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.
{"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}
Tommy R. Lundberg, Andrea Tryfonos, Lisa M.J. Eriksson, Helene Rundqvist, Eric Rullman, Mats Holmberg, Salwan Maqdasy, Jennifer Linge, Olof Dahlqvist Leinhard, Stefan Arver, Daniel P. Andersson, Anna Wiik, Thomas Gustafsson
Background
Longitudinal studies investigating hormone therapy in transgender individuals are rare and often limited to 1- to 2-year follow-up periods.
Objectives and Methods
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; n = 17, age 25 ± 5 years) and transgender women (TW; n = 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.
Results
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 (p = 0.003) but was statistically unchanged in TW. Muscle fat infiltration changed (p < 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.
Conclusion
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.
{"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, Andrea Tryfonos, Lisa M.J. Eriksson, Helene Rundqvist, Eric Rullman, Mats Holmberg, Salwan Maqdasy, Jennifer Linge, Olof Dahlqvist Leinhard, Stefan Arver, Daniel P. Andersson, Anna Wiik, 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> < 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}
Adrian Schweigler, Elisa Hennings, Stefanie Aeschbacher, Désirée Carmine, Tobias Reichlin, Nicolas Rodondi, Annina Stauber, Peter Ammann, Giorgio Moschovitis, Lucy Bolt, Andrea Demarchi, Andreas S. Mueller, Danielle Reneau, Michael Coslovsky, Christine S. Zuern, Leo H. Bonati, David Conen, Stefan Osswald, Michael Kühne, Philipp Krisai, for the Swiss-AF Investigators
{"title":"Kidney function estimated by creatinine and cystatin C and adverse cardiovascular outcomes in patients with atrial fibrillation","authors":"Adrian Schweigler, Elisa Hennings, Stefanie Aeschbacher, Désirée Carmine, Tobias Reichlin, Nicolas Rodondi, Annina Stauber, Peter Ammann, Giorgio Moschovitis, Lucy Bolt, Andrea Demarchi, Andreas S. Mueller, Danielle Reneau, Michael Coslovsky, Christine S. Zuern, Leo H. Bonati, David Conen, Stefan Osswald, Michael Kühne, Philipp Krisai, 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}
Jon Jarløv Rasmussen, Yeliz Bulut, Niels Brandt-Jacobsen, Jan Frystyk, Jakob Albrethsen, Mario Thevis, Niels Jørgensen, Morten Schou, Anders Juul, Caroline Kistorp
{"title":"Effects of letrozole therapy in former users of anabolic steroids: A randomized clinical trial","authors":"Jon Jarløv Rasmussen, Yeliz Bulut, Niels Brandt-Jacobsen, Jan Frystyk, Jakob Albrethsen, Mario Thevis, Niels Jørgensen, Morten Schou, Anders Juul, 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}
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.
Methods
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.
Results
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.
Conclusions
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.
{"title":"An electronic medical record retrieval system can be used to identify missed diagnosis in patients with primary ciliary dyskinesia","authors":"Wangji Zhou, Qiaoling Chen, Yaqi Wang, Anhui Guo, Aohua Wu, Xueqi Liu, Jinrong Dai, Shuzhen Meng, Christopher Situ, Yaping Liu, Kai-Feng Xu, Weiguo Zhu, 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}
Osman Ahmed, Vladimir S. Shavva, Laura Tarnawski, Wanmin Dai, Filip Borg, Viggo V. Olofsson, Ting Liu, Peter Saliba-Gustafsson, Christian Simini, Matteo Pedrelli, Otto Bergman, Giuseppe Danilo Norata, Paolo Parini, Anders Franco-Cereceda, Per Eriksson, Stephen G. Malin, Hanna M. Björck, Peder S. Olofsson
Background and objectives
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 (PNPLA3) 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.
Methods
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.
Results
The PNPLA3I148M 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 PNPLA3, 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 O-acyltransferase (SOAT) 2-only-HepG2, primary human hepatic stellate, and hepatic stellate cell-like LX2 cells significantly increased levels of PNPLA3 and SREBF2-target genes, whereas knockdown of SREBF2 attenuated this effect.
Conclusions
Collectively, these observations suggest statin-associated regulation of PNPLA3 and DNL in liver. The potential interaction between PNPLA3 genotype and metabolic status should be considered in future studies in the context of statin therapy for MASLD.
{"title":"Statin-associated regulation of hepatic PNPLA3 in patients without known liver disease","authors":"Osman Ahmed, Vladimir S. Shavva, Laura Tarnawski, Wanmin Dai, Filip Borg, Viggo V. Olofsson, Ting Liu, Peter Saliba-Gustafsson, Christian Simini, Matteo Pedrelli, Otto Bergman, Giuseppe Danilo Norata, Paolo Parini, Anders Franco-Cereceda, Per Eriksson, Stephen G. Malin, Hanna M. Björck, 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<sup>I148M</sup> 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}
Anna Åkesson, Linnea Malmgren, Felicia Leion, Ulf Nyman, Anders Christensson, Jonas Björk, Anders Grubb
Background
In 2015, a selective decrease in the glomerular filtration of middle-sized molecules such as cystatin C compared to small molecules such as creatinine was first described and tentatively termed “Shrunken pore syndrome.” Numerous studies have thereafter found an association between this syndrome (defined by a low eGFRcystatin C to eGFRcreatinine ratio) and mortality and morbidity. In 2023, the syndrome was renamed selective glomerular hypofiltration syndromes (SGHS) as shrunken pores are not the only pathophysiological mechanism. Recently, some studies have used the difference between eGFRcystatin C and eGFRcreatinine to describe a similar disorder, and this investigation compares the two measures.
Methods
Using a cohort of 2781 adults with a median follow-up of 5.6 years, referred for determination of glomerular filtration rate (GFR), estimated GFR (eGFR) was determined using four equations. SGHS was defined using the eGFRdifference and the eGFRratio and association to mortality investigated through adjusted Cox proportional hazard models. From each adjusted regression model, Harrell's C-index and 95% confidence intervals were calculated.
Results
Both measures were associated with mortality. No significant differences concerning hazard ratios or Harrell's C-index were found between the two measures to estimate mortality, and both identified SGHS and increased mortality in a subpopulation of 567 “healthy” individuals with no prior diagnosis and with no kidney disorder according to the kidney disease improving global outcomes-criteria.
Conclusion
The eGFRdifference is not superior to the eGFRratio in diagnosing SGHS or estimating mortality. However, as the two measures do not identify the same subpopulation, using them simultaneously might improve risk stratification.
背景：2015 年，人们首次描述了胱抑素 C 等中等大小分子与肌酐等小分子相比肾小球滤过率选择性下降的现象，并将其暂称为 "缩孔综合征"。此后，大量研究发现，该综合征（定义为低 eGFR 胱抑素 C 与 eGFR 肌酐比值）与死亡率和发病率之间存在关联。2023 年，该综合征被重新命名为选择性肾小球低滤过综合征（SGHS），因为毛孔缩小并不是唯一的病理生理机制。最近，一些研究利用 eGFRcystatin C 和 eGFRcreatinine 之间的差异来描述一种类似的疾病，本研究对这两种测量方法进行了比较：通过对中位随访时间为 5.6 年的 2781 名成年人进行队列研究，采用四种方程确定了肾小球滤过率（GFR）的估算值（eGFR）。使用 eGFRdifference 和 eGFRratio 对 SGHS 进行定义，并通过调整后的 Cox 比例危险模型研究其与死亡率的关系。根据每个调整后的回归模型，计算出 Harrell 的 C 指数和 95% 的置信区间：结果：这两项指标都与死亡率有关。根据肾脏病改善全球结果标准，在 567 名既往未确诊又无肾脏疾病的 "健康 "人群中，这两种估算死亡率的方法在危险比或 Harrell's C 指数方面均未发现明显差异：在诊断 SGHS 或估算死亡率方面，eGFRdifference 并不优于 eGFRratio。然而，由于这两种测量方法不能识别相同的亚人群，同时使用可能会改善风险分层。
{"title":"Different ways of diagnosing selective glomerular hypofiltration syndromes such as shrunken pore syndrome and the associated increase in mortality","authors":"Anna Åkesson, Linnea Malmgren, Felicia Leion, Ulf Nyman, Anders Christensson, Jonas Björk, Anders Grubb","doi":"10.1111/joim.20035","DOIUrl":"10.1111/joim.20035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In 2015, a selective decrease in the glomerular filtration of middle-sized molecules such as cystatin C compared to small molecules such as creatinine was first described and tentatively termed “Shrunken pore syndrome.” Numerous studies have thereafter found an association between this syndrome (defined by a low eGFR<sub>cystatin C</sub> to eGFR<sub>creatinine</sub> ratio) and mortality and morbidity. In 2023, the syndrome was renamed selective glomerular hypofiltration syndromes (SGHS) as shrunken pores are not the only pathophysiological mechanism. Recently, some studies have used the difference between eGFR<sub>cystatin C</sub> and eGFR<sub>creatinine</sub> to describe a similar disorder, and this investigation compares the two measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using a cohort of 2781 adults with a median follow-up of 5.6 years, referred for determination of glomerular filtration rate (GFR), estimated GFR (eGFR) was determined using four equations. SGHS was defined using the eGFR<sub>difference</sub> and the eGFR<sub>ratio</sub> and association to mortality investigated through adjusted Cox proportional hazard models. From each adjusted regression model, Harrell's C-index and 95% confidence intervals were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both measures were associated with mortality. No significant differences concerning hazard ratios or Harrell's C-index were found between the two measures to estimate mortality, and both identified SGHS and increased mortality in a subpopulation of 567 “healthy” individuals with no prior diagnosis and with no kidney disorder according to the kidney disease improving global outcomes-criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The eGFR<sub>difference</sub> is not superior to the eGFR<sub>ratio</sub> in diagnosing SGHS or estimating mortality. However, as the two measures do not identify the same subpopulation, using them simultaneously might improve risk stratification.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 1","pages":"79-92"},"PeriodicalIF":9.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666512","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}
Mehrsa Jalalizadeh, Keini Buosi, Cristiane F. Giacomelli, Patricia A.F. Leme, Karen L. Ferrari, Franciele A.V. Dionato, Wandrey R.S. Brito, Natália S. Brunetti, Aline R. Maia, Joseane Morari, Ana C. Pagliarone, Alessandro S. Farias, Licio A. Velloso, Maria A.F. Queiroz, Antonio C.R. Vallinoto, Marcio C. Bajgelman, Leonardo O. Reis
Background
Bacillus Calmette–Guérin (BCG) injected during the COVID-19 convalescence period was safe and enhanced recovery from anosmia and dysgeusia in the acute phase.
Objectives
To report the long-term results of the BATTLE trial, BCG vaccine in adults with mild COVID-19.
Methods
Design: Double-blind, placebo-controlled, randomized (1:1) clinical trial. Intervention: BCG intradermal vaccine and placebo. Patients: A total of 157 BCG and 142 placebo recipients participated in the 6-month follow-up, and 97 BCG and 95 placebo recipients participated in the 12-month follow-up. Measurements: Long COVID symptoms and mechanistic analyses.
Results
BCG reduced hearing problems at 6 months (odds ratio [OR] = 0.26) and sleeping, concentration, memory, and vision problems at 12 months (OR = 0.45, 0.36, 0.38, and 0.36, respectively). Sensitivity analyses confirmed that long COVID-19 symptoms were reduced at the 6- and 12-month follow-ups (p = 0.010 and 0.031, respectively). BCG's crossover interaction paradoxically increased hair loss in women and decreased it in men at 6 months (p = 0.032). BCG immunomodulation is likely mediated through inhibition of Fas ligand expression in the blood and increased induction of IL6, IL10, interferon-induced transmembrane protein 3, and angiotensin-converting enzyme 2 in cultured human macrophages.
Conclusion
Long-term follow-up of the BATTLE trial participants revealed that BCG protects against long COVID development if administered within the COVID-19 convalescence period. The response to BCG was subject-specific, including a paradoxical crossover interaction based on sex. Limitations: Not tested for previous mycobacterial exposure; loss to follow-up, particularly at 12 months.
{"title":"Therapeutic BCG vaccine protects against long COVID: The BATTLE randomized clinical trial","authors":"Mehrsa Jalalizadeh, Keini Buosi, Cristiane F. Giacomelli, Patricia A.F. Leme, Karen L. Ferrari, Franciele A.V. Dionato, Wandrey R.S. Brito, Natália S. Brunetti, Aline R. Maia, Joseane Morari, Ana C. Pagliarone, Alessandro S. Farias, Licio A. Velloso, Maria A.F. Queiroz, Antonio C.R. Vallinoto, Marcio C. Bajgelman, Leonardo O. Reis","doi":"10.1111/joim.20033","DOIUrl":"10.1111/joim.20033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bacillus Calmette–Guérin (BCG) injected during the COVID-19 convalescence period was safe and enhanced recovery from anosmia and dysgeusia in the acute phase.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To report the long-term results of the BATTLE trial, BCG vaccine in adults with mild COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Design: Double-blind, placebo-controlled, randomized (1:1) clinical trial. Intervention: BCG intradermal vaccine and placebo. Patients: A total of 157 BCG and 142 placebo recipients participated in the 6-month follow-up, and 97 BCG and 95 placebo recipients participated in the 12-month follow-up. Measurements: Long COVID symptoms and mechanistic analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BCG reduced hearing problems at 6 months (odds ratio [OR] = 0.26) and sleeping, concentration, memory, and vision problems at 12 months (OR = 0.45, 0.36, 0.38, and 0.36, respectively). Sensitivity analyses confirmed that long COVID-19 symptoms were reduced at the 6- and 12-month follow-ups (<i>p</i> = 0.010 and 0.031, respectively). BCG's crossover interaction paradoxically increased hair loss in women and decreased it in men at 6 months (<i>p</i> = 0.032). BCG immunomodulation is likely mediated through inhibition of Fas ligand expression in the blood and increased induction of IL6, IL10, interferon-induced transmembrane protein 3, and angiotensin-converting enzyme 2 in cultured human macrophages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Long-term follow-up of the BATTLE trial participants revealed that BCG protects against long COVID development if administered within the COVID-19 convalescence period. The response to BCG was subject-specific, including a paradoxical crossover interaction based on sex. Limitations: Not tested for previous mycobacterial exposure; loss to follow-up, particularly at 12 months.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 1","pages":"60-78"},"PeriodicalIF":9.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666166","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}
Anne-Laure Faucon, Stefania Lando, Charikleia Chrysostomou, Julia Wijkström, Sigrid Lundberg, Rino Bellocco, Mårten Segelmark, Marie Evans, Juan-Jesús Carrero
Background
Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide, little is known about their long-term outcomes.
Methods
In patients with chronic kidney disease (CKD) stage 3–5 enrolled in the Swedish Renal Registry, we compared risks of hospitalization, kidney replacement therapy (KRT), major cardiovascular events (MACE), and death of the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD], and membranous nephropathy [MN]), and patients with CKD due to the most common non-communicable diseases (control-CKD).
Results
We identified 2396 patients with glomerular disease (97% biopsy-proven, 69% men, 57 years, eGFR 29 mL/min/1.73 m2, uACR 88 mg/mmol, 1524 with IgAN, 398 FSGS, 94 MCD, and 380 MN) and 37,697 controls (64% men, 74 years, eGFR 25 mL/min/1.73 m2, uACR 23 mg/mmol), mainly with diabetic nephropathy and nephroangiosclerosis. The median follow-up was 6.3 (3.3; 9.9) years. Compared with control-CKD, patients with primary glomerular diseases generally had a lower risk of hospitalization, MACE (adjusted hazard ratios [HRs] ranging from 0.44 to 0.88 depending on the etiology) and death (HRs ranging 0.45–0.76). Patients with IgAN and FSGS had a faster eGFR decline and a higher rate of KRT (HRs 1.26 [95%CI: 1.15–1.37] and 1.34 [1.15–1.57], respectively). Conversely, patients with MN and MCD had a lower KRT rate and slower eGFR decline.
Conclusion
Despite having a lower relative risk of hospitalization, cardiovascular events and mortality, patients with IgAN and FSGS are at higher risk of CKD progression than the most common etiologies of CKD, emphasizing the need for more stringent treatment strategies in these patients.
{"title":"Primary glomerular diseases and long-term adverse health outcomes: A nationwide cohort study","authors":"Anne-Laure Faucon, Stefania Lando, Charikleia Chrysostomou, Julia Wijkström, Sigrid Lundberg, Rino Bellocco, Mårten Segelmark, Marie Evans, Juan-Jesús Carrero","doi":"10.1111/joim.20024","DOIUrl":"10.1111/joim.20024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide, little is known about their long-term outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In patients with chronic kidney disease (CKD) stage 3–5 enrolled in the Swedish Renal Registry, we compared risks of hospitalization, kidney replacement therapy (KRT), major cardiovascular events (MACE), and death of the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD], and membranous nephropathy [MN]), and patients with CKD due to the most common non-communicable diseases (control-CKD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 2396 patients with glomerular disease (97% biopsy-proven, 69% men, 57 years, eGFR 29 mL/min/1.73 m<sup>2</sup>, uACR 88 mg/mmol, 1524 with IgAN, 398 FSGS, 94 MCD, and 380 MN) and 37,697 controls (64% men, 74 years, eGFR 25 mL/min/1.73 m<sup>2</sup>, uACR 23 mg/mmol), mainly with diabetic nephropathy and nephroangiosclerosis. The median follow-up was 6.3 (3.3; 9.9) years. Compared with control-CKD, patients with primary glomerular diseases generally had a lower risk of hospitalization, MACE (adjusted hazard ratios [HRs] ranging from 0.44 to 0.88 depending on the etiology) and death (HRs ranging 0.45–0.76). Patients with IgAN and FSGS had a faster eGFR decline and a higher rate of KRT (HRs 1.26 [95%CI: 1.15–1.37] and 1.34 [1.15–1.57], respectively). Conversely, patients with MN and MCD had a lower KRT rate and slower eGFR decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Despite having a lower relative risk of hospitalization, cardiovascular events and mortality, patients with IgAN and FSGS are at higher risk of CKD progression than the most common etiologies of CKD, emphasizing the need for more stringent treatment strategies in these patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 1","pages":"22-35"},"PeriodicalIF":9.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613230","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}
This meta-analysis aimed to determine the incidence and overall risk of major adverse cardiovascular events (MACEs) related to immune checkpoint inhibitors (ICIs).
Methods
We systematically searched all cohort studies, including the available MACE data in cancer patients receiving ICIs, in PubMed, Embase, and the Cochrane Library, from their inception to September 5, 2023. The primary outcome was the incidence of MACEs associated with ICI exposure, and the secondary outcome was the overall risk of MACEs associated with ICI exposure versus non-ICI exposure controls. Risk ratios with 95% confidence intervals were used in the random- or fixed-effects models.
Results
Overall, 26 cohort studies met the inclusion criteria, involving 109,883 cancer patients. In the median follow-up period ranging from 3.3 to 55.2 months, the incidence of MACEs associated with ICI exposure was 8.22%, ranging from 0.55% to 3.98%, among the nine MACEs, including myocarditis, tachyarrhythmia, pericarditis, pericardial effusions, cardiovascular death, myocardial infarction, heart failure, stroke, and conduction disorder. The incidence of MACE associated with non-ICI exposure was 3.84%, ranging from 0.81% to 4.72%. The risks of all-grade MACEs and pericardial effusions were significantly higher in the ICI group than in the non-ICI controls. ICI treatment, age, male sex, and prior radiation therapy were significantly associated with MACEs.
Conclusion
The risk of MACEs during ICI treatment in patients with cancer is more common than is currently recognized. ICI use is closely associated with an increased risk of MACEs. Patients at risk were older, male, and had a history of radiation therapy.
{"title":"Association among major adverse cardiovascular events with immune checkpoint inhibitors: A systematic review and meta-analysis","authors":"Haixia Li, Yanfei Zheng, Bin Li, Yinghao Zhi, Mingxian Chen, Jing Zeng, Qian Jiao, Yuxuan Tao, Xinmei Liu, Zican Shen, Jiahui Zhang, Weizhe Zhao, Dong Chen","doi":"10.1111/joim.20028","DOIUrl":"10.1111/joim.20028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This meta-analysis aimed to determine the incidence and overall risk of major adverse cardiovascular events (MACEs) related to immune checkpoint inhibitors (ICIs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We systematically searched all cohort studies, including the available MACE data in cancer patients receiving ICIs, in PubMed, Embase, and the Cochrane Library, from their inception to September 5, 2023. The primary outcome was the incidence of MACEs associated with ICI exposure, and the secondary outcome was the overall risk of MACEs associated with ICI exposure versus non-ICI exposure controls. Risk ratios with 95% confidence intervals were used in the random- or fixed-effects models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 26 cohort studies met the inclusion criteria, involving 109,883 cancer patients. In the median follow-up period ranging from 3.3 to 55.2 months, the incidence of MACEs associated with ICI exposure was 8.22%, ranging from 0.55% to 3.98%, among the nine MACEs, including myocarditis, tachyarrhythmia, pericarditis, pericardial effusions, cardiovascular death, myocardial infarction, heart failure, stroke, and conduction disorder. The incidence of MACE associated with non-ICI exposure was 3.84%, ranging from 0.81% to 4.72%. The risks of all-grade MACEs and pericardial effusions were significantly higher in the ICI group than in the non-ICI controls. ICI treatment, age, male sex, and prior radiation therapy were significantly associated with MACEs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The risk of MACEs during ICI treatment in patients with cancer is more common than is currently recognized. ICI use is closely associated with an increased risk of MACEs. Patients at risk were older, male, and had a history of radiation therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 1","pages":"36-46"},"PeriodicalIF":9.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613221","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}
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