Therapeutic Advances in Gastroenterology最新文献

{"title":"The relationship of KRAS expression with KRAS status, prognosis, and tumor-infiltrated T lymphocytes in colorectal cancer.","authors":"Yebohao Zhou, Ziwei Zeng, Ze Li, Lei Ruan, Hao Xie, Fujin Ye, Liang Huang, Huashan Liu, Liang Kang","doi":"10.1177/17562848241249387","DOIUrl":"https://doi.org/10.1177/17562848241249387","url":null,"abstract":"<p><strong>Background: </strong>The significance of Kirsten rat sarcoma viral oncogene (KRAS) mutation in colorectal cancer (CRC) is well established; yet, its association with KRAS expression and prognosis warrants further investigation. While high KRAS expression is commonly linked with poorer prognosis in other cancers, its role in CRC remains relatively understudied.</p><p><strong>Objective: </strong>To explore the correlation between KRAS expression, KRAS status, prognosis, and tumor-infiltrating T lymphocyte density in CRC.</p><p><strong>Design: </strong>Single-center retrospective study.</p><p><strong>Methods: </strong>Conducted between 2010 and 2020, this study utilized tumor samples to assess KRAS expression and quantify CD3+/CD8+ T lymphocytes. The Cox proportional hazards model and linear regression analysis were employed to examine the relationship between KRAS expression, prognosis, and tumor-infiltrating T lymphocytes.</p><p><strong>Results: </strong>This study included 265 CRC patients who underwent radical surgery. No significant association was observed between KRAS expression and KRAS status (<i>p</i> > 0.05). High KRAS expression was associated with poorer overall survival and disease-free survival (<i>p</i> < 0.05). Subgroup analysis revealed that high KRAS expression remained indicative of a worse prognosis in the group with mismatch repair-deficient (dMMR) and KRAS mutant type (<i>p</i> < 0.05). Multivariate analysis confirmed KRAS expression as an unfavorable prognostic factor (<i>p</i> < 0.05). However, the significance of KRAS expression was lost in the dMMR and KRAS mutant-type group regarding overall survival (<i>p</i> > 0.05). Notably, KRAS expression showed a negative correlation with the density of CD8+ T lymphocytes in tumor tissue (<i>p</i> < 0.05), a finding also observed in the dMMR group (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>No association was found between KRAS expression and KRAS mutation status in CRC. Higher KRAS expression was indicative of poorer prognosis for CRC patients, except for those with proficient mismatch repair and KRAS wild type. In addition, in patients with dMMR, KRAS expression was associated with a lower density of CD8+ T lymphocytes in tumor tissue.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960272","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}

{"title":"P-CAB <i>versus</i> PPI in the eradication of <i>Helicobacter pylori</i>: a systematic review and network meta-analysis.","authors":"Yutong Jiang, Rongrong Zhang, Yuxuan Fang, Ruixia Zhao, Yu Fu, Pingping Ren, Qingqing Zhan, Mingyi Shao","doi":"10.1177/17562848241241223","DOIUrl":"10.1177/17562848241241223","url":null,"abstract":"<p><strong>Background: </strong>The efficacy and safety of potassium-competitive acid blockers (P-CABs) in the eradication of <i>Helicobacter pylori</i> (Hp) remains controversial when compared with proton pump inhibitors (PPIs).</p><p><strong>Objectives: </strong>The current study set out to compare the differences in the eradication rate and adverse reactions between eradication regimens based on P-CAB or PPI drugs and the differences between the vonoprazan-based and the tegoprazan-based regimens to explore the efficacy and safety of different Hp eradication regimens.</p><p><strong>Data sources and methods: </strong>Databases including PubMed, EMBASE, Cochrane Library, and WOS were searched from the inception of these databases up to July 2023, and eligible randomized controlled trials (RCTs) were included. The outcome measures were the eradication rate and the incidence of adverse reactions of different regimens in treating Hp. The results were estimated as relative risk (RR) and its 95% confidence interval (CI), and R 4.2.1 software was used to perform the network meta-analysis (NMA).</p><p><strong>Results: </strong>A total of 20 studies were included in the analysis, involving 5815 patients with Hp. In terms of eradication rate, the 2-week vonoprazan-based triple regimen (V-Tri-2w) was the best, which was superior to the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 0.9, 95% CI: (0.85-0.95)] and the 1-week tegoprazan-based triple regimen [T-Tri-1w, RR = 0.79, 95% CI: (0.64-0.97)]; the 2-week tegoprazan-based quadruple regimen (T-Qua-2w) was superior to the 1-week PPI-based triple regimen [P-Tri-1w, RR = 0.82, 95% CI: (0.67-0.99)], and there was no difference between the remaining tegoprazan-based regimens and the PPI-based or vonoprazan-based regimens. In terms of the incidence of adverse reactions, the 2-week vonoprazan-based binary regimen (V-Bi-2w) was lower than that of the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 1.98, 95% CI: (1.57-2.52)]; there was no significant difference between 1 and 2 weeks for each regimen, such as the vonoprazan-based triple regimen [RR = 1.11, 95% CI: (0.82-1.52)].</p><p><strong>Conclusion: </strong>In the eradication treatment of Hp, the efficacy and safety of vonoprazan-based regimens are generally better than those of PPI-based regimens. Among them, the V-Tri-2w regimen has the highest eradication rate and may be the preferred choice for Hp eradication.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946059","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}

{"title":"Differences in the risk of clinical failure between thiopurine and methotrexate in bio-naïve patients with Crohn's disease: a Korean nationwide population-based study.","authors":"Yu Kyung Jun, Eunjeong Ji, Hye Ran Yang, Yonghoon Choi, Cheol Min Shin, Young Soo Park, Nayoung Kim, Dong Ho Lee, Hyuk Yoon","doi":"10.1177/17562848241248321","DOIUrl":"10.1177/17562848241248321","url":null,"abstract":"<p><strong>Background: </strong>Although immunomodulators are widely prescribed in patients with Crohn's disease (CD), it is unclear whether there is a difference in treatment outcomes between thiopurines and methotrexate (MTX).</p><p><strong>Objective: </strong>To compare the risk of clinical failure between thiopurines and MTX in bio-naïve patients with CD.</p><p><strong>Design: </strong>Nationwide, population-based study.</p><p><strong>Methods: </strong>We used claims data from the Korean National Health Insurance Service. After inverse probability of treatment weighting, logistic regression and Cox proportional hazard analyses were used to evaluate the risk of clinical failure in bio-naïve patients with CD treated with thiopurine (thiopurine group) or MTX (MTX group).</p><p><strong>Results: </strong>Overall, 10,296 adult and pediatric patients with CD [9912 (96.3%) and 384 (3.7%) in the thiopurine and MTX groups, respectively] were included. The odds ratios (ORs) of failure to induce remission were significantly higher in the MTX group than in the thiopurine group [adjusted OR (aOR), 1.115; 95% confidence interval (CI), 1.045-1.190; <i>p</i> = 0.001]. However, the opposite result was observed only in patients without concomitant steroid use: the MTX group had a lower risk of induction failure than the thiopurine group (aOR, 0.740; 95% CI, 0.673-0.813; <i>p</i> < 0.001). The risk of overall maintenance failure was higher in the MTX group than in the thiopurine group [adjusted hazard ratio (aHR), 1.117; 95% CI, 1.047-1.191; <i>p</i> = 0.001]. The risk of overall maintenance failure was higher in the standard-dose MTX group than in the low-dose MTX group (aHR, 1.296; 95% CI, 1.134-1.480; <i>p</i> < 0.001). There was no significant difference in the risk of maintenance failure according to the administration route of MTX.</p><p><strong>Conclusion: </strong>Thiopurine is more effective than MTX in inducing and maintaining remission in bio-naïve patients with CD; however, the concomitant use of steroids influences inducing remission.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916484","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}

{"title":"Explorative cost-effectiveness analysis of colorectal cancer recurrence detection with next-generation sequencing liquid biopsy in Spain, France, and Germany.","authors":"Wendelin Schramm, Yasmin Hollenbenders, Maximilian Kurscheidt","doi":"10.1177/17562848241248246","DOIUrl":"10.1177/17562848241248246","url":null,"abstract":"<p><strong>Background: </strong>Next-generation sequencing liquid biopsy (NGS-LB) for colorectal cancer (CRC) detection and surveillance remains an expensive technology as economies of scale have not yet been realized. Nevertheless, the cost of sequencing has decreased while sensitivity has increased, raising the question of whether cost-effectiveness (CE) has already been achieved from the perspective of European healthcare systems.</p><p><strong>Objectives: </strong>This health economic (HE) modeling study explores the CE of NGS-LB for CRC based on direct treatment costs compared to standard care without liquid biopsy in Spain, France, and Germany.</p><p><strong>Methods: </strong>A structured literature search was used to collect evidence from 2009 to 2020 on the stage-dependent quality of life (quality-adjusted life-years, QALY), efficacy, and total direct treatment costs (TDC) of NGS-LB. A decision-analytic Markov model was developed. Over the remaining lifetime, cumulative life expectancy (LE), TDC, and QALYs were calculated for 60-year-old men and women in CRC stage III with different assumed effects of NGS-LB of 1% or 3% on improved survival and reduced stage progression, respectively.</p><p><strong>Results: </strong>The use of NGS-LB increases LE by 0.19 years in Spanish men (France: 0.19 years, Germany: 0.13 years) and by 0.21 years in Spanish women (France: 0.21 years, Germany: 0.14 years), respectively. The 3% discounted cost per QALY gained was 35,571.95 € for Spanish men (France: 31,705.15 €, Germany: 37,537.68 €) and 35,435.71 € for Spanish women (France: 31,295.57 €, Germany: 38,137.08 €) in the scenario with 3% improved survival and reduced disease progression. Compared to the other two countries, Germany has by far the highest TDC, which can amount to >80k euros in the last treatment year.</p><p><strong>Conclusion: </strong>In this explorative HE modeling study, NGS-LB achieves generally accepted CE levels in CRC treatment from the health system perspective in three major European economies under assumptions of small improvements in cancer recurrence and survival. Confirmation of these findings through clinical trials is encouraged.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913285","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}

{"title":"Biomarkers in inflammatory bowel disease: a practical guide.","authors":"Jennie Clough, Michael Colwill, Andrew Poullis, Richard Pollok, Kamal Patel, Sailish Honap","doi":"10.1177/17562848241251600","DOIUrl":"10.1177/17562848241251600","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a costly condition in terms of morbidity and healthcare utilization, with an increasing prevalence now approaching 1% in the Western world. Endoscopic assessment of IBD remains the gold standard for diagnosis, evaluation of treatment response and determination of post-operative recurrence, but is expensive and invasive. Biomarkers can facilitate non-invasive disease assessment, with C-reactive protein and faecal calprotectin as the most widely available biomarkers in current clinical practice. This narrative review summarizes the evidence for their use in both UC and CD and offers practical guidance for healthcare providers taking into account the limitations of biomarker interpretation. We present evidence for the future use of novel biomarkers in IBD and discuss how biomarker discovery could deliver the goal of precision medicine in IBD.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913282","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}

{"title":"Long-term real-world data of ustekinumab in Crohn's disease: the Stockholm ustekinumab study.","authors":"Francesca Bello, Samer Muhsen, Haider Sabhan, Alexandra Borin, Fredrik Johansson, Charlotte Höög, Ole Forsberg, Christina Wennerström, Charlotte Söderman, Mikael Lördal, Sven Almer","doi":"10.1177/17562848241242700","DOIUrl":"https://doi.org/10.1177/17562848241242700","url":null,"abstract":"<p><strong>Background: </strong>Ustekinumab is used to treat inflammatory bowel disease mainly in patients failing anti-tumour necrosis factor (TNF)-agents.</p><p><strong>Objectives: </strong>To provide real-world data in unselected patients with Crohn's disease (CD), treated with ustekinumab.</p><p><strong>Design: </strong>Longitudinal retrospective study at four hospitals in Stockholm, Sweden.</p><p><strong>Methods: </strong>Disease activity (Harvey-Bradshaw index and physician global assessment), laboratory parameters, endoscopic findings and drug persistence were assessed. Follow-up data were obtained in patients that stopped ustekinumab.</p><p><strong>Results: </strong>In total, 322 patients (median age 38 years, 48% women) were included. All had luminal disease and 22% also fistulizing disease. A total of 271 (84%) had failed ⩾1 and 148 (46%) ⩾2 anti-TNF drugs; 34% failed vedolizumab. At inclusion, 93% had active disease; 28% were on oral corticosteroids and 18% on thiopurines. The median follow-up on treatment was 13.5 months; overall 67% were followed at least 24 months. By intention to treat analysis, response rate at 3 and 12 months was 43% and 42%, respectively. Among patients with ongoing ustekinumab, 19% were in steroid-free remission at 3 months and 64% at 12 months. The median faecal calprotectin level decreased from 460 µg/g at baseline to 156 µg/g at 3 months and was 182 µg/g at 12 months. C-reactive protein remained stable at 4 mg/L whereas serum albumin increased slightly. About 31% of patients were withdrawn during the first 12 months, mainly due to persisting disease activity 21%, adverse events 5%, bowel surgery 0.6% or malignancy 0.3%. The overall persistence on ustekinumab was 88%, 51%, 34% and 20% at 3, 12, 24 and 36 months, respectively. Within 12 months following withdrawal of ustekinumab in 121 patients, 64% had active disease most of the time, 68% needed another biologic and 24% underwent surgery.</p><p><strong>Conclusion: </strong>Among difficult-to-treat patients with CD, ustekinumab was effective in the majority, with high drug persistence at 12 and 24 months in combination with a favourable safety profile.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11036920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865845","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}

{"title":"The emerging therapies are reshaping the first-line treatment for advanced hepatocellular carcinoma: a systematic review and network meta-analysis.","authors":"Wei Peng, Yangxun Pan, Lan Xie, Zhoutian Yang, Zhiwei Ye, Jinbin Chen, Juncheng Wang, Dandan Hu, Li Xu, Zhongguo Zhou, Minshan Chen, Aiping Fang, Yaojun Zhang","doi":"10.1177/17562848241237631","DOIUrl":"https://doi.org/10.1177/17562848241237631","url":null,"abstract":"<p><strong>Background: </strong>Given the superior performance of various therapies over sorafenib in advanced hepatocellular carcinoma (HCC) and the absence of direct comparisons, it is crucial to explore the efficacy of these treatments in phase III randomized clinical trials.</p><p><strong>Objectives: </strong>The goal is to identify which patients are most likely to benefit significantly from these emerging therapies, contributing to more personalized and informed clinical decision-making.</p><p><strong>Design: </strong>Systematic review and network meta-analysis.</p><p><strong>Data sources and methods: </strong>PubMed, Embase, ClinicalTrials.gov, and international conference databases have been searched from 1 January 2010 to 1 December 2023.</p><p><strong>Results: </strong>After screening, 17 phase III trials encompassing 18 treatments were included. In the whole-population network meta-analysis, the newly first-line tremelimumab plus durvalumab (Tre + Du) was found to be comparable with atezolizumab plus bevacizumab (Atezo + Beva) in providing the best overall survival (OS) benefit [hazard ratio (HR) 1.35, 95% confidence interval (CI): 0.93-1.92]. Concerning OS benefits, sintilimab plus bevacizumab biosimilar (Sint + Beva), camrelizumab plus rivoceranib (Camre + Rivo), and lenvatinib plus pembrolizumab (Lenva + Pemb) appear to exhibit similar effects to Tre + Du and Atezo + Beva. In the context of progression-free survival, Atezo + Beva seemed to outperform Tre + Du (HR: 0.66 CI: 0.49-0.87), while the effects are comparable to Sint + Beva, Camre + Rivo, and Lenva + Pemb. Upon comparison between Asia-Pacific and non-Asia-Pacific cohorts, as well as between hepatitis B virus (HBV)-infected and non-HBV-infected populations, immune checkpoint inhibitor (ICI)-based treatments seemed to exhibit heightened efficacy in the Asia-Pacific group and among individuals with HBV infection. However, combined ICI-based therapies did not show more effectiveness than molecular-targeted drugs in patients without macrovascular invasion and/or extrahepatic spread. As for grades 3-5 adverse events, combined therapies showed comparable safety to sorafenib and lenvatinib.</p><p><strong>Conclusion: </strong>Compared with sorafenib and lenvatinib, combination therapies based on ICIs significantly improved the prognosis of advanced HCC and demonstrated similar safety. At the same time, the optimal treatment approach should be tailored to individual patient characteristics, such as etiology, tumor staging, and serum alpha-fetoprotein levels. With lower incidence rates of treatment-related adverse events and non-inferior efficacy compared to sorafenib, ICI monotherapies should be prioritized as a first-line treatment approach for patients who are not suitable candidates for ICI-combined therapies.</p><p><strong>Trial registration: </strong>PROSPERO, CRD42022288172.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11032067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862818","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}

{"title":"In era of immunotherapy: the value of trastuzumab beyond progression in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer.","authors":"Hui Wang, Caiyun Nie, Weifeng Xu, Jing Li, He Gou, Huifang Lv, Beibei Chen, Jianzheng Wang, Yingjun Liu, Yunduan He, Jing Zhao, Xiaobing Chen","doi":"10.1177/17562848241245455","DOIUrl":"https://doi.org/10.1177/17562848241245455","url":null,"abstract":"<p><strong>Background: </strong>For patients with human epidermal growth factor receptor-2 (HER2)-positive advanced or metastatic gastric cancer who have progressed on first-line trastuzumab therapy, the clinical value of the continuous use of trastuzumab beyond progression (TBP) is controversial.</p><p><strong>Objectives: </strong>The present study was conducted to evaluate the efficacy and explore new treatment strategies of TBP for patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer in the era of cancer immunotherapy.</p><p><strong>Design: </strong>Retrospective analysis.</p><p><strong>Methods: </strong>Patients with HER2-positive advanced or metastatic gastric cancer who have failed first-line treatment based on trastuzumab-targeted therapy from June 2019 to December 2020 were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Survival curves of patients were estimated by the Kaplan-Meier method and compared using the log-rank test.</p><p><strong>Results: </strong>In all, 30 patients received TBP with chemotherapy, immunotherapy, or anti-angiogenic therapy, and the other 26 patients received treatment of physician's choice without trastuzumab. The median PFS in the TBP and non-TBP population was 6.0 [95% confidence interval (CI) = 3.8-8.2] and 3.5 (95% CI = 2.2-4.8) months, respectively (<i>p</i> = 0.038), and the median OS was 12.3 (95% CI = 10.4-14.2) and 9.0 (95% CI = 6.6-11.4) months (<i>p</i> = 0.008). The patients who received TBP treatment had more favorable PFS and OS than the non-TBP population. In the TBP group, patients who received trastuzumab plus chemotherapy and immunotherapy had higher ORR (40.0% <i>versus</i> 16.7%), DCR (90.0% <i>versus</i> 50.0%), and showed a significant improvement in PFS (7.0 <i>versus</i> 1.9 m) compared to TBP with chemotherapy alone. Subgroup analysis suggested that patients with male, HER2 positive with immunohistochemistry score 3+ and PFS of first-line treatment less than 6 months had a greater benefit from TBP. The incidence of Grade 3-4 adverse events in the TBP and non-TBP groups was 43.3% and 38.5%.</p><p><strong>Conclusion: </strong>The continuous use of TBP improves PFS and OS in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer with well-tolerated toxicity. In the era of immunotherapy, TBP combined with chemotherapy and immunotherapy may further enhance the clinical benefit and provide a new treatment strategy.</p><p><strong>Trial registration: </strong>This study is a retrospective study, which does not require clinical registration.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11010747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872141","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}

{"title":"Long-term safety of tenapanor in people with irritable bowel syndrome with constipation from the T3MPO-3 study: plain language summary of publication.","authors":"Anthony J Lembo, Susan Edelstein, David P Rosenbaum, Ceciel Rooker, Jeffrey D Roberts, William D Chey","doi":"10.1177/17562848241237196","DOIUrl":"https://doi.org/10.1177/17562848241237196","url":null,"abstract":"","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11005483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853253","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}

{"title":"Systematic review of metabolomic alterations in ulcerative colitis: unveiling key metabolic signatures and pathways.","authors":"Meiling Liu, Siyi Guo, Liang Wang","doi":"10.1177/17562848241239580","DOIUrl":"10.1177/17562848241239580","url":null,"abstract":"<p><strong>Background: </strong>Despite numerous metabolomic studies on ulcerative colitis (UC), the results have been highly variable, making it challenging to identify key metabolic abnormalities in UC.</p><p><strong>Objectives: </strong>This study aims to uncover key metabolites and metabolic pathways in UC by analyzing existing metabolomics data.</p><p><strong>Design: </strong>A systematic review.</p><p><strong>Data sources and methods: </strong>We conducted a comprehensive search in databases (PubMed, Cochrane Library, Embase, and Web of Science) and relevant study references for metabolomic research on UC up to 28 December 2022. Significant metabolite differences between UC patients and controls were identified, followed by an analysis of relevant metabolic pathways.</p><p><strong>Results: </strong>This review incorporated 78 studies, identifying 2868 differentially expressed metabolites between UC patients and controls. The metabolites were predominantly from 'lipids and lipid-like molecules' and 'organic acids and derivatives' superclasses. We found 101 metabolites consistently altered in multiple datasets within the same sample type and 78 metabolites common across different sample types. Of these, 62 metabolites exhibited consistent regulatory trends across various datasets or sample types. Pathway analysis revealed 22 significantly altered metabolic pathways, with 6 pathways being recurrently enriched across different sample types.</p><p><strong>Conclusion: </strong>This study elucidates key metabolic characteristics in UC, offering insights into molecular mechanisms and biomarker discovery for the disease. Future research could focus on validating these findings and exploring their clinical applications.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10981261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337344","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}