Ivermectin administration is associated with lower gastrointestinal complications and greater ventilator-free days in ventilated patients with COVID-19: A propensity score analysis

IntroductionCOVID-19 patients have been reported to have digestive symptoms with poor outcome. Ivermectin, an antiparasitic drug, has been used in COVID-19 patients. The objective of this study was to evaluate whether ivermectin has effects on gastrointestinal complications and ventilator-free days in ventilated patients with COVID-19.MethodsCOVID-19 patients who were mechanically ventilated in the ICU were included in this study. The ventilated patients who received ivermectin within 3 days after admission were assigned to the Ivermectin group, and the others were assigned to the Control group. Patients in the Ivermectin group received ivermectin 200 μg/kg via nasal tube. The incidence of gastrointestinal complications and ventilator-free days within 4 weeks from admission were evaluated as clinical outcomes using a propensity score with the inverse probability weighting method.ResultsWe included 88 patients in this study, of whom 39 patients were classified into the Ivermectin group, and 49 patients were classified into the Control group. The hazard ratio for gastrointestinal complications in the Ivermectin group as compared with the Control group was 0.221 (95% confidence interval [CI], 0.057 to 0.855; p = 0.029) in a Cox proportional-hazard regression model. The odds ratio for ventilator-free days as compared with the Control group was 1.920 (95% CI, 1.076 to 3.425; p = 0.027) in a proportional odds logistic regression model.ConclusionsIvermectin improved gastrointestinal complications and the number of ventilator-free days in severe COVID-19 patients undergoing mechanical ventilation. Prevention of gastrointestinal symptoms by SARS-Cov-2 might be associated with COVID-19 outcome.     

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     

Differential diagnosis of diarrhoea in patients with neuroendocrine tumours:A systematic review

BACKGROUND Approximately 20% of patients with neuroendocrine tumours(NETs) develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion.Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs(GEP-NETs),other causes to consider include pancreatic enzyme insufficiency(PEI),bile acid malabsorption and small intestinal bacterial overgrowth.If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea,these treatments may be ineffective against the diarrhoea,risking detrimental effects to patient quality of life.AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.METHODS Electronic databases(MEDLINE,Embase and the Cochrane Library) were searched from inception to September 12,2018 using terms for NETs and diarrhoea.Congresses,systematic literature review bibliographies and included articles were also hand-searched.Any study designs and publication types were eligible for inclusion if relevant data on a cause(s) of diarrhoea in patients with GEP-NETs were reported.Studies were screened by two independent reviewers at abstract and full-text stages.Framework synthesis was adapted to synthesise quantitative and qualitative data.The definition of qualitative data was expanded to include all textual data in any section of relevant publications.RESULTS Forty-seven publications(44 studies) were included,comprising a variety of publication types,including observational studies,reviews,guidelines,case reports,interventional studies,and opinion pieces.Most reported on PEI on/after treatment with somatostatin analogs;9.5%-84% of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI.Where reported,14.3%–50.7% of patients received pancreatic enzyme replacement therapy.Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption(80%),small intestinal bacterial overgrowth(23.6%-62%),colitis(20%) and infection(7.1%).Diagnostic approaches included faecal elastase,breath tests,tauroselcholic(selenium-75) acid(Se HCAT) scan and stool culture,although evidence on the effectiveness or diagnostic accuracy of these approaches was limited.Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation.From the identified evidence,if diarrhoea is assumed to be CS diarrhoea,consequences include uncontrolled diarrhoea,malnutrition,and perceived ineffectiveness of CS treatment.Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team,including gastroenterologists.CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use.This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches,to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.     

痛泻四神汤腹泻型肠易激综合征的胃肠激素水平变化及临床意义观察

目的:探究痛泻四神汤对腹泻型肠易激综合征胃肠激素水平的影响。方法:选取2017年2月至2018年6月西安市中医医院收治的腹泻型肠易激综合征患者124例作为研究对象,按照就诊顺序编号随机分为对照组和观察组,每组62例。对照组给予西医常规治疗,观察组在对照组基础上加用痛泻四神汤加减治疗,均治疗2周。观察和比较2组治疗前后淋巴细胞指标CD3^+、CD4^+、CD8^+、CD4^+/CD8^+变化,观察并比较2组治疗前后胃肠激素指标血浆胃动素(MOT)、降钙素相关基因肽(CGRP)、血管活性肠肽(VIP)、生长抑素(SS)、一氧化氮(NO)变化;观察并比较2组治疗前后在γ-干扰素(IFN-γ)、5-羟色胺(5-HT)、神经肽Y(NPY)含量变化;观察并比较2组治疗前后临床症状腹痛、腹胀、肠鸣失气、急躁易怒、神疲乏力、纳呆食少症状评分变化;治疗过程中进行不良反应记录,治疗结束后进行统计。结果:1)2组患者治疗前CD3^+、CD4^+、CD8^+、CD4^+/CD8^+比较,差异无统计学意义(P>0.05),治疗后2组CD3^+、CD4^+、CD4^+/CD8^+较治疗前均显著上升,CD8^+显著下降(均P<0.05);治疗后观察组患者CD3^+、CD4^+、CD4^+/CD8^+显著高于对照组,CD8^+显著低于对照组(P<0.05)。2)2组治疗前MOT、CGRP、VIP、SS、NO比较,差异无统计学意义(P>0.05),治疗后2组MOT、NO较治疗前显著升高,CGRP、VIP、SS显著下降(P<0.05);治疗后观察组CGRP、VIP、SS显著低于对照组,MOT、NO显著高于对照组(P<0.05)。3)2组治疗前IFN-γ、5-HT、NPY比较,差异无统计学意义(P>0.05),治疗后2组IFN-γ、5-HT、NPY较治疗前均显著下降(P<0.05);治疗后观察组IFN-γ、5-HT、NPY显著低于对照组(P<0.05)。4)2组治疗前腹痛、腹胀、肠鸣失气、急躁易怒、神疲乏力、纳呆食少积分比较,差异无统计学意义(P>0.05),治疗后2组以上各症状评分较治疗前显著下降(P<0.05);治疗后观察组以上各积分显著低于对照组(P<0.05)。5)2组口干、头痛、皮疹、胃肠道反应发生率比较,差异无统计学意义(P>0.05)。结论:痛泻四神汤能改善腹泻型肠易激综合征胃肠激素水平,改善临床症状,提高机体免疫力,提高疗效。     

单兆伟运用温经汤治疗女性肾虚泄泻经验

全国名中医、孟河医派传人单兆伟教授擅长胃肠病诊治,临证擅用《金匮要略》温经汤治疗女性肾虚型泄泻。认为温经汤的主要适应证是肝肾虚寒型的女性腹泻和(或)月经不调,肝脾肾三脏虚寒、寒凝而瘀、虚瘀相因、寒热错杂是温经汤证的病机特点,泄下清谷、脉象沉细或细涩、舌质淡黯有齿痕或瘀点是温经汤的主要应用指证。     

胫神经腓肠肌内侧头肌支切断的小腿减肥术

目的探索缩小小腿腓肠肌改善小腿外形的手术方法。方法通过窝皮肤皱襞4~5cm横切口,切断胫神经腓肠肌内侧头肌支,使腓肠肌内侧头失神经萎缩,达到小腿减肥的目的。测量并记录小腿周径和外形的变化。结果本组16例患者行胫神经腓肠肌内侧头肌支切断术后,小腿最大周径平均缩小(3.5±1.1)cm。小腿内侧曲线变得平缓。患者术后可立即下地行走,无明显肿胀。随访半年,站立、行走等日常活动未受影响。结论行胫神经腓肠肌内侧头肌支切断术,可缩小小腿,改善小腿外形,方法简便、安全,效果明显,同时不影响患者的行走功能。     

Cytochrome P450 3A4 and P-glycoprotein Activity and Assimilation of Tacrolimus in Transplant Patients with Persistent Diarrhea

Renal transplant recipients suffering from persistent diarrhea have been repeatedly reported to have increased tacrolimus (Tac) trough levels. This study aimed to explore this phenomenon in detail in 15 renal transplant recipients with diarrhea, whose immunosuppression consisted of corticosteroids, mofetil mycophenolate and Tac. Both hepatic and intestinal CYP3A4 and PGP activity, important determinants of Tac bioavailability, were assessed, together with global CYP activity and investigations for gastrointestinal infection, function and morphology. Global CYP, CYP3A4, PGP and trough/dose levels of Tac were compared with diarrhea-free controls. In addition, a pharmacokinetic study of Tac was performed in 11 patients affected by diarrhea versus 9 controls. As expected, diarrhea was associated with increased Tac trough levels. An even stronger, significant increase of dose-normalized Tac levels was observed between 90 and 360 min after Tac intake. Time to peak concentration and drug half-life, however, were not altered. In addition, a concomitant decrease (+/-50%) of intestinal PGP activity was noticed in patients with diarrhea. For global CYP, CYP3A4 and hepatic PGP activity no such differences were noted. This pattern was not influenced by the specific cause of diarrhea. These data strongly suggest that persistent diarrhea is associated with an increased oral bioavailability of Tac.