and 1 referred for coronary artery bypass grafting. Careful attempt at antegrade intraluminal CTO intervention done at a center with remote surgical backup is feasible in selected patients.

Hyperlipidemia: Management with Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors.

Coronary artery disease is the leading cause of death in United States. Hyperlipidemia is an independent and potentially reversible risk factor for coronary artery disease. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, collectively known as statins, have been the mainstay of pharmacologic therapy. Their availability, ease of administration, low cost, and strong evidence behind safety and efficacy makes them one of the most widely prescribed lipid-lowering agents. However, some patients may be intolerant to statins, and few others suffer from very high serum levels of cholesterol in which statin therapy alone or in combination with other cholesterol-lowering agents is insufficient in reducing serum lipid levels to achieve desired levels. In 2015, the Food and Drug Administration approved a new family of lipid-lowering agents, collectively known as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.PCSK9 inhibitors are biologically active molecules that decrease serum low-density lipoprotein cholesterol compared with statin therapy alone. They serve as an alternative to statins for patients who are intolerant to statin or as supplemental therapy in those patients for whom lower levels in serum low-density lipoprotein cholesterol are not achieved by statins alone. This article discusses PCSK9 inhibitors, their mechanism of action, indications, efficacy, safety, costs and limitations.

Clinical and echocardiographic predictors of new-onset atrial fibrillation in patients admitted with blunt trauma.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia after trauma or burn injury; however, its predisposing factors are not well known. Moreover, little is known about its effect on mortality and other short-term clinical outcomes. OBJECTIVES: This study is aimed at identifying risk factors for new-onset AF in patients admitted with blunt trauma or burn injuries at a Level 1 academic trauma center, and to determine its effects on the short-term clinical outcomes. METHODS: This case-control study compared patients with new-onset AF with a cohort of patients without AF during the hospital stay after trauma or burn injury. Patients with prior AF or lack of transthoracic echocardiogram were excluded. Demographic, clinical factors including injury severity score and echocardiographic parameters were compared in both cohorts. Risks of short-term clinical outcomes, namely persistent AF, new stroke, myocardial infarction, or death, were compared. RESULTS: Older age, sepsis, CHADS2-VASC score >1, larger left atrium (LA) size, left ventricular hypertrophy (LVH), and left ventricular diastolic dysfunction imposed a significant risk for new-onset AF on univariate analysis. On multivariate, independent predictors of new-onset AF were LA dilation and LVH. LA enlargement increased odds of new-onset AF by 23-fold (OR 23; CI: 5.7-92, P < 0.0001) and the presence of LVH increased the odds of new-onset AF more than 20-fold (OR 20.8; CI: 5-87, P < 0.0001). CONCLUSIONS: Dilated LA and LVH are independent predictors of new-onset AF in the patients with blunt trauma or burn. New-onset AF did not confer increased risk for in-hospital mortality.

When the gold standard is not always golden: The value of invasive hemodynamic assessment to overcome the pitfalls of echocardiography in challenging cases of mitral stenosis.

Mitral stenosis is a uncommon valvular lesion in the developed countries. Noninvasive evaluation is the first-line modality for assessment of mitral stenosis, however the noninvasive methods may have limitations in certain cases. Invasive hemodynamics can be used as adjunct tool for assessment of mitral stenosis in such difficult cases. Mitral valve using three-dimensional planimetry is a promising technique for assessment of mitral stenosis.

Heart Failure Increases the Risk of Adverse Renal Outcomes in Patients With Normal Kidney Function.

BACKGROUND: Heart failure (HF) is associated with poor cardiac outcomes and mortality. It is not known whether HF leads to poor renal outcomes in patients with normal kidney function. We hypothesized that HF is associated with worse long-term renal outcomes. METHODS AND RESULTS: Among 3 570 865 US veterans with estimated glomerular filtration rate (eGFR) ≥60 mL min-1 1.73 m-2 during October 1, 2004 to September 30, 2006, we identified 156 743 with an International Classification of Diseases, Ninth Revision, diagnosis of HF. We examined the association of HF with incident chronic kidney disease (CKD), the composite of incident CKD or mortality, and rapid rate of eGFR decline (slopes steeper than -5 mL min-1 1.73 m-2 y-1) using Cox proportional hazard analyses and logistic regression. Adjustments were made for various confounders. The mean±standard deviation baseline age and eGFR of HF patients were 68±11 years and 78±14 mL min-1 1.73 m-2 and in patients without HF were 59±14 years and 84±16 mL min-1 1.73 m-2, respectively. HF patients had higher prevalence of hypertension, diabetes mellitus, cardiac, peripheral vascular and chronic lung diseases, stroke, and dementia. Incidence of CKD was 69.0/1000 patient-years in HF patients versus 14.5/1000 patient-years in patients without HF, and 22% of patients with HF had rapid decline in eGFR compared with 8.5% in patients without HF. HF patients had a 2.12-, 2.06-, and 2.13-fold higher multivariable-adjusted risk of incident CKD, composite of CKD or mortality, and rapid eGFR decline, respectively. CONCLUSIONS: HF is associated with significantly higher risk of incident CKD, incident CKD or mortality, and rapid eGFR decline. Early diagnosis and management of HF could help reduce the risk of long-term renal complications.

Association of Pre-Operative Albuminuria with Post-Operative Outcomes after Coronary Artery Bypass Grafting.

The effect on post-operative outcomes after coronary artery bypass graft (CABG) surgery is not clear. Among 17,812 patients who underwent CABG during October 1,2006-September 28,2012 in any Department of US Veterans Affairs (VA) hospital, we identified 5,968 with available preoperative urine albumin-creatinine ratio (UACR) measurements. We examined the association of UACR<30, 30-299 and >=300 mg/g with 30/90/180/365-day and overall all-cause mortality, and hospitalization length >10 days, and with acute kidney injury(AKI). Mean ± SD baseline age and eGFR were 66 ± 8 years and 77 ± 19 ml/min/1.73 m(2), respectively. 788 patients (13.2%) died during a median follow-up of 3.2 years, and 26.8% patients developed AKI (23.1%-Stage 1; 2.9%-Stage 2; 0.8%-Stage 3) within 30 days of CABG. The median lengths of stay were 8 days (IQR: 6-13 days), 10 days (IQR: 7-14 days) and 12 days (IQR: 8-19 days) for groups with UACR < 30 mg/g, 30-299 mg/g and ≥300 mg/g, respectively. Higher UACR conferred 72 to 85% higher 90-, 180-, and 365-day mortality compared to UACR<30 mg/g (odds ratio and 95% confidence interval for UACR≥300 vs. <30 mg/g: 1.72(1.01-2.95); 1.85(1.14-3.01); 1.74(1.15-2.61), respectively). Higher UACR was also associated with significantly longer hospitalizations and higher incidence of all stages of AKI. Higher UACR is associated with significantly higher odds of mortality, longer post-CABG hospitalization, and higher AKI incidence.