Think Twice: De-implementation of Laboratory Testing After Colorectal Surgery.

BACKGROUND: Clinically unindicated laboratory testing contributes to low-value care. Most postoperative day 1 laboratory tests after colorectal surgery are normal. However, no published interventions have shown that reducing overall postoperative laboratory testing is safe. OBJECTIVE: This study aimed to investigate the impact of reducing postoperative laboratory testing after colorectal surgery. DESIGN: This is a quality improvement study. SETTINGS: The study was conducted at an academic center with an enhanced recovery after surgery program that included 5 daily laboratory tests until discharge. PATIENTS: All adults undergoing colorectal or small-bowel surgery formed intervention and nonintervention cohorts based on surgeons who chose to opt into the study. Preimplementation (November 2019-October 2021), there were 545 intervention and 577 nonintervention patients. Postimplementation (November 2021-March 2023), there were 448 intervention and 437 nonintervention patients. INTERVENTIONS: The intervention included 3 postoperative day 1 laboratory tests and subsequent clinically indicated laboratory tests. MAIN OUTCOME MEASURES: Outcome measures included laboratory tests and days free of laboratory work. RESULTS: Postintervention, the intervention group had a 33% reduction in laboratory tests per hospital stay, a 26% reduction in laboratory tests per day, and a 49% increase in laboratory test-free days. There was no difference in length of stay (4 vs 4; p = 0.79) or readmissions (14.9% vs 12.9%; p = 0.39). The nonintervention group had no significant changes in laboratory work or laboratory test-free days, with no differences in length of stay (4 vs 4; p = 0.49) or readmissions (11.1% vs 11.0%; p = 0.96). LIMITATIONS: Demographics and complication rates were not reported. CONCLUSIONS: An intervention targeting reflexive laboratory testing after colorectal surgery resulted in safe, significant, sustained reductions in postoperative laboratory work, with substantial cost savings. These findings prompted a change in the laboratory order set to an opt-out system, and laboratory work reduction approaches have been implemented within other surgical divisions. Continuation and spread of these efforts are instrumental for prioritization of high-value surgical care. See Video Abstract . PINSELO DOS VECES ELIMINACIN DE LAS PRUEBAS DE LABORATORIO DESPUS DE LA CIRUGA COLORRECTAL: ANTECEDENTES:Las pruebas de laboratorio clínicamente no indicadas contribuyen a una atención de bajo valor. La mayoría de los análisis de laboratorio del primer día post operatorios de una cirugía colorrectal son normales. Sin embargo, ninguna intervención publicada ha demostrado que reducir las pruebas de laboratorio post operatorias generales sea seguro.OBJETIVO:El objetivo de este estudio fue investigar el impacto de reducir las pruebas de laboratorio pos toperatorias después de la cirugía colorrectal.DISEÑO:Este es un estudio de mejora de la calidad.AJUSTES:El estudio se llevó a cabo en un centro académico con un programa mejorado de recuperación después de la cirugía que incluye 5 laboratorios diarios hasta el alta.PACIENTES:Todos los adultos sometidos a cirugía colorrectal o de intestino delgado formaron cohortes de intervención y no intervención basadas en los cirujanos que optaron por participar en el estudio. Antes de la implementación (noviembre de 2019 - octubre de 2021) había 545 pacientes con intervención y 577 sin intervención. Después de la implementación (noviembre de 2021 - marzo de 2023) hubo 448 pacientes con intervención y 437 sin intervención.INTERVENCIONES:La intervención incluyó 3 laboratorios post operatorios del primer día y laboratorios posteriores clínicamente indicados.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas de resultado incluyeron pruebas de laboratorio y días sin laboratorio.RESULTADOS:Después de la intervención, el grupo de intervención tuvo una reducción del 33 % en laboratorios por estancia hospitalaria, una reducción del 26 % en laboratorios por día y un aumento del 49 % en los días sin laboratorio. No hubo diferencias en la duración de la estancia hospitalaria (4 frente a 4; p = 0,79) ni en los reingresos (14,9% frente a 12,9%; p = 0,39). El grupo de no intervención no tuvo cambios significativos en el trabajo de laboratorio o en los días sin laboratorio, sin diferencias en la duración de la estadía (4 versus 4; p = 0,49) o reingresos (11,1% versus 11,0%; p = 0,96).LIMITACIONES:No se informaron datos demográficos ni tasa de complicaciones.CONCLUSIONES:Una intervención dirigida a pruebas de laboratorio reflexivas después de la cirugía colorrectal resultó en reducciones seguras, significativas y sostenidas en el trabajo de laboratorio post operatorio, con ahorros sustanciales de costos. Estos hallazgos provocaron un cambio en el orden del laboratorio establecido hacia un sistema de exclusión voluntaria, y se han implementado enfoques de reducción del trabajo de laboratorio en otras divisiones quirúrgicas. La continuación y difusión de estos esfuerzos son fundamentales para priorizar la atención quirúrgica de alto valor. (Traducción-Dr. Mauricio Santamaria ).

Efficacy of cannabinoids in neurodevelopmental and neuropsychiatric disorders among children and adolescents: a systematic review.

A better understanding of the endocannabinoid system and a relaxation in regulatory control of cannabis globally has increased interest in the medicinal use of cannabinoid-based products (CBP). We provide a systematic review of the rationale and current clinical trial evidence for CBP in the treatment of neuropsychiatric and neurodevelopmental disorders in children and adolescents. A systematic search of MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Trials was performed to identify articles published after 1980 about CBP for medical purposes in individuals aged 18 years or younger with selected neuropsychiatric or neurodevelopmental conditions. Risk of bias and quality of evidence was assessed for each article. Of 4466 articles screened, 18 were eligible for inclusion, addressing eight conditions (anxiety disorders (n = 1); autism spectrum disorder (n = 5); foetal alcohol spectrum disorder (n = 1); fragile X syndrome (n = 2); intellectual disability (n = 1); mood disorders (n = 2); post-traumatic stress disorder (n = 3); and Tourette syndrome (n = 3)). Only one randomised controlled trial (RCT) was identified. The remaining seventeen articles included one open-label trial, three uncontrolled before-and-after trials, two case series and 11 case reports, thus the risk of bias was high. Despite growing community and scientific interest, our systematic review identified limited and generally poor-quality evidence for the efficacy of CBP in neuropsychiatric and neurodevelopmental disorders in children and adolescents. Large rigorous RCTs are required to inform clinical care. In the meantime, clinicians must balance patient expectations with the limited evidence available.

The Correlation between Vitamin D Levels and the Risk of Postoperative Recurrence in Crohn's Disease.

BACKGROUND AND AIMS: Vitamin D deficiency has been associated with disease activity in Crohn's disease (CD). We assessed whether there is a correlation between vitamin D levels and the risk of postoperative recurrence in CD. METHODS: CD patients who underwent surgery were identified from a prospectively maintained database at the University of Chicago. The primary endpoint was the correlation of serum 25-hydroxy vitamin D levels measured at 6-12 months after surgery and the proportion of patients in endoscopic remission, defined as a simple endoscopic score for CD of 0. Clinical, biological (C-reactive protein), and histologic recurrences were also studied. RESULTS: Among a total of 89 patients, 17, 46, and 26 patients had vitamin D levels of <15, 15-30, and >30 ng/mL, respectively. Patients with higher vitamin D levels were significantly more likely to be in endoscopic remission compared to those with lower levels (23, 42, and 67% in ascending tertile order; p = 0.028). On multivariate analysis, vitamin D >30 ng/mL (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07-0.66, p = 0.006) and anti-tumor necrosis factor agent treatment (OR 0.25, 95% CI 0.08-0.83, p = 0.01) were associated with reduced risk of endoscopic recurrence. Rates of clinical, biological, and histologic remission trended to be higher in patients with higher vitamin D levels (p = 0.17, 0.55, 0.062, respectively). CONCLUSION: In the present study, higher vitamin D level was associated with lower risk of postoperative endoscopic CD recurrence. Further, studies are warranted to assess the role of vitamin D in postoperative CD recurrence.

Exposure to Anti-tumor Necrosis Factor Medications Increases the Incidence of Pouchitis After Restorative Proctocolectomy in Patients With Ulcerative Colitis.

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.

Abnormal Pouchogram Predicts Pouch Failure Even in Asymptomatic Patients.

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.

Outcome of elective switching to vedolizumab in inflammatory bowel disease patients under tumor necrosis factor antagonist-maintained clinical remission.

BACKGROUND AND AIM: Vedolizumab (VDZ) has been used in inflammatory bowel disease (IBD) patients who failed anti-tumor necrosis factor (TNF) therapy. This study was to examine long-term outcome of IBD patients switching to VDZ from anti-TNF agents for reasons other than failure of therapy. METHODS: Inflammatory bowel disease patients at the University of Chicago IBD center who were in clinical remission with anti-TNF therapy and then electively changed to VDZ due to reasons other than loss of response were retrospectively analyzed. The primary outcome was the durability of clinical remission maintained by VDZ as assessed by Kaplan-Meier survival analysis. The proportion of patients in clinical and endoscopic remission at 6-12 months after switching to VDZ therapy was analyzed. RESULTS: A total of 41 patients (36 with Crohn's disease and 5 with ulcerative colitis) met the inclusion criteria and were in clinical remission at the time of switch. The majority of patients switched therapy due to adverse effects (56.1%) or infections (14.6%). During a median duration of 30 months (range 7-52) of VDZ therapy, 34 (82.9%) were in VDZ-maintained clinical remission. One (2.4%) and four (9.8%) patients discontinued VDZ due to flare and adverse effects, respectively. Endoscopic remission was present in 25 of 30 patients (83.3%) who had a follow-up colonoscopy. CONCLUSIONS: Vedolizumab was effective and safe in maintaining remission in IBD patients who switched from anti-TNF agents due to reasons other than failure of therapy. Our results suggest that switching anti-TNF remitters to VDZ treatment is a safe practice in specific patient populations.

Risk of Postoperative Complications Among Inflammatory Bowel Disease Patients Treated Preoperatively With Vedolizumab.

OBJECTIVES: Vedolizumab is increasingly used to treat patients with ulcerative colitis (UC) and Crohn's disease (CD), however, its safety during the perioperative period remains unclear. We compared the 30-day postoperative complications among patients treated preoperatively with vedolizumab, anti-tumor necrosis factor (TNF)-α agents or non-biological therapy. METHODS: The retrospective study cohort was comprised of patients receiving vedolizumab, anti-TNF-α agents or non-biological therapy within 4 weeks of surgery. The rates of 30-day postoperative complications were compared between groups using univariate and multivariate analysis. Propensity score-matched analysis was performed to compare the outcome between groups. RESULTS: Among 443 patients (64 vedolizumab, 129 anti-TNF-α agents, and 250 non-biological therapy), a total of 144 patients experienced postoperative complications (32%). In multivariate analysis, age >65 (odds ratio (OR) 3.56, 95% confidence interval (CI) 1.30-9.76) and low-albumin (OR 2.26, 95% CI 1.28-4.00) were associated with increased risk of 30-day postoperative complications. For infectious complications, steroid use (OR 3.67, 95% CI 1.57-8.57, P=0.003) and low hemoglobin (OR 3.03, 95% CI 1.32-6.96, P=0.009) were associated with increased risk in multivariate analysis. Propensity score matched analysis demonstrated that the risks of postoperative complications were not different among patients preoperatively receiving vedolizumab, anti-TNF-α agents or non-biological therapy (UC, P=0.40; CD, P=0.35). CONCLUSIONS: In the present study, preoperative vedolizumab exposure did not affect the risk of 30-day postoperative complications in UC and CD. Further, larger studies are required to confirm our findings.

Intestinal Stomas-Postoperative Stoma Care and Peristomal Skin Complications.

Intestinal stomas are necessary for several colon and rectal conditions and represent a major change in the new ostomate's daily life. Though dehydration is the most frequent etiology requiring readmission, irritant contact dermatitis and a host of other peristomal skin conditions are more common complications for ostomates. Wound, ostomy, and continence nurses are invaluable resources to both ostomy patients and providers. A few simple interventions can prevent or resolve most common peristomal complications. Good stoma care is possible in a resource-poor environment.

Dynamic Article: Tandem Robotic Technique of Extralevator Abdominoperineal Excision and Rectus Abdominis Muscle Harvest for Immediate Closure of the Pelvic Floor Defect.

BACKGROUND: Extralevator abdominoperineal excision for distal rectal cancers involves cylindrical excision of the mesorectum with wide division of the levator ani muscles. Although this technique has been shown to decrease local cancer recurrence and improve survival, it leaves the patient with a considerable pelvic floor defect that may require reconstruction. OBJECTIVE: We developed an innovative technique of robotic extralevator abdominoperineal excision combined with robotic harvest of the rectus abdominis muscle flap for immediate reconstruction of the pelvic floor defect. DESIGN: This was a retrospective review pilot study. SETTING: This study was conducted at a tertiary care cancer center. PATIENTS: Three patients who underwent robotic extralevator abdominoperineal excision with robotic rectus abdominis flap harvest for distal rectal adenocarcinoma were included. MAIN OUTCOMES MEASURES: Intraoperative and postoperative outcomes included operative time, intraoperative complications, length of hospital stay, wound complications, incidence of perineal hernia, persistent pain, and functional limitations. RESULTS: Three patients underwent this procedure. The median operative time was 522 minutes with median hospital stay of 6 days. One patient experienced perineal wound complication requiring limited incision and drainage followed by complete healing of the wound by secondary intention. The other 2 patients did not experience any wound complications. Longest follow-up was 16 months. None of the patients developed perineal hernias during this time period. LIMITATIONS: The small sample size and retrospective nature were limitations. CONCLUSIONS: This technique confers multiple advantages including improved visualization and dexterity within the pelvis and accurate wide margins at the pelvic floor. An incisionless robotic flap harvest with preservation of the anterior rectus sheath obviates the risk of ventral hernia while providing robust tissue closure of the radiated abdominoperineal excision wound. This technique may result in faster postoperative recovery, decreased morbidity, improved functional outcomes and cosmesis. Further studies are needed to prospectively analyze this approach (Supplemental Digital Content 1, video abstract, http://links.lww.com/DCR/A188).

Fetal alcohol spectrum disorder resources for health professionals: a scoping review protocol.

INTRODUCTION: People with fetal alcohol spectrum disorder (FASD) encounter a range of health and allied health providers and require specialised support to ensure health services are provided safely and effectively. Not all health professionals possess the knowledge or expertise required for the identification, assessment, referral and management of FASD. Accessible resources for understanding and managing FASD can help create awareness in health professionals and ensure patients receive the correct diagnosis and timely access to the necessary supports and services. The aim of this scoping review is to identify and analyse FASD resources for health professionals. METHODS AND ANALYSIS: A comprehensive search of eight databases (MEDLINE, Scopus, PsycINFO, CINAHL, PubMED, EMBASE, Web of Science and Trip Medical Database) and nine grey literature databases (FASD Hub, NOFASD Australia, National Organisation for FASD, FASD United, HealthInfoNet, Proof Alliance, Child Family Community Australia, Foundation for Alcohol Research & Education and the Australian Department of Health websites) will be conducted using three search engines including PubMed, Ovid and Google advanced search (search dates: October 2021 to May 2022). Consultations will also be carried out with international and national experts in the diagnosis/management of FASD to obtain any additional relevant published or unpublished resources. Inclusion criteria were developed to guide the selection of resources that are publicly available, primarily focused on FASD and curated for health professionals for the identification, management or referral of FASD. Critical appraisal process will be executed using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE II) tool to assess the quality of selected resources. ETHICS AND DISSEMINATION: Ethical approval is not required for the scoping review. Scoping review results will be presented at relevant national and international conferences and published in peer-reviewed journals. Search results will be made available to ensure reproducibility and transparency.

Bigiswun Kid Project: a longitudinal study of adolescents living with high rates of prenatal alcohol exposure, fetal alcohol spectrum disorder and early life trauma in remote Australian Aboriginal communities.

INTRODUCTION: The Lililwan Project was the first Australian population-based prevalence study of fetal alcohol spectrum disorder (FASD) using active case ascertainment. Conducted in 2010-2011, the study included 95% of all eligible children aged 7-9 years living in the very remote Aboriginal communities of the Fitzroy Valley, Western Australia. Women from Marninwarntikura Women's Resource Centre, a local Aboriginal-led organisation, are concerned that some participants from the study are struggling in adolescence so partnered with researchers from the University of Sydney to follow up the Lililwan cohort in 2020-2022 at age 17-19 years.The overarching aim of the Bigiswun Kid Project is to identify adolescents' needs and build knowledge to inform services to improve the health and well-being of adolescents in remote Aboriginal communities. The specific aims are to: (1) provide a voice to adolescents and their families to understand the health and well-being status of the Lililwan cohort at 17-19 years. (2) Examine relationships between exposures during pregnancy, birth characteristics, and health and neurodevelopment at 7-9 years, and positive/adverse adolescent outcomes at 17-19 years. This information will identify prenatal and early life factors that predict good health and well-being in adolescence. (3) Determine whether management plans provided in the Lililwan Project were followed, and identify past and present service gaps, support needs and barriers to service use. (4) Determine if key physical characteristics of FASD change between childhood and adolescence in this Aboriginal population. ETHICS AND DISSEMINATION: Approved by the Kimberley Aboriginal Health Planning Forum and relevant ethics committees.

Factors associated with anti-tumor necrosis factor effectiveness to prevent postoperative recurrence in Crohn's disease.

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.

Primary Colonic Medullary Carcinoma With Exclusive Squamous Differentiation.

BACKGROUND/AIM: Medullary carcinoma (MC) of the colon is a rare subtype of colorectal adenocarcinoma (CRC) with unique histomorphology and frequent mismatch repair (MMR) deficiency. MC with exclusive squamous differentiation has not been reported. We report an unusual case of MC with squamous differentiation and tested this differentiation potential in other MMR-deficient CRC cases. CASE REPORT: A 68-year-old woman presented with a large ascending colon mass and biopsy showed squamoid tumor morphology with immunoprofile concerning for squamous cell carcinoma (SCC). She underwent right hemicolectomy. Immunohistochemistry and next-generation sequencing (NGS) were performed for tumor classification. Macroscopically, the tumor was large and locally advanced. It metastasized to the lung without lymph node metastasis. Microscopically, the tumor cells were monotonous with cytological features of both MC and SCC. Immunostains were diffusely positive for p40 and CK5/6, but negative for other lineage markers including CDX2, CK20, and SATB2. The tumor was MMR deficient with loss of MLH1 and PMS2. NGS confirmed BRAF V600E mutation. In comparison, a tissue microarray comprising 64 previously diagnosed MMR deficient CRC was tested for squamous differentiation, and only 1 case showed focal CK5/6 expression, but none was positive for p40. CONCLUSION: MC with exclusive squamous differentiation not only posed significant diagnostic challenges, but also unveiled unrecognized differentiation plasticity in this tumor type.

A naturally occurring brominated furanone covalently modifies and inactivates LuxS.

Halogenated furanones, a group of natural products initially isolated from marine red algae, are known to inhibit bacterial biofilm formation, swarming, and quorum sensing. However, their molecular targets and the precise mode of action remain elusive. Herein, we show that a naturally occurring brominated furanone covalently modifies and inactivates LuxS (S-ribosylhomocysteine lyase, EC 4.4.1.21), the enzyme which produces autoinducer-2 (AI-2).

Challenges in IBD Research: Pragmatic Clinical Research.

Pragmatic clinical research is part of five focus areas of the Challenges in IBD research document, which also includes preclinical human IBD mechanisms, environmental triggers, novel technologies, and precision medicine. The Challenges in IBD research document provides a comprehensive overview of current gaps in inflammatory bowel diseases (IBD) research and delivers actionable approaches to address them. It is the result of multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient centric research prioritization. In particular, the pragmatic clinical research section is focused on highlighting gaps that need to be addressed in order to optimize and standardize IBD care. Identified gaps include: 1) understanding the incidence and prevalence of IBD; 2) evaluating medication positioning to increase therapeutic effectiveness; 3) understanding the utility of therapeutic drug monitoring (TDM); 4) studying pain management; and 5) understanding healthcare economics and resources utilization. To address these gaps, there is a need to emphasize the use of emerging data sources and real-world evidence to better understand epidemiologic and therapeutic trends in IBD, expanding on existing data to better understand how and where we should improve care. Proposed approaches include epidemiological studies in ethnically and geographically diverse cohorts to estimate incidence and prevalence of IBD and impact of diversity on treatment patterns and outcomes. The implementation of new clinical trial design and methodologies will be essential to evaluate optimal medication positioning, appropriate use of TDM in adults and children, and multidisciplinary approaches to IBD pain management and its impact on healthcare resources.

'Millennials': Perceived generational opportunities and intergenerational conflict in Australia.

OBJECTIVE: To investigate the perceptions of intergenerational conflict and lifelong opportunities of the Millennial cohort. METHODS: Data were collected in the Attitudes to Ageing in Australia Study as part of the 2015-2017 national Australian Survey of Social Attitudes (n = 2049, aged 18 and older). Variations by age cohorts and individual characteristics were examined in descriptive analyses and binary logistic regressions. RESULTS: Overall, the majority of people at all ages thought opportunities were worse for younger people than for baby boomers, but few perceived strong conflict between younger and older people. Millennials were the most likely to perceive strong conflict. People rendered 'disadvantaged' by their socio-economic positions were more likely to perceive better opportunities for younger people and strong intergenerational conflict. CONCLUSION: Policymakers should address the barriers that Millennials and other socio-economically disadvantaged people face to improve their lifelong opportunities and address increasing social inequalities in Australia.

The Use of Vedolizumab in Preventing Postoperative Recurrence of Crohn's Disease.

Background: Clinical and endoscopic recurrence are common after surgery in Crohn's disease (CD). Vedolizumab has been increasingly used to treat CD, however, its effectiveness in preventing postoperative recurrence remains unknown. We aimed to investigate the use of vedolizumab in the postoperative setting and compare the risk of recurrence between patients receiving vedolizumab and anti-tumor necrosis factor (TNF)-α agents. Methods: Medical records of CD patients who underwent surgery between April 2014 and June 2016 were reviewed. We first analyzed how frequently vedolizumab is used to prevent postoperative recurrence and compared the patient characteristics with those being treated with other therapies. Furthermore, the rates of endoscopic remission, defined as a simple endoscopic score for CD of 0, at 6-12 months after surgery were compared between patients receiving vedolizumab and anti-TNF-α agents. Clinical, biological, and histologic outcomes such as Harvey-Bradshaw index, C-reactive protein, and histologic inflammation also were compared between the 2 groups. Risks of recurrence were assessed by univariate, multivariate, and propensity score-matched analyses. Results: Among 203 patients that underwent a CD related surgery, 22 patients received vedolizumab as postoperative treatment. There were 58, 38, and 16 patients who received anti-TNF-α agents, immunomodulators, and metronidazole, respectively, whereas 69 patients were monitored without any medication. Patients receiving vedolizumab were young and frequently had perianal disease. Patients postoperatively treated with vedolizumab or anti-TNF-α agents were mostly treated with the same agent pre- and postoperatively. Rate of endoscopic remission at 6-12 months in the vedolizumab group was 25%, which was significantly lower as compared to anti-TNF-α agent group (66%, P = 0.01). Vedolizumab use was the only factor that was associated with an increased risk of endoscopic recurrence on both univariate (odds ratio (OR) 5.58, 95% confidence interval (CI) 1.51-24.3, P = 0.005) and multivariate analysis (OR 5.77, 95%CI 1.71-19.4, P = 0.005). The results were supported by a propensity score-matched analysis demonstrating lower rates of endoscopic remission (25 vs 69%, P = 0.03) in patients treated with vedolizumab as compared to anti-TNF-α agents. Conclusion: In the present retrospective cohort study of real-world experience, vedolizumab was shown to be commonly used as postoperative treatment for CD especially in high risk patients. Multivariate and propensity score-matched analyses showed that postoperative endoscopic recurrence in CD was higher with vedolizumab than with anti-TNF-α agents, but further investigation including controlled trials is required before determining the utility of vedolizumab in preventing postoperative recurrence of CD.

A comparison of the risk of postoperative recurrence between African-American and Caucasian patients with Crohn's disease.

BACKGROUND: Many patients with Crohn's disease will develop complications that require surgery. Recurrence after surgery is common. AIM: To assess racial differences in postoperative recurrence between African-Americans and Caucasians. METHODS: Medical records of Crohn's disease patients who underwent surgery (ileal, colonic, or ileocolonic resection) between June 2014 and June 2016 were reviewed. The primary endpoints were clinical and endoscopic remission at 6-12 months after a Crohn's disease surgery. Secondary outcomes included biological and histologic remission. Risks of recurrence were assessed by univariate, multivariate, and propensity score-matched analysis. RESULTS: Thirty-six African-American and 167 Caucasian patients with Crohn's disease were included for analysis. There was no difference in disease location, disease behaviour, type of surgery performed, and pre- or postoperative medication use between the two groups. The rate of endoscopic remission did not differ between African-American and Caucasian patients (50% vs 42%, P = 0.76), and race did not influence the risk of endoscopic recurrence on univariate, multivariate, or propensity score-matched analysis. The rate of clinical remission was significantly lower in African-American patients compared to Caucasian patients (36% vs. 63%, P = 0.008). African-American race was significantly associated with clinical recurrence on univariate (odds ratio (OR) 6.76, 95% CI 1.50-30.40; P = 0.01), multivariate (OR 5.02, 95% CI 1.60-15.80; P = 0.006), and propensity-matched analysis (68% vs. 32% in Caucasians, P = 0.005). Rates of biologic and histologic remission were similar between the two groups on all analyses. CONCLUSIONS: We found that African-American patients with Crohn's disease have a similar degree of objective measures of mucosal inflammation after surgery including endoscopic recurrence as compared to Caucasian patients. However, African-American race was significantly associated with clinical recurrence, suggesting the presence of ethnic variation in postoperative presentation in Crohn's disease.

Imprecision in patient reports of dizziness symptom quality: a cross-sectional study conducted in an acute care setting.

OBJECTIVE: To quantify precision in patient reports of different attributes of dizziness. PATIENTS AND METHODS: In a cross-sectional study, we interviewed consecutive adult patients with dizziness at 2 urban academic emergency departments (EDs) from July 2, 2005, to August 26, 2005. We excluded patients who were too sick for an interview or who posed a risk to the interviewer. We included those who were "dizzy, light-headed, or off-balance" for 7 days or less or previously "bothered" by the same conditions. We assessed descriptions of dizziness quality elicited by 4 questions in different formats (open-ended, multiresponse, single-choice, and directed). Clarity was assessed qualitatively (vague, circular) and quantitatively (overlap of types of dizziness). Consistency was measured by frequency of mismatched responses across question formats. Reliability was determined by test-retest. RESULTS: Of 1,342 patients screened, 872 (65%) were dizzy, light-headed, or off-balance in the past 7 days (n=677) or previously bothered by dizziness (n=195). Among these 872 patients with dizziness, 44% considered dizziness "the main reason" or "part of the reason" for the ED visit. Open-ended descriptions were frequently vague or circular. A total of 62% selected more than 1 dizziness type on the multiresponse question. On the same question, 54% did not pick 1 or more types endorsed previously in open description. Of 218 patients not identifying vertigo, spinning, or motion on the first 3 questions, 70% confirmed "spinning or motion" on directed questioning. Asked to choose the single best descriptor, 52% picked a different response on retest approximately 6 minutes later. By comparison, reports of dizziness duration and triggers were clear, consistent, and reliable. CONCLUSION: Descriptions of the quality of dizziness are unclear, inconsistent, and unreliable, casting doubt on the validity of the traditional approach to the patient with dizziness. Alternative approaches, emphasizing timing and triggers over type, should be investigated.