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Background Enhanced recovery protocols (ERP) are a multimodal approach to standardize perioperative care. To substantiate the benefit of a pediatric-centered pathway, we compared outcomes of children treated with pediatric ERP (pERP) versus adult (aERP) pathways. We aimed to compare components of each pathway to create a new comprehensive pERP to reduce variation in care. Methods Retrospective study of children (≤18 y) undergoing elective colorectal surgery from August 2015 to April 2019 at a single institution managed with pERP versus aERP. Multivariable linear and logistic regression, adjusting for demographics and operation characteristics, were used to compare outcomes. Results Out of 100 hospitalizations (72 patients) were identified, including 37 treated with pERP. pERP patients were, on average, younger (13 versus 16 y), more likely to be ASA III (70% versus 30%), and more likely to receive regional (32% versus 3%) or neuraxial (35% versus 8%) anesthesia. Epidural use was an independent risk factor for longer length of stay (P = 0.000). After adjustment, pERP patients had similar LOS and time to oral intake, but shorter foley duration. pERP patients used significantly fewer opioids and were less likely to return to the operating room within 30 d. 30-d readmissions and ED visits were also lower, but this was not statistically significant. Conclusions At our institution, data from both ERPs contributed formation of a synthesized pathway and reflected the pERP approach to opioid utilization and the aERP approach to earlier enteral nutrition.

Introduction Enhanced recovery after surgery (ERAS) pathways in adult colorectal surgery are known to reduce complications, readmissions, and length of stay (LOS). However, there is a paucity of ERAS data for pediatric colorectal surgery. Methods A 2014–2018 single-institution, retrospective cohort study was performed on pediatric colorectal surgery patients (2–18 years) pre- and post-ERAS pathway implementation. Bivariate analysis and linear regression were used to determine if ERAS pathway implementation reduced total morphine milligram equivalents per kilogram (MME/kg), LOS, and time to oral intake. Results 98 (70.5%) and 41 (29.5%) patients were managed with ERAS and non-ERAS pathways, respectively. There was no statistical difference in age, sex, diagnosis, or use of laparoscopic technique between cohorts. The ERAS cohort experienced a significant reduction in total MME/kg, Foley duration, time to oral intake, and LOS with no increase in complications. The presence of an ERAS pathway reduced the total MME/kg (− 0.071, 95% CI − 0.10, − 0.043) when controlling for covariates. Conclusion The use of an ERAS pathway reduces opioid utilization, which is associated with a reduction in LOS and expedites the initiation of oral intake, in colorectal pediatric surgery patients. Pediatric ERAS pathways should be incorporated into the care of pediatric patients undergoing colorectal surgery. Level of evidence Level III evidence. Type of study Retrospective cohort study.

Background The intestinal microbiota play a key role in the onset, progression, and recurrence of Crohn disease (CD). Most microbiome studies assay fecal material, which does not provide region-specific information on mucosally adherent bacteria that directly interact with host systems. Changes in luminal oxygen have been proposed as a contributor to CD dybiosis. Methods The authors generated 16S rRNA data using colonic and ileal mucosal bacteria from patients with CD and without inflammatory bowel disease. We developed profiles reflecting bacterial abundance within defined aerotolerance categories. Bacterial diversity, composition, and aerotolerance profiles were compared across intestinal regions and disease phenotypes. Results Bacterial diversity decreased in CD in both the ileum and the colon. Aerotolerance profiles significantly differed between intestinal segments in patients without inflammatory bowel disease, although both were dominated by obligate anaerobes, as expected. In CD, high relative levels of obligate anaerobes were maintained in the colon and increased in the ileum. Relative abundances of similar and distinct taxa were altered in colon and ileum. Notably, several obligate anaerobes, such as Bacteroides fragilis, dramatically increased in CD in one or both intestinal segments, although specific increasing taxa varied across patients. Increased abundance of taxa from the Proteobacteria phylum was found only in the ileum. Bacterial diversity was significantly reduced in resected tissues of patients who developed postoperative disease recurrence across 2 independent cohorts, with common lower abundance of bacteria from the Bacteroides, Streptococcus, and Blautia genera. Conclusions Mucosally adherent bacteria in the colon and ileum show distinct alterations in CD that provide additional insights not revealed in fecal material.

Background & Aims Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn’s disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets and functional consequences are unknown. Methods microRNA-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by quantitative polymerase chain reaction in colonic IECs. Functional characterization of activin receptor-like kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2-dimensional cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan–Meier estimator. Results ALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3’-untranslated region reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in a 5-ethynyl-2-deoxyuridine proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling increased colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared with healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a transepithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and was associated with a higher risk of endoscopic relapse in CD patients. Conclusions Decreased colonic ALK1 disrupted colonic IEC barrier integrity and was associated with poor clinical outcomes in CD patients., Graphical abstract

Reactive oxygen species (ROS) release seed dormancy through an unknown mechanism. We used different seed dormancy-breaking treatments to decipher the dynamics and localization of ROS production during seed germination. We studied the involvement of ROS in the breaking of Arabidopsis seed dormancy by cold stratification, gibberellic acid (GA

Background Fecal diversion after ileal pouch anal anastomosis (IPAA) in children with ulcerative colitis (UC) remains controversial. We hypothesize that a modified two-stage IPAA omitting diverting ileostomy (DI) after IPAA, found to be safe in adults, would produce similar results in children. Methods Retrospective, single-institution study of children (≤18 years) undergoing staged total proctocolectomy with IPAA from 2014 to 2020. Traditional two-stage and three-stage approaches including DI after IPAA were compared to two-stage approach without DI. Results 32 patients were included; of these, 7 (22%), 14 (44%), and 11 (34%) patients underwent traditional two-stage, modified two-stage, or three-stage IPAA, respectively. Following IPAA, modified two-stage patients had shorter operative time, decreased opioid utilization, quicker return to regular diet, and shorter stoma duration. After IPAA, there was similar postoperative length of stay, complication rates, readmissions, visits to the emergency department, or unplanned return to the operating room (OR) within 30 days. Anastomotic leak occurred in 2 patients; both were managed nonoperatively without evidence of pouch dysfunction. Conclusion Modified two-stage IPAA with omission of DI after the IPAA stage is safe to perform in pediatric UC patients. Prospective studies with larger sample sizes are needed to identify risk factors associated with operative complications.

IMPORTANCE: Factors contributing to underrepresentation of women in surgery are incompletely understood. Pro-male bias and stereotype threat appear to contribute to gender imbalance in surgery. OBJECTIVES: To evaluate the association between pro-male gender bias and career engagement and the effect of stereotype threat on skill performance among trainees in academic surgery. DESIGN, SETTING, AND PARTICIPANTS: A 2-phase study with a double-blind, randomized clinical trial component was conducted in 3 academic general surgery training programs. Residents were recruited between August 1 and August 15, 2018, and the study was completed at the end of that academic year. In phase 1, surveys administered 5 to 6 months apart investigated the association of gender bias with career engagement. In phase 2, residents were randomized 1:1 using permuted-block design stratified by site, training level, and gender to receive either a trigger of or protection against stereotype threat. Immediately after the interventions, residents completed the Fundamentals of Laparoscopic Surgery (FLS) assessment followed by a final survey. A total of 131 general surgery residents were recruited; of these 96 individuals with academic career interests met eligibility criteria; 86 residents completed phase 1. Eighty-five residents were randomized in phase 2, and 4 residents in each arm were lost to follow-up. INTERVENTION: Residents read abstracts that either reported that women had worse laparoscopic skill performance than men (trigger of stereotype threat [A]) or had no difference in performance (protection against stereotype threat [B]). MAIN OUTCOMES AND MEASURES: Association between perception of pro-male gender bias and career engagement survey scores (phase 1) and stereotype threat intervention and FLS scores (phase 2) were the outcomes. Intention-to-treat analysis was conducted. RESULTS: Seventy-seven residents (38 women [49.4%]) completed both phases of the study. The association between pro-male gender bias and career engagement differed by gender (interaction coefficient, −1.19; 95% CI, −1.90 to −0.49; P = .02); higher perception of bias was associated with higher engagement among men (coefficient, 1.02; 95% CI, 0.19-2.24; P = .04), but no significant association was observed among women (coefficient, −0.25; 95% CI, −1.59 to 1.08; P = .50). There was no evidence of a difference in FLS score between interventions (mean [SD], A: 395 [150] vs B: 367 [157]; P = .51). The response to stereotype threat activation was similar in men and women (interaction coefficient, 15.1; 95% CI, −124.5 to 154.7; P = .39). The association between stereotype threat activation and FLS score differed by gender across levels of susceptibility to stereotype threat (interaction coefficient, −35.3; 95% CI, −47.0 to −23.6; P = .006). Higher susceptibility to stereotype threat was associated with lower FLS scores among women who received a stereotype threat trigger (coefficient, −43.4; 95% CI, −48.0 to −38.9; P = .001). CONCLUSIONS AND RELEVANCE: Perception of pro-male bias and gender stereotypes may influence career engagement and skill performance, respectively, among surgical trainees. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03623009

ObjectiveIntestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn’s disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets are unknown.DesignMiR-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by qPCR in colonic IECs. Functional characterization of Activin Receptor-Like Kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2 dimensional-cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator.ResultsALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3’-UTR reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in an EdU proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling directed the fate of colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared to healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a trans-epithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and associated with a higher risk of endoscopic relapse in CD patients.ConclusionDecreased colonic ALK1 disrupted colonic IEC barrier integrity and associated with deteriorated clinical outcomes in CD patients.

Background Rates of readmission after colorectal surgery (CRS) range from 9% to 25% and cost the US $300 million annually. The aim of this study was to identify risk factors for 30-d readmission after CRS. Our hypothesis was that transfer from an outside hospital before CRS increases incidence of 30-d readmission. Methods Using the Healthcare Cost and Utilization Project Nationwide Readmissions Database, a retrospective analysis of surviving adult patients who underwent inpatient colon and/or rectal resection from 2010 to 2014 was performed. Using multivariable logistic regression, we assessed the direct effect of potential risk factors for readmission, including demographics, hospital characteristics, comorbidities, indication for CRS, and transfer status to the index hospital where the CRS was performed. Results A total of 336,792 patients were included, and 13% (n = 43,546) were readmitted within 30 d. Overall, 1% of patients (n = 3652) were transferred from another hospital for surgery, and these patients were more likely to be older, have comorbidities, have public insurance, and have low income. After adjustment, age, insurance type, household income, comorbidities, and primary indication for CRS were all significant predictors of readmission. Transfer status did not meaningfully impact the incidence of readmission after accounting for patient and hospital characteristics (aOR 1.08, 95% CI 1.00, 1.18). Patients with primary indications of trauma (aOR 1.88, 95% CI 1.48, 2.38), inflammatory bowel disease (aOR 1.64, 95% CI 1.1.56, 1.71), and ischemia (aOR 1.77, 95% CI 1.1.59, 1.97) were most likely to be readmitted. Patients treated at a rural nonteaching hospital, compared with those at a urban teaching hospital, were significantly less likely to be readmitted (aOR 0.80, 95% CI 0.76, 0.83). Conclusions Preoperative factors, such as patient comorbidities and primary indications for CRS, are important risk factors for postoperative readmission. Although transfer status does not independently predict readmission, it serves as a proxy for a high-risk group of patients that could be targeted for future interventions.

Background Ulcerative colitis patients have been historically treated with standard single, 2-, and 3-stage operative approaches. We perform a variant 2-stage procedure beginning with total abdominal colectomy and end ileostomy followed by completion proctectomy and ileal pouch-anal anastomosis (IPAA) without a diverting loop ileostomy. This study evaluates the effectiveness of this innovative alternative. Study design Patients with ulcerative colitis, admitted to the University of North Carolina Hospital between 2003 and 2010 for IPAA, were eligible for inclusion. The 3-year cumulative incidence of pouch leaks among patients undergoing variant 2-stage were compared with those undergoing classic 2-stage, using inverse probability-of-treatment weighted Kaplan- Meier survival curves, and 95% CIs were estimated using nonparametric bootstrapping. Results There were 248 patients who underwent IPAA; 139 (56.1%) underwent classic 2-stage and 109 (43.9%) underwent variant 2-stage. After standardization, there was no significant difference in the 3-year cumulative incidence of pouch leaks between patients undergoing variant 2-stage, compared with the standard single- or 2-stage procedure (risk difference 0.01; 95% CI −0.08, 0.15). At the time of the first surgical procedure, patients undergoing a variant 2-stage were more likely to have lower BMIs (median 22.5 kg/m 2 vs 26.7 kg/m 2 ; p Conclusions Variant 2-stage IPAA is a safe and effective operative approach with comparable outcomes in a more acute population based on BMI, steroid use, and urgency of operation.

Background Streamlined discharge communication in transitions of care improvement models improve patient satisfaction, improve patient self-efficacy, and reduce readmissions. Yet, significant variability and quality exists in the After Visit Summary (AVS) which is used to guide the post-discharge needs of the patient. Objectives We sought assess the feasibility, fidelity, acceptability, and effectiveness of a standardized, patient-centered AVS. Methods Our multiprofessional and multidisciplinary stakeholder team was led by two physicians and had significant institutional support. We employed a tailored, hybrid implementation strategy, blending components from Lean methodology, the Institute for Healthcare Model for Improvement, and the Consolidated Framework for Implementation Research. We assessed the feasibility (e.g. quality of AVS, usability of template), fidelity (e.g. template utilization rates), acceptability (e.g. direct stakeholder feedback, paging-system audit, patient call logs), and effectiveness (e.g. 30-day readmission rates and patient-centeredness) of our intervention (e.g. standardized, patient-centered AVS). Results Our AVS template was written at a third grade reading level but retained all clinically-relevant information. Providers and patients approved of the template with 66% mean utilization (range 41% to 80%). After our intervention, we observed decreased 30-day readmissions (19.7% to 16.0%). Notably, after the introduction of AVS template, pages sent decreased by 3.67 pages weekly (95% CI=[−15.7, 14.0]), but this estimate was imprecise. Conclusions Reducing variability and improving the quality of discharge communication, not only improves patient outcomes, but may also improve workflow for providers. These improved team dynamics are important to assess when considering an intervention that is operationalized by time and resource deprived employees.

Background Risk factors for the development of chronic antibiotic dependent pouchitis (CADP) are not well understood. Methods Using multivariable logistic regression, we compared clinical factors between 194 patients with acute antibiotic responsive pouchitis or CADP. Results Individuals with CADP were significantly older (40.9 vs 30.8 years, P < 0.001) and demonstrated a longer disease duration before IPAA (10.3 vs 7.0 years, P = 0.004). Age ≥55 years at the time of IPAA was significantly associated with CADP (adjusted odds ratio = 4.35, 95% confidence interval = 1.01–18.7). Conclusions Although older age should not represent a barrier to IPAA, further studies evaluating etiologies of this association are warranted., In this study of patients with ulcerative colitis who underwent a colectomy with ileal pouch-anal anastomosis, patients age 55 years and older at the time of surgery had an increased risk of developing chronic antibiotic dependent pouchitis.

A healthy 65-year-old woman presents to the emergency room with a 12-hour history of sudden onset severe lower abdominal pain. This is her first episode. She reports nausea, vomiting, and anorexia. Her last colonoscopy was at age 60, and was normal, except for diverticulosis of the sigmoid colon. Physical examination is significant for fever, tachycardia, and generalized abdominal pain with rebound tenderness. Pertinent laboratory findings include a leukocytosis and metabolic acidosis. A computed tomography (CT) scan is obtained and is consistent with freely perforated diverticulitis, including a thickened sigmoid colon, free fluid in the pelvis and free air noted near the diaphragm (Figure 1). The surgeon completes the patient evaluation, recommends initiation of IV fluid resuscitation and antibiotics, and plans to go immediately to the operating room for surgical resection.

Background The functional determinants of H3K4me3, their potential dependency on histone H2B monoubiquitination, and their contribution to defining transcriptional regimes are poorly defined in plant systems. Unlike in Saccharomyces cerevisiae, where a single SET1 protein catalyzes H3K4me3 as part of COMPlex of proteins ASsociated with Set1 (COMPASS), in Arabidopsis thaliana, this activity involves multiple histone methyltransferases. Among these, the plant-specific SET DOMAIN GROUP 2 (SDG2) has a prominent role. Results We report that SDG2 co-regulates hundreds of genes with SWD2-like b (S2Lb), a plant ortholog of the Swd2 axillary subunit of yeast COMPASS. We show that S2Lb co-purifies with the AtCOMPASS core subunit WDR5, and both S2Lb and SDG2 directly influence H3K4me3 enrichment over highly transcribed genes. S2Lb knockout triggers pleiotropic developmental phenotypes at the vegetative and reproductive stages, including reduced fertility and seed dormancy. However, s2lb seedlings display little transcriptomic defects as compared to the large repertoire of genes targeted by S2Lb, SDG2, or H3K4me3, suggesting that H3K4me3 enrichment is important for optimal gene induction during cellular transitions rather than for determining on/off transcriptional status. Moreover, unlike in budding yeast, most of the S2Lb and H3K4me3 genomic distribution does not rely on a trans-histone crosstalk with histone H2B monoubiquitination. Conclusions Collectively, this study unveils that the evolutionarily conserved COMPASS-like complex has been co-opted by the plant-specific SDG2 histone methyltransferase and mediates H3K4me3 deposition through an H2B monoubiquitination-independent pathway in Arabidopsis. Electronic supplementary material The online version of this article (10.1186/s13059-019-1705-4) contains supplementary material, which is available to authorized users.

The functional determinants of histone H3 Lys-4 trimethylation (H3K4me3), their potential dependency on histone H2B monoubiquitination (H2Bub) and their contribution to defining transcriptional regimes are poorly defined in plant systems. Unlike inS. cerevisiae, where a single SET1 protein catalyzes H3 Lys-4 trimethylation as part of COMPASS (COMPlex of proteins ASsociated with Set1), inArabidopsis thalianathis activity involves multiple histone methyltransferases (HMTs). Among these, the plant-specific SDG2 (SET DOMAIN GROUP2) has a prominent role. We report that SDG2 co-regulates hundreds of genes with SWD2-like b (S2Lb), a plant ortholog of the Swd2 axillary subunit of yeast COMPASS. S2Lb co-purifies with the AtCOMPASS core subunit WDR5 from a high-molecular weight complex, and both S2Lb and SDG2 directly influence H3K4me3 enrichment over highly transcribed genes.S2Lbknockout triggers pleiotropic developmental phenotypes at the vegetative and reproductive stages, including reduced fertility and seed dormancy. Notwithstanding,s2lbseedlings display little transcriptomic defects as compared to the large repertoire of genes targeted by S2Lb, SDG2 or H3 Lys-4 trimethylation, suggesting that H3K4me3 enrichment is important for optimal gene induction during cellular transitions rather than for determining on/off transcriptional status. Moreover, unlike in budding yeast, most of the S2Lb and H3K4me3 genomic distribution does not rely on a trans-histone crosstalk with histone H2B monoubiquitination. Collectively, this study unveils that the evolutionarily conserved COMPASS-like complex has been coopted by the plant-specific SDG2 HMT and mediates H3K4me3 deposition through an H2Bub-independent pathway in Arabidopsis.

BACKGROUND. Crohn’s disease (CD) is highly heterogeneous, due in large part to variability in cellular processes that underlie the natural history of CD, thereby confounding effective therapy. There is a critical need to advance understanding of the cellular mechanisms that drive CD heterogeneity. METHODS. We performed small RNA sequencing of adult colon tissue from CD and NIBD controls. Colonic epithelial cells and immune cells were isolated from colonic tissues, and microRNA-31 (miR-31) expression was measured. miR-31 expression was measured in colonoid cultures generated from controls and patients with CD. We performed small RNA-sequencing of formalin-fixed paraffin-embedded colon and ileum biopsies from treatment-naive pediatric patients with CD and controls and collected data on disease features and outcomes. RESULTS. Small RNA-sequencing and microRNA profiling in the colon revealed 2 distinct molecular subtypes, each with different clinical associations. Notably, we found that miR-31 expression was a driver of these 2 subtypes and, further, that miR-31 expression was particularly pronounced in epithelial cells. Colonoids revealed that miR-31 expression differences are preserved in this ex vivo system. In adult patients, low colonic miR-31 expression levels at the time of surgery were associated with worse disease outcome as measured by need for an end ileostomy and recurrence of disease in the neoterminal ileum. In pediatric patients, lower miR-31 expression at the time of diagnosis was associated with future development of fibrostenotic ileal CD requiring surgery CONCLUSIONS. These findings represent an important step forward in designing more effective clinical trials and developing personalized CD therapies. FUNDING. This work was supported by CCF Career Development Award (SZS), R01-ES024983 from NIEHS (SZS and TSF), 1R01DK104828-01A1 from NIDDK (SZS and TSF), P01-DK094779-01A1 from NIDDK (SZS), P30-DK034987 from NIDDK (SZS), 1-16-ACE-47 ADA Pathway Award (PS), UNC Nutrition Obesity Research Center Pilot & Feasibility Grant P30DK056350 (PS), CCF PRO-KIIDS NETWORK (SZS and PS), UNC CGIBD T32 Training Grant from NIDDK (JBB), T32 Training Grant (5T32GM007092-42) from NIGMS (MH), and SHARE from the Helmsley Trust (SZS). The UNC Translational Pathology Laboratory is supported, in part, by grants from the National Cancer Institute (3P30CA016086) and the UNC University Cancer Research Fund (UCRF) (PS).

This article was migrated. The article was marked as recommended. The surgical discharge summary allows the perioperative care team to summarize a recent hospitalization and relay important information to a variety of invested parties including other healthcare providers, outpatient caregivers, and the surgical patient. The inpatient care team can promote a smooth transition of care and empower outpatient providers and the patient to foster a confident progression through recovery. We describe twelve tips for a streamlined, successful discharge summary geared towards the surgical intern. A successful surgical discharge summary begins with patient and caregiver collaboration, communication and teamwork, and culminates with concise documentation. These tips reflect a review of the current literature and rely on the clinical expertise of an interdisciplinary surgical team. Our aim is to empower surgical educators and trainees to understand the complexity of discharge planning, and to improve the efficiency with which it can be completed and the quality of the discharge process at their training hospitals.