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Background: Drug-induced acute interstitial nephritis (DI-AIN) represents a common cause of acute kidney injury. Early withdrawal of the culprit drug and corticosteroid therapy remains the mainstay of treatment.This study aimed to develop and validate a predictive nomogram to assess the probability of recovery of kidney function at 6 months after treatment., Methods: Multicenter, retrospective, observational study in 13 nephrology departments. Patients with biopsy proven DI-AIN treated with corticosteroids between 1996-2023 were included. Dataset was randomly divided into training (n=164) and validation sets (n=60). Least absolute shrinkage and selection operator regression was used to screen the main predictors of complete (creatinine increase <25% of the last value before DI-AIN) or no recovery of kidney function (serum creatinine ≥75% or need for dialysis)., Results: The study group comprised 224 patients with DI-AIN: 51 (31%) in the training group and 19 (32%) in the validation set, achieved complete recovery at 6 months. Conversely, 33 (20%) and 8 (13%) patients in each set showed no recovery at 6 months. Clinical characteristics were well balanced between training and validation sets. The selected variables were age (under/above 65 years), gender, degree of interstitial fibrosis and time to corticosteroids initiation (under/above 7 days). Based on multivariable logistic regression model, a nomogram was developed. The area under the curve (AUC) of the nomogram was 0.79 (95% confidence interval: 0.71-0.88) indicating a good discriminative power. Bootstrap self-sampling was performed 1000 times for validation of the model. Calibration plot revealed that the predicted outcomes aligned well with the observations. Decision curve analysis suggested that the model had clinical benefit., Conclusions: We developed and validated a nomogram to predict kidney recovery at 6 months in DI-AIN patients treated with corticosteroids. This tool helps clinicians estimate prognosis and optimize corticosteroid therapy's intensity and duration for better treatment outcomes., (© The Author(s) 2025. Published by Oxford University Press on behalf of the ERA.)

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a 12% survival rate, highlighting the need for novel therapies. c-MYC overexpression, driven by upstream mutations and amplifications, reprograms tumor metabolism and promotes proliferation, migration and metastasis. This study identifies ELOVL6, a fatty acid elongase regulated by c-MYC, as a potential therapeutic target. Using PDAC mouse models and cell lines, we show that c-MYC directly upregulates ELOVL6 during tumor progression. Genetic or chemical inhibition of ELOVL6 reduces proliferation and migration by altering fatty acid composition, affecting membrane rigidity, permeability and pinocytosis. These changes increase Abraxane uptake and show a synergistic effect when combined with ELOVL6 inhibition in vitro. In vivo, ELOVL6 interference significantly suppresses tumor growth and improves Abraxane response, prolonging survival. These findings position ELOVL6 as a promising target for improving PDAC treatment outcomes., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Genetic defects affecting steroid biosynthesis cause cortisol deficiency and differences of sex development; among these defects are recessive mutations in the steroidogenic enzymes CYP11A1 and CYP11B, whose function is supported by reducing equivalents donated by ferredoxin reductase (FDXR) and ferredoxin. So far, mutations in the mitochondrial flavoprotein FDXR have been associated with a progressive neuropathic mitochondriopathy named FDXR-related mitochondriopathy (FRM), but cortisol insufficiency has not been documented. However, patients with FRM often experience worsening or demise following stress associated with infections. We investigated 2 female patients with FRM carrying the potentially novel homozygous FDXR mutation p.G437R with ambiguous genitalia at birth and sudden death in the first year of life; they presented with cortisol deficiency and androgen excess compatible with 11-hydroxylase deficiency. In addition, steroidogenic FDXR-variant cell lines reprogrammed from 3 patients with FRM fibroblasts displayed deficient mineralocorticoid and glucocorticoid production. Finally, Fdxr-mutant mice allelic to the severe p.R386W human variant showed reduced progesterone and corticosterone production. Therefore, our comprehensive studies show that human FDXR variants may cause compensated but possibly life-threatening adrenocortical insufficiency in stress by affecting adrenal glucocorticoid and mineralocorticoid synthesis through direct enzyme inhibition, most likely in combination with disturbed mitochondrial redox balance.

Introduction: Heart transplant (HT) survival has barely improved in the last decades, which is unsatisfactory for many HT recipients. The development of anti-human leukocyte antigen (anti-HLA) antibodies in HT patients is associated with a cardiac allograft dysfunction. The mechanisms leading to this damage are unclear. The Multimodality Evaluation Of Antibody-Mediated Injury In Heart Transplantation (LEONE-HT) study aimed to thoroughly describe the damage inflicted on the myocardium by anti-HLA antibodies., Methods and Analysis: The LEONE-HT study is a cohort study with a cross-sectional approach in which HT patients with positive anti-HLA antibodies are compared with coetaneous HT patients with negative anti-HLA antibodies. All patients will undergo a state-of-the-art multimodal assessment, including imaging techniques, coronary anatomy and physiology evaluations and histological and immunological analyses. The individual and combined primary outcomes of structural graft injuries and longitudinal secondary outcomes are to be compared between the exposed and non-exposed groups with univariate and multivariable descriptive analyses., Ethics and Dissemination: The LEONE-HT study is carried out in accordance with the principles set out in the Declaration of Helsinki and the International Conference on Harmonization guidelines for good clinical practice and following national laws and regulations. The study design, objectives and participant centers have been communicated to clinicaltrials.gov (NCT05184426). The LEONE-HT study counts on the support of patient associations to disseminate the objectives and results of the research. This study was funded by the Spanish Ministry of Science and Innovation and the Spanish Society of Cardiology.

Objectives: The aim of this study was to evaluate the potential biologic effects caused by the successive placement of biodegradable polydioxanone (PDO) stents in the rabbit trachea. PDO stents could eventually induce a fibroproliferative reaction in the submucosa that could be beneficial in the treatment of malacia due to an increase in its consistency without impairing the tracheal lumen., Methods: Sixteen adult NZ rabbits were distributed into 3 groups with different survival times according to the number of stents placed: 1 stent (14 weeks), 2 stents (28 weeks) and 3 stents (42 weeks). Stent insertion was performed endoscopically in the cervical trachea of the animal. Histopathological studies included Masson's trichrome staining for submucosal fibrosis and Safranin O to assess the structural integrity of cartilage. Potential inflammatory changes were analysed by means of immunohistochemistry determining the number of CD45-positive cells., Results: Stent placement was successful in every case. Histological studies did not show a statistically significant increase in tracheal wall collagen area and cartilage structure was not modified in those rabbits with 1 or more PDO stents inserted compared to non-stented tracheal sections. Furthermore, no statistically significant changes in the number of CD45+ cells were observed in stented tracheal segments compared to normal tracheal tissues., Conclusions: According to our data, successive PDO stenting caused mild inflammatory changes in the tracheal wall and no increase in the collagen matrix, and the cartilaginous support was not modified during a long follow-up period (up to 42 weeks). These findings suggest that they may be safe and show good biocompatibility in the long term., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Metastatic disease in the kidney is relatively uncommon compared to other body sites. In most cases it presents as a unilateral and unifocal mass in the tubulointerstitial region. Intraglomerular metastases are even rarer, and their diagnosis is hampered by the limitations of imaging techniques in detecting them. We describe the finding of intraglomerular metastases in a patient affected by a malignant melanoma considered to be in partial remission, with no evidence of melanoma progression on the previously performed computed tomography scan. This patient developed rapidly progressive kidney failure, proteinuria, and hematuria with dysmorphic red blood cells in the urine sediment. Kidney biopsy showed a marked crescentic proliferation caused by tumor cells, which even invaded the proximal convoluted tubule. Melanoma cells were also found in the lumina of the glomerular capillaries, distending their basement membranes. Our case describes the histologic and electron microscopic findings of this form of intraglomerular metastasis and reminds us of its inclusion in the differential diagnosis of rapidly progressive kidney failure., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)