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PubMed2026

Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock.

BACKGROUND: Whether treatment with balanced crystalloid fluid leads to better outcomes than 0.9% saline in children treated for septic shock is debated. METHODS: In this pragmatic clinical trial conducted at 47 emergency departments in five countries, patients (2 months to <18 years of age) with suspected septic shock and abnormal perfusion were randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) at 30 days after enrollment or hospital discharge, whichever occurred first. RESULTS: Of 9041 enrolled patients, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the 0.9%-saline group withdrew from the trial, leaving 4235 and 4247 patients, respectively, for analysis. A primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group and in 124 (3.0%) in the 0.9%-saline group (difference, 0.4 percentage points; 95% confidence interval [CI], -0.5 to 1.3; risk ratio, 1.10; 95% CI, 0.88 to 1.40; P = 0.85). The median number of hospital-free days during 28 days after enrollment was 23 (interquartile range, 19 to 25) in both groups. Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and in 1383 (49.0%) in the 0.9%-saline group; hypernatremia in 52 (1.8%) and 89 (3.1%), respectively; and hyperlactatemia in 260 (19.8%) and 228 (16.7%). No differences in other safety outcomes or adverse events were seen. CONCLUSIONS: Among children treated for septic shock, no significant difference was seen in the incidence of death, new renal-replacement therapy, or persistent kidney dysfunction when fluid resuscitation was administered with balanced fluid as compared with 0.9% saline. (Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; PRoMPT BOLUS ClinicalTrials.gov number, NCT04102371.).

Adolescent↗

PubMed2026

Efficacy and safety of human albumin combined with furosemide in acute decompensated heart failure with hepatic dysfunction.

BACKGROUND: Congestion is the most common clinical presentation on admission of patients with acute decompensated heart failure (ADHF). Finding effective ways to alleviate congestion has become a pivotal management step. This study sought to investigate the efficacy and safety of intravenous (IV) albumin use in conjunction with furosemide in patients hospitalized for ADHF with hepatic dysfunction in terms of subjective regression of congestion symptoms and worsening renal function. METHODS: This prospective, open-label, randomized-pragmatic trial recruited 241 patients with hepatic dysfunction hospitalized for ADHF. Patients (78 years, 54% female) were assigned to receive IV albumin with furosemide or IV furosemide alone. The coprimary study endpoints were patients' global assessment of symptoms score, quantified as the area under the curve (AUC) of the score on a visual analog scale, and the change in creatinine levels over 72 hours from admission. RESULTS: The experimental treatment group demonstrated a greater improvement in patients' global assessment of symptoms scores (AUCbaseline-72 h 3,767 vs 3,457 points; P < .001) and a milder increase in creatinine levels (0.07 vs 0.18 mg/dL; P = .045) than the IV furosemide group. The length of stay was 1 day shorter (4 vs 5 days; P < .001) and the incidence of worsening renal function was lower (25% vs 38%; P = .037) in the experimental treatment group. CONCLUSIONS: In this hypothesis generating study, among patients with ADHF and hepatic dysfunction, concomitant use of IV albumin and furosemide for the first 72 hours resulted in a significant improvement in subjective perception symptoms of decongestion and a milder increase in creatinine levels than IV furosemide alone.

Aged↗

PubMed2026

Chronic neurological diseases with acute respiratory failure in a real-life cohort: insights into ICU and long-term survival-A retrospective study.

BACKGROUND: Patients with chronic neurological diseases (CND) are at increased risk of pulmonary complications that often require ICU admission. This study aimed to identify clinical factors associated with ICU mortality and long-term survival in patients with CND who developed acute respiratory failure (ARF). METHODS: This retrospective cohort study was conducted in a level III respiratory ICU. Patients with pre-existing CND admitted to the ICU with ARF were included. ICU mortality was analyzed using multivariable logistic regression. Long-term survival after ICU discharge was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mortality timing was further characterized using hazard function analysis. RESULTS: A total of 220 patients were included; the most common neurological diagnoses were dementia (37.3%), stroke (22.7%), and amyotrophic lateral sclerosis (14.1%). ICU mortality was 33.6%. Higher APACHE II scores were independently associated with increased ICU mortality (OR 1.076 per point increase; 95% CI 1.029-1.126; p < 0.001). Long-term survival differed significantly by post-discharge respiratory support strategy, with Kaplan-Meier analysis demonstrating more favorable survival patterns among patients receiving home non-invasive mechanical ventilation (NIMV) (p = 0.003). In Cox regression analysis, age, home NIMV, and feeding modality at discharge were independently associated with long-term outcomes. Survival analyses revealed an early clustering of deaths within the first months after ICU discharge, particularly among patients with dementia. CONCLUSIONS: In patients with CND, acute physiological severity was the main determinant of ICU mortality, whereas long-term survival after ICU discharge was poor, with deaths clustering within the first months thereafter. Post-discharge respiratory support and nutritional management should be individualized according to the expected clinical trajectory and patient values.

Humans↗

PubMed2026

Promoter Methylation of HOXA5 and NDRG2 in Multiple Myeloma Patients with Renal Impairment.

Renal impairment (RI) is frequently caused by multiple myeloma (MM), which makes clinical care more difficult if renal function deteriorates or renal failure develops. Thus, in this investigation, we looked at the relationship between HOXA5&NDRG2 promoter methylation in MM patients and evaluated their prognostic potential in predicting RI risk in MM patients. This study included 60 control volunteers and 120 MM patients. The promoter methylations of HOXA5&NDRG2 were quantitatively evaluated by real-time PCR (qPCR) after the extraction of gDNA from whole blood and then treated with bisulfite. The promoter methylation percentages of HOXA5&NDRG2 were significantly increased in MM patients (77.16 ± 2.43&45.49 ± 2.16;p < 0.05) when compared to controls (4.47 ± 0.61&3.33 ± 0.31,respectively), in stage II&III patients when compared to stage I patients and in patients with age ≥ 60 years when compared to patients with age < 60 years. While only the methylation percentage of NDRG2 promoter was significantly increased in MM patients with RI (53.61 ± 3.21,p < 0.05) when compared to MM patients without RI (37.37 ± 2.04). Results obtained from ROC curve revealed that both HOXA5&NDRG2 promoter methylation were good diagnostic tools for MM. The NDRG2 promoter methylation was good prognostic biomarker could predict renal while HOXA5 promoter in the prediction of MM staging. The Kaplan-Meier survival test showed that patients with higher HOXA5&NDRG2 promoter methylation had a shorter OS and a worse prognosis. Only NDRG2 promoter hypermethylation was significantly associated with the risk of RI development in MM patients. HOXA5&NDRG2 promoter hypermethylation may have roles in the molecular etiology of MM and could be used as a treatment regimen.

Humans↗

PubMed2026

Soluble CD163 as a Non-Invasive Biomarker in Autoimmune Nephrological and Rheumatological Diseases.

Autoimmune nephrological and rheumatological diseases involve macrophage-driven inflammation, yet disease activity is often assessed using invasive or non-specific measures. Soluble CD163 (sCD163), released from activated monocytes and macrophages, is emerging as a biomarker of macrophage-mediated inflammation in these conditions. This narrative review summarizes current evidence on the diagnostic, prognostic, and disease-monitoring potential of sCD163 measured in blood, urine, and synovial fluid in autoimmune nephrological and rheumatological diseases. This review is based on a narrative analysis of selected publications investigating the clinical utility of sCD163 in autoimmune kidney and rheumatic diseases, with emphasis on correlations with disease activity, histopathological findings, and clinical outcomes. Urinary sCD163 shows excellent diagnostic accuracy for active lupus nephritis (area under the receiver operating characteristic [AUROC] 0.89-0.998), correlates with histological activity index (but not chronicity), and distinguishes ongoing inflammation from chronic damage during treatment. In IgA nephropathy, it predicts remission failure and greater benefit from corticosteroids. In ANCA-associated vasculitis, it identifies active renal involvement (AUROC 0.95 in multicenter cohorts). In rheumatoid arthritis (RA), serum sCD163 correlates with early disease activity, predicts radiographic progression, and detects subclinical macrophage activation in remission. In spondylarthritis, synovial fluid sCD163 reflects a disease-specific M2-polarized macrophage phenotype distinct from RA. Utility is compartmentalized: urinary levels indicate intrarenal macrophage activation, synovial fluid local joint inflammation, and serum systemic activation. sCD163 is a promising macrophage-specific biomarker across autoimmune diseases, but its compartmentalized nature requires context-specific measurement. Before clinical implementation, assay standardization, multicenter validation, and interventional trials showing the benefit of sCD163-guided management are needed.

Humans↗

PubMed2026

Cardiovascular Drug Access in Australia and New Zealand: New PBS and PHARMAC Listings, 2023-2025.

BACKGROUND: Cardiovascular disease is a leading cause of death in Australia and New Zealand. Publicly subsidised access to new cardiovascular medications is governed by the PBS (Pharmaceutical Benefits Scheme) in Australia and PHARMAC (Pharmaceutical Management Agency) in New Zealand, yet no consolidated resource catalogues recent listings across both jurisdictions. METHODS: We reviewed all new cardiovascular drug listings and indications on the PBS and PHARMAC schedules from 1 January 2023 to 31 December 2025. PBS data were obtained from the PBS Pricing and Policy Branch through the Cardiac Society for Australia and New Zealand. PHARMAC data were obtained via direct communication with PHARMAC and cross-referenced with public schedule information. Pivotal trial evidence, restriction criteria, and prescribing considerations were extracted from published literature and regulatory documents. RESULTS: Five new cardiovascular drugs were PBS-listed (inclisiran, mavacamten, tafamidis, icosapent ethyl and migalastat), two existing drugs received new cardiovascular indications (empagliflozin and dapagliflozin for heart failure with preserved ejection fraction) and prasugrel was relisted for acute coronary syndrome. One major change occurred on the PHARMAC schedule (empagliflozin for heart failure with reduced ejection fraction). CONCLUSIONS: The 2023-2025 period has seen notable additions to cardiovascular pharmacotherapy in Australia, including the first cardiac myosin inhibitor, the first transthyretin stabiliser, expanded lipid lowering therapy options, and extension of SGLT2 inhibitor coverage across the heart failure ejection fraction spectrum. A pronounced access disparity persists between Australia and New Zealand.

New Zealand↗

PubMed2026

Nephropathies Associated with Sickle Cell Trait and How to Study Them.

Sickle cell trait (SCT), which carries a single point mutation in the hemoglobin-β (HBB) gene, has long been considered a benign condition. However, epidemiological evidence challenges this assumption, revealing that individuals with SCT face an elevated risk of renal dysfunction. However, this field of study remains ill-defined as it has focused on sickle cell disease (SCD), where renal complications are severe. As SCT is more prevalent than SCD, consequences of nephropathies in this group translate into a substantial and largely unaddressed public health burden. Clinical data, primarily observational, implicate age and sex in the development of SCT-associated nephropathies. These manifestations span glomerular hyperfiltration, tubular damage, hematuria, renal papillary necrosis, renal medullary carcinoma, and progression to chronic kidney disease, all complications that cluster disproportionately in older male individuals. Despite this, the mechanistic basis of SCT nephropathy, the thresholds at which renal injury becomes clinically significant, and the optimal strategies for early identification and prevention remain inadequately defined. In vitro studies have primarily focused on SCD blood cell biology, with SCT receiving comparatively little attention. Humanized murine models (i.e., Berkeley and Townes) have recapitulated some SCT-associated renal phenotypes but need to be more fully characterized. This review aims to provide an overview of the biology of sickle cell trait nephropathies, the gaps in our knowledge, and the model systems we can use to fill those gaps.

Journal Article↗

PubMed2026

Prognostic value of early changes in the frontal QRS-T angle in patients with heart failure and left bundle branch block undergoing cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in selected patients with heart failure (HF). The frontal QRS-T angle (FQTA), reflecting ventricular depolarization-repolarization heterogeneity, has been associated with major adverse cardiovascular events (MACE). We aimed to assess the prognostic value of changes in the FQTA after CRT in predicting long-term MACE. METHODS: A total of 223 consecutive HF patients with left bundle branch block who underwent CRT between 2018 and 2022 were retrospectively analyzed. The FQTA was measured before and after CRT, and the change (ΔFQTA) was calculated. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff value for predicting the primary outcome, MACE. Patients were subsequently stratified according to this cutoff value. Independent predictors were identified using multivariable Cox proportional hazards regression analysis. RESULTS: ROC analysis identified 22.5° as the optimal cutoff value for predicting MACE (AUC: 0.711; 95% CI: 0.642-0.781; p < 0.001). During a mean follow-up of 34.6 ± 17.6 months, patients with ΔFQTA <22.5° had a significantly higher incidence of MACE compared with those with greater angle reduction (44.7% vs. 11.9%; p < 0.001). In multivariable Cox regression analysis, chronic kidney disease (HR: 2.517; p = 0.002) and ΔFQTA <22.5° (HR: 4.56; p < 0.001) were independently associated with MACE. CONCLUSION: A greater reduction in FQTA after CRT is associated with improved long-term outcomes and may serve as a practical electrocardiographic marker for risk stratification.

Humans↗

PubMed2026

Empagliflozin and functional aerobic capacity in individuals with increased risk of heart failure: The Empire Prevent Cardiac trial.

BACKGROUND: Higher maximal oxygen consumption (VO₂ max) is associated with lower risk of developing heart failure (HF). Empagliflozin improves VO2 max in HF with reduced ejection fraction, but the effect on VO2 max in individuals at risk of HF remain unknown. OBJECTIVE: This study aimed to evaluate the effect of 180 days treatment with empagliflozin compared to placebo on VO2 max, daily physical activity level, and quality of life (QoL) in individuals with overweight or obesity and risk of HF. METHOD: This investigator-initiated, double-blinded, randomized, placebo-controlled, multicenter trial included elderly individuals with body mass index >28 kg/m2 and at least one additional risk factor for HF, including hypertension, ischemic heart disease, stroke, or chronic kidney disease. Individuals with HF or type 2 diabetes mellitus were excluded. The primary endpoint was the mean difference in change of VO2 max. The secondary outcome was objectively measured physical activity level. QoL was an explorative outcome. RESULTS: Among 191 randomized individuals (94 empagliflozin, 97 placebo), 89% had hypertension and 66% ischemic heart disease. At baseline, 69% were male, median age was 68 years, median body mass index 31.9 kg/m², mean left ventricular ejection fraction 65 ± 9%, and mean VO₂ max 18.1 ± 4.3 mL/min/kg. Empagliflozin did not change VO2 max with an estimated treatment difference of -0.2 mL/min/kg (97.5% confidence interval -1.2 to 0.8), adjusted P = 1.00. No significant treatment differences were observed for neither daily physical activity nor QoL. CONCLUSIONS: Empagliflozin did not affect VO2 max, physical activity level, or QoL in elderly individuals with overweight or obesity and risk of HF.

Humans↗

PubMed2026

Design, rationale, and baseline patient characteristics for the Sickle Cell Disease and CardiovAscular Risk-Red cell Exchange (SCD-CARRE) trial.

BACKGROUND: Despite wide utilization of automated red blood cell exchange (RBCX) transfusion in adult patients with sickle cell disease (SCD), no consensus or quality efficacy data exist on its use. The Sickle Cell Disease and CardiovAscular Risk- Red cell Exchange (SCD-CARRE) trial tests the hypothesis that an automated chronic RBCX transfusion strategy reduces acute health care encounters and death while improving quality of life and end-organ function (cardiac, pulmonary and renal) in participants with SCD that are at high risk of death. METHODS: Adult patients with SCD with elevated tricuspid regurgitant jet velocity (TRV) and/or chronic kidney disease were considered to be at high risk of death and were randomly assigned to RBCX plus standard of care vs standard of care alone. Participants assigned to RBCX received 12 months of exchange transfusions to maintain target pretransfusion hemoglobin S% < 30%, post-transfusion hemoglobin S% < 20%, and post-transfusion hemoglobin concentration ≥10 g/dL. All study participants were managed according to NHLBI/ASH/ATS Expert Panel guidelines. The primary endpoint was the number of SCD acute health care encounters or death over 13 months. Secondary endpoints included measures of cardiovascular and renal function, exercise capacity, patient reported outcomes (all collected at baseline, and months 4, 8, and 12), and transfusion-related adverse events (collected monthly). RESULTS: Between 2020 and 2025, the SCD-CARRE trial randomized 173 participants at 23 sites across 3 countries. Enrolled participants had mean (SD) age of 45.8 (11.8) years and 54% were female. At baseline, participants had average TRV of 2.8 (0.5) m/s such that 45.9% had a TRV between 2.5 to 2.9 m/sec and 28.1% had a TRV ≥ 3.0 m/sec. The median (Q1, Q3) eGFR in this cohort was 60 (36, 110) mL/min/1.73 m2. The median (Q1, Q3) 6-minute walk test distance was 375 meters (309, 439), the median daily steps were 3,728 (2,187, 5,821), and participants experienced a median (Q1, Q3) of 2 (1, 5) pain episodes in the year prior to randomization. The trial results are pending. CONCLUSIONS: The SCD-CARRE trial successfully enrolled a cohort of n = 173 adults with SCD. This study highlights a rationale to evaluate the effect of automated chronic RBCX transfusion strategy plus standard of care as compared to standard of care alone in SCD patients at high risk of death with a focus on patient centered outcomes, preservation of cardiovascular function, end-organ complications and death. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT04084080, https://clinicaltrials.gov/study/NCT04084080.

Adult↗

PubMed2026

Efficacy of sodium-glucose cotransporter 2 inhibitors after acute myocardial infarction: Are the benefits limited to patients with diabetes? A systematic review and meta-analysis.

BACKGROUND: Acute myocardial infarction remains one of the leading causes of death worldwide. Recently, studies have focused on evaluating the effectiveness of SGLT2 inhibitors in this scenario. Objectives We aimed to perform a meta-analysis comparing the efficacy of SGLT2 inhibitors vs standard care. METHODS: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) and observational studies comparing patients with acute myocardial infarction using iSGLT2 inhibitors and standard care. Statistical analyses were conducted using R software (v 4.3.2) and a random-effects model was employed for all outcomes. RESULTS: A total of 31,378 patients were included, with 10,897 (34.7%) assigned to the SGLT2 inhibitor group. Among these studies, three were randomized controlled trials (RCTs). There was a significant difference in reduction of HF readmissions (OR 0.61; p < 0.01), all-cause mortality (OR 0.62; p < 0.01;) and stroke (OR 0.67; p < 0.01;). However, there was no significant difference in cardiovascular death, rehospitalization for any cause and recurrence of acute MI. Meta regression and subgroup analysis showed a trend toward better outcomes in the diabetic and non-STEMI population. CONCLUSIONS: SGLT2 inhibitors were associated with lower HF rehospitalization, stroke, and all-cause mortality after acute MI, mainly in observational studies. Benefits appeared greater in diabetic and non-STEMI patients. Dedicated RCTs focusing on diabetic, particularly non-STEMI, populations are needed to confirm these findings. KEY POINTS: What is already known on this topic: SGLT2 inhibitors have demonstrated cardiovascular and renal benefits in patients with heart failure and type 2 diabetes mellitus. However, their role in the acute myocardial infarction (AMI) setting remains uncertain, particularly regarding post-AMI outcomes such as heart failure readmissions, mortality, and recurrent ischemic events, with current evidence derived from heterogeneous and predominantly observational studies. WHAT THIS STUDY ADDS: This meta-analysis, including over 31,000 patients, suggests that SGLT2 inhibitors are associated with reductions in heart failure readmissions, all-cause mortality, and stroke following AMI. These associations were more consistently observed in patients with type 2 diabetes and in non-ST-segment elevation myocardial infarction (NSTEMI) populations. However, randomized controlled trials showed neutral results, and the observed benefits were mainly driven by observational studies. Meaning: These findings should be interpreted as hypothesis-generating. While SGLT2 inhibitors may represent a potential therapeutic strategy in selected post-AMI populations, particularly patients with diabetes and NSTEMI, current evidence does not support routine early in-hospital initiation. Dedicated randomized trials specifically enrolling diabetic post-AMI patients are required to clarify optimal timing and clinical benefit.

Humans↗

PubMed2026

Comparative Efficacy of Insulin and Alternative Therapies for Hypertriglyceridemia-Associated Acute Pancreatitis: A Systematic Review and Network Meta-Analysis.

BACKGROUND AND AIMS: Hypertriglyceridemia-induced acute pancreatitis is associated with high triglyceride levels and may lead to significant clinical complications. Rapid TG-lowering strategies, including insulin, therapeutic plasma exchange (TPE), heparin, hemofiltration, and conservative management, are used in clinical practice; however, their comparative efficacy and impact on clinical outcomes remain uncertain. METHODS: Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and International Prospective Register of Systematic Reviews (PROSPERO) registration (CRD420251239674), we searched PubMed, Embase, Web of Science, Scopus, CINAHL, Google Scholar, and Cochrane. Primary outcomes included TG reduction, C-reactive protein (CRP), length of stay, mortality, and organ failure. Secondary outcomes included renal and respiratory failure. Random-effects network meta-analyses estimated mean differences or relative risks with 95% confidence intervals; treatments were ranked using the Surface Under the Cumulative Ranking curve (SUCRA). Predefined sensitivity analyses were conducted according to study design (RCTs) and risk of bias (ROB). RESULTS: Across predominantly observational evidence, no intervention demonstrated statistically significant superiority over insulin-based therapy for mortality, organ failure, or length of stay, and no consistent clinical benefit was observed despite differences in biochemical TG reduction. Although some interventions showed relatively favorable SUCRA rankings across selected outcomes, these findings were not consistently supported by statistically significant or high-certainty evidence. In RCT-restricted analyses, therapeutic plasma exchange (TPE) significantly reduced TG levels versus insulin (MD - 620.0; p = 0.03) and CRP versus conservative therapy (MD - 0.80; p < 0.01), while insulin plus heparin was associated with shorter hospital stay (MD - 1.60 days; p < 0.01). However, faster triglyceride reduction did not consistently translate into improved mortality, organ failure, ICU-related outcomes, or length of stay. CONCLUSION: Despite improvements in biochemical markers, the clinical significance of rapid TG reduction in HTG-AP remains uncertain, as these effects were not consistently associated with improvements in mortality, organ failure, ICU-related outcomes, or hospital length of stay. Given that most available evidence was derived from nonrandomized studies and that the certainty of evidence was predominantly low or very low, adequately powered randomized controlled trials are needed to determine whether accelerated triglyceride lowering improves clinically meaningful patient outcomes.

Humans↗

PubMed2026

RNA in situ hybridization based TRIM63 characterization in tubulocystic renal cell carcinoma.

Explore the source record for details and available documents.

Cystic↗

PubMed2026

Identification of molecular subtypes in clear cell renal cell carcinoma based on chromatin regulators and tumor immune microenvironment profiling.

In the histological classification of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) accounts for the highest proportion and is the most common subtype. Despite advances in management, it continues to be associated with considerable incidence and mortality. Although surgery and systemic therapies are available, their efficacy is constrained by pronounced intratumoral heterogeneity and treatment resistance. Identifying robust biomarkers and clarifying the underlying biological mechanisms are therefore essential to improving diagnosis, risk stratification and therapeutic decision-making. In this work, we identified two ccRCC molecular subtypes displaying divergent chromatin regulator (CR) profiles and different clinical prognoses. Using the genes differentially expressed between these subgroups, we constructed a CR-related score (CRS) that effectively stratified patients according to survival. More analysis concluded that the low expression of CR was more linked with the immune-activated tumors, which encompassed the immune pathway enrichment, as well as the elevation of numerous immune cell subtypes. Moreover, elevated CRS was associated with improved immunotherapy responsiveness. Drug-sensitivity analyses nominated several candidate agents, and SMARCD3 knockdown in 786-O cells inhibited proliferation and migration and reduced sensitivity to masitinib. Collectively, these findings support the prognostic and therapeutic relevance of CR-related states in ccRCC and provide a framework for future experimental validation of chromatin-regulated tumor-immune interactions.

Humans↗

PubMed2026

Perioperative safety and survival outcomes of robot-assisted partial nephrectomy in elderly patients with localized renal cell carcinoma: an overlap-weighted Asian cohort study.

The value of robot-assisted partial nephrectomy (RAPN) in elderly Asian patients with localized renal cell carcinoma (RCC) remains insufficiently defined. We retrospectively analyzed 339 patients (≥ 70 years) with localized RCC treated at a single Asian center between 2015 and 2025, including 119 undergoing partial nephrectomy (PN) and 220 undergoing radical nephrectomy (RN). Propensity score overlap weighting (OW) was applied to compare PN versus RN and, within the PN cohort, RAPN versus laparoscopic partial nephrectomy (LPN). Three open partial nephrectomy cases were summarized descriptively and retained only in exploratory sensitivity analyses. Weighted logistic regression and Cox models with robust standard errors evaluated Clavien-Dindo grade ≥ II complications and overall survival (OS). After OW, PN was associated with better early postoperative renal functional preservation than RN but a greater incidence of grade ≥ II complications (36.4% vs. 17.6%; weighted p < 0.001); OS was similar. Within the PN cohort, RAPN had longer operative time than LPN (weighted p = 0.030), whereas warm ischemia time, early postoperative eGFR, and grade ≥ II complications (31.8% vs. 40.4%; weighted p = 0.414) were not significantly different. Exploratory analyses favored RAPN, but only one death occurred in this group, and residual confounding remains possible. PN may preserve early renal function in selected older patients, while RAPN appears feasible in experienced centers; its survival association remains hypothesis-generating.

Humans↗

PubMed2026

Thymosin-ɑ1 for people with chronic hepatitis B.

RATIONALE: Chronic hepatitis B is a global public health concern. It is caused by infection with the hepatitis B virus (HBV). The goal of treating chronic HBV infection is to prevent progression to chronic hepatitis, cirrhosis, hepatic decompensation, liver failure, hepatocellular carcinoma, and death. Individual studies have evaluated various immunomodulatory therapies with inconsistent results. Thymosin-ɑ1 is known to have antiviral effects; however, results of randomised clinical trials on the effects of thymosin-α1 as a potential treatment for people with chronic HBV have been inconsistent. OBJECTIVES: To assess the benefits and harms of thymosin-ɑ1 therapy in people with chronic hepatitis B. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, four other databases and six trials registers, in addition to reference checking, citation searching, and contacting study authors to identify trials for inclusion. The latest search date was 10 June 2026. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) that evaluated thymosin-α1 at any dose, route of administration, or formulation type, in people with chronic hepatitis B regardless of age, sex, or ethnicity. Thymosin-α1 could have been administered as monotherapy, in combination with an additional drug, or in addition to standard medical treatment and compared with placebo, no intervention, the same additional drug, or the same standard medical treatment. OUTCOMES: Our critical outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Among our important outcomes were HBV-related morbidity, HBV-related mortality, non-serious adverse events, and the proportion of people without histological improvements. RISK OF BIAS: We used the Cochrane Risk of bias 2 tool (RoB 2) to assess risk of bias. SYNTHESIS METHODS: We followed Cochrane methods. We conducted meta-analyses for predefined outcomes using data from the longest follow-up period, irrespective of the risk of bias judgements. We presented dichotomous outcome results as risk ratios (RRs) and continuous outcome results as mean differences, with 95% confidence intervals (CIs) at their longest follow-ups. We used the random-effects model for our primary analyses. We used GRADE to assess the certainty of the evidence for each outcome. INCLUDED STUDIES: We included 10 RCTs conducted in Bangladesh, China, Italy, Korea, Singapore, and Taiwan, with 1349 randomised participants (range: 12 to 690; 1045 (77.5%) were male). Among the trials reporting age, none included participants younger than 17 years (age range: 17 to 75 years). The trials were published between 1991 and 2018, and assessed thymosin-ɑ1 in adults with chronic hepatitis B infection, with or without comorbidities. Only two trials mentioned comorbidities (cirrhosis and acute-on-chronic liver failure). The trials compared thymosin-ɑ1, with or without a cointervention, with placebo or no intervention, or with the same cointervention. The control interventions were placebos in two trials and no intervention in two. The remaining six trials administered co-interventions, such as interferon, pegylated interferon, lamivudine, and standard medical therapy (entecavir or tenofovir), and entecavir. Follow-ups ranged from six months to five years after the end of treatment (median: 12 months). Four trials were funded by industry, five by research grants, and one provided no information. All 10 trials (11 records) provided data on at least one outcome in our review. We identified no ongoing trials. Sixteen studies are awaiting assessment due to incomplete reporting. We received no responses to our enquiries. SYNTHESIS OF RESULTS: Thymosin-ɑ1, compared with the control interventions, may reduce all-cause mortality (RR 0.53, 95% CI 0.29 to 0.96; I² = 0%; 3 studies, 907 participants; very low-certainty evidence), serious adverse events (RR 0.72, 95% CI 0.53 to 0.99; I² = 0%; 5 studies, 1056 participants; low-certainty evidence), HBV-related mortality (RR 0.53, 95% CI 0.29 to 0.96; I² = 0%; 3 studies, 907 participants; very low-certainty evidence), non-serious adverse events (RR 0.47, 95% CI 0.27 to 0.83; I² = 0%; 5 studies, 300 participants; very low-certainty evidence), and may have little to no effect on health-related quality of life (MD 0.70, 95% CI -2.55 to 3.95; I² not applicable; 1 study, 161 participants; very low-certainty evidence; score range: 0 to 100; the higher the score, the better) and on histological improvement (RR 0.51, 95% CI 0.13 to 2.06; I² = 74%; 2 studies, 702 participants; very low-certainty evidence). The evidence is very uncertain about the effect of thymosin-ɑ1 on hepatitis B-related morbidity (RR 0.86, 95% CI 0.54 to 1.40; I² = 3%; 3 studies, 854 participants; very low-certainty evidence). We judged the certainty of evidence to be low for serious adverse events and very low for the remaining outcomes. Reasons for downgrading were mainly due to study limitations, including overall high or some concerns for risk of bias; imprecision of the pooled effect estimates (including wide or very wide confidence intervals crossing the line of no effect, and small participant numbers); and inconsistency due to substantial heterogeneity (I² = 74%). The test for subgroup differences provided no evidence of differences in effect according to thymosin‑α1 administration for any outcome (P ≥ 0.05). AUTHORS' CONCLUSIONS: We assessed the certainty of evidence as very low for all outcomes except for serious adverse events (low). Therefore, we are not sure whether thymosin-α1 monotherapy versus placebo or no intervention, or with the same co-interventions, reduces all-cause mortality, serious adverse events, HBV-related mortality, and non-serious adverse events, nor whether it has any effect on quality of life (based on one trial) and histological improvement. The effect of thymosin-ɑ1 on HBV-related morbidity is very uncertain. We observed no statistically significant differences between trials with and without cointerventions. We found no ongoing trials. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD014610.

Humans↗

PubMed2026

Diurnal differences in the effects of heat exposure on renal function: A randomized controlled crossover trial.

High temperature is a major risk factor for kidney injury, and population exposure to nighttime heat is increasing as the climate warms. However, whether renal responses to heat exposure differ between daytime and nighttime remains unclear. Forty-one healthy adults participated in a randomized crossover experiment conducted in a controlled laboratory setting. Participants were exposed to heat (32°C during daytime; 30°C during nighttime) and thermoneutral conditions (26°C) for 8 h. Blood and urine samples were collected before and after each exposure to examine various renal biomarkers reflecting glomerular filtration function, tubular injury, and early kidney stress. Heat exposure affected both blood and urinary biomarkers of kidney function, with notable diurnal differences in renal responses. Daytime heat exposure primarily affected blood markers of glomerular filtration, increasing creatinine by 7.67% (95% CI: 4.73%-10.61%) and cystatin C by 3.05% (95% CI: 0.17%-5.93%), while reducing estimated glomerular filtration rate by 0.05% (95% CI: 0.02%-0.08%). In contrast, nighttime heat exposure predominantly elevated urinary biomarkers of early kidney stress, including insulin-like growth factor-binding protein 7 (58.40%, 95% CI: 27.66%-89.14%), kidney injury molecule-1 (47.25%, 95% CI: 18.91%-75.59%), and tissue inhibitor of metalloproteinases-2 (51.88%, 95% CI: 22.26%-81.51%). Moreover, increases in insulin-like growth factor-binding protein 7 were significantly greater at night than during the day. Sleep-related parameters, including sleep quality, duration, and heart rate variability, partially mediated nighttime heat effects on renal responses. These results indicated that heat exposure induced different diurnal patterns in renal responses.

Humans↗

PubMed2026

Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics and the Pharmacokinetics of Balcinrenone When Dosed with a P-gp Inhibitor.

Balcinrenone (AZD9977) is a novel selective non-steroidal mineralocorticoid receptor antagonist with a distinct mode of action being developed as a fixed-dose combination with the sodium-glucose cotransporter-2 inhibitor dapagliflozin for the treatment of heart failure with impaired kidney function, and chronic kidney disease. In this Phase 1 randomized open-label three-way crossover study we investigated the effect of food on balcinrenone/dapagliflozin pharmacokinetics, and the pharmacokinetics of balcinrenone when dosed with a P-glycoprotein (P-gp) inhibitor. Fourteen healthy participants were administered an oral capsule of balcinrenone/dapagliflozin 40 mg/10 mg in three dosing periods: fasted (reference), fed (high-fat, high-calorie meal) and with a P-gp inhibitor (quinidine 300 mg × 2). Balcinrenone exposure was comparable in the fed and fasted states (geometric mean ratios [GMRs] [90% CI]: maximum plasma concentration [Cmax] 1.05 [0.88, 1.25]; area under the plasma concentration-time curve from time 0 to infinity [AUCinf] 1.12 [1.06, 1.19]). In the fed state, dapagliflozin AUCinf was comparable to the fasted state (GMR [90% CI] 1.05 [1.01, 1.09]), whereas Cmax was decreased (GMR [90% CI] 0.59 [0.51, 0.69]), in line with previous dapagliflozin food interaction studies. Co-administration with quinidine increased balcinrenone exposure: GMRs (90% CI) 1.48 (1.24, 1.76) and 1.24 (1.17, 1.31) for Cmax and AUCinf, respectively, but AUC fold increase was <2, the level used for classification of sensitive P-gp substrates. All interventions were well tolerated. In conclusion, this study supports dosing of balcinrenone/dapagliflozin without regard to food. Balcinrenone is not considered a sensitive P-gp substrate. No P-gp based dosing precautions are warranted based on this study.

Adult↗