Medical sciences (Basel, Switzerland)最新文献

{"title":"SGLT2 Inhibitors in Nephrolithiasis: Emerging Evidence and What Urologists Need to Know.","authors":"Marius Ivănuță, Dragoș Puia, Ana-Maria Ivănuță, Alexandra Haută, Ionuț Nistor, Cătălin Pricop","doi":"10.3390/medsci14050555","DOIUrl":"10.3390/medsci14050555","url":null,"abstract":"<p><strong>Background: </strong>Nephrolithiasis frequently coexists with type 2 diabetes, obesity, gout, chronic kidney disease, and other cardiometabolic disorders. Sodium-glucose cotransporter 2 (SGLT2) inhibitors may influence stone formation through effects on glucosuria, natriuresis, urine volume, urinary citrate, pH, urate handling, and relative supersaturation. This review aimed to examine the current mechanistic, biochemical, and clinical evidence linking SGLT2 inhibition to nephrolithiasis, with particular attention to its relevance for urological practice.</p><p><strong>Methods: </strong>A clinically oriented narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. The final search was performed on 1 July 2026. A total of 15 studies were included. Randomised trials, pooled and post hoc analyses, observational and comparative-effectiveness studies, meta-analyses, human mechanistic studies, and relevant experimental investigations were considered. Evidence was synthesised narratively according to biological mechanisms, urinary chemistry and relative supersaturation, randomised evidence, and observational clinical outcomes. Clinical stone events were analysed separately from surrogate urinary endpoints.</p><p><strong>Results: </strong>SGLT2 inhibition is associated with reproducible increases in urinary citrate and variable effects on urine volume, urinary pH, and the excretion of calcium, phosphate, and urate. Short-term mechanistic studies suggest reductions in calcium phosphate supersaturation and, in selected uric acid stone formers, uric acid supersaturation, whereas effects on calcium oxalate supersaturation remain inconsistent. Observational studies and secondary analyses of randomised trials generally indicate fewer nephrolithiasis events among SGLT2 inhibitor users; however, most outcomes were based on adverse-event reporting or administrative codes and lacked stone composition, standardised imaging, urinary phenotyping, and recurrence adjudication.</p><p><strong>Conclusions: </strong>SGLT2 inhibitors may favourably modify selected lithogenic pathways, but their effects appear phenotype-dependent and have not yet been shown to directly prevent stone recurrence. They should not be initiated solely for the prevention of nephrolithiasis. In patients with established cardiovascular, renal, or metabolic indications, their potential urinary effects may represent an additional benefit. Dedicated long-term randomised studies with stone-specific endpoints are required.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational and AI-Enabled Imaging Biomarkers for Predicting and Assessing Immunotherapy Response in Oral Squamous Cell Carcinoma: A Systematic Review with Functional Meta-Synthesis.","authors":"Carlos M Ardila, Anny M Vivares-Builes, Eliana Pineda-Vélez","doi":"10.3390/medsci14050554","DOIUrl":"10.3390/medsci14050554","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Computational and artificial intelligence (AI)-enabled imaging biomarkers are increasingly being investigated for immunotherapy-response assessment in oral squamous cell carcinoma (OSCC), but the evidence is heterogeneous. This systematic review identified, critically appraised, and synthesized imaging biomarkers used to predict or assess observed immunotherapy response in OSCC. <b>Methods:</b> PubMed/MEDLINE, Embase, and Scopus were searched from inception to 31 July 2026, without language restrictions. The protocol was registered in PROSPERO. Eligible studies evaluated quantitative, radiomic, machine-learning, or related medical-imaging biomarkers against pathological or radiological response. Risk of bias was assessed using design-specific tools, supplemented by a radiomics-specific methodological appraisal. A structured Synthesis Without Meta-analysis was prespecified. <b>Results:</b> Seven reports were included, covering pretreatment prediction, early/on-treatment dynamic assessment, and post-neoadjuvant/preoperative response assessment. Pretreatment-computed tomography and magnetic resonance imaging radiomics showed discriminatory performance, whereas baseline positron emission tomography uptake alone was not consistently associated with pathological response. Longitudinal fibroblast activation protein inhibitor positron emission tomography changes were associated with a major pathological response, and magnetic resonance imaging habitat and longitudinal habitat models showed higher within-study discrimination when combined with clinical information. No computational model had independent external validation specifically in an OSCC population, and no three independent studies were sufficiently comparable for meta-analysis. <b>Conclusions:</b> Computational imaging is promising across several stages of immunotherapy-response assessment. However, based on current evidence, none of the reviewed imaging biomarkers or models can yet be considered ready for routine clinical use. Prospective multicenter OSCC-specific validation and standardized imaging and analytical pipelines are needed to establish generalizability and clinical utility.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atrial Fibrillation in Retinal Artery Occlusion: A Systematic Review and Meta-Analysis.","authors":"Aurelia Mihaela Nica, Madalina Andreea Beldie, Samer Andrei Nica, Minela Aida Maranduca, Cosmin Victor Ganea, Paula Cristina Morariu, Maria Mihaela Godun, Roxana Elena Ciuntu, Camelia Margareta Bogdanici, Mariana Floria","doi":"10.3390/medsci14050553","DOIUrl":"10.3390/medsci14050553","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Retinal artery occlusion (RAO) represents an ischemic event of the anterior circulation, driven by impaired blood flow through the ophthalmic branches of the internal carotid artery. Atrial fibrillation (AF) is an increasingly recognized cardioembolic source in patients with RAO, yet its prevalence remains poorly characterized. We conducted a systematic review and meta-analysis to estimate the pooled prevalence of AF in RAO patients and to summarize evidence on its incidence and association with this condition. <b>Methods</b>: Four databases were searched through April 2025, updated on 18 August 2026. Studies reporting AF prevalence, incidence, or association in adults with RAO were included. Pooled prevalence was estimated using the Freeman-Tukey double arcsine transformation with a random-effects model. Subgroup analyses, meta-regression, and sensitivity analyses were performed to explore heterogeneity. <b>Results</b>: Sixty-two studies were included in the qualitative synthesis, of which 58 reported AF prevalence data. Among the 36 studies comprising 139,222 patients, the pooled AF prevalence was 11.53% (95% CI: 9.41-13.82; I² = 99.2%; prediction interval: 2.00-26.9%). AF prevalence was significantly higher in patients aged ≥70 years (15.86%) and in central RAO cohorts (16.54%). Incident AF following RAO ranged from 10.5% to 41%, increasing progressively with monitoring intensity. The pooled odds ratio for the AF-RAO association was 1.56 (95% CI: 1.06-2.29). <b>Conclusions</b>: AF affects approximately one in nine patients with RAO, though with substantial uncertainty across populations (prediction interval 2.00-26.9%); the extent to which this exceeds the general-population estimates independent of age, cardiovascular risk profile, and geographic factors remains uncertain. These findings support cardiac rhythm surveillance following RAO diagnosis in selected patients, although its effect on clinical outcomes remains to be established prospectively.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effects of Behavioral Analysis Therapy of Feelings and Brief Focal Psychotherapy: Protocol for a Randomized Controlled Assessor-Blinded Clinical Trial.","authors":"Manoel Victor Fernandes Marques, Emerson Arcoverde Nunes, Rodrigo Costa de Oliveira, Nicole Leite Galvão Coelho, Glauco Francisco Silva, Mariana Dantas de Carvalho Vilar, Grasiela Piuvezam","doi":"10.3390/medsci14050551","DOIUrl":"10.3390/medsci14050551","url":null,"abstract":"<p><strong>Background: </strong>Brief psychotherapies have been shown to improve clinical symptoms within a limited number of sessions without compromising treatment quality.</p><p><strong>Objectives: </strong>This study aims to test the effects of the experimental Behavioral Analysis Therapy of Feelings (BATF) in a randomized controlled trial design.</p><p><strong>Methods: </strong>This randomized, controlled, assessor-blinded clinical trial compares BATF with Brief Focal Psychotherapy in individuals presenting symptoms of anxiety and/or depression. Participants with substance use disorders, tobacco or alcohol use, pregnancy, or use of oral contraceptives will be excluded. Participants will be randomized in a 1:1 ratio with stratification by clinical condition. Outcomes will be assessed at baseline, Week 4, and Week 13 using the Hamilton Anxiety Rating Scale, the Montgomery-Åsberg Depression Rating Scale, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, and the Pittsburgh Sleep Quality Index. In addition to clinical outcomes, exploratory salivary and blood biomarkers associated with stress, inflammation, and neurobiological function will be evaluated. The trial is registered in the Brazilian Clinical Trials Registry (RBR-10p45rdg) and has Universal Trial Number U1111-1313-4499.</p><p><strong>Conclusions: </strong>This protocol describes a randomized controlled trial comparing BATF with Brief Focal Psychotherapy. The study is designed to generate preliminary evidence on the effects of the intervention in anxiety and depressive symptoms.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Abnormalities and Associated Clinical Features in Polycythemia Vera.","authors":"Ugo Testa, Germana Castelli, Elvira Pelosi","doi":"10.3390/medsci14050552","DOIUrl":"10.3390/medsci14050552","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Myeloproliferative neoplasms are a group of clonal myeloid malignancies that affect bone marrow and include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). PV is caused in most patients by the <i>JAK2-V617F</i> mutation and is characterized at the phenotypic level by overproduction and accumulation of red blood cells. PV is associated with significant morbidity, including risk of thrombotic events and of hematologic evolution (myelofibrotic or leukemic transformation) and reduced survival. In addition to the <i>JAK2-V617F</i> mutation, PV patients display additional molecular abnormalities. The aim of this study is to review recent studies investigating molecular abnormalities observed in PV. <b>Methods</b>: An extensive search of the most recent literature was performed, selecting and critically analyzing the most relevant studies. <b>Results</b>: The studies carried out in recent years have provided an extensive molecular analysis of PV, showing its heterogeneity, characterized in many patients by the presence of additional cytogenetic and gene mutations that contribute to the disease development and evolution. <b>Conclusions</b>: PV is a complex disease that needs to be carefully characterized at the molecular level at diagnosis, to be monitored in time to predict the risk for thrombotic complications and hematologic evolution and to receive an adequate treatment.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twenty-Two Years of Prenatal Testing for Suspected Monogenic Disorders: A Retrospective Single-Center Experience in Western Romania.","authors":"Miruna Gug, Nicoleta Andreescu, Eugen Dan Chicea, Adrian Rațiu, Simona Farcaș, Ioana Marin, Stelian Țîcău, Cristina Gug","doi":"10.3390/medsci14050548","DOIUrl":"10.3390/medsci14050548","url":null,"abstract":"<p><strong>Background/objectives: </strong>Prenatal testing strategies for suspected monogenic disorders have changed considerably over the past decades, alongside evolving referral indications and increasing availability of genomic technologies. Longitudinal, practice-based data describing these changes within routine clinical care remain limited, particularly in Central and Eastern Europe. We describe changes in referral indications, testing strategies, and molecular findings over 22 years in a single-center retrospective descriptive case series from Western Romania.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 52 pregnancies investigated for suspected monogenic disorders between 2004 and 2026. Forty pregnancies were evaluated through a diagnostic pathway, while a separate group of 12 pregnancies underwent cell-free DNA (cfDNA)-based monogenic screening; these were analyzed as distinct clinical pathways. For the diagnostic pathway, clinical indications, testing strategies, and molecular findings were analyzed across three retrospectively defined study periods (2004-2013, 2014-2019, and 2020-2026).</p><p><strong>Results: </strong>Within the diagnostic pathway, referral patterns shifted from predominantly family-history-based testing (55.6% of cases in 2004-2013) toward indications arising from positive parental carrier screening and fetal ultrasound abnormalities in later study periods. Testing strategies expanded from predominantly targeted single-gene testing and multiplex ligation-dependent probe amplification (MLPA) to include gene panels and whole-exome sequencing (WES). Among 34 pregnancies with fetal molecular evaluation, 7 (20.6%) had a confirmed disease-causing finding, 9 (26.5%) had carrier-only outcomes, 15 (44.1%) were classified as unaffected, and 3 (8.8%) had non-classic molecular findings. Incidental or additional molecular findings beyond the primary testing indication were identified in 6 of 34 pregnancies with fetal molecular evaluation (17.6%) and required case-specific interpretation and genetic counseling. The 12 cfDNA-based monogenic screening pregnancies constituted a separate, non-diagnostic screening pathway and were analyzed independently from the diagnostic pathway.</p><p><strong>Conclusions: </strong>Over 22 years, referral indications for suspected monogenic disorders broadened alongside an expansion of prenatal testing strategies from predominantly targeted familial testing to a wider range of genomic approaches. These findings describe temporal changes within a single-center clinical practice and should not be interpreted as evidence that changes in testing strategy improved diagnostic performance or pregnancy outcomes. Invasive diagnostic testing and cfDNA-based monogenic screening represent distinct clinical pathways and should be interpreted separately.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Rapid Progression to Long-Lasting Complete Response: A Wide Range of Ripretinib Activity for Metastatic GIST-A Real-World Cohort.","authors":"Hanna T Frumin Edri, Walid Shalata, Ilia Berezhnov, Tanzila Tairov, Tatiana Bobrovitsky, Dan Mirelman, Esther Tahover, Ofer Purim, Yuval Dadon, Katerina Shulman, Gali Perl, Gil Bar Sela, Maria Passhak, Ronen Brenner","doi":"10.3390/medsci14050549","DOIUrl":"10.3390/medsci14050549","url":null,"abstract":"<p><p><b>Background</b>: Ripretinib, a switch-control kinase inhibitor approved for advanced gastrointestinal stromal tumor (GIST), inhibits primary and secondary <i>KIT</i> and <i>PDGFRA</i> mutations. Real-world data from Western and Middle Eastern populations remain limited. We report outcomes from a molecularly characterized Israeli multicenter cohort. <b>Methods</b>: We conducted a multicenter retrospective cohort study across seven university-affiliated medical centers in Israel. Patients with advanced GIST receiving Ripretinib at any treatment line were eligible. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and response was assessed according to modified RECIST v1.1. <b>Results</b>: Sixteen patients were identified (median age, 67.5 years; 75.0% received Ripretinib in the fourth-line setting). KIT exon 11 mutations were present in 62.5% of patients, including five with secondary resistance mutations involving exon 13 or exons 17/18. Median PFS was 7.0 months (95% CI, 2.0-13.0) and median OS was 14.7 months (95% CI, 4.4-NR). Individual outcomes varied substantially, with PFS ranging from 2.0 to 60.2 months and OS from 2.2 to 60.2 months. Three patients achieved complete responses, with PFS of 20.0, 33.6, and 60.2 months. ORR was 56.3% (CR, <i>n</i> = 3; PR, n = 6) and DCR was 81.3%. No dose reductions or treatment discontinuations due to adverse events were documented; however, adverse events were recorded in only 4 of 16 patients. <b>Conclusions</b>: Ripretinib demonstrated clinical activity in this small, heavily pre-treated cohort. The relatively high ORR and wide variability in outcomes should be interpreted cautiously given the small sample size, retrospective design, and absence of central radiological review. Durable responses were observed in some patients with KIT exon 11 and secondary exon 17/18 mutations, but this exploratory observation does not establish a predictive molecular subgroup. Larger prospective studies with systematic molecular, radiological, and safety assessment are warranted.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperoncotic Albumin (20%) Versus Crystalloids for Mortality in Adults with Sepsis and Septic Shock: An Updated Systematic Review and Meta-Analysis.","authors":"Christian J Wiedermann, Gianni Turcato, Arian Zaboli, Michael Joannidis","doi":"10.3390/medsci14050550","DOIUrl":"10.3390/medsci14050550","url":null,"abstract":"<p><p><b>Background/Objective:</b> Hyperoncotic albumin (20%) has been proposed for sepsis; however, the randomized evidence is inconclusive, and the 2026 Surviving Sepsis Campaign guidelines now suggest crystalloids alone while permitting albumin on a case-by-case basis. We updated the evidence, restricting the intervention to hyperoncotic albumin (≥20%) and the comparator exclusively to crystalloids, and examined whether the benefit was confined to septic shock. <b>Methods:</b> We searched PubMed, EMBASE, and Cochrane CENTRAL (March 2024-March 2026), supplementing a previously published meta-analysis. Randomized trials of hyperoncotic albumin versus crystalloids in adults with sepsis or septic shock reporting all-cause mortality were included. The primary outcome was mortality at the longest follow-up, pooled as risk ratios (RRs) using random-effects models. Given negligible heterogeneity, the estimate was reported under standard, Hartung-Knapp-Sidik-Jonkman (HKSJ), truncated-HKSJ, and fixed-effects methods, with a Bayesian sensitivity analysis. A pre-specified subgroup contrasted septic shock with sepsis without shock. This review was registered in PROSPERO (CRD420261334243). <b>Results:</b> Eight RCTs (<i>n</i> = 3707) provided the data; all administered 20% albumin. Overall, albumin was not robustly associated with reduced mortality (RR 0.94; I² = 0%), significant only under the pre-registered HKSJ correction (0.91-0.98) but null under the standard, truncated-HKSJ, and fixed-effects models (0.87-1.03, <i>p</i> = 0.17), identifying this as a low-heterogeneity artifact. In septic shock (k = 6), the effect was larger and consistent (RR 0.90, 0.82-0.99, <i>p</i> = 0.03), with no benefit in sepsis without shock (RR 1.10; interaction <i>p</i> = 0.08). The certainty was low (GRADE). <b>Conclusions:</b> In adults with sepsis, hyperoncotic albumin was not associated with a statistically significant reduction in all-cause mortality, and the certainty of evidence was low (GRADE). This is consistent with the 2026 Surviving Sepsis Campaign guidelines, which permit case-by-case use of albumin in this setting but do not recommend its routine use. Adequately powered randomized trials are required.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting MicroRNA-21 in Chronic Kidney Disease: Lessons from the Lademirsen Story.","authors":"Verica Stankovic Popovic, Aleksandar Sic, Selena Gajic, Dusan Vicentijevic, Ana Bontic, Jelena Pavlovic, Aleksandra Kezic, Marko Baralic","doi":"10.3390/medsci14050547","DOIUrl":"10.3390/medsci14050547","url":null,"abstract":"<p><p>MicroRNA-21 (miR-21) has long been regarded as one of the most promising molecular targets in chronic kidney disease (CKD) because of its consistent upregulation across diverse renal disorders and its involvement in fibrosis, inflammation, oxidative stress, and metabolic dysfunction. Strong preclinical evidence demonstrated that inhibition of miR-21 reduced kidney injury, preserved renal function, and improved survival in multiple experimental models, particularly Alport syndrome, leading to the clinical development of the antisense oligonucleotide lademirsen. However, despite a compelling biological rationale and encouraging animal data, the phase 2 HERA trial failed to demonstrate a clinically meaningful effect on the rate of kidney function decline, resulting in discontinuation of the program. This review examines the biological functions of miR-21 in CKD, summarizes the experimental and clinical evidence that supported its therapeutic development, and critically analyzes the factors that may explain the discrepancy between preclinical success and clinical failure. Particular attention is given to the distinction between disease-associated biomarkers and true therapeutic drivers, the limitations of animal models, disease heterogeneity, timing of intervention, and the complex regulatory networks underlying progressive kidney fibrosis. Rather than representing the end of miR-21 research, the experience with lademirsen provides valuable insights into the challenges of translating RNA-based therapies into clinical practice. Future therapeutic strategies will likely require earlier intervention, improved patient selection, robust biomarkers of target engagement, and combination approaches that address the multifactorial nature of CKD. The lessons learned from the lademirsen program may help guide the development of the next generation of RNA therapeutics for kidney disease.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Technostress and Insulin Resistance Risk: A Cross-Sectional Analysis of 104,175 Spanish Workers Using TyG, TyG-BMI, METS-IR, and SPISE Indices.","authors":"Marta González Rivas, Ángel Arturo López-González, Diego González Carrasco, Carla Busquets-Cortés, María Teófila Vicente-Herrero, José Ignacio Ramírez-Manent","doi":"10.3390/medsci14050545","DOIUrl":"10.3390/medsci14050545","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Technostress has emerged as a growing occupational health concern in increasingly digitalized workplaces. Although its psychological consequences have been extensively investigated, little is known about its potential association with metabolic health and insulin resistance. This study aimed to evaluate the relationship between technostress and insulin resistance risk using four validated surrogate markers in a large cohort of Spanish workers. &lt;b&gt;Methods:&lt;/b&gt; A cross-sectional study was conducted among 104,175 Spanish workers who underwent routine occupational health assessments. Technostress was assessed using a 15-item questionnaire covering five technostress dimensions and was analyzed using four operational categories (low, moderate, high, and very high). Insulin resistance risk was assessed using the triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), the metabolic score for insulin resistance (METS-IR), and the single-point insulin sensitivity estimator (SPISE). Sociodemographic characteristics, lifestyle habits, anthropometric measurements, and biochemical parameters were also recorded. Modified Poisson regression with robust variance estimation was used to estimate crude and adjusted prevalence ratios (PRs) for increased insulin resistance risk according to technostress level. Firth penalized logistic regression was additionally performed as a sensitivity analysis to address sparse-data bias and separation. &lt;b&gt;Results:&lt;/b&gt; Higher technostress levels were associated with progressively less favorable anthropometric and metabolic profiles. The prevalence of increased insulin resistance risk rose significantly across technostress categories for all markers evaluated (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). For TyG, prevalence increased from 3.8% in the low technostress group to 54.3% in the very high technostress group. Corresponding increases were observed for TyG-BMI (0.2% to 78.2%), METS-IR (0.0% to 45.2%), and elevated SPISE-IR values (0.0% to 57.5%). After adjustment for age, sex, educational level, physical activity, adherence to the Mediterranean diet, and smoking status, higher technostress remained associated with a higher prevalence of increased insulin resistance risk. A clear graded cross-sectional pattern was observed, with the strongest associations found among workers reporting very high technostress. &lt;b&gt;Conclusions:&lt;/b&gt; Higher technostress was associated with a higher prevalence of increased insulin resistance risk according to TyG, the primary outcome, with a clear graded cross-sectional pattern across technostress categories. Associations were also observed for the secondary BMI-containing indices (TyG-BMI, METS-IR, and SPISE-IR), which should be interpreted as complementary rather than independent evidence. Given the cross-sectional design and the pronounced clustering of technostress with adiposity and lifestyle characteristics, residual confounding cannot be excluded and causal inference is not possible.&lt;","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}