Type 1 diabetes human enteroid studies reveal major changes in the intestinal epithelial compartment.

Lack of understanding of the pathophysiology of gastrointestinal (GI) complications in type 1 diabetes (T1D), including altered intestinal transcriptomes and protein expression represents a major gap in the management of these patients. Human enteroids have emerged as a physiologically relevant model of the intestinal epithelium but establishing enteroids from individuals with long-standing T1D has proven difficult. We successfully established duodenal enteroids using endoscopic biopsies from pediatric T1D patients and compared them with aged-matched enteroids from healthy subjects (HS) using bulk RNA sequencing (RNA-seq), and functional analyses of ion transport processes. RNA-seq analysis showed significant differences in genes and pathways associated with cell differentiation and proliferation, cell fate commitment, and brush border membrane. Further validation of these results showed higher expression of enteroendocrine cells, and the proliferating cell marker Ki-67, significantly lower expression of NHE3, lower epithelial barrier integrity, and higher fluid secretion in response to cAMP and elevated calcium in T1D enteroids. Enteroids established from pediatric T1D duodenum identify characteristics of an abnormal intestinal epithelium and are distinct from HS. Our data supports the use of pediatric enteroids as an ex-vivo model to advance studies of GI complications and drug discovery in T1D patients.

Impact of a novel pre-hospital stroke notification programme on acute stroke care key performance indicators in Hong Kong: a multicentre prospective cohort study with historical controls.

INTRODUCTION: Early identification and initiation of reperfusion therapy is essential for suspected acute ischaemic stroke. A pre-hospital stroke notification (PSN) protocol using FASE (facial drooping, arm weakness, speech difficulties, and eye palsy) was implemented to improve key performance indicators (KPIs) in acute stroke care delivery. We assessed KPIs and clinical outcomes before and after PSN implementation in Hong Kong. METHODS: This prospective cohort study with historical controls was conducted in the Accident and Emergency Departments of four public hospitals in Hong Kong. Patients were screened using the PSN protocol between August 2021 and February 2022. Suspected stroke patients between August 2020 and February 2021 were included as historical controls. Door-to-needle (DTN) and door-to-computed tomography (DTC) times before and after PSN implementation were compared. Clinical outcomes including National Institutes of Health Stroke Scale score at 24 hours and modified Rankin Scale score at 3 months after intravenous recombinant tissue-type plasminogen activator (IV-rtPA) were also assessed. RESULTS: Among the 715 patients (266 PSN and 449 non-PSN) included, 50.8% of PSN patients and 37.7% of non-PSN patients had a DTC time within 25 minutes (P<0.001). For the 58 PSN and 134 non-PSN patients given IV-rtPA, median DTN times were 67 and 75.5 minutes, respectively (P=0.007). The percentage of patients with a DTN time within 60 minutes was higher in the PSN group than in the non-PSN group (37.9% vs 21.6%; P=0.019). No statistically significant differences in clinical outcomes were observed. CONCLUSION: Although the PSN protocol shortened DTC and DTN times, clinical outcomes did not significantly differ.

The Air-Liquid Interface Reorganizes Membrane Lipids and Enhances the Recruitment of Slc26a3 to Lipid-Rich Domains in Human Colonoid Monolayers.

Cholesterol-rich membrane domains, also called lipid rafts (LRs), are specialized membrane domains that provide a platform for intracellular signal transduction. Membrane proteins often cluster in LRs that further aggregate into larger platform-like structures that are enriched in ceramides and are called ceramide-rich platforms (CRPs). The role of CRPs in the regulation of intestinal epithelial functions remains unknown. Down-regulated in adenoma (DRA) is an intestinal Cl-/HCO3- antiporter that is enriched in LRs. However, little is known regarding the mechanisms involved in the regulation of DRA activity. The air-liquid interface (ALI) was created by removing apical media for a specified number of days; from 12-14 days post-confluency, Caco-2/BBe cells or a colonoid monolayer were grown as submerged cultures. Confocal imaging was used to examine the dimensions of membrane microdomains that contained DRA. DRA expression and activity were enhanced in Caco-2/BBe cells and human colonoids using an ALI culture method. ALI causes an increase in acid sphingomyelinase (ASMase) activity, an enzyme responsible for enhancing ceramide content in the plasma membrane. ALI cultures expressed a larger number of DRA-containing platforms with dimensions >2 µm compared to cells grown as submerged cultures. ASMase inhibitor, desipramine, disrupted CRPs and reduced the ALI-induced increase in DRA expression in the apical membrane. Exposing normal human colonoid monolayers to ALI increased the ASMase activity and enhanced the differentiation of colonoids along with basal and forskolin-stimulated DRA activities. ALI increases DRA activity and expression by increasing ASMase activity and platform formation in Caco-2/BBe cells and by enhancing the differentiation of colonoids.

Human migration-based graph convolutional network for PM2.5 forecasting in post-COVID-19 pandemic age.

Due to the coronavirus disease 2019 pandemic, local authorities always implanted non-pharmaceutical interventions, such as maintaining social distance to reduce human migration. Besides, previous studies have proved that human migration highly influenced air pollution concentration in an area. Therefore, this study aims to explore whether human migration can work as a significant factor in the post-pandemic age to help PM2.5 concentration forecasting. In this work, we first analyze the variations of PM2.5 in 11 cities of Hubei from 2015 to 2020 and further compare PM2.5 trends with the migration trends of Hubei province in 2020. Experimental results indicate that the human migration indirectly affected the urban PM2.5 concentration. Then, we established a graph data structure based on the migration network describing the migration flow size between any two areas in the Hubei province and proposed a migration attentive graph convolutional network (MAGCN) for forecasting PM2.5. Combined with the migration data. The proposed model can attentively aggregate the information of neighbor nodes through migration weights. Experimental results indicate that the proposed MAGCN can forecast PM2.5 concentration accurately.

A framework for automated gene selection in genomic applications.

PURPOSE: An efficient framework to identify disease-associated genes is needed to evaluate genomic data for both individuals with an unknown disease etiology and those undergoing genomic screening. Here, we propose a framework for gene selection used in genomic analyses, including applications limited to genes with strong or established evidence levels and applications including genes with less or emerging evidence of disease association. METHODS: We extracted genes with evidence for gene-disease association from the Human Gene Mutation Database, OMIM, and ClinVar to build a comprehensive gene list of 6,145 genes. Next, we applied stringent filters in conjunction with computationally curated evidence (DisGeNET) to create a restrictive list limited to 3,929 genes with stronger disease associations. RESULTS: When compared to manual gene curation efforts, including the Clinical Genome Resource, genes with strong or definitive disease associations are included in both gene lists at high percentages, while genes with limited evidence are largely removed. We further confirmed the utility of this approach in identifying pathogenic and likely pathogenic variants in 45 genomes. CONCLUSION: Our approach efficiently creates highly sensitive gene lists for genomic applications, while remaining dynamic and updatable, enabling time savings in genomic applications.

Personalized prediction of transcranial magnetic stimulation clinical response in patients with treatment-refractory depression using neuroimaging biomarkers and machine learning.

BACKGROUND: Functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate (sgACC) may serve as a biomarker for transcranial magnetic stimulation (rTMS) treatment response. The first aim was to establish whether this finding is veridical or artifactually induced by the pre-processing method. Furthermore, alternative biomarkers were identified and the clinical utility for personalized medicine was examined. METHODS: Resting-state fMRI data were collected in medication-refractory depressed patients (n = 70, 16 males) before undergoing neuronavigated left DLPFC rTMS. Seed-based analyses were performed with and without global signal regression pre-processing to identify biomarkers of short-term and long-term treatment response. Receiver Operating Characteristic curve and supervised machine learning analyses were applied to assess the clinical utility of these biomarkers for the classification of categorical rTMS response. RESULTS: Regardless of the pre-processing method, DLPFC-sgACC connectivity was not associated with treatment outcome. Instead, poorer connectivity between the sgACC and three clusters (peak locations: frontal pole, superior parietal lobule, occipital cortex) and DLPFC-central opercular cortex were observed in long-term nonresponders. The identified connections could serve as acceptable to excellent markers. Combining the features using supervised machine learning reached accuracy rates of 95.35% (CI=82.94-100.00) and 88.89% (CI=63.96-100.00) in the cross-validation and test dataset, respectively. LIMITATIONS: The sample size was moderate, and features for machine learning were based on group differences. CONCLUSIONS: Long-term nonresponders showed greater disrupted connectivity in regions involving the central executive network. Our findings may aid the development of personalized medicine for medication-refractory depression.

Decision rule to predict pneumonia in children presented with acute febrile respiratory illness.

BACKGROUND: It is a frequent challenge for physicians to identify pneumonia in patients with acute febrile respiratory symptoms, particularly in stable pediatric patients without respiratory distress. A decision rule is required to assist judgement on the need of ordering a chest radiograph. METHOD: This was a multicenter prospective study in 3 emergency departments. Children younger than 6 years old with an acute onset of fever and respiratory symptoms were recruited. Split sample method was adopted for derivation and validation of the Pediatric Acute Febrile Respiratory Illness rule (PAFRI Rule). PAFRI was derived from logistic regression with weighting based on adjusted odds ratios. RESULTS: Out of 967 children evaluated, 530 had taken chest radiograph examination, with 91 demonstrated evidence of pneumonia on radiograph. PAFRI Rule was derived from logistic regression with 5 weighed predictors: duration of fever <3 days (0 points), 3-4 days (2 points), 5-6 days (4 points), ≥7 days (5 points), chills (2 points), nasal symptoms (-2 points), abnormal chest examination (3 points), SpO2 ≤96% or tachypnea (3 points). The Area under ROC curve of the PAFRI Rule, the Bilkis Decision Rule and Bilkis Simpler Rule were 0.733, 0.600 and 0.579 respectively. A PAFRI score of ≥0 gives a sensitivity of 91.7% and negative predictive value of 97.7%. CONCLUSION: PAFRI rule can be used as a reference tool for guiding the need for taking Chest radiograph examination for pediatric patients. While promising, the PAFRI rule requires further validation. WHAT'S KNOWN ON THIS SUBJECT: It is often a challenge for physicians to identify pneumonia in children acutely febrile with respiratory symptoms, particularly in those who are stable without respiratory distress. The decision to order chest radiograph was based on clinical assessment with heterogenous practice. A valid and verified clinical prediction rule for ordering chest radiograph examination for stable febrile children without signs of respiratory distress would therefore assist in management of this group of patients. WHAT THIS STUDY ADDS: The PAFRI rule, based on parameters from clinical bedside assessment, can be used as a reference tool for guiding the need for referral to emergency department or taking use of chest radiograph for pediatric patients, and triaging for higher priority of clinical care.

Inhibition of CFTR-mediated intestinal chloride secretion as potential therapy for bile acid diarrhea.

Bile acid diarrhea (BAD) is common with ileal resection, Crohn's disease, and diarrhea-predominant irritable bowel syndrome. Here, we demonstrate the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor (R)-benzopyrimido-pyrrolo-oxazine-dione-27 (BPO-27) in reducing bile acid-induced fluid and electrolyte secretion in colon. Short-circuit current measurements in human T84 colonic epithelial cells and planar colonic enteroid cultures showed a robust secretory response following mucosal but not serosal addition of chenodeoxycholic acid (CDCA) or its taurine conjugate, which was fully blocked by CFTR inhibitors, including (R)-BPO-27. (R)-BPO-27 also fully blocked CDCA-induced secretory current in murine colon. CFTR activation by CDCA primarily involved Ca2+ signaling. In closed colonic loops in vivo, luminal CDCA produced a robust secretory response, which was reduced by ∼70% by (R)-BPO-27 or in CFTR-deficient mice. In a rat model of BAD produced by intracolonic infusion of CDCA, (R)-BPO-27 reduced the elevation in stool water content by >55%. These results implicate CFTR activation in the colon as a major prosecretory mechanism of CDCA, a bile acid implicated in BAD, and support the potential therapeutic efficacy of CFTR inhibition in bile acid-associated diarrheas.-Duan, T., Cil, O., Tse, C. M., Sarker, R., Lin, R., Donowitz, M., Verkman, A. S. Inhibition of CFTR-mediated intestinal chloride secretion as potential therapy for bile acid diarrhea.

Attentional Bias Modification Training for Patients with Generalised Anxiety Disorder: a Randomised Controlled Study.

BACKGROUND: Hypervigilance to threat is a mechanism contributing to generalised anxiety disorder (GAD). Although attentional bias modification training (ABMT) is designed to reduce attention to threat, its use as a mechanistically focused psychological intervention for GAD has not been examined. We aimed to investigate the effect of a brief ABMT on reducing anxiety, worry, and attentional bias in outpatients with GAD, and to determine the association between change in attentional bias and changes in anxiety and worry. METHODS: This was a parallel-group, double-blind, randomised controlled trial. Patients with GAD who had no changes after medication treatment for the past 8 weeks were randomly allocated to either the treatment or control group to receive 4 weekly sessions of ABMT or sham ABMT, respectively, in addition to standard care. Anxiety was measured using the Hamilton Anxiety Rating Scale and the State-Trait Anxiety Inventory - trait anxiety subscale. Pathological worry was measured using the Penn State Worry Questionnaire. Attentional bias was measured using the bias score. RESULTS: A total of 33 participants were allocated to the treatment (n = 17) or control (n = 16) groups. Both groups reported a significant reduction in levels of anxiety and worry after intervention, but the reduction was not greater after ABMT than sham ABMT. There was no significant change in attentional bias after ABMT; change in attentional bias was not correlated to changes in anxiety and worry. CONCLUSION: The efficacy of the brief ABMT as a mechanistically focused treatment for GAD was not supported. The small sample size and short duration of treatment may have rendered the results inconclusive.

Calibration of wrist-worn ActiWatch 2 and ActiGraph wGT3X for assessment of physical activity in young adults.

BACKGROUND: The validity of Actiwatch 2 in assessing sleep was evident, but its validity in assessing physical activity (PA) level was unknown. RESEARCH QUESTION: The objective of this study was to validate the wrist-worn Actiwatch 2 and ActiGraph wGT3X as a measurement of PA level against energy expenditure measured by indirect calorimetry. METHODS: Twenty-seven university students aged 18-26 were recruited from July 2016 to May 2017. They were instructed to run at different speeds (4, 6, 8, 10, and 12 km/h) on a treadmill, each speed for 10 min. Oxygen consumption and carbon dioxide production of the subjects was measured by indirect calorimetry using the Cosmed K4b2 gas analyzer. Each subjects wore a single pair of accelerometers (Actiwatch 2 and ActiGraph wGT3X) on both wrists. RESULTS: All the accelerometers were strongly correlated (ρ=0.83-0.94, all p-values <0.001), and all four accelerometers were strongly correlated with the METs obtained from the Cosmed K4b2 (ρ=0.72-0.74, all p-values <0.001). Regression analysis showed that the non-dominant wrist-worn Actiwatch 2 cutoff cpm for moderate and vigorous PA were 399 and 1,404, respectively; for the ActiGraph wGT3X-BT the corresponding cutoffs were 4,514 and 15,044, respectively. The goodness-of-fit of the MET prediction equations were all >75%. When classifying the activities as either sedentary, light activity, moderate-intensity activity, or vigorous-intensity activity using the MET prediction equations, the agreements between the four accelerometers and that by the Cosmed K4b2 were high, all AUCs were above 80% except those of the Actiwatch worn on the left (non-dominant) wrist. The Bland-Altman plots show that, for all four accelerometers, the biases were close to zero and error variances were largest when the mean measurements were around 6 METs. SIGNIFICANCE: We showed that wrist-worn Actiwatch 2 and ActiGraph wGT3X-BT were strongly correlated in PA assessment.

Enterohemorrhagic E. coli (EHEC)-Secreted Serine Protease EspP Stimulates Electrogenic Ion Transport in Human Colonoid Monolayers.

One of the characteristic manifestations of Shiga-toxin-producing Escherichia coli (E. coli) infection in humans, including EHEC and Enteroaggregative E. coli O104:H4, is watery diarrhea. However, neither Shiga toxin nor numerous components of the type-3 secretion system have been found to independently elicit fluid secretion. We used the adult stem-cell-derived human colonoid monolayers (HCM) to test whether EHEC-secreted extracellular serine protease P (EspP), a member of the serine protease family broadly expressed by diarrheagenic E. coli can act as an enterotoxin. We applied the Ussing chamber/voltage clamp technique to determine whether EspP stimulates electrogenic ion transport indicated by a change in short-circuit current (Isc). EspP stimulates Isc in HCM. The EspP-stimulated Isc does not require protease activity, is not cystic fibrosis transmembrane conductance regulator (CFTR)-mediated, but is partially Ca2+-dependent. EspP neutralization with a specific antibody reduces its potency in stimulating Isc. Serine Protease A, secreted by Enteroaggregative E. coli, also stimulates Isc in HCM, but this current is CFTR-dependent. In conclusion, EspP stimulates colonic CFTR-independent active ion transport and may be involved in the pathophysiology of EHEC diarrhea. Serine protease toxins from E. coli pathogens appear to serve as enterotoxins, potentially significantly contributing to watery diarrhea.

Producer experience with transitioning to automatic milking: Cow training, challenges, and effect on quality of life.

Despite the growing popularity of automatic milking systems (AMS), or milking robots, in Canada, little documentation is available on how Canadian dairy producers experience the transition to this milking technology. The objective of this national study was to document the experiences of Canadian dairy producers during the transition to, and use of, AMS. This paper reports on producers' experiences with cow training, challenges during the transition and their solutions, and effect of the AMS on quality of life. The AMS producers (n = 217) were surveyed from 8 Canadian provinces. Overall, producers experienced a positive transition to AMS. Producers perceived that AMS improved profitability, quality of their lives and their cows' lives, and had met expectations, despite experiencing some challenges during transition such as learning to use the technology and data, cow training, demanding first few days, and changing health management. Less than half of the AMS producers (42%) trained cows or heifers to use the AMS before the first milking with the robot. Producers who implemented training before first milking reported that it took an average of 1 wk to train a cow or heifer to use the AMS. Producers reported it took a median of 30 d for an entire herd to adapt to the AMS, whether or not cow training took place. On average, 2% of a herd was culled for not adapting, or not voluntarily milking, when otherwise physically and behaviorally normal. With AMS, producers suggested they gained more time flexibility, found work to be less stressful and physically demanding, found employee management easier, and had improved herd health and management. The vast majority (86%) of producers would recommend others to transition to AMS.

Effects of vedolizumab, adalimumab and infliximab on biliary inflammation in individuals with primary sclerosing cholangitis and inflammatory bowel disease.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic biliary disease associated with inflammatory bowel disease (IBD) with no known cure. AIM: To evaluate the effect of biological therapies on PSC progression in IBD patients. METHODS: We performed a retrospective cohort study of 88 cases (75 unique patients with 12 patients treated >1 biologics) of IBD (48 ulcerative colitis, 24 Crohn's disease and 3 indeterminate colitis) with concomitant PSC who received biological therapy (42 infliximab, 19 adalimumab, 27 vedolizumab) between June 2002 and October 2017. Hepatic biochemistries were compared using the paired t-test (patients served as their own controls) ≤3 months before and 6-8 and 12-14 months after biological initiation. Radiographic information of biliary stenosis and liver fibrosis were obtained via abdominal ultrasound, abdominal magnetic resonance imaging and magnetic resonance elastography. RESULTS: Use of adalimumab was associated with a significant decrease in alkaline phosphatase (ALP) after 6-8 months (P = 0.03; mean change -70 U/L, standard deviation [SD] 88 U/L) compared to vedolizumab (mean change +50 U/L, SD 142 U/L) or infliximab (mean change +37 U/L, SD 183 U/L) but the change was not significant after 12-14 months (P = 0.24). No significant decreases were observed with AST, ALT, total or direct bilirubin, elastography score or radiographic imaging of biliary tree dilation/strictures with any biological therapy after 6-8 or 12-14 months. CONCLUSIONS: Current evidence suggests that biological therapies used for the treatment of IBD are not effective treatments for PSC. Further study is needed to elucidate any potential beneficial effect of adalimumab on PSC.

Clinical and biomechanical changes following a 4-month toe-out gait modification program for people with medial knee osteoarthritis: a randomized controlled trial.

OBJECTIVE: To compare changes in knee pain, function, and loading following a 4-month progressive walking program with or without toe-out gait modification in people with medial tibiofemoral knee osteoarthritis. DESIGN: Individuals with medial knee osteoarthritis were randomized to a 4-month program to increase walking activity with (toe-out) or without (progressive walking) concomitant toe-out gait modification. The walking program was similar between the two groups, except that the gait modification group was trained to walk with 15° more toe-out. Primary outcomes included: knee joint pain (WOMAC), foot progression angles and knee joint loading during gait (knee adduction moment (KAM)). Secondary outcomes included WOMAC function, timed stair climb, and knee flexion moments during gait. RESULTS: Seventy-nine participants (40 in toe-out group, 39 in progressive walking group) were recruited. Intention-to-treat analysis showed no between-group differences in knee pain, function, or timed stair climb. However, the toe-out group exhibited significantly greater changes in foot progression angle (mean difference = -9.04° (indicating more toe-out), 95% CI: -11.22°, -6.86°; P < 0.001), late stance KAM (mean difference = -0.26 %BW*ht, 95% CI: -0.39 %BW*ht, -0.12 %BW*ht, P < 0.001) and KAM impulse (-0.06 %BW*ht*s, 95% CI: -0.11 %BW*ht*s, -0.01 %BW*ht*s; P = 0.031) compared to the progressive walking group at follow-up. The only between-group difference that remained at a 1-month retention assessment was foot progression angle, with greater changes in the toe-out group (mean difference = -6.78°, 95% CI: -8.82°, -4.75°; P < 0.001). CONCLUSIONS: Though both groups experienced improvements in self-reported pain and function, only the toe-out group experienced biomechanical improvements. TRIALS REGISTRY NUMBER: NCT02019108.

Impact of automatic milking systems on dairy cattle producers' reports of milking labour management, milk production and milk quality.

Automatic milking systems (AMS), or milking robots, are becoming widely accepted as a milking technology that reduces labour and increases milk yield. However, reported amount of labour saved, changes in milk yield, and milk quality when transitioning to AMS vary widely. The purpose of this study was to document the impact of adopting AMS on farms with regards to reported changes in milking labour management, milk production, milk quality, and participation in dairy herd improvement (DHI) programmes. A survey was conducted across Canada over the phone, online, and in-person. In total, 530 AMS farms were contacted between May 2014 and the end of June 2015. A total of 217 AMS producers participated in the General Survey (Part 1), resulting in a 41% response rate, and 69 of the respondents completed the more detailed follow-up questions (Part 2). On average, after adopting AMS, the number of employees (full- and part-time non-family labour combined) decreased from 2.5 to 2.0, whereas time devoted to milking-related activities decreased by 62% (from 5.2 to 2.0 h/day). Median milking frequency was 3.0 milkings/day and robots were occupied on average 77% of the day. Producers went to fetch cows a median of 2 times/day, with a median of 3 fetch cows or 4% of the herd per robot/day. Farms had a median of 2.5 failed or incomplete milkings/robot per day. Producers reported an increase in milk yield, but little effect on milk quality. Mean milk yield on AMS farms was 32.6 kg/cow day. Median bulk tank somatic cell count was 180 000 cells/ml. Median milk fat on AMS farms was 4.0% and median milk protein was 3.3%. At the time of the survey, 67% of producers were current participants of a DHI programme. Half of the producers who were not DHI participants had stopped participation after adopting AMS. Overall, this study characterized impacts of adopting AMS and may be a useful guide for making this transition.

Choosing an Appropriate Physical Exercise to Reduce Stereotypic Behavior in Children with Autism Spectrum Disorders: A Non-randomized Crossover Study.

Considerable evidence has shown that physical exercise could be an effective treatment in reducing stereotypical autism spectrum disorder (ASD) behaviors in children. The present study seeks to examine the underlying mechanism by considering the theoretical operant nature of stereotypy. Children with ASD (n = 30) who exhibited hand-flapping and body-rocking stereotypies were asked to participate in both control (story-time) and experimental (ball-tapping-exercise intervention) conditions. The experimental condition comprised 15 min of ball tapping during which the children were asked to tap a plastic ball as many times as they could. Results indicated that hand-flapping stereotypy was significantly reduced but body-rocking stereotypy following the ball-tapping-exercise intervention was not. These results not only confirm the positive impact of exercise intervention on stereotypic behavior as shown in many previous studies, but further suggest that physical exercise should be matched with the biomechanics of stereotypy to produce a desirable behavioral benefit.

Postoperative outcomes in vedolizumab-treated Crohn's disease patients undergoing major abdominal operations.

BACKGROUND: Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. AIM: We sought to compare 30-day postoperative infectious complication rate among vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. METHODS: A retrospective review of all Crohn's disease patients who received vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. RESULTS: One hundred Crohn's disease patients received vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002). CONCLUSIONS: Twenty-six per cent of Crohn's disease patients who received vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30-day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30-day postoperative surgical site infection on multivariable analysis. While vedolizumab-treated Crohn's disease patients may be a sicker cohort of patients, it is important to consider these findings with regard to preoperative counselling, operative timing and primary closure of wounds.