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Background: The modified pouchitis disease activity index (mPDAI) based on clinical symptoms and endoscopic findings is used to diagnose pouchitis, but validated instruments to monitor pouchitis are still lacking. We recently established an endoscopic classification that described 7 endoscopic phenotypes with different outcomes. We assessed symptoms and compared mPDAIs among phenotypes in inflammatory bowel disease (IBD)., Methods: We retrospectively reviewed pouchoscopies and classified them into 7 main phenotypes: normal ( n  = 25), afferent limb (AL) involvement ( n  = 4), inlet involvement ( n  = 14), diffuse ( n  = 7), focal inflammation of the pouch body ( n  = 25), cuffitis ( n  = 18), and pouch-related fistulas ( n  = 10) with a single phenotype were included. Complete-case analysis was conducted., Results: One hundred and three IBD patients were included. The median mPDAI was 0 (IQR 0-1.0) in patients with a normal pouch. Among inflammatory phenotypes, the highest median mPDAI was 4.0 (IQR 2.25-4.75) in cuffitis, followed by 3.0 (IQR 2.5-4.0) in diffuse inflammation, 2.5 (IQR 1.25-4.0) in inlet involvement, 2.5 (IQR 2.0-3.5) in AL involvement, 2.0 (IQR 1.0-3.0) in focal inflammation, and 1.0 (IQR 0.25-2.0) in the fistula phenotype. Perianal symptoms were frequently observed in pouch-related fistulas (8/10, 80%) and cuffitis (13/15, 87%). Among patients with cuffitis, all had incomplete emptying (6/6, 100%)., Conclusions: We correlated the mPDAI with the endoscopic phenotypes and described the limited utility of symptoms in distinguishing between inflammatory phenotypes. Further studies are warranted to understand which symptoms should be monitored for each phenotype and whether mPDAI can be minimized after pouch normalization., Competing Interests: S.A., J.E.O., N.A.C., V.R., L.R.G., Y.Y., C.T., J.R., K.B.S., R.D.H., K.U., B.D.S., N.H.H., and A.S. have no relevant disclosures. R.D.C. is on the speaker’s bureau from AbbVie and Takeda. He is a consultant/advisor for AbbVie Laboratories, BM/celgene, Eli Lilly, Gilead Sciences, Janssen, Pfizer, Takeda, UCB Pharma. He has received clinical trial support/grants from Abbvie, BMS/Celgene, Boehringer Ingelheim, Crohn’s and Colitis Foundation of America, Genentech, Gilead Sciences, Hollister, Medimmune, Mesoblast Ltd., Osiris Therpeutics, Pfizer, Receptos, RedHill Biopharma, Sanofi-Aventis, Schwarz Pharma, Seres Therapeutics, Takeda Pharma, UCB Pharma. His wife is on the board of directors of Aerpio Therapeutics, Novus Therapeutics, Vital Therapeutics, Inc, and NantKwest. M.A.R. has served as a consultant for Pfizer. S.R.D. has served as a consultant for Pfizer and is on the speaker’s bureau for AbbVie. J.P. has received grant support from AbbVie and Takeda. He has served as a consultant for Veraste,. CVS Caremark and is on the advisory board for Takeda, Janssen and Pfizer. E.B.C. is the founder and chief medical officer of AVnovum Therapeutics. D.T.R. has received grant support from Takeda; and has served as a consultant for Abbvie, Altrubio, Amgen, AvaloTherapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Chronicles Health, ClostraBio, Connect BioPharma, Cytoki Pharma, Douglas Pharmaceuticals, EcoR1, Ferring Pharma, Image Analysis Group, Index Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Odyssey Therapeutics, Pfizer, Prometheus Biosciences, Reistone Biopharma, Samsung Neurologica, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Takeda, Tissium S.A., and Trellus Health., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Introduction: Concerns have been voiced regarding the possibility of health risks to the operating room personnel from exposure to surgical smoke generated from electrocautery., Methods: Ovid Medline was queried using search terms "surgical smoke", "electrosurgery," "smoke evacuator". The NIOSH Health Hazard Evaluations Database was searched using terms, "hospital", "operating room", "Ames", "mutagen", and "salmonella"., Results: Levels of pollutants in the breathable airspace within the operating room have been repeatedly shown to be very low. Absolute counts of particulate matter in the operating room are low when compared to other environments. The possibility for virus transmission with electrocautery in the operating room is unknown., Conclusions: The risks related to the exposure to electrocautery surgical smoke have been overstated. Rigid mandates requiring smoke evacuators in all situations are not justified at this time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Patients with inflammatory bowel disease (IBD) who undergo proctocolectomy with ileal pouch-anal anastomosis may develop pouchitis. We previously proposed a novel endoscopic classification of pouchitis describing 7 phenotypes with differing outcomes. This study assessed phenotype transitions over time., Methods: We classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb (AL) involvement, (3) inlet (IL) involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch-related fistulas noted more than 6 months after ileostomy takedown. Among 2 endoscopic phenotypes, the phenotype that was first identified was defined as the primary phenotype, and the phenotype observed later was defined as the subsequent phenotype., Results: We retrospectively reviewed 1359 pouchoscopies from 426 patients (90% preoperative diagnosis of ulcerative colitis). The frequency of primary phenotype was 31% for AL involvement, 42% for IL involvement, 28% for diffuse inflammation, 72% for focal inflammation, 45% for cuffitis, 18% for pouch-related fistulas, and 28% for normal pouch. The most common subsequent phenotype was focal inflammation (64.8%), followed by IL involvement (38.6%), cuffitis (37.8%), AL involvement (25.6%), diffuse inflammation (23.8%), normal pouch (22.8%), and pouch-related fistulas (11.9%). Subsequent diffuse inflammation, pouch-related fistulas, and AL or IL stenoses significantly increased the pouch excision risk. Patients who achieved subsequent normal pouch were less likely to have pouch excision than those who did not (8.1% vs 15.7%; P = .15)., Conclusions: Pouch phenotype and the risk of pouch loss can change over time. In patients with pouch inflammation, subsequent pouch normalization is feasible and associated with favorable outcome., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

N-(2-thioethyl)-2-aminobenzamide (TEAB), a novel glycan auxiliary, was synthesized and its utility was evaluated. The auxiliary was conjugated to glycans by reductive amination with the water-stable reagent 2-picoline borane complex. Glycan products, which ranged from 1 to 7 linked hexoses, were all isolated in yields ranging from 60% to 90% after purification by reverse-phase chromatography. The novel conjugate introduces a convenient, shelf-stable thiol directly onto the desired free glycans with purification advantages and direct modification with efficient reactions through alkenes, halides, epoxides, disulfides, and carboxylates in yields of 49% to 93%. Subsequently, a thiol-selective modification of the BSA protein was used to generate a neoglycoprotein with a bifunctional PEG-maleimide linker. To further illustrate the utility of a thiol motif, 2-thiopyridine activation of a thiol-containing support facilitated the covalent chromatographic purification of labeled glycans in yields up to 63%. Finally, initial proof of concept of implementation in a light printed microarray was explored and validated through FITC-labeled concanavalin A binding. In conclusion, the thiol-functionalized glycans produced greatly expand the diversity of bioconjugation tools that can be developed with glycans and enable a variety of biological investigations.

Background: Surgeons are often asked to provide a diverting colostomy to enable healing or simplify management of sacral pressure ulcers. However, little evidence exists regarding the safety of a diversion in this often compromised patient population. We hypothesized that malnourished patients with sacral pressure ulcers have poor outcomes with fecal diversion., Methods: ACS-NSQIP (2012-2018) was used to identify patients who underwent elective diverting colostomy for sacral pressure ulcers. Demographics, comorbidities, and perioperative details were recorded. Postoperative complications and 30-day mortality were compared between patients with moderate/severe hypoalbuminemia (< 2.5 g/dL) vs those with albumin > 2.5 g/dL., Results: We identified a total of 863 patients who underwent elective diverting colostomy for sacral pressure ulcer. Mean age was 57.5 years old. Rate of associated comorbidities was high, with most patients classified as ASA class 3 or 4. Over 40% of patients had a preoperative albumin level < 2.5 g/dL. Thirty-day overall postoperative mortality was 6.7%. This was significantly higher in patients with hypoalbuminemia (11.4% vs. 3.5%, p < 0.001). On multivariable regression analysis, preoperative albumin < 2.5 g/dL was independently associated with mortality (OR 1.92, p = 0.039). Other factors associated with mortality included increased age (OR 1.04 per year, p < 0.001), preoperative sepsis (OR 1.66, p = 0.003), and Black race (OR 2.2, p = 0.01)., Conclusions: Diverting colostomy performed for patients with sacral pressure ulcers is associated with a substantial risk of postoperative death. Surgeons should carefully consider risks of diversion in this patient population, especially in malnourished patients with hypoalbuminemia., (© 2022. The Society for Surgery of the Alimentary Tract.)

Background: Despite significant differences in surgical outcomes between pediatric and adult patients with ulcerative colitis (UC) undergoing colectomy, counseling on pediatric outcomes has largely been guided by data from adults. We compared differences in pouch survival between pediatric and adult patients who underwent total proctocolectomy with ileal pouch-anal anastomosis (IPAA)., Methods: This was a retrospective single-center study of patients with UC treated with IPAA who subsequently underwent pouchoscopy between 1980 and 2019. Data were collected via electronic medical records. We stratified the study population based on age at IPAA. Differences between groups were assessed using t tests and chi-square tests. Kaplan-Meier curves were used to compare survival probabilities. Differences between groups were assessed using a log-rank test., Results: We identified 53 patients with UC who underwent IPAA before 19 years of age and 329 patients with UC who underwent IPAA at or after 19 years of age. Subjects who underwent IPAA as children were more likely to require anti-tumor nerosis factor (TNF) postcolectomy compared with adults (41.5% vs 25.8%; P < .05). Kaplan-Meier estimates revealed that pediatric patients who underwent IPAA in the last 10 years had a 5-year pouch survival probability that was 28% lower than that of those who underwent surgery in the 1990s or 2000s (72% vs 100%; P < .001). Further, children who underwent IPAA and received anti-TNF therapies precolectomy had the most rapid progression to pouch failure when compared with anti-TNF-naive children and with adults who were either exposed or naive precolectomy (P < .05)., Conclusions: There are lower rates of pouch survival for children with UC who underwent IPAA following the uptake of anti-TNF therapy compared with both historical pediatric control subjects and contemporary adults., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The endoscopic appearance in patients with "pouchitis" after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) can be quite heterogenous. Patients with an endoscopic phenotype resembling Crohn's disease (CD) are at high risk of pouch loss., Aims: We aimed to assess how the histopathology of colectomy specimens predicts endoscopic pouch phenotypes in UC., Methods: We retrospectively assessed pouchoscopies from patients with UC who underwent IPAA and classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb involvement, (3) inlet involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch with fistulas noted ≥ 6 months from ileostomy takedown. We assessed the clinical and pathological data including deep, focal inflammation, granulomas, and terminal ileal involvement in the colectomy specimens. Logistic regression analysis was performed to identify contributing factors to each phenotype., Results: This study included 1,203 pouchoscopies from 382 patients with UC. On multivariable analysis, deep inflammation was significantly associated with pouch fistulas (Odds ratio 3.27; 95% confidence interval 1.65-6.47; P = 0.0007). Of the 75 patients with deep inflammation, only two patients (2.7%) were diagnosed with CD based on pathology review. Terminal ileal involvement significantly increased the risk of afferent limb involvement (Odds ratio 2.96; 95% confidence interval 1.04-8.47; P = 0.04). There were no significant associations between other microscopic features and phenotypes., Conclusions: We identify histologic features of colectomy specimens in UC that predict subsequent pouch phenotypes. Particularly, deep inflammation in the resected colon was significantly associated with pouch fistulas, a pouch phenotype with poor prognosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: We assessed the effectiveness of anti-TNF agents and its associated factors to prevent endoscopic and clinical postoperative recurrence (POR) in Crohn's disease (CD)., Methods: From a prospectively-maintained database, we retrieved 316 CD patients who underwent intestinal resection (2011-2017). Endoscopic (Rutgeerts index ≥ i2 at 6 months) and clinical (recurrence of symptoms leading to hospitalization or therapeutic escalation) POR were assessed., Results: In 117 anti-TNF-naïve patients, anti-TNF therapy was more effective than immunosuppressive agents (odds ratio [OR], 8.8; 95% confidence interval [CI], 1.8-43.9; P= 0.008) and no medication/5-aminosalicylates (OR, 5.2; 95% CI, 1.0-27.9; P= 0.05) to prevent endoscopic POR. In 199 patients exposed to anti-TNF prior to the surgery, combination with anti-TNF and immunosuppressive agents was more effective than anti-TNF monotherapy (OR, 2.32; 95% CI, 1.02-5.31; P= 0.046) to prevent endoscopic POR. Primary failure to anti-TNF agent prior to surgery was predictive of anti-TNF failure to prevent endoscopic POR (OR, 2.41; 95% CI, 1.10-5.32; P= 0.03). When endoscopic POR despite anti-TNF prophylactic medication (n = 55), optimizing anti-TNF and adding an immunosuppressive drug was the most effective option to prevent clinical POR (hazard ratio, 7.38; 95% CI, 1.54-35.30; P= 0.012). Anti-TNF therapy was the best option to prevent clinical POR (hazard ratio, 3.10; 95% CI, 1.09-8.83; P= 0.034) in patients with endoscopic POR who did not receive any biologic to prevent endoscopic POR (n = 55)., Conclusions: Anti-TNF was the most effective medication to prevent endoscopic and clinical POR. Combination with anti-TNF and immunosuppressive agents should be considered in patients previously exposed to anti-TNF.

Background: Heterogeneous laborious analytical methodologies for the determination of urinary lactulose and mannitol limit their utility in intestinal permeability testing., Methods: We developed an assay using a Shimadzu HPLC system, an Aminex HPX87C column, and refractive index detection. The test was calibrated using a series of dilutions from standard stock solutions of lactulose and mannitol 'spiked' into urine samples. The utility to quantify urinary excretion during the dual sugar absorption test over 6 h was also determined., Results: Lactulose and mannitol were eluted isocratically at 5.7 and 10.1 min, respectively, with water as a mobile phase at a flow rate of 0.3 mL min -1 , 858 psi, 60 °C. The calibration curves for both sugars were linear up to 500 µg mL -1 with a limit of detection in standard solutions at 4 µg mL -1 and in 'spiked' urine samples at 15 µg mL -1 . The intra-assay and inter-assay CVs were between 2.0-5.1% and 2.0-5.1% for lactulose and 2.5-4.4% and 2.8-3.9% for mannitol. The urinary profiles of the 6 h absorption of lactulose and mannitol showed similar peak-retention times to standard solutions and were well-resolved at 5.9 and 10.4 min, respectively., Conclusions: The assay was easy to automate, using commonly available equipment and convenient requiring no prior laborious sample derivatization. The simplicity, reproducibility, and robustness of this assay facilitates its use in routine clinical settings for the quantification of intestinal permeability.

Background & Aims: Pouchitis is a common complication of ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis who have undergone colectomy. Pouchitis has been considered a single entity despite a broad array of clinical and endoscopic patterns. We developed a novel classification system based on the pattern of inflammation observed in pouches and evaluated the contributing factors and prognosis of each phenotype., Methods: We identified 426 patients (384 with ulcerative colitis) treated with proctocolectomy and IPAA who subsequently underwent pouchoscopies at the University of Chicago between June 1997 and December 2019. We retrospectively reviewed 1359 pouchoscopies and classified them into 7 main pouch phenotypes: (1) normal, (2) afferent limb involvement, (3) inlet involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch with fistulas noted 6 months after ileostomy takedown. Logistic regression analysis was used to assess factors contributing to each phenotype. Pouch survival was estimated by the log-rank test and the Cox proportional hazards model., Results: Significant contributing factors for afferent limb involvement were a body mass index of 25 or higher and hand-sewn anastomosis, for inlet involvement the significant contributing factor was male sex; for diffuse inflammation the significant contributing factors were extensive colitis and preoperative use of anti-tumor necrosis factor drugs, for cuffitis the significant contributing factors were stapled anastomosis and preoperative Clostridioides difficile infection. Inlet stenosis, diffuse inflammation, and cuffitis significantly increased the risk of pouch excision. Diffuse inflammation was associated independently with pouch excision (hazard ratio, 2.69; 95% CI, 1.34-5.41; P = .005)., Conclusions: We describe 7 unique IPAA phenotypes with different contributing factors and outcomes, and propose a new classification system for pouch management and future interventional studies., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Increased global industrialization has increased air pollution resulting in 3 million annual deaths globally. Air pollutants could have different health effects, so specific models to identify the different immune effects are needed. The aim of this study was to determine the immune effects and lung function of acute exposure to two different pollution sources using a mouse model. Three intranasal challenges with either urban dust or diesel particulate matter resulted in significant (P < 0.001) immune cell infiltration into the lung, which was mostly because of an increased (P < 0.001) percentage of neutrophils. We found that exposure to either urban dust or diesel particulate matter significantly increased the lung tissue concentration of the neutrophil chemoattractant cytokine CXCL5 when compared with naïve controls. The urban dust challenge also significantly increased the concentration of the proinflammatory cytokine CCL20, but diesel particulate matter did not. The urban dust challenge significantly (P < 0.001) decreased tissue compliance and ability to stretch, and increased total airways constriction and lung tissue stiffness. In comparison, diesel particulate matter exposure slightly, but significantly (P = 0.022), increased tissue compliance and did not affect other lung function parameters. Although both urban dust and diesel particulate matter induced immune cell infiltration into the lung resulting in lung inflammation, their detrimental effects on cytokine production and lung function were quite different. This may be attributed to the variation in particulates that comprise these pollutants that directly interact with the lung tissue and consequently elicit a different functional response., (© 2020 Australian and New Zealand Society for Immunology, Inc.)

The conversion of an aldehyde into a nitrile can be efficiently performed using O-phenylhydroxylamine hydrochloride in buffered aqueous solutions. The reported method is specifically optimized for aqueous-soluble substrates including carbohydrates. Several reducing sugars including monosaccharides, disaccharides, and silyl-protected saccharides were transformed into cyanohydrins in high yields. The reaction conditions are also suitable for the formation of nitriles from various types of hydrophobic aldehyde substrates. Furthermore, cyanide can be eliminated from cyanohydrins, analogous to the Wohl degradation, by utilizing a readily-removed weakly basic resin as a promoter., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Bioactive compounds including anthocyanins and other polyphenols are associated with reduced lung inflammation and improved lung function in asthma and other lung diseases. This study investigated the effects of a Boysenberry and apple juice concentrate, high in cyanidin glycosides, ellagitannins, and chlorogenic acid, on a mouse model of allergic airways inflammation. Male C57BL/6J mice were orally gavaged with 2.5 mg/kg of total anthocyanins (TAC) from BerriQi® Boysenberry and apple juice concentrate (0.2 mg/kg human equivalent dose) or water control 1 hr before an acute intranasal ovalbumin (OVA) challenge and were gavaged again 2 days after the intranasal challenge. Consumption of BerriQi® Boysenberry and apple juice concentrate significantly decreased OVA-induced infiltrating eosinophils, neutrophils, and T cells in the lung, and mucous production. Quantification of gene expression for arginase (Arg1), chitinase 3-like 3 (Ym-1), found in inflammatory zone (Fizz1), which have been associated with an anti-inflammatory macrophage phenotype (M2), found significantly increased Arg1 expression in the lung in the Boysenberry and apple juice concentrate treatment group. There was also increased production of M2-associated cytokines C-X-C motif chemokine ligand (CXCL) 10 and C-C motif chemokine ligand (CCL) 4. These results suggest that consumption of BerriQi® Boysenberry and apple juice concentrate promoted a shift toward an anti-inflammatory environment within the lung leading to reduced immune cell infiltration and tissue damage., Competing Interests: None of the other authors declare any other Competing Interest., (© 2021 The New Zealand Institute for Plant and Food Research Ltd. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: This study aims to evaluate sarcopenia defined by skeletal muscle index (SMI) with cutoffs adjusted for sex and body mass index as a predictive marker for postoperative outcomes among individuals with inflammatory bowel disease., Methods: The SMI was measured using the cross-sectional computed tomography images at the lumbar spine. Multivariate logistic regression was performed to identify independent risk factors of postoperative complications., Results: Ninety-one patients were included in the study. In multivariate analysis, sarcopenia (odds ratio = 5.37; confidence interval: 1.04-27.6) was predictive of infectious postoperative complications., Conclusions: Sarcopenia as defined by the SMI is a predictor for 30-day postoperative infection complications in inflammatory bowel disease surgeries., (© The Author(s) 2020. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Objective: Review the long-term outcomes of the side-to-side isoperistaltic strictureplasty (SSIS) and its effects on bowel preservation in Crohn disease (CD)., Summary Background Data: The first SSIS was performed 25 years ago as an alternative to resection in the treatment of extensive fibrostenosing jejuno-ileal CD., Methods: Prospective study (January 1992-December 2016) of all patients with a SSIS performed by the authors. Long-term outcomes were evaluated radiographically, endoscopically, and histopathologically., Results: Sixty patients [14.4% of patients with jejuno-ileal bowel CD; 31 females; median age 36 (12-69) years] underwent 61 SSIS's for partial intestinal obstruction. Median length of preserved small bowel was 50 (20-148) cm. Associated strictureplasties and bowel resection were performed in 44% and 80%, respectively. Postoperative mortality occurred in 1 (PE on POD#8) and postoperative morbidity in 7 (12%). There were no sutureline dehiscences. SSIS resulted in resolution of preoperative symptoms in all. After a median follow-up of 11 years (range 1 mo-25 yrs), symptomatic recurrence was observed in 61%: 15 patients at the SSIS and 19 away from it (2 cases unclear location; 7 patients with >1 recurrence). Of 15 recurrences at SSIS's, 11 required surgical treatment (revision or strictureplasty in 6, SSIS removal in 5). Fifty-one patients (86%) maintain the original SSIS to date., Conclusions: SSIS is a safe, effective, and durable strictureplasty in patients with extensive fibrostenosing CD of the small bowel. Half the surgical recurrences on SSIS can be managed by subsequent revision or strictureplasty. The majority of patients maintain the original SSIS after a median follow-up of 11 years.

The extraordinary spread of the novel coronavirus (COVID-19) has dramatically and rapidly changed the way in which we provide medical care for patients with all diagnoses. Conservation of resources, social distancing, and the risk of poor outcomes in COVID-19-positive cancer patients have forced practitioners and surgeons to completely rethink routine care. The treatment of patients with rectal cancer requires both a multidisciplinary approach and a significant amount of resources. It is therefore imperative to rethink how rectal cancer treatment can be aligned with the current COVID-19 pandemic paradigms. In this review, we discuss evidence-based recommendations to optimize oncological outcomes during the COVID-19 pandemic.

Objectives: We examined the acute effects of anthocyanin-rich New Zealand blackcurrant extract and a placebo on hemodynamics during 120 min of sedentary sitting in healthy males. Additionally, we investigated whether changes in resting hemodynamics altered repeated isometric hand-grip exercise performance and post exercise forearm blood flow (FBF). Methods: Ten healthy males completed two trials during which they ingested either blackcurrant extract (1.87 mg total anthocyanins/kg bodyweight) or placebo powder. Heart rate, blood pressure and forearm blood flow were measured, and venous blood was sampled, prior to and 30, 60, 90 and 120 min-post ingestion. Participants remained seated for the duration of each trial. At 120 min post-ingestion participants completed as many repetitions of isometric hand-grip contractions as possible. Results: Heart rate, blood pressure and mean arterial pressure changed over time (all p < 0.001) but did not differ between treatments. A treatment x time interaction for FBF ( p = 0.025) and forearm vascular resistance (FVR) ( p = 0.002) was found. No difference in the number of isometric hand-grip contractions was observed between treatments ( p = 0.68) nor was there any treatment x time interaction in post-exercise FBF ( p = 0.997). Plasma endothelin-1 ( p = 0.023) and nitrate ( p = 0.047) changed over time but did not differ between treatments (both p > 0.1). Plasma nitrite did not change over time ( p = 0.732) or differ between treatments ( p = 0.373). Conclusion: This study demonstrated that acute ingestion of a single dose of blackcurrant extract maintained FBF and FVR during an extended period of sitting; however, this did not influence exercise performance during hand-grip exercise., (Copyright © 2020 Barnes, Perry, Hurst and Lomiwes.)

Background: Blackcurrants have come to be regarded as a superfood because of their high polyphenol content, namely anthocyanins. While many berry types have been studied, blackcurrant-anthocyanins may be the superior berry when it comes to athletic performance. The purpose of the review was to evaluate the effects of blackcurrant supplementation on athletic performance, oxidative markers, cognition, and side effects., Methods: Systematic review and meta-analysis. Review manager software (version 5.3) was used for the meta-analysis. The risks of bias was independently assessed using the guidelines and criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. The data sources for the search included MEDLINE (Ovid), Google Scholar databases, additional references lists, conference proceedings and grey literature until August 2019. Eligibility Criteria included all blackcurrant (New Zealand derived) interventions, randomised control trials, human participants, placebo-controlled only., Results: A total of 16 separate studies met the criteria for inclusion in the systematic review, with 9 studies contributing to this sport performance meta-analysis. There was an improvement in sport performance when supplementing with blackcurrant, 0.45 (95% CI 0.09-0.81, p = 0.01). The effective dose appears to be between 105 and 210 mg of total blackcurrant anthocyanins, prior to exercise. There were insufficient studies reporting oxidative markers, cognitive effects or biomarkers, and/or side effects to comment on the mechanism of action., Conclusion: Blackcurrant has a small, but significant, effect on sport performance, with no known detrimental side effects.

Background: Regular exercise is essential to a healthy lifestyle but evokes an oxidative and inflammatory stress. Depending upon its intensity and duration this can result in either beneficial adaptive changes or underlying tissue damage that impacts upon long-term health and individual sporting training schedules. Functional foods containing plant bioactives have potential to support exercise through management of the detrimental aspects of exercise and complement ergonomic adaptive benefits. Aim: Previously we reported that a single consumption of a 3.2 mg/kg New Zealand blackcurrant anthocyanin-rich extract (BAE) 1 h before a 30 min rowing exercise attenuated moderate exercise-mediated oxidative stress and supported innate immunity. Here we evaluate whether the efficacy of a single consumption of BAE 1 h prior to exercise is changed after extended daily BAE consumption for 5 weeks. Results: On week 1, a single consumption of BAE 1 h before a 30 min row mediated a significant ( p < 0.05) 46% reduction in post-exercise-induced malondialdehyde (MDA) by 2 h compared to a 30% reduction in the placebo group. Similar efficacy was observed 5 weeks later after daily consumption of BAE. In addition, daily BAE consumption for 5 weeks improved the efficacy to (a) resolve acute inflammation, and (b) increased plasma IL-10, salivary beta-defensin 2 (BD2) and secretory IgA. Although no change in plasma antioxidant capacity was detected, a significant ( p < 0.009) positive correlation between plasma IL-10 and plasma antioxidant capacity ( R 2 = 0.35) was observed on week 6 after 5 week BAE consumption suggesting IL-10 influences antioxidant properties. Using a differentiated myotubule cell-line revealed that whilst IL-10 had no direct antioxidant neutralizing action, longer-term exposure (24 h) attenuated 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH)-induced myotubule oxidative stress, supporting a putative role for IL-10 in the modulation of cellular antioxidant systems. Conclusions: Daily consumption of BAE for 5 weeks serves to enhance the exercise recovery effectiveness of a single consumption of BAE and promotes beneficial/protective antioxidant/anti-inflammatory cellular events that facilitate exercise recovery., (Copyright © 2020 Hurst, Lyall, Wells, Sawyer, Lomiwes, Ngametua and Hurst.)

Background: Pouchitis is the most frequent complication after IPAA in patients with ulcerative colitis. Antibiotics represent the mainstay of treatment, suggesting a crucial role of dysbiosis in the pathogenesis of this condition. Anti-tumor necrosis factor agents have been shown to adversely impact the gut microbiome and local host immunity., Objective: The aim of this study is to assess the effect of prior exposure to biologics on the development of pouchitis in patients who have ulcerative colitis., Design: This is a retrospective case-control study., Settings: This study was conducted at a tertiary-care IBD center., Patients: Consecutive patients with ulcerative colitis who underwent restorative proctocolectomy between 2000 and 2010 were included., Main Outcome Measures: The primary outcome measured was the incidence of pouchitis., Results: Four hundred seventeen patients with ulcerative colitis who underwent IPAA were included. The incidence of pouchitis was 40.4%. There were no differences in patient demographics, disease-specific factors, surgical approach, and short-term postoperative complications between patients who developed pouchitis compared to those that did not. Patients exposed to anti-tumor necrosis factor agents or preoperative steroids were significantly more likely to develop pouchitis (anti-tumor necrosis factor: 47.9% vs 36.5%, p = 0.027; steroids: 41.7% vs 23.3%, p = 0.048). However, on multivariable analysis, only anti-tumor necrosis factor therapy was an independent predictor for pouchitis (p = 0.05). Pouchitis was not associated with adverse long-term outcomes., Limitations: The retrospective design was a limitation of this study., Conclusion: In a large cohort of patients undergoing IPAA for ulcerative colitis with at least a 5-year follow-up, anti-tumor necrosis factor exposure was the only independent risk factor for the development of pouchitis. These agents may "precondition" the pouch to develop pouchitis through alterations in the microbiome and/or local host immunity of the terminal ileum. See Video Abstract at http://links.lww.com/DCR/B19. LA EXPOSICIÓN A MEDICAMENTOS ANTI-TNF AUMENTA LA INCIDENCIA DE POUCHITIS DESPUÉS DE LA PROCTOCOLECTOMÍA RESTAURADORA EN PACIENTES CON COLITIS ULCEROSA:: La pouchitis es la complicación más frecuente después de la anastomosis anal de bolsa ileal en pacientes con colitis ulcerosa. Los antibióticos representan el pilar del tratamiento, lo que sugiere un papel crucial de la disbiosis en la patogénesis de esta afección. Se ha demostrado que los agentes anti-TNF tienen un impacto adverso en la microbiota intestinal y en la inmunidad local del huésped.El objetivo de este estudio es evaluar el efecto de la exposición previa a terapía biológica sobre el desarrollo de la pouchitis en pacientes con colitis ulcerosa.Estudio retrospectivo de casos y controles.Centro de tercer nivel de atención en enfermedades inflamatorias intestinales.Pacientes consecutivos con colitis ulcerosa que se sometieron a proctocolectomía restaurativa entre 2000-2010.Incidencia de pouchitis.Cuatrocientos diecisiete pacientes con colitis ulcerativa se sometieron a anastomosis anal de bolsa ileal. La incidencia de pouchitis fue del 40.4%. No hubo diferencias en la demografía del paciente, los factores específicos de la enfermedad, el abordaje quirúrgico y las complicaciones postoperatorias a corto plazo entre los pacientes que desarrollaron pouchitis en comparación con los que no lo hicieron. Los pacientes expuestos a agentes anti-TNF o esteroides preoperatorios fueron significativamente más propensos a desarrollar pouchitis (anti-TNF: 47.9% vs 36.5%, p = 0.027; esteroides: 41.7% vs 23.3%, p = 0.048). Sin embargo, en el análisis multivariable, solo la terapia anti-TNF fue un predictor independiente para la pouchitis (p = 0.05). La pouchitis no se asoció con resultados adversos a largo plazo.Diseño retrospectivo.En una gran cohorte de pacientes sometidos a anastomosis anal de bolsa ileal para la colitis ulcerosa con al menos 5 años de seguimiento, la exposición a terapía anti-TNF fue el único factor de riesgo independiente para el desarrollo de pouchitis. Estos agentes pueden "precondicionar" la bolsa para desarrollar una pouchitis a través de alteraciones en el microbioma y / o inmunidad local del huésped del íleon terminal. Vea el Resumen del video en http://links.lww.com/DCR/B19.

Background and Aims: Recurrence of Crohn's disease after surgical resection and primary anastomosis is an important clinical challenge. Previous studies have demonstrated the benefit of imidazole antibiotics, but have been limited by adverse events and medication intolerance. We evaluated whether administration of low-dose metronidazole [250 mg three times per day] for 3 months reduces endoscopic postoperative recurrence rates., Methods: We performed a retrospective cohort study of patients with Crohn's disease who underwent ileal resection with a primary anastomosis and subsequently received care at our center. We compared the cases who received low-dose metronidazole for 3 months with control patients who did not receive this therapy. Data collected included demographics, risk factors for recurrence, and medications before and after surgery. The primary end point was the number of patients with ≥i2 [Rutgeerts] endoscopic recurrence by 12 months. Variables found to be predictive in univariate analysis at p < 0.10 were introduced in the Cox model for multivariate analysis., Results: In all, 70 patients with Crohn's disease [35 cases and 35 controls] met inclusion criteria. Risk factors for Crohn's recurrence were similar between groups. The number of patients with ≥i2 endoscopic recurrence within 12 months following ileal resection was significantly lower in the metronidazole group [7 of 35 patients; 20%] compared with the number in the control group [19 of 35 patients; 54.3%] [p = 0.0058]. Eight participants [22.9%] in the metronidazole group experienced adverse events, and 3 of these patients [8.6%] discontinued the therapy., Conclusion: Low-dose metronidazole reduces endoscopic recurrence of Crohn's disease postoperatively and is well tolerated. This intervention should be considered as a therapy option following ileocolonic resection., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Affective responses experienced during exercise are a significant determinant on exercise adherence. We have previously demonstrated that consumption of New Zealand (NZ) blackcurrants preserves cognition by attenuating the feeling of fatigue. This positive affective response correlated with the ability of blackcurrant polyphenols to support monoamine neurotransmission via inhibition of monoamine oxidase-B (MAO-B) activity. Here we explore how the consumption of a NZ blackcurrant juice (BJ) influenced affective responses and potential ergogenic action on the motivation to adhere to a low impact walking exercise., Methods: In a parallel randomized controlled study (Trial registration #: ACTRN12617000319370p, registered 28th February 2017, http://www.anzctr.org.au/ ), 40 healthy sedentary male and female participants drank a BJ or matched placebo (PLA) (n = 20 per group), 1 h prior to a self-motivated treadmill walk, where heart rate and affective responses (exertion [ES] or feeling / mood [FS]) scores) were recorded at 3 or 5 min intervals. Blood glucose, lactate, malondialdehyde (MDA) and platelet MAO-B activity were measured pre- and post-exercise and comparisons were conducted using with Student's t-tests. Subjective data were analysed using 2-way ANOVA with appropriate post hoc tests., Results: Consuming a BJ 1 h prior to exercise caused a 90% decline in platelet MAO-B activity. The exercise had no significant (p > 0.05) effect on blood lactate, glucose or plasma MDA levels. Assessment of affective responses over the first 60 mins (adjusting for participant drop-out) revealed a time-dependent ES increase in both groups, with ES reported by participants in the BJ group consistently lower than those in the PLA group (p < 0.05). FS declined in PLA and BJ groups over 60 mins, but an inverse relationship with ES was only observed within the PLA group (r 2  = 0.99, p = 0.001). Whilst the average time walked by participants in the BJ group was 11 mins longer than the PLA group (p = 0.3), and 30% of the BJ group achieving > 10 km compared to only 10% for the PLA group (p = 0.28), statistical significance was not achieved., Conclusion: Our findings demonstrate that drinking a polyphenolic-rich NZ blackcurrant juice 1 h prior to exercise supports positive affective responses during a self-motivated exercise.

Aim: To evaluate blackcurrant anthocyanin-rich extract (BAE) consumption on time- and dose-dependent plasma anthocyanin bioavailability and conduct a pilot study to explore the potential effect of BAE in promoting recovery from exercise-induced oxidative stress, and maintenance of circulating neutrophil function. Methods: Time- and dose-dependent blackcurrant anthocyanin bioavailability was assessed using LC-MS in 12 participants over 6 h after the ingestion of a placebo or BAE containing 0.8, 1.6, or 3.2 mg/kg total anthocyanins. In a separate pilot intervention exercise trial, 32 participants consumed either a placebo or 0.8, 1.6, or 3.2 mg/kg BAE (8 individuals per group), and then 1 h later performed a 30 min row at 70% VO 2 max. Blood was collected during the trial for oxidative, antioxidant, inflammatory, and circulating neutrophil status. Results: Consumption of BAE caused a time- and dose-dependent increase in plasma anthocyanins, peaking at 2 h after ingestion of 3.2 mg/kg BAE (217 ± 69 nM). BAE consumed 1 h prior to a 30 min row had no effect on plasma antioxidant status but hastened the recovery from exercise-induced oxidative stress: By 2 h recovery, consumption of 1.6 mg/kg BAE prior to exercise caused a significant ( P < 0.05) 34 and 32% decrease in post-exercise plasma oxidative capacity and protein carbonyl levels, respectively, compared to placebo. BAE consumption prior to exercise dose-dependently attenuated a small, yet significant ( P < 0.01) transient 13 ± 2% decline in circulating neutrophils observed in the placebo group immediately post-exercise. Furthermore, the timed consumption of either 1.6 or 3.2 mg/kg BAE attenuated a 17 ± 2.4% ( P < 0.05) decline in neutrophil phagocytic capability of opsonised FITC- Escherichia coli observed 6 h post-exercise in the placebo group. Similarly, a dose-dependent increase in neutrophil surface expression of complement receptor-3 complex (CR3, critical for effective phagocytosis of opsonised microbes), was observed 6 h post-exercise in both 1.6 and 3.2 mg/kg BAE intervention groups. Conclusions: Consumption of BAE (>1.6 mg/kg) 1 h prior to exercise facilitated recovery from exercise-induced oxidative stress and preserved circulating neutrophil function. This study provides data to underpin a larger study designed to evaluate the efficacy of timed BAE consumption on post-exercise recovery and innate immunity.

Background: Anastomotic complications after restorative total proctocolectomy with IPAA for ulcerative colitis alter functional outcomes and quality of life and may lead to pouch failure. Routine contrast enema of the pouch assesses anastomotic integrity before ileostomy reversal, but its clinical use is challenged., Objective: The purpose of this research was to assess the relationship among preoperative clinical characteristics, abnormal pouchography, and long-term pouch complications., Design: This was a retrospective chart review., Settings: The study was conducted at a tertiary care center between 2000 and 2010., Patients: Ulcerative colitis patients with IPAA undergoing pouchography before ileostomy closure were included., Main Outcome Measures: Patient demographics, incidence of pouch-related complications, and findings on pouchogram were recorded. Primary outcome was pouch failure, defined as excision or permanent diversion of the ileoanal pouch. Independent predictors of pouch failure were determined by multivariate regression., Results: A total of 262 patients with ulcerative colitis were included. Contrast extravasation was seen in 27 patients (10.3%): 14 (51.9%) were clinically asymptomatic at the time of pouchogram. Six (22.2%) of 27 patients with extravasation developed pouch failure despite normalization of the pouchogram before ileostomy closure. Forty patients (15.3%) were found to have pouch-anal anastomotic stenosis; only 1 developed pouch failure. Pre-IPAA serum albumin and hemoglobin levels were inversely associated with contrast extravasation (serum albumin: OR = 0.42; hemoglobin: OR = 0.77; p < 0.05). Contrast extravasation was associated with delayed takedown operation (average = 67 d), increased risk (OR = 5.25; p < 0.01), and shorter time (median = 32.0 vs 72.5 mo; HR = 5.88; p < 0.05) to pouch failure, as well as increased risk of pouch-related complications (p < 0.05)., Limitations: The study was limited by its retrospective nature and small number of patients who developed pouch failure., Conclusions: Pouchography before ileostomy takedown is useful in identifying patients with ulcerative colitis at risk for postoperative complications. Radiologic resolution of IPAA-related leak does not reliably predict healing; caution is warranted in this subgroup. See Video Abstract at http://links.lww.com/DCR/A818.

CCL11, a chemokine, is linked to the early development of airways eosinophilia in allergic asthma. Therefore, CCL11 production is a target for abrogating eosinophilic-driven airway inflammation. Blackcurrants are high in compounds that regulate inflammation, particularly anthocyanins. In this study, we investigated the effect of oral blackcurrant supplementation on allergen-induced eosinophilia and CCL11 production; we also profiled key compounds in blackcurrants that were linked to this effect. Ten milligram per kilogram (total anthocyanins) of a commercially available, anthocyanin-rich New Zealand "Ben Ard" blackcurrant extract ("Currantex 30") attenuated ovalbumin-induced inflammation, eosinophilia (by 52.45 ± 38.50%), and CCL11 production (by 48.55 ± 28.56%) in a mouse model of acute allergic lung inflammation. Ten blackcurrant polyphenolic extracts were also found to suppress CCL11 secretion by stimulated human lung epithelial cells in vitro. Correlation analysis identified potential blackcurrant polyphenolic anthocyanin constituents specifically delphinidins and cyanidins, involved in CCL11 suppression. Our findings show oral supplementation with New Zealand blackcurrant is effective in reducing lung inflammation, and highlight the potential benefit of developing cultivars with specific polyphenolic profiles for the creation of functional foods with desirable biological activity., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Allergic asthma is an inflammatory lung disease that is partly sustained by the chemokine eotaxin-3 (CCL26), which extends eosinophil migration into tissues long after allergen exposure. Modulation of CCL26 could represent a means to mitigate airway inflammation. Here we evaluated procyanidin A2 as a means of modulating CCL26 production and investigated interactions with the known inflammation modulator, Interferon γ (IFNγ). We used the human lung epithelial cell line A549 and optimized the conditions for inducing CCL26. Cells were exposed to a range of procyanidin A2 or IFNγ concentrations for varied lengths of time prior to an inflammatory insult of interleukin-4 (IL-4) for 24 h. An enzyme-linked immunosorbent assay was used to measure CCL26 production. Exposing cells to 5 μM procyanidin A2 (prior to IL-4) reduced CCL26 production by 35% compared with control. Greatest inhibition by procyanidin A2 was seen with a 2 h exposure prior to IL-4, whereas IFNγ inhibition was greatest at 24 h. Concomitant incubation of procyanidin A2 and IFNγ did not extend the inhibitory efficacy of procyanidin A2. These data provide evidence that procyanidin A2 can modulate IL-4-induced CCL26 production by A549 lung epithelial cells and that it does so in a manner that is different from IFNγ., Competing Interests: The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

The cytokine response to heavy exertion varies widely for unknown reasons, and this study evaluated the relative importance of glycogen depletion, muscle damage, and stress hormone changes on blood and muscle cytokine measures. Cyclists ( N = 20) participated in a 75-km cycling time trial (168 ± 26.0 min), with blood and vastus lateralis muscle samples collected before and after. Muscle glycogen decreased 77.2 ± 17.4%, muscle IL-6, IL-8, and MCP-1 mRNA increased 18.5 ± 2.8-, 45.3 ± 7.8-, and 8.25 ± 1.75-fold, and muscle IL-6, IL-8, and MCP-1 protein increased 70.5 ± 14.1%, 347 ± 68.1%, and 148 ± 21.3%, respectively (all, P < 0.001). Serum myoglobin and cortisol increased 32.1 ± 3.3 to 242 ± 48.3 mg/mL, and 295 ± 27.6 to 784 ± 63.5 nmol/L, respectively (both P < 0.001). Plasma IL-6, IL-8, and MCP-1 increased 0.42 ± 0.07 to 18.5 ± 3.8, 4.07 ± 0.37 to 17.0 ± 1.8, and 96.5 ± 3.7 to 240 ± 21.6 pg/mL, respectively (all P < 0.001). Increases in muscle IL-6, IL-8, and MCP-1 mRNA were unrelated to any of the outcome measures. Muscle glycogen depletion was related to change in plasma IL-6 ( r = 0.462, P = 0.040), with change in myoglobin related to plasma IL-8 ( r = 0.582, P = 0.007) and plasma MCP-1 ( r = 0.457, P = 0.043), and muscle MCP-1 protein ( r = 0.588, P = 0.017); cortisol was related to plasma IL-8 ( r = 0.613, P = 0.004), muscle IL-8 protein ( r = 0.681, P = 0.004), and plasma MCP-1 ( r = 0.442, P = 0.050). In summary, this study showed that muscle IL-6, IL-8, and MCP-1 mRNA expression after 75-km cycling was unrelated to glycogen depletion and muscle damage, with change in muscle glycogen related to plasma IL-6, and changes in serum myoglobin and cortisol related to the chemotactic cytokines IL-8 and MCP-1.

Lung fibrosis negatively impacts on lung function in chronic asthma and is linked to the development of profibrotic macrophage phenotypes. Epidemiological studies have found that lung function benefits from increased consumption of fruit high in polyphenols. We investigated the effect of boysenberry consumption, in both therapeutic and prophylactic treatment strategies in a mouse model of chronic antigen-induced airway inflammation. Boysenberry consumption reduced collagen deposition and ameliorated tissue remodeling alongside an increase in the presence of CD68+CD206+arginase+ alternatively activated macrophages in the lung tissue. The decrease in tissue remodeling was associated with increased expression of profibrolytic matrix metalloproteinase-9 protein in total lung tissue. We identified alternatively activated macrophages in the mice that consumed boysenberry as a source of the matrix metalloproteinase-9. Oral boysenberry treatment may moderate chronic tissue remodeling by supporting the development of profibrolytic alternatively activated macrophages expressing matrix metalloproteinase-9. Regular boysenberry consumption therefore has the potential to moderate chronic lung remodeling and fibrosis in asthma and other chronic pulmonary diseases., (Copyright © 2016 the American Physiological Society.)

Background: Ulcerative colitis is frequently treated with total proctocolectomy and ileal pouch-anal anastomosis reconstruction. Causes of pouch failure and criteria for improved patient selection remain poorly understood. We aimed to identify risk factors for pouch failure., Methods: We performed a retrospective chart review of patients in a prospectively maintained database. Consecutive patients undergoing ileal pouch-anal anastomosis for inflammatory bowel disease between 2000 and 2010 at our institution were included. The primary outcome was pouch failure, defined as permanent ostomy diversion or pouch excision., Results: Of 417 total patients, 28 (6.7%) patients developed pouch failure. Pouch failure was associated with female gender, anastomotic leak, Crohn's disease of the pouch and preoperative Clostridium difficile colitis. The use of anti-tumor necrosis factor alpha biologics was not associated with pouch failure. Notably, 14.9% of patients were diagnosed with preoperative C. difficile colitis, a factor independently associated with pouch failure (hazard ratio 3.02; 95% confidence interval, 1.23-7.44; P = 0.016). C. difficile colitis did not contribute to failure by increasing the incidence of anastomotic leak but was associated with a diagnosis of Crohn's disease of the pouch (adjusted hazard ratio 2.27 [1.08-4.79]; P = 0.031). Anastomotic leak (P < 0.001) and pelvic abscess requiring drainage (P = 0.031) were other independent risk factors for pouch failure., Conclusions: In addition to previously known risk factors, history of preoperative C. difficile colitis was associated with pouch failure after reconstruction, suggesting the need for further study into the role of the gut-associated microbiome in pouch outcomes.

Background: Whilst the use of the mannitol/lactulose test for intestinal permeability has been long established it is not known whether the doses of these sugars modify transit time Similarly it is not known whether substances such as aspirin that are known to increase intestinal permeability to lactulose and mannitol and those such as ascorbic acid which are stated to be beneficial to gastrointestinal health also influence intestinal transit time., Methods: Gastric and intestinal transit times were determined with a SmartPill following consumption of either a lactulose mannitol solution, a solution containing 600 mg aspirin, a solution containing 500 mg of ascorbic acid or an extract of blackcurrant, and compared by doubly repeated measures ANOVA with those following consumption of the same volume of a control in a cross-over study in six healthy female volunteers. The dominant frequencies of cyclic variations in gastric pressure recorded by the Smartpill were determined by fast Fourier transforms., Results: The gastric transit times of lactulose mannitol solutions, of aspirin solutions and of blackcurrant juice did not differ from those of the control. The gastric transit times of the ascorbic acid solutions were significantly shorter than those of the other solutions. There were no significant differences between the various solutions either in the total small intestinal or colonic transit times. The intraluminal pHs during the initial quartiles of the small intestinal transit times were lower than those in the succeeding quartiles. This pattern did not vary with the solution that was consumed. The power of the frequencies of cyclic variation in intragastric pressure recorded by the Smartpill declined exponentially with increase in frequency and did not peak at the reported physiological frequencies of gastric contractile activity., Conclusions: Whilst the segmental residence times were broadly similar to those using other methods, the high degree of variation between subjects generally precluded the identification of all but gross variation between treatments. The lack of any differences between treatments in either total small or large intestinal transit times indicates that the solutions administered in the lactulose mannitol test of permeability had no consistent influence on the temporal pattern of absorption. The negatively exponential profile and lack of any peaks in the frequency spectra of cyclic variation in gastric intraluminal pressure that were consistent with reported physiological frequencies of contractile activity profile suggests that the principal source of this variation is stochastic likely resulting from the effects of external events occasioned by normal daily activities on intra-abdominal pressure., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12615000596505.

Background: For medically refractory or obstructive Crohn's disease (CD), ostomy surgery remains an important therapeutic option. Outcomes and complications of this approach have not been well described in the era of biological therapies. Our study aims to characterize CD patients undergoing ostomy creation and assess outcome predictors., Methods: We performed a retrospective chart review of CD patients who underwent ostomy creation in our center from 2011 to 2014. Data collected include patient demographics, detailed disease- and surgery-related variables, and clinical outcomes after 26 weeks of follow-up., Results: Of the 112 patients, 54 % were female, the median age was 39 years (range 19-78), the median disease duration was 13 years (range 0-50), 54 % had ileo-colonic disease, 55 % had stricturing phenotype, and 59 % had perianal disease. Sixty-two percent received end ostomies, and 38 % received loop ostomies. The leading indications for surgery were stricturing, fistulizing, and perianal disease (35 %). Forty-three (38 %) patients had 76 major complications, including dehydration (22 cases), intra-abdominal infection (16), and obstruction (14). Increased major postoperative complications correlated with penetrating disease (p = 0.02, odds ratio [OR] = 5.52, 95 % confidence interval [CI] = 1.25-24.42), the use of narcotics before surgery (p = 0.04, OR = 2.54, 95 % CI = 1.02-6.34), and loop ostomies (p = 0.004, OR = 4.2, 95 % CI = 1.57-11.23)., Conclusions: Penetrating phenotype, the use of narcotics before surgery, and loop ostomies are associated with major complications in CD patients undergoing ostomy creation. These findings may influence risk management of CD patients needing ostomies.

Objectives: The purpose of this study was to correlate post-exercise muscle glycogen levels with changes in plasma cytokine, and muscle mRNA cytokine expression and protein content., Methods: Twenty-four male runners (age 36.5 ± 1.8 years, VO2max 60.0 ± 1.5 mL⋅kg(-1) ⋅ min(-1)) ran twice (separated by 4 weeks) on treadmills to exhaustion at 70% VO2max (average time and distance of 2.24 ± 0.09 h and 24.9 ± 1.1 km). Muscle biopsies from the vastus lateralis and blood samples were collected before and after each run, with IL-6, IL-8, and MCP-1 measured in muscle (mRNA and protein) and plasma. Data from the two runs were averaged., Results: Participants experienced a 35.3 ± 4.2% decrease (P < 0.001) in skeletal muscle glycogen content (67.5 ± 2.8 to 44.3 ± 3.7 mmol⋅kg(-1) wet weight). Muscle mRNA expression for IL-6, IL-8, and MCP-1 increased 7.34 ± 0.90-, 13.9 ± 2.3-, and 4.10 ± 0.60-fold, respectively (all, P < 0.001). Skeletal muscle IL-6, IL-8, and MCP-1 protein content increased 35.8 ± 10.6, 80.6 ± 12.1, and 105 ± 17.9%, respectively (all, P ≤ 0.005). Plasma IL-6, IL-8, and MCP-1 increased 47.1 ± 10.0-, 2.6 ± 0.3-, and 1.6 ± 0.1-fold, respectively (all, P < 0.001). Post-exercise muscle glycogen concentrations were negatively correlated with run time to exhaustion (r = -0.70, P < 0.001), and changes in muscle IL-6 protein content (r = -0.44, P = 0.049), plasma IL-6 (r = -0.72, P < 0.001), IL-8 (r = -0.60, P = 0.002), and MCP-1 (r = -0.589, P = 0.002), but not with changes in muscle IL-8 and MCP-1 protein content, or muscle mRNA expression for IL-6, IL-8, and MCP-1., Conclusion: Prolonged and intensive running increased muscle mRNA expression, muscle protein content, and plasma levels for IL-6, IL-8, and MCP-1, and post-run muscle glycogen levels were most strongly related to plasma cytokine levels.

Ascorbic acid in combination with aspirin has been used to prevent aspirin-induced oxidative GI damage. We aimed to determine whether ascorbic acid reduces or prevents aspirin-induced changes in intestinal permeability over a 6-hr period using saccharidic probes mannitol and lactulose. The effects of administration of 600 mg aspirin alone, 500 mg ascorbic acid alone and simultaneous dosage of both agents were compared in a cross-over study in 28 healthy female volunteers. These effects were also compared with that of a placebo. The ability of ascorbic acid to mitigate the effects of aspirin when administered either half an hour before or after dosage with aspirin was also assessed in 19 healthy female volunteers. The excretion of lactulose over the 6-hr period was augmented after consumption of either aspirin or ascorbic acid compared with that after consumption of placebo. Dosage with ascorbic acid alone augmented the excretion of lactulose more than did aspirin alone. Simultaneous dosage with both agents augmented the excretion of lactulose in an additive manner. The timing of dosage with ascorbic acid in relation to that with aspirin had no significant effect on the excretion of the two sugars. These findings indicate that ascorbic acid does not prevent aspirin-induced increase in gut permeability rather that both agents augment it to a similar extent. The additive effect on simultaneous dosage with both agents in augmenting the absorption of lactulose suggests that each influences paracellular permeability by different pathways., (© 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Purpose: Perineal wounds after complete proctectomy are at risk for failure, with dramatic consequences on patients' health and quality of life. This study is aimed at identifying risk factors for wound complications in patients undergoing primary closure of the perineal defect after total proctectomy., Methods: Data from 284 patients undergoing total proctectomy from 2002 to 2012 either at the University of Chicago Medical Center or the Catholic University of Rome Hospital were collected and analyzed., Results: Overall, the perineal wound complication rate was 21.8%. Successful conservative management was accomplished in 45.2% of cases. Complications occurred significantly more often in patients with a higher Charlson score index, with the diagnosis of rectal cancer, who had received preoperative radiation and who had a surgical drain placed at the time of initial surgery. Neoadjuvant radiation was the only significant risk factor at multivariate analysis (OR 4.40). In the rectal cancer subgroup, younger age, female gender, and preoperative radiation were predictors of wound complications. Based on that, a 3-point score (radiation, age, and gender (RAG)) was developed. Patients with a score of 3 had a 50% risk of developing a perineal wound complication., Conclusions: Perineal wound complications are a common and burdensome problem after total proctectomy. Preoperative radiation is the single most significant and controllable risk factor predicting perineal wound failure. In the presence of multiple, non-modifiable risk factors, alternative approaches to primary closure should be considered in managing complex perineal defects.

This study aimed to determine how small heat shock proteins (sHSPs) protect myofibrillar proteins from μ-calpain degradation during ageing. Immunoprecipitation experiments with M. longissimus dorsi (LD) from Angus heifers (n = 14) examined the interaction between αβ-crystallin, desmin, titin, HSP20, HSP27 and μ-calpain. Results showed that αβ-crystallin associated with desmin, titin, HSP20, HSP27 and μ-calpain. Exogenous αβ-crystallin reduced desmin and titin degradations in myofibrillar extracts and attenuated μ-calpain activity. In a second experiment, bull LD (n = 94) were aged at -1.5°C for up to 28 days post mortem. μ-Calpain autolysed faster in high ultimate pH (pH(u)) meat (pH(u)≥6.2) and this was concomitant with the more rapid degradation of titin and filamin in this pH(u) group. Desmin stability in intermediate pH(u) meat (pH(u) 5.8 to 6.19) may be due to the protection of myofibril-bound sHSPs combined with the competitive inhibition of μ-calpain by sHSPs., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Lactulose mannitol ratio tests are clinically useful for assessing disorders characterised by changes in gut permeability and for assessing mixing in the intestinal lumen. Variations between currently used test protocols preclude meaningful comparisons between studies. We determined the optimal sampling period and related this to intestinal residence., Methods: Half-hourly lactulose and mannitol urinary excretions were determined over 6 hours in 40 healthy female volunteers after administration of either 600 mg aspirin or placebo, in randomised order at weekly intervals. Gastric and small intestinal transit times were assessed by the SmartPill in 6 subjects from the same population. Half-hourly percentage recoveries of lactulose and mannitol were grouped on a basis of compartment transit time. The rate of increase or decrease of each sugar within each group was explored by simple linear regression to assess the optimal period of sampling., Key Results: The between subject standard errors for each half-hourly lactulose and mannitol excretion were lowest, the correlation of the quantity of each sugar excreted with time was optimal and the difference between the two sugars in this temporal relationship maximal during the period from 2½-4 h after ingestion. Half-hourly lactulose excretions were generally increased after dosage with aspirin whilst those of mannitol were unchanged as was the temporal pattern and period of lowest between subject standard error for both sugars., Conclusion: The results indicate that between subject variation in the percentage excretion of the two sugars would be minimised and the differences in the temporal patterns of excretion would be maximised if the period of collection of urine used in clinical tests of small intestinal permeability were restricted to 2½-4 h post dosage. This period corresponds to a period when the column of digesta column containing the probes is passing from the small to the large intestine.

Eosinophil recruitment to the airways is a characteristic feature of allergic asthma. Eotaxins are potent chemokines that regulate the recruitment of eosinophils to sites of inflammation. Of these, CCL26 is linked to persistent eosinophil recruitment in the later phase of an allergic response. We evaluated the effectiveness of 10 different blackcurrant cultivar polyphenolic extracts in suppressing CCL26 secretion in stimulated human alveolar epithelial cells. Correlation analysis to identify the potential blackcurrant composition constituent(s) involved in CCL26 suppression and the effects of the four major anthocyanins present in blackcurrants to validate results was conducted. All blackcurrant polyphenolic extracts suppressed CCL26 secretion by lung alveolar cells; however, differential efficacy was observed, which was attributed to their cultivar-specific polyphenolic composition profiles. We identified that the ratio of concentrations of delphinidin glycosides to cyanidin glycosides in the blackcurrant cultivars was an important determinant in influencing CCL26 suppression in lung cells. Our findings support the potential use of blackcurrants or blackcurrant-derived foods/ingredients in managing lung inflammation and the development of specific cultivars as functional foods/ingredients with beneficial biological activities.

The effects of inflammatory changes on the absorption of different-sized probes and their permeability ratios are poorly understood. The aim of the present study was to determine the effects of a pharmacological agent on the permeability of the gut mucosa to saccharidic probes of larger and smaller molecular weight. Permeability was assessed by half-hourly urinary excretion of a combined dose of d-mannitol, l-rhamnose and lactulose following consumption of a single 600 mg dose of aspirin and compared with a placebo in a cross-over study in 20 healthy female volunteers. The temporal patterns of excretion of all probes were bimodal, being best fitted by polynomial functions. The relatively small early peak was evident for at least 4 h for smaller sugars, but was less evident with lactulose, being overshadowed by a larger second peak. These conclusions were further supported by separate analyses of the segments of the temporal plots between 2.5 and 4 h and between 4.5 and 6 h. The forms of these curves did not change significantly following dosing with aspirin. A greater proportion of the total dose of mannitol than rhamnose was excreted over the collection period. Following the consumption of aspirin, the cumulative rate of excretion of the smaller sugars (i.e. mannitol and rhamnose) was significantly reduced whereas that of lactulose was increased over the 6 h collection period. Aspirin has opposite effects on the absorption of larger and smaller probes, influencing the outcome of the test. These results have important consequences for the design and comparison of clinical tests of permeability., (© 2013 Wiley Publishing Asia Pty Ltd.)

Asthma is an allergy-mediated inflammatory disease characterised by infiltration of the airway with mast cells, lymphocytes, and eosinophils. The disease is induced by co-ordination of T-helper cell type 2 (Th2) cytokines and inflammatory signal molecules. Fruits and vegetables are a rich source of polyphenolic bioactive compounds, which have been observed to have health-promoting properties when consumed by humans. In particular, fruit-derived proanthocyanins and anthocyanins have been found to attenuate lung inflammation. Epidemiological studies have revealed correlations between fruit consumption and a lower prevalence of respiratory symptoms and lower incidence of non-specific lung diseases. In this review we summarise the current understanding of the pathophysiologic mechanism(s) involved in the development of allergic airway disease. We also review evidence of the beneficial effects of plant-derived foods, their components and metabolites in allergic airway inflammation arising from in vitro and rodent studies, epidemiological studies and human intervention trials. The mechanism, biological relevance and functional benefits, such as immune modulation (e.g. reduction in cytokine and eotaxin production), antioxidant ability, tissue remodelling and tight junction function are also discussed.

Background: Little is known about the impact of obesity on morbidity in patients with inflammatory bowel disease (IBD) who are undergoing laparoscopic resections. The aim of this study was to evaluate outcomes in a consecutive series of normal weight (NW), overweight (OW), and obese (OB) patients undergoing elective laparoscopic colorectal surgery for IBD., Study Design: This study is a retrospective analysis of a prospectively collected, Institutional Review Board-approved IBD database., Results: Laparoscopic colorectal resection was performed in 626 patients (335 NW, 206 OW, and 85 OB) between August 2002 and December 2011. Operative time and blood loss were significantly higher in the OW and OB groups compared with the NW group (p = 0.001 and p < 0.001). No differences were observed in terms of intraoperative blood transfusions (p = 0.738) or complications (p = 0.196). The OW and OB groups had a significantly higher conversion rate (p = 0.049 and p = 0.037) and a longer incision compared with the NW group (p = 0.002 and p < 0.001). Obesity was an independent predictor of conversion to open surgery. No significant differences between groups were observed in terms of overall 30-day postoperative morbidity (p = 0.294) and mortality (p = 0.796). Long-term complications occurred in 6.3% NW, 7.3% OW, and 4.7% OB patients (p = 0.676). Incisional hernias were more common in the OB group compared with the NW group (p = 0.020). On multivariate analysis, obesity was not an independent risk factor for either early or late postoperative complications., Conclusions: Obesity increases the complexity of laparoscopic resections in IBD with higher blood loss, operative time, and conversion rates, without worsening outcomes., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The impact of infliximab on the postoperative course of patients with IBD is under debate., Objective: The aim of this study was to evaluate the influence of infliximab on perioperative outcomes in patients undergoing elective laparoscopic resection for IBD., Design: This study is a retrospective analysis of a prospectively collected, institutional review board-approved database. SETTING, PATIENTS, INTERVENTIONS: Patients undergoing laparoscopic resection on preoperative infliximab (infliximab group) were compared with patients who did not receive infliximab (noninfliximab group)., Main Outcome Measures: The short-term and long-term morbidity and mortality rates were assessed., Results: Elective laparoscopic resection for IBD was performed on 518 patients from January 2004 through June 2011; 142 patients were treated with infliximab preoperatively. Both groups had similar demographics, type and severity of IBD, comorbidities, and type of surgery. A significantly higher number of patients in the infliximab group had been on aggressive medical therapy to control symptoms of IBD during the month preceding surgery, including steroids (73.9 vs 58.8%, p = 0.002) and immunosuppressors (32.4 vs 20.5%, p = 0.006). Operative time and blood loss were similar (p = 0.50 and p = 0.34). Intraoperative complication rate was 2.1% in both groups. No significant differences were observed in terms of the conversion rate to laparotomy (6.3% vs 9.3%, p = 0.36), overall 30-day postoperative morbidity (p = 0.93), or mortality (p = 0.61). The rates of anastomotic leak (2.1% vs 1.3%, p = 0.81), infections (12% vs 11.2%, p = 0.92), and thrombotic complications (3.5% vs 5.6%, p = 0.46) were similar. Subgroup analyses confirmed similar rates of overall, infectious, and thrombotic complications regardless of whether patients had ulcerative colitis or Crohn's disease., Limitations: This study is subject to the limitations of a retrospective design., Conclusions: Infliximab is not associated with increased rates of postoperative complications after laparoscopic resection.

Background: The objective of this study was to assess the regional geometry of the Heineke-Mikulicz (HM) strictureplasty. The HM intestinal strictureplasty is commonly performed for the treatment of stricturing Crohn's disease of the small intestine. This procedure shifts relatively normal proximal and distal tissue to the point of narrowing and thus increases the luminal diameter. The overall effect on the regional geometry of the HM strictureplasty, however, has not been previously described in detail., Methods: HM strictureplasties were created in latex tubing and cast with an epoxy resin. The resultant casts of the lumens were then imaged using computed tomography. Using 3-dimensional vascular reconstruction software, the cross-sectional areas were determined and the surface geometry was examined., Results: The HM strictureplasty, while increasing the lumen at the point of the stricture, also results in a counterproductive luminal narrowing proximal and distal to the strictureplasty. Within the model used, cross-sectional area was diminished 25% to 50% below baseline. This effect is enhanced when 2 strictureplasties are placed in close proximity to each other., Conclusions: The HM strictureplasty results in alterations in the regional geometry that may result in a compromise of the lumen proximal and distal to the location of the strictureplasty. When 2 HM strictureplasties are created in close proximity to each other, care should be undertaken to assure that the lumen of the intervening segment is adequate.

Background: Individuals with ulcerative colitis (UC) are at increased risk for colorectal cancer. The standard method of surveillance for neoplasia in UC by colonoscopy is invasive and can miss flat lesions. We sought to identify a gene expression signature in nondysplastic mucosa without active inflammation that could serve as a marker for remote neoplastic lesions., Methods: Gene expression was analyzed by complementary DNA microarray in 5 normal controls, 4 UC patients without dysplasia, and 11 UC patients harboring remote neoplasia. Common gene ontology pathways of significantly differentially expressed genes were identified. Expression of genes which were progressively and significantly upregulated from controls to UC without neoplasia, to UC with remote neoplasia were evaluated by real-time polymerase chain reaction. Several gene products were also examined by immunohistochemistry., Results: Four hundred and sixty-eight genes were significantly upregulated, and 541 genes were significantly downregulated in UC patients with neoplasia compared with UC patients without neoplasia. Nine genes (ACSL1, BIRC3, CLC, CREM, ELTD1, FGG, S100A9, THBD, and TPD52L1) were progressively and significantly upregulated from controls to nondysplastic UC to UC with neoplasia. Immunostaining of proteins revealed increased expression of S100A9 and REG1α in UC-associated cancer and in nondysplastic tissue from UC patients harboring remote neoplasia compared with UC patients without neoplasia and controls., Conclusions: Gene expression changes occurring as a field effect in the distal colon of patients with chronic UC identify patients harboring remote neoplastic lesions. These markers may lead to a more accurate and less invasive method of detection of neoplasia in patients with inflammatory bowel disease.

Background: We explored the temporal dynamics of the lactulose mannitol test and the influence of a single dose of aspirin., Methods: Twenty healthy female volunteers each received 600 mg aspirin or placebo in random sequence and were subsequently dosed with 10 g lactulose and 5 g mannitol, their urine collected every half hour for 6h., Key Results: The lactulose:mannitol ratios (LMR) of urine samples collected over the entire 6-h period were significantly higher than those collected in the first 3 h. Greater quantities of mannitol were excreted over the first than the subsequent 3 h. A similar pattern of temporal variation in mannitol excretion was found in smokers and non-smokers and was maintained following administration of a single 600 mg dose of aspirin. The rates at which lactulose was excreted were relatively constant over the entire 6 h period of collection, but mean levels were increased over the entire 6 h following the administration of aspirin. The effect of aspirin did not differ significantly between smokers and non-smokers., Conclusions & Inferences:   While the LMR test is sufficiently sensitive to reproducibly detect the increase in intestinal permeability resulting from a single 600 mg oral dose of aspirin, the temporal patterns of excretion of mannitol and lactulose differ both in the presence and absence of aspirin. Hence, variation in sampling period and in method of dosage are likely to influence the result and it is preferable to examine the patterns of absorption of component sugars separately with due regard to the method of dosage., (© 2012 Blackwell Publishing Ltd.)

Background: Exercise-induced muscle damage (EIMD) is accompanied by localized oxidative stress / inflammation which, in the short-term at least, is associated with impaired muscular performance. Dietary antioxidants have been shown to reduce excessive oxidative stress; however, their effectiveness in facilitating recovery following EIMD is not clear. Blueberries demonstrate antioxidant and anti-inflammatory properties. In this study we examine the effect of New Zealand blueberries on EIMD after strenuous eccentric exercise., Methods: In a randomized cross-over design, 10 females consumed a blueberry smoothie or placebo of a similar antioxidant capacity 5 and 10 hours prior to and then immediately, 12 and 36 hours after EIMD induced by 300 strenuous eccentric contractions of the quadriceps. Absolute peak and average peak torque across the knee, during concentric, isometric, and eccentric actions were measured. Blood biomarkers of oxidative stress, antioxidant capacity, and inflammation were assessed at 12, 36 and 60 hours post exercise. Data were analyzed using a two-way ANOVA., Results: A significant (p < 0.001) decrease in isometric, concentric and eccentric torque was observed 12 hours following exercise in both treatment groups. During the 60 hour recovery period, a significant (p = 0.047) interaction effect was seen for peak isometric tension suggesting a faster rate of recovery in the blueberry intervention group. A similar trend was observed for concentric and eccentric strength. An increase in oxidative stress and inflammatory biomarkers was also observed in both treatment groups following EIMD. Although a faster rate of decrease in oxidative stress was observed in the blueberry group, it was not significant (p < 0.05) until 36 hours post-exercise and interestingly coincided with a gradual increase in plasma antioxidant capacity, whereas biomarkers for inflammation were still elevated after 60 hours recovery., Conclusions: This study demonstrates that the ingestion of a blueberry smoothie prior to and after EIMD accelerates recovery of muscle peak isometric strength. This effect, although independent of the beverage's inherent antioxidant capacity, appears to involve an up-regulation of adaptive processes, i.e. endogenous antioxidant processes, activated by the combined actions of the eccentric exercise and blueberry consumption. These findings may benefit the sporting community who should consider dietary interventions that specifically target health and performance adaptation.