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

Super Alloy Coatings for Enhanced Corrosion and Oxidation Resistance in Extreme Environments

The use of super alloy coatings is an innovative method for enhancing the durability of materials against the detrimental effects of corrosion and oxidation, especially in areas with severe circumstances. This study explores the forefront of super alloy coatings, examining their significant role in minimising the adverse effects of corrosive and oxidative processes on materials working in harsh conditions. This study highlights the transformative potential of super alloy coatings in extending the lifespan and enhancing the reliability of critical components. It achieves this by presenting a comprehensive overview of the fundamental principles, fabrication methodologies, and practical applications associated with these coatings. As many sectors navigate more difficult environments, the effective incorporation of advanced coatings presents a potential direction, advancing the field of materials science and guaranteeing consistent performance in the presence of significant challenges. The emergence of super alloy coatings represents a significant transformation in the field of corrosion and oxidation control, providing a robust defence against the persistent deteriorating factors seen in highly challenging settings. The combination of complex production procedures and superior material qualities empowers these coatings to strengthen materials, therefore assuring their durability

Antimycobacterial effect of IFNG (interferon gamma)-induced autophagy depends on HMOX1 (heme oxygenase 1)-mediated increase in intracellular calcium levels and modulation of PPP3/calcineurin-TFEB (transcription factor EB) axis

<p>IFNG (interferon gamma)-induced autophagy plays an important role in the elimination of intracellular pathogens, such as <i>Mycobacterium tuberculosis</i> (Mtb). However, the signaling cascade that leads to the increase in autophagy flux in response to IFNG is poorly defined. Here, we demonstrate that HMOX1 (heme oxygenase 1)-generated carbon monoxide (CO) is required for the induction of autophagy and killing of Mtb residing in macrophages in response to immunomodulation by IFNG. Interestingly, IFNG exposure of macrophages induces an increase in intracellular calcium levels that is dependent on HMOX1 generated CO. Chelation of intracellular calcium inhibits IFNG-mediated autophagy and mycobacterial clearance from macrophages. Moreover, we show that IFNG-mediated increase in intracellular calcium leads to activation of the phosphatase calcineurin (PPP3), which dephosphorylates the TFEB (transcription factor EB) to induce autophagy. PPP3-mediated activation and nuclear translocation of TFEB are critical in IFNG-mediated mycobacterial trafficking and survival inside the infected macrophages. These findings establish that IFNG utilizes the PPP3-TFEB signaling axis for inducing autophagy and regulating mycobacterial growth. We believe this signaling axis could act as a therapeutic target for suppression of growth of intracellular pathogens.</p