Objective: To investigate the value of histological evaluation in predicting endoscopic relapse among patients with ulcerative colitis (UC) who were in endoscopic remission, and to compare the usefulness of various histological scoring systems. Methods: Histological sections from 61 patients with UC who were in endoscopic remission were retrospectively analyzed, at Peking University Third Hospital, Beijing, China from January 2015 to June 2021. They were subdivided into endoscopic persistent remission group (remission group, n=31, Mayo endoscopic score 0) and endoscopic relapse group (relapse group, n=30, Mayo endoscopic score≥1) according to the results of the first endoscopic reexamination after the biopsy. Histological evaluation was performed using the Geboes score (GS) and its simplified version (SGS), the Nancy index (NI) and the Robarts histopathological index (RHI). The median and maximum histological scores for each case in all biopsies were recorded. Univariate comparisons were performed using chi-squares and multivariate analysis using binary logistic regression. The values of four histological evaluation systems for predicting endoscopic relapse among UC patients in endoscopic remission were analyzed using receiver operating characteristic (ROC) curves. Results: Significant differences were observed between the remission and relapse groups. The differences were more pronounced in the maximum histological scores; the mean and highest results of area under the ROC curve scores (AUC) for GS, SGS, NI, and RHI were 0.657, 0.668, 0.682, 0.691, and 0.866, 0.863, 0.864, 0.869, respectively. The differences were statistically significant (P<0.05). The corresponding best cut-offs were GS≥2B.1, SGS≥2B.1, NI≥2, and RHI≥2.5, respectively, which meant mild active inflammation histologically, while there was no statistical difference of AUC among the four histological scoring indices (P>0.05). Univariate and multivariate analyses revealed statistically significant differences in the number of neutrophils in the epithelium and lamina propria (P<0.05). Conclusions: Biopsies from UC patients in endoscopic remission may still have histological active inflammation which appears to correlate with endoscopic relapse. Four commonly used histological scoring systems can be used to assess the risk of endoscopic relapse among UC patients in endoscopic remission. The patients who more likely have endoscopic relapse seem to have a histological score greater than the cut-off value (i.e., mild histological activity). The maximum histological scores can accurately predict the risk of endoscopic relapse, while the presence of epithelial and laminar propria neutrophil infiltrates can independently predict the endoscopic relapse in these patients. Considering the utility and convenience in routine practice, NI is recommended for evaluating histological inflammatory activity.
目的： 探讨组织学评估对溃疡性结肠炎（ulcerative colitis，UC）内镜缓解患者的内镜复发预测价值，并对不同组织学评估标准进行比较。 方法： 回顾性分析北京大学第三医院2015年1月1日至2021年6月30日61例UC内镜缓解患者的组织学切片，根据在该次活检后12~36个月内最近一次内镜复查结果分为内镜随访持续缓解组31例（缓解组，Mayo内镜评分0）和内镜随访复发组（复发组，Mayo内镜评分≥1）30例，采用Geboes评分（GS）及简化版GS（SGS）、Nancy指数（NI）和Robarts的组织病理学指数（RHI）进行组织学评估，取每例全部活检组织块组织学评分的中位数值和最高值；采用卡方检验进行组间单个指标比较，二元Logistic回归分析进行多因素分析，受试者工作特征（ROC）曲线分析4种组织学评价体系对内镜缓解UC患者内镜复发的预测价值。 结果： 不同分级系统组织学评分在缓解组和复发组患者间均差异有统计学意义（P<0.05），组织学评分最高值的组间比较差异更显著；两组患者GS、SGS、NI和RHI的平均值和最高值的ROC曲线下面积（AUC值）分别为0.657、0.668、0.682、0.691和0.866、0.863、0.864、0.869，差异有统计学意义（P<0.05），对应的最佳截止值分别为GS≥2B.1，SGS≥2B.1，NI≥2和RHI≥2.5，提示组织学具有轻度活动性炎症，4种评分体系的AUC值之间差异无统计学意义（P>0.05）。单因素和多因素分析结果显示上皮和固有层内中性粒细胞数量在组间差异有统计学意义（P<0.05）。 结论： 内镜缓解UC患者的活检组织中可能仍旧存在组织学活动性炎，并与患者内镜复发具有相关性，4种不同的常用组织学指标体系均可应用于内镜缓解UC患者内镜复发风险的评估，当内镜缓解UC患者的组织学评分大于截止值时（组织学可见轻度活动性炎）发生内镜复发的可能性增高，采用评分最高的组织块评分能更好地预测患者内镜复发的风险。各项评分指标中，上皮和固有层内可见中性粒细胞浸润对患者内镜复发具有独立预测价值，考虑到实用性和操作的方便性，推荐日常工作中采用NI作为组织学炎症活动的评级体系。.

Objective: This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD(+) R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods: The clinical data of 26 patients with FLT3-ITD(+) R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results: A total of 26 patients with FLT3-ITD(+) R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95%CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment (P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion: The Gilt-based combination therapy is highly effective in treating FLT3-ITD(+) R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients\' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients\' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.
目的： 探讨Gilteritinib（Gilt）为基础的方案桥接异基因造血干细胞移植（allo-HSCT）对伴FMS样酪氨酸激酶3（FLT3）基因内部串联重复（ITD）突变的复发难治性急性髓系白血病（R/R AML）患者的安全性、有效性，以及移植后Gilt维持治疗对FLT3-ITD阳性R/R AML患者预后的影响。 方法： 回顾性分析2019年8月至2023年1月苏州大学附属第一医院收治的26例伴FLT3-ITD突变的R/R AML患者。统计所有纳入患者的复合完全缓解（CRc）率、总生存（OS）期、无病生存（DFS）期和不良反应。 结果： 26例FLT3-ITD突变阳性R/R AML患者中，男14例，女12例，中位年龄38（18~65）岁。难治18例，复发8例。用药第14~21天疗效：完全缓解（CR）率为26.9%（7/26），CR伴血液学不完全恢复（CRi）率为57.7%（15/26），部分缓解（PR）率为7.7%（2/26），CRc率为84.6%（22/26），微小残留病（MRD）转阴率为65.4%。所有患者12、24个月累计OS率分别为79.0%和72.0%。中位OS期未达到。中位随访时间为16.0个月。全部治疗有效患者12、24个月累计DFS率分别为78.0%和71.0%。中位DFS期未达到。接受allo-HSCT的患者中位OS期未达到，较未接受allo-HSCT的患者（3.3个月，95%CI 2.2~4.3个月）显著延长（P=0.005）。移植后是否应用Gilt维持治疗的患者中位OS期均未达到，且移植后维持治疗的患者OS明显优于移植后未进行维持治疗的患者（P=0.019）。本研究中FLT3-ITD基因突变清除率为38.5%，且FLT3-ITD基因突变转阴的患者中位OS期未达到，明显长于未转阴的患者（15.0个月）（P=0.018）。Gilt为基础的方案最常见的3级及以上血液学不良反应包括白细胞减少（76.9%）、中性粒细胞减少（76.9%）、中性粒细胞减少性发热（61.5%）、血小板减少（69.2%）和贫血（57.7%）。其中1例患者在移植后口服Gilt维持治疗时出现分化综合征，治疗后好转。 结论： Gilt为基础的方案桥接allo-HSCT治疗FLT3-ITD突变阳性R/R AML患者的CRc率较高，MRD转阴率也较高，起效迅速，有效延长患者生存期。此外，FLT3-ITD基因突变清除率较高，且桥接移植和移植后Gilt维持治疗明显改善患者生存。治疗过程中不良事件的监测和管理至关重要。.

BACKGROUND: Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease. Clinicians now have the unique opportunity to provide individualized treatment that can achieve and sustain remission in many patients. However, issues of primary non-response (PNR) and secondary loss of response (SLOR) to non-tumour necrosis factor inhibitor (TNFi) therapies remains a common problem. Specific issues include the choice of optimization of therapy, identifying when dose optimization will recapture response, establishing optimal dose for escalation and when to switch therapy.
OBJECTIVE: To explores the issues of PNR and SLOR to non-TNFi therapies.
METHODS: This review explores the current evidence and literature to elucidate management options in cases of PNR/SLOR. It will also explore potential predictors for response following SLOR/PNR to therapies including the role of therapeutic drug monitoring (TDM).
RESULTS: In the setting of PNR and loss of response to alpha-beta7-integrin inhibitors and interleukin (IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response. For Janus kinase inhibitors dose optimization can be utilized to recapture response with loss of response.
CONCLUSIONS: The role of TDM in the setting of advanced non-TNFi therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future.

OBJECTIVE: Recent research has shown that Western-style diets have been associated with an increased risk of inflammatory bowel diseases (IBD). Our aim was to examine the link between an anti-inflammatory diet and the maintenance of IBD remission, as well as to assess the potential therapeutic advantages of this dietary approach in preserving IBD remission.
METHODS: The inclusion and exclusion criteria were applied to a total of 189 individuals with IBD, with 21 individuals not meeting the criteria. Therefore, 168 eligible patients were enrolled in the study and allocated to either an anti-inflammatory diet or a regular diet, based on their personal preference.
RESULTS: A cohort of 168 IBD adult patients was recruited for the study: 88 patients with ulcerative colitis and 80 with Crohn\'s disease. The intervention group received an anti-inflammatory diet consisting of the removal of red and processed meat, fried foods, high-lactose foods, fast food, white bread, sugar, and vegetable oils rich in omega-6 for a period of 1 year. The clinical response was maintained in 80 patients (95.2%) in the intervention group and in 72 patients (85.7%) in the control group (p-value=0.036). Although not statistically significant, fecal calprotectin was higher in the control group than in the intervention group at follow-up.
CONCLUSIONS: Patients who adhered to an anti-inflammatory diet exhibited a higher rate of maintenance of clinical remission. Furthermore, improvement in inflammation tests was observed in the intervention group, reinforcing the proposition that IBD is a lifestyle-related disease.

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Long-term data on ustekinumab in real-life Crohn\'s disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab\'s clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn\'s disease patient cohort with a three-year follow-up. Crohn\'s disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn\'s Disease (SES-CD)) were collected for three-years\' time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn\'s disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn\'s disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications.

BACKGROUND: The global rise in diabetes, particularly in India, poses a significant public health challenge, with factors such as limited awareness, financial strain, and cultural considerations hindering its effective management. Although lifestyle changes have shown promising results, their consistent implementation and maintenance continue to pose challenges. Most studies have focused primarily on dietary modifications, overlooking other essential aspects of lifestyle intervention. The DiRemI study aims to address these gaps by evaluating the efficacy of a comprehensive one-year program that combines diet, exercise, psychological support, and medical management to achieve weight loss, diabetes remission, and improved glycemic control among patients with type 2 diabetes (T2D) in India, while also considering the unique needs of the Indian population.
METHODS: The DiRemI study is a prospective, open-label, matched-group trial aimed at assessing the impact of a one-year online integrated intensive lifestyle intervention (ILI) comprising dietary modifications, physical activity, psychological support, and medical management on weight loss and remission in adult T2D patients (aged 30-70 years), with a body mass index (BMI) between 25 and 35 kg/m2, and disease duration of <15 years. ILI will be compared with routine medical care (RMC). Participants will be recruited from three clinics: one providing ILI and two others providing RMC. The co-primary outcome will be weight loss and remission at 12 months, with a follow-up at 18 months. The proposed sample size is 360 participants (180 each in intervention and control group).
CONCLUSIONS: The DiRemI study represents the first large-scale remission study in India to show the effectiveness of an integrated approach in the remission and management of T2D and its complications. The findings of this study hold the potential to report evidence-based strategies for managing T2D both in India and globally, thus alleviating the substantial burden of diabetes on public health systems.
BACKGROUND: Clinical Trials Registry, India (Registered Number: CTRI/2023/06/053885).

<b><br>Introduction:</b> Obesity's associated comorbidities and treatment costs have risen significantly, highlighting the importance of early weight loss strategies. Bariatric surgeries like Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) have been effective in promoting weight loss and improving type 2 diabetes mellitus (T2DM) management.</br> <b><br>Aim:</b> The aim was to determine whether Roux-en-Y gastric bypass is more effective than vertical sleeve gastrectomy in the remission of type 2 diabetes mellitus (T2DM).</br> <b><br>Methods:</b> A systematic review and meta-analysis was performed. A literature search was performed in the databases Web of Science, Medline/PubMed, Embase, Scopus, and Medline/Ovid. A total of 1323 results were identified; after screening, 14 articles were selected and included in the systematic review. Primary and secondary outcomes were measured by RR with a 95% CI.</br> <b><br>Results:</b> The primary outcome of T2DM remission was 15% in favor of VSG (RR: 1.15, [95% CI: 1.04-1.28]). For secondary outcomes, hypertension remission was 7% in favor of VSG (RR: 1.07, [95% CI: 1.00-1.16]). Remission of dyslipidemia was 16% in favor of VSG (RR: 1.16, [95% CI: 1.06-1.26]). BMI after surgery was in favor of RYGB (MD: -1.31, [95% CI: -1.98 to -0.64]). For weight loss, the results favored VSG (MD: 6.50, [95% CI: 4.99-8.01]). In relation to total cholesterol, they were 65% favorable for RYGB (MD: -0.35, [95% CI: -0.46 to -0.24]), with a value of p <0.05. For LDL values, our results were 69% favorable for RYGB (MD: -0.31, [95% CI: -0.45 to -0.16]), p <0.01 value.</br> <b><br>Conclusions:</b> Laparoscopic sleeve gastrectomy is more effective in T2DM remission, hypertension remission, dyslipidemia remission, and weight loss compared to Roux-en-Y gastric bypass. Roux-en-Y gastric bypass is more effective at lowering BMI, total cholesterol, LDL, and TG compared to laparoscopic sleeve gastrectomy.</br>.

Background: The Mayo Score [MS], endoscopic Mayo Score [eMS] and the Ulcerative Colitis Index of Severity [UCEIS] are employed in the assessment of ulcerative colitis [UC] severity. This study compared the aforementioned indices in terms of predictory value for response to remission induction treatment with anti-TNF and anti-integrin biologics. Methods: A total of 38 patients were retrospectively evaluated in the study, 23 male and 15 female, aged 18-74 years old who had undergone a total of 53 biological therapy courses with either infliximab [IFX] or vedolizumab [VDZ] at the Department of Gastroenterology of the Medical University of Łódź. The clinical and endoscopic activity of UC was assessed at the outset of biological therapy and the 14th week remission induction assessment juncture. Results: The study analyzed 19 IFX and 34 VDZ treatment courses. The response rate of patients receiving IFX reached 73.67% and the response rate was 58.82% for VDZ. The mean MS, eMS and UCEIS improved among all patient groups: 8.316 ± 1.974 to 4.158 ± 2.218 (p < 0.05), 2.632 ± 0.597 to 1.790 ± 0.713 (p < 0.05) and 4.790 ± 1.745 to 3.000 ± 1.453 (p < 0.05) for IFX, 7.088 ± 2.234 to 3.618 ± 2.412 (p < 0.05), 2.706 ± 0.524 to 1.677 ± 1.065 (p < 0.05) and 4.235 ± 1.350 to 2.735 ± 1.880 (p < 0.05) for VDZ. Conclusions: The outcome assessment in induction treatment of UC includes clinical data and endoscopic evaluation. Severity of inflammatory lesion activity according to the eMS and UCEIS indices correlates with the overall disease presentation as evaluated with MS. The UCEIS provides an overall better predictor for biological induction treatment when compared with the eMS in both patient groups, particularly in those receiving VDZ. It provides a promising alternative to the eMS and can be employed for both initial disease severity assessment as well as for treatment response monitoring.