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     

A Proposal for an Alternative Approach to Particle Size Method Development During Early-Stage Small Molecule Pharmaceutical Development

Particle size analysis in the pharmaceutical industry has long been a source of debate regarding how best to define measurement accuracy; the degree to which the result of a measurement or calculation conforms to the true value. Defining a “true” value for the size of a particle can be challenging as the output of its measurement will differ because of variations in measurement approaches, instrumental differences and calculation methods. Consequently, for “real” particles, a universal “true” value does not exist and accuracy is therefore not a definable characteristic. Accordingly, precision is then a measure of the ability to reproducibly achieve a measurement of unknown relevance.This article proposes, in place of accuracy, a means to define the “appropriateness” of a measurement in line with the critical quality attributes (CQA) of the material being characterized. The decision as to whether the measurement is correct should involve a link to the CQA; that is, correlation should be demonstrated, without which the measured particle size cannot be defined as a critical material attribute.Correspondingly, methods should also be able to provide sufficient precision to demonstrate discrimination relating to variation in the CQA. The benefits and challenges of this approach are discussed.     

中药生产过程质量控制关键技术研究进展

中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方面的关键共性问题进行解析,综述了中药生产过程质量控制体系中工艺过程理解、生产过程实时分析方法开发、过程控制策略建立3个方面的研究进展;并结合企业研究实践,介绍了质量源于设计(quality by design,Qb D)、过程分析技术(process analytical technology,PAT)、实验设计(design of experiment,DOE)、多变量统计分析等关键技术在上述3个研究方向中的应用进展,分析了实际工业应用的难点问题并对其应用前景进行展望,旨在为中药企业应用和提升生产过程质量控制技术提供参考。     

Bronchial Artery Embolization in Pediatric Pulmonary Hemorrhage: A Single-Center Experience

PurposeTo explore the safety and effectiveness of bronchial artery (BA) embolization (BAE) in children with pulmonary hemorrhage.Materials and MethodsBetween February 2016 and February 2019, 41 patients (median age, 4 y; interquartile range, 2.3-8 y; median weight, 17.6 kg; interquartile range, 12.3–23.6 kg) underwent BAE. The indication of BAE included massive hemoptysis in 10 patients (24.4%), recurrent hemoptysis in 18 patients (43.9%), and refractory anemia in 13 patients (31.7%). The main etiology of pulmonary hemorrhage included pulmonary hemosiderosis (58.5%), congenital heart disease (17.1%), and infection (14.6%). A retrospective review was conducted of clinical outcomes of BAE.ResultsThere were 44 embolization sessions, with a total of 137 embolized vessels. Pulmonary hemorrhage was caused by BAs in 30 cases, nonbronchial systemic arteries plus BAs in 10, and nonbronchial systemic arteries in 1. Embolic particles were used in 30 cases (24 polyvinyl alcohol [PVA] and 6 microsphere), coils in 9 cases, and particles plus coils in 5 cases (4 PVA and 1 microsphere). Technical success (ability to embolize abnormal vessel) was achieved in 97.6% of patients (40 of 41), and clinical success (complete or partial resolution of hemoptysis within 30 days of embolization) was achieved in 90.2% (37 of 41). There was 1 procedure-related complication (2.4%) of cerebral infarction and 1 death from multiple-organ dysfunction (2.4%). Bleeding-free survival rates at 6, 12, 24, and 36 months were 92.5%, 83.9%, 83.9%, and 70.8%, respectively.ConclusionsBAE is a safe and effective procedure in children with pulmonary hemorrhage.     

Family correlates of daughter's and son's locus of control expectancies during childhood

Children who expect they can bring about good outcomes and avoid bad outcomes tend to experience more personal successes. Little is known about factors that contribute to these ‘control expectancies’. The purpose of the present study was to determine whether children's internal control expectancies occur in the context of parents’ internal control expectancies, low family strain, and high family cohesiveness and whether these factors are more strongly related to daughters’ than sons’ control expectancies. A community sample of 85 children aged 9–11 years and their parents (85 mothers; 63 fathers) completed rating scales. Fathers’ more internal control expectancies and mothers’ reports of fewer family strains were associated with daughters’ but not sons’ greater internal control expectancies, and greater family cohesiveness was related to both daughters’ and sons’ internal control orientations. These findings suggest that family factors may contribute to children's, particularly daughters’, development of internal control expectancies.     

品管圈活动在喜疗妥联合新鲜马铃薯外敷治疗小儿输液外渗中的应用效果分析

目的探讨品管圈活动在喜疗妥联合新鲜马铃薯外敷治疗小儿输液外渗中的应用效果。方法选取我院2016年8月至2018年12月收治的输液外渗患儿100例,随机分为两组各50例。对照组给予50%硫酸镁湿敷治疗与常规护理,干预组采用喜疗妥联合新鲜马铃薯外敷,进行品管圈活动。对比两组的临床疗效、损伤痊愈时间和完全消肿时间。结果干预组的总有效率为90.00%,高于对照组的74.00%(P <0.05)。干预组的损伤痊愈时间和完全消肿时间短于对照组(P <0.05)。结论品管圈活动在喜疗妥联合新鲜马铃薯外敷治疗小儿输液外渗中的效果较好,可缩短临床症状消失时间,加快康复进程。     

Evaluating the inhibitory potential of Withania somnifera on platelet aggregation and inflammation enzymes: An in vitro and in silico study

Context Withania somnifera (L.) Dunal is traditionally used for treating various ailments, but lacks scientific evaluation.

Objective This study evaluates Withania somnifera (WS) for its effect on platelet activity and inflammatory enzymes.

Materials and methods Aqueous and ethanolic (1:1) leaf extracts were subjected to in vitro indirect haemolytic activity using Naja naja venom, human platelet aggregation was quantified for lipid peroxidation using arachidonic acid (AA) as agonist and 5-lipoxygenase (5-LOX) levels were determined using standard spectrometric assays. Further, molecular docking was performed by the ligand fit method using molegro software package (Molegro ApS, Aarhus, Denmark).

Results The study found that aqueous and ethanol extracts have very negligible effect (15%) with an IC₅₀ value of 13.8?mg/mL on PLA₂ from Naja naja venom. Further, extracts of WS also had very little effect (18%) with an IC₅₀ value of 16.6?mg/mL on malondialdehyde (MDA) formation. However, a 65% inhibition of 5-LOX with an IC₅₀ value of 0.92?mg/mL was observed in 1:1 ethanol extracts. The same was evident from SAR model with the active ingredient withaferin A binding predominantly on Phe 77, Tyr 98, Arg 99, Asp 164, Leu 168, Ser 382, Arg 395, Tyr 396 and Tyr 614 with an atomic contact energy value of??128.96 compared to standard phenidone (?103.61). Thus, the current study validates the application of WS for inflammatory diseases.

Conclusion This study reveals the inhibitory potential of W. somnifera on inflammatory enzymes and platelet aggregation. Thus, WS can serve as a newer, safer and affordable medicine for inflammatory diseases.