The association between klotho and kidney and cardiovascular outcomes: a comprehensive systematic review and meta-analysis.

Background: Chronic kidney disease (CKD) and end-stage renal disease (ESKD) are significant global health challenges associated with progressive kidney dysfunction and numerous complications, including cardiovascular disease and mortality. This study aims to explore the potential association between plasma klotho levels and various prognostic outcomes in CKD and ESKD, including all-cause mortality, cardiovascular events, metabolic syndrome development and adverse renal events necessitating renal replacement therapies. Methods: A literature search was conducted through 3 June 2024 using the electronic databases Cochrane Library, Ovid MEDLINE, CINAHL, Web of Science, SCOPUS and PubMed. This systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Fourteen studies were included. For all-cause mortality, comparing CKD patients with low versus high klotho levels showed a significant association {odds ratio [OR] 1.81 [95% confidence interval (CI) 1.34-2.44], P = .0001}, with substantial heterogeneity (I 2 = 69%). Excluding one study reduced heterogeneity (I 2 = 43%) while maintaining significance [OR 1.97 (95% CI 1.45-2.66), P < .0001]. Cardiovascular mortality was higher in patients with low klotho levels [OR 2.11 (95% CI 1.61-2.76), P < .00001], with low heterogeneity (I 2 = 25%). Excluding one study eliminated heterogeneity (I 2 = 0%) while maintaining significance [OR 2.39 (95% CI 1.83-3.12), P < .00001]. Composite cardiovascular events did not differ significantly between low and high klotho groups [OR 1.51 (95% CI 0.82-2.77), P = .18], but with high heterogeneity (I 2 = 72%). Patients with low klotho levels had a higher risk of adverse renal events [OR 2.36 (95% CI 1.37-4.08), P = .002], with moderate heterogeneity (I 2 = 61%). Sensitivity analysis reduced heterogeneity (I 2 = 0%) while maintaining significance [OR 3.08 (95% CI 1.96-4.85), P < .00001]. Specifically, for ESKD or kidney replacement therapy risk, low klotho levels were associated with an increased risk [OR 2.30 (95% CI 1.26-4.21), P = .007]. Similarly, CKD progression risk was higher in patients with lower klotho levels [OR 2.48 (95% CI 1.45-4.23), P = .0009]. Conclusion: Lower serum klotho levels serve as a significant predictor of adverse outcomes, including increased risks of all-cause mortality, cardiovascular mortality and progression to end-stage kidney disease among CKD patients.

COVID-19 associated bacterial infections in intensive care unit: a case control study.

We described the secondary bacterial infections (SBI) among COVID-19 patients in comparison with non-COVID-19 patients. We performed a retrospective case-control study between January 01, 2020 and April 01, 2022. Including the adult patients, who stayed ≥ 72 h in intensive care unit (ICU). In total 405 patients were included, 135 had (33.3%) COVID-19, with similar age and gender. The length of stay in ICU was not different (11.4 vs 8.2, p = 0.109), however mean intubation days were higher among COVID-19 cases (6.5 vs 3.8, p = 0.005), SBI were more common among COVID-19 cases (34% vs 10.7%, p < 0.001). Among the patients with pneumonia, the rate of gram-positive bacteria was higher in COVID-19 group than the control group (39% vs 5%, p = 0.006). The predictors for SBI were having COVID-19 (OR: 2.3, Cl 1.25-4.32, p = 0.008), days of intubation (OR: 1.05, Cl 1.01-1.10, p = 0.004), and being male (OR: 2, Cl 1.12-3.58, p = 0.018). The predictors of mortality were COVID-19 (OR: 2.38, Cl 1.28-4.42, p = 0.006), days of intubation (OR: 1.06, Cl 1.03-1.09, p < 0.001), active hematologic malignancy (OR: 3.1, Cl: 1.33-7.28, p = 0.09), active solid tumors (OR: 2.44, Cl 1.21-4.91, p = 0.012), and coronary artery diseases (OR: 1.8, Cl 1.01-3.52, p = 0.045). The most common SBI in COVID-19 patients were methicillin-sensitive Staphylococcus aureus. No carbapenem-resistant Enterobacterales related infections were detected in COVID-19 patients.

ANTIBACDUS-PAN: Antibacterial Utilization among Adult Patients Before and During COVID-19 Pandemic within 12-Months Period: A Tertiary Hospital Pharmacoepidemiology Study.

Objective: Irrational use of antibacterials is a concern during the COVID-19 pandemic. Hospital pharmacoepidemiology studies are important for evaluating the rational use of medicines, especially antibacterials, during pandemics. Defined daily doses (DDD) and drug utilization 90% (DU90%) are established methods for the evaluation of drug utilization. We aimed to evaluate antibacterial utilization in a tertiary hospital setting at Koç University Hospital (KUH). Materials and Methods: This cross-sectional, descriptive study was retrospectively conducted with data extracted from KUH Inpatient Electronic Order System (CP) and was carried out for a period of one year. Antibacterial utilization of adult (aged ≥ 18 years) inpatients, who were prescribed at least one type of systemic antibacterial (ATC code J01), was evaluated using the recommended parameter DDD/100 admission and compared between 6 months before COVID-19 and during COVID-19 periods. March 11, 2020, the very first COVID-19 diagnosed case in Turkey, was set as the cutoff date of the 6-month period for the selection of the compared antibacterials using the DU90% method. Results: Finally, 3280 of 5942 and 2605 of 4942 prescriptions for pre-COVID-19 and COVID-19 periods were included, respectively. Antibacterial utilization according to DDD/100 admissions increased from 193.96 to 201.26 DDD/100 admissions after the initiation of COVID-19 pandemic. The most utilized antibacterials were piperacillin and enzyme inhibitors in pre-COVID-19 period, whereas meropenem was utilized the most during COVID-19 period. Azithromycin utilization increased by 656.24%, whereas clarithromycin utilization decreased by 52.12%. Antibacterials were utilized most in general surgery department, with an increase of 17.57%. Conclusion: There is an increase in antibacterial utilization in KUH during COVID-19 pandemic, especially reserved antibacterials, which is a concern for antibacterial resistance.

Hypofractionated frameless gamma knife radiosurgery for large metastatic brain tumors.

Hypofractionated stereotactic radiosurgery has become an alternative for metastatic brain tumors (METs). We aimed to analyze the efficacy and safety of frameless hypofractionated Gamma Knife radiosurgery (hfGKRS) in the management of unresected, large METs. All patients who were managed with hfGKRS for unresected, large METs (> 4 cm3) between June 2017 and June 2020 at a single center were reviewed in this retrospective study. Local control (LC), progression-free survival (PFS), overall survival (OS), and toxicities were investigated. A total of 58 patients and 76 METs with regular follow-up were analyzed. LC rate was 98.5% at six months, 96.0% at one year, and 90.6% at 2 years during a median follow-up of 12 months (range, 2-37). The log-rank test indicated no difference in the distribution of LC for any clinical or treatment variable. PFS was 86.7% at 6 months, 66.6% at 1 year, and 58.5% at 2 years. OS was 81% at 6 months, 63.6% at one year, and 50.7% at 2 years. On the log-rank test, clinical parameters such as control status of primary cancer, presence of extracranial metastases, RTOG-RPA class, GPA group, and ds-GPA group were significantly associated with PFS and OS. Patients presented with grade 1 (19.0%), grade 2 (3.5%) and grade 3 (5.2%) side effects. Radiation necrosis was not observed in any patients. Our current results suggest that frameless hfGKRS for unresected, large METs is a rational alternative in selected patients with promising results.