Nationwide outcomes of newborns with rectosigmoid versus long-segment Hirschsprung disease

PurposeHirschsprung Disease (HD) is a common congenital intestinal disorder. While aganglionosis most commonly affects the rectosigmoid colon (rectosigmoid HD), outcomes for patients in which aganglionosis extends to more proximal segments (long-segment HD) remain understudied. This study sought to compare postoperative outcomes among newborns with rectosigmoid and long-segment HD.MethodsThe Nationwide Readmission Database was queried from 2016 to 2018 for newborns with HD. Newborns were stratified into those with rectosigmoid or long-segment HD. Those who received no rectal biopsy or pull-through procedure during their newborn hospitalization were excluded. A propensity score-matched analysis (PSMA) of newborns with either type of HD was constructed utilizing 17 covariates including demographics, comorbidities, and congenital-perinatal conditions.ResultsThere were 1280 newborns identified with HD (82% rectosigmoid HD, 18% long-segment HD). Patients with rectosigmoid HD had higher rates of laparoscopic resections (35% vs. 12%) and less frequently received a concomitant ostomy (14% vs. 84%), both p < 0.001. Patients with long-segment HD were more likely to have a delayed diagnosis (12% vs. 5%) and require multiple bowel operations (19% vs. 4%), both p < 0.001. They experienced higher rates of complications, including small bowel obstructions (10% vs. 1%), infections (45% vs. 20%), and Hirschsprung-associated enterocolitis (11% vs. 5%), all p < 0.001. After PSMA, newborns with long-segment HD were found to have a longer length of stay and higher hospitalization costs.ConclusionNewborns with long-segment HD experience significant delays in diagnosis, surgery, and complications compared to those with rectosigmoid HD. This information should be utilized to improve healthcare delivery for this patient population.Type of StudyRetrospective comparative study.Level of EvidenceIII.     

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     

Decreased Incidence of Hirschsprung-Associated Enterocolitis During COVID-19 Across United States Children's Hospitals

BackgroundThe Coronavirus Disease 2019 pandemic provided a natural experiment to study the effect of social distancing on the risk of developing Hirschsprung's Associated Enterocolitis (HAEC).MethodsUsing the Pediatric Health Information System (PHIS), a retrospective cohort study of children (<18 years) with Hirschsprung's Disease (HSCR) across 47 United States children's hospitals was performed. The primary outcome was HAEC admissions per 10,000 patient-days. The exposure (COVID-19) was defined as April 2020–December 2021. The unexposed (historical control) period was April 2018–December 2019. Secondary outcomes included sepsis, bowel perforation, intensive care unit (ICU) admission, mortality, and length of stay.ResultsOverall, we included 5707 patients with HSCR during the study period. There were 984 and 834 HAEC admissions during the pre-pandemic and pandemic periods, respectively (2.6 vs. 1.9 HAEC admissions per 10,000 patient-days, incident rate ratio [95% confidence interval]: 0.74 [0.67, 0.81], p < 0.001). Compared to pre-pandemic, those with HAEC during the pandemic were younger (median [IQR]: 566 [162, 1430] days pandemic vs. 746 [259, 1609] days pre-pandemic, p < 0.001) and more likely to live in the lowest quartile of median household income zip codes (24% pandemic vs. 19% pre-pandemic, p = 0.02). There were no significant differences in rates of sepsis (6.1% pandemic vs. 6.1% pre-pandemic, p > 0.9), bowel perforation (1.3% pandemic vs. 1.2% pre-pandemic, p = 0.8), ICU admissions (9.6% pandemic vs. 12% pre-pandemic, p = 0.2), mortality (0.5% pandemic vs. 0.6% pre-pandemic, p = 0.8), or length of stay (median [interquartile range]: 4 [(Pastor et al., 2009; Gosain and Brinkman, 2015) 2,112,11 days pandemic vs. 5 [(Pastor et al., 2009; Tang et al., 2020) 2,102,10 days pre-pandemic, p = 0.4).ConclusionsThe COVID-19 pandemic was associated with significantly decreased incidence of HAEC admissions across US children's hospitals. Possible etiologies such as social distancing should be explored.Level of evidenceII.     

NF-κB活化在氯化钆诱导ANP肺泡巨噬细胞凋亡中的作用

目的：观察氯化钆（GdCl3）诱导急性坏死性胰腺炎(ANP)肺泡巨噬细胞(AM)凋亡时核因子-κB（NF-κB）表达情况,探讨NF-κB在其中的作用及机制。
方法：36只SD大鼠随机分为正常对照组,ANP组,GdCl3治疗组。逆行性胰胆管注射5%牛磺胆酸钠建立ANP大鼠模型,正常对照组大鼠以同法注入生理盐水,GdCl3治疗组制模后即刻自阴茎背静脉注射GdCl3。各组大鼠于成模后6 h经支气管肺泡灌洗获取AM,检测支气管肺泡灌洗液(BALF)中TNF-α和IL-1β含量及肺组织髓过氧化物酶(MPO)水平。用琼脂糖凝胶电泳、流式细胞仪检测AM的凋亡情况;Western-blot检测AM中NF-κB活性。同时对肺组织行病理学检查。
结果：ANP组TNF-α和IL-1β含量高于对照组（P<0.05）,而治疗组显著低于ANP组（P<0.05）。仅治疗组DNA电泳见典型的细胞凋亡的梯状条带。对照组,ANP组,治疗组AM凋亡率分别为（10.81±0.86）%,（6.47±1.52）%,（17.41±3.36）%,3组间差异均有统计学意义（P<0.05）;Western-blot检测3组AM中NF-κB表达的相对灰度值分别为（0.80±0.05）,（1.96±0.15）,（1.42±0.10）,3组间差异亦有统计学意义（P<0.05）。AM的凋亡率与NF-κB活性呈负相关（r＝-0.554,P<0.01）。
结论：GdCl3可能通过抑制NF-κB的活化诱导大鼠ANP肺泡巨噬细胞凋亡,从而减轻肺损伤。     

The timing of enterostomy reversal after necrotizing enterocolitis

Background/Purpose

Newborns undergoing surgery for necrotizing enterocolitis (NEC) often require a stoma. The study purpose is to determine if the timing of stoma closure impacts the postoperative course.

Methods

After obtaining institutional review board approval, records of patients with NEC who received a stoma between 2003 and 2007 at 2 pediatric institutions were reviewed. Data collected included time interval between stoma creation and closure, indication for closure, postoperative complications, time to feeds, and length of neonatal intensive care unit and hospital stays. For analysis purposes, patients were divided in 2 groups: 1, stoma closed within 10 weeks; and 2, stoma closed more than 10 weeks after construction.

Results

There were 37 patients: 13 in group 1 and 24 in group 2. Group 1 babies were ventilated longer postoperation (7.69 vs 1.08 days, P = .0006). They required total parenteral nutrition for more days (51.62 vs 16.30 days, P = .0486). Group 1 patients took longer to reach full po (19.08 vs 7.86 days, P = .027), and they had a longer length of stay postreversal (113.08 vs 31.32 days, P = .0373). No differences were observed in survival rates or anastomotic complications.

Conclusion

The timing of stoma reversal significantly impacts the postoperative course after NEC. Unless seriously indicated, stoma closure should be deferred until at least 10 weeks postcreation.     

Mortality of necrotizing enterocolitis expressed by birth weight categories

Purpose

Low birth weight is the most important risk factor for developing necrotizing enterocolitis (NEC). We aimed to establish birth weight-based benchmarks for in-hospital mortality in neonates with NEC.

Methods

Five hundred eleven centers belonging to the Vermont Oxford Network prospectively evaluated 71,808 neonates with birth weight of 501 to 1500 g between January 2005 and December 2006. The primary outcome variable was in-hospital mortality.

Results

Birth weight was divided into 4 categories by 250-g increments. The NEC risk (P < .001) and mortality (P < .001) decreased with higher birth weight category. Necrotizing enterocolitis was associated with a significant odds ratio for death for each category (P < .001). Across groups, the odds ratio for NEC mortality increased with higher birth weight category (category 1 = 1.6 vs category 4 = 9.9; P < .001).

Conclusion

The in-hospital mortality rate of neonates with NEC remains high and is significantly related to birth weight category. Although the risk and absolute mortality of NEC decrease with higher birth weight, the odds ratios indicate that NEC has a relatively greater impact upon mortality at higher birth weight. These data afford birth weight-based mortality benchmarks that may be useful in assessing single center NEC outcomes and facilitating comparisons between centers.     

氯膦酸二钠脂质体对大鼠重症急性胰腺炎肺损伤的影响及与Akt、MAPK（ERK1/2）通路的关系

目的:探讨氯膦酸二钠脂质体(LC)对大鼠重症急性胰腺炎(SAP)肺损伤的影响及与Akt、MAPK(ERK1/2)通路的关系。方法:将48只SD大鼠随机均分为假手术组、SAP模型组(模型组)、SAP模型+LC处理组(LC组),后两组采用膜下注射5%牛磺胆酸钠制作SAP模型,并分别于造模后尾静脉注射空白脂质体与LC。各组分别于术后2、6h后检测血清淀粉酶(AMS)、IL-6、TNF-α的含量,观察肺组织病理学变化,及肺组织中Akt和MAPK(ERK1/2)的表达。结果:与假手术组比较,模型组与LC组血清AMS、IL-6及TNF-α含量、肺组织病理学评分,肺组织Akt和MAPK(ERK1/2)表达水平均明显升高,且均随时间延长而更加明显(均P0.05),但LC组的上述指标在各时间点上均明显低于模型组(均P0.05)。结论:LC有减轻大鼠SAP肺损伤的作用,机制可能与肺泡巨噬细胞吞噬LC后,Akt和MAPK(ERK1/2)信号通路抑制,从而减少炎症细胞因子的释放有关。     

Necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a neonatal surgical emergency with potentially devastating consequences. Pre-term infants of very low birth weight are most at risk with several genetic and environmental risk factors identified. The local microbial environment plays a key role in early life to help reduce the risk of NEC. Breast milk has also shown to be protective. The disease is characterized by infection, inflammation and ischaemia of the bowel that can extend from a small segment to most of its length. The diagnosis is made based on clinical, biochemical and radiological features with perforation the most widely accepted indication for surgery. When conservative management fails, a laparotomy is indicated with the aim of resecting necrotic bowel and preserving intestinal length. Complications include strictures, stoma morbidity, short-bowel syndrome and poor neurodevelopmental outcomes. Preventative strategies include the use of probiotics and encouraging the use of breast milk.     

Hyperbaric oxygen as adjuvant therapy in the management of necrotizing fasciitis

BACKGROUND: Necrotizing fasciitis (NF) is an uncommon but serious infection of fascia and skin associated with considerable morbidity and mortality. One modality proposed for improving the outcome of this condition is hyperbaric oxygen (HBO) therapy. This is a form of medical treatment that involves intermittent inhalation of 100% oxygen under pressures exceeding the atmosphere. The aim of this article is to review current practice and evidence for the use of HBO as adjunctive therapy in the management of NF. METHODS: A survey of published English literature through searches of Medline and PubMed was carried out using the following key words: "necrotizing fasciitis," "Fournier's gangrene," "necrotizing soft tissue infections," "hyperbaric oxygen therapy," "and hyperbaric oxygen chambers." RESULTS: The results of studies on the use of HBO therapy in NF are inconsistent. Some studies have demonstrated that HBO can improve patient survival and decrease the number of debridements required to achieve wound control, whereas others have failed to show any beneficial effect. CONCLUSIONS: Encouraging results have been achieved with the addition of HBO therapy to standard treatment regimes, thus justifying further research in this field. More robust evidence by way of a prospective randomized trial is necessary before widespread and routine use of HBO in the management of NF can be recommended.     

新生儿坏死性小肠结肠炎伴发肠穿孔危险因素的回顾性研究

目的:探讨新生儿坏死性小肠结肠炎（NEC）伴发肠穿孔的危险因素。方法:回顾性分析55例NEC伴发肠穿孔患儿（NEC伴发肠穿孔组）的临床资料,并随机选取110例同期收治的NEC未伴发肠穿孔 患儿为对照组,采用单因素和多因素Logistic回归分析,总结NEC伴发肠穿孔的危险因素。结果:NEC并发败血症（OR=2.557）、凝血功能障碍（OR=4.075）、低钾血症（OR=5.180）是肠穿孔的独立危险 因素（P＜0.05）,而高胎龄（OR=0.884）为保护因素（P＜0.05）。上述3个独立危险因素联合对NEC伴发肠穿孔的预测价值最高,ROC曲线下面积为0.875,特异性和灵敏性分别为79.2%、81.8%。结论: NEC伴发败血症、凝血功能障碍、低钾血症是NEC伴发肠穿孔的独立危险因素。三者联合对NEC伴发肠穿孔有较高预测价值。