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":"https://doi.org/10.1111/joim.20032","url":null,"abstract":"<p><strong>Background and objectives: </strong>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.</p><p><strong>Methods: </strong>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><p><strong>Results: </strong>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 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/10.1111/joim.20035","url":null,"abstract":"<p><strong>Background: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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><p><strong>Conclusion: </strong>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>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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.
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":"https://doi.org/10.1111/joim.20033","url":null,"abstract":"<p><strong>Background: </strong>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><p><strong>Objectives: </strong>To report the long-term results of the BATTLE trial, BCG vaccine in adults with mild COVID-19.</p><p><strong>Methods: </strong>Design: Double-blind, placebo-controlled, randomized (1:1) clinical trial.</p><p><strong>Intervention: </strong>BCG intradermal vaccine and placebo.</p><p><strong>Patients: </strong>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.</p><p><strong>Measurements: </strong>Long COVID symptoms and mechanistic analyses.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Limitations: </strong>Not tested for previous mycobacterial exposure; loss to follow-up, particularly at 12 months.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"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":"https://doi.org/10.1111/joim.20024","url":null,"abstract":"<p><strong>Background: </strong>Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide, little is known about their long-term outcomes.</p><p><strong>Methods: </strong>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><p><strong>Results: </strong>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><p><strong>Conclusion: </strong>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>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: 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":"https://doi.org/10.1111/joim.20028","url":null,"abstract":"<p><strong>Background: </strong>This meta-analysis aimed to determine the incidence and overall risk of major adverse cardiovascular events (MACEs) related to immune checkpoint inhibitors (ICIs).</p><p><strong>Methods: </strong>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><p><strong>Results: </strong>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><p><strong>Conclusion: </strong>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>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"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}
Ilaria Mastrorosa, Alessandro Cozzi Lepri, Cosmo Del Borgo, Silvia Rosati, Martina Rueca, Loredana Sarmati, Claudio Mastroianni, Massimo Fantoni, Fabrizio Maggi, Emanuele Nicastri, Enrico Girardi, Miriam Lichtner, Andrea Antinori, Valentina Mazzotta
Objectives: To estimate the risk of COVID-19-related hospitalization and death (CovH/D), among high-risk individuals early treated for COVID-19 and to identify associated factors.
Methods and results: A multicenter cohort of 12,475 high-risk outpatients (female 50.2%, median age 70 years [IQR 57-80], fully vaccinated 79.1%, immunocompromised 23.2%) treated with monoclonal antibodies or antivirals for mild-to-moderate COVID-19 (March 2021-May 2023) in the Lazio region, Italy. The unadjusted risk of CovH/D by Day 30 was 3.08% (95% CI 2.7%-3.4%). By means of logistic regression models, which included a specific set of potential confounders for each exposure of interest, we observed a higher risk for the elderly, unvaccinated and immunocompromised participants. Using the "Delta period" as a reference, a decreased risk was observed for Omicron waves.
Conclusions: Despite the administration of COVID-19 early treatment and the decreasing risk of CovH/D across the calendar periods, the elderly, the unvaccinated and the immunocompromised people remain at high risk of clinical progression.
{"title":"Incidence and predictors of clinical failure after early treatment for mild-to-moderate COVID-19 in high-risk individuals: A multicentric cohort study.","authors":"Ilaria Mastrorosa, Alessandro Cozzi Lepri, Cosmo Del Borgo, Silvia Rosati, Martina Rueca, Loredana Sarmati, Claudio Mastroianni, Massimo Fantoni, Fabrizio Maggi, Emanuele Nicastri, Enrico Girardi, Miriam Lichtner, Andrea Antinori, Valentina Mazzotta","doi":"10.1111/joim.20030","DOIUrl":"https://doi.org/10.1111/joim.20030","url":null,"abstract":"<p><strong>Objectives: </strong>To estimate the risk of COVID-19-related hospitalization and death (CovH/D), among high-risk individuals early treated for COVID-19 and to identify associated factors.</p><p><strong>Methods and results: </strong>A multicenter cohort of 12,475 high-risk outpatients (female 50.2%, median age 70 years [IQR 57-80], fully vaccinated 79.1%, immunocompromised 23.2%) treated with monoclonal antibodies or antivirals for mild-to-moderate COVID-19 (March 2021-May 2023) in the Lazio region, Italy. The unadjusted risk of CovH/D by Day 30 was 3.08% (95% CI 2.7%-3.4%). By means of logistic regression models, which included a specific set of potential confounders for each exposure of interest, we observed a higher risk for the elderly, unvaccinated and immunocompromised participants. Using the \"Delta period\" as a reference, a decreased risk was observed for Omicron waves.</p><p><strong>Conclusions: </strong>Despite the administration of COVID-19 early treatment and the decreasing risk of CovH/D across the calendar periods, the elderly, the unvaccinated and the immunocompromised people remain at high risk of clinical progression.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613223","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}
Ida Gruber, Barbara Kollerits, Lukas Forer, Silvia Di Maio, Johanna F. Schachtl-Riess, Azin Kheirkhah, Sebastian Schönherr, Ulla T. Schultheiss, Anna Köttgen, Kai-Uwe Eckardt, Stefan Coassin, Claudia Lamina, Florian Kronenberg