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Chronic Pancreatitis and Pregnancy: Genetics Matter 慢性胰腺炎与怀孕遗传因素
IF 3.6 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000698
Y. Hernandez-Barco, J. McNabb-Baltar
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引用次数: 0
Deep Learning in High-Resolution Anoscopy: Assessing the Impact of Staining and Therapeutic Manipulation on Automated Detection of Anal Cancer Precursors. 高分辨率肛门镜中的深度学习:评估染色和治疗操作对自动检测肛门癌前兆的影响。
IF 3.6 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000681
Miguel Mascarenhas Saraiva, Lucas Spindler, Nadia Fathallah, Hélene Beaussier, Célia Mamma, Tiago Ribeiro, João Afonso, Mariana Carvalho, Rita Moura, Pedro Cardoso, Francisco Mendes, Miguel Martins, Julien Adam, João Ferreira, Guilherme Macedo, Vincent de Parades

Introduction: High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell carcinoma (ASCC) precursors. Preliminary studies on the application of artificial intelligence (AI) models to this modality have revealed promising results. However, the impact of staining techniques and anal manipulation on the effectiveness of these algorithms has not been evaluated. We aimed to develop a deep learning system for automatic differentiation of high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion in HRA images in different subsets of patients (nonstained, acetic acid, lugol, and after manipulation).

Methods: A convolutional neural network was developed to detect and differentiate high-grade and low-grade anal squamous intraepithelial lesions based on 27,770 images from 103 HRA examinations performed in 88 patients. Subanalyses were performed to evaluate the algorithm's performance in subsets of images without staining, acetic acid, lugol, and after manipulation of the anal canal. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve were calculated.

Results: The convolutional neural network achieved an overall accuracy of 98.3%. The algorithm had a sensitivity and specificity of 97.4% and 99.2%, respectively. The accuracy of the algorithm for differentiating high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion varied between 91.5% (postmanipulation) and 100% (lugol) for the categories at subanalysis. The area under the curve ranged between 0.95 and 1.00.

Discussion: The introduction of AI to HRA may provide an accurate detection and differentiation of ASCC precursors. Our algorithm showed excellent performance at different staining settings. This is extremely important because real-time AI models during HRA examinations can help guide local treatment or detect relapsing disease.

简介:高分辨率肛门镜检查(HRA)是检测肛门鳞状细胞癌(ASCC)前兆的黄金标准。关于将人工智能(AI)模型应用于该模式的初步研究显示了良好的结果。然而,染色技术和肛门操作对这些算法有效性的影响尚未得到评估。我们旨在开发一种深度学习系统,用于自动区分不同亚组患者(未染色、醋酸、鲁戈尔和操作后)HRA 图像中的高级别(HSIL)与低级别(LSIL)鳞状上皮内病变:方法:根据 88 名患者 103 次 HRA 检查的 27,770 张图像,开发了一种卷积神经网络 (CNN),用于检测和区分高级别和低级别肛门鳞状上皮内病变。我们还进行了子分析,以评估算法在无染色、醋酸、鲁戈尔和肛管操作后的图像子集中的性能。计算了灵敏度、特异性、准确性、阳性和阴性预测值以及曲线下面积(AUC):结果:CNN 的总体准确率为 98.3%。该算法的灵敏度和特异度分别为 97.4% 和 99.2%。该算法区分 HSIL 和 LSIL 的准确率介于 91.5%(操作后)和 100%(鲁戈)之间。AUC介于0.95和1.00之间:将人工智能引入 HRA 可以准确检测和区分 ASCC 前体。我们的算法在不同的染色设置下都表现出卓越的性能。这一点极为重要,因为 HRA 检查中的实时人工智能模型有助于指导局部治疗或检测复发疾病。
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引用次数: 0
Higher and Sustained Cell-Mediated Immune Responses After 3 Doses of mRNA COVID-19 Vaccine in Patients With Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy. 接受抗肿瘤坏死因子治疗的炎症性肠病患者接种三次 mRNA COVID-19 疫苗后,细胞介导的免疫反应更强更持久
IF 3.6 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000688
Freddy Caldera, Stacey Rolak, Francis A Farraye, Brian M Necela, Davitte Cogen, Emily E Zona, Trevor L Schell, Oscar Ramirez Ramirez, Mazen Almasry, Kelly Chun, Mary S Hayney, Keith L Knutson

Introduction: Studies suggest that the generation of durable T-cell immunity following coronavirus disease 2019 (COVID-19) vaccination protects against severe disease. The aim of this study was to measure cell-mediated immune response (CMIR) 1-2 months and 6 months after a third dose of a COVID-19 mRNA vaccine.

Methods: This prospective study (HumoRal and CellULar initial and Sustained immunogenicity in patients with inflammatory bowel disease [IBD]) evaluated CMIR at 28-65 days (t 1 ) after dose 2, 28-65 days (t 2 ) (n = 183) and 6 months (±45 days) (t 3 ) (n = 167) after a third dose of an mRNA COVID-19 vaccine. A small cohort had blood sample available 28-65 days (t 4 ) (n = 55) after a fourth dose. Primary outcomes were CMIR at (t 2 ) and (t 3 ). Secondary outcomes included the effect of immunosuppressing IBD medications on CMIR and response at (t 4 ).

Results: All patients had measurable CMIR at all time points. CMIR increased at t 2 compared with that at t 1 (median 1,467 responding cells per million (interquartile range [IQR] 410-5,971) vs 313 (94-960) P < 0.001). There was no significant waning in t 2 vs t 3 or significant boosting at t 4 . Those on anti-tumor necrosis factor monotherapy had a higher CMIR compared with those not on this therapy at t 2 (4,132 [IQR 1,136-8,795] vs 869 [IQR 343-3,221] P < 0.001) and t 3 (2,843 [IQR 596-6,459] vs 654 [IQR 143-2,067] P < 0.001). In univariable analysis, anti-tumor necrosis factor monotherapy was associated with a higher CMIR at t 2 ( P < 0.001) and t 3 ( P < 0.001) and confirmed in a multivariable model ( P < 0.001).

Discussion: A third dose of a COVID-19 vaccine boosts CMIR, and the response is sustained in patients with IBD.

简介:研究表明,接种 COVID-19 疫苗后产生的持久 T 细胞免疫可预防严重疾病。本研究的目的是在接种第三剂 COVID-19 mRNA 疫苗一至两个月和六个月后测量细胞介导的免疫反应(CMIR):这项前瞻性研究(HERCULES)评估了接种第二剂后28-65天(t1)、接种第三剂mRNA COVID-19疫苗后28-65天(t2)(约183人)和六个月(+/-45天)(t3)(约167人)的细胞介导免疫反应。一小部分人在接种第四剂疫苗后 28-65 天(t4)(55 人)可获得血液。主要结果是(t2)和(t3)的CMIR。次要结果包括免疫抑制 IBD 药物对 CMIR 的影响和(t4)时的反应:所有患者在所有时间点都有可测量的 CMIR。与 t1 时相比,t2 时的 CMIR 有所增加(中位数为每百万应答细胞 1467 个(四分位数间距(IQR)410-5971)vs 313 个(94-960)p< 0.001)。第2阶段与第3阶段相比,没有明显的减弱,第4阶段也没有明显的增强。与未接受抗肿瘤坏死因子单药治疗的患者相比,接受抗肿瘤坏死因子单药治疗的患者在第2个疗程时的CMIR更高(4132(IQR 1136-8795) vs. 869 (IQR 343-3221) p 结论:COVID治疗的第3个疗程应在第4个疗程时进行:第三剂COVID-19疫苗可提高CMIR,而且IBD患者的反应可持续。
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引用次数: 0
Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis: A Multicenter, Cross-Sectional Study. 慢性胰腺炎的全身中性粒细胞明胶酶相关脂质体改变:一项多中心横断面研究
IF 3.6 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000686
Kristyn Gumpper-Fedus, Kaylin Chasser, Valentina Pita-Grisanti, Molly Torok, Timothy Pfau, Thomas A Mace, Rachel M Cole, Martha A Belury, Stacey Culp, Phil A Hart, Somashekar G Krishna, Luis F Lara, Mitchell L Ramsey, William Fisher, Evan L Fogel, Chris E Forsmark, Liang Li, Stephen Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Darwin L Conwell, Zobeida Cruz-Monserrate

Introduction: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations.

Methods: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear cells (PBMCs) from controls (n = 16), AP/RAP (n = 17), and CP (n = 15) were measured by cytometry by time-of-flight.

Results: Plasma NGAL was elevated in subjects with CP compared with controls (area under the curve [AUC] = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, body mass index, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared with CP without diabetes ( P < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower, whereas dihomo-γ-linolenic and adrenic acids were elevated in CP ( P < 0.05). Linoleic acid was elevated in CP with diabetes compared with CP subjects without diabetes ( P = 0.0471).

Discussion: Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.

背景:慢性胰腺炎(CP)是一种进行性纤维炎症性疾病,缺乏治疗方法和生物标志物。中性粒细胞明胶酶相关脂联素(NGAL)是一种在炎症过程中升高的促炎细胞因子,可与亚油酸等脂肪酸(FAs)结合。我们假设全身性 NGAL 可作为 CP 的生物标记物,并与脂肪酸一起提供有关炎症和代谢改变的信息:免疫测定法测定 NGAL,气相色谱法测定血浆中的 FA 组成(n = 171),这些血浆来自一项多中心研究,包括对照组(n = 50)、急性和复发性急性胰腺炎(AP/RAP)(n = 71)和 CP(n = 50)。对照组(16 人)、急性胰腺炎/复发性急性胰腺炎(17 人)和慢性胰腺炎(15 人)的外周血单核细胞(PBMCs)通过 CyTOF 进行测量:结果:与对照组(AUC = 0.777)或 AP/RAP 组(AUC = 0.754)相比,在与性别、年龄、体重指数和吸烟(对照组 AUC = 0.874;AP/RAP 组 AUC = 0.819)进行的单变量和多变量分析中,CP 患者血浆 NGAL 升高。与无糖尿病的 CP 相比,有糖尿病的 CP 的 NGAL 升高(p < 0.001)。NGAL + PBMC 群体将 CP 与对照组(AUC = 0.950)或 AP/RAP (AUC = 0.941)区分开来。CP 中亚油酸含量较低,而二氢-γ-亚麻酸和肾上腺酸含量升高(P < 0.05)。与未患糖尿病的 CP 受试者相比,患有糖尿病的 CP 中亚油酸升高(p = 0. 0471):结论:血浆 NGAL 升高和 NGAL + PBMCs 的差异表明免疫反应发生了转变,可作为 CP 的生物标志物。FAs和NGAL水平的潜在相互作用为代谢病理生理学提供了见解,并改进了CP的诊断分类。
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引用次数: 0
Celestial Insights: Unraveling the Role of miR-3682-3p in Hepatocellular Carcinoma. 天体的洞察力:揭示 miR-3682-3p 在肝细胞癌中的作用。
IF 3.6 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000690
Pei-Dong Miao, Ying Li, Yu-Dong Jiang

Abstract: Hepatocellular carcinoma (HCC) remains a formidable oncological challenge, calling for innovative therapeutic strategies to improve patient outcomes. MicroRNAs have emerged as key regulators in cancer, and miR-3682-3p shows potential as a diagnostic and prognostic biomarker in HCC. We conducted a comprehensive study to uncover its role in HCC biology, revealing dysregulation and clinical associations. Target gene analysis provided insights into potential molecular mechanisms. Moreover, we explored its impact on the tumor microenvironment, immune cell infiltration, and therapy responses. Our findings highlight miR-3682-3p as a promising candidate for further investigations and potential therapeutic strategies in HCC management.

肝细胞癌(HCC)仍然是一项严峻的肿瘤挑战,需要创新的治疗策略来改善患者的预后。微RNA(miRNA)已成为癌症的关键调控因子,而miR-3682-3p则显示出作为HCC诊断和预后生物标志物的潜力。我们进行了一项全面的研究,以揭示其在 HCC 生物学中的作用、失调和临床关联。通过靶基因分析,我们了解了潜在的分子机制。此外,我们还探讨了它对肿瘤微环境、免疫细胞浸润和治疗反应的影响。我们的研究结果突显了 miR-3682-3p 是一种有希望在 HCC 治疗中得到进一步研究和潜在治疗策略的候选基因。
{"title":"Celestial Insights: Unraveling the Role of miR-3682-3p in Hepatocellular Carcinoma.","authors":"Pei-Dong Miao, Ying Li, Yu-Dong Jiang","doi":"10.14309/ctg.0000000000000690","DOIUrl":"10.14309/ctg.0000000000000690","url":null,"abstract":"<p><strong>Abstract: </strong>Hepatocellular carcinoma (HCC) remains a formidable oncological challenge, calling for innovative therapeutic strategies to improve patient outcomes. MicroRNAs have emerged as key regulators in cancer, and miR-3682-3p shows potential as a diagnostic and prognostic biomarker in HCC. We conducted a comprehensive study to uncover its role in HCC biology, revealing dysregulation and clinical associations. Target gene analysis provided insights into potential molecular mechanisms. Moreover, we explored its impact on the tumor microenvironment, immune cell infiltration, and therapy responses. Our findings highlight miR-3682-3p as a promising candidate for further investigations and potential therapeutic strategies in HCC management.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risk of Anxiety, Depression, and Attention-Deficit/Hyperactivity Disorder in Pediatric Patients With Inflammatory Bowel Disease: A Population-Based Cohort Study. 炎症性肠病患儿焦虑、抑郁和多动症的风险:一项基于人群的队列研究。
IF 3.6 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000657
Rebecca Kristine Kappel, Tania Hviid Bisgaard, Gry Poulsen, Tine Jess

Introduction: Inflammatory bowel disease (IBD) is associated with depression and anxiety in adults, but data are scarce on risk of psychiatric diseases in children with IBD. We aimed to estimate the risk of anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD) in patients with pediatric-onset IBD.

Methods: We performed a nationwide, register-based cohort study including all patients with pediatric-onset IBD diagnosed in Denmark during 1998-2018, resulting in 3,559 patients matched 1:5 on age, sex, municipality of residence, and time period, resulting in 17,795 reference individuals. We used Cox regression to calculate hazard ratios for each outcome after a diagnosis with IBD.

Results: Patients with pediatric-onset IBD had an increased risk of depression (hazard ratio [HR] 1.50; 95% confidence interval [CI] 1.26-1.80) and of using antidepressants (HR, 1.54; 95% CI, 1.39-1.71) and, surprisingly, a reduced risk of using methylphenidate (HR, 0.75; 95% CI, 0.58-0.98). Patients with both IBD subtypes (Crohn's disease and ulcerative colitis) had an increased risk of using antidepressants and developing depression, which was particularly high in patients with Crohn's disease (HR, 1.73; 95% CI, 1.35-2.22). Patients with ulcerative colitis had reduced risk of using methylphenidate (HR, 0.63; 95% CI, 0.43-0.93) and a reduced-although not statistically significant-risk of being diagnosed with ADHD compared with the background population.

Discussion: Patients with pediatric-onset IBD have a 50% increased risk of developing depression, which is important for healthcare providers to be aware of and manage. Remarkably, we found a reduced risk of receiving methylphenidate and being diagnosed with ADHD, which merits further investigation.

引言:炎症性肠病(IBD)与成人的抑郁和焦虑有关,但关于IBD儿童患精神疾病风险的数据很少。我们旨在评估儿童发作性炎症性肠病患者患焦虑、抑郁或注意力缺陷/多动障碍的风险,得到17795个参考个体。我们使用Cox回归来计算诊断为IBD后每种结果的风险比。结果:儿童发作性IBD患者患抑郁症的风险增加(风险比[HR]1.50,95%置信区间[CI]1.26-1.80),使用抗抑郁药的风险增加,令人惊讶的是,使用哌甲酯的风险降低了(HR 0.75,95%CI 0.58-0.98)。患有两种IBD亚型(克罗恩病[CD]和溃疡性结肠炎[UC])的患者使用抗抑郁药和患抑郁症的风险增加,与背景人群相比,UC患者使用哌甲酯的风险降低(HR 0.63,95%CI 0.43-0.93),被诊断为多动症的风险降低,尽管没有统计学意义。讨论:儿科发作的IBD患者患抑郁症的风险增加了50%,这对医疗保健提供者的意识和管理很重要。值得注意的是,我们发现服用哌甲酯和被诊断为多动症的风险降低了,这值得进一步研究。
{"title":"Risk of Anxiety, Depression, and Attention-Deficit/Hyperactivity Disorder in Pediatric Patients With Inflammatory Bowel Disease: A Population-Based Cohort Study.","authors":"Rebecca Kristine Kappel, Tania Hviid Bisgaard, Gry Poulsen, Tine Jess","doi":"10.14309/ctg.0000000000000657","DOIUrl":"10.14309/ctg.0000000000000657","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory bowel disease (IBD) is associated with depression and anxiety in adults, but data are scarce on risk of psychiatric diseases in children with IBD. We aimed to estimate the risk of anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD) in patients with pediatric-onset IBD.</p><p><strong>Methods: </strong>We performed a nationwide, register-based cohort study including all patients with pediatric-onset IBD diagnosed in Denmark during 1998-2018, resulting in 3,559 patients matched 1:5 on age, sex, municipality of residence, and time period, resulting in 17,795 reference individuals. We used Cox regression to calculate hazard ratios for each outcome after a diagnosis with IBD.</p><p><strong>Results: </strong>Patients with pediatric-onset IBD had an increased risk of depression (hazard ratio [HR] 1.50; 95% confidence interval [CI] 1.26-1.80) and of using antidepressants (HR, 1.54; 95% CI, 1.39-1.71) and, surprisingly, a reduced risk of using methylphenidate (HR, 0.75; 95% CI, 0.58-0.98). Patients with both IBD subtypes (Crohn's disease and ulcerative colitis) had an increased risk of using antidepressants and developing depression, which was particularly high in patients with Crohn's disease (HR, 1.73; 95% CI, 1.35-2.22). Patients with ulcerative colitis had reduced risk of using methylphenidate (HR, 0.63; 95% CI, 0.43-0.93) and a reduced-although not statistically significant-risk of being diagnosed with ADHD compared with the background population.</p><p><strong>Discussion: </strong>Patients with pediatric-onset IBD have a 50% increased risk of developing depression, which is important for healthcare providers to be aware of and manage. Remarkably, we found a reduced risk of receiving methylphenidate and being diagnosed with ADHD, which merits further investigation.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Subclinical Cognitive Impairment in Chronic Pancreatitis Is Associated With Reduced Mobility and Quality of Life. 慢性胰腺炎患者的亚临床认知障碍与行动能力和生活质量下降有关。
IF 3.6 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000685
Marko Damm, Katharina George, Jonas Rosendahl, Robin Greinert

Introduction: This study explores how chronic pancreatitis (CP) relates to subclinical cognitive impairment (SCI) and its prevalence, characteristics, risk factors, and effects on patients' quality of life (QoL) and physical performance.

Methods: Patients with fulfilled CP criteria in imaging were prospectively enrolled. Overt encephalopathy, neurodegenerative disorders, decompensated cirrhosis, and sepsis were exclusion criteria. All patients underwent psychometric testing and assessment of health-related QoL, such as mobility and strength. SCI was diagnosed when at least 1 test of the psychometric test battery was pathological.

Results: Seventy-one patients were enrolled. The etiology was toxic (alcohol/smoking) in most (49%) of the cases. SCI was prevalent in 41% of the patients while 25% had only 1 and 16% had 2 or more pathological tests. Patients with SCI exhibited diminished overall QoL scores ( P = 0.048), primarily affecting physical functionality ( P < 0.001). This was reaffirmed in mobility tests, where patients with SCI were slower in the timed up-and-go test ( P = 0.008) and showed increased prevalence of abnormal chair rising tests ( P = 0.004). Among all variables analyzed, only alcohol abuse was an independent risk factor of SCI (odds ratio 3.46; P = 0.02) in a multivariable regression model together with the variables age, sex, education, and compensated cirrhosis. Despite SCI affecting global QoL, sleep disturbance seemed to be the strongest variable independently associated with impaired QoL (odds ratio 9.9; P = 0.001).

Discussion: The largest study to the subject to date shows that SCI is common in patients with CP and is linked to significant morbidity. These findings suggest the need for addressing modifiable risk factors in patients with CP to improve outcomes.

研究目的本研究探讨慢性胰腺炎(CP)与亚临床认知障碍(SCI)的关系、其发病率、特征、风险因素、对患者生活质量(QoL)和身体表现的影响:方法:前瞻性地纳入了影像学检查符合 CP 标准的患者。排除标准包括:显性脑病、神经退行性疾病、失代偿性肝硬化或败血症。所有患者都接受了心理测试和健康相关的 QoL 评估,如活动能力和力量。如果心理测试中至少有一项测试出现病理变化,则可诊断为 SCI:共有 71 名患者入选。大多数病例(49%)的病因是中毒性(酗酒/吸烟)。41%的患者患有 SCI,25%的患者只有一项病理测试,16%的患者有两项或两项以上病理测试。SCI 患者的总体 QoL 评分降低(p=0.048),主要影响身体功能(p 结论:这是迄今为止关于该主题的最大规模研究:这项迄今为止规模最大的研究表明,SCI 在 CP 患者中很常见,并与严重的发病率有关。这些研究结果表明,有必要解决 CP 患者中可改变的风险因素,以改善预后。
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引用次数: 0
Prognostic Nutritional Index as a Prognostic Factor for Very Early-Stage Hepatocellular Carcinoma. 作为极早期肝细胞癌预后因素的预后营养指数。
IF 3.6 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000678
Chun-Ting Ho, Elise Chia-Hui Tan, Pei-Chang Lee, Chi-Jen Chu, Yi-Hsiang Huang, Teh-Ia Huo, Ming-Chih Hou, Jaw-Ching Wu, Chien-Wei Su

Introduction: Field factors play more important roles in predicting the outcomes of patients compared with tumor factors in early-stage hepatocellular carcinoma (HCC). However, the prognostic ability of noninvasive serum marker scores for hepatic fibrosis and liver functional reserve on very early-stage HCC is still not yet determined. We aimed to investigate the performance of these serum marker scores in predicting the prognoses of patients with very early-stage HCC.

Methods: A total of 446 patients with very early-stage HCC from 2012 to 2022 were retrospectively enrolled. Serum biomarkers and prognostic scores determining overall survival (OS) were analyzed by Cox proportional hazards model. We compared the Akaike information criterion among the prognostic nutritional index (PNI), aspartate aminotransferase-to-platelet ratio index, albumin-bilirubin (ALBI) score, EZ (easy)-ALBI score, modified ALBI score, fibrosis-4 score, and lymphocyte-to-monocyte ratio to determine the predictability on the OS.

Results: After a median follow-up of 41.0 months (interquartile range 36.9-45.1 months), 81 patients died, with a 5-year OS rate of 71.0%. Among the noninvasive serum marker scores, PNI had the best performance in predicting the OS with the lowest Akaike information criterion (846.407) compared with other scores. Moreover, we stratified the patients into high-risk (PNI <45) and low-risk (PNI ≥45) groups. It showed that the 5-year OS rates were 83.4% and 60.8% in the low-risk and high-risk PNI groups, respectively ( P < 0.001).

Discussion: PNI had the best performance in predicting the OS for patients with very early-stage HCC.

导言:与肿瘤因素相比,现场因素在预测早期肝细胞癌(HCC)患者的预后方面发挥着更重要的作用。然而,肝纤维化和肝功能储备的非侵入性血清标志物评分对极早期 HCC 的预后能力尚未确定。我们旨在研究这些血清标志物评分在预测极早期 HCC 患者预后方面的表现:方法:回顾性纳入2012年至2022年期间的446例极早期HCC患者。血清生物标志物和决定总生存期(OS)的预后评分通过Cox比例危险模型进行分析。我们比较了预后营养指数(PNI)、谷草转氨酶与血小板比值指数(APRI)、白蛋白-胆红素(ALBI)评分、EZ(easy)-ALBI评分、改良ALBI评分、纤维化(FIB)-4评分和淋巴细胞与单核细胞比值(LMR)之间的阿凯克信息标准(AIC),以确定对OS的预测能力:中位随访时间为41.0个月(四分位数间距IQR为36.9-45.1个月),81名患者死亡,5年OS率为71.0%。在非侵入性血清标志物评分中,与其他评分相比,PNI在预测OS方面表现最佳,AIC(846.407)最低。此外,我们还将患者分为高风险组(PNI=45)。结果显示,PNI 低风险组和高风险组的 5 年 OS 率分别为 83.4% 和 60.8%(P 结论:PNI 在预测癌症 OS 方面表现最佳:PNI在预测极早期HCC患者的OS方面表现最佳。
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引用次数: 0
A Multicenter Long-Term Cohort Study of Eosinophilic Esophagitis Variants and Their Progression to Eosinophilic Esophagitis Over Time. 一项关于嗜酸性粒细胞食管炎变体及其随时间演变为嗜酸性粒细胞食管炎的多中心长期队列研究。
IF 3.6 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000664
Thomas Greuter, Alex Straumann, Yuniel Fernandez-Marrero, Nina Germic, Aref Hosseini, Apinya Chanwangpong, Shida Yousefi, Dagmar Simon, Margaret H Collins, Christian Bussmann, Mirna Chehade, Evan S Dellon, Glenn T Furuta, Nirmala Gonsalves, Ikuo Hirano, Fouad J Moawad, Luc Biedermann, Ekaterina Safroneeva, Alain M Schoepfer, Hans-Uwe Simon

Introduction: Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined.

Methods: Patients from 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)histological, and molecular features were determined and compared with EoE and healthy controls.

Results: We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression, indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months).

Discussion: Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis.

背景:嗜酸性粒细胞食管炎(EoE)变异型最近被定性为具有类似 EoE 的食管功能障碍症状,但无明显食管嗜酸性粒细胞增多的病症。其病程和严重程度尚待确定:结果:我们纳入了 54 名食管水肿患者:我们共纳入了 54 名食道炎变异型患者(类食道炎 53.7%;淋巴细胞性食道炎 13.0%;非特异性食道炎 33.3%)。在 8 名类 EoE 食管炎患者中,EoE 在中位数 14 个月(IQR 3.6-37.6)后出现。随着时间的推移,病情发展速度加快(第 1 年 17.6%,第 3 年 32.0%,第 6 年 62.2%)。连续 RNA 测序分析显示,只有 7 个基因与这种进展有关(TSG6 和 ALOX15 是前 3 个上调基因),而之前被削弱的 Th2 通路也出现了上调。免疫染色证实了嗜酸性粒细胞相关蛋白(TSG6、ALOX15)的参与,并发现在进展过程中 GATA3 阳性细胞的数量显著增加,这表明了 Th1/Th2 的转换。35.2%的患者从一种咽喉炎变异型(基线)转变为另一种变异型(随访期间)(中位观察时间为17.3个月):结论:咽喉炎变异型向咽喉炎的转变表明存在疾病谱。少数几个基因似乎与肠易激综合征的进展相关,这些基因上调了先前减弱的 Th2 信号。这些基因(包括作为Th1/Th2转换调节因子的GATA3)可能是疾病早期发病机制的潜在治疗靶点。
{"title":"A Multicenter Long-Term Cohort Study of Eosinophilic Esophagitis Variants and Their Progression to Eosinophilic Esophagitis Over Time.","authors":"Thomas Greuter, Alex Straumann, Yuniel Fernandez-Marrero, Nina Germic, Aref Hosseini, Apinya Chanwangpong, Shida Yousefi, Dagmar Simon, Margaret H Collins, Christian Bussmann, Mirna Chehade, Evan S Dellon, Glenn T Furuta, Nirmala Gonsalves, Ikuo Hirano, Fouad J Moawad, Luc Biedermann, Ekaterina Safroneeva, Alain M Schoepfer, Hans-Uwe Simon","doi":"10.14309/ctg.0000000000000664","DOIUrl":"10.14309/ctg.0000000000000664","url":null,"abstract":"<p><strong>Introduction: </strong>Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined.</p><p><strong>Methods: </strong>Patients from 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)histological, and molecular features were determined and compared with EoE and healthy controls.</p><p><strong>Results: </strong>We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression, indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months).</p><p><strong>Discussion: </strong>Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic Factors Associated With Adverse Pregnancy Outcomes in Chronic Pancreatitis. 慢性胰腺炎患者不良妊娠结局的相关遗传因素
IF 3.6 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000691
Di Wu, Nan Ru, Yuan-Chen Wang, Guo-Xiu Ma, Tian-Yu Shi, Si-Huai Xiong, Ai-Jun You, Lei Wang, Liang-Hao Hu, Zhao-Shen Li, Wen-Bin Zou, Zhuan Liao

Introduction: The effects of genetic factors on pregnancy outcomes in chronic pancreatitis (CP) patients remain unclear. We evaluated the impacts of clinical features and mutations in main CP-susceptibility genes ( SPINK1 , PRSS1 , CTRC , and CFTR ) on pregnancy outcomes in Chinese CP patients.

Methods: This was a prospective cohort study with 14-year follow-up. The sample comprised female CP patients with documented pregnancy and known genetic backgrounds. Adverse pregnancy outcomes were compared between patients with and without gene mutations. Univariate and multivariate analyses were performed to determine the impact factors for adverse pregnancy outcomes.

Results: Totally, 160 female CP patients with a pregnancy history were enrolled; 59.4% of patients carried pathogenic mutations in CP-susceptibility genes. Adverse pregnancy outcomes occurred in 38 patients (23.8%); the prevalence of adverse outcomes was significantly higher in those harboring gene mutations than those without (30.5% vs 13.8%, P = 0.015). Notably, the rates of preterm delivery (12.6% vs 3.1%, P = 0.036) and abortion (17.9% vs 4.6%, P = 0.013) were remarkably higher in patients with gene mutations (especially SPINK1 mutations) than those without. In multivariate analyses, both CP-susceptibility gene mutations (odds ratio, 2.52; P = 0.033) and SPINK1 mutations (odds ratio, 2.60; P = 0.037) significantly increased the risk of adverse pregnancy outcomes. Acute pain attack during pregnancy was another risk factor for adverse pregnancy outcomes.

Discussion: Pathogenic mutations in CP-susceptibility genes, especially SPINK1 , were independently related to adverse pregnancy outcomes in CP patients. Significant attention should be paid to pregnant females harboring CP-susceptibility gene mutations (ClinicalTrials.gov: NCT06055595).

目的:遗传因素对慢性胰腺炎(CP)患者妊娠结局的影响仍不清楚。我们评估了中国 CP 患者的临床特征和主要 CP 易感基因(SPINK1、PRSS1、CTRC、CFTR)突变对妊娠结局的影响:这是一项为期 14 年的前瞻性队列研究。样本包括有妊娠记录且已知遗传背景的女性 CP 患者。比较了有基因突变和无基因突变患者的不良妊娠结局。对不良妊娠结局的影响因素进行了单变量和多变量分析:共有 160 名有妊娠史的女性 CP 患者入选,其中 59.4% 的患者携带 CP 易感基因的致病突变。38名患者(23.8%)出现了不良妊娠结局;携带基因突变者的不良妊娠结局发生率明显高于未携带基因突变者(30.5% vs 13.8%,P = 0.015)。值得注意的是,基因突变(尤其是 SPINK1 基因突变)患者的早产率(12.6% vs 3.1%,P = 0.036)和流产率(17.9% vs 4.6%,P = 0.013)明显高于无基因突变者。在多变量分析中,CP 易感基因突变(几率比 [OR],2.52;P = 0.033)和 SPINK1 基因突变(OR,2.60;P = 0.037)都显著增加了不良妊娠结局的风险。妊娠期急性疼痛发作是不良妊娠结局的另一个风险因素:结论:CP 易感基因(尤其是 SPINK1)的致病突变与 CP 患者的不良妊娠结局密切相关。结论:CP易感基因尤其是SPINK1的致病突变与CP患者的不良妊娠结局有独立的相关性,应特别关注携带CP易感基因突变的孕妇。(ClinicalTrials.gov: NCT06055595)。
{"title":"Genetic Factors Associated With Adverse Pregnancy Outcomes in Chronic Pancreatitis.","authors":"Di Wu, Nan Ru, Yuan-Chen Wang, Guo-Xiu Ma, Tian-Yu Shi, Si-Huai Xiong, Ai-Jun You, Lei Wang, Liang-Hao Hu, Zhao-Shen Li, Wen-Bin Zou, Zhuan Liao","doi":"10.14309/ctg.0000000000000691","DOIUrl":"10.14309/ctg.0000000000000691","url":null,"abstract":"<p><strong>Introduction: </strong>The effects of genetic factors on pregnancy outcomes in chronic pancreatitis (CP) patients remain unclear. We evaluated the impacts of clinical features and mutations in main CP-susceptibility genes ( SPINK1 , PRSS1 , CTRC , and CFTR ) on pregnancy outcomes in Chinese CP patients.</p><p><strong>Methods: </strong>This was a prospective cohort study with 14-year follow-up. The sample comprised female CP patients with documented pregnancy and known genetic backgrounds. Adverse pregnancy outcomes were compared between patients with and without gene mutations. Univariate and multivariate analyses were performed to determine the impact factors for adverse pregnancy outcomes.</p><p><strong>Results: </strong>Totally, 160 female CP patients with a pregnancy history were enrolled; 59.4% of patients carried pathogenic mutations in CP-susceptibility genes. Adverse pregnancy outcomes occurred in 38 patients (23.8%); the prevalence of adverse outcomes was significantly higher in those harboring gene mutations than those without (30.5% vs 13.8%, P = 0.015). Notably, the rates of preterm delivery (12.6% vs 3.1%, P = 0.036) and abortion (17.9% vs 4.6%, P = 0.013) were remarkably higher in patients with gene mutations (especially SPINK1 mutations) than those without. In multivariate analyses, both CP-susceptibility gene mutations (odds ratio, 2.52; P = 0.033) and SPINK1 mutations (odds ratio, 2.60; P = 0.037) significantly increased the risk of adverse pregnancy outcomes. Acute pain attack during pregnancy was another risk factor for adverse pregnancy outcomes.</p><p><strong>Discussion: </strong>Pathogenic mutations in CP-susceptibility genes, especially SPINK1 , were independently related to adverse pregnancy outcomes in CP patients. Significant attention should be paid to pregnant females harboring CP-susceptibility gene mutations (ClinicalTrials.gov: NCT06055595).</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Clinical and Translational Gastroenterology
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