Cts-Clinical and Translational Science最新文献

{"title":"Modulation of Inflammatory Indices by Omega-3 Fatty Acids Supplementation in Hemodialysis: A Clinical Trial Approach.","authors":"Hanieh Shafaei Kachaei, Khadijeh Abbasi Mobarakrh, Fatemeh Azaryan, Mahdieh Torkaman, Seyed Ali Askarpour, Asma Rajabi Harsini, Fatemeh Sadat Fahimzad, Mahdi Mousavi Mele, Marziyeh Hoseinzadeh Liavoli, Neda Masoomi Golujeh, Sanaz Ataie Kashki, Sara Khoshdooz, Saeid Doaei, Masoud Khosravi, Maryam Gholamalizadeh","doi":"10.1111/cts.70531","DOIUrl":"https://doi.org/10.1111/cts.70531","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is closely associated with systemic inflammation. This randomized controlled trial aimed to evaluate the effects of omega-3 fatty acids supplementation on inflammatory markers in patients with CKD undergoing hemodialysis. Eligible participants with CKD receiving hemodialysis were randomly assigned to either an intervention group or a control group. The intervention group received three capsules of omega-3 fatty acids (3 g/day) for two months, while the control group received placebo capsules containing medium-chain triglyceride (MCT) oil. Inflammatory markers, including C-reactive protein (CRP) and interleukin-6 (IL-6), were measured both before and after the interventions. The results showed that CRP levels increased from 9.86 ± 12.64 to 11.46 ± 22.23 mg/L in the intervention group and from 5.24 ± 9.01 to 5.61 ± 7.93 mg/L in the control group (p = 0.11). Similarly, IL-6 levels increased from 17.84 ± 14.08 to 81.82 ± 66.22 pg/mL in the intervention group and from 14.96 ± 18.41 to 56.73 ± 115.45 pg/mL in the control group (p = 0.53). No statistically significant group differences were observed after adjusting for confounders such as age, sex, body mass index (BMI), smoking, dietary intake, and pre-existing diseases. The study findings showed that a two-month intake of omega-3 fatty acids supplements did not have a significant impact on reducing the levels of inflammatory markers in CKD patients undergoing hemodialysis. Larger trials with longer durations are warranted. Study Highlights What is the Current Knowledge on the Topic? ○ Omega-3 fatty acids have anti-inflammatory properties and are reported to be potentially beneficial in reducing inflammation associated with CKD, but the evidence regarding the effectiveness of omega-3 supplements in reducing inflammatory markers in this population remains inconsistent. What Question did this Study Address? ○ What is the effect of omega-3 fatty acids supplementation for 2 months on CRP and IL-6 levels in patients with CKD undergoing hemodialysis? What Does This Study Add to Our Knowledge? ○ Contrary to previous studies, this study found that omega-3 fatty acids supplementation did not significantly reduce CRP or IL-6 levels compared with placebo over 2 months and that short-term supplementation is not sufficient to reduce systemic inflammation in hemodialysis patients. How Might this Change Clinical Pharmacology or Translational Science? ○ These findings suggest that short-term omega-3 fatty acids supplementation may not be sufficient in reducing inflammatory markers in CKD patients undergoing hemodialysis and highlight the need for larger-scale clinical trials with different doses and longer durations to investigate nutritional or pharmacological strategies.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"19 5","pages":"e70531"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147788121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supply and Demand in the Mathematics of Rare Disease Drug Development: Why Choosing the Right Model Is Crucial.","authors":"Marshall L Summar, Janet Woodcock","doi":"10.1111/cts.70551","DOIUrl":"https://doi.org/10.1111/cts.70551","url":null,"abstract":"<p><p>Clinical trials for rare diseases face a fundamental mathematical challenge that conventional randomized controlled trial (RCT) designs cannot overcome. With approximately 95% of the estimated 10,000-16,000 rare diseases lacking approved therapies, and drug development programs failing at rates exceeding 75% in non-oncology indications, the field confronts a stark reality: Traditional trial designs demand patient numbers that simply do not exist. This perspective article examines the critical mismatch between the statistical requirements of different trial designs (the \"demand\") and the actual patient populations available for study (the \"supply\"). We demonstrate mathematically that alternative trial designs-particularly patient-as-own-control and natural history comparator models-can reduce required sample sizes by 5- to 20-fold while maintaining statistical rigor. We further point out that a substantial proportion of rare disease trial failures stem not from therapeutic inefficacy but from recruitment and retention challenges inherent to underpowered RCT designs-challenges that are directly addressable through appropriately matched trial design. Given that most rare disease development programs receive only one opportunity to demonstrate efficacy, the continued application of inappropriate statistical models represents both a scientific failure and an ethical and economic challenge to the rare disease community. We propose that regulatory agencies formalize acceptance of alternative trial designs for rare diseases, supported by explicit mathematical frameworks that transparently account for genetic heterogeneity, pediatric populations, and the statistical efficiency gains achieved through within-subject correlation.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"19 5","pages":"e70551"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing IBD Management: A Literature Review on the Role of Non-Invasive Blood-Based Biomarkers in Predicting and Assessing Pharmacodynamic Response to Treatment.","authors":"Mohamed Hassanein, Li Xi, Rathi D Ryan, Zhan Harold Ye, Nessy Tania, Yamato Sano, Joshua Varghese, Diogo Branquinho, Anna Sapone","doi":"10.1111/cts.70562","DOIUrl":"https://doi.org/10.1111/cts.70562","url":null,"abstract":"<p><p>Reliable biomarkers that enable noninvasive, longitudinal assessment of disease activity and therapeutic response remain a major unmet need in inflammatory bowel disease (IBD). While colonic biopsies are the gold standard for evaluating mucosal inflammation, their invasive nature and limited spatial and temporal resolution constrain their utility in routine monitoring and clinical trials. Blood-based biomarkers offer a complementary approach, providing minimally invasive, readily accessible measures that can be repeatedly sampled over time. Emerging blood-derived signatures, including gene expression profiles and circulating molecular inflammation scores, capture systemic immune activity and have shown promise in predicting treatment response, disease flares, and pharmacodynamic (PD) effects of therapies. Recent advances utilizing multi-omics technologies and machine learning methods have further improved the predictive performance of blood-based biomarkers, particularly in the context of biologic therapies such as anti-tumor necrosis factor agents. Despite these advances and growing promises, challenges related to validation, standardization, and clinical integration persist. This review focused on recent advances in blood-based biomarkers for IBD, with an emphasis on their use in predicting treatment response and assessing pharmacodynamic effects in clinical trials.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"19 5","pages":"e70562"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promising Drugs Require Proper Testing.","authors":"Jean-Jacques Parienti","doi":"10.1111/cts.70568","DOIUrl":"https://doi.org/10.1111/cts.70568","url":null,"abstract":"","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"19 5","pages":"e70568"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147788111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elranatamab: Mechanism of Action, Clinical, and Translational Science.","authors":"Mohamed Elmeliegy, Andrea Viqueira, Erik Vandendries, Pooneh Soltantabar, Hoi-Kei Lon, Kamrine Poels, Blerta Shtylla, Donald Irby, Kristin Bompiani-Myers, Thomas O'Brien, Jennifer Hibma","doi":"10.1111/cts.70554","DOIUrl":"10.1111/cts.70554","url":null,"abstract":"<p><p>Elranatamab (ELREXFIO) is a humanized bispecific antibody approved for patients with relapsed/refractory multiple myeloma (RRMM). Elranatamab engages CD3 on T cells and B-cell maturation antigen (BCMA) on myeloma cells to induce T cell-mediated myeloma cell cytolysis. The recommended subcutaneous elranatamab dosing consists of fixed step-up doses of 12 mg on day 1 and 32 mg on day 4 to mitigate the incidence and severity of cytokine release syndrome (CRS), followed by the full fixed dose of 76 mg once weekly (QW) from weeks 2 to 24. In responders, 76 mg QW is reduced to every 2 weeks (Q2W) after ≥ 6 QW cycles and to every 4 weeks after ≥ 6 Q2W cycles. The full dose (76 mg QW) results in a higher probability of achieving an objective response versus lower doses without worsening the safety profile. This regimen was based on the collective safety, efficacy, pharmacokinetic, and pharmacodynamic data from MagnetisMM-1, -2, -3, and -9. In the pivotal MagnetisMM-3 study, in patients with BCMA-naive RRMM, elranatamab resulted in a 61.0% overall response rate; 37.4% achieved complete response or stringent complete response. Median duration of response was not yet reached; the probability of maintaining response at 30 months was 61.0%. Median progression-free and overall survival were 17.2 and 24.6 months, respectively. In MagnetisMM-3 patients, common adverse events (≥ 40%; any grade/grade 3/4) included infections (71.7%/38.5%), CRS (58.8%/0.5%), anemia (53.5%/42.2%), neutropenia (46.0%/44.4%), and diarrhea (42.8%/3.2%). Elranatamab demonstrated deep and durable responses, a manageable safety profile, and low-grade CRS with predictable timing. Elranatamab is being further evaluated as monotherapy or combination therapy in earlier treatment lines.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"19 5","pages":"e70554"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feed-Forward Deep Neural Networks Predict Substrate-Specific Effects of Transporter Variants to Explain Drug Response Variability.","authors":"Yoomi Park, Yitian Zhou, Ming Xiao, Anne T Nies, Volker M Lauschke","doi":"10.1111/cts.70592","DOIUrl":"https://doi.org/10.1111/cts.70592","url":null,"abstract":"<p><p>Genetic variants in drug transporter genes shape the interindividual variability in drug response. However, their functional interpretation has remained limited due to the substrate dependence of variant effects. Existing predictors are substrate-agnostic and cannot capture how a single amino acid change differentially affects transport across drugs. Here, we present the substrate-specific effect predictor (SSEP), the first model to predict transporter variant effects in a substrate-dependent manner. SSEP integrates curated in vitro uptake assays with deep mutational scanning data, leveraging multiscale features extracted from modeled variant-substrate complexes. Based on a feed-forward deep neural network architecture, SSEP provides quantitative, substrate-specific activity scores that correlate with experimental uptake data (Spearman's ρ = 0.64) across multiple transporter families (OCT1, MATE, CNT, and OATP) and substrate classes (biguanides, tetraethylammonium, selective serotonin agonists, sympathomimetics and opiates). In benchmarking analyses, SSEP showed higher concordance (Kruskal-Wallis p = 1.11 × 10^-41) with experimental uptake than commonly used substrate-agnostic predictors. Application of SSEP on UK Biobank data revealed that OCT1 (SLC22A1) variant burden weighted by metformin-specific SSEP scores was significantly associated with maintenance dose (β = 30 mg/day per unit increase in predicted functional burden; p = 0.033), whereas substrate-agnostic weights showed no association (p = 0.78). Together, these results show that SSEP enables quantitative, drug-specific prediction of transporter variant effects, thereby improving the identification of clinically relevant transporter variants in population-scale data.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"19 5","pages":"e70592"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: \"Promising Drugs Require Proper Testing\": Let's Not Confuse Pharmacodynamics With Clinical Efficacy.","authors":"Inès Ben Ghezala, Marc Bardou","doi":"10.1111/cts.70567","DOIUrl":"10.1111/cts.70567","url":null,"abstract":"","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"19 5","pages":"e70567"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147788114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Urinary Exosomal microRNAs Associated With Subclinical Acute T-Cell-Mediated Rejection in Kidney Transplant Recipients.","authors":"Soichiro Tajima, Miori Ono, Yuto Kawazoe, Hiroshi Noguchi, Tomohiro Shigematsu, Takashi Ogino, Shoji Nakamura, Takahiro Nakamura, Keizo Kaku, Takeshi Hirota, Ichiro Ieiri, Mayako Uchida","doi":"10.1111/cts.70572","DOIUrl":"https://doi.org/10.1111/cts.70572","url":null,"abstract":"<p><p>This study aimed to evaluate the diagnostic utility of urinary exosomal microRNAs (miRNAs) in subclinical rejection following kidney transplantation by comparing miRNA expression profiles in urinary exosomes between patients with no evidence of rejection and patients with subclinical T-cell-mediated rejection (sc-TCMR), as confirmed by protocol kidney biopsies performed 3 months after transplantation. To elucidate these differences, a comprehensive miRNA expression analysis was conducted using microarray profiling. Consequently, 38 urinary exosomal miRNAs were detected, among which three were upregulated and five were downregulated in patients with sc-TCMR. To further evaluate the diagnostic value of these miRNAs, quantitative real-time PCR analysis was performed using urinary exosomes collected at the time of protocol biopsy from 70 kidney transplant recipients. This analysis confirmed that miR-5100 and miR-7975 were differentially expressed in patients with sc-TCMR at the time of the 12-month protocol biopsy. Importantly, miR-7975 demonstrated the ability to distinguish among three groups-no evidence of rejection, borderline changes, and sc-TCMR-with high diagnostic accuracy, as indicated by an area under the receiver operating characteristic curve of 0.825. In vitro, exposure of proximal tubular epithelial cells to transforming growth factor-beta 1 resulted in a reduction in miR-7975 expression within urinary exosomes, implicating these cells as a potential source of exosomal miR-7975. Collectively, these findings suggest that urinary exosomal miR-7975 may serve as a promising noninvasive biomarker for diagnosing and monitoring sc-TCMR, offering valuable insights for future research and clinical applications.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"19 5","pages":"e70572"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147823137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological Considerations for AI-Powered Chatbots in Oral Cancer Awareness: Stakeholder Diversity, Instrument Transparency, and Safety Auditing.","authors":"Carlos Fernando Mourão, Luiz Eduardo Juliasse, Rodrigo Dos Santos Pereira","doi":"10.1111/cts.70566","DOIUrl":"https://doi.org/10.1111/cts.70566","url":null,"abstract":"","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"19 5","pages":"e70566"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147788138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1 Multiple-Dose, Open-Label, Pharmacokinetic Study of Nirmatrelvir/Ritonavir in Healthy Lactating Women.","authors":"Jacqueline Gerhart, Narayan Cheruvu, Kathleen Pelletier, Kyle Matschke, Haihong Shi, Josué Kunjom Mfopou, Jennifer Hammond, Ravi Shankar P Singh","doi":"10.1111/cts.70552","DOIUrl":"https://doi.org/10.1111/cts.70552","url":null,"abstract":"<p><p>In accordance with the Centers for Disease Control and Prevention recommendations, pregnant women and those with a recent pregnancy (i.e., lactating) are considered at high risk of developing severe COVID-19 and qualify for treatment with nirmatrelvir/ritonavir. However, clinical data are lacking in this population because breastfeeding women were excluded from the nirmatrelvir/ritonavir clinical development program and pivotal Phase 2/3 studies. We report findings from a prospective Phase 1 trial (NCT05441215) designed and conducted in accordance with the US Food and Drug Administration guidance on clinical lactation studies that evaluated the pharmacokinetics and safety of multiple oral doses of nirmatrelvir/ritonavir in healthy lactating women using paired breast milk and maternal plasma data. Eight participants were enrolled and completed the study. After administration of nirmatrelvir/ritonavir 300 mg/100 mg to steady-state, the concentrations of both nirmatrelvir and ritonavir in breast milk were consistently lower than maternal plasma. Based on standard infant breast milk consumption (150 mL/kg/day), the mean absolute daily doses of nirmatrelvir and ritonavir that an infant would receive were 0.1595 and 0.0057 mg/kg/day, respectively, representing 1.8% and 0.19% of the bodyweight-normalized maternal dose. All treatment-emergent adverse events were mild to moderate in severity. No deaths, serious or severe adverse events, dose reductions, interruptions, or discontinuations were reported. In conclusion, nirmatrelvir/ritonavir 300 mg/100 mg was safe and well tolerated in healthy lactating women, with infant exposure considered to be low and well within the acceptability criteria of < 10% of the body weight-normalized maternal dose.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"19 5","pages":"e70552"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}