Journal of Internal Medicine最新文献

{"title":"Regarding: Apixaban, edoxaban and rivaroxaban, but not dabigatran, are associated with higher mortality compared to vitamin K antagonists","authors":"Enrico Brunetti, Roberto Presta, Mario Bo","doi":"10.1111/joim.20044","DOIUrl":"10.1111/joim.20044","url":null,"abstract":"","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 1","pages":"117-118"},"PeriodicalIF":9.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma brain-derived tau correlates with cerebral infarct volume","authors":"Fernando Gonzalez-Ortiz,&nbsp;Lukas Holmegaard,&nbsp;Björn Andersson,&nbsp;Cecilia Brännmark,&nbsp;Christian Blomstrand,&nbsp;Henrik Zetterberg,&nbsp;Katarina Jood,&nbsp;Kaj Blennow,&nbsp;Christina Jern,&nbsp;Tara M. Stanne","doi":"10.1111/joim.20041","DOIUrl":"10.1111/joim.20041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A blood-based biomarker that accurately reflects neuronal injury in acute ischemic stroke could be an easily accessible and cost-effective complement to clinical and radiological evaluation. Here, we investigate whether plasma levels of the novel biomarker brain-derived tau (BD-tau) reflect cerebral infarct volumes and whether BD-tau can improve clinical outcome prediction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The present study included 713 consecutive cases from two different hospital-based cohorts, <i>the</i> <i>Sahlgrenska Academy Study on Ischemic Stroke</i> (<i>SAHLSIS</i>) and <i>SAHLSIS phase 2</i> (<i>SAHLSIS2</i>). Acute stroke severity was determined by the Scandinavian Stroke Scale converted to the National Institutes of Health stroke scale (NIHSS) in <i>SAHLSIS</i> and by the NIHSS in <i>SAHLSIS2</i>. All participants were assessed for functional outcome 3 months after stroke by the modified Rankin Scale, and 254 participants in <i>SAHLSIS</i> had quantitative neuroimaging available.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Plasma BD-tau concentrations and cerebral infarct volumes were highly correlated (<i>ρ</i> 0.72, <i>p</i> &lt; 0.001). BD-tau improved the prognostic accuracy of suffering an unfavorable outcome over age and stroke severity in the whole cohort. However, the gain in predictive power was dependent on stroke severity and infarct location. The largest improvement was observed for mild ischemic strokes (NIHSS &lt;5; area under the curve [AUC] = 0.73 for age + NIHSS versus AUC = 0.84 with addition of BD-tau; DeLong <i>p</i> 0.02), posterior circulation stroke (AUC = 0.75 vs. AUC = 0.84; DeLong <i>p</i> 0.06) and more specifically for infarcts in the brainstem/cerebellum (AUC = 0.74 vs. 0.87; DeLong <i>p</i> 0.009).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Plasma BD-tau can provide information on the extent of acute neuronal damage in ischemic stroke and adds prognostic value for outcome, especially for mild and posterior circulation strokes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 2","pages":"173-185"},"PeriodicalIF":9.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Race and ethnicity dynamics in survival to 100 years in the United States","authors":"Nadine Ouellette,&nbsp;Thomas Perls","doi":"10.1111/joim.20031","DOIUrl":"10.1111/joim.20031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>After age 85, the U.S. non-Hispanic Black population mortality rate becomes less than that of the White population (called the Black–White mortality crossover). It is not known how this survival advantage compares to Asian and Hispanic groups, and whether differences persist to age 100+ years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The U.S. period life table data were extracted to obtain life expectancy at birth and at ages 70, 85, and 100 years according to year, sex, and race and ethnicity. Age-specific death rates and adult modal age at death were calculated. We computed period probabilities of survival to age 100, from ages 70, 80, and 90. Pseudo-birth cohort calculations were undertaken to enable comparison with period-based results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 2019, the Black–White mortality crossover occurred at 86–88 years and persisted at ages 100 and 100+. Life expectancies at age 100 for non-Hispanic Black, Hispanic, and Asian populations were similar and were significantly greater than the non-Hispanic White population. From 2006 to 2019, the probability of survival from 70 and 80 years to age 100 was highest for the Hispanic population, followed by non-Hispanic Black and then non-Hispanic White populations. Probability of survival from age 90 to 100 years was similar for all but the non-Hispanic White population, which had a comparatively lower probability of survival. When Asian population data became available in 2019, this population had the highest probability of survival to age 100, starting from ages 70, 80, and 90 years. Pseudo-cohort results displayed patterns consistent with those observed over calendar years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Race- and ethnicity-based variation in mortality between ages 85 and 100+ years suggests differences in environmental and possibly genetic influences upon risk for exceptional longevity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 1","pages":"2-21"},"PeriodicalIF":9.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wild-type transthyretin cardiac amyloidosis and aortic stenosis: Can carpal tunnel syndrome help distinguish the chicken from the egg?","authors":"Marc-Antoine Delbarre,&nbsp;Gagan Deep Chadha,&nbsp;Mohamed-Salah Annabi,&nbsp;Refaat Nouri,&nbsp;Amira Zaroui,&nbsp;Paul Blanc-Durand,&nbsp;Diana Rasolonirina,&nbsp;Mounira Kharoubi,&nbsp;Ancuta Bejan,&nbsp;Arnaut Galat,&nbsp;Silvia Oghina,&nbsp;Philippe Pibarot,&nbsp;Christophe Tribouilloy,&nbsp;Thibaud Damy","doi":"10.1111/joim.20042","DOIUrl":"10.1111/joim.20042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The frequent association between transthyretin wild-type (TTRwt) cardiac amyloidosis (CA) and aortic stenosis (AS) suggests a bidirectional relationship: TTRwt-CA could induce AS and vice versa. Systemic manifestations may highlight this interaction: systemic amyloidogenesis would lead to systemic symptoms, CA, and AS, whereas the myocardial stresses induced by degenerative AS might promote local amyloidogenesis without systemic symptoms. Carpal tunnel syndrome (CTS) is the most frequently reported extracardiac symptom. Through a comparison of TTRwt-CA patients with and without CTS, we sought to determine whether CTS serves as a reliable indicator of systemic involvement and its impact on cardiac and valvular characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>A total of 411 consecutive patients with TTRwt-CA were included. CTS, present in 70.3%, was associated with a younger age (80 vs. 84 years, <i>p</i> &lt; 0.001), more extracardiac symptoms, and advanced CA, with greater cardiac remodeling and a higher heart-to-mediastinum ratio (1.63 vs. 1.54; <i>p</i> = 0.012) compared to patients without CTS. AS was present in 21% and 31% of patients with and without CTS, respectively (<i>p</i> = 0.024). Except for AS, these associations remained significant after adjusting for confounding factors. In severe AS, patients with CTS exclusively exhibited low-flow low-gradient (LFLG) AS and less severe class of aortic valvular calcium score (5.6% vs. 60%; <i>p</i> = 0.006) compared to those without CTS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that CTS may delineate two phenotypes in TTRwt-CA: a systemic phenotype associated with advanced CA and poorly calcified LFLG AS, and a cardiac phenotype characterized by less severe CA and a mixed pattern of highly calcified AS, suggesting disparate pathophysiologies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 2","pages":"186-200"},"PeriodicalIF":9.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat-induced kidney disease: Understanding the impact","authors":"Carl-Gustaf Elinder","doi":"10.1111/joim.20037","DOIUrl":"10.1111/joim.20037","url":null,"abstract":"<p>Research on Mesoamerican Nephropathy, chronic kidney disease of unknown cause and chronic kidney disease of nontraditional cause has been going on for more than 20 years. Thousands of manual workers, especially in agriculture, are affected. The disease has been reported in different countries and regions, not only from heat-stressed sugarcane cutters in Central America but also from other occupational groups with strenuous work in hot environments. The cause of this disease is still debated. A multitude of causative factors have been suggested, including agrochemicals, water quality, infections, and heavy metals. The evidence that heat stress is the major cause of kidney disease is convincing, whereas the support for alternative causes is weak. Associations between exposure and kidney damage are strong, consistent, and specific, occur after acute and chronic exposure, display dose-effect and dose–response relationships, are plausible, and coherent. Improving working conditions by providing hydration, rest, and shade to heat-stress-exposed workers is beneficial. Continued global warming will increase the number of people at risk for dangerous heat exposure and kidney disease.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 1","pages":"101-112"},"PeriodicalIF":9.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal changes in regional fat and muscle composition and cardiometabolic biomarkers over 5 years of hormone therapy in transgender individuals","authors":"Tommy R. Lundberg,&nbsp;Andrea Tryfonos,&nbsp;Lisa M.J. Eriksson,&nbsp;Helene Rundqvist,&nbsp;Eric Rullman,&nbsp;Mats Holmberg,&nbsp;Salwan Maqdasy,&nbsp;Jennifer Linge,&nbsp;Olof Dahlqvist Leinhard,&nbsp;Stefan Arver,&nbsp;Daniel P. Andersson,&nbsp;Anna Wiik,&nbsp;Thomas Gustafsson","doi":"10.1111/joim.20039","DOIUrl":"10.1111/joim.20039","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Longitudinal studies investigating hormone therapy in transgender individuals are rare and often limited to 1- to 2-year follow-up periods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives and Methods</h3>\u0000 \u0000 <p>We examined changes in body composition, muscle volumes, and fat distribution as well as muscle strength, arterial stiffness, and cardiometabolic biomarkers in both transgender men (TM; <i>n</i> = 17, age 25 ± 5 years) and transgender women (TW; <i>n</i> = 16, age 28 ± 5 years) at baseline and after 1 and 5–6 years of hormone therapy in a longitudinal prospective cohort design. Whole-body and regional fat and muscle volumes were analyzed using magnetic resonance imaging, and blood samples were taken.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Skeletal muscle size increased in TM (21% after 6 years) and decreased in TW (7% after 5 years). Muscle strength increased 18% after 6 years in TM (<i>p</i> = 0.003) but was statistically unchanged in TW. Muscle fat infiltration changed (<i>p</i> &lt; 0.05) almost completely toward the affirmed sex phenotype after 1 year of therapy in both TM and TW. The most notable changes in fat volume distribution were that TW increased total adiposity but decreased visceral fat volume, whereas TM showed increased visceral fat (70%) and liver fat but relatively stable total adipose tissue levels. Although arterial stiffness and blood pressure did not change, there was a significant increase in triglyceride and LDL cholesterol levels and a decrease in HDL levels in TM after 6 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These unique longitudinal data underscore the importance of continued clinical monitoring of the long-term health effects of gender-affirming hormone therapy in both TW and, perhaps especially, TM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 2","pages":"156-172"},"PeriodicalIF":9.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kidney function estimated by creatinine and cystatin C and adverse cardiovascular outcomes in patients with atrial fibrillation","authors":"Adrian Schweigler,&nbsp;Elisa Hennings,&nbsp;Stefanie Aeschbacher,&nbsp;Désirée Carmine,&nbsp;Tobias Reichlin,&nbsp;Nicolas Rodondi,&nbsp;Annina Stauber,&nbsp;Peter Ammann,&nbsp;Giorgio Moschovitis,&nbsp;Lucy Bolt,&nbsp;Andrea Demarchi,&nbsp;Andreas S. Mueller,&nbsp;Danielle Reneau,&nbsp;Michael Coslovsky,&nbsp;Christine S. Zuern,&nbsp;Leo H. Bonati,&nbsp;David Conen,&nbsp;Stefan Osswald,&nbsp;Michael Kühne,&nbsp;Philipp Krisai,&nbsp;for the Swiss-AF Investigators","doi":"10.1111/joim.20036","DOIUrl":"10.1111/joim.20036","url":null,"abstract":"","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 3","pages":"335-338"},"PeriodicalIF":9.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of letrozole therapy in former users of anabolic steroids: A randomized clinical trial","authors":"Jon Jarløv Rasmussen,&nbsp;Yeliz Bulut,&nbsp;Niels Brandt-Jacobsen,&nbsp;Jan Frystyk,&nbsp;Jakob Albrethsen,&nbsp;Mario Thevis,&nbsp;Niels Jørgensen,&nbsp;Morten Schou,&nbsp;Anders Juul,&nbsp;Caroline Kistorp","doi":"10.1111/joim.20040","DOIUrl":"10.1111/joim.20040","url":null,"abstract":"","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 1","pages":"113-116"},"PeriodicalIF":9.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An electronic medical record retrieval system can be used to identify missed diagnosis in patients with primary ciliary dyskinesia","authors":"Wangji Zhou,&nbsp;Qiaoling Chen,&nbsp;Yaqi Wang,&nbsp;Anhui Guo,&nbsp;Aohua Wu,&nbsp;Xueqi Liu,&nbsp;Jinrong Dai,&nbsp;Shuzhen Meng,&nbsp;Christopher Situ,&nbsp;Yaping Liu,&nbsp;Kai-Feng Xu,&nbsp;Weiguo Zhu,&nbsp;Xinlun Tian","doi":"10.1111/joim.20034","DOIUrl":"10.1111/joim.20034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disease. Due to difficulty accessing diagnostic services and a lack of awareness of the syndrome, clinicians often fail to recognize the classic phenotype, leading to missed diagnoses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Relevant medical records were accessed through The BIG DATA QUERY AND ANALYSIS SYSTEM of Peking Union Medical College Hospital from September 1, 2012 to March 31, 2024. The search strategy included the following key terms: (bronchiectasis OR atelectasis OR recurrent cough OR recurrent expectoration OR hemoptysis) AND (sinusitis OR nasal polyps OR otitis media OR neonatal pneumonia OR neonatal respiratory distress OR ectopic pregnancy OR infertility OR artificial insemination OR assisted reproduction OR hydrocephalus OR congenital heart disease OR organ laterality defect OR right-sided heart OR semen OR consanguineous marriage). Patients were filtered according to inclusion and exclusion criteria, and those with clinical suspicion of PCD were invited for screening, which included nasal nitric oxide and whole exome sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 874 medical records were retrieved. After filtering based on inclusion and exclusion criteria, 65 patients with clinical suspicion of PCD were identified, 21 of whom accepted our invitation to complete PCD-related screening. Among them, four were diagnosed with PCD, one was diagnosed with cystic fibrosis, and one was diagnosed with immunodeficiency-21.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This is the first study to use an electronic medical record retrieval system to identify missed diagnoses PCD. We believe that the methods used in this study can be extended to other rare diseases in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 1","pages":"93-100"},"PeriodicalIF":9.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statin-associated regulation of hepatic PNPLA3 in patients without known liver disease","authors":"Osman Ahmed,&nbsp;Vladimir S. Shavva,&nbsp;Laura Tarnawski,&nbsp;Wanmin Dai,&nbsp;Filip Borg,&nbsp;Viggo V. Olofsson,&nbsp;Ting Liu,&nbsp;Peter Saliba-Gustafsson,&nbsp;Christian Simini,&nbsp;Matteo Pedrelli,&nbsp;Otto Bergman,&nbsp;Giuseppe Danilo Norata,&nbsp;Paolo Parini,&nbsp;Anders Franco-Cereceda,&nbsp;Per Eriksson,&nbsp;Stephen G. Malin,&nbsp;Hanna M. Björck,&nbsp;Peder S. Olofsson","doi":"10.1111/joim.20032","DOIUrl":"10.1111/joim.20032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and objectives</h3>\u0000 \u0000 <p>Statins are used for metabolic dysfunction-associated steatotic liver disease (MASLD) (NAFLD) treatment, but their role in this context is unclear. Genetic variants of patatin-like phospholipase domain containing 3 (<i>PNPLA3</i>) are associated with MASLD susceptibility and statin treatment efficacy. Access to liver biopsies before established MASLD is limited, and statins and PNPLA3 in early liver steatosis are thus difficult to study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Liver biopsies were collected from 261 patients without known liver disease at surgery and stratified based on statin use and criteria for the metabolic syndrome (MS). Genotypes and transcript levels were measured using Illumina and Affymetrix arrays, and metabolic and lipoprotein profiles by clinical assays. Statin effects on PNPLA3, de novo lipogenesis (DNL), and lipid accumulation were further studied in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The PNPLA3^I148M genetic variant was associated with significantly lower hepatic levels of cholesterol synthesis-associated transcripts. Patients with MS had significantly higher hepatic levels of MASLD and lipogenesis-associated transcripts than non-MS patients. Patients with MS on statin therapy had significantly higher hepatic levels of <i>PNPLA3</i>, acetyl-CoA carboxylase alpha, and ATP citrate lyase, and statin use was associated with higher plasma fasting glucose, insulin, and HbA1c. Exposure of hepatocyte-like HepG2 cells to atorvastatin promoted intracellular accumulation of triglycerides and lipogenesis-associated transcripts. Atorvastatin-exposure of HepG2, sterol <i>O</i>-acyltransferase <i>(SOAT) 2</i>-only-HepG2, primary human hepatic stellate, and hepatic stellate cell-like LX2 cells significantly increased levels of <i>PNPLA3</i> and SREBF2-target genes, whereas knockdown of SREBF2 attenuated this effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Collectively, these observations suggest statin-associated regulation of PNPLA3 and DNL in liver. The potential interaction between <i>PNPLA3</i> genotype and metabolic status should be considered in future studies in the context of statin therapy for MASLD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 1","pages":"47-59"},"PeriodicalIF":9.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}