Journal of Internal Medicine最新文献_第10页

Effect on C-reactive protein levels of the addition of ezetimibe, bempedoic acid, or colchicine to statin treatment: A network meta-analysis 在他汀类药物治疗中添加依折麦布、贝美多酸或秋水仙碱对 C 反应蛋白水平的影响：网络荟萃分析

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2024-07-11 DOI: 10.1111/joim.13824

Sining Xie, Federica Galimberti, Elena Olmastroni, Alberico L. Catapano, Manuela Casula

<p>Dear Editor,</p><p>Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality worldwide. Although several therapeutic options are available to reduce LDL-cholesterol (LDL-C), many patients continue to experience major cardiovascular (CV) events. In ASCVD, inflammation plays a critical role, contributing significantly to residual CV risk [<span>1</span>]. Several anti-inflammatory therapies have been evaluated to reduce CV risk, and recently, the U.S. Food and Drug Administration approved the use of low-dose colchicine to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, or CV death in adult patients with established ASCVD or multiple CV risk factors [<span>2, 3</span>]. Meta-analyses have shown that low-dose colchicine (0.5–1.0 mg) can lead to a reduction in C-reactive protein (CRP) levels by −0.36 mg/L (95%CI, −0.51 to −0.20) in patients with coronary artery disease [<span>4, 5</span>], and by −0.66 mg/L (95%CI, −0.98 to −0.35) in patients with acute MI [<span>6</span>], which translates into a 35% and 44% reduction in major CV events, respectively. Nevertheless, some studies have suggested an anti-inflammatory effect with some lipid-lowering therapies. In a recent meta-analysis involving 171,668 subjects from 53 randomized control trials (RCTs), we demonstrated a reduction in serum CRP concentration with statins (−0.65 mg/L [95%CI, −0.87 to −0.43]), bempedoic acid (−0.43 mg/L [95%CI, −0.67 to −0.20]), and ezetimibe (−0.28 mg/L [95%CI, −0.48 to −0.08]), which was independent of LDL-C changes [<span>7</span>].</p><p>Given the growing interest in targeting inflammation to further reduce CV risk and the recent inclusion of colchicine among CV preventive therapies [<span>8</span>], it appears of interest to compare the effect of available therapies on plasma CRP levels. Therefore, we sought to quantify the additional effect of adding colchicine to statins on CRP levels and to compare the effect of bempedoic acid, ezetimibe, or colchicine added to background statin treatment.</p><p>Because no trial directly compares the impact on CRP levels of colchicine versus lipid-lowering therapies, we performed a network meta-analysis according to the PRISMA guidelines. PubMed, Web of Science, EMBASE, Cochrane Library, and ClinicalTrial.gov were searched from inception to November 2023. Inclusion criteria were as follows: (1) RCTs in human, parallel design, phase II, III, or IV; (2) English language; (3) using ezetimibe, bempedoic acid, or colchicine as interventions on top of statin treatment (defined as more than 80% patients treated with statins at baseline); (4) reporting the effect on CRP levels; (5) with an intervention duration of more than 3 weeks.</p><p>Pooled estimates were assessed by both fixed-effect and random-effects models within a Bayesian hierarchical setting, assuming equal heterogeneity across all comparisons. When significant heterogeneity was detected (as determine

亲爱的编辑，动脉粥样硬化性心血管疾病（ASCVD）仍然是全球发病率和死亡率的主要原因。尽管有多种治疗方法可以降低低密度脂蛋白胆固醇（LDL-C），但许多患者仍会发生重大心血管（CV）事件。在 ASCVD 中，炎症起着至关重要的作用，在很大程度上导致了残余 CV 风险[1]。最近，美国食品和药物管理局批准使用小剂量秋水仙碱来降低已确诊 ASCVD 或有多种 CV 危险因素的成年患者发生心肌梗死（MI）、中风、冠状动脉血运重建或 CV 死亡的风险 [2，3]。荟萃分析表明，小剂量秋水仙碱（0.5-1.0 毫克）可使冠心病患者的 C 反应蛋白（CRP）水平降低-0.36 毫克/升（95%CI，-0.51 至-0.20）[4, 5]，使急性心肌梗死患者的 C 反应蛋白水平降低-0.66 毫克/升（95%CI，-0.98 至-0.35）[6]，从而使主要心血管事件分别减少 35% 和 44%。然而，一些研究表明，某些降脂疗法具有抗炎作用。在最近一项涉及 53 项随机对照试验 (RCT) 171,668 例受试者的荟萃分析中，我们发现他汀类药物（-0.65 mg/L [95%CI, -0.87 to -0.43]）、贝美多酸（-0.43 mg/L [95%CI, -0.67 to -0.20]）和依折麦布（-0.28 mg/L [95%CI, -0.鉴于针对炎症进一步降低 CV 风险的兴趣日益浓厚，以及最近将秋水仙碱纳入 CV 预防疗法[8]，比较现有疗法对血浆 CRP 水平的影响似乎很有意义。因此，我们试图量化在他汀类药物中添加秋水仙碱对 CRP 水平的额外影响，并比较在他汀类药物治疗基础上添加贝美多克酸、依折麦布或秋水仙碱的效果。由于没有试验直接比较秋水仙碱与降脂疗法对 CRP 水平的影响，我们根据 PRISMA 指南进行了网络荟萃分析。我们检索了从开始到 2023 年 11 月的 PubMed、Web of Science、EMBASE、Cochrane Library 和 ClinicalTrial.gov。纳入标准如下(1) 人类、平行设计、II、III 或 IV 期的 RCT；(2) 英语；(3) 在他汀类药物治疗的基础上使用依折麦布、贝美多酸或秋水仙碱作为干预措施（定义为 80% 以上的患者在基线时接受过他汀类药物治疗）；(4) 报告对 CRP 水平的影响；(5) 干预持续时间超过 3 周。在贝叶斯分层设置中，通过固定效应和随机效应模型对汇总估计值进行了评估，假定所有比较的异质性相同。如果检测到明显的异质性（由 t2 和 I2 统计量确定，p < 0.05），则显示随机效应模型的结果。我们使用科克伦偏倚风险（RoB）工具[9]对各项研究进行了评估。通过排除 RoB 评估中的高风险试验，进行了敏感性分析。所有分析均采用 R 软件包 gemtc（4.3.2 版）进行。共纳入了来自 30 项 RCT 的 22287 名受试者（表 S1；中位随访时间：4.5 个月）（其中 22 项 RCT 涉及依折麦布[18386 名受试者]，3 项 RCT 涉及贝贝多克酸[2961 名受试者]，5 项 RCT 涉及秋水仙碱[940 名受试者]）。配对荟萃分析表明，与单独使用他汀类药物相比，在他汀类药物中加入秋水仙碱可使 CRP 水平降低-0.75 mg/L（95% CI，-0.88 至-0.61）（图 1a）。在网络荟萃分析中，在他汀治疗中添加秋水仙碱与添加依折麦布（-0.22 mg/L [95% CI, -0.69 to 0.30]）或贝美多酸（-0.44 mg/L [95% CI, -1.05 to 0.23]）直接比较无显著差异（图 1b，图 S1）。在他汀类药物治疗基础上添加的本贝多酸和依折麦布在降低 CRP 水平方面没有显著差异（-0.22 mg/L [95% CI, -0.72 to 0.29]）（图 1b）。总之，我们的分析表明，在他汀类药物治疗的基础上，依折麦布、贝贝多酸或秋水仙碱的抗炎效果在短期内似乎不相上下，并进一步提出了秋水仙碱对哪些患者最有益的问题。总的来说，我们的数据表明，如果患者在他汀类药物治疗后低密度脂蛋白胆固醇未达标，因此符合联合降脂治疗的条件，那么在服用依折麦布或贝贝多酸后，其 CRP 降低效果将与服用秋水仙碱后的效果相当。

{"title":"Effect on C-reactive protein levels of the addition of ezetimibe, bempedoic acid, or colchicine to statin treatment: A network meta-analysis","authors":"Sining Xie, Federica Galimberti, Elena Olmastroni, Alberico L. Catapano, Manuela Casula","doi":"10.1111/joim.13824","DOIUrl":"10.1111/joim.13824","url":null,"abstract":"<p>Dear Editor,</p><p>Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality worldwide. Although several therapeutic options are available to reduce LDL-cholesterol (LDL-C), many patients continue to experience major cardiovascular (CV) events. In ASCVD, inflammation plays a critical role, contributing significantly to residual CV risk [<span>1</span>]. Several anti-inflammatory therapies have been evaluated to reduce CV risk, and recently, the U.S. Food and Drug Administration approved the use of low-dose colchicine to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, or CV death in adult patients with established ASCVD or multiple CV risk factors [<span>2, 3</span>]. Meta-analyses have shown that low-dose colchicine (0.5–1.0 mg) can lead to a reduction in C-reactive protein (CRP) levels by −0.36 mg/L (95%CI, −0.51 to −0.20) in patients with coronary artery disease [<span>4, 5</span>], and by −0.66 mg/L (95%CI, −0.98 to −0.35) in patients with acute MI [<span>6</span>], which translates into a 35% and 44% reduction in major CV events, respectively. Nevertheless, some studies have suggested an anti-inflammatory effect with some lipid-lowering therapies. In a recent meta-analysis involving 171,668 subjects from 53 randomized control trials (RCTs), we demonstrated a reduction in serum CRP concentration with statins (−0.65 mg/L [95%CI, −0.87 to −0.43]), bempedoic acid (−0.43 mg/L [95%CI, −0.67 to −0.20]), and ezetimibe (−0.28 mg/L [95%CI, −0.48 to −0.08]), which was independent of LDL-C changes [<span>7</span>].</p><p>Given the growing interest in targeting inflammation to further reduce CV risk and the recent inclusion of colchicine among CV preventive therapies [<span>8</span>], it appears of interest to compare the effect of available therapies on plasma CRP levels. Therefore, we sought to quantify the additional effect of adding colchicine to statins on CRP levels and to compare the effect of bempedoic acid, ezetimibe, or colchicine added to background statin treatment.</p><p>Because no trial directly compares the impact on CRP levels of colchicine versus lipid-lowering therapies, we performed a network meta-analysis according to the PRISMA guidelines. PubMed, Web of Science, EMBASE, Cochrane Library, and ClinicalTrial.gov were searched from inception to November 2023. Inclusion criteria were as follows: (1) RCTs in human, parallel design, phase II, III, or IV; (2) English language; (3) using ezetimibe, bempedoic acid, or colchicine as interventions on top of statin treatment (defined as more than 80% patients treated with statins at baseline); (4) reporting the effect on CRP levels; (5) with an intervention duration of more than 3 weeks.</p><p>Pooled estimates were assessed by both fixed-effect and random-effects models within a Bayesian hierarchical setting, assuming equal heterogeneity across all comparisons. When significant heterogeneity was detected (as determine","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 3","pages":"302-305"},"PeriodicalIF":9.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13824","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589086","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}

引用次数: 0

Olympic Games: When the haematocrit does not fit, the athlete is not always a cheat 奥运会：当血细胞比容不符合要求时，运动员并不一定是作弊。

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2024-07-09 DOI: 10.1111/joim.13822

Nada Maaziz, Laurent Martin, Alexandre Marchand, Betty Gardie, François Girodon

<p>Dear Editor,</p><p>The upcoming Olympic Games will be accompanied by intense testing for doping, which is unfortunately not uncommon in top-level sporting circles. Among classic doping products used in endurance sports, erythropoietin (EPO) drug, the biological copy of the main EPO hormone responsible for substantial increases in haemoglobin (Hb) concentration and haematocrit (Ht), is one of the originals, both in terms of its age (available since the 1980s) and frequency of use (61 doping cases worldwide in 2022) [<span>1</span>].</p><p>The history of the Olympic Games is associated with the discovery of mutations in the EPO receptor gene, <i>EPOR</i>, in the 1990s. The first mutation was identified in Eero Mäntyranta, who won multiple Olympic and world champion medals in cross-country skiing [<span>2</span>]. At that time, no technique was available to identify blood doping using EPO drug, or transfusion, for which methods were validated in the early 2000s [<span>3</span>].</p><p>Here, we report two cases in which top-level athletes were disqualified solely on the basis of high Hb and Ht values. These athletes were found to be carriers of familial polycythaemia associated with functionally tested pathogenic mutations in genes involved in the hypoxia-sensing pathway several years after their disqualification from the sporting world, underlining the importance of having recourse to specialized testing before making serious accusations.</p><p>A 34-year-old male, who started playing soccer at a young age, applied to enter a sports-study high school when he was 16 years old. His application was rejected due to the presence of high Hb and Ht values (Table 1). The doctor overseeing his case suspected doping, leading to the man's subsequent ban from sports study in high school and competitions. Eighteen years later, his son was diagnosed with polycythaemia, suggesting familial erythrocytosis and samples from the father and son were analysed using NGS sequencing with a gene panel dedicated to the exploration of polycythaemia. A pathogenic mutation (p.Asp525Gly) in <i>EPAS1</i> was identified in the father and son and three other relatives segregating with a polycythaemia phenotype. The <i>EPAS1</i> gene encodes the hypoxia-inducible factor HIF2α, which regulates the expression of EPO when oxygen concentrations go down.</p><p>The second medical record concerns a top-level national Taekwondo athlete, for whom a routine examination revealed high Ht and Hb values (Table 1), leading to definitive banishment from competition. Ten years later, the patient's sister was referred to the hospital for absolute idiopathic polycythaemia. Given the sister's history of polycythaemia, the hypoxia-regulating genes were sequenced, which revealed a pathogenic mutation in the <i>EGLN1</i> gene (p.Trp334Arg). <i>EGLN1</i> encodes the PHD2 protein, which plays a major role in the degradation of HIF2α. This mutation was found in the athlete and her sister, as well as in thr

亲爱的编辑，在即将举行的奥运会期间，兴奋剂检测工作将十分激烈。在耐力运动中使用的经典兴奋剂产品中，红细胞生成素（EPO）药物是主要 EPO 激素的生物复制品，可大幅提高血红蛋白（Hb）浓度和血细胞比容（Ht），无论从其使用年代（自 20 世纪 80 年代起就可使用）还是使用频率（2022 年全球共发生 61 例兴奋剂案件）来看，它都是原创产品之一[1]。第一个基因突变是在埃罗-曼蒂兰塔（Eero Mäntyranta）身上发现的，他曾多次获得越野滑雪奥运冠军和世界冠军奖牌[2]。当时，还没有任何技术可用于识别使用 EPO 药物或输血的血液兴奋剂，而这种方法在本世纪初得到了验证[3]。在这里，我们报告了两例仅因 Hb 和 Ht 值过高而被取消资格的顶级运动员。这些运动员在被取消运动资格数年后才被发现是家族性多发性红细胞增多症的携带者，而这些多发性红细胞增多症与参与缺氧传感通路的基因中的功能测试致病突变有关，这凸显了在做出严重指控之前进行专业检测的重要性。他在 16 岁时申请进入体育高中学习，但由于 Hb 和 Ht 值偏高（表 1），他的申请被拒。主治医生怀疑他服用了兴奋剂，因此禁止他参加高中体育学习和比赛。18 年后，他的儿子被诊断出患有多发性红细胞增多症，提示为家族性红细胞增多症，并使用 NGS 测序技术对父子俩的样本进行了分析，该测序技术使用的基因面板专门用于研究多发性红细胞增多症。在这对父子及其他三名亲属中发现了 EPAS1 的致病突变（p.Asp525Gly），该突变与多发性红细胞增多症表型分离。EPAS1 基因编码缺氧诱导因子 HIF2α，当氧气浓度降低时，HIF2α 可调节 EPO 的表达。第二份病历涉及一名国家顶级跆拳道运动员，例行检查发现其 Ht 和 Hb 值偏高（表 1），最终被禁止参加比赛。十年后，患者的姐姐因绝对性特发性多发性红细胞症转诊到医院。考虑到妹妹的多发性红细胞症病史，对其缺氧调节基因进行了测序，结果发现 EGLN1 基因发生了致病性突变（p.Trp334Arg）。EGLN1 编码 PHD2 蛋白，该蛋白在 HIF2α 的降解过程中起主要作用。尽管这两份病例报告令人遗憾地强调了过去区分血液兴奋剂和非典型高白蛋白的困难，但它们也显示了科学的进步，尤其是基因分析，现在可以为不常见的病例带来答案。自 2009 年以来，对高水平运动员的血液学参数进行了纵向跟踪，高 Hb 不再与使用兴奋剂相混淆[4]。最近，在 EPO 基因中发现的单核苷酸多态性（c.577del）与亚洲运动员的非典型 EPO 特征有关，目前在得出使用兴奋剂的结论前已将其考虑在内[5]。EPOR 的种系突变是第一个被证明能提高运动成绩的与红细胞生成有关的突变。我们在此表明，与氧有关的基因 EGLN1/PHD2 和 EPAS1/HIF2A 也应被列入越来越多的影响运动成绩基因的名单中。我们认为，运动员的高 Hb 值或 Ht 值需要使用 NGS 测序和专门的基因小组进行检测，以确定与遗传性红细胞增多症有关的基因异常。Nada Maaziz和Betty Gardie负责基因分析。François Girodon、Nada Maaziz 和 Betty Gardie 撰写了手稿。劳伦特-马丁（Laurent Martin）和亚历山大-马尔尚（Alexandre Marchand）审阅了手稿。弗朗索瓦-吉罗东指导了这项研究。所有作者都参与了这项研究，并批准了最终手稿。作者声明与本研究工作无潜在利益冲突，本研究未获得任何外部资助。

{"title":"Olympic Games: When the haematocrit does not fit, the athlete is not always a cheat","authors":"Nada Maaziz, Laurent Martin, Alexandre Marchand, Betty Gardie, François Girodon","doi":"10.1111/joim.13822","DOIUrl":"10.1111/joim.13822","url":null,"abstract":"<p>Dear Editor,</p><p>The upcoming Olympic Games will be accompanied by intense testing for doping, which is unfortunately not uncommon in top-level sporting circles. Among classic doping products used in endurance sports, erythropoietin (EPO) drug, the biological copy of the main EPO hormone responsible for substantial increases in haemoglobin (Hb) concentration and haematocrit (Ht), is one of the originals, both in terms of its age (available since the 1980s) and frequency of use (61 doping cases worldwide in 2022) [<span>1</span>].</p><p>The history of the Olympic Games is associated with the discovery of mutations in the EPO receptor gene, <i>EPOR</i>, in the 1990s. The first mutation was identified in Eero Mäntyranta, who won multiple Olympic and world champion medals in cross-country skiing [<span>2</span>]. At that time, no technique was available to identify blood doping using EPO drug, or transfusion, for which methods were validated in the early 2000s [<span>3</span>].</p><p>Here, we report two cases in which top-level athletes were disqualified solely on the basis of high Hb and Ht values. These athletes were found to be carriers of familial polycythaemia associated with functionally tested pathogenic mutations in genes involved in the hypoxia-sensing pathway several years after their disqualification from the sporting world, underlining the importance of having recourse to specialized testing before making serious accusations.</p><p>A 34-year-old male, who started playing soccer at a young age, applied to enter a sports-study high school when he was 16 years old. His application was rejected due to the presence of high Hb and Ht values (Table 1). The doctor overseeing his case suspected doping, leading to the man's subsequent ban from sports study in high school and competitions. Eighteen years later, his son was diagnosed with polycythaemia, suggesting familial erythrocytosis and samples from the father and son were analysed using NGS sequencing with a gene panel dedicated to the exploration of polycythaemia. A pathogenic mutation (p.Asp525Gly) in <i>EPAS1</i> was identified in the father and son and three other relatives segregating with a polycythaemia phenotype. The <i>EPAS1</i> gene encodes the hypoxia-inducible factor HIF2α, which regulates the expression of EPO when oxygen concentrations go down.</p><p>The second medical record concerns a top-level national Taekwondo athlete, for whom a routine examination revealed high Ht and Hb values (Table 1), leading to definitive banishment from competition. Ten years later, the patient's sister was referred to the hospital for absolute idiopathic polycythaemia. Given the sister's history of polycythaemia, the hypoxia-regulating genes were sequenced, which revealed a pathogenic mutation in the <i>EGLN1</i> gene (p.Trp334Arg). <i>EGLN1</i> encodes the PHD2 protein, which plays a major role in the degradation of HIF2α. This mutation was found in the athlete and her sister, as well as in thr","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 2","pages":"213-214"},"PeriodicalIF":9.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13822","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562198","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}

引用次数: 0

Adherence to guideline-recommended care of late-onset hypertension in females versus males: A population-based cohort study 女性与男性对晚期高血压指南推荐护理的依从性：基于人群的队列研究。

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2024-07-08 DOI: 10.1111/joim.13821

Ann Bugeja, Celine Girard, Manish M Sood, Claire E Kendall, Ally Sweet, Ria Singla, Pouya Motazedian, Amanda J Vinson, Marcel Ruzicka, Gregory L. Hundemer, Greg Knoll, Daniel I McIsaac

Background

Sex-based disparities in cardiovascular outcomes may be improved with appropriate hypertension management.

Objective

To compare the evidence-based evaluation and management of females with late-onset hypertension compared to males in the contemporary era.

Methods

Design: Retrospective population-based cohort study.

Setting: Ontario, Canada.

Participants: Residents aged ≥66 years with newly diagnosed hypertension between January 1, 2010, and December 31, 2017.

Exposure: Sex (female vs. male).

Outcomes and Measures: We used Poisson and logistic regression to estimate adjusted sex-attributable differences in the performance of guideline-recommended lab investigations. We estimated adjusted differences in time to the prescription of, and type of, first antihypertensive medication prescribed between females and males, using Cox regression.

Results

Among 111,410 adults (mean age 73 years, 53% female, median follow-up 6.8 years), females underwent a similar number of guideline-recommended investigations (adjusted incidence rate ratio, 0.997 [95% confidence interval [CI] 0.99–1.002]) compared to males. Females were also as likely to complete all investigations (0.70% females, 0.77% males; adjusted odds ratio, 0.96 [95% CI 0.83–1.11]). Females were slightly less likely to be prescribed medication (adjusted hazard ratio [aHR] 0.98 [95% CI 0.96–0.99]) or, among those prescribed, less likely to be prescribed first-line medication (aHR, 0.995 [95% CI 0.994–0.997]).

Conclusions

Compared to males, females with late-onset hypertension were equally likely to complete initial investigations with comparable prescription rates. These findings suggest that there may be no clinically meaningful sex-based differences in the initial management of late-onset hypertension to explain sex-based disparities in cardiovascular outcomes.

背景：适当的高血压管理可改善心血管疾病预后中的性别差异：通过适当的高血压管理可改善心血管预后中的性别差异：比较当代对晚发高血压女性患者与男性患者的循证评估和管理：方法：设计：设计：基于人群的回顾性队列研究：地点：加拿大安大略省：2010年1月1日至2017年12月31日期间新诊断出高血压的年龄≥66岁的居民.暴露：性别（女性与男性）.结果与测量：我们使用泊松回归和逻辑回归估算了指南推荐的实验室检查结果的调整后性别可归因差异。我们使用 Cox 回归估算了调整后的女性和男性首次处方抗高血压药物的时间和类型差异：在 111,410 名成年人（平均年龄 73 岁，53% 为女性，中位随访时间 6.8 年）中，女性接受指南推荐检查的次数与男性相似（调整后发病率比为 0.997 [95% 置信区间 [CI]0.99-1.002]）。女性完成所有检查的几率也与男性相当（女性为 0.70%，男性为 0.77%；调整后的几率比为 0.96 [95% CI 0.83-1.11]）。女性接受处方药物治疗的可能性略低（调整后危险比[aHR] 0.98 [95% CI 0.96-0.99]），在处方药物中，女性接受一线药物治疗的可能性较低（aHR，0.995 [95% CI 0.994-0.997]）：结论：与男性相比，女性晚发性高血压患者同样有可能完成初步检查，且处方率相当。这些研究结果表明，在晚发性高血压的初始管理中，可能不存在临床上有意义的性别差异，从而无法解释心血管结果的性别差异。

{"title":"Adherence to guideline-recommended care of late-onset hypertension in females versus males: A population-based cohort study","authors":"Ann Bugeja, Celine Girard, Manish M Sood, Claire E Kendall, Ally Sweet, Ria Singla, Pouya Motazedian, Amanda J Vinson, Marcel Ruzicka, Gregory L. Hundemer, Greg Knoll, Daniel I McIsaac","doi":"10.1111/joim.13821","DOIUrl":"10.1111/joim.13821","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sex-based disparities in cardiovascular outcomes may be improved with appropriate hypertension management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To compare the evidence-based evaluation and management of females with late-onset hypertension compared to males in the contemporary era.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p><i>Design</i>: Retrospective population-based cohort study.</p>\u0000 \u0000 <p><i>Setting</i>: Ontario, Canada.</p>\u0000 \u0000 <p><i>Participants</i>: Residents aged ≥66 years with newly diagnosed hypertension between January 1, 2010, and December 31, 2017.</p>\u0000 \u0000 <p><i>Exposure</i>: Sex (female vs. male).</p>\u0000 \u0000 <p><i>Outcomes and Measures</i>: We used Poisson and logistic regression to estimate adjusted sex-attributable differences in the performance of guideline-recommended lab investigations. We estimated adjusted differences in time to the prescription of, and type of, first antihypertensive medication prescribed between females and males, using Cox regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 111,410 adults (mean age 73 years, 53% female, median follow-up 6.8 years), females underwent a similar number of guideline-recommended investigations (adjusted incidence rate ratio, 0.997 [95% confidence interval [CI] 0.99–1.002]) compared to males. Females were also as likely to complete all investigations (0.70% females, 0.77% males; adjusted odds ratio, 0.96 [95% CI 0.83–1.11]). Females were slightly less likely to be prescribed medication (adjusted hazard ratio [aHR] 0.98 [95% CI 0.96–0.99]) or, among those prescribed, less likely to be prescribed first-line medication (aHR, 0.995 [95% CI 0.994–0.997]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Compared to males, females with late-onset hypertension were equally likely to complete initial investigations with comparable prescription rates. These findings suggest that there may be no clinically meaningful sex-based differences in the initial management of late-onset hypertension to explain sex-based disparities in cardiovascular outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 3","pages":"280-290"},"PeriodicalIF":9.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553822","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}

引用次数: 0

Regarding: IL-1β/DNA complex elevation distinguishes autoinflammatory disorders from autoimmune and infectious diseases 关于IL-1β/DNA 复合物升高可将自身炎症性疾病与自身免疫性疾病和传染性疾病区分开来。

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2024-07-08 DOI: 10.1111/joim.13818

Lian Wei Zhou, Manling Li, Wenbo Li

引用次数: 0

Authors reply: IL-1β/DNA complex elevation distinguishes autoinflammatory disorders from autoimmune and infectious diseases 作者回复：IL-1β/DNA 复合物的升高可将自身炎症性疾病与自身免疫性疾病和传染性疾病区分开来。

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2024-07-08 DOI: 10.1111/joim.13819

Anastasia-Maria Natsi, Efstratios Gavriilidis, Christina Antoniadou, Evangelos Papadimitriou, Vasileios Papadopoulos, Victoria Tsironidou, Dimitris Anastasios Palamidas, Loukas Chatzis, Eleni Sertaridou, Dimitrios Tsilingiris, Dimitrios T. Boumpas, Athanasios G. Tzioufas, Charalampos Papagoras, Konstantinos Ritis, Panagiotis Skendros

引用次数: 0

Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs 脊髓小脑共济失调 4 型是由 ZFHX3 基因的 GGC 扩增引起的，与突出的自主神经功能障碍和运动神经元体征有关。

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2024-07-07 DOI: 10.1111/joim.13815

Martin Paucar, Daniel Nilsson, Martin Engvall, José Laffita-Mesa, Cilla Söderhäll, Mikael Skorpil, Christer Halldin, Patrik Fazio, Kristina Lagerstedt-Robinson, Göran Solders, Maria Angeria, Andrea Varrone, Mårten Risling, Hong Jiao, Inger Nennesmo, Anna Wedell, Per Svenningsson

Background

Spinocerebellar ataxia 4 (SCA4), characterized in 1996, features adult-onset ataxia, polyneuropathy, and linkage to chromosome 16q22.1; its underlying mutation has remained elusive.

Objective

To explore the radiological and neuropathological abnormalities in the entire neuroaxis in SCA4 and search for its mutation.

Methods

Three Swedish families with undiagnosed ataxia went through clinical, neurophysiological, and neuroimaging tests, including PET studies and genetic investigations. In four cases, neuropathological assessments of the neuroaxis were performed. Genetic testing included short read whole genome sequencing, short tandem repeat analysis with ExpansionHunter de novo, and long read sequencing.

Results

Novel features for SCA4 include dysautonomia, motor neuron affection, and abnormal eye movements. We found evidence of anticipation; neuroimaging demonstrated atrophy in the cerebellum, brainstem, and spinal cord. [¹⁸F]FDG-PET demonstrated brain hypometabolism and [¹¹C]Flumazenil-PET reduced binding in several brain lobes, insula, thalamus, hypothalamus, and cerebellum. Moderate to severe loss of Purkinje cells in the cerebellum and of motor neurons in the anterior horns of the spinal cord along with pronounced degeneration of posterior tracts was also found. Intranuclear, mainly neuronal, inclusions positive for p62 and ubiquitin were sparse but widespread in the CNS. This finding prompted assessment for nucleotide expansions. A polyglycine stretch encoding GGC expansions in the last exon of the zink finger homeobox 3 gene was identified segregating with disease and not found in 1000 controls.

Conclusions

SCA4 is a neurodegenerative disease caused by a novel GGC expansion in the coding region of ZFHX3, and its spectrum is expanded to include dysautonomia and neuromuscular manifestations.

背景：脊髓小脑共济失调4（SCA4）于1996年定性，以成人发病的共济失调、多发性神经病为特征，与染色体16q22.1有关联；其潜在的突变一直难以确定：探讨 SCA4 整个神经轴的放射学和神经病理学异常，并寻找其基因突变：三个未确诊共济失调的瑞典家庭接受了临床、神经电生理和神经影像学检查，包括 PET 研究和遗传学调查。在四个病例中，对神经轴进行了神经病理学评估。基因检测包括短读数全基因组测序、短串联重复分析（ExpansionHunter de novo）和长读数测序：结果：SCA4 的新特征包括自主神经功能障碍、运动神经元病变和眼球运动异常。我们发现了预后的证据；神经影像学显示小脑、脑干和脊髓萎缩。[18F]FDG-PET显示大脑代谢低下，[11C]氟马西尼-PET减少了几个脑叶、岛叶、丘脑、下丘脑和小脑的结合。还发现小脑普肯野细胞和脊髓前角运动神经元中度至重度缺失，后束明显退化。核内（主要是神经元）p62 和泛素阳性包涵体稀少，但在中枢神经系统中广泛存在。这一发现促使对核苷酸扩增进行评估。结果发现，在zink finger homeobox 3基因的最后一个外显子中，编码GGC扩增的多甘氨酸伸展与疾病分离，而在1000例对照中没有发现：结论：SCA4 是一种由 ZFHX3 编码区中的新型 GGC 扩增引起的神经退行性疾病，其病谱扩大到包括自主神经功能障碍和神经肌肉表现。

{"title":"Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs","authors":"Martin Paucar, Daniel Nilsson, Martin Engvall, José Laffita-Mesa, Cilla Söderhäll, Mikael Skorpil, Christer Halldin, Patrik Fazio, Kristina Lagerstedt-Robinson, Göran Solders, Maria Angeria, Andrea Varrone, Mårten Risling, Hong Jiao, Inger Nennesmo, Anna Wedell, Per Svenningsson","doi":"10.1111/joim.13815","DOIUrl":"10.1111/joim.13815","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinocerebellar ataxia 4 (SCA4), characterized in 1996, features adult-onset ataxia, polyneuropathy, and linkage to chromosome 16q22.1; its underlying mutation has remained elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To explore the radiological and neuropathological abnormalities in the entire neuroaxis in SCA4 and search for its mutation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three Swedish families with undiagnosed ataxia went through clinical, neurophysiological, and neuroimaging tests, including PET studies and genetic investigations. In four cases, neuropathological assessments of the neuroaxis were performed. Genetic testing included short read whole genome sequencing, short tandem repeat analysis with ExpansionHunter de novo, and long read sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Novel features for SCA4 include dysautonomia, motor neuron affection, and abnormal eye movements. We found evidence of anticipation; neuroimaging demonstrated atrophy in the cerebellum, brainstem, and spinal cord. [<sup>18</sup>F]FDG-PET demonstrated brain hypometabolism and [<sup>11</sup>C]Flumazenil-PET reduced binding in several brain lobes, insula, thalamus, hypothalamus, and cerebellum. Moderate to severe loss of Purkinje cells in the cerebellum and of motor neurons in the anterior horns of the spinal cord along with pronounced degeneration of posterior tracts was also found. Intranuclear, mainly neuronal, inclusions positive for p62 and ubiquitin were sparse but widespread in the CNS. This finding prompted assessment for nucleotide expansions. A polyglycine stretch encoding GGC expansions in the last exon of the zink finger homeobox 3 gene was identified segregating with disease and not found in 1000 controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SCA4 is a neurodegenerative disease caused by a novel GGC expansion in the coding region of <i>ZFHX3</i>, and its spectrum is expanded to include dysautonomia and neuromuscular manifestations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 3","pages":"234-248"},"PeriodicalIF":9.0,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13815","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553825","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}

引用次数: 0

Performance of novel collagen turnover biomarkers to detect increased liver stiffness in MASLD 新型胶原蛋白周转生物标志物在检测 MASLD 中肝脏硬度增加方面的性能。

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2024-07-03 DOI: 10.1111/joim.13813

Hannes Hegmar, Thomas Wiggers, Patrik Nasr, Johan Vessby, Stergios Kechagias, Nils Nyhlin, Hanns-Ulrich Marschall, Åsa Danielsson Borssén, Rickard Strandberg, Morten Karsdal, Diana Julie Leeming, Mattias Ekstedt, Hannes Hagström

Background

Cleavage products from collagen formation and degradation hold potential as first-line biomarkers for the risk of advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we evaluated the performance of PRO-C3, PRO-C6, C4M, PRO-C18L, and the clinical score ADAPT (age, diabetes, PRO-C3, and platelet count) to detect patients with an LSM >8 kPa or >12 kPa in comparison to the Fibrosis-4 Index (FIB-4).

Methods

Serum from patients with MASLD (n = 269) from six Swedish University Hospitals was analyzed using enzyme-linked immunosorbent assay-based methods. Liver stiffness measurement (LSM) by vibration-controlled transient elastography was performed. The area under the curve (AUC), calibration curves, and net benefit analysis were used.

Results

An LSM >8 kPa was found in 108 (40.1%) patients. PRO-C3, PRO-C6, C4M, and PRO-C18L had AUCs ranging from 0.48 to 0.62. ADAPT had the highest AUC (0.73, 95% confidence interval [CI] = 0.67–0.79) to detect patients >8 kPa, compared to FIB-4 (0.71, (95%CI = 0.64–0.77, p = 0.35), and had a higher net benefit compared to FIB-4 from a probability threshold of 15%. FIB-4 and ADAPT performed equally well to detect patients with an LSM >12 kPa, AUC 0.76 versus 0.76, p = 0.93.

Conclusions

ADAPT seems to be marginally better than FIB-4 in identifying patients with an LSM >8 kPa. However, the clinical utility of ADAPT as a first line test is uncertain, especially in low-risk populations. The overall performance of FIB-4 was similar to that of ADAPT in detecting patients with an LSM of >12 kPa. Altogether, the results suggest that ADAPT might be useful to detect earlier stages of fibrosis in MASLD, but that FIB-4 remains a first-line test for advanced fibrosis.

背景：胶原形成和降解的裂解产物有可能成为代谢功能障碍相关性脂肪性肝病（MASLD）患者晚期纤维化风险的一线生物标志物。在此，我们评估了 PRO-C3、PRO-C6、C4M、PRO-C18L 和临床评分 ADAPT（年龄、糖尿病、PRO-C3 和血小板计数）与纤维化-4 指数（FIB-4）相比在检测 LSM >8 kPa 或 >12 kPa 患者方面的性能：方法：采用基于酶联免疫吸附试验的方法对瑞典六所大学医院的 MASLD 患者（n = 269）的血清进行分析。采用振动控制瞬态弹性成像技术测量肝脏硬度（LSM）。采用曲线下面积（AUC）、校准曲线和净效益分析：结果：108 例（40.1%）患者的 LSM >8 kPa。PRO-C3、PRO-C6、C4M 和 PRO-C18L 的 AUC 在 0.48 至 0.62 之间。与FIB-4（0.71，95%CI = 0.64-0.77，p = 0.35）相比，ADAPT检测出>8 kPa患者的AUC最高（0.73，95%置信区间[CI] = 0.67-0.79），与FIB-4相比，从15%的概率阈值来看，ADAPT的净获益更高。FIB-4 和 ADAPT 在检测 LSM >12 kPa 的患者方面表现相当，AUC 为 0.76 对 0.76，p = 0.93：在识别 LSM >8 kPa 患者方面，ADAPT 似乎略优于 FIB-4。然而，ADAPT作为一线检测的临床实用性尚不确定，尤其是在低风险人群中。在检测 LSM >12 kPa 的患者方面，FIB-4 的总体性能与 ADAPT 相似。总之，这些结果表明，ADAPT 可能有助于检测 MASLD 早期纤维化阶段，但 FIB-4 仍是晚期纤维化的一线检测方法。

{"title":"Performance of novel collagen turnover biomarkers to detect increased liver stiffness in MASLD","authors":"Hannes Hegmar, Thomas Wiggers, Patrik Nasr, Johan Vessby, Stergios Kechagias, Nils Nyhlin, Hanns-Ulrich Marschall, Åsa Danielsson Borssén, Rickard Strandberg, Morten Karsdal, Diana Julie Leeming, Mattias Ekstedt, Hannes Hagström","doi":"10.1111/joim.13813","DOIUrl":"10.1111/joim.13813","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cleavage products from collagen formation and degradation hold potential as first-line biomarkers for the risk of advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we evaluated the performance of PRO-C3, PRO-C6, C4M, PRO-C18L, and the clinical score ADAPT (<span>a</span>ge, <span>d</span>i<span>a</span>betes, <span>P</span>RO-C3, and pla<span>t</span>elet count) to detect patients with an LSM >8 kPa or >12 kPa in comparison to the Fibrosis-4 Index (FIB-4).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Serum from patients with MASLD (<i>n</i> = 269) from six Swedish University Hospitals was analyzed using enzyme-linked immunosorbent assay-based methods. Liver stiffness measurement (LSM) by vibration-controlled transient elastography was performed. The area under the curve (AUC), calibration curves, and net benefit analysis were used.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>An LSM >8 kPa was found in 108 (40.1%) patients. PRO-C3, PRO-C6, C4M, and PRO-C18L had AUCs ranging from 0.48 to 0.62. ADAPT had the highest AUC (0.73, 95% confidence interval [CI] = 0.67–0.79) to detect patients >8 kPa, compared to FIB-4 (0.71, (95%CI = 0.64–0.77, <i>p</i> = 0.35), and had a higher net benefit compared to FIB-4 from a probability threshold of 15%. FIB-4 and ADAPT performed equally well to detect patients with an LSM >12 kPa, AUC 0.76 versus 0.76, <i>p</i> = 0.93.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ADAPT seems to be marginally better than FIB-4 in identifying patients with an LSM >8 kPa. However, the clinical utility of ADAPT as a first line test is uncertain, especially in low-risk populations. The overall performance of FIB-4 was similar to that of ADAPT in detecting patients with an LSM of >12 kPa. Altogether, the results suggest that ADAPT might be useful to detect earlier stages of fibrosis in MASLD, but that FIB-4 remains a first-line test for advanced fibrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 2","pages":"177-186"},"PeriodicalIF":9.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496519","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}

引用次数: 0

Revealing the distinct clinical patterns and relapse risk factors in seronegative IgG4-RD patients: A retrospective cohort study over a decade 揭示血清阴性 IgG4-RD 患者的独特临床模式和复发风险因素：一项历时十年的回顾性队列研究。

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2024-06-24 DOI: 10.1111/joim.13814

Yu Peng, Mu Wang, Ruijie Sun, Yuxue Nie, Nianyi Zhang, Xin He, Boyuan Sun, Linyi Peng, Yunyun Fei, Jiaxin Zhou, Mengtao Li, Wen Zhang

Objectives

Our study aimed to investigate the distinct clinical patterns of seronegative IgG4-related disease (IgG4-RD) patients.

Methods

We retrospectively enrolled 698 treatment-naïve IgG4-RD patients in this study. Patients were divided into four different subgroups according to their baseline serum IgG4 levels. The distinct clinical patterns of seronegative IgG4-RD patients were revealed through the comparison of baseline clinical data and disease prognosis among the different subgroups. COX regression analyses were used to investigate the risk factors for disease relapse and to construct the nomogram model.

Results

Seronegative IgG4-RD patients account for a minority of IgG4-RD patients (49/698, 7.02%). The proportions of seronegative IgG-RD patients in our study and several Asian cohorts were significantly lower than those of the European and American cohorts. Seronegative IgG4-RD patients got lower serum IgG levels (p < 0.0001), lower eosinophil count (p < 0.0001), lower serum IgE levels (p < 0.0001)), lower IgG4-RD responder index (RI) scores (p < 0.0001), and fewer affected organ numbers (p < 0.0001) compared with other subgroups, whereas they were more likely to manifest fibrotic type with some special organ involvement. Younger age at onset, GCs monotherapy, elevated C-reactive protein level, and elevated erythrocyte sedimentation rate level are the risk factors for the disease relapse of seronegative IgG4-RD patients. An effective nomogram model predicting disease relapse of seronegative IgG4-RD patients was constructed. Seronegative IgG4-RD patients with scores >84.65 at baseline were susceptible to suffering from disease relapse.

Conclusions

Distinct clinical features and multiple risk factors for disease relapse of seronegative IgG4-RD patients have been revealed in this study. A nomogram model was constructed to effectively predict disease relapse during the follow-up period.

研究目的我们的研究旨在探讨血清阴性 IgG4 相关疾病（IgG4-RD）患者的独特临床模式：我们回顾性地纳入了 698 例未经治疗的 IgG4-RD 患者。根据基线血清 IgG4 水平，患者被分为四个不同的亚组。通过比较不同亚组的基线临床数据和疾病预后，揭示了血清阴性 IgG4-RD 患者不同的临床模式。COX回归分析用于研究疾病复发的风险因素并构建提名图模型：血清阴性IgG4-RD患者在IgG4-RD患者中占少数（49/698，7.02%）。在我们的研究和几个亚洲队列中，血清阴性 IgG-RD 患者的比例明显低于欧美队列。血清阴性 IgG4-RD 患者的血清 IgG 水平较低（p 84.65），容易复发：结论：本研究揭示了血清阴性 IgG4-RD 患者疾病复发的独特临床特征和多种风险因素。结论：本研究揭示了血清反应呈阴性的 IgG4-RD 患者复发的独特临床特征和多种风险因素，并构建了一个提名图模型，可有效预测随访期间的疾病复发。

{"title":"Revealing the distinct clinical patterns and relapse risk factors in seronegative IgG4-RD patients: A retrospective cohort study over a decade","authors":"Yu Peng, Mu Wang, Ruijie Sun, Yuxue Nie, Nianyi Zhang, Xin He, Boyuan Sun, Linyi Peng, Yunyun Fei, Jiaxin Zhou, Mengtao Li, Wen Zhang","doi":"10.1111/joim.13814","DOIUrl":"10.1111/joim.13814","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Our study aimed to investigate the distinct clinical patterns of seronegative IgG4-related disease (IgG4-RD) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively enrolled 698 treatment-naïve IgG4-RD patients in this study. Patients were divided into four different subgroups according to their baseline serum IgG4 levels. The distinct clinical patterns of seronegative IgG4-RD patients were revealed through the comparison of baseline clinical data and disease prognosis among the different subgroups. COX regression analyses were used to investigate the risk factors for disease relapse and to construct the nomogram model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seronegative IgG4-RD patients account for a minority of IgG4-RD patients (49/698, 7.02%). The proportions of seronegative IgG-RD patients in our study and several Asian cohorts were significantly lower than those of the European and American cohorts. Seronegative IgG4-RD patients got lower serum IgG levels (<i>p </i>< 0.0001), lower eosinophil count (<i>p</i> < 0.0001), lower serum IgE levels (<i>p </i>< 0.0001)), lower IgG4-RD responder index (RI) scores (<i>p</i> < 0.0001), and fewer affected organ numbers (<i>p </i>< 0.0001) compared with other subgroups, whereas they were more likely to manifest fibrotic type with some special organ involvement. Younger age at onset, GCs monotherapy, elevated C-reactive protein level, and elevated erythrocyte sedimentation rate level are the risk factors for the disease relapse of seronegative IgG4-RD patients. An effective nomogram model predicting disease relapse of seronegative IgG4-RD patients was constructed. Seronegative IgG4-RD patients with scores >84.65 at baseline were susceptible to suffering from disease relapse.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Distinct clinical features and multiple risk factors for disease relapse of seronegative IgG4-RD patients have been revealed in this study. A nomogram model was constructed to effectively predict disease relapse during the follow-up period.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 2","pages":"200-212"},"PeriodicalIF":9.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454117","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}

引用次数: 0

Making the best use of quantitative fecal immunochemical test results in colorectal cancer screening 在大肠癌筛查中充分利用粪便免疫化学定量检测结果。

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2024-06-18 DOI: 10.1111/joim.13812

Hermann Brenner, Michael Hoffmeister

<p>Fecal immunochemical tests (FITs) have become the most widely used tests for colorectal cancer (CRC) screening [<span>1</span>]. They detect the vast majority of CRCs and some proportion of advanced precancerous neoplasms [<span>2</span>], and modeling studies suggest that annual or biennial FIT-based screening programs have the potential to substantially lower the burden of CRC incidence and mortality [<span>3</span>]. Yet, uncertainty prevails with respect to the optimal use of FITs regarding a number of key parameters of screening programs, such as the starting age of screening, screening intervals, and positivity thresholds of FITs. In this issue, Westerberg et al. reported most valuable results from the baseline exam of the large Swedish SCREESCO screening trial that may inform the design and planning of screening programs [<span>4</span>]. In particular, the study allows thorough evaluation of the tradeoffs between increasing the positive predictive value (PPV) and the decreasing numbers needed to undergo colonoscopy (“numbers needed to scope”, NNS) on one hand, and decreasing sensitivity on the other hand, when increasing the FIT positivity threshold from 10 μg hemoglobin (Hb)/g feces to higher levels. These data may be most valuable for multiple purposes, including the provision of key background information for more comprehensive modeling of the effectiveness and cost-effectiveness of various screening strategies.</p><p>However, in the interpretation of the results, a number of additional factors require careful consideration. In the SCREESCO trial, two FITs per screening round were applied, and the overall test result was rated as positive if one of the two FITs showed an Hb concentration >10 μg/g feces in the baseline scenario, or >20, 40, 60, 80, 120, or 160 μg/g in the alternative scenarios. By contrast, in most screening programs, just one FIT is employed per screening round. Defining the result as positive if one of two tests is positive increases the sensitivity and decreases the specificity compared to the application of a single test. This implies that comparable positivity rates and sensitivity would be expected at somewhat lower cutoffs in one-sample rather than two-sample testing, which should be kept in mind in interpreting the presented data. It remains an open question whether two-sample testing is worth the extra effort and cost. Possibly, (almost) equivalent results as those reported by Westerberg et al. could be obtained with one-sample testing by lowering the FIT cutoff [<span>5</span>]. Further analyses of the dataset by Westerberg et al. may offer unique opportunities to answer this question.</p><p>Another important aspect to keep in mind is that all the results reported by Westerberg et al. refer to a first-round FIT screening. With annual or biennial FIT-based screening, as recommended and practiced in many countries, the prevalences of advanced neoplasms will decrease at subsequent screening rounds. Altho

Westerberg 等人的研究无法解决的一个问题是，缺乏粪便中 Hb 浓度低于 10 μg Hb/g 粪便的参与者的结肠镜检查结果，作者对此进行了仔细讨论。因此，只能得出相对灵敏度而非绝对灵敏度，而且目前还不清楚各类 FIT 阳性参与者的肿瘤发病率与绝大多数 FIT 阴性筛查参与者的肿瘤发病率相比如何。这些信息可以从其他在结肠镜筛查背景下进行的研究中获得[9]。这些数据显示，即使是粪便 Hb 浓度在 10-25 μg/g 粪便之间的 "低阳性范围 "人群，与绝大多数 Hb 浓度低于 8 μg/g 粪便的 80% 筛查参与者相比，携带任何 AN 的风险也要高出 3.5 倍。在 "低阳性范围 "中，风险已经大大增加，这表明 Westerberg 等人观察到，与 10 μg Hb/g 临界值相比，FIT 临界值越高，PPV 越高，NNS 越低，但这不应被解释为支持提高 FIT 临界值。尽管在某些情况下，由于结肠镜检查资源有限，较高的临界值可能是不可避免的，但与绝大多数筛查人群相比，在基于 FIT 检测出 AN 风险增加≥3.5 倍后，似乎有必要进行结肠镜随访。随机对照试验（RCT）从概念提出到获得长期发病率和死亡率结果需要很长的时间，而且样本量非常大，即使只比较两种不同的筛查策略也是如此。这极大地限制了 RCT 在评估创新筛查方法时的实施和使用。精心设计的模型研究可能是及时评估新型筛查策略的一种有前途的合理补充方法[10]。Westerberg 等人报告的关于 FIT 诊断性能参数的详细结果，以及来自筛查结肠镜队列的数据，可能对基于 FIT 和替代筛查方法的建模研究非常有价值：赫尔曼-布伦纳：写作-原稿；写作-审阅和编辑；构思。迈克尔-霍夫迈斯特作者无利益冲突需要声明。

{"title":"Making the best use of quantitative fecal immunochemical test results in colorectal cancer screening","authors":"Hermann Brenner, Michael Hoffmeister","doi":"10.1111/joim.13812","DOIUrl":"10.1111/joim.13812","url":null,"abstract":"<p>Fecal immunochemical tests (FITs) have become the most widely used tests for colorectal cancer (CRC) screening [<span>1</span>]. They detect the vast majority of CRCs and some proportion of advanced precancerous neoplasms [<span>2</span>], and modeling studies suggest that annual or biennial FIT-based screening programs have the potential to substantially lower the burden of CRC incidence and mortality [<span>3</span>]. Yet, uncertainty prevails with respect to the optimal use of FITs regarding a number of key parameters of screening programs, such as the starting age of screening, screening intervals, and positivity thresholds of FITs. In this issue, Westerberg et al. reported most valuable results from the baseline exam of the large Swedish SCREESCO screening trial that may inform the design and planning of screening programs [<span>4</span>]. In particular, the study allows thorough evaluation of the tradeoffs between increasing the positive predictive value (PPV) and the decreasing numbers needed to undergo colonoscopy (“numbers needed to scope”, NNS) on one hand, and decreasing sensitivity on the other hand, when increasing the FIT positivity threshold from 10 μg hemoglobin (Hb)/g feces to higher levels. These data may be most valuable for multiple purposes, including the provision of key background information for more comprehensive modeling of the effectiveness and cost-effectiveness of various screening strategies.</p><p>However, in the interpretation of the results, a number of additional factors require careful consideration. In the SCREESCO trial, two FITs per screening round were applied, and the overall test result was rated as positive if one of the two FITs showed an Hb concentration >10 μg/g feces in the baseline scenario, or >20, 40, 60, 80, 120, or 160 μg/g in the alternative scenarios. By contrast, in most screening programs, just one FIT is employed per screening round. Defining the result as positive if one of two tests is positive increases the sensitivity and decreases the specificity compared to the application of a single test. This implies that comparable positivity rates and sensitivity would be expected at somewhat lower cutoffs in one-sample rather than two-sample testing, which should be kept in mind in interpreting the presented data. It remains an open question whether two-sample testing is worth the extra effort and cost. Possibly, (almost) equivalent results as those reported by Westerberg et al. could be obtained with one-sample testing by lowering the FIT cutoff [<span>5</span>]. Further analyses of the dataset by Westerberg et al. may offer unique opportunities to answer this question.</p><p>Another important aspect to keep in mind is that all the results reported by Westerberg et al. refer to a first-round FIT screening. With annual or biennial FIT-based screening, as recommended and practiced in many countries, the prevalences of advanced neoplasms will decrease at subsequent screening rounds. Altho","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 2","pages":"118-120"},"PeriodicalIF":9.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13812","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417043","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}

引用次数: 0

Colonoscopy findings after increasing two-stool faecal immunochemical test (FIT) cut-off: Cross-sectional analysis of the SCREESCO randomized trial 提高双凳粪便免疫化学检验 (FIT) 临界值后的结肠镜检查结果：SCREESCO 随机试验的横断面分析。

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2024-06-06 DOI: 10.1111/joim.13810

Marcus Westerberg, Julia Eriksson, Chris Metcalfe, Christian Löwbeer, Anders Ekbom, Robert Steele, Lars Holmberg, Anna Forsberg

Background

We determined the impact of an increased two-stool faecal immunochemical test (FIT) cut-off on colonoscopy positivity and relative sensitivity and specificity in the randomized controlled screening trial screening of Swedish colons conducted in Sweden.

Methods

We performed a cross-sectional analysis of participants in the FIT arm that performed FIT between March 2014 and 2020 within the study registered with ClinicalTrials.gov, NCT02078804, who had a faecal haemoglobin concentration of at least 10 µg/g in at least one of two stool samples and who underwent a colonoscopy (n = 3841). For each increase in cut-off, we computed the positive predictive value (PPV), numbers needed to scope (NNS), sensitivity and specificity for finding colorectal cancer (CRC) and advanced neoplasia (AN; advanced adenoma or CRC) relative to cut-off 10 µg/g.

Results

The PPV for AN increased from 23.0% (95% confidence intervals [CI]: 22.3%–23.6%) at cut-off 10 µg/g to 28.8% (95% CI: 27.8%–29.7%) and 33.1% (95% CI: 31.9%–34.4%) at cut-offs 20 and 40 µg/g, respectively, whereas the NNS to find a CRC correspondingly decreased from 41 to 27 and 19. The PPV for AN was higher in men than women at each cut-off, for example 31.5% (95% CI: 30.1%–32.8%) in men and 25.6% (95% CI: 24.3%–27.0%) in women at 20 µg/g. The relative sensitivity and relative specificity were similar in men and women at each cut-off.

Conclusion

A low cut-off of around 20–40 µg/g allows detection and removal of many AN compared to 10 µg/g while reducing the number of colonoscopies in both men and women.

背景：我们确定了在瑞典进行的瑞典结肠随机对照筛查试验中，提高两凳粪便免疫化学检验（FIT）截止值对结肠镜检查阳性率以及相对敏感性和特异性的影响：我们对 2014 年 3 月至 2020 年期间在 ClinicalTrials.gov, NCT02078804 登记的研究中进行了 FIT 试验的 FIT 组参与者进行了横断面分析，这些参与者在两个粪便样本中至少有一个样本的粪便血红蛋白浓度至少为 10 µg/g，并且接受了结肠镜检查（n = 3841）。每提高一个临界值，我们都会计算相对于临界值 10 µg/g 的阳性预测值 (PPV)、所需检查人数 (NNS)、发现结直肠癌 (CRC) 和晚期肿瘤 (AN; 晚期腺瘤或 CRC) 的灵敏度和特异性：AN的PPV从临界值10微克/克时的23.0%（95%置信区间[CI]：22.3%-23.6%）分别增加到临界值20微克/克和40微克/克时的28.8%（95%置信区间：27.8%-29.7%）和33.1%（95%置信区间：31.9%-34.4%），而发现CRC的NNS则相应地从41下降到27和19。在每个临界值下，男性 AN 的 PPV 均高于女性，例如，在 20 µg/g 临界值下，男性为 31.5%（95% CI：30.1%-32.8%），女性为 25.6%（95% CI：24.3%-27.0%）。在每个临界值下，男性和女性的相对敏感性和相对特异性相似：结论：与 10 微克/克相比，20-40 微克/克的低临界值可以检测并清除许多 AN，同时减少男性和女性的结肠镜检查次数。

{"title":"Colonoscopy findings after increasing two-stool faecal immunochemical test (FIT) cut-off: Cross-sectional analysis of the SCREESCO randomized trial","authors":"Marcus Westerberg, Julia Eriksson, Chris Metcalfe, Christian Löwbeer, Anders Ekbom, Robert Steele, Lars Holmberg, Anna Forsberg","doi":"10.1111/joim.13810","DOIUrl":"10.1111/joim.13810","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>We determined the impact of an increased two-stool faecal immunochemical test (FIT) cut-off on colonoscopy positivity and relative sensitivity and specificity in the randomized controlled screening trial screening of Swedish colons conducted in Sweden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a cross-sectional analysis of participants in the FIT arm that performed FIT between March 2014 and 2020 within the study registered with ClinicalTrials.gov, NCT02078804, who had a faecal haemoglobin concentration of at least 10 µg/g in at least one of two stool samples and who underwent a colonoscopy (<i>n</i> = 3841). For each increase in cut-off, we computed the positive predictive value (PPV), numbers needed to scope (NNS), sensitivity and specificity for finding colorectal cancer (CRC) and advanced neoplasia (AN; advanced adenoma or CRC) relative to cut-off 10 µg/g.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The PPV for AN increased from 23.0% (95% confidence intervals [CI]: 22.3%–23.6%) at cut-off 10 µg/g to 28.8% (95% CI: 27.8%–29.7%) and 33.1% (95% CI: 31.9%–34.4%) at cut-offs 20 and 40 µg/g, respectively, whereas the NNS to find a CRC correspondingly decreased from 41 to 27 and 19. The PPV for AN was higher in men than women at each cut-off, for example 31.5% (95% CI: 30.1%–32.8%) in men and 25.6% (95% CI: 24.3%–27.0%) in women at 20 µg/g. The relative sensitivity and relative specificity were similar in men and women at each cut-off.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A low cut-off of around 20–40 µg/g allows detection and removal of many AN compared to 10 µg/g while reducing the number of colonoscopies in both men and women.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 2","pages":"187-199"},"PeriodicalIF":9.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13810","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282500","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}

引用次数: 0