Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans.

A mysterious feature of Crohn's disease (CD) is the extra-intestinal manifestation of "creeping fat" (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria.

Disease-specific alterations in the enteric virome in inflammatory bowel disease.

Decreases in the diversity of enteric bacterial populations are observed in patients with Crohn's disease (CD) and ulcerative colitis (UC). Less is known about the virome in these diseases. We show that the enteric virome is abnormal in CD and UC patients. In-depth analysis of preparations enriched for free virions in the intestine revealed that CD and UC were associated with a significant expansion of Caudovirales bacteriophages. The viromes of CD and UC patients were disease and cohort specific. Importantly, it did not appear that expansion and diversification of the enteric virome was secondary to changes in bacterial populations. These data support a model in which changes in the virome may contribute to intestinal inflammation and bacterial dysbiosis. We conclude that the virome is a candidate for contributing to, or being a biomarker for, human inflammatory bowel disease and speculate that the enteric virome may play a role in other diseases.

Blinded Intraoperative Quantitative Indocyanine Green Metrics Associate With Intestinal Margin Acceptance in Colorectal Surgery.

BACKGROUND: Indocyanine green is a useful tool in colorectal surgery. Quantitative values may enhance and standardize its application. OBJECTIVE: To determine whether quantitative indocyanine green metrics correlate with standard subjective indocyanine green perfusion assessment in acceptance or rejection of anastomotic margins. DESIGN: Prospective single-arm, single-institution cohort study. Surgeons viewed subjective indocyanine green images but were blinded to quantitative indocyanine green metrics. SETTING: Tertiary academic center. PATIENTS: Adults undergoing planned intestinal resection. MAIN OUTCOME MEASURES: Accepted perfusion and rejected perfusion of the intestinal margin were defined by the absence or presence of ischemia by subjective indocyanine green and gross inspection. The primary outcomes included quantitative indocyanine green values, maximum fluorescence, and time-to-maximum fluorescence in accepted compared to rejected perfusion. Secondary outcomes included maximum fluorescence and time-to-maximum fluorescence values in anastomotic leak. RESULTS: There were 89 perfusion assessments comprising 156 intestinal segments. Nine segments were subjectively assessed to have poor perfusion by visual inspection and subjective indocyanine green. Maximum fluorescence (% intensity) exhibited higher intensity in accepted perfusion (accepted perfusion 161% [82%-351%] vs rejected perfusion 63% [10%-76%]; p = 0.03). Similarly, time-to-maximum fluorescence (seconds) was earlier in accepted perfusion compared to rejected perfusion (10 seconds [1-40] vs 120 seconds [90-120]; p < 0.01). Increased BMI was associated with higher maximum fluorescence. Anastomotic leak did not correlate with maximum fluorescence or time-to-maximum fluorescence. LIMITATIONS: Small cohort study, not powered to measure the association between quantitative indocyanine green metrics and anastomotic leak. CONCLUSIONS: We demonstrated that blinded quantitative values reliably correlate with subjective indocyanine green perfusion assessment. Time-to-maximum intensity is an important metric in perfusion evaluation. Quantitative indocyanine green metrics may enhance intraoperative intestinal perfusion assessment. Future studies may attempt to correlate quantitative indocyanine green values with anastomotic leak. See Video Abstract . LAS MTRICAS CUANTITATIVAS INTRAOPERATORIAS CIEGAS DEL VERDE DE INDOCIANINA SE ASOCIAN CON LA ACEPTACIN DEL MARGEN INTESTINAL EN LA CIRUGA COLORRECTAL: ANTECEDENTES:El verde de indocianina es una herramienta útil en la cirugía colorrectal. Los valores cuantitativos pueden mejorar y estandarizar su aplicación.OBJETIVO:Determinar si las métricas cuantitativas de verde de indocianina se correlacionan con la evaluación subjetiva estándar de perfusión de verde de indocianina en la aceptación o rechazo de los márgenes anastomóticos.DISEÑO:Estudio de cohorte prospectivo de un solo brazo y de una sola institución. Los cirujanos vieron imágenes subjetivas de verde de indocianina, pero no conocían las métricas cuantitativas de verde de indocianina.AJUSTE:Centro académico terciario.PACIENTES:Adultos sometidos a resección intestinal planificada.PRINCIPALES MEDIDAS DE RESULTADO:La perfusión aceptada y la perfusión rechazada del margen intestinal se definieron por la ausencia o presencia de isquemia mediante verde de indocianina subjetiva y la inspección macroscópica. Los resultados primarios fueron los valores cuantitativos de verde de indocianina, la fluorescencia máxima y el tiempo hasta la fluorescencia máxima en la perfusión aceptada en comparación con la rechazada. Los resultados secundarios incluyeron la fluorescencia máxima y el tiempo hasta alcanzar los valores máximos de fluorescencia en la fuga anastomótica.RESULTADOS:Se realizaron 89 evaluaciones de perfusión, comprendiendo 156 segmentos intestinales. Se evaluó subjetivamente que 9 segmentos tenían mala perfusión mediante inspección visual y verde de indocianina subjetiva. La fluorescencia máxima (% de intensidad) mostró una mayor intensidad en la perfusión aceptada [Perfusión aceptada 161% (82-351) vs Perfusión rechazada 63% (10-76); p = 0,03]. De manera similar, el tiempo hasta la fluorescencia máxima (segundos) fue más temprano en la perfusión aceptada en comparación con la rechazada [10 s (1-40) frente a 120 s (90-120); p < 0,01]. Aumento del índice de masa corporal asociado con una fluorescencia máxima más alta. La fuga anastomótica no se correlacionó con la fluorescencia máxima ni con el tiempo hasta la fluorescencia máxima.LIMITACIONES:Estudio de cohorte pequeño, sin poder para medir la asociación entre las mediciones cuantitativas del verde de indocianina y la fuga anastomótica.CONCLUSIÓN:Demostramos que los valores cuantitativos ciegos se correlacionan de manera confiable con la evaluación subjetiva de la perfusión de verde de indocianina. El tiempo hasta la intensidad máxima es una métrica importante en la evaluación de la perfusión. Las métricas cuantitativas de verde de indocianina pueden mejorar la evaluación de la perfusión intestinal intraoperatoria. Los estudios futuros pueden intentar correlacionar los valores cuantitativos de verde de indocianina con la fuga anastomótica. (Traducción-Dr. Yolanda Colorado).

Comparative Persistence of Non-tumor Necrosis Factor (TNF) vs. TNF Antagonists for Post-operative Prophylaxis in Crohn's Disease (CD).

BACKGROUND: The comparative safety and effectiveness of available biologics for post-operative prophylaxis in Crohn's disease (CD) is uncertain. Drug persistence may serve as a real-world proxy for tolerability and effectiveness. We evaluated the comparative persistence of non-TNF and TNF antagonists for post-operative prophylaxis and their comparative effectiveness for preventing early endoscopic post-operative recurrence (POR). METHODS: We conducted a single-center, retrospective study of surgically naïve CD subjects undergoing ileocecal or small bowel resection between 1/1/2000 and 12/31/2021 and prescribed a biologic for post-operative prophylaxis. We compared the risk of prophylaxis failure (requiring recurrent surgery or discontinuation of therapy due to persistent POR despite optimized drug level or dose escalation, immunogenicity, and/or adverse event) and early endoscopic POR (Rutgeert's score ≥ i2 within 15 months postoperatively) between non-TNF and TNF antagonist prophylaxis using Cox proportional hazard and logistic regression, respectively, adjusting for demographic and disease characteristics. RESULTS: The study included 291 subjects (81% TNF antagonists). After multivariable adjustment, non-TNF antagonist prophylaxis was associated with a significantly lower risk of prophylaxis failure than TNF antagonists (hazard ratio 0.26; 95% confidence interval (CI) [0.13-0.53]). Prophylaxis with non-TNF and TNF antagonists had similar risk of early endoscopic POR (odds ratio 0.66; 95% CI [0.32-1.36]). Stratifying the non-TNF antagonists by anti-integrin and anti-IL12/23 yielded similar results. CONCLUSION: In a cohort of surgically naïve CD subjects prescribed a biologic for post-operative prophylaxis, non-TNF antagonists had greater persistence than TNF antagonists with similar risk for early endoscopic POR. If confirmed by large, prospective studies, these findings can inform post-operative management strategies in CD.

Risk Factors for Microscopic Disease Positivity at Ileocolic Resection Margins for Crohn's Disease.

INTRODUCTION: Interest in microscopic margin positivity during surgical resection of medical-refractory Crohn's disease has been renewed with multiple recent studies showing an association between microscopic margin positivity with disease recurrence. Our aim was to determine risk factors for microscopic margin disease positivity following ileocolic resection (ICR). MATERIALS AND METHODS: A prospectively-maintained database of patients with Crohn's disease undergoing ICR at a tertiary-referral center was queried. Margin positivity was defined as the presence of cryptitis, erosion, transmural inflammation with lymphoid aggregates, or architectural distortion at either ileal (proximal) or colonic (distal) margins. RESULTS: Amongst 584 patients, 97 patients had a positive microscopic margin (17%) of which 46% had a positive proximal margin, 17% had a positive distal margin, and 13% had both positive and distal margins. Using multivariable logistic regression analysis, index ICR was associated with less odds of positive margin (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.24-0.89, p=0.02), and granuloma presence was associated with increased odds (OR 2.26, 95% CI 1.23-4.21, p=0.01). CONCLUSION: We found that repeat ileocolic resection and granuloma presence were predictors of microscopic margin disease.

Genetic coding variant in complement factor B (CFB) is associated with increased risk for perianal Crohn's disease and leads to impaired CFB cleavage and phagocytosis.

OBJECTIVE: Perianal Crohn's disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in Complement Factor B (CFB). DESIGN: Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed. Serological and clinical variables were analysed by regression analyses. Risk allele of rs4151651 was introduced into human CFB plasmid by site-directed mutagenesis. Binding of recombinant G252 or S252 CFB to C3b and its cleavage was determined in cell-free assays. Macrophage phagocytosis in presence of recombinant CFB or serum from CFB risk, or protective CD or healthy subjects was assessed by flow cytometry. RESULTS: Perianal complications were associated with colonic involvement, OmpC and ASCA serology, and serology quartile sum score. We identified a genetic association for pCD (rs4151651), a non-synonymous SNP (G252S) in CFB, in all three cohorts. Recombinant S252 CFB had reduced binding to C3b, its cleavage was impaired, and complement-driven phagocytosis and cytokine secretion were reduced compared with G252 CFB. Serine 252 generates a de novo glycosylation site in CFB. Serum from homozygous risk patients displayed significantly decreased macrophage phagocytosis compared with non-risk serum. CONCLUSION: pCD-associated rs4151651 in CFB is a loss-of-function mutation that impairs its cleavage, activation of alternative complement pathway, and pathogen phagocytosis thus implicating the alternative complement pathway and CFB in pCD aetiology.

Prospective Cohort Study to Investigate the Safety of Preoperative Tumor Necrosis Factor Inhibitor Exposure in Patients With Inflammatory Bowel Disease Undergoing Intra-abdominal Surgery.

BACKGROUND & AIMS: Whether preoperative treatment of inflammatory bowel disease (IBD) with tumor necrosis factor inhibitors (TNFis) increases the risk of postoperative infectious complications remains controversial. The primary aim of this study was to determine whether preoperative exposure to TNFis is an independent risk factor for postoperative infectious complications within 30 days of surgery. METHODS: We conducted a multicenter prospective observational study of patients with IBD undergoing intra-abdominal surgery across 17 sites from the Crohn's & Colitis Foundation Clinical Research Alliance. Infectious complications were categorized as surgical site infections (SSIs) or non-SSIs. Current TNFi exposure was defined as use within 12 weeks of surgery, and serum was collected for drug-level analyses. Multivariable models for occurrence of the primary outcome, any infection, or SSI were adjusted by predefined covariates (age, sex, preoperative steroid use, and disease type), baseline variables significantly associated (P < .05) with any infection or SSI separately, and TNFi exposure status. Exploratory models used TNFi exposure based on serum drug concentration. RESULTS: A total of 947 patients were enrolled from September 2014 through June 2017. Current TNFi exposure was reported by 382 patients. Any infection (18.1% vs 20.2%, P = .469) and SSI (12.0% vs 12.6%, P = .889) rates were similar in patients currently exposed to TNFis and those unexposed. In multivariable analysis, current TNFi exposure was not associated with any infection (odds ratio, 1.050; 95% confidence interval, 0.716-1.535) or SSI (odds ratio, 1.249; 95% confidence interval, 0.793-1.960). Detectable TNFi drug concentration was not associated with any infection or SSI. CONCLUSIONS: Preoperative TNFi exposure was not associated with postoperative infectious complications in a large prospective multicenter cohort.

Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

BACKGROUND & AIMS: There are limited data on outcomes of biologic therapy in Hispanic patients with inflammatory bowel diseases (IBDs). We compared risk of hospitalization, surgery, and serious infections in Hispanic vs non-Hispanic patients with IBD in a multicenter, electronic health record-based cohort of biologic-treated patients. METHODS: We identified adult patients with IBD who were new users of biologic agents (tumor necrosis factor α [TNF-α] antagonists, ustekinumab, vedolizumab) from 5 academic institutions in California between 2010 and 2017. We compared the risk of all-cause hospitalization, IBD-related surgery, and serious infections in Hispanic vs non-Hispanic patients using 1:4 propensity score matching and survival analysis. RESULTS: We compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% TNF-α antagonist-treated; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% TNF-α antagonist-treated; 27% with prior biologic exposure). After propensity score matching, Hispanic patients were younger (37 ± 15 vs 40 ± 16 y; P = .02) and had a higher burden of comorbidities (Elixhauser index, >0; 37% vs 26%; P < .01), without any differences in patterns of medication use, burden of inflammation, and hospitalizations. Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01-1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07-3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99-3.05). CONCLUSIONS: In a multicenter, propensity score-matched cohort of biologic-treated patients with IBD, Hispanic patients experienced higher rates of hospitalization, surgery, and serious infections. Future studies are needed to investigate the biological, social, and environmental drivers of these differences.

Comparative Safety and Effectiveness of Biologic Therapy for Crohn's Disease: A CA-IBD Cohort Study.

BACKGROUND & AIMS: We compared the safety and effectiveness of tumor necrosis factor α (TNF-α) antagonists vs vedolizumab vs ustekinumab in patients with Crohn's disease (CD) in a multicenter cohort (CA-IBD). METHODS: We created an electronic health record-based cohort of adult patients with CD who were initiating a new biologic agent (TNF-α antagonists, ustekinumab, vedolizumab) from 5 health systems in California between 2010 and 2017. We compared the risk of serious infections (safety) and all-cause hospitalization and inflammatory bowel disease-related surgery (effectiveness) between different biologic classes using propensity score (PS) matching. RESULTS: As compared with TNF-α antagonists (n = 1030), 2:1 PS-matched, ustekinumab-treated patients with CD (n = 515) experienced a lower risk of serious infections (hazard ratio [HR], 0.36; 95% CI, 0.20-0.64), without any difference in the risk of hospitalization (HR, 0.99; 95% CI, 0.89-1.21) or surgery (HR, 1.08; 95% CI, 0.69-1.70). Compared with vedolizumab (n = 221), 1:1 PS-matched, ustekinumab-treated patients with CD (n = 221) experienced a lower risk of serious infections (HR, 0.20; 95% CI, 0.07-0.60), without significant differences in risk of hospitalization (HR, 0.76; 95% CI, 0.54-1.07) or surgery (HR, 1.42; 95% CI, 0.54-3.72). Compared with TNF-α antagonists (n = 442), 2:1 PS-matched, vedolizumab-treated patients with CD (n = 221) had a similar risk of serious infections (HR, 1.53; 95% CI, 0.84-2.78), hospitalization (HR, 1.32; 95% CI, 0.98-1.77), and surgery (HR, 0.63; 95% CI, 0.27-1.47). High comorbidity burden, concomitant opiate use, and prior hospitalization were associated with serious infections and hospitalization in biologic-treated patients with CD. CONCLUSION: In a multicenter cohort of biologic-treated patients with CD, ustekinumab was associated with a lower risk of serious infections compared with TNF-α antagonists and vedolizumab, without any differences in risk of hospitalization or surgery. The risk of serious infections was similar for TNF-α antagonists vs vedolizumab.

CORE-IBD: A Multidisciplinary International Consensus Initiative to Develop a Core Outcome Set for Randomized Controlled Trials in Inflammatory Bowel Disease.

BACKGROUND & AIMS: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease. METHODS: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists. RESULTS: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities. CONCLUSIONS: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC.

Management of Perianal Crohn's Disease.

Perianal Crohn's disease affects 25%-35% of patients with Crohn's disease and has proven to be one of the most difficult complications of the disease to treat. Patients with perianal Crohn's disease have lower health-related quality of life scores typically related to pain and fecal incontinence. In addition, patients with perianal Crohn's disease have higher rates of hospitalizations, surgeries, and overall healthcare costs. A multidisciplinary approach is necessary for the successful management of Crohn's disease with perianal fistula. Medical management is required to treat the underlying immune dysregulation to heal the luminal inflammation and the inflammation within the fistula tracts. Current options for medical therapy include biologics, dual therapy with thiopurines, therapeutic drug monitoring, and a close follow-up. Surgical management is critical to drain abscesses before immunosuppressive therapy and place setons when appropriate. Once the patient's inflammatory burden is well managed, definitive surgical therapies including fistulotomies, advancement flaps, and ligation of intersphincteric fistula tract procedures can be considered. Most recently, the use of stem cell therapy in the treatment of perianal fistula has given new hope to the cure of perianal fistula in Crohn's disease. This review will outline the most current data in the medical and surgical management of perianal Crohn's disease.

Long-term Outcomes and Factors Predicting Outcome of IPAA When Used Intentionally for Well-Defined Crohn's Disease.

BACKGROUND: Crohn's disease is considered a contraindication for IPAA. In our prior study, when IPAA was used intentionally for well-defined Crohn's disease, we found a high incidence of recurrent disease with a low incidence of pouch failure. OBJECTIVE: This study aimed to replicate these findings in a larger cohort over a longer period. DESIGN: Retrospective review of a prospective IBD registry. SETTINGS: Large IBD referral center. PATIENTS: Patients with preoperative colorectal Crohn's disease requiring surgery were included in the study. INTERVENTION: IPAA. MAIN OUTCOME MEASURES: Long-term Crohn's disease recurrence, pouch failure, and pouch function. RESULTS: Forty-six patients were identified. Crohn's disease was diagnosed on the basis of perianal disease (n = 18; 39%), small-bowel disease (n = 16; 35%), noncaseating granuloma (n = 10; 22%), and discontinuous inflammation (colorectal skip lesions) (n = 11; 24%). After a median follow-up of 93 (7-291) months, 22 patients (48%) developed recurrent Crohn's disease based on afferent limb disease (n = 14; 30%) or pouch fistulizing disease (n = 8; 18%). Only 4 patients (9%) developed pouch failure. No clinical factor was associated with Crohn's disease recurrence. Young age at the time of surgery and short duration of disease before IPAA were associated with pouch fistula recurrence ( p = 0.003 and p = 0.03, respectively). Most patients (86%) reported excellent continence, with no urgency (67%) and median stool frequency of 6 (range, 3-9) per day. LIMITATION: Retrospective nature and relatively small sample size. CONCLUSION: This largest reported series examining the intentional use of IPAA in Crohn's disease showed a high (48%) incidence of postoperative Crohn's disease with a low (9%) incidence of pouch failure. Young age and short disease course before surgery were risk factors for poor outcomes. Highly motivated patients with colorectal Crohn's disease may consider IPAA and avoid a definitive ileostomy. See Video Abstract at http://links.lww.com/DCR/C171 . RESULTADOS A LARGO PLAZO Y FACTORES PREDICTORES DE RESULTADOS DE LA ANASTOMOSIS ILEOANAL CON RESERVORIO CUANDO SE USA INTENCIONALMENTE PARA LA ENFERMEDAD DE CROHN BIEN DEFINIDA: ANTECEDENTES: La enfermedad de Crohn (EC) se considera una contraindicación para la anastomosis ileoanal con reservorio (IPAA). Nuestro estudio previo de IPAA cuando fue usada intencionalmente para EC bien definida mostró una alta incidencia de enfermedad recurrente con una baja incidencia de falla del reservorio.OBJETIVO: Replicar estos hallazgos en una cohorte más grande durante un período más largo.DISEÑO: Revisión retrospectiva de una base de datos prospectiva de enfermedad inflamatoria intestinal.ESCENARIO: Un centro grande de referencia de EII.PACIENTES: EC colorrectal preoperatoria con necesidad de tratamiento quirúrgico.INTERVENCIÓN: Anastomosis ileoanal con reservorio.RESULTADOS PRINCIPALES: Recurrencia de EC a largo plazo, falla del reservorio y función del reservorio.RESULTADOS: Cuarenta y seis pacientes fueron identificados. El diagnóstico de EC se basó en enfermedad perianal (n = 18; 39%), enfermedad del intestino delgado (n = 16; 35%), granuloma no caseificante (n = 10; 22%) e inflamación discontinua (lesiones salteadas colorrectales) (n = 11; 24%). Después de una mediana de seguimiento de 93 (7-291) meses, 22 (48 %) pacientes desarrollaron EC recurrente debido a enfermedad del asa aferente (n = 14; 30%) o enfermedad fistulizante del reservorio (n = 8; 18%). Solo 4 (9%) pacientes desarrollaron falla del reservorio. Ningún factor clínico se asoció con la recurrencia de EC. La edad joven en el momento de la cirugía y la corta duración de la enfermedad antes de IPAA se asociaron con la recurrencia de la fístula del reservorio ( p = 0.003 y p = 0.03, respectivamente). El recuento de plaquetas preoperatorio más alto fue la única característica clínica significativamente asociada con el fracaso del reservorio ( p = 0.02). La mayoría de los pacientes (86%) reportaron una continencia excelente, sin urgencia (67%) y una mediana de frecuencia evacuatoria de 6 (rango, 3-9) por día.LIMITACIONES: Naturaleza retrospectiva y tamaño de muestra relativamente pequeño.CONCLUSIÓN: Esta serie, la más grande reportada que examina el uso intencional de IPAA en la EC mostró una incidencia alta (48Rectal Cancer: Clinical and Molecular Predictors of a Complete Response to Total Neoadjuvant Therapy%) de EC posoperatoria con una incidencia baja (9%) de falla del reservorio. La edad joven y el curso corto de la enfermedad antes de la cirugía fueron factores de riesgo para pobres resultados. Pacientes altamente motivados con EC colorrectal pueden considerar una IPAA y evitar una ileostomía permanente. Consulte Video Resumen en http://links.lww.com/DCR/C171 . (Traducción-Dr. Jorge Silva Velazco ).

Prospective Randomized Trial of Immediate Postoperative Use of Regular Diet Versus Clear Liquid Diet in Major Colorectal Surgery.

BACKGROUND: Enhanced recovery protocols are becoming standard practice after major colorectal surgery. An increasing body of evidence suggests that early feeding should be encouraged; however, whether a clear liquid diet or solid diet should be given immediately after surgery is undetermined. OBJECTIVE: Evaluate whether regular diet was superior to clear liquid diet beginning on postoperative day 0 after major colorectal surgery. DESIGN: Superiority trial design. SETTING: Urban tertiary center. PATIENTS: Consecutive patients undergoing abdominal colorectal surgery from September 2017 to June 2018. INTERVENTIONS: Eligible patients received either 1) clear liquid diet on postoperative day 0 with advancement to regular diet on postoperative day 1 or 2) regular diet on postoperative day 0 and continuing for the duration of patients' recovery. MAIN OUTCOME MEASURES: The primary end point was diet tolerance, defined by the absence of vomiting by postoperative day 2. RESULTS: A total of 105 patients were randomly assigned with 53 in the clear liquid diet group and 52 in the regular diet group. All randomly assigned patients were included in the analysis. The rate of diet tolerance by postoperative day 2 was similar between groups. Rates of ileus, antiemetic usage, narcotic usage, time to return of bowel function, and pain/nausea/bloating scores were similar between the 2 groups. Significantly more patients in the clear liquid diet group (91%) tolerated their diet than did the regular diet group (71%) on postoperative day 0 ( p = 0.01). LIMITATIONS: Diet tolerance was only monitored during inpatient stay. The rate of postoperative ileus was difficult to capture as its clinical definition encompassed a wide range of symptoms. CONCLUSIONS: Regular diet immediately after abdominal colorectal surgery was not superior to a clear liquid diet with respect to diet tolerance by postoperative day 2. Furthermore, starting regular diet on postoperative day 0 was not associated with any outcome benefits compared to clear liquid diet. ENSAYO PROSPECTIVO ALEATORIZADO SOBRE EL USO POSTOPERATORIO INMEDIATO DE UNA DIETA NORMAL VERSUS UNA DIETA DE LQUIDOS CLAROS EN CIRUGAS MAYORES COLORRECTALES: ANTECEDENTES:Los protocolos de recuperación mejorada se están convirtiendo en una práctica estandarizada tras una cirugía mayor colorrectal. La creciente evidencia sugiere la alimentación temprana debe ser estimulada, sin embargo, no se ha determinado si se debe administrar una dieta de líquidos claros o una dieta sólida inmediatamente después de la cirugía.OBJETIVO:Evaluar si la dieta regular fue superior a la dieta de líquidos claros a partir del día cero del postoperatorio tras una cirugía mayor colorrectal.DISEÑO:Diseño de prueba de superioridad.AJUSTE:Centro terciario urbano.PACIENTES:Pacientes consecutivos sometidos a cirugía abdominal colorrectal desde septiembre de 2017 hasta junio de 2018INTERVENCIONES:Los pacientes elegibles recibieron ya sea 1) dieta de líquidos claros en el día 0 del postoperatorio con avance a la dieta regular en el día 1 del postoperatorio o 2) dieta regular en el día 0 del postoperatorio y continuaron durante la recuperación de los pacientes.PRINCIPALES MEDIDAS DE RESULTADO:El criterio principal de valoración fue la tolerancia a la dieta, definida por la ausencia de vómitos en el segundo día posoperatorio.RESULTADOS:Un total de 105 pacientes fueron aleatorizados con 53 en el grupo de dieta de líquidos claros y 52 en el grupo de dieta regular. Todos los pacientes aleatorizados fueron incluidos en el análisis. La tasa de tolerancia a la dieta en el segundo día postoperatorio fue similar entre los grupos. Las tasas de íleo, del uso de antieméticos, del uso de narcóticos, del tiempo de recuperación de la función intestinal y puntajes de dolor/náuseas/distensión abdominal fueron similares entre los dos grupos. Significativamente más pacientes en el grupo de dieta de líquidos claros (91%) toleraron su dieta comparada al grupo de dieta regular (71%) en el día postoperatorio 0 ( p = 0,01).LIMITACIONES:La tolerancia a la dieta solo fue monitorizada durante la estadía hospitalaria. La tasa de íleo postoperatorio fue difícil de registrar debido a que su definición clínica abarcaba una amplia variedad de síntomas.CONCLUSIONES:La dieta regular inmediatamente después de la cirugía abdominal colorrectal no fue superior a una dieta de líquidos claros con respecto a la tolerancia de la dieta en el día 2 del postoperatorio. Además, comenzar una dieta regular el día cero del postoperatorio no se asoció con ningún beneficio en los resultados en comparación con la dieta de líquidos claros. (Traducción-Dr. Osvaldo Gauto ).

Efficacy of Anal Sphincter Division During Fistulotomy in Anal Fissure-Associated Fistula.

BACKGROUND: A subset of chronic anal fissures beget focal infection, leading to concomitant fistula. The optimal management of fissure-associated fistula is unknown. OBJECTIVE: This study aimed to characterize healing rates and effects of fistulotomy in fissure-associated fistula. DESIGN: Retrospective study. SETTING: Urban tertiary center. PATIENTS: Adults who underwent fistulotomy for a fistula associated with a chronic anal fissure were included in the study. However, those with Crohn's disease, a history of lateral internal sphincterotomy, and a fistula not amenable to fistulotomy were excluded. INTERVENTIONS: Patients were managed with fistulotomy. Fissures were otherwise managed conservatively with a step-up approach. MAIN OUTCOME MEASURES: The primary end point was healing, defined as resolution of symptoms and both fistula and fissure wounds within 1 year. Subgroup analysis compared those who underwent subcutaneous fistulotomy (group A) with those who underwent fistulotomy involving anal sphincter fibers (group B). RESULTS: Twenty-four of 38 patients (63%) healed with a median overall follow-up of 6.6 months (4.2-14.1). The overall median time to healing was 4.4 months (2.2-6.0). No clinical or pathologic factors predicted healing. In subgroup analysis, overall subcutaneous fistulotomy healing rates were nonstatically lower at 46% (6/13) compared to fistulotomy involving anal sphincter fibers at 72% (18/25; p = 0.16). There was no difference in time to healing (subcutaneous fistulotomy, 6.7 mo [5.2-8.4] vs fistulotomy involving sphincter, 5.1 mo [2.1-7.0]; p = 0.36). LIMITATIONS: The limitations include treatment bias, with increased utilization of chemical sphincter-relaxing agents in those who did not heal. Findings are not applicable to complex fistulas, Crohn's disease, or atypical fissures. CONCLUSIONS: Patients presenting with chronic fissure and associated subcutaneous, intersphincteric, or low transphincteric fistula are successfully managed with fistulotomy. Patients with a subcutaneous fistula tract exhibited nonstatistically significantly lower rates of healing. See Video Abstract at http://links.lww.com/DCR/C145 . EFICACIA DE LA DIVISIN ESFINTRICA DURANTE LA FISTULOTOMA EN CASOS DE FSTULA ASOCIADA A FISURA ANAL: ANTECEDENTES: Ciertos subgrupos de fisuras anales crónicas ocasionan infección localizada, induciendo la aparición de una fístula anal concomitante. Se desconoce el manejo óptimo de la fístula concomitante a una fisura anal.OBJETIVO: Se trata de caracterizar las tasas de curación y el efecto de la fistulotomía en el tratamiento de la fístula concomitante a la fisura anal.DISEÑO: Estudio retrospectivo.EMPLAZAMIENTO: Centro terciario urbano.PACIENTES: Adultos sometidos a fistulotomía por una fístula concomitante a una fisura anal crónica. Se excluyeron la enfermedad de Crohn, el antecedente de una esfinterotomía lateral interna y las fístulas no susceptibles de fistulotomía.INTERVENCIONES: Los pacientes fueron manejados con una fistulotomía clasica. Por lo demás, las fisuras se trataron de forma conservadora con un enfoque médico escalonado.PRINCIPALES MEDIDAS DE RESULTADO: El criterio principal de valoración fué la cura definitiva, determinada como la resolución completa de los síntomas y de las heridas tanto de la fístula como de la fisura en el plazo de un año. El análisis de los subgrupos comparó los que se sometieron a una fistulotomía subcutánea (grupo A) versus una fistulotomía que involucró las fibras del esfínter anal interno (grupo B).RESULTADOS: 24/38 pacientes (63%) curaron con una mediana de seguimiento global de 6,6 meses (4,2-14,1). El tiempo medio general de curación fue de 4,4 meses (2,2-6,0). Ningún factor clínico o patológico predijo la cura. En el análisis de subgrupos, las tasas generales de cura de la fistulotomía subcutánea no fueron estadísticamente más bajas de 46 % (6/13) comparados con la fistulotomía que involucró las fibras del esfínter anal interno en 72 % (18/25; p = 0,16). No hubo diferencia en el tiempo de cicatrización [fistulotomía subcutánea 6,7 meses (5,2-8,4) conparada a la fistulotomía y esfínterotomía parcial interna a 5,1 meses (2,1-7,0); p = 0,36].LIMITACIONES: Sesgo del tratamiento, con mayor utilización de agentes químicos relajantes de la musculatura esfínteriana en aquellos pacientes que no sanaron. No aplicable a fístulas complejas, enfermedad de Crohn o fisuras atípicas.CONCLUSIÓNES: Los pacientes que presentan fisura crónica y fístula subcutánea, inter-esfintérica o trans-esfintérica baja concomitante se manejan con éxito con una fistulotomía. Los pacientes con un trayecto de fístula subcutánea exhibieron tasas de curación más bajas y no estadísticamente significativas. Consulte Video Resumen en http://links.lww.com/DCR/C145 . (Traducción-Dr. Xavier Delgadillo ).

Preoperative CT Indices Predict Nonreach Before IPAA.

BACKGROUND: IPAA aims to restore continence to patients after total proctocolectomy. However, some patients have inadequate small-bowel mesenteric length to achieve reconstruction. No preoperative risk stratification tools of native anatomy exist. OBJECTIVE: We report CT-guided measurements of anatomic landmarks to predict nonreach before IPAA. DESIGN: This is a single-institution retrospective analysis of a prospective database. SETTING: This study was conducted at Cedars-Sinai between January 2007 and December 2021. PATIENTS: Patients with IBD undergoing a 2- or 3-stage IPAA with a preoperative abdominal CT using either an enterography protocol or IV contrast sufficient to visualize mesenteric vasculature were included in the study. CT mesenteric indices were assessed, including total length (representing length required for the pouch to reach the anal canal), mesenteric length (inherent length of small-bowel mesentery), and mobilization length (the difference between total length and mesenteric length). MAIN OUTCOME MEASURES: The primary outcome was IPAA nonreach. The secondary outcomes were association of clinical variables and CT mesenteric indices. RESULTS: Six of 59 patients (10%) experienced nonreach. Mobilization length was longer in the nonreach group by 5.8 cm ( p = 0.01), and mesenteric length was shorter by 3.5 cm ( p = 0.04). Mobilization length ≥17 cm provided 100% sensitivity and 69% specificity (OR 1.46, area under the curve 0.84, p = 0.004) for nonreach. Similarly, a mesenteric length <14.6 cm demonstrated 100% sensitivity and 49% specificity for IPAA nonreach (area under the curve 0.75, p = 0.03). LIMITATIONS: The retrospective nature of the study precluded a standardized imaging protocol. External validation will be required because of the small sample size. CONCLUSIONS: CT-based measurements of length, specifically mesenteric and mobilization length, predict nonreach before IPAA. This method is noninvasive, readily available, and may be useful for preoperative patient counseling and operative planning. See Video Abstract at http://links.lww.com/DCR/C140 . LOS NDICES DE TOMOGRAFA COMPUTARIZADA PREOPERATORIA PREDICEN LA AUSENCIA DE ALCANCE ANTES DE LA ANASTOMOSIS DEL RESERVORIO ILEALANAL: ANTECEDENTES:La anastomosis del reservorio ileoanal tiene como objetivo restaurar la continencia en los pacientes después de una proctocolectomía total. Sin embargo, algunos pacientes tienen una longitud mesentérica del intestino delgado inadecuada para lograr la reconstrucción. No existen herramientas de estratificación del riesgo preoperatorio de la anatomía nativa.OBJETIVO:Informamos mediciones guiadas por tomografía computarizada de puntos de referencia anatómicos para predecir la falta de alcance antes de la anastomosis ileoanal con reservorio.DISEÑO:Este es un análisis retrospectivo de una sola institución de una base de datos prospectiva.AJUSTE:Este estudio se realizó en Cedars-Sinai entre Enero de 2007 y Diciembre de 2021.PACIENTES:Pacientes con enfermedad inflamatoria intestinal que se someten a una anastomosis anal con reservorio ileal en 2 o 3 etapas con una tomografía computarizada abdominal preoperatoria utilizando un protocolo de enterografía o contraste intravenoso suficiente para visualizar la vasculatura mesentérica. Se evaluaron los índices mesentéricos de tomografía computarizada, incluida la longitud total (que representa la longitud requerida para que la bolsa alcance el canal anal), la longitud mesentérica (longitud inherente del mesenterio del intestino delgado) y la longitud de movilización (la diferencia entre la longitud total y la longitud mesentérica).PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue falta de alcance de la anastomosis del reservorio ileoanal. Los resultados secundarios fueron la asociación de variables clínicas y los índices mesentéricos de tomografía computarizada.RESULTADOS:Seis de 59 (10%) pacientes experimentaron falta de alcance. La longitud de movilización fue mayor en el grupo sin alcance en 5,8 cm ( p = 0,01) y la longitud mesentérica fue menor en 3,5 cm ( p = 0,04). La longitud de movilización ≥17 cm proporcionó una sensibilidad del 100% y una especificidad del 69% (OR 1,46, AUC 0,84, p = 0,004) para la falta de alcance. De manera similar, una longitud mesentérica <14,6 cm demostró una sensibilidad del 100% y una especificidad del 49% para la falta de alcance de la anastomosis del reservorio ileoanal (AUC 0,75, p = 0,03).LIMITACIONES:La naturaleza retrospectiva del estudio impidió un protocolo de imágenes estandarizado. Se requerirá una validación externa debido al pequeño tamaño de la muestra.CONCLUSIONES:Las mediciones de longitud basadas en tomografía computarizada, específicamente la longitud mesentérica y de movilización, predicen la falta de alcance antes de la anastomosis anal con bolsa ileo. Este método no es invasivo, está fácilmente disponible y puede ser útil para el asesoramiento preoperatorio del paciente y la planificación quirúrgica. Consulte el Video Resumen en https://links.lww.com/DCR/C140 . (Traducción-Dr. Yesenia Rojas-Khalil ).

High Complication Rate After Early Ileostomy Closure: Early Termination of the Short Versus Long Interval to Loop Ileostomy Reversal After Pouch Surgery Randomized Trial.

BACKGROUND: In patients with ulcerative colitis who undergo IPAA, a diverting ileostomy is used to diminish the severity of anastomotic complications. Typically, the ileostomy is closed after an interval of 2 to 4 months. The safety of earlier closure of the ileostomy after pouch surgery is unknown. OBJECTIVE: This study aimed to compare postoperative outcomes in patients randomly assigned to early (7-12 days) or late (≥8 weeks) ileostomy closure after ileal pouch construction. DESIGN: This was a multicenter, prospective randomized trial. SETTING: The study was conducted at colorectal surgical units at select United States hospitals. PATIENTS: Adults with ulcerative colitis who underwent 2- or 3-stage proctocolectomy with IPAA were included. MAIN OUTCOME MEASURES: The primary outcomes included Comprehensive Complication Index at 30 days after ileostomy closure. The secondary outcomes included complications, severe complications, reoperations, and readmissions within 30 days of ileostomy closure. RESULTS: The trial was stopped after interim analysis because of a high rate of complications after early ileostomy closure. Among 36 patients analyzed, 1 patient (3%) had unplanned proctectomy with end-ileostomy. Of the remaining 35 patients, 28 patients (80%) were clinically eligible for early closure and underwent radiologic assessment. There were 3 radiologic failures. Of the 25 remaining patients, 22 patients (88%) were randomly assigned to early closure (n = 10) or late closure (n = 12), and 3 patients were excluded. Median Comprehensive Complication Index was 14.8 (0-54) and 0 (0-23) after early and late closure (p = 0.02). One or more complications occurred in 7 patients (70%) after early closure and in 2 patients (17%) after late closure (p = 0.01)' and complications were severe in 3 patients (30%) after early closure and 0 patients after late closure (p = 0.04). Reoperation was required in 1 patient (10%) and 0 patients (p = 0.26) after early closure and readmission was required in 7 patients (70%) and 1 patient (8%) after late closure (p = 0.003). LIMITATIONS: This study was limited by early study closure and selection bias. CONCLUSIONS: Early closure of a diverting ileostomy in patients with ulcerative colitis who underwent IPAA is associated with an unacceptably high rate of complications. See Video Abstract at http://links.lww.com/DCR/C68. ALTA TASA DE COMPLICACIONES DESPUS DEL CIERRE PRECOZ DE LA ILEOSTOMA TERMINACIN TEMPRANA DEL ENSAYO ALEATORIZADO DE INTERVALO CORTO VERSUS LARGO PARA LA REVERSIN DE LA ILEOSTOMA EN ASA DESPUS DE LA CIRUGA DE RESERVORIO ILEAL: ANTECEDENTES:En los pacientes con colitis ulcerosa que se someten a una anastomosis del reservorio ileoanal, se utiliza una ileostomía de derivación para disminuir la gravedad de las complicaciones de la anastomosis. Por lo general, la ileostomía se cierra después de un intervalo de 2 a 4 meses. Se desconoce la seguridad del cierre más temprano de la ileostomía después de la cirugía de reservorio.OBJETIVO:Comparar los resultados posoperatorios en pacientes asignados al azar al cierre temprano (7-12 días) o tardío (≥ 8 semanas) de la ileostomía después de la construcción de un reservorio ileal.DISEÑO:Este fue un ensayo aleatorizado prospectivo multicéntrico.ESCENARIO:El estudio se realizó en unidades quirúrgicas colorrectales en hospitales seleccionados de los Estados Unidos.PACIENTES:Se incluyeron adultos con colitis ulcerosa que se sometieron a proctocolectomía en 2 o 3 tiempos con anastomosis ileoanal con reservorio.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios incluyeron el Índice Integral de Complicaciones a los 30 días después del cierre de la ileostomía. Los resultados secundarios incluyeron complicaciones, complicaciones graves, reoperaciones y readmisiones dentro de los 30 días posteriores al cierre de la ileostomía.RESULTADOS:El ensayo se detuvo después del análisis interino debido a una alta tasa de complicaciones después del cierre temprano de la ileostomía. Entre los 36 pacientes analizados, 1 (3%) tuvo una proctectomía no planificada con ileostomía terminal. De los 35 pacientes restantes, 28 (80%) fueron clínicamente elegibles para el cierre temprano y se sometieron a una evaluación radiológica. Hubo 3 fracasos radiológicos. De los 25 pacientes restantes, 22 (88 %) se asignaron al azar a cierre temprano (n = 10) o tardío (n = 12) y 3 fueron excluidos. La mediana del Índice Integral de Complicaciones fue de 14,8 (0-54) y 0 (0-23) después del cierre temprano y tardío (p = 0,02). Una o más complicaciones ocurrieron en 7 pacientes (70%) después del cierre temprano y 2 (17%) pacientes después del cierre tardío (p = 0,01) y fueron graves en 3 (30%) y 0 pacientes, respectivamente (p = 0,04). Requirieron reintervención en 1 (10%) y 0 (p = 0,26) y reingreso en 7 (70%) y 1 (8%) pacientes (p = 0,003).LIMITACIONES:Este estudio estuvo limitado por el cierre temprano del estudio; sesgo de selección.CONCLUSIONES:El cierre temprano de una ileostomía de derivación en pacientes con colitis ulcerosa con anastomosis de reservorio ileoanal se asocia con una tasa inaceptablemente alta de complicaciones. Consulte Video Resumen en http://links.lww.com/DCR/C68. (Traducción-Dr. Felipe Bellolio).

Feasibility of opioid-free surgery for inflammatory bowel disease.

AIM: Patients undergoing colorectal surgery or those with inflammatory bowel disease (IBD) are particularly at risk for opioid-related complications and progression to long-term opioid dependence. The aim of this work is to explore the real-world possibility of perioperative opioid avoidance in colorectal surgery and IBD. METHOD: We conducted a retrospective analysis of patients aggregated from two prospective studies on multimodal postoperative pain control conducted at a single tertiary referral centre. All patients underwent major colorectal surgery with bowel resection. Patients with chronic preoperative opioid use were excluded. Opioid use was measured in oral morphine equivalents (OME) each postoperative day (POD) and cumulatively for the first 72 h. RESULTS: Our cohort of 209 patients included 148 (71%) with IBD and 61 (29%) non-IBD patients. IBD patients required significantly more opioids cumulatively over the first 72 postoperative hours compared with non-IBD patients [median OME 77 mg (interquartile range 33-148 mg) vs. 4 mg (interquartile range 17-82 mg), respectively; p = 0.001]. Five percent of IBD patients achieved opioid-free postoperative pain control during the entire 72 h postoperative period compared with 12% of non-IBD patients. Only 7% of IBD patients avoided opioid use on POD 1 compared with 20% of non-IBD patients (p = 0.02); however the number of IBD patients increased to 16% on POD 2 then 40% on POD 3, closely resembling the non-IBD cohort at 49% (p = 0.22). CONCLUSION: In the era of modern enhanced recovery protocols and minimally invasive techniques, we show that early postoperative opioid avoidance is feasible in a limited number of IBD patients after colorectal surgery.

SupportiNg operAtive Photographic documentation in ileocolonic CROHN's disease surgery: The SNAPCROHN study.

BACKGROUND: There are reported variations in the intraoperative management of Crohn's disease. This consensus statement aimed to develop a standardised protocol for photographic documentation of intraoperative findings and critical procedural steps in ileocolonic Crohn's disease surgery. METHODS: Colorectal surgeons with a specialist interest in minimally invasive surgery and inflammatory bowel disease were invited as committee members to develop a survey on the use of photo-documentation in Crohn's disease surgery. A 15 item survey was developed on ethical considerations and applications of photo-documentation in audit and quality control, research, and training. RESULTS: There was strong agreement on the potential application of intraoperative photo-documentation in Crohn's disease for training, research, quality control and tertiary referrals. Reviewers agreed that intraoperative staging required photo-documentation of strictures, skip lesions, perforations, fat wrapping and mesenteric disease. The necessary steps to be photo-documented were very specific to Crohn's disease surgery, such as views of anastomosis and strictureplasties, and extent of resection(s). CONCLUSIONS: Our consensus statement identified several items for appropriate intraoperative photo-documentation in Crohn's disease surgery, to be used as an adjunct to accurate annotation of intraoperative findings and procedures.

Altered Intestinal ACE2 Levels Are Associated With Inflammation, Severe Disease, and Response to Anti-Cytokine Therapy in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: The host receptor for severe acute respiratory syndrome coronavirus 2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small bowel (SB). Our aim was to identify factors influencing intestinal ACE2 expression in Crohn's disease (CD), ulcerative colitis (UC), and non-inflammatory bowel disease (IBD) controls. METHODS: Using bulk RNA sequencing or microarray transcriptomics from tissue samples (4 SB and 2 colonic cohorts; n = 495; n = 387 UC; n = 94 non-IBD), we analyzed the relationship between ACE2 with demographics and disease activity and prognosis. We examined the outcome of anti-tumor necrosis factor and anti-interleukin-12/interleukin-23 treatment on SB and colonic ACE2 expression in 3 clinical trials. Univariate and multivariate regression models were fitted. RESULTS: ACE2 levels were consistently reduced in SB CD and elevated in colonic UC compared with non-IBD controls. Elevated SB ACE2 was also associated with demographic features (age and elevated body mass index) associated with poor coronavirus disease 2019 outcomes. Within CD, SB ACE2 was reduced in patients subsequently developing complicated disease. Within UC, colonic ACE2 was elevated in active disease and in patients subsequently requiring anti-tumor necrosis factor rescue therapy. SB and colonic ACE2 expression in active CD and UC were restored by anti-cytokine therapy, most notably in responders. CONCLUSIONS: Reduced SB but elevated colonic ACE2 levels in IBD are associated with inflammation and severe disease, but normalized after anti-cytokine therapy, suggesting compartmentalization of ACE2-related biology in SB and colonic inflammation. The restoration of ACE2 expression with anti-cytokine therapy might be important in the context of severe acute respiratory syndrome coronavirus 2 infection and potentially explain reports of reduced morbidity from coronavirus disease 2019 in IBD patients treated with anti-cytokines.

Effect of Obesity on Risk of Hospitalization, Surgery, and Serious Infection in Biologic-Treated Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

INTRODUCTION: Obesity is variably associated with treatment response in biologic-treated patients with inflammatory bowel diseases (IBD). We evaluated the association between obesity and risk of hospitalization, surgery, or serious infections in patients with IBD in new users of biologic agents in a large, multicenter, electronic health record (EHR)-based cohort (CA-IBD). METHODS: We created an EHR-based cohort of adult patients with IBD who were new users of biologic agents (tumor necrosis factor [TNF-α] antagonists, ustekinumab, and vedolizumab) between January 1, 2010, and June 30, 2017, from 5 health systems in California. Patients were classified as those with normal body mass index (BMI), overweight, or obese based on the World Health Organization classification. We compared the risk of all-cause hospitalization, IBD-related surgery, or serious infections among patients with obesity vs those overweight vs those with normal BMI, using Cox proportional hazard analyses, adjusting for baseline demographic, disease, and treatment characteristics. RESULTS: Of 3,038 biologic-treated patients with IBD (69% with Crohn's disease and 76% on TNF-α antagonists), 28.2% (n = 858) were overweight, and 13.7% (n = 416) were obese. On a follow-up after biologic initiation, obesity was not associated with an increased risk of hospitalization (adjusted hazard ratio [aHR] vs normal BMI, 0.90; [95% confidence interval, 0.72-1.13]); IBD-related surgery (aHR, 0.62 [0.31-1.22]); or serious infection (aHR, 1.11 [0.73-1.71]). Similar results were observed on stratified analysis by disease phenotype (Crohn's disease vs ulcerative colitis) and index biologic therapy (TNF-α antagonists vs non-TNF-α antagonists). DISCUSSION: In a multicenter, EHR-based cohort of biologic-treated patients with IBD, obesity was not associated with hospitalization, surgery, or serious infections. Further studies examining the effect of visceral obesity on patient-reported and endoscopic outcomes are needed.