medRxiv : the preprint server for health sciences最新文献

{"title":"Association of prior tuberculosis with altered cardiometabolic profiles of people with HIV: A comparative cross-sectional study in Uganda.","authors":"Joseph Baruch Baluku, Diana Karungi, Brenda Namanda, Sharon Namiiro, Shamim Katusabe, Angut Mary Madalen, Martin Nabwana, Ronald Olum, Felix Bongomin, Edwin Nuwagira, Grace Kansiime, Christian Kraef, Megan Shaughnessy, Joshua Rhein, David Meya","doi":"10.1101/2025.03.19.25324234","DOIUrl":"https://doi.org/10.1101/2025.03.19.25324234","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease (CVD) is the leading cause of mortality among people with HIV (PWH), but the influence of co-infections like tuberculosis (TB) on CVD risk remains underexplored. We aimed to compare cardiometabolic profiles of PWH with and without prior TB to determine if prior TB is associated with distinct cardiometabolic profiles.</p><p><strong>Methods: </strong>We conducted a comparative, cross-sectional study at a tertiary hospital in Kampala, Uganda. Participants were randomly sampled PWH aged ≥18 years on antiretroviral therapy. Specifically, we enrolled PWH with and without prior active TB (ratio of 1:1). Anthropometric measurements, blood pressure, fasting blood glucose (FBG), lipid profile, and glycated hemoglobin were assessed.</p><p><strong>Results: </strong>A total of 396 participants were enrolled (196 TB survivors and 200 controls). TB survivors had higher median FBG (5.5 vs. 5.1 mmol/l, p<0.001) and a higher prevalence of DM (17.9% vs. 9.5%, p=0.015). However, they had lower body mass index (23.0 vs. 25.1 kg/m², p<0.001) and waist circumference (81.0 vs. 84.0 cm, p=0.026). TB survivors had higher HDL-c levels (1.0 vs. 0.8 mmol/l, p<0.001), lower LDL-c levels (2.7 vs. 3.1 mmol/l, p<0.001) and lower prevalence of dyslipidemia (81.7% vs. 96.5%, p<0.001). Prior TB was independently associated with higher prevalence of elevated FBG (adjusted prevalence ratio (aPR) 1.79, 95% CI 1.10-2.92) and DM (aPR 2.34, 95% CI 1.11-4.94), but decreased risk of obesity (aPR 0.42, 95% CI 0.20-0.88).</p><p><strong>Conclusion: </strong>TB survivors with HIV exhibit a higher risk of DM but lower risk of obesity compared to those without a history of TB, indicating a need for blood glucose monitoring among TB survivors.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757120","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":"Uptake and timing of viral load testing and frequency of viraemic episodes during pregnancy in South Africa.","authors":"Nelly Jinga, Karl-Günter Technau, Kate Clouse, Nkosinathi Ngcobo, Cornelius Nattey, Candice Hwang, Anna Grimsrud, Amy Wise, Nicola van Dongen, Thalia Ferreira, Maanda Mudau, Mhairi Maskew","doi":"10.1101/2025.03.19.25324178","DOIUrl":"https://doi.org/10.1101/2025.03.19.25324178","url":null,"abstract":"<p><strong>Background: </strong>Repeated monitoring of viral load (VL) among pregnant women living with HIV (WLWH) is critical in vertical transmission prevention. For women who are newly diagnosed with HIV during pregnancy, a subsequent VL is recommended three months after ART initiation, and for all women living with HIV, follow-up VL is required every six months throughout pregnancy and breastfeeding [2]. Here, we describe the uptake and timing of VL testing and frequency and distribution of viraemic episodes during pregnancy.</p><p><strong>Methods: </strong>We linked prospective cohort data from WLWH whose infants were born at Rahima Moosa Mother and Child Hospital (RMMCH) in Johannesburg, South Africa (2013-2018) to laboratory data from the National Health Laboratory Services national HIV cohort. We report the uptake and timing of VL testing, and frequency of viremia and viral suppression. We also explore factors associated with having at least one or more VL test.</p><p><strong>Results: </strong>Data from 4,064 women with known dates of entry into antenatal care and delivery during the study period were analysed. Overall, less than half (46%) completed VL testing during pregnancy. Most VL were conducted during the third trimester (67%). Only 5% (n=100) were during the first trimester and 11% within 7 days of delivery. Three-quarters of tests during pregnancy indicated viral suppression (VL <400 copies/mL), 7% viraemic (VL 400-1000 copies/mL), and 19% high grade viraemia (VL >1000 copies/mL). We found that being older (≥35) and being engaged in HIV care prior to pregnancy were significantly associated with VL testing during pregnancy.</p><p><strong>Conclusion: </strong>With less than half of pregnant women living with HIV in this study having a VL measure during their pregnancy, and VL testing occurring late in pregnancy, this study highlights critical gaps in providing quality HIV care to women and prevention of vertical transmission.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757255","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":"Unsupervised Ensemble Learning for Efficient Integration of Pre-trained Polygenic Risk Scores.","authors":"Chenyin Gao, Justin D Tubbs, Yi Han, Min Guo, Sijia Li, Erica Ma, Dailin Luo, Jordan W Smoller, Phil H Lee, Rui Duan","doi":"10.1101/2025.01.06.25320058","DOIUrl":"10.1101/2025.01.06.25320058","url":null,"abstract":"<p><p>The growing availability of pre-trained polygenic risk score (PRS) models has enabled their integration into real-world applications, reducing the need for extensive data labeling, training, and calibration. However, selecting the most suitable PRS model for a specific target population remains challenging, due to issues such as limited transferability, data heterogeneity, and the scarcity of observed phenotype in real-world settings. Ensemble learning offers a promising avenue to enhance the predictive accuracy of genetic risk assessments, but most existing methods often rely on observed phenotype data or additional genome-wide association studies (GWAS) from the target population to optimize ensemble weights, limiting their utility in real-time implementation. Here, we present the UN supervised en Semble PRS ( <i>UNSemblePRS</i> ), an unsupervised ensemble learning framework, that combines pre-trained PRS models without requiring phenotype data or summaries from the target population. Unlike traditional supervised approaches, UNSemblePRS aggregates models based on prediction concordance across a curated subset of candidate PRS models. We evaluated UNSemblePRS using both continuous and binary traits in the All of Us database, demonstrating its scalability and robust performance across diverse populations. These results underscore UNSemblePRS as an accessible tool for integrating PRS models into real-world contexts, offering broad applicability as the availability of PRS models continues to expand.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019498","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":"Leveraging Unstructured Data in Electronic Health Records to Detect Adverse Events from Pediatric Drug Use - A Scoping Review.","authors":"Su Golder, Karen O'Connor, Guillermo Lopez-Garcia, Nicholas Tatonetti, Graciela Gonzalez-Hernandez","doi":"10.1101/2025.03.20.25324320","DOIUrl":"https://doi.org/10.1101/2025.03.20.25324320","url":null,"abstract":"<p><p>Adverse drug events (ADEs) in pediatric populations pose significant public health challenges, yet research on their detection and monitoring remains limited. This scoping review evaluates the use of unstructured data from electronic health records (EHRs) to identify ADEs in children. We searched six databases, including MEDLINE, Embase and IEEE Xplore, in September 2024. From 984 records, only nine studies met our inclusion criteria, indicating a significant gap in research towards identify ADEs in children. We found that unstructured data in EHRs can indeed be of value and enhance pediatric pharmacovigilance, although its use has been so far very limited. Traditional Natural Language Processing (NLP) methods have been employed to extract ADEs, but the approaches utilized face challenges in generalizability and context interpretation. These challenges could be addressed with recent advances in transformer-based models and large language models (LLMs), unlocking the use of EHR data at scale for pediatric pharmacovigilance.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757107","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":"A mechanistic neural network model predicts both potency and toxicity of antimicrobial combination therapies.","authors":"Harkirat Singh Arora, Katherine Lev, Aaron Robida, Ramraj Velmurugan, Sriram Chandrasekaran","doi":"10.1101/2025.03.19.25324270","DOIUrl":"https://doi.org/10.1101/2025.03.19.25324270","url":null,"abstract":"<p><p>Antimicrobial resistance poses a major global threat due to the diminishing efficacy of current treatments and limited new therapies. Combination therapy with existing drugs offers a promising solution, yet current empirical methods often lead to suboptimal efficacy and inadvertent toxicity. The high cost of experimentally testing numerous combinations underscores the need for data-driven methods to streamline treatment design. We introduce CALMA, an approach that predicts the potency and toxicity of multi-drug combinations in <i>Escherichia coli</i> and <i>Mycobacterium tuberculosis</i> . CALMA identified synergistic antimicrobial combinations involving vancomycin and isoniazid that were antagonistic for toxicity, which were validated using <i>in vitro</i> cell viability assays in human cell lines and through mining of patient health records that showed reduced side effects in patients taking combinations identified by CALMA. By combining mechanistic modelling with deep learning, CALMA improves the interpretability of neural networks, identifies key pathways influencing drug interactions, and prioritizes combinations with enhanced potency and reduced toxicity.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757117","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":"Plant based enteral nutrition outperforms artificial nutrition in mitigating consequences of antibiotic-induced dysbiosis in mice and humans.","authors":"Mona Chatrizeh, Jianmin Tian, Matthew Rogers, Firuz Feturi, Guojun Wu, Brian Firek, Roman Nikonov, Lauren Cass, Alexandra Sheppeck, Rafael G Ramos-Jiménez, Lavnish Ohja, Ali Caroll, Mathew Henkel, Justin Azar, Rajesh K Aneja, Brian Campfield, Dennis Simon, Michael J Morowitz","doi":"10.1101/2025.03.19.25323813","DOIUrl":"https://doi.org/10.1101/2025.03.19.25323813","url":null,"abstract":"<p><p>Malnutrition, gut inflammation, and antibiotic induced dysbiosis (AID) are omnipresent risk factors for poor clinical outcomes among critically ill patients. We previously showed that commercially available plant-based enteral nutrition (PBEN) preserves a commensal microbiome when compared to commonly used forms of commercially available artificial enteral nutrition (AEN). This study reveals that PBEN is superior to artificial enteral nutrition (AEN) in recovering from antibiotic-induced dysbiosis (AID) in mice and humans. PBEN effectively mitigates anemia, leukopenia, restores naïve lymphocyte populations, and reduces bone marrow myeloid cell expansion. Animals randomized to PBEN also fared better in response to infectious challenges after antibiotics. A pilot clinical study validated these findings, showing increased gut commensals, reduced pathogens, and improved leukocyte balance in critically ill patients receiving PBEN compared to AEN. These results suggest PBEN offers a practical dietary approach to mitigate antibiotic-associated complications and improve clinical outcomes among hospitalized patients requiring supplemental nutrition.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756928","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":"Benchmarking pathology foundation models for non-neoplastic pathology in the placenta.","authors":"Zehao Peng, Marina A Ayad, Yaxing Jing, Teresa Chou, Lee A D Cooper, Jeffery A Goldstein","doi":"10.1101/2025.03.19.25324282","DOIUrl":"https://doi.org/10.1101/2025.03.19.25324282","url":null,"abstract":"<p><p>Machine learning (ML) applications within diagnostic histopathology have been extremely successful. While many successful models have been built using general-purpose models trained largely on everyday objects, there is a recent trend toward pathology-specific foundation models, trained using histopathology images. Pathology foundation models show strong performance on cancer detection and subtyping, grading, and predicting molecular diagnoses. However, we have noticed lacunae in the testing of foundation models. Nearly all the benchmarks used to test them are focused on cancer. Neoplasia is an important pathologic mechanism and key concern in much of clinical pathology, but it represents one of many pathologic bases of disease. Non-neoplastic pathology dominates findings in the placenta, a critical organ in human development, as well as a specimen commonly encountered in clinical practice. Very little to none of the data used in training pathology foundation models is placenta. Thus, placental pathology is doubly out of distribution, representing a useful challenge for foundation models. We developed benchmarks for estimation of gestational age, classifying normal tissue, identifying inflammation in the umbilical cord and membranes, and in classification of macroscopic lesions including villous infarction, intervillous thrombus, and perivillous fibrin deposition. We tested 5 pathology foundation models and 4 non-pathology models for each benchmark in tasks including zero-shot K-nearest neighbor classification and regression, content-based image retrieval, supervised regression, and whole-slide attention-based multiple instance learning. In each task, the best performing model was a pathology foundation model. However, the gap between pathology and non-pathology models was diminished in tasks related to inflammation or those in which a supervised task was performed using model embeddings. Performance was comparable among pathology foundation models. Among non-pathology models, ResNet consistently performed worse, while models from the present decade showed better performance. Future work could examine the impact of incorporating placental data into foundation model training.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756883","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":"Loneliness in adults with cardiovascular disease and their social and emotional support needs: Implications for Hispanic adults from the 2023 Behavioral Risk Factor Surveillance System.","authors":"Derek S Falk, Esmeralda Melgoza, Alberto Cabrera, Christian E Vazquez","doi":"10.1101/2025.03.19.25324276","DOIUrl":"https://doi.org/10.1101/2025.03.19.25324276","url":null,"abstract":"<p><strong>Objectives: </strong>Loneliness and social isolation pose significant risks for an individual's physical, mental, and social health including higher incidence of cardiovascular disease (CVD), poorer patient reported outcomes, and earlier mortality compared to those not experiencing loneliness or social isolation. The objective of this study was to assess loneliness and social and emotional support among adults aged 18 years and older who have CVD in the US.</p><p><strong>Design: </strong>Using the 2023 Behavioral Risk Factor Surveillance System's social determinants and health equity module, we examined the distribution of US adults with CVD, compared the prevalence of CVD by Hispanic ethnicity, and conducted multivariable logistic regressions assessing the relationship of independent variables with loneliness and social and emotional support.</p><p><strong>Results: </strong>The proportion of adults with CVD who felt lonely sometimes, usually, and always was 44.6%. Hispanic adults who felt lonely (56.3% vs. 43.0%; P<0.0001) and did not receive needed social and emotional support (13.7% vs. 9.8%; P=0.0162) experienced a higher prevalence of CVD than their non-Hispanic adult counterparts who felt lonely and did not receive needed social and emotional support. Adults with CVD who reported rarely or never receiving needed social and emotional support (odds ratio [OR]: 1.42; confidence interval [CI]: 1.14-1.77) had 42% higher odds of feeling lonely, compared to adults who indicated receiving social and emotional support sometimes, usually, or always. Among Hispanic adults with CVD, widowed/divorced/separated adults (OR: 2.30; CI: 1.46-3.61), urban residents (OR: 2.14; CI: 1.05-4.36), and unemployed adults (OR: 3.26; CI: 1.93-5.51) had higher odds of feeling lonely compared to married, rural, and employed adults.</p><p><strong>Conclusion: </strong>This study demonstrates significant disparities in loneliness and social and emotional support in CVD among US adults, with Hispanics experiencing a disadvantage in both outcomes. Future studies should examine strategies to improve social connection for those experiencing disparities.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757130","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":"Reduced Penetrance is Common Among Predicted Loss-of-Function Variants and is Likely Driven by Residual Allelic Activity.","authors":"David R Blair, Neil Risch","doi":"10.1101/2024.09.23.24314008","DOIUrl":"10.1101/2024.09.23.24314008","url":null,"abstract":"<p><p>Loss-of-function genetic variants (LoFs) often result in severe phenotypes, including autosomal dominant diseases driven by haploinsufficiency. Due to low carrier frequencies, their penetrance is generally unknown but typically variable. Here, we investigate the penetrance of >6,000 predicted LoFs (pLoFs) linked to 91 haploinsufficient diseases using a cohort of ≈24,000 carriers with linked electronic health record data. We find evidence for widespread reduced penetrance, which persisted after accounting for variant annotation artifacts, missed diagnoses, and incomplete clinical data. We thus hypothesized that many pLoFs have incomplete penetrance, which may be driven by residual allelic activity. To test this, we trained machine learning models to predict pLoF penetrance using variant-specific genomic features that may correlate with incomplete loss-of-function. The models were predictive of pLoF penetrance across a range of diseases and variant types, including those with prior clinical evidence for pathogenicity. This suggests that many pLoFs have incomplete penetrance due to residual allelic activity, complicating disease prognostication in asymptomatic carriers.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484852","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":"Effects of Dulaglutide on Ectopic Fat Deposition in Chronic Kidney Disease (CKD): A Pilot and Feasibility Study (GLIMP).","authors":"Ragibe Gulsah Dilaver, Rengin Elsurer Afsar, Rachelle Crescenzi, Jorge Gamboa, Talat Alp Ikizler","doi":"10.1101/2025.03.19.25324266","DOIUrl":"https://doi.org/10.1101/2025.03.19.25324266","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with chronic kidney disease (CKD) often exhibit ectopic fat accumulation, including intermuscular adipose tissue (IMAT), which is associated with metabolic and muscular dysfunctions. This study aimed to evaluate the effects of dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on reducing IMAT and improving metabolic and physical functions in patients with CKD stage 3-4.</p><p><strong>Methods: </strong>Seven patients were recruited between April 2022 and November 2023. A 12-week dulaglutide (1.5 mg/wk) intervention was conducted with pre-and post-treatment assessments, including magnetic resonance imaging (MRI) for the IMAT evaluation and systemic physical performance battery test (SPPB) for physical performance evaluation. Their body mass indexes (BMI) were calculated and blood samples were analyzed for inflammatory and metabolic markers, including high sensitive C-reactive protein (Hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), glucose, insulin resistance (IR), total cholesterol, triglyceride, adiponectin, leptin, and leptin-adiponectin ratio (LAR) before and after treatment. Paired t-tests and Mann-Whitney U tests were used for statistical analysis, with significance set at p < 0.05.</p><p><strong>Results: </strong>Out of 58 assessed patients with CKD stage 3-4, 7 were enrolled, with 5 completing the full 12-week dulaglutide treatment. The total 7 people had a mean age of 59 years, mean BMI of 31.4 kg/m², and baseline eGFR of 31.7 mL/min/1.73m². IMAT decreased in 4 patients and increased in 3 patients, with no statistically significant changes overall (p = 0.69). The quadriceps muscle cross-sectional area (CSA) also showed no significant difference (p = 0.73). BMI and serum leptin levels significantly decreased after treatment (p < 0.05), while other inflammatory and metabolic markers, and physical performance scores showed no significant changes. No serious adverse events were reported.</p><p><strong>Conclusions: </strong>This study examined the effects of a 12-week dulaglutide treatment on IMAT accumulation in patients with CKD stage 3-4. While BMI significantly decreased, changes in IMAT were modest and not statistically significant, with potential but unproven clinical and metabolic benefits. Many metabolic and inflammatory markers improved, though not statistically significantly, and physical performance remained unchanged. Muscle CSA and function were maintained, which may alleviate concerns about potential GLP-1RA-induced muscle loss. Dulaglutide was well-tolerated, with minimal side effects. The small sample size and short duration highlight the need for further research.</p><p><strong>Trial registration: </strong>Name of the Registry : ClinicalTrials.gov Trial Registration Number : NCT05254418 Date of Registration : 2022-02-01.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757098","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}