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}
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":"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}
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":"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}
<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}
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":"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}
Abdul Mannan Khan Minhas, Marat Fudim, Erin D. Michos, Dmitry Abramov
Background
The COVID-19 pandemic, which started in 2020, resulted in greater all-cause mortality in 2020 and in subsequent years. Whether all-cause mortality remains elevated in 2023 compared to pre-pandemic numbers is unknown.
Methods and results
The United States (US) Center for Disease Control Wide-Ranging, Online Data for Epidemiologic Research database was used to compare mortality rates between 2019 and provisional data for 2022 and 2023. Age-adjusted mortality rates (AAMRs) for all-cause as well as top causes of mortality were collected. Mortality based on subgroups by sex, age, and ethnicity was also collected. All-cause AAMRs between 2018 and 2023 per 100,000 individuals were 723.6, 715.2, 835.4, 879.7, (provisionally) 798.8, and (provisionally) 738.3, respectively, with AAMRs in 2023 remaining above 2019 pre-pandemic levels. Similar trends were noted in subgroups based on sex, ethnicity, and most age groups. Mortality attributed directly to COVID-19 peaked in 2021 as the 3rd leading cause of death and dropped to the 10th leading cause in 2023. Provisional mortality rate trends for 2023 suggest that rates for diseases of the heart increased during the pandemic but appear to have returned to or dipped below pre-pandemic levels.
Conclusion
Provisional 2023 all-cause mortality rates in the US have decreased from the 2021 peak associated with the COVID-19 pandemic but remain above the pre-pandemic baseline. Mortality from some conditions, including diseases of the heart, appears to have recovered from the impact of the COVID-19 pandemic.
{"title":"Has mortality in the United States returned to pre-pandemic levels? An analysis of provisional 2023 data","authors":"Abdul Mannan Khan Minhas, Marat Fudim, Erin D. Michos, Dmitry Abramov","doi":"10.1111/joim.13811","DOIUrl":"10.1111/joim.13811","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The COVID-19 pandemic, which started in 2020, resulted in greater all-cause mortality in 2020 and in subsequent years. Whether all-cause mortality remains elevated in 2023 compared to pre-pandemic numbers is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>The United States (US) Center for Disease Control Wide-Ranging, Online Data for Epidemiologic Research database was used to compare mortality rates between 2019 and provisional data for 2022 and 2023. Age-adjusted mortality rates (AAMRs) for all-cause as well as top causes of mortality were collected. Mortality based on subgroups by sex, age, and ethnicity was also collected. All-cause AAMRs between 2018 and 2023 per 100,000 individuals were 723.6, 715.2, 835.4, 879.7, (provisionally) 798.8, and (provisionally) 738.3, respectively, with AAMRs in 2023 remaining above 2019 pre-pandemic levels. Similar trends were noted in subgroups based on sex, ethnicity, and most age groups. Mortality attributed directly to COVID-19 peaked in 2021 as the 3rd leading cause of death and dropped to the 10th leading cause in 2023. Provisional mortality rate trends for 2023 suggest that rates for diseases of the heart increased during the pandemic but appear to have returned to or dipped below pre-pandemic levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Provisional 2023 all-cause mortality rates in the US have decreased from the 2021 peak associated with the COVID-19 pandemic but remain above the pre-pandemic baseline. Mortality from some conditions, including diseases of the heart, appears to have recovered from the impact of the COVID-19 pandemic.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 2","pages":"168-176"},"PeriodicalIF":9.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13811","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141198838","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}
The hypothalamic–pituitary–adrenal axis is an extremely dynamic system with a combination of both circadian and ultradian oscillations. This state of ‘continuous dynamic equilibration’ provides a platform that is able to anticipate events, is sensitive in its response to stressors, remains robust during perturbations of both the internal and external environments and shows plasticity to adapt to a changed environment. In this review, we describe these oscillations of glucocorticoid (GC) hormones and why they are so important for GC-dependent gene activation in the brain and liver, and their consequent effects on the regulation of synaptic and memory function as well as appetite control and metabolic regulation. Abnormalities of mood, appetite and metabolic regulation are well-known consequences of GC therapy, and we suggest that the pattern of GC treatment and hormone replacement should be a much higher priority for endocrinologists and the pharmaceutical industry. One of the major impediments to our research on the importance of these cortisol rhythms in our patients has been our inability to measure repeated levels of hormones across the day in patients in their home or work surroundings. We describe how new wearable methodologies now allow the measurement of 24-h cortisol profiles – including during sleep – and will enable us to define physiological normality and allow us both to develop better diagnostic tests and inform, at an individual patient level, how to improve replacement therapy.
{"title":"Circadian and ultradian rhythms: Clinical implications","authors":"Stafford L. Lightman, Becky L. Conway-Campbell","doi":"10.1111/joim.13795","DOIUrl":"10.1111/joim.13795","url":null,"abstract":"<p>The hypothalamic–pituitary–adrenal axis is an extremely dynamic system with a combination of both circadian and ultradian oscillations. This state of ‘continuous dynamic equilibration’ provides a platform that is able to anticipate events, is sensitive in its response to stressors, remains robust during perturbations of both the internal and external environments and shows plasticity to adapt to a changed environment. In this review, we describe these oscillations of glucocorticoid (GC) hormones and why they are so important for GC-dependent gene activation in the brain and liver, and their consequent effects on the regulation of synaptic and memory function as well as appetite control and metabolic regulation. Abnormalities of mood, appetite and metabolic regulation are well-known consequences of GC therapy, and we suggest that the pattern of GC treatment and hormone replacement should be a much higher priority for endocrinologists and the pharmaceutical industry. One of the major impediments to our research on the importance of these cortisol rhythms in our patients has been our inability to measure repeated levels of hormones across the day in patients in their home or work surroundings. We describe how new wearable methodologies now allow the measurement of 24-h cortisol profiles – including during sleep – and will enable us to define physiological normality and allow us both to develop better diagnostic tests and inform, at an individual patient level, how to improve replacement therapy.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 2","pages":"121-138"},"PeriodicalIF":9.0,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13795","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141198837","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}
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
<p>IL-1-mediated autoinflammatory diseases (AID) consist of a heterogeneous group of innate immunity disorders [<span>1</span>]. Despite increasing awareness and research, differential diagnosis, particularly from other febrile conditions, allowing the timely initiation of appropriate therapy remains challenging because no diagnostic assay suitable for everyday clinical practice exists. In this context, several reports have shown that circulating levels of free IL-1 are neither informative nor correlated with disease causality and/or flare [<span>2</span>]. However, previous studies indicated that the release of neutrophil extracellular traps (NETs) carrying IL-1β on their DNA structure is a prominent feature of inflammatory attacks in familial Mediterranean fever and other AID [<span>3, 4</span>]. Despite the established role of microscopy methods to study NETs [<span>5</span>], we sought to develop a simple assay, not dependent on freshly isolated neutrophils, which could easily determine the amount of IL-1β being in complex with extracellular DNA in circulation and evaluate its diagnostic utility in AID.</p><p>First, we confirmed by immunofluorescence microscopy that neutrophils, ex vivo isolated from representative patients suffering from inflammatory attacks of a typical AID, were characterized by spontaneous formation of IL-1β-enriched NETs (Fig. 1A–F). These results were consistent with the high amounts of IL-1β detected in complex with circulating DNA, as determined by a novel “in-house” IL-1β/DNA complex-specific ELISA assay in plasma samples concurrently isolated from the same patients (Fig. 1G). Additionally, the mean fluorescence intensity of microscopy sections correlated well with IL-1β/DNA complex values (Fig. 1H).</p><p>Next, considering that circulating IL-1β/DNA complex levels were consistent with IL-1β-bearing NETs, we extended our study by evaluating the IL-1β/DNA complex assay in different control groups of well-characterized patients with inflammatory disorders. Significantly higher values of IL-1β/DNA complexes in AID flare, compared to active autoimmune rheumatic diseases (ARD), acute infections (INF), and healthy individuals were observed (Fig. 1I). These results were further supported by immunofluorescence microscopy in randomly selected patients from the control groups (Fig. S1). A cut-off of >0.050 arbitrary units was sufficient to distinguish AID from either INF or ARD with a sensitivity of 92.0% and a specificity of 86.4% (AUC of the ROC 0.922 ± 0.042; <i>p</i> < 10<sup>−6</sup>) (Fig. 1J, Table S1). Of note, levels of circulating free IL-1β and cell-free DNA, as measured simultaneously by a commercially available IL-1β ELISA and SYTOX-green dye, respectively, did not differ among groups (Fig. 1K,L). Moreover, in the total number of samples, IL-1β/DNA complex values did not correlate with free IL-1β (Fig. 1M) or cell-free DNA levels (Fig. 1N). These data suggest that the IL-1β/DNA complex assay can selectively
IL-1介导的自身炎症性疾病（AID）是一组异质性的先天性免疫疾病[1]。尽管人们的认识和研究不断提高，但鉴别诊断（尤其是与其他发热性疾病的鉴别诊断）以及及时启动适当的治疗仍具有挑战性，因为目前还没有适合日常临床实践的诊断方法。在这种情况下，一些报告显示，循环中的游离 IL-1 水平既不能提供信息，也与疾病的因果关系和/或发作无关[2]。然而，先前的研究表明，中性粒细胞胞外捕获物（NET）的 DNA 结构上携带 IL-1β 是家族性地中海热和其他 AID 炎症发作的一个显著特征[3, 4]。首先，我们通过免疫荧光显微镜证实，从典型 AID 炎症发作的代表性患者体内分离出的中性粒细胞具有自发形成富含 IL-1β 的 NET 的特征（图 1A-F）。这些结果与通过新型 "内部 "IL-1β/DNA 复合物特异性酶联免疫吸附测定法检测到的大量 IL-1β 与循环 DNA 的复合物相吻合（图 1G）。此外，显微镜切片的平均荧光强度与IL-1β/DNA复合物的值有很好的相关性（图1H）。接下来，考虑到循环中的IL-1β/DNA复合物水平与携带IL-1β的NET一致，我们扩大了研究范围，在不同的对照组中对IL-1β/DNA复合物检测进行了评估，这些对照组都是特征明确的炎症性疾病患者。与活动性自身免疫性风湿病 (ARD)、急性感染 (INF) 和健康人相比，在 AID 爆发期观察到的 IL-1β/DNA 复合物值明显更高（图 1I）。从对照组中随机抽取的患者的免疫荧光显微镜进一步证实了这些结果（图 S1）。0.050任意单位的临界值足以将AID与INF或ARD区分开来，灵敏度为92.0%，特异度为86.4%（ROC的AUC为0.922 ± 0.042；p为10-6）（图1J，表S1）。值得注意的是，用市售的 IL-1β 酶联免疫吸附法和 SYTOX 绿色染料同时测定的循环游离 IL-1β 和游离细胞 DNA 水平在各组间没有差异（图 1K、L）。此外，在所有样本中，IL-1β/DNA 复合物值与游离 IL-1β（图 1M）或细胞游离 DNA 水平（图 1N）不相关。这些数据表明，IL-1β/DNA 复合物测定可选择性地检测与细胞外 DNA 结合的 IL-1β 量，而不受循环 DNA 总量或游离 IL-1β （无论高低）的影响。最后，在一组 AID 患者中，使用 IL-1 抑制剂 Anakinra 或 canakinumab 成功治疗后，IL-1β/DNA 复合物显著减少（图 1O）。有关研究小组、IL-1β/DNA 复合物测定原理（包括使用 canakinumab 或 DNase 进行体外抑制研究以评估其可靠性）以及所采用的方法和统计信息的详细信息，请参阅 "辅助信息 "部分。总之，我们提供的新证据表明，用 ELISA 评估血浆中 IL-1β/DNA 复合物的水平是一种灵敏而特异的工具，具有很高的诊断效用，有助于将 AID 与其他急性炎症性疾病进行鉴别诊断。它还可以作为评估接受 IL-1 抑制剂治疗的患者的治疗反应的一种方法。这些初步结果为更大规模的多中心研究铺平了道路，这些研究对于进一步验证该测定在异质性炎症性疾病中的诊断/预后效用非常重要：构思；指导：Konstantinos Ritis 和 Panagiotis Skendros。方法学：Anastasia-Maria Natsi、Efstratios Gavriilidis、Vasileios Papadopoulos 和 Dimitrios Tsilingiris。调查：Anastasia-Maria Natsi、Efstratios Gavriilidis、Christina Antoniadou、Evangelos Papadimitriou、Victoria Tsironidou、Dimitris Anastasios Palamidas、Loukas Chatzis、Eleni Sertaridou、Charalampos Papagoras、Dimitrios T. Boumpas 和 Athanasios G. Tzioufas。可视化：Anastasia-Maria Natsi、Efstratios Gavriilidis、Christina Antoniadou 和 Vasileios Papadopoulos。资金获取；项目管理：Panagiotis Skendros。写作-原稿：Anastasia-Maria Natsi、Efstratios Gavriilidis、Christina Antoniadou、Vasileios Papadopoulos、Konstantinos Ritis 和 Panagiotis Skendros。
{"title":"IL-1β/DNA complex elevation distinguishes autoinflammatory disorders from autoimmune and infectious diseases","authors":"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","doi":"10.1111/joim.13809","DOIUrl":"10.1111/joim.13809","url":null,"abstract":"<p>IL-1-mediated autoinflammatory diseases (AID) consist of a heterogeneous group of innate immunity disorders [<span>1</span>]. Despite increasing awareness and research, differential diagnosis, particularly from other febrile conditions, allowing the timely initiation of appropriate therapy remains challenging because no diagnostic assay suitable for everyday clinical practice exists. In this context, several reports have shown that circulating levels of free IL-1 are neither informative nor correlated with disease causality and/or flare [<span>2</span>]. However, previous studies indicated that the release of neutrophil extracellular traps (NETs) carrying IL-1β on their DNA structure is a prominent feature of inflammatory attacks in familial Mediterranean fever and other AID [<span>3, 4</span>]. Despite the established role of microscopy methods to study NETs [<span>5</span>], we sought to develop a simple assay, not dependent on freshly isolated neutrophils, which could easily determine the amount of IL-1β being in complex with extracellular DNA in circulation and evaluate its diagnostic utility in AID.</p><p>First, we confirmed by immunofluorescence microscopy that neutrophils, ex vivo isolated from representative patients suffering from inflammatory attacks of a typical AID, were characterized by spontaneous formation of IL-1β-enriched NETs (Fig. 1A–F). These results were consistent with the high amounts of IL-1β detected in complex with circulating DNA, as determined by a novel “in-house” IL-1β/DNA complex-specific ELISA assay in plasma samples concurrently isolated from the same patients (Fig. 1G). Additionally, the mean fluorescence intensity of microscopy sections correlated well with IL-1β/DNA complex values (Fig. 1H).</p><p>Next, considering that circulating IL-1β/DNA complex levels were consistent with IL-1β-bearing NETs, we extended our study by evaluating the IL-1β/DNA complex assay in different control groups of well-characterized patients with inflammatory disorders. Significantly higher values of IL-1β/DNA complexes in AID flare, compared to active autoimmune rheumatic diseases (ARD), acute infections (INF), and healthy individuals were observed (Fig. 1I). These results were further supported by immunofluorescence microscopy in randomly selected patients from the control groups (Fig. S1). A cut-off of >0.050 arbitrary units was sufficient to distinguish AID from either INF or ARD with a sensitivity of 92.0% and a specificity of 86.4% (AUC of the ROC 0.922 ± 0.042; <i>p</i> < 10<sup>−6</sup>) (Fig. 1J, Table S1). Of note, levels of circulating free IL-1β and cell-free DNA, as measured simultaneously by a commercially available IL-1β ELISA and SYTOX-green dye, respectively, did not differ among groups (Fig. 1K,L). Moreover, in the total number of samples, IL-1β/DNA complex values did not correlate with free IL-1β (Fig. 1M) or cell-free DNA levels (Fig. 1N). These data suggest that the IL-1β/DNA complex assay can selectively ","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 3","pages":"298-301"},"PeriodicalIF":9.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13809","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160821","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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