Sining Xie, Federica Galimberti, Elena Olmastroni, Alberico L. Catapano, Manuela Casula
Dear Editor,
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 [1]. 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 [2, 3]. 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 [4, 5], and by −0.66 mg/L (95%CI, −0.98 to −0.35) in patients with acute MI [6], 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 [7].
Given the growing interest in targeting inflammation to further reduce CV risk and the recent inclusion of colchicine among CV preventive therapies [8], 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.
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.
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
{"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":null,"pages":null},"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}
Nada Maaziz, Laurent Martin, Alexandre Marchand, Betty Gardie, François Girodon
Dear Editor,
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) [1].
The history of the Olympic Games is associated with the discovery of mutations in the EPO receptor gene, EPOR, in the 1990s. The first mutation was identified in Eero Mäntyranta, who won multiple Olympic and world champion medals in cross-country skiing [2]. 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 [3].
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.
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 EPAS1 was identified in the father and son and three other relatives segregating with a polycythaemia phenotype. The EPAS1 gene encodes the hypoxia-inducible factor HIF2α, which regulates the expression of EPO when oxygen concentrations go down.
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 EGLN1 gene (p.Trp334Arg). EGLN1 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
{"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":null,"pages":null},"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}
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.
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":null,"pages":null},"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}
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":null,"pages":null},"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}
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.
{"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":null,"pages":null},"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}
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.
{"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":null,"pages":null},"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}
Fecal immunochemical tests (FITs) have become the most widely used tests for colorectal cancer (CRC) screening [1]. They detect the vast majority of CRCs and some proportion of advanced precancerous neoplasms [2], 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 [3]. 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 [4]. 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.
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 [5]. Further analyses of the dataset by Westerberg et al. may offer unique opportunities to answer this question.
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":null,"pages":null},"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}
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.
{"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":null,"pages":null},"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}
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