Intragraft interleukin 2 mRNA expression during acute cellular rejection and left ventricular total wall thickness after heart transplantation

OBJECTIVE: To assess whether diastolic graft function is influenced by intragraft interleukin 2 (IL-2) messenger RNA (mRNA) expression in rejecting cardiac allografts. DESIGN: 16 recipients of cardiac allografts were monitored during the first three months after transplantation. The presence of IL-2 mRNA in endomyocardial biopsies (n = 123) was measured by reverse transcriptase polymerase chain reaction. To determine heart function, concurrent M mode and two dimensional Doppler echocardiograms were analysed. RESULTS: Histological signs of acute rejection (International Society for Heart and Lung Transplantation (ISHLT) rejection grade > 2) were strongly associated with IL-2 mRNA expression (IL-2 mRNA was present in 12 of 20 endomyocardial biopsies (60%) with acute rejection and in 24 of 103 endomyocardial biopsies (23%) without acute rejection, p = 0.002). No significant relation was found between either histology or IL-2 mRNA expression alone and the studied echocardiographic parameters. However, stratification of the echocardiographic data into those of patients with and those without acute rejection showed that during acute rejection IL-2 mR

KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD): executive summary

The Kidney Disease: Improving Global Outcomes (KDIGO) 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) represents the first KDIGO guideline on this subject. Its scope includes nomenclature, diagnosis, prognosis, and prevalence; kidney manifestations; chronic kidney disease (CKD) management and progression, kidney failure, and kidney replacement therapy; therapies to delay progression of kidney disease; polycystic liver disease; intracranial aneurysms and other extrarenal manifestations; lifestyle and psychosocial aspects; pregnancy and reproductive issues; pediatric issues; and approaches to the management of people with ADPKD. The guideline has been developed with patient partners, clinicians, and researchers around the world, with the goal to generate a useful resource for healthcare providers and patients by providing actionable recommendations. The development of this guideline followed an explicit process of evidence review and appraisal, based on a rigorous, formal systematic literature review. The strength of recommendations follows the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The guideline also provides practice points serving to direct clinical care or activities relating to areas for which a systematic review was not conducted. Limitations of the evidence are discussed. Research recommendations to address gaps in knowledge, and implications for policy and payment, are provided. The guideline targets a broad audience of healthcare providers, people living with ADPKD, and stakeholders involved in the various aspects of ADPKD care

Leukotriene-receptor antagonists versus placebo in the treatment of asthma in adults and adolescents a systematic review and meta-analysis

Background: Leukotriene-receptor antagonists (LTRAs) are recommended as an alternative treatment in patients with mild asthma, but their effect compared with placebo is unclear. Purpose: To determine the benefits and harms of LTRAs as monotherapy or in combination with inhaled corticosteroids compared with placebo in adults and adolescents with asthma. Data Sources: MEDLINE and the Cochrane Central Register of Controlled Trials from inception through June 2015. Study Selection: Peer-reviewed, English-language, randomized, controlled trials in patients with asthma that reported the effect of LTRAs versus placebo on measures of asthma control. Data Extraction: Three researchers extracted data on study population, interventions, outcome measures, and adverse events. One researcher assessed risk of bias. Data Synthesis: Of the 2008 abstracts that were screened, 50 trials met eligibility criteria. Random-effects meta-analyses of 6 trials of LTRA monotherapy showed that LTRAs reduced the risk for an exacerbation (summary risk ratio [RR], 0.60 [95% CI, 0.44 to 0.81]). In 4 trials of LTRAs as add-on therapy to inhaled corticosteroids, the summary RR for exacerbation was 0.80 (CI, 0.60 to 1.07). Leukotriene-receptor antagonists either as monotherapy or as add-on therapy to inhaled corticosteroids increased FEV1, whereas FEV1 percentage of predicted values was improved only in trials of LTRA monotherapy. Adverse event rates were similar in the intervention and comparator groups. Limitation: Variation in definitions and reporting of outcomes, high risk of bias in some studies, heterogeneity of findings, possible selective outcome reporting bias, and inability to assess the effect of asthma severity on summary estimates. Conclusion: Leukotriene-receptor antagonists as monotherapy improved asthma control compared with placebo, but which patients are most likely to respond to treatment with LTRAs remains unclear. Primary Funding Source: National Institutes of Health