Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group

Background/PurposeA small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients.MethodsRetrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale.ResultsThere were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD.ConclusionMore than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment.Level of EvidenceLevel 4     

基于中医古籍文献的升降散应用溯源及探析

通过对中医古籍中有关升降散论述的文献梳理,全面探讨其内涵。本方是在大黄、僵蚕为雏形的基础上增加蝉蜕、姜黄而成方,几经易名,终在杨璿《伤寒瘟疫条辨》中为后人所熟知。本方广泛用于治疗瘟疫,以丸剂、散剂为主,方便携带,便于服用;重用大黄旨在祛邪、逐秽;应用时视人之体质强弱和量其毒之轻重而判断用药多寡,并辅以米酒、生蜜等以顾护正气。杨璿将其由治疗“热疫”的专方扩展为治疗“表里三焦大热”的通用方剂,扩大了本方治疗疾病范围。     

炎症性肠病患儿血清Th17相关细胞因子表达及其意义

目的　探讨儿童IBD患者血清中Th17相关细胞因子的表达水平及其临床意义。方法　收集2017年4月至2019年5月在西安交通大学附属儿童医院消化科住院治疗的儿童IBD患者40例，以同期21例非炎症性疾病儿童作为对照组。采集受检者血清标本，通过酶联免疫吸附试验检测白细胞介素-17A（IL-17A）、 IL-17F、 IL-21、 IL-22、 IL-25的表达水平。结果　IL-17A、 IL-17F、 IL-21和IL-22在溃疡性结肠炎（UC）及克罗恩病（CD）患儿血清中表达明显升高，IL-25明显降低（P＜0.05）；IL-17A、 IL-17F及IL-21血清水平与UC患儿疾病活动度呈正相关（P＜0.05）；IL-21在UC患儿血清中的表达与IL-17A和IL-17F的表达呈正相关（P＜0.05）。结论　Th17相关细胞因子在IBD患儿血清中表达失调，为进一步研究Th17细胞在儿童IBD中的作用提供了依据；IL-17A、 IL-17F、 IL-21血清水平与UC患儿疾病活动度呈正相关，表明其可能是Th17细胞触发儿童UC的重要促炎细胞因子。     

利咽散结方对自发性高血压大鼠血压及相关炎性因子的影响

目的研究利咽散结方对自发性高血压大鼠血压及相关炎性因子的影响。方法将36只自发性高血压大鼠随机分为利咽散结方组、氨氯地平组、模型组,每组12只。正常WKY大鼠12只作为正常组。利咽散结方组给予利咽散结方药液15.6 g/kg灌胃,氨氯地平组给予氨氯地平药液0.001 g/kg灌胃,模型组和正常组均给予等体积的蒸馏水灌胃,均1次/d,连续8周。测量各组大鼠灌胃前及灌胃2周、4周、6周、8周后血压,末次灌胃结束后用ELISA法测定血清炎性因子肿瘤坏死因子(TNF-α)、超敏C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)水平。结果利咽散结方组与氨氯地平组灌胃2周、4周、6周、8周后收缩压与舒张压均显著低于同期模型组(P均<0.05);利咽散结方组灌胃2周、4周、6周、8周后收缩压均显著高于同期氨氯地平组(P<0.05),而舒张压与同期氨氯地平组比较差异均无统计学意义(P均>0.05)。模型组血清TNF-α、hs-CRP、IL-6水平均明显高于正常组(P均<0.05),IL-10水平明显低于正常组(P<0.05);利咽散结方组与氨氯地平组血清TNF-α、hs-CRP、IL-6水平均明显低于模型组(P均<0.05),且利咽散结方组均明显低于氨氯地平组(P均<0.05);利咽散结方组与氨氯地平组血清IL-10水平均明显高于模型组(P均<0.05),且利咽散结方组明显高于氨氯地平组(P<0.05)。结论利咽散结方可显著降低自发性高血压大鼠血压,其降收缩压效果不如氨氯地平,降舒张压效果与氨氯地平相近,其作用机制可能与调节炎性因子水平有关。     

高渗盐水和甘露醇在动脉瘤性蛛网膜下腔出血患者降低颅内压中的应用

目的比较3%高渗盐水和20%甘露醇治疗重症动脉瘤性蛛网膜下腔出血所致颅内压增高的疗效.方法25例动脉瘤性蛛网膜下腔出血患者出现颅内压增高事件时, 随机交替接受等渗透剂量的160 mL 3%高渗盐水与150 mL 20%甘露醇进行降低颅内压治疗, 连续监测患者颅内压、平均动脉压、脑灌注压及中心静脉压.记录有效降低颅内压持续时间、颅内压最大降幅及其时间, 用药前及用药后1 h、3 h血钠水平及血浆渗透压.结果3%高渗盐水和20%甘露醇均可降低颅内压(均 P < 0.01), 两者的降低颅内压作用持续时间及颅内压降幅差异均无统计学意义(均 P >0.05).患者脑灌注压较用药前均上升(均 P < 0.01), 平均动脉压先上升后下降, 但差异无统计学意义( P >0.05).患者中心静脉压稍有波动, 但差异均无统计学意义(均 P >0.05).20%甘露醇治疗后患者血钠下降, 3%高渗盐水治疗后患者血钠值上升, 变化均有统计学意义(均 P < 0.05).20%甘露醇及3%高渗盐水治疗后患者血浆渗透压均先上升后下降, 变化均有统计学意义(均 P < 0.01). 结论3%高渗盐水可作为治疗动脉瘤性蛛网膜下腔出血所致颅内压增高患者的一线治疗药物.     

Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials

Objective: Report efficacy findings from three clinical trials (one phase 2 and two phase 3 [OPUS-1, OPUS-2]) of lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease (DED).

Research design and methods: Three 84-day, randomized, double-masked, placebo-controlled trials. Adults (≥18 years) with DED were randomized (1:1) to lifitegrast 5.0% or matching placebo. Changes from baseline to day 84 in signs and symptoms of DED were analyzed.

Main outcome measures: Phase 2, pre-specified endpoint: inferior corneal staining score (ICSS; 0–4); OPUS-1, coprimary endpoints: ICSS and visual-related function subscale (0–4 scale); OPUS-2, coprimary endpoints: ICSS and eye dryness score (EDS, VAS; 0–100).

Results: Fifty-eight participants were randomized to lifitegrast 5.0% and 58 to placebo in the phase 2 trial; 293 to lifitegrast and 295 to placebo in OPUS-1; 358 to lifitegrast and 360 to placebo in OPUS-2. In participants with mild-to-moderate baseline DED symptomatology, lifitegrast improved ICSS versus placebo in the phase 2 study (treatment effect, 0.35; 95% CI, 0.05–0.65; p?=?0.0209) and OPUS-1 (effect, 0.24; 95% CI, 0.10–0.38; p?=?0.0007). Among more symptomatic participants (baseline EDS ≥40, recent artificial tear use), lifitegrast improved EDS versus placebo in a post hoc analysis of OPUS-1 (effect, 13.34; 95% CI, 2.35–24.33; nominal p?=?0.0178) and in OPUS-2 (effect, 12.61; 95% CI, 8.51–16.70; p?<?0.0001).

Limitations: Trials were conducted over 12 weeks; efficacy beyond this period was not assessed.

Conclusions: Across three trials, lifitegrast improved ICSS in participants with mild-to-moderate baseline symptomatology in two studies, and EDS in participants with moderate-to-severe baseline symptomatology in two studies. Based on the overall findings from these trials, lifitegrast shows promise as a new treatment option for signs and symptoms of DED.