Accuracy of ChatGPT in Common Gastrointestinal Diseases: Impact for Patients and Providers.

Since its release in 2022, Chat Generative Pre-Trained Transformer (ChatGPT) became the most rapidly expanding consumer software application in history,1 and its role in medicine is underscored by its potential to enhance patient education and physician-patient communication. Previous studies in gastroenterology and hepatology have focused primarily on the earlier Generative Pre-Trained Transformer 3 (GPT-3) model, with none investigating ChatGPT's ability to generate supportive references for its responses, or its applicability as a physician educational tool.2-6 Our study evaluated the accuracy of the more recent ChatGPT, powered by GPT-4, in addressing frequently asked questions by patients on irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colonoscopy and colorectal cancer (CRC) screening, questions on CRC screening from a physician perspective, and reference generation and suitability.

Real-world effectiveness and safety of ustekinumab and vedolizumab in elderly patients with Crohn's disease.

Studies report favorable efficacy and safety profiles of ustekinumab (UST) and vedolizumab (VDZ) in Crohn's disease (CD), but effectiveness and safety data in elderly patients with CD is lacking. We retrospectively analyzed 78 elderly patients (39 each UST and VDZ) and found that patients on UST and VDZ experienced similar rates of clinical response, remission and mucosal healing despite high proportion of prior biologic exposure. Both UST and VDZ appear to be effective and safe in this at-risk CD population. Further large studies are needed to validate our findings.

Novel Genetic Risk Variants and Clinical Predictors Associated With Primary Sclerosing Cholangitis in Patients With Ulcerative Colitis.

INTRODUCTION: Patients with ulcerative colitis (UC) who are likely to have primary sclerosing cholangitis (PSC) should be identified because PSC can influence UC clinical behavior and outcomes.The aim of this study was to establish a model incorporating clinical and genetic risk predictors that identifies patients with UC at risk of developing PSC. METHODS: We conducted a retrospective case-control study. Inflammatory bowel disease cohorts from multiple institutions were used as discovery and replicate datasets. Quality control criteria, including minor allele frequency, call rates, Hardy-Weinberg equilibrium, cryptic relatedness, and population stratification (through principal components), were used. Discriminative accuracy was evaluated with area under the receiver operating characteristic curve. RESULTS: Fifty-seven of 581 patients (9.8%) with UC had PSC. Multivariate analysis showed that patients with UC-PSC had more extensive disease (odds ratio [OR], 5.42; P = 1.57E-04), younger diagnosis age (younger than 20 years; OR, 2.22; P = 0.02), and less smoking (OR, 0.42; P = 0.02) than those with UC. After linkage disequilibrium pruning and multivariate analyses, 3 SNPs (rs3131621 at 6p21.33; rs9275596 and rs11244 at 6p21.32) at the HLA region were found associated with a 2- to 3-fold increased risk of PSC. Our model demonstrated good discriminatory power (area under the receiver operating characteristic curve, 88%). DISCUSSION: Three variants in HLA (6p21.3) region significantly distinguished patients with UC-PSC from patients with UC alone. Once further validated in an independent large cohort, our model could be used to identify patients with UC at risk of PSC, and it could also help guide disease management.

A novel murine model of pyoderma gangrenosum reveals that inflammatory skin-gut crosstalk is mediated by IL-1ß-primed neutrophils.

Pyoderma gangrenosum (PG) is a debilitating skin condition often accompanied by inflammatory bowel disease (IBD). Strikingly, ~40% of patients that present with PG have underlying IBD, suggesting shared but unknown mechanisms of pathogenesis. Impeding the development of effective treatments for PG is the absence of an animal model that exhibits features of both skin and gut manifestations. This study describes the development of the first experimental drug-induced mouse model of PG with concomitant intestinal inflammation. Topical application of pyrimidine synthesis inhibitors on wounded mouse skin generates skin ulcers enriched in neutrophil extracellular traps (NETs) as well as pro-inflammatory cellular and soluble mediators mimicking human PG. The mice also develop spontaneous intestinal inflammation demonstrated by histologic damage. Further investigations revealed increased circulating low density IL-1ß primed neutrophils that undergo enhanced NETosis at inflamed tissue sites supported by an increase in circulatory citrullinated histone 3, a marker of aberrant NET formation. Granulocyte depletion dampens the intestinal inflammation in this model, further supporting the notion that granulocytes contribute to the skin-gut crosstalk in PG mice. We anticipate that this novel murine PG model will enable researchers to probe common disease mechanisms and identify more effective targets for treatment for PG patients with IBD.

Long-term Outcomes of Perianal Fistulas in Pediatric Crohn's Disease.

BACKGROUND: Approximately 30% of Crohn's disease-related perianal fistulas heal in the adult population with conventional medical and surgical interventions. This healing rate remains unknown in pediatric patients. OBJECTIVE: This study aimed to determine the healing rate of pediatric perianal Crohn's fistulas and identify factors associated with healing. DESIGN: Retrospective case series. SETTING: A quaternary referral center. PATIENTS: Patients aged <18 years with a Crohn's perianal fistula, seen between January 1, 1991, and August 1, 2021, were included in the study. INTERVENTIONS: Multivariable logistic regression to identify factors independently associated with perianal fistula healing. MAIN OUTCOME MEASURES: Healing of Crohn's perianal fistula at the date of last clinical encounter, defined as the clinical note reporting a healed fistula or normal perianal examination. RESULTS: A total of 91 patients aged <18 years with a Crohn's disease-related perianal fistula were identified (59% female, 76% white). The mean (SD) age at Crohn's diagnosis was 12 (±4) years. The mean follow-up after Crohn's diagnosis was 10 (±7) years. Overall, 89% of patients had a perianal fistula, 2% had an anovaginal fistula, and 10% had an ileal pouch-associated fistula. Patients underwent a median (interquartile range) of 2 (1-5) operations. A seton was placed in 60% of patients, 47% underwent abscess drainage, and 44% underwent fistulotomy or fistulectomy. Fistula healing occurred in 71% of patients over a median of 1.3 (0.4-2.5) years. Seven patients (7%) underwent proctectomy, and 3 (3%) underwent ileal pouch excision. After multivariable adjustment, younger age at diagnosis of perianal fistula was associated with an increased likelihood of healing (OR 0.56 for each increased year; 95% CI, 0.34-0.92). LIMITATIONS: Retrospective, single institution. CONCLUSIONS: Over two-thirds of fistulas heal in pediatric Crohn's disease patients with conventional surgical and medical intervention. Younger age at fistula development is associated with an increased likelihood of healing. See Video Abstract at http://links.lww.com/DCR/C185 . RESULTADOS A LARGO PLAZO DE LAS FSTULAS PERIANALES EN LA ENFERMEDAD DE CROHN EN PACIENTES PEDITRICOS: ANTECEDENTES:Aproximadamente el 30% de las fístulas perianales relacionadas con la enfermedad de Crohn se curan en la población adulta con intervenciones médicas y quirúrgicas convencionales. Esta tasa de curación sigue siendo desconocida en pacientes pediátricos.OBJETIVO:Determinar la tasa de curación de las fístulas de Crohn perianales en población pediátrica e identificar los factores asociados con la curación.DISEÑO:Serie de casos retrospectiva.ESCENARIO:Un centro de referencia cuaternario.PACIENTES:Pacientes menores de 18 años con fístula(s) perianal(es) por enfermedad de Crohn, atendidos entre el 1 de enero de 1991 y el 1 de agosto de 2021.INTERVENCIONES:Regresión logística multivariable para identificar factores asociados de forma independiente con la cicatrización de la fístula perianal.PRINCIPALES MEDIDAS DE RESULTADO:Curación de la fístula perianal de Crohn en la fecha del último encuentro clínico, definida como la nota clínica que informa una fístula curada o un examen perianal normal.RESULTADOS:Se identificó un total de 91 pacientes <18 años de edad con una fístula perianal relacionada con la enfermedad de Crohn (59% mujeres, 76% blancos). La edad media (DE) al diagnóstico de Crohn fue de 12 (±4) años. El seguimiento medio tras el diagnóstico de Crohn fue de 10 (±7) años. En general, el 89 % de los pacientes tenía fístula perianal, el 2 % tenía fístula anovaginal y el 10 % de los pacientes tenía fístula asociada a reservorio ileal. Los pacientes fueron sometidos a una mediana (RIC) de 2 (1-5) operaciones. En el 60% de los pacientes se colocó sedal, en el 47% se drenó el absceso y en el 44% se realizó fistulotomía o fistulectomía. La curación de la fístula se produjo en el 71% de los pacientes durante una mediana de 1,3 (0,4-2,5) años. Siete pacientes (7%) se sometieron a proctectomía y 3 (3%) se sometieron a escisión del reservorio ileal. Después del ajuste multivariable, la edad más joven en el momento del diagnóstico de la fístula perianal se asoció con una mayor probabilidad de curación (OR 0,56 por cada año de aumento, IC del 95%, 0,34-0,92).LIMITACIONES:Retrospectivo, institución única.CONCLUSIONES:Más de dos tercios de las fístulas se curan en pacientes pediátricos con enfermedad de Crohn con intervención médica y quirúrgica convencional. Una edad más joven en el momento del desarrollo de la fístula se asocia con una mayor probabilidad de curación. Consulte Video Resumen en http://links.lww.com/DCR/C185 . (Traducción--Dr. Felipe Bellolio ).

Intra-abdominal septic complications after ileocolic resection increases risk for endoscopic and surgical postoperative Crohn's disease recurrence.

BACKGROUND: Postoperative recurrence [POR] of Crohn's disease following ileocolonic resection is common. The impact of immediate postoperative intra-abdominal septic complications [IASC] on endoscopic and surgical recurrence has not been elucidated. AIMS: To evaluate if IASC is associated with an increased risk for endoscopic and surgical POR. METHODS: This was a retrospective study of adult Crohn's disease patients undergoing ileocolonic resection with primary anastomosis between 2009 and 2020. IASC was defined as anastomotic leak or intra-abdominal abscess within 90 days of the date of surgery. Multivariable logistic and Cox proportional hazard modelling were performed to assess the impact of IASC on endoscopic POR [modified Rutgeerts' score ≥ i2b] at index postoperative ileocolonoscopy and long-term surgical recurrence. RESULTS: In 535 Crohn's disease patients [median age 35 years, 22.1% active smokers, 35.7% one or more prior resection] had an ileocolonic resection with primary anastomosis. A minority of patients [N = 47; 8.8%] developed postoperative IASC. In total, 422 [78.9%] patients had one or more postoperative ileocolonoscopies, of whom 163 [38.6%] developed endoscopic POR. After adjusting for other risk factors for postoperative recurrence, postoperative IASC was associated with significantly greater odds (adjusted odds ratio [aOR]: 2.45 [1.23-4.97]; p = 0.01) and decreased time (adjusted hazards ratio [aHR]: 1.60 [1.04-2.45]; p = 0.03] to endoscopic POR. Furthermore, IASC was associated with increased risk (aOR: 2.3 [1.04-4.87] p = 0.03) and decreased survival-free time [aHR: 2.53 [1.31-4.87]; p = 0.006] for surgical recurrence. CONCLUSION: IASC is associated with an increased risk for endoscopic and surgical POR of Crohn's disease. Preoperative optimization to prevent IASC, in addition to postoperative biological prophylaxis, may help reduce the risk for endoscopic and surgical POR.

Computable Phenotype of a Crohn's Disease Natural History Model.

BACKGROUND: Analytic tools to study important clinical issues in complex, chronic diseases such as Crohn's disease (CD) include randomized trials, claims database studies, or small longitudinal epidemiologic cohorts. Using natural language processing (NLP), we sought to define the computable phenotype health state of pediatric and adult CD and develop patient-level longitudinal histories for health outcomes. METHODS: We defined 6 health states for CD using a subjective symptom-based assessment (symptomatic/asymptomatic) and an objective disease state assessment (active/inactive/no testing). Gold standard for the 6 health states was derived using an iterative process during review by our CD experts. We calculated the transition probabilities to estimate the time to transitions between the various health states using nonparametric Kaplan-Meier estimation and a Markov model. Finally, we determined a standard utility measure from clinical patients assigned to different health states. RESULTS: The NLP computable phenotype health state model correctly ascertained the objective test results and symptoms 96% and 85% of the time, respectively, based on a blinded chart evaluation. In our model, >25% of patients who begin as asymptomatic/active transition to symptomatic/active over the following year. For both adult and pediatric CD health states, the utility assessments of a symptomatic/inactive health state closely resembled a symptomatic/active health state. CONCLUSIONS: Our methodology for a computable phenotype health state demonstrates the application of real-world data to define progression and optimal management of a chronic disease such as CD. The application of the model has the potential to lead to a better understanding of the true impact of a therapeutic intervention and can provide long-term cost-effectiveness analyses for a new therapy. HIGHLIGHTS: Using natural language processing, we defined the computable phenotype health state of Crohn's disease and developed patient-level longitudinal histories for health outcomes.Our methodology demonstrates the application of real-world data to define the progression of a chronic disease.The application of the model has the potential to provide better understanding of the true impact of a new therapy.

Mild neoterminal ileal post-operative recurrence of Crohn's disease conveys higher risk for severe endoscopic disease progression than isolated anastomotic lesions.

There are conflicting data assessing the impact of isolated post-operative anastomotic inflammation on future disease progression. The aim of this study was to determine the relative risk of severe disease progression in post-operative Crohn's disease (CD) patients with isolated anastomotic disease. METHODS: Retrospective cohort study of adult CD patients undergoing ileocolonic resection between 2009 and 2020. Patients with a post-operative ileocolonoscopy ≤18 months from surgery and ≥1 subsequent ileocolonoscopy were included. Disease activity was assessed using the modified Rutgeerts' score (RS). Primary outcome was severe endoscopic progression, defined as i3 or i4 disease, on immediate subsequent ileocolonoscopy and during entire post-operative follow-up. Secondary outcome was surgical recurrence. RESULTS: One hundred and ninety-nine CD patients had an ileocolonoscopy ≤18 months from surgery, index RS of i0-i2b and ≥1 subsequent ileocolonoscopy. At index ileocolonoscopy, 34.7% had i0 disease, 16.1% i1, 24.6% i2a and 24.6% i2b. On multivariable logistic regression, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR 5.53; P < 0.001) and i2a disease patients (aOR 2.63; P = 0.03). However, i2a disease did not confer increased risk compared to i0 or i1 disease (P = 0.09). Furthermore, i2b patients experienced severe endoscopic progression significantly earlier than i0 or i1 disease (aHR 4.68; P < 0.001), whereas i2a disease did not differ from i0 or i1 disease (P = 0.25). Surgical recurrence was not associated with index RS i0-i2b (P = 0.86). CONCLUSION: Post-operative ileal disease recurrence, not isolated anastomotic inflammation, confers increased risk for severe endoscopic disease progression. Location of CD recurrence may impact optimal management strategies.

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients.

INTRODUCTION: The efficacy and safety profile of ustekinumab (UST) in Crohn's disease (CD) is favorable; however, data in elderly patients are lacking. We aimed to assess the safety and efficacy of UST in elderly CD. METHODS: We performed a retrospective cohort study of CD patients classified as elderly (age ≥ 65 years at UST initiation) or nonelderly (<65 years) treated at a large, tertiary referral center. Outcomes assessed were clinical (measured by physician global assessment [PGA]) and steroid-free response, remission, adverse events, and postsurgical complications were compared by age category. Multivariable regression modeling and survival analysis was also performed. RESULTS: In total, 117 patients (elderly n = 39, nonelderly n = 78) were included in the study. Elderly patients had predominantly moderate disease (87.2%), while nonelderly had a higher proportion of severe disease activity (44.9%) (p = 0.001), though no differences in baseline endoscopic activity, prior biologic use, or steroid or immunomodulator use at baseline existed (p > 0.05 all). While nearly 90% patients in both groups experienced clinical response to UST, compared to nonelderly, elderly patients were less likely to achieve complete clinical remission (28.2% vs. 52.6%, p = 0.01). On regression modeling, age was not associated with clinical outcomes (p > 0.05 all). Mucosal healing was achieved in 26% elderly and 30% nonelderly patients (p = 0.74). There were no significant differences in infusion reactions (2.6% vs. 6.4%, p = 0.77), infection (5.2% vs. 7.7%, p = 0.7), or postsurgical complications (p = 0.99) by age category. CONCLUSION: UST is safe and effective in elderly CD. Although limited by sample size and retrospective design, such real-world data can inform biologic positioning in this IBD population.

Malignancy risk in individuals with familial adenomatous polyposis receiving biologics and immunomodulators.

Clinicians may be hesitant to prescribe biologics or immunomodulators to individuals with familial adenomatous polyposis (FAP) and comorbid inflammatory disease (CID) because of increased cancer risk. Our aim was to compare the risk of malignancy in FAP individuals with inflammatory bowel (IBD) and/or rheumatic disease that received biologics/immunomodulators to those who did not. Individuals with FAP and CID were included in the study. We compared the incidence of cancer between individuals exposed to biologics/immunomodulators compared to unexposed from the date of diagnosis of comorbid disease till last follow up or death. Hazard ratio (HR) for cancer was computed using Cox regression model and compared by exposure status to biologic/immunomodulators. 25 individuals with FAP and a comorbid inflammatory disease were identified including 9 (36%) with IBD and 16 (64%) with rheumatic disease. 14 (56%) were exposed to a biologic and or immunomodulator. Median duration of biologic/immunomodulator exposure was 48 (2-180) months. 3 (21.4%) in the exposed group compared to 1 (9.1%) in the unexposed group developed cancer with a HR for exposure of 1.92 (CI 0.2-18.5, p = 0.57). Median duration of follow up after the diagnosis of inflammatory disease was 10 (5.5-17.0) years in the exposed and 6 (3.0-15.0) years in the unexposed group. In the exposed group, 1 patient developed gastric and 2 developed colon cancer. One unexposed patient developed medullary thyroid cancer. There is a possible trend of more cancers in the group that received biologics/immunomodulators-but given the small number of patients and p-value, there may be no difference at all. This preliminary finding warrants study in a larger cohort.

Test Characteristics of Cross-sectional Imaging and Concordance With Endoscopy in Postoperative Crohn's Disease.

BACKGROUND & AIMS: Postoperative Crohn's disease (CD) surveillance relies on endoscopic monitoring. The role of cross-sectional imaging is less clear. We evaluated the concordance of cross-sectional enterography with endoscopic recurrence and the predictive ability of radiography for future CD postoperative recurrence. METHODS: We performed a multi-institution retrospective cohort study of postoperative adult patients with CD who underwent ileocolonoscopy and cross-sectional enterography within 90 days of each other following ileocecal resection. Imaging studies were interpreted by blinded, expert CD radiologists. Patients were categorized by presence of endoscopic postoperative recurrence (E+) (modified Rutgeerts' score ≥i2b) or radiographic disease activity (R+) and grouped by concordance status. RESULTS: A total of 216 patients with CD with paired ileocolonoscopy and imaging were included. A majority (54.2%) exhibited concordance (34.7% E+/R+; 19.4% E-/R-) between studies. The plurality (41.7%; n = 90) were E-/R+ discordant. Imaging was highly sensitive (89.3%), with low specificity (31.8%), in detecting endoscopic postoperative recurrence. Intestinal wall thickening, luminal narrowing, mural hyper-enhancement, and length of disease on imaging were associated with endoscopic recurrence (all P < .01). Radiographic disease severity was associated with increasing Rutgeerts' score (P < .001). E-/R+ patients experienced more rapid subsequent endoscopic recurrence (hazard ratio, 4.16; P = .033) and increased rates of subsequent endoscopic (43.8% vs 22.7%) and surgical recurrence (20% vs 9.5%) than E-/R- patients (median follow-up, 4.5 years). CONCLUSIONS: Cross-sectional imaging is highly sensitive, but poorly specific, in detecting endoscopic disease activity and postoperative recurrence. Advanced radiographic disease correlates with endoscopic severity. Patients with radiographic activity in the absence of endoscopic recurrence may be at increased risk for future recurrence, and closer monitoring should be considered.

Mesenteric Excision and Exclusion for Ileocolic Crohn's Disease: Feasibility and Safety of an Innovative, Combined Surgical Approach With Extended Mesenteric Excision and Kono-S Anastomosis.

INTRODUCTION: Ileocolic resection for Crohn's disease traditionally does not include a high ligation of the ileocolic pedicle, and most commonly is performed with a stapled side-to-side ileocolic anastomosis. The mesentery has recently been implicated in the pathophysiology of Crohn's disease. Two techniques have been developed and are associated with reduced postoperative recurrence: the Kono-S anastomosis that excludes diseased mesentery and extended mesenteric excision that resects diseased mesentery. We aimed to assess the technical feasibility and safety of a novel combination of techniques: mesenteric excision and exclusion. TECHNIQUES: This initial report is a single-center descriptive study of consecutive adults who underwent mesenteric excision and exclusion for primary or recurrent ileocolic Crohn's disease from September 2020 to June 2021. Medication exposure and endoscopic balloon dilation before surgery were recorded. Phenotype was classified using the Montreal Classification. Thirty-day outcomes were reported. A video of the mesenteric excision and exclusion including the Kono-S anastomosis is presented. RESULTS: Twenty-two patients with ileocolic Crohn's disease underwent mesenteric excision and exclusion: 100% had strictures, 59% had fistulas, 81% were on biologics, and 27% had previous ileocolic resection(s). Seventy-two percent underwent laparoscopic procedures, a mesenteric defect was closed in 86%, omental flaps were fashioned in 77%, and 3 patients were diverted. Median operative time was 175 minutes. Median postoperative stay was 4 days. At 30 days, there were 2 readmissions for reintervention: 1 seton placement and 1 percutaneous drainage of a sterile collection. There were no cases of intra-abdominal sepsis or anastomotic leak. CONCLUSIONS: Mesenteric excision and exclusion represents an innovative, progressive, and promising approach that appears to be highly feasible and safe. Further study is warranted to determine if mesenteric excision and exclusion is associated with reduced postoperative recurrence of ileocolic Crohn's disease.

Accessory Splenic Artery Causing Massive Gastrointestinal Bleed.

The presentation of an upper gastrointestinal bleed secondary to an accessory splenic artery is a rare circumstance described only in 2 previous case reports. This report is the first to describe an upper gastrointestinal bleed consequent of a submucosal accessory splenic artery arising from the left phrenic artery, requiring multiple endoscopies and endovascular embolization. Vascular anatomic variants can pose a challenge to treatment, especially when they are unknown. This case adds to the limited number of case reports involving accessory splenic arteries.

Hypoalbuminaemia, Not Biologic Exposure, Is Associated with Postoperative Complications in Crohn's Disease Patients Undergoing Ileocolic Resection.

BACKGROUND: There are limited data on the postoperative outcomes in Crohn's disease patients exposed to preoperative ustekinumab or vedolizumab. We hypothesised that preoperative biologic use in Crohn's disease is not associated with postoperative complications after ileocolic resection. METHODS: Crohn's disease patients who underwent ileocolic resection over 2009-2019 were identified at a large regional health system. Preoperative biologic use within 12 weeks of surgery was categorised as no biologic, anti-tumour necrosis factor, vedolizumab, or ustekinumab. The primary endpoint was 90-day intra-abdominal septic complication. Risk factors included preoperative medical therapies, demographics, disease characteristics, laboratory values, and surgical approach. Regression models assessed the association of biologic use with intra-abdominal septic complication. RESULTS: A total of 815 Crohn's disease patients who underwent an ileocolic resection were included [62% no biologic, 31.4% anti-tumour necrosis factor, 3.9% vedolizumab, 2.6% ustekinumab]. Primary anastomosis was performed in 85.9% of patients [side-to-side 48.8%, end-to-side 26%, end-to-end 25%] in primarily a stapled [77.2%] manner. Minimally invasive approach was used in 41.4%. The 90-day postoperative intra-abdominal sepsis rate of 810 patients was 12%, abscess rate was 9.6%, and anastomotic leak rate was 3.2%. Multivariable regression modelling controlling for confounding variables demonstrated that preoperative biologic use with anti-tumour necrosis factor [p = 0.21], vedolizumab [p = 0.17], or ustekinumab [p = 0.52] was not significantly associated with intra-abdominal septic complication. Preoperative albumin < 3.5 g/dl was independently associated with intra-abdominal septic complication (odds ratio [OR] 1.76 [1.03, 3.01]). CONCLUSIONS: In Crohn's disease patients undergoing ileocolic resection, preoperative biologics are not associated with 90-day postoperative intra-abdominal septic complication. Preoperative biologic exposure should not delay necessary surgery.

Adipokine Resistin Levels at Time of Pediatric Crohn Disease Diagnosis Predict Escalation to Biologic Therapy.

BACKGROUND: Hypertrophy of visceral adipose tissue (VAT) is a hallmark of Crohn disease (CD). The VAT produces a wide range of adipokines, biologically active factors that contribute to metabolic disorders in addition to CD pathogenesis. The study aim was to concomitantly evaluate serum adipokine profiles and VAT volumes as predictors of disease outcomes and treatment course in newly diagnosed pediatric patients with CD. METHODS: Pediatric patients ages 6 to 20 years were enrolled, and their clinical data and anthropometric measurements were obtained. Adipokine levels were measured at 0, 6, and 12 months after CD diagnosis and baseline in control patients (CP). The VAT volumes were measured by magnetic resonance imaging or computed tomography imaging within 3 months of diagnosis. RESULTS: One hundred four patients undergoing colonoscopy were prospectively enrolled: 36 diagnosed with CD and 68 CP. The serum adipokine resistin and plasminogen activator inhibitor (PAI)-1 levels were significantly higher in patients with CD at diagnosis than in CP. The VAT volume was similar between CD and CP. Baseline resistin levels at the time of diagnosis in patients with CD who were escalated to biologics was significantly higher than in those not treated using biologic therapy by 12 months (29.8 ng/mL vs 13.8 ng/mL; P = 0.004). A resistin level of ≥29.8 ng/mL at the time of diagnosis predicted escalation to biologic therapy in the first year after diagnosis with a specificity of 95% (sensitivity = 53%; area under the curve = 0.82; P = 0.015 for model with log-scale). There was a significantly greater reduction in resistin (P = 0.002) and PAI-1 (P = 0.010) at the 12-month follow-up in patients on biologics compared with patients who were not treated using biologics. CONCLUSIONS: Serum resistin levels at diagnosis of pediatric CD predict the escalation to biologic therapy at 12 months, independent of VAT volumes. Resistin and PAI-1 levels significantly improved in patients with CD after treatment using biologics compared with those not on biologics. These results suggest the utility of resistin as a predictive biomarker in pediatric CD.

Gastrointestinal manifestations of COVID-19.

Gastrointestinal (GI) symptoms are seen in patients with COVID-19. The prevalence could be as high as 50%, but most studies show ranges from 16% to 33%. Presenting with GI symptoms increases the risk of testing positive for SARs-CoV-2. Approximately 50% of patients with COVID-19 have detectable virus in their stool. Having GI symptoms has been associated with more severe disease. Management of GI symptoms is mainly supportive. Healthcare providers should be aware of the GI manifestations of COVID-19 and perform SARS-CoV-2 testing for patients presenting with digestive changes, especially in those with respiratory symptoms.

Differences in Biologic Utilization and Surgery Rates in Pediatric and Adult Crohn's Disease: Results From a Large Electronic Medical Record-derived Cohort.

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic illness that affects both the pediatric and adult populations with an increasing worldwide prevalence. We aim to identify a large, single-center cohort of patients with CD using natural language processing (NLP) in combination with codified data and extract surgical rates and medication usage from the electronic medical record (EMR). METHODS: Patients with CD were identified from the entire Cleveland Clinic EMR using ICD codes and CD-specific terms identified by NLP to fit a logistic regression model. Cohorts were developed for pediatric-onset (younger than 18 years) and adult-onset (18 years and older) CD. Surgeries were identified using current procedural terminology (CPT) codes and NLP. Crohn's disease-related medications were extracted using physician orders in the EMR. RESULTS: Patients with pediatric-onset (n = 2060) and adult-onset (n = 4973) CD were identified from 2000 to 2017 with a positive predictive value of 98.5%. Rate of CD-related abdominal surgery over time was significantly higher in adult-onset compared with pediatric-onset CD (10-year surgery rate 49.9% vs 37.7%, respectively; P < 0.001). Treatment with biologics was significantly higher in pediatric vs adult-onset CD cohorts (63.6% vs 49.2%; P < 0.001). The overall rate of CD-related abdominal surgery was significantly higher in those who received <6 months of a biologic compared with ≥6 months of a biologic for both cohorts (pediatric 64.1% vs 39.1%, P ≤ 0.001; adult 69.3% vs 56.5%, P ≤ 0.001). Additionally, 60.9% in pediatric-onset CD and 43.5% in adult-onset CD treated with ≥6 months of biologic therapy have not required abdominal surgery. On multivariable analysis, perianal surgery was a significant risk factor for abdominal surgery in both cohorts. CONCLUSION: We used a combination of codified and NLP data to establish the largest, North American, single-center EMR cohort of pediatric- and adult-onset CD patients and determined that biologics are associated with lower rates of surgery over time, potentially altering the natural history of the disease.

Systematic review: medical therapy for fibrostenosing Crohn's disease.

BACKGROUND: Medical therapy and/or endoscopic balloon dilation with intralesional therapies are options for the treatment of small bowel fibrostenotic Crohn's disease (CD). AIM: To perform a systematic review summarising evidence for efficacy of systemic and endoscopic intralesional medical therapy in established small bowel strictures in adult CD patients. METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL and Scopus was conducted. Primary outcomes were rates of surgical resection and repeat endoscopic dilation. Pooled event rates from random effects models across studies with 95% confidence intervals were reported. RESULTS: Ten studies describing systemic medical therapy and eight studies of intralesional injection were included. One randomised controlled trial each for systemic therapy and intrastricture injection were identified. Only observational studies were found for systemic biologic therapies, which exclusively included tumour necrosis factor (TNF) antagonists, while intralesional therapies all involved corticosteroids except for one study that evaluated infliximab. Pooled event rates for surgical resection after systemic and intralesional therapy were 28.3% (95% CI: 18.2%-41.3%) and 18.5% (95% CI: 8.3%-36.2%), respectively over a median follow-up of 23 months (range 5.5-105.8), and 21.8 months (range 5-47). Risk of repeat endoscopic balloon dilation in those with intralesional therapy was 58.3% (95% CI: 36.6%-77.3%) over a median follow-up of 21.8 months (range 5-47). CONCLUSIONS: There are no favoured therapies for patients with stricturing small bowel CD. Data are lacking for ustekinumab and vedolizumab. No endoscopic intralesional medications provided a clear benefit for prevention of repeat EBD or surgery.