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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 Q2 GASTROENTEROLOGY & HEPATOLOGY 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。
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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 Q2 GASTROENTEROLOGY & HEPATOLOGY 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。
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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 Q2 GASTROENTEROLOGY & HEPATOLOGY 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
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 Q2 GASTROENTEROLOGY & HEPATOLOGY 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
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 Q2 GASTROENTEROLOGY & HEPATOLOGY 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":" ","pages":"e00664"},"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 Q2 GASTROENTEROLOGY & HEPATOLOGY 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":" ","pages":"e00691"},"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
Bowel Stiffness Assessed by Shear-Wave Ultrasound Elastography Predicts Disease Behavior Progression in Patients With Crohn's Disease. 剪切波超声弹性成像技术评估的肠道硬度可预测克罗恩病患者的病情发展。
IF 3.6 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000684
Yu-Jun Chen, Jin-Shen He, Shan-Shan Xiong, Man-Ying Li, Shu-Ling Chen, Bai-Li Chen, Yun Qiu, Qing-Qing Xia, Yao He, Zhi-Rong Zeng, Min-Hu Chen, Xiao-Yan Xie, Ren Mao

Introduction: There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression.

Methods: We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively.

Results: A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792).

Discussion: Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.

目的:克罗恩病(CD)患者的疾病行为进展缺乏可靠的预测指标。实时剪切波弹性成像(SWE)是一种评估组织硬度的新方法。然而,它在评估克罗恩病方面的价值尚未得到研究。我们旨在探讨诊断时的 SWE 和其他超声参数在预测 CD 行为进展方面的价值:我们回顾性地收集了患有非狭窄性非穿透性疾病(基于蒙特利尔分类的 B1 表型)的 CD 患者的数据。所有患者均在基线期接受了肠道超声检查并接受了随访。终点定义为疾病行为进展为狭窄性(B2)或穿透性(B3)疾病。对基线特征与后续终点之间的关系进行了 Cox 回归分析。此外,还建立了一个多变量提名图来定量预测疾病行为进展的风险:共有 130 名 B1 表型的 CD 患者入选。27名患者(20.8%)发展为B2或B3疾病,中位随访时间为33个月。多变量分析发现,SWE是疾病行为进展的唯一独立预测因子(HR 1.08,95% CI 1.03-1.12,P=0.001)。在临界值为 12.75 kPa 时,危险比出现了逆转。包含 SWE 和其他临床特征的提名图显示出良好的预测性能(AUC=0.792):结论:使用SWE评估的肠道僵硬度是CD患者疾病行为进展的独立预测指标。结论:使用SWE评估肠道僵硬度是CD患者病情发展的独立预测指标,诊断时SWE大于12.75 kPa的CD患者易发展为狭窄性或穿透性疾病。
{"title":"Bowel Stiffness Assessed by Shear-Wave Ultrasound Elastography Predicts Disease Behavior Progression in Patients With Crohn's Disease.","authors":"Yu-Jun Chen, Jin-Shen He, Shan-Shan Xiong, Man-Ying Li, Shu-Ling Chen, Bai-Li Chen, Yun Qiu, Qing-Qing Xia, Yao He, Zhi-Rong Zeng, Min-Hu Chen, Xiao-Yan Xie, Ren Mao","doi":"10.14309/ctg.0000000000000684","DOIUrl":"10.14309/ctg.0000000000000684","url":null,"abstract":"<p><strong>Introduction: </strong>There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression.</p><p><strong>Methods: </strong>We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively.</p><p><strong>Results: </strong>A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792).</p><p><strong>Discussion: </strong>Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":"e00684"},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545870","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
Incidence of Pancreatic Injury and Pancreatitis in Patients Treated With Immune Checkpoint Inhibitors. 接受免疫检查点抑制剂治疗的患者中胰腺损伤和胰腺炎的发病率。
IF 3.6 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000667
Yasuki Hori, Itaru Naitoh, Aya Naiki-Ito, Tatsuya Kawai, Michihiro Yoshida, Akihisa Kato, Kenta Kachi, Hidenori Sahashi, Akihisa Adachi, Tadashi Toyohara, Yusuke Kito, Tatsuhito Yamamoto, Satoru Takahashi, Hiromi Kataoka

Introduction: Immune checkpoint inhibitors (ICIs) are being increasingly used to treat advanced malignancies. ICI-induced pancreatic injury (ICI-PI), which is an immune-related adverse event that may be a risk factor of ICI-associated pancreatitis, is not well documented in the literature.

Methods: Consecutive patients who received ICIs for advanced malignancies from August 2015 through October 2022 were analyzed for the incidence of ICI-PI based on the Common Terminology Criteria for Adverse Events and ICI-associated pancreatitis. The imaging, clinical, and pathological findings of ICI-associated pancreatitis were also assessed.

Results: This study enrolled 843 patients. In multivariable analyses, dual or simultaneous immunotherapy and ≥10 cycles of ICI administration were significant predictive factors for all grades of pancreatic injury, including grade ≥3. Notably, patients who received simultaneous immunotherapy exhibited a higher incidence of grade ≥3 pancreatic injuries compared with those receiving asynchronous immunotherapy in univariable analysis ( P = 0.032). One-fifth of the patients (16/70) with grade ≥3 pancreatic injuries had imaging evidence of pancreatitis similar to mild acute pancreatitis. ICI-associated pancreatitis was observed in 5.7% (48/843) of patients, including 1.8% (15/843) with moderate-to-severe pancreatitis (grade ≥2). Symptomatic cases (0.36%, 3/843) were treated with steroids with favorable outcomes. Immunohistochemistry for CD4 and CD8 revealed greater infiltration of CD8 + than CD4 + lymphocytes.

Discussion: Simultaneous immunotherapy and dual immunotherapy are risk factors of ICI-PI. Although most patients diagnosed with ICI-PI and ICI-associated pancreatitis were asymptomatic and had a low mortality likelihood, long-term outcomes, including endocrine and exocrine function, should be carefully monitored.

目的:免疫检查点抑制剂(ICIs)正被越来越多地用于治疗晚期恶性肿瘤。ICI诱导的胰腺损伤(ICI-PI)是一种与免疫相关的不良事件,可能是ICI相关性胰腺炎的风险因素,但在文献中并没有很好的记录:根据不良事件通用术语标准和ICI相关性胰腺炎,对2015年8月至2022年10月期间接受ICI治疗的晚期恶性肿瘤连续患者的ICI-PI发生率进行了分析。同时还评估了ICI相关性胰腺炎的影像学、临床和病理学结果:这项研究共纳入了 843 例患者。在多变量分析中,双重或同步免疫疗法以及≥10个ICI用药周期是所有等级胰腺损伤(包括≥3级)的重要预测因素。值得注意的是,在单变量分析中,与接受异步免疫疗法的患者相比,接受同步免疫疗法的患者胰腺损伤≥3级的发生率更高(P = 0.032)。在胰腺损伤≥3级的患者中,五分之一(16/70)的胰腺炎影像学证据与轻度急性胰腺炎相似。5.7%(48/843)的患者出现 ICI 相关性胰腺炎,其中 1.8%(15/843)的患者出现中重度胰腺炎(≥ 2 级)。有症状的病例(0.36%,3/843)接受了类固醇治疗,结果良好。CD4和CD8免疫组化显示,CD8+淋巴细胞的浸润程度高于CD4+淋巴细胞:结论:同时免疫治疗和双重免疫治疗是 ICI-PI 的危险因素。尽管大多数确诊为 ICI-PI 和 ICI 相关性胰腺炎的患者无症状且死亡率较低,但仍应仔细监测其长期预后,包括内分泌和外分泌功能。
{"title":"Incidence of Pancreatic Injury and Pancreatitis in Patients Treated With Immune Checkpoint Inhibitors.","authors":"Yasuki Hori, Itaru Naitoh, Aya Naiki-Ito, Tatsuya Kawai, Michihiro Yoshida, Akihisa Kato, Kenta Kachi, Hidenori Sahashi, Akihisa Adachi, Tadashi Toyohara, Yusuke Kito, Tatsuhito Yamamoto, Satoru Takahashi, Hiromi Kataoka","doi":"10.14309/ctg.0000000000000667","DOIUrl":"10.14309/ctg.0000000000000667","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICIs) are being increasingly used to treat advanced malignancies. ICI-induced pancreatic injury (ICI-PI), which is an immune-related adverse event that may be a risk factor of ICI-associated pancreatitis, is not well documented in the literature.</p><p><strong>Methods: </strong>Consecutive patients who received ICIs for advanced malignancies from August 2015 through October 2022 were analyzed for the incidence of ICI-PI based on the Common Terminology Criteria for Adverse Events and ICI-associated pancreatitis. The imaging, clinical, and pathological findings of ICI-associated pancreatitis were also assessed.</p><p><strong>Results: </strong>This study enrolled 843 patients. In multivariable analyses, dual or simultaneous immunotherapy and ≥10 cycles of ICI administration were significant predictive factors for all grades of pancreatic injury, including grade ≥3. Notably, patients who received simultaneous immunotherapy exhibited a higher incidence of grade ≥3 pancreatic injuries compared with those receiving asynchronous immunotherapy in univariable analysis ( P = 0.032). One-fifth of the patients (16/70) with grade ≥3 pancreatic injuries had imaging evidence of pancreatitis similar to mild acute pancreatitis. ICI-associated pancreatitis was observed in 5.7% (48/843) of patients, including 1.8% (15/843) with moderate-to-severe pancreatitis (grade ≥2). Symptomatic cases (0.36%, 3/843) were treated with steroids with favorable outcomes. Immunohistochemistry for CD4 and CD8 revealed greater infiltration of CD8 + than CD4 + lymphocytes.</p><p><strong>Discussion: </strong>Simultaneous immunotherapy and dual immunotherapy are risk factors of ICI-PI. Although most patients diagnosed with ICI-PI and ICI-associated pancreatitis were asymptomatic and had a low mortality likelihood, long-term outcomes, including endocrine and exocrine function, should be carefully monitored.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":"e00667"},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138799644","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
Increased Intestinal Permeability and Decreased Resiliency of the Intestinal Barrier in Alcoholic Liver Disease. 酒精性肝病的肠道渗透性增加和肠道屏障复原力降低。
IF 3.6 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-04-01 DOI: 10.14309/ctg.0000000000000689
Garth R Swanson, Kanika Garg, Maliha Shaikh, Ali Keshavarzian

Introduction: Only 20%-30% of individuals with alcohol use disorder (AUD) develop alcoholic liver disease (ALD). While the development of gut-derived endotoxemia is understood to be a required cofactor, increased intestinal permeability in ALD is not completely understood.

Methods: We recruited 178 subjects-58 healthy controls (HCs), 32 with ALD, 53 with AUD but no liver disease (ALC), and 35 with metabolic dysfunction-associated steatotic liver disease (MASLD). Intestinal permeability was assessed by a sugar cocktail as a percentage of oral dose. The permeability test was repeated after an aspirin challenge in a subset.

Results: Five-hour urinary lactulose/mannitol ratio (primarily representing small intestinal permeability) was not statistically different in HC, ALC, ALD, and MASLD groups ( P = 0.40). Twenty-four-hour urinary sucralose (representing whole gut permeability) was increased in ALD ( F = 5.3, P < 0.01) and distinguished ALD from ALC; 24-hour sucralose/lactulose ratio (primarily representing colon permeability) separated the ALD group ( F = 10.2, P < 0.01) from the MASLD group. After aspirin challenge, intestinal permeability increased in all groups and ALD had the largest increase.

Discussion: In a group of patients, we confirmed that (i) the ALD group has increased intestinal permeability compared with the HC, ALC, or MASLD group. In addition, because small bowel permeability (lactulose/mannitol ratio) is normal, the disruption of intestinal barrier seems to be primarily in the large intestine; (ii) decreased resiliency of intestinal barrier to injurious agents (such as NSAID) might be the mechanism for gut leak in subset of AUD who develop ALD.

目标:只有20-30%的酒精使用障碍(AUD)患者会发展为酒精性肝病(ALD)。虽然肠道内毒素血症的发生被认为是一个必要的辅助因素,但人们对 ALD 中肠道通透性的增加并不完全了解:我们招募了 178 名受试者--58 名健康对照组(HC)、32 名 ALD 患者、53 名有 AUD 但无肝病(ALC)的患者和 35 名非酒精性脂肪肝(NAFLD)患者。肠道渗透性通过鸡尾酒糖占口服剂量的百分比进行评估。一部分人在接受阿司匹林挑战后重复了渗透性测试:5小时尿液乳糖/甘露糖醇(L/M)比率(主要代表小肠渗透性)在HC、ALC、ALD和NAFLD中无统计学差异(P=0.40)。24 小时尿三氯蔗糖(代表整个肠道通透性)在 ALD 中增加(F= 5.3,p < 0.01),并将 ALD 与 ALC 区分开来;24 小时三氯蔗糖/乳果糖(S/L)比率(主要代表结肠通透性)将 ALD 组区分开来(F= 10.2,p 结论:在一组患者中,我们证实:(1) 与 HC、ALC 或 NAFLD 相比,ALD 的肠道通透性增加。此外,由于小肠通透性(L/M 比值)正常,肠道屏障的破坏似乎主要发生在大肠;(2) 肠道屏障对损伤性制剂(如非甾体抗炎药)的恢复能力降低,可能是发生 ALD 的 AUD 亚组肠道渗漏的机制。
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引用次数: 0
Suboptimal Performance of Microscopic Colitis Diagnosis Codes: A Bottleneck for Epidemiologic Insights. 微小结肠炎诊断代码的次优表现:流行病学洞察力的瓶颈。
IF 3.6 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-03-25 DOI: 10.14309/ctg.0000000000000696
Richard J Giza, Marisa E Millenson, David J Levinthal, Ravy K Vajravelu

Introduction: Administrative health data could contribute to generalizable microscopic colitis insights, but International Classification of Diseases (ICD) codes for microscopic colitis have not been validated.

Methods: We identified individuals who received care for diarrhea in the Veterans Health Administration and classified them by receipt of microscopic colitis ICD codes. We reviewed random samples of charts to calculate the positive predictive value (PPV) and negative predictive value (NPV). We then calculated the sensitivity and specificity in clinically relevant cohorts.

Results: The PPV was 0.790 and the NPV was 0.995. In a cohort of individuals with diarrhea who underwent colonoscopy, the sensitivity and specificity were 0.734 and 0.996, respectively.

Conclusion: Alternative ascertainment methods for microscopic colitis are needed because ICD codes have suboptimal performance.

导言:行政健康数据有助于深入了解微小结肠炎,但微小结肠炎的国际疾病分类(ICD)代码尚未得到验证:我们确定了在退伍军人健康管理局接受过腹泻治疗的人员,并根据微小结肠炎的 ICD 编码对他们进行了分类。我们对病历进行了随机抽样,以计算阳性预测值 (PPV) 和阴性预测值 (NPV)。然后,我们计算了临床相关组群的灵敏度和特异性:结果:PPV 为 0.790,NPV 为 0.995。在接受结肠镜检查的腹泻患者队列中,灵敏度和特异性分别为 0.734 和 0.996:结论:由于 ICD 代码的性能不够理想,因此需要采用其他方法来确定微小结肠炎。
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引用次数: 0
期刊
Clinical and Translational Gastroenterology
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