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.

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.

Resolution of syphilis-related rapidly progressive glomerulonephritis with penicillin therapy: Case report
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Renal manifestations of syphilis are variable, with membranous nephropathy being the most commonly described lesion. Rapidly progressive glomerulonephritis (RPGN) is rare and there is only one case report in the literature describing syphilis-associated crescentic glomerulonephritis. We report a rare case of RPGN secondary to latent syphilis, which resolved with penicillin treatment in the absence of immunosuppressive therapy. A 28-year-old Black male with a history of HIV was evaluated for severe acute kidney injury, nephrotic-range proteinuria, and active urine sediment. Serologies for glomerulonephritis were negative. Rapid plasma reagin and treponema pallidum particle agglutination assay were reactive, confirming syphilis diagnosis. Kidney biopsy revealed focal and segmental necrotizing and crescentic lesion. Patient received weekly benzathine penicillin (PCN) for 3 weeks, and renal function improved to baseline. This dramatic improvement happened with PCN alone, a finding which has not been previously reported. We recommend that syphilis be considered in the differential diagnosis of all patients with proteinuria or suspected glomerulonephritis.

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.

Recurrent Pyroglutamic Acidosis Related to Therapeutic Acetaminophen.

Pyroglutamic acid, an intermediate in glutathione metabolism, can lead to elevated anion gap metabolic acidosis as rare complication of acetaminophen therapy in adults. Acquired pyroglutamic acidosis has been observed primarily in settings associated with glutathione deficiency. Risk factors for glutathione deficiency include critical illness, chronic liver or kidney disease, advanced age, female gender, alcohol abuse, malnutrition, pregnancy, antiepileptic drugs, and chronic acetaminophen use. Diagnosis of pyroglutamic acidosis requires both the exclusion of common etiologies of increased anion gap metabolic acidosis and a high index of suspicion. Treatment involves discontinuation of acetaminophen, supportive care, and addressing risk factors for glutathione deficiency. The current report describes an ambulatory patient with multiple risk factors for glutathione deficiency, who developed recurrent pyroglutamic acidosis due to acetaminophen use with therapeutic blood levels of acetaminophen.

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.

Racial Differences in Association of Serum Calcium with Mortality and Incident Cardio- and Cerebrovascular Events.

CONTEXT: Abnormalities in calcium metabolism may potentially contribute to the development of vascular disease. Calcium metabolism may be different in African American (AA) vs white individuals, but the effect of race on the association of serum calcium with clinical outcomes remains unclear. OBJECTIVE: This study sought to examine race-specific associations of serum calcium levels with mortality and with major incident cardiovascular events. DESIGN AND SETTING: This was a historical cohort study in the U.S. Department of Veterans Affairs health care facilities. PARTICIPANTS: Participants included veterans (n = 1 967 622) with estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2. MAIN OUTCOME MEASURES: The association between serum calcium levels with all-cause mortality, incident coronary heart disease (CHD), and ischemic stroke incidence was examined in multivariable adjusted Cox proportional hazards models, including an interaction term for calcium and race. RESULTS: The association of calcium with all-cause mortality was U-shaped in both AA and white patients, but race modified the association of calcium with all-cause mortality. Compared with white patients, AA patients experienced lower risk of mortality when calcium was ≥ 8.8 mg/dL, with a statistically significant interaction (P < .001). Conversely, AA vs white race was associated with higher mortality when calcium was < 8.8 mg/dL. Calcium showed no significant association with ischemic stroke or CHD in both races; and race did not modify these associations (P = .37 and 0.11, respectively for interaction term). CONCLUSIONS: Race modified the U-shaped association between calcium and all-cause mortality. Serum calcium is not associated with incident stroke or CHD in either AA or white patients. The race-specific difference in the association of calcium levels with mortality warrants further examination.

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.

Intracardiac echocardiography: clinical utility and application.

Intracardiac echocardiography (ICE) broadens the spectrum of available echocardiographic techniques and provides the operator direct visualization of cardiac structures in real time. ICE has clear advantages over fluoroscopy, transthoracic echocardiography, and transesophageal echocardiography as the imaging modality of choice in the cardiac catheterization and electrophysiological laboratories. With the development of steerable phased array catheters with low frequency and Doppler qualities, there is marked improvement in visualization of left-sided structures from the right heart. Appropriate utilization of ICE is likely to maximize safety and efficacy of complex interventional procedures and may improve patient outcomes. Future advances in ICE imaging will further improve the ease of device guidance and, in combination with new imaging modalities, could dramatically improve other applications of echocardiography which may result in improved patient outcomes. This review describes the technical evolution of ICE, the use of ICE in guiding percutaneous interventional procedures and possible future applications of ICE in the ever-growing field of interventional cardiology.

Safety and efficacy of ibutilide in cardioversion of atrial flutter and fibrillation.

This article reviews the safety and efficacy of ibutilide for use in patients with atrial fibrillation and flutter. Ibutilide, a class III antiarrhythmic agent, is primarily used for conversion of atrial flutter and fibrillation and is a good alternative to electrical cardioversion. Ibutilide has a conversion rate of up to 75% to 80% in recent-onset atrial fibrillation and flutter; the conversion rate is higher for atrial flutter than for atrial fibrillation. It is also safe in the conversion of chronic atrial fibrillation/flutter among patients receiving oral amiodarone therapy. Ibutilide pretreatment facilitates transthoracic defibrillation and decreases the energy requirement of electrical cardioversion by both monophasic and biphasic shocks. Pretreatment with ibutilide before electrical defibrillation has a conversion rate of 100% compared with 72% with no pretreatment. Ibutilide is also safe and efficient in the treatment of atrial fibrillation in patients who have had cardiac surgery, and in accessory pathway-mediated atrial fibrillation Where the conversion rate of ibutilide is as high as 95%. There is up to a 4% risk of torsade de pointes and a 4.9% risk of monomorphic ventricular tachycardia. Hence, close monitoring in an intensive care unit setting is warranted during and at least for 4 hours after drug infusion. The anticoagulation strategy is the same as for any other mode of cardioversion.

Vascular changes and black hole phenomenon after coronary brachytherapy: a pathologically distinct entity.

Restenosis remains an important issue even after coronary brachytherapy despite its efficacy in the treatment for in-stent restenosis. The acute and chronic changes in vascular wall are unique following brachytherapy. The restenotic tissue post coronary brachytherapy is relatively acellular and appears echolucent in intravascular ultrasound examination. This is dubbed the "black hole" phenomenon. Despite the similarity in the mode of action of brachytherapy and drug eluting stent implantation, the black hole phenomenon seems to be uncommon after drug-eluting stent implantation except in those patients who have had prior brachytherapy, bare-metal placement and after treatment of saphenous venous graft stenosis. It is possible that not all neointima in stents are created equal. We should propose that neointima be considered primary neointima if it forms after bare metal stenting, secondary neointima if it forms after CBT or DES, and perhaps tertiary if after combined CBT and DES. This type of classification may prove useful for research or clinical purposes. Almost certainly black hole phenomenon results from a modified neointima. However, we do not know whether this is the same restenotic tissue that was present before CBT but just depleted of its cellular element secondary to autolysis or a newly formed tertiary neointima? It is also not clear whether the changes in vascular wall and restenosis are similar after CBT or drug-eluting stent placement. However, there are some unique vascular changes that seem to be common after both of these procedures.