Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Kidney Outcomes across Baseline Cardiovascular-Kidney-Metabolic Conditions: A Systematic Review and Meta-Analyses.

BACKGROUND: The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on kidney outcomes in patients with varying combinations of heart failure, chronic kidney disease, and type 2 diabetes mellitus have not been quantified. METHODS: PubMed and Scopus were queried up to December 2023 for primary and secondary analysis of placebo-controlled trials of SGLT2i in patients with heart failure, chronic kidney disease, or type 2 diabetes mellitus. Outcomes of interest were composite kidney endpoint (combination of estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2, sustained doubling of serum creatinine, varying percent change in eGFR, and need for kidney replacement therapy), rate of eGFR slope decline and albuminuria progression. Hazard ratios (HR) and mean differences with their 95% confidence intervals (CI) were extracted onto an excel sheet, and the results were then pooled using a random-effect model through Review Manager (version 5.3, Cochrane Collaboration). RESULTS: Eleven trials (n=80,928 patients) were included. Compared with the placebo, SGLT2i reduced the risk of the composite kidney endpoint by 41% (hazard ratio 0.59; 95%CI 0.42-0.83) in heart failure with reduced ejection fraction, 36% (hazard ratio 0.64;95%CI 0.55-0.73) in chronic kidney disease, and 38% (hazard ratio 0.62;95%CI 0.56-0.69) in type 2 diabetes mellitus. A similar pattern of benefit was observed in combinations of these comorbidities, as well as patients without baseline heart failure, chronic kidney disease, or type 2 diabetes mellitus. SGLT2i slowed the rate of eGFR slope decline and reduced the risk of sustained doubling of serum creatinine by 36% (hazard ratio 0.64; 95%CI 0.56-0.72) in the overall population, and a consistent effect on kidney outcomes was observed in most subpopulations with available data. CONCLUSIONS: SGLT2i improved kidney outcomes in cohorts with heart failure, chronic kidney disease, and type 2 diabetes mellitus, and these effects were consistent across patients with different combinations of these comorbidities.

Therapeutic Outcomes Following Isolated Transcatheter Tricuspid Valve Repair: A Systematic Review and Meta-analysis.

Tricuspid regurgitation (TR) is traditionally treated surgically, but isolated transcatheter tricuspid valve repair (ITTVR) offers a less invasive option. This study conducts a meta-analysis and systematic review to evaluate ITTVR outcomes in patients with TR. Database searches until March 2023 identified studies assessing ITTVR safety and efficacy in moderate/severe TR patients. Primary outcomes analyzed were severe TR, NYHA functional class improvement, and 6-minute walking distance. Meta-analyses used Risk ratio (RR) or mean difference with a random effects model. The review included 25 studies with 2421 patients. ITTVR improved NYHA functional class (RR: 3.262), reduced TR severity (RR: 0.303), and enhanced 6-minute walking distance (MD: +47.077 m). Echocardiographic parameters improved, including reductions in TR vena contracta, TR EROA, septolateral tricuspid annular diameter, RVEDD, RV FAC, and TAPSE. LVEF and PASP showed no significant changes. ITTVR improves functional outcomes and echocardiographic parameters in TR patients.

Utility of Cerebral Embolic Protection Devices in Transcatheter Procedures: A Systematic Review and Meta-Analysis.

With the emergence of the largest randomized control trial to date-the Stroke Protection With Sentinel During Transcatheter Aortic Valve Replacement (PROTECTED TAVR) study-we sought to conduct an updated meta-analyses to evaluate the utility of CEP devices on both clinical outcomes and neuroimaging parameters. Electronic databases were queried through November 2022 for clinical trials comparing the utility of Cerebral Embolic Protection (CEP) devices in Transcatheter Aortic Valve Replacement (TAVR) with non-CEP TAVR procedures. Meta-analyses were performed using the generic inverse variance technique, and a random-effects model, and results are presented as weighted mean differences (WMD) for continuous outcomes, and hazard ratios (HR) for dichotomous outcomes. Outcomes of interest included stroke, disabling stroke, nondisabling stroke, bleeding, mortality, vascular complications, new ischemic lesions, acute kidney injury (AKI), and total lesion volume. Thirteen studies (8 RCTs, 5 observational studies) consisting of 128,471 patients were included in the analysis. Results from our meta-analyses showed a significant reduction in stroke (OR: 0.84 [0.74-0.95]; P < 0.01; I2 = 0%), disabling stroke (OR: 0.37 [0.21-0.67]; P < 0.01; I2 = 0%) and bleeding events (OR: 0.91 [0.83-0.99]; P = 0.04; I2 = 0%) through CEP device use in TAVR. The use of CEP devices had no significant impact on nondisabling stroke (OR: 0.94 [0.65-1.37]; P < 0.01; I2 = 0%), mortality (OR: 0.78 [0.53-1.14]; P < 0.01; I2 = 17%), vascular complications (OR: 0.99 [0.63-1.57]; P < 0.01; I2 = 28%), AKI (OR: 0.78 [0.46-1.32]; P < 0.01; I2 = 0%), new ischemic lesions (MD: -1.72 [-4.01, 0.57]; P < 0.001; I2 = 95%) and total lesion volume (MD: -46.11 [-97.38, 5.16]; P < 0.001; I2 = 81%). The results suggest that CEP device use was associated with a lower risk of disabling stroke and bleeding events in patients undergoing TAVR.

Frequency of COVID-19 vaccine side effects and its associated factors among the vaccinated population of Pakistan: A cross-sectional study.

Background: Coronavirus disease 2019 (COVID-19) vaccine side effects have an important role in the hesitancy of the general population toward vaccine administration. Therefore, this study was conducted to document the COVID-19 vaccine side effects in our population. Materials and Methods: An online survey-based, cross-sectional study was carried out from September 1, 2021, to October 1, 2021, to document the side effects of the COVID-19 vaccine among the general public. The questionnaire included participants' sociodemographic data, type of vaccine, comorbidities, previous COVID-19 infection, and assessment of side effects reported by them. Results: The majority of the participants were <20 years of age (62.2%), females (74.9%), belonged to the educational sector (58.1%), residents of Sindh (65.7%), and were previously unaffected by COVID-19 infection (73.3%). Sinovac (38.7%) followed by Sinopharm (30.4%) and Moderna (18.4%) were administered more frequently. Commonly reported side effects were injection site pain (82%), myalgia (55%), headache (46%), fatigue/malaise (45%), and fever (41%). Vaccine side effects were more likely to be reported with the first dose as compared to the second dose. On regression analysis, factors associated with occurrence of side effects included younger age (odds ratio [OR]: 6.000 [2.065-17.431], p < 0.001), female gender (OR: 2.373 [1.146-4.914], p = 0.020), marital status (OR: 0.217 [0.085-0.556], p < 0.001), graduate level of education (OR: 0.353 [0.153-0.816], p = 0.015), and occupation being either retired, freelancers, or social workers (OR: 0.310 [0.106-0.909]), p = 0.033). Previous infection with COVID-19 (p = 0.458) and comorbidities were found unrelated (p = 0.707) to the occurrence of side effects. Conclusion: The overall prevalence of local side effects was quite higher than the systemic ones. Further large-scale studies on vaccine safety are required to strengthen public confidence in the vaccination drive.

Aqueous humor sCD44 concentration and visual field loss in primary open-angle glaucoma.

PURPOSE: To correlate aqueous humor soluble CD44 (sCD44) concentration, visual field loss, and glaucoma risk factors in primary open-angle glaucoma (POAG) patients. METHODS: Aqueous samples were obtained by paracentesis from normal and glaucoma patients who were undergoing elective surgery and analyzed for sCD44 concentration by enzyme-linked immunosorbent assay. RESULTS: In normal aqueous (n=124) the sCD44 concentration was 5.88+/-0.27 ng/mL, whereas in POAG aqueous (n=90) the sCD44 concentration was 12.76+/-0.66 ng/mL, a 2.2-fold increase (P<0.000001). In POAG patients with prior successful filtration surgery (n=13), the sCD44 concentration was decreased by 43% to 7.32+/-1.44 (P=0.001) in comparison with POAG patients without filtration surgery; however, the sCD44 concentration in the prior successful filtration subgroup with no medications and normal intraocular pressure was 12.62+/-3.81 (P=0.05) compared with normal. The sCD44 concentration of normal pressure glaucoma patients was 9.19+/-1.75 ng/mL, a 1.6-fold increase compared with normal (P=0.02). Race and intraocular pressure pulse amplitude were significant POAG risk factors in this cohort of patients. In both normal and POAG patients with mild and moderate visual field loss, sCD44 concentration was greater in African Americans than in whites (P=0.04). CONCLUSIONS: sCD44 concentration in the aqueous of POAG patients correlated with the severity of visual field loss in all stages in white patients and in mild to moderate stages in African American patients. sCD44 concentration in aqueous is a possible protein biomarker of visual field loss in POAG.