Acute kidney injury in patients treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery

Total Factor Productivity Change in the Middle East Banking: The Case of Jordanian Banks at the Turn of the Millennium

This paper analyzes the total factor productivity developments in the Middle East banking, by drawing on the experience of Jordanian banks at the start of the new millennium. In order to control for the effects of different specifications of banking technology on the results, this study estimates the productivity and efficiency growth scores under two alternative approaches, production and intermediation models. On average, under the former model, we found 79% technical efficiency and 3.2% productivity growth, while under the later model we found 92% technical efficiency and 3.3% productivity growth for the sector. One implication is that the Jordanian banks can obtain considerable resource savings if they can catch up with the best practice banks. Among the organizational forms operating in this emerging market, we found that commercial banks generally outperform both investment and Islamic banks in terms of efficiency and total factor productivity growth

Costs of medication in older patients: before and after comprehensive geriatric assessment

Background: Polypharmacy and inappropriate drug use cause numerous complications, such as cognitive impairment, frailty, falls, and functional dependence. The present study aimed to determine the effect of the comprehensive geriatric assessment (CGA) on polypharmacy, potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs), and to evaluate the economic reflections of medication changes

Metabolic Syndrome Induces Release of Smaller Extracellular Vesicles from Porcine Mesenchymal Stem Cells

Mesenchymal stromal/stem cells (MSCs) belong to the endogenous cellular reparative system, and can be used exogenously in cell-based therapy. MSCs release extracellular vesicles (EVs), including exosomes and microvesicles, which mediate some of their therapeutic activity through intercellular communication. We have previously demonstrated that metabolic syndrome (MetS) modifies the cargo packed within swine EV, but whether it influences their phenotypical characteristics remains unclear. This study tested the hypothesis that MetS shifts the size distribution of MSC-derived EVs. Adipose tissue-derived MSC-EV subpopulations from Lean ( n = 6) and MetS ( n = 6) pigs were characterized for number and size using nanoparticle-tracking analysis, flow cytometry, and transmission electron microscopy. Expression of exosomal genes was determined using next-generation RNA-sequencing (RNA-seq). The number of EV released from Lean and MetS pig MSCs was similar, yet MetS-MSCs yielded a higher proportion of small-size EVs (202.4 ± 17.7 nm vs. 280.3 ± 15.1 nm), consistent with exosomes. RNA-seq showed that their EVs were enriched with exosomal markers. Lysosomal activity remained unaltered in MetS-MSCs. Therefore, MetS alters the size distribution of MSC-derived EVs in favor of exosome release. These observations may reflect MSC injury and membrane recycling in MetS or increased expulsion of waste products, and may have important implications for development of adequate cell-based treatments

COVID-19 pneumonia in patients with impaired fasting glucose, newly diagnosed diabetes and pre-existing diabetes: a tertiary center experience

COVID-19 infection is known to increase mortality in patients with diabetes. We aim to demonstrate the differences in disease course and clinical outcomes of patients with COVID-19 regarding the presence of impaired fasting glucose, pre-existing diabetes mellitus (DM) or new-onset DM. 236 patients with positive reverse transcription-PCR tests for SARS-CoV-2 were included in this single-center, retrospective observational study between March 2020 and May 2021. Laboratory results, comorbidities, medications and imaging findings were noted. Logistic regression was used to estimate associated factors for admission to the intensive care unit (ICU). 43 patients with normal glucose, 53 with impaired fasting glucose, 60 with newly diagnosed DM, and 80 with pre-existing DM were classified. Patients with pre-existing DM had higher fasting glucose and glycated hemoglobin than the other groups (p<0.001 for all). Patients with newly diagnosed DM were more likely to need dexamethasone 6 mg (p=0.001). In both newly diagnosed diabetes and impaired fasting glucose groups, 250 mg methylprednisolone was needed at higher rates (p=0.002). Newly diagnosed DM had higher rates of intubation (21.6%) and more mortality (20.0%) (p=0.045 and p=0.028, respectively). Mortality and hospitalization in the ICU were lower in the group receiving antidiabetic treatment. The risk of ICU attendance was higher in patients with impaired fasting glucose (HR=1.71, 95% CI: 0.48 to 6.08) and newly diagnosed DM (HR=1.88, 95% CI: 0.57 to 6.17), compared with pre-existing DM and non-diabetics. Newly diagnosed DM and impaired fasting glucose are associated with increased mortality and intubation in inpatients with COVID-19

Coupling high-rate activated sludge process with aerobic granular sludge process for sustainable municipal wastewater treatment

Achieving a neutral/positive energy balance without compromising discharge standards is one of the main goals of wastewater treatment plants (WWTPs) in terms of sustainability. Aerobic granular sludge (AGS) technology promises high treatment performance with low energy and footprint requirement. In this study, high-rate activated sludge (HRAS) process was coupled to AGS process as an energy-efficient pre-treatment option in order to increase energy recovery from municipal wastewater and decrease the particulate matter load of AGS process. Three different feeding strategies were applied throughout the study. AGS system was fed with raw municipal wastewater, with the effluent of HRAS process, and with the mixture of the effluent of HRAS process and raw municipal wastewater at Stage 1, Stage 2 and Stage 3, respectively. Total suspended solids (TSS), chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), and total phosphorus (TP) concentrations in the effluent were less than 10 mg/L, 60 mg/L, 0.4 mg/L, and 1.3 mg/L respectively at all stages. Fluctuations were observed in the denitrification performance due to changes in the influent COD/total nitrogen (TN) ratio. This study showed that coupling HRAS process with AGS process by feeding the AGS process with the mixture of HRAS process effluent and raw municipal wastewater could be an appropriate option for both increasing the energy recovery potential of WWTPs and enabling high effluent quality.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.BT/Environmental Biotechnolog

Impact of primary sedimentation on granulation and treatment performance of municipal wastewater by aerobic granular sludge process

Aerobic granules contain microorganisms that are responsible for carbon, nitrogen, and phosphorus removal in aerobic granular sludge (AGS) process in which aerobic/anoxic/anaerobic layers (from surface to core) occur in a single granule. Optimizing the aerobic granular sludge (AGS) process for granulation and efficient nutrient removal can be challenging. The aim of this study was to examine the impact of settling prior to AGS process on granulation and treatment performance of the process. For this purpose, synthetic wastewater mimicking municipal wastewater was fed directly (Stage 1), and after primary sedimentation (Stage 2) to a laboratory-scale AGS system. In full-scale wastewater treatment plants, primary sedimentation is used to remove particulate organic matter and produce primary sludge which is sent to anaerobic digesters to produce biogas. Performances obtained in both stages were compared in terms of treatment efficiency, granule settling behavior, and granule morphology. Granulation was achieved in both stages with more than 92% chemical oxygen demand (COD) removal efficiencies in each stage. High nutrient removal was obtained in Stage 1 since anaerobic phase was long enough (i.e., 50 min) to hydrolyze particulate matter to become available for PAOs. Primary sedimentation caused a decrease in influent organic load and COD/N ratio, as a result, low nitrogen and phosphorus removal efficiencies were observed in Stage 2 compared to Stage 1. With this study, the effect of the primary sedimentation on the biological removal performance of AGS process was revealed. COD requirement for nutrient removal in AGS systems should be assessed by considering energy generation via biogas production from primary sedimentation sludge.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.BT/Environmental Biotechnolog

Factors Affecting Inadequate Empirical Antimicrobial Therapy and the Clinical Course of Upper Urinary Tract Infections in Elderly Patients: A Multicenter Study

Introduction: In this study, we aimed to determine the risk factors associated with inadequate empirical antibiotherapy (IEAT) and hospital-related mortality in elderly patients being treated for upper urinary tract infections (UTI)

Acute kidney injury in patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery