Outcomes In Crohn's Disease Patients Research Articles

The impact of crohn's disease on patients undergoing total knee arthroplasty.

The knee joint remains the most affected joint in extra-intestinal manifestations of Crohn's disease (CD). Given the increasing prevalence of CD and overall demand for total knee arthroplasty (TKA), it is likely that an increasing number of patients with CD will require TKA. The purpose of this study was to assess the inpatient postoperative complication in patients with CD undergoing TKA. We queried the Nationwide Inpatient Sample (NIS) database between the years of 2016 to 2019, including a total of 558,371 patients who underwent primary TKA. Among these, 1461 were in the CD group and 556,910 were in the non-CD group (controls). Data pertaining to demographics, length of stay (LOS), total healthcare cost, mortality, and in-hospital complications (blood loss anemia, blood transfusion, periprosthetic infection, periprosthetic dislocation, periprosthetic mechanical complication, acute renal failure, myocardial infarction, pneumonia, pulmonary embolism, deep vein thrombosis, superficial/deep surgical site infection, and wound dehiscence) were compared between the two groups. Patients diagnosed with CD had higher postoperative complications such as blood loss anemia (OR: 1.22, 95% CI: 1.07-1.39, p = 0.004), periprosthetic infection (OR: 1.80, 95% CI: 1.23-2.63, p = 0.006), and the need for blood transfusion (OR: 1.447, 95% CI: 1.01-2.06, p = 0.044) in comparison to the control group. In-hospital mortality and acute renal failure were similar in both groups. The CD group had a significantly prolonged LOS (2.54 vs. 2.35 days, p < 0.001). No statistically significant difference was noted concerning in-hospital charges between the two groups. CD patients undergoing TKA experienced increased LOS and postoperative complications. However, these complications were minor and did not affect total hospital cost. Further prospective cohort studies could build upon the findings described to continue to maximize outcomes in CD patients undergoing TKA, which might extend to other cohorts.

Preoperative Exclusive Enteral Nutrition Is Associated With Reduced Skin and Soft Tissue and Intra-abdominal Infections in Patients With Crohn's Disease Undergoing Intestinal Surgery: Results from a Meta-Analysis.

Malnutrition is an independent risk factor for adverse postoperative outcomes and is common among patients with Crohn's disease (CD). The objective of this meta-analysis was to precisely quantify the association of preoperative exclusive enteral nutrition (EEN) and total parenteral nutrition (TPN) with surgical outcomes in patients undergoing intestinal surgery for CD. PubMed, Embase, and Scopus were queried for comparative studies evaluating the impact of preoperative nutritional support on postoperative outcomes in patients undergoing surgery for CD. Random effects modeling was used to compute pooled estimates of risk difference. Heterogeneity was assessed using I2. Fourteen studies, all nonrandomized cohort studies, met inclusion criteria for studying EEN. After pooling data from 14 studies (874 EEN treated and 1044 control patients), the relative risk of intra-abdominal septic complications was decreased 2.1-fold in patients receiving preoperative EEN (relative risk 0.47, 95% confidence interval [CI], 0.35-0.63, I2 = 0.0%). After pooling data from 9 studies (638 EEN treated and 819 control patients), the risk of skin and soft tissue infection was decreased 1.6-fold (relative risk 0.63; 95% CI, 0.42-0.94, I2 = 42.7%). No significant differences were identified in duration of surgery, length of bowel resected, or operative blood loss. Among the 9 studies investigating TPN, no significant differences were identified in infectious outcomes. Preoperative nutritional optimization with EEN was associated with reduced risk of infectious complications in CD patients undergoing intestinal surgery. Preoperative nutritional support with EEN should be considered for optimizing outcomes in CD patients requiring bowel resection surgery.

Residual abnormalities on CTE predict adverse outcomes in Crohn's disease with endoscopic healing

BackgroundResidual abnormalities on computed tomography enterography (CTE) in Crohn's disease (CD) with endoscopic healing (EH) may have prognostic implications and affect therapeutic strategy. MethodsCD patients with EH who underwent CTE between March 2015 and June 2022 were enrolled. CTE findings of the terminal ileum and the most severe segment of colon at the time of EH were assessed respectively for each patient. Cox regression analysis and Kaplan-Meier curves were used to evaluate the association between residual abnormalities and adverse outcomes. ResultsA total of 140 patients (217 digestive segments) were included. Mesenteric edema (hazard ratio [HR] = 3.61, 95% CI = 1.81–7.20, P<0.001), fibrofatty proliferation (HR = 3.40, 95% CI = 1.97–5.85, P<0.001) and active small bowel inflammation (HR = 2.74, 95% CI = 1.59–4.71, P<0.001) were risk factors for clinical relapse. Furthermore, we built a scoring system using the three parameters. Radiologic score ≥ 1 was the best threshold to predict clinical relapse (HR = 4.56, 95% CI = 2.54–8.19, P<0.001) and it was validated in different outcomes. ConclusionThe scoring system based on three residual abnormalities on CTE can predict adverse outcomes in CD patients with EH.

Impact of the first wave of COVID-19 on Crohn's disease after the end of "zero-COVID" policy in China.

The incidence and severity of coronavirus disease 2019 (COVID-19) among Crohn's disease (CD) patients are unknown in China. This study aimed to clarify the clinical courses and outcomes of CD patients in the first COVID-19 wave after the end of "zero-COVID" policy in China. Clinical characteristics, including vaccination doses and medications of 880 CD patients from a prospective cohort were collected for analysis. Of the enrolled patients (n = 880) who underwent nucleic acid or antigen testing for COVID-19 from Dec 7, 2022, to Jan 7, 2023, 779 (88.5%) were infected with COVID-19. Among the infected patients, 755 (96.9%) were mild, 14 (1.8%) were moderate, one patient with leukemia died of cerebral hemorrhage (mortality, 0.1%) and only 9 (1.2%) were asymptomatic. Fever, cough, headache and appetite loss were the most frequently observed symptoms in general, respiratory, neurological and gastrointestinal manifestations, respectively. The age and disease duration were significantly higher (40/32, 5.6/3.6, all p < 0.05) in moderate patients than those in mild patients. All other clinical characteristics, including CD activity and medication exposure, showed no significant differences between the above two groups. Furthermore, no significant difference in vaccination or comorbidities was observed between the two groups. Most CD patients contracted the Omicron infection and experienced mild disease courses in the first COVID-19 wave attack after China ended the "zero-COVID" policy irrespective of vaccination dose or comorbidities.

Has the therapeutical ceiling been reached in Crohn's disease randomized controlled trials? A systematic review and meta-analysis.

The availability of biological agents for inflammatory bowel disease has increased over the past years. In this systematic review and meta-analysis, we aimed to explore time trends in clinical response and clinical remission rates in Crohn's disease (CD) patients treated with biologics while discussing the need for new strategies. MEDLINE, Cochrane, and ISI Web of Science databases were searched for randomized placebo-controlled trials with biological agents in moderate-to-severe CD patients. Sub-group and meta-regression analyses compared treatment and placebo by calculating the pooled odds ratios of clinical remission and clinical response, across time categories and publication year. We also estimated the proportion of patients achieving clinical remission and clinical response by comparing both groups according to the publication year. Twenty-five trials were included in the systematic review, which enrolled 8879 patients between 1997 and 2022. The clinical remission and clinical response odds, in induction and maintenance, have been constant over time, as no statistically significant differences were found between time categories (interaction p-values: clinical remission [induction, p=0.19; maintenance, p=0.24]; clinical response [induction, p=0.43; maintenance, p=0.59]). In meta-regression analyses, publication year did not influence these outcomes (clinical remission [induction, OR 1.01{95% CI 0.97-1.05}, p=0.72; clinical response [induction, OR 1.01{95% CI 0.97-1.04]; p=0.63; maintenance, OR 1.03{95% CI 0.98-1.07}; p=0.21]), with the exception of clinical remission in maintenance studies, which presented a decreased effect (odds ratio 0.97{95% CI 0.94-1.00}, p=0.03]). Our review highlights that the odds of clinical outcomes in CD patients receiving biological treatment relative to placebo have been stable in the last decades.

P364 Presence of malnutrition adversely affects short-term clinical outcomes in a sample of patients with Crohn's disease (CD)

Abstract Background Malnutrition in patients with CD has been suggested to affect the disease course, leading to more frequent flare-ups, disease-related complications and longer hospitalizations. The aim of the present study was to assess the effect of malnutrition on several clinical outcomes of patients with CD. Methods Data regarding medical history, disease classification and basic anthropometric characteristics were collected at baseline. Disease activity was assessed endoscopically and using the Harvey-Bradshaw Index (HBI&amp;lt;5 indicates remission). Malnutrition was assessed with the GLIM (Global Leadership Initiative on Malnutrition) criteria and SGA (Subjective Global Assessment). Patients were followed-up at 6 and 12 months and clinical outcomes (need for hospitalization, corticosteroids and antibiotics’ use, change of biologic agents, surgery) were recorded. Results At baseline 237 patients (54.8% males, 41.2±14.1 years, 37.2% with active disease) were evaluated. Prevalence of malnutrition at baseline was 13.5% and 22.9% based on GLIM and SGA, respectively, and was higher in active disease compared to remission (GLIM: 25% vs. 6.7%, p&amp;lt;0.001, SGA: 41.9% vs. 11.5%, p&amp;lt;0.001). Outcomes of 237 patients were recorded at 6 months and of 233 at 12 months. Presence of malnutrition at baseline, according to GLIM criteria, was associated with an increased likelihood of need for intensification or change of biologic agent (OR: 2.66, 95% CI: 1.14-6.24, p=0.02], surgery (OR: 3.73, 95% CI: 1.02-13.70, p=0.04) and overall adverse outcome (OR: 2.33, 95% CI: 0.99-5.49, p=0.05) after adjustment for age, sex, disease location and disease activity at baseline. Similar results were observed when malnutrition was diagnosed with SGA only for need for intensification or change of biologic agent (OR: 5,78 (1,52, 21,92), p=0,01] after adjustment for age, sex, disease location and disease activity at baseline. No statistically significant associations were observed between presence of malnutrition (either diagnosed with GLIM criteria or SGA) and disease-related outcomes at 12 months. Conclusion Presence of malnutrition was associated with short-term (within 6 months) adverse clinical outcomes, such as need to intensify the therapeutic regimen, need for surgical interventions due to disease complications and a worse overall disease outcome in CD patients. No effect of malnutrition diagnosis on the examined clinical outcomes was observed at 12 months of follow-up.

Incidence and impact of venous thromboembolism in hospitalized patients with Crohn-disease

Abstract Background Prevalence of Crohn's disease (CD) is high in North America and in Europe ranging between 100 and 350 patient-cases per 100,000 citizens. CD is characterized by chronic inflammation with a progressive course and is often associated with different intestinal as well as extra-intestinal complications. CD is associated with both, other inflammatory diseases such as ankylosing spondylitis and psoriasis as well as venous thromboembolism (VTE). CD causes an activation of coagulation system, which might be the main reason for an increased risk of thromboembolic complications. Beside previous study results regarding higher VTE risk of patients with CD in comparison to the general population, particularly, data on impact of VTE on survival and risk factors for the occurrence of VTE in CD are sparse. Purpose The objectives of our study were to provide evidence about the current and past prevalence of VTE events in hospitalized patients with CD and to investigate the impact of VTE on outcomes of CD patients. Methods The German nationwide inpatient sample was screened for patients admitted due to CD (ICD-code K50) (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005–2018, own calculations). CD hospitalizations were stratified for VTE and risk factors for VTE and impact of VTE on in-hospital case-fatality rate were investigated. Results Overall, 333,975 patients-cases with hospital admissions due to CD were counted in Germany (median age 38.0 [IQR 24.0–52.0] years, 56.0% females) during the observational period between 2005 and 2018. VTE rate increased slightly from 0.6% to 0.7% (β 0.000097 [95% CI 0.000027 to 0.000167], P=0.007) from 2005 to 2018 and with age-decade of life (β 0.0017 [95% CI 0.0016 to 0.0019], P&amp;lt;0.001). In total, 0.7% (n=2,295) of the CD inpatients had an event of VTE. Patients with VTE were in median 12 years older (49.0 [34.0–62.0] vs. 37.0 [24.0–52.0] years, P&amp;lt;0.001) and CD colon-manifestations were more prevalent in those patients (32.0% vs. 27.7%, P&amp;lt;0.001). Age ≥70 years, obesity, colon-involvement, cancer, surgery, thrombophilia, and heart failure were strongly associated with higher risk of VTE in CD patients. In-hospital death occurred 15-times more often in CD with VTE than without (4.5% vs. 0.3%, P&amp;lt;0.001). VTE was independently associated with substantially increased in-hospital case-fatality rate (OR 9.31 [95% CI 7.54–11.50], P&amp;lt;0.001). Conclusions VTE is a life-threatening event in hospitalized CD patients associated with 9.3-fold increased case-fatality rate. Older age, obesity, colon involvement, cancer, surgery, thrombophilia and heart failure were strong risk factors for VTE in patients with CD. Funding Acknowledgement Type of funding sources: None.

Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn's disease under infliximab therapy.

BACKGROUNDInfliximab trough level (ITL) severely affects therapeutic outcomes of Crohn’s disease (CD) patients under infliximab (IFX). Recently, frontier research has focused on identifying ITL based on different therapeutic targets. Although previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy, studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and overseas. AIMTo explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance therapy.METHODSCD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were collected. ITL and inflammatory biomarkers were continuously monitored during the therapy. The Step I study was conducted from weeks 14 to 54 of IFX treatment. The Step II study was conducted from weeks 54 to 108 of IFX treatment. Endoscopic outcomes were defined as endoscopic activity (Crohn’s disease endoscopic index of severity score > 2 points or Rutgeerts score > i1) and endoscopic remission (Crohn’s disease endoscopic index of severity score ≤ 2 points or Rutgeerts ≤ i1). Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage.RESULTSAt week 14, low ITL [odds ratio (OR) = 0.666, 95% confidence interval (CI): 0.514-0.862, P < 0.01] and high fecal calprotectin (FCP) level (OR = 1.002, 95%CI: 1.001-1.004, P < 0.01) increased the risk of endoscopic activity at week 54. At week 54, low ITL (OR = 0.466, 95%CI: 0.247-0.877, P < 0.01) and high C-reactive protein (CRP) level (OR = 1.590, 95%CI: 1.007-2.510, P < 0.01) increased the risk of endoscopic activity at week 108. At week 14, ITL ≤ 5.60 μg/mL [area under the curve (AUC) = 0.83, 95%CI: 0.73-0.90, P < 0.001] and FCP > 238 μg/g (AUC = 0.82, 95%CI: 0.72-0.89, P < 0.001) moderately predicted endoscopic activity at week 54. ITL ≤ 5.60 μg/mL in combination with FCP > 238 μg/g indicated 82.0% possibility of endoscopic activity. At week 54, ITL ≤ 2.10 μg/mL (AUC = 0.85, 95%CI: 0.72-0.93, P < 0.001) and CRP > 3.00 mg/L (AUC = 0.73, 95%CI: 0.60-0.84, P = 0.012) moderately predicted moderate endoscopic activity at week 108. ITL ≤ 2.10 μg/mL in combination with CRP > 3.00 mg/L indicated 100.0% possibility of endoscopic activity. From weeks 14 to 54 of IFX treatment, patients with ITL > 5.60 μg/mL had higher rate of endoscopic relapse free survival than those with ITL ≤ 5.60 μg/mL (95.83% vs 46.67%). From weeks 54 to 108 of IFX treatment, patients with ITL > 2.10 μg/mL had higher rate of endoscopic survival free relapsed rate than those with ITL ≤ 2.10 μg/mL (92.68% vs 30.77%).CONCLUSIONCombination of ITL, CRP, and FCP contribute to long-term endoscopic prognosis monitoring. During IFX maintenance treatment, low ITL, high CRP level, and high FCP level were independent risk factors of CD patients with clinical remission in adverse endoscopy outcomes within 1-year follow-up.

Increased colonic expression of ACE2 associates with poor prognosis in Crohn\u2019s disease

The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn's disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course. We examined the expression of colonic ACE2 in 67 adult CD and 14 NIBD control patients using RNA-seq and quantitative (q) RT-PCR. We validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan–Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients. Colonic ACE2 expression was significantly higher in a subset of adult CD patients which was defined as the ACE2-high CD subset. IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of CD diagnosis, and a Cox regression analysis found that high ACE2 levels is an independent risk factor for surgery (OR 2.17; 95% CI, 1.10–4.26; p = 0.025). Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that can impact CD disease-related outcomes.

Postoperative outcomes after preoperative ustekinumab exposure in patients with Crohn's disease: a systematic review and meta-analysis.

BackgroundRecent studies have reported conflicting data on the risk of postoperative complications in patients with Crohn’s disease (CD) exposed to ustekinumab (UST) preoperatively. We performed a systematic review and meta-analysis to better assess and quantify the risk of postoperative complications in this population undergoing major abdomino-pelvic surgery.MethodsWe conducted a comprehensive search of multiple electronic databases and conference proceedings (earliest inception through October 2020) to identify studies that reported the postoperative outcomes in CD patients with preoperative UST exposure. We estimated and compared the pooled rates of postoperative complications, including intra-abdominal sepsis, surgical site infection, any infection, any adverse event, readmission, and reoperation.ResultsA total of 5 studies were included in the analysis. The last dose of the drug was at most 16 weeks prior to abdomino-pelvic surgery. A total of 172 CD patients (61% female; median age 35 years) were included. The pooled rate of any complication and any infectious complications was 23.5% (95% confidence interval [CI] 16-33.1) and 20.2% (95%CI 10.3-35), respectively. There was no difference in rates of intra-abdominal sepsis between the UST group (7.2%, 95%CI 3-16.4) and the anti-tumor necrosis factor (TNF) group (11.9%, 95%CI 5.9-22.5; P = 0.4). The rates of readmission and reoperation in the UST group were 17.4% (95%CI 7.9-34) and 14.6% (95%CI 9-22.7), respectively.ConclusionsThe postoperative complication rate in patients with preoperative UST exposure may be similar to that for anti-TNF medication. Preoperative exposure to UST does influence postoperative complication risk. Future prospective studies are needed to validate these findings.

Characteristics and predictors of postoperative outcome of Crohn disease patients requiring abdominal surgery: a series of 1 048 cases from a single inflammatory bowel disease centre

Objective: To examine the clinical characteristics, the potential relative factors for postoperative abdominal septic complications, and prognosis factors of surgical recurrence of Crohn disease (CD) patients after the first surgery. Methods: All the CD patients from Department of General Surgery, Jinling Hospital, Medical School of Nanjing University who had undergone at least one abdominal surgery from January 2007 to December 2017 were included for retrospective analysis. Hospital records were reviewed for information on clinical characteristics. Relative factors of postoperative abdominal septic complications were accessed by Logistic regression models, and prognosis factors of surgical recurrence were accessed by Cox proportional hazards regression models. Results: There were 1 048 patients included (733 males and 315 females), accounting for 1 513 operations. The age was 31(17) years and the length of resected small bowel was 30.0(40.0) cm at the first resection, 20.0(35.0) cm at the second resection, and 20.0(23.5) cm at the third resection. The length of resected small bowel was 25.0(40.0) cm at any resection. At the first abdominal surgery, 70.99%(744/1 048) patients were aged between 17 and 40 years, 66.98%(702/1 048) patients had ileocolonic disease, and 60.40%(633/1 048) patients had penetrating behavior. Penetrating behavior (OR=8.594, 95%CI: 3.397 to 21.740, P<0.01) and current smoking status (OR=2.671, 95%CI: 1.044 to 6.832, P=0.040) were significantly associated with an increased risk of postoperative septic complications, whereas staged operation (OR=0.360, 95%CI: 0.184 to 0.707, P=0.003) was associated with a decreased risk. Male gender (HR=1.500, 95%CI: 1.128 to 1.995, P=0.005), upper gastrointestinal disease (HR=1.526, 95%CI: 1.033 to 2.255, P=0.034), penetrating behavior (HR=1.506, 95%CI: 1.132 to 2.003, P=0.005) and emergency surgery (HR=1.812, 95%CI: 1.375 to 2.387, P<0.01) were significantly associated with an increased risk of postoperative surgical recurrence, whereas staged operation (HR=0.361, 95%CI: 0.227 to 0.574, P<0.01) was significantly associated with a decreased risk. Conclusions: In this cohort of CD patients receiving abdominal surgery from an inflammatory bowel disease center, the median age was 31 years and the median length of resected small bowel was 30 cm, at first resection. Patients who have risk factors of adverse postoperative outcome may be benefited from staged surgical approach.

Low psoas muscle area is associated with postoperative complications in Crohn's disease.

Crohn's disease (CD) is associated with increased postoperative morbidity. Sarcopenia correlates with increased morbidity and mortality in various medical conditions. We assessed correlations of the lean body mass marker and psoas muscle area (PMA), with postoperative outcomes in CD patients undergoing gastrointestinal surgery. We included patients with CD who underwent gastrointestinal surgery between June 2009 and October 2018 and had CT/MRI scans within 8 weeks preoperatively. PMA was measured bilaterally on perioperative imaging. Of 121 patients, the mean age was 35.98 ± 15.07 years; 51.2% were male. The mean BMI was 21.56 ± 4 kg/m2. The mean PMA was 95.12 ± 263.2cm2. Patients with postoperative complications (N = 31, 26%) had significantly lower PMA compared with patients with a normal postoperative recovery (8.5 ± 2.26 cm2 vs. 9.85 ± 2.68 cm2, P = 0.02). A similar finding was noted comparing patients with anastomotic leaks to those without anastomotic leaks (7.48 ± 0.1 cm2 vs. 9.6 ± 2.51 cm2, P = 0.04). PMA correlated with the maximum degree of complications per patient, according to the Clavien-Dindo classification (Spearman's coefficient = -0.26, P = 0.004). Patients with major postoperative complications (Clavien-Dindo ≥ 3) had lower mean PMA (8.12 ± 2.75 cm2 vs. 9.71 ± 2.57 cm2, P = 0.03). Associations were similar when stratifying by gender and operation urgency. On multivariate analysis, PMA (HR = 0.72/cm2, P = 0.02), operation urgency (HR = 3.84, P < 0.01), and higher white blood cell count (HR = 1.14, P = 0.02) were independent predictive factors for postoperative complications. PMA is an easily measured radiographic parameter associated with postoperative complications in patients with CD undergoing bowel resection.

Linking Strain Engraftment in Fecal Microbiota Transplantation With Maintenance of Remission in Crohn’s Disease

Crohn's disease (CD) is a chronic gastrointestinal disease resulting from the dysfunctional interplay between genetic susceptibility, the immune system, and commensal intestinal microbiota. Emerging evidence suggests that treatment by suppression of the immune response and replacement of the microbiota through fecal microbiota transplantation (FMT) is a promising approach for the treatment of CD. We obtained stool metagenomes from CD patients in remission and assessed gut microbiome composition before and after FMT at the species and strain levels. Longitudinal follow-up evaluation allowed us to identify the gain, loss, and strain replacement of specific species and link these events to the maintenance of remission in CD. We found that FMT had a significant long-term effect on patient microbial compositions, although this was primarily driven by the engraftment of donor species, which remained at low abundance. Thirty-eight percent of FMT-driven changes were strain replacements, emphasizing the importance of detailed profiling methods, such as metagenomics. Several instances of long-term coexistence between donor and patient strains were also observed. Engraftment of some Actinobacteria, and engraftment or loss of Proteobacteria, were related to better disease outcomes in CD patients who received FMT, and transmission of Bacteroidetes was deleterious. Our results suggest clades that may be beneficial to transmit/eliminate through FMT, and provide criteria that may help identify personalized FMT donors to more effectively maintain remission in CD patients. The framework established here creates a foundation for future studies centered around the application of FMT and defined microbial communities as a therapeutic approach for treating CD.

SURGICAL STRATEGIES IN MULTIDISCIPLINARY MANAGEMENT OF CROHN'S DISEASE

Despite significant advances in medical therapy, particularly biological agents, a significant number of patients still need surgery as an important therapeutic tool in Crohn's disease (CD). The role of a surgeon in the multidisciplinary team in inflammatory bowel disease care is essential. Discussion with gastroenterologists, radiologists and dietitians to proper define the best timing of surgery after optimization and the best surgical strategy that will be used impact in better postoperative outcomes in CD patients. In this review the authors discuss important aspects involved in the surgical strategies of the multidisciplinary management of CD, including preoperative planning and optimization, the definition of the more adequate approach and technique according to the disease location, and adequate prevention of postoperative recurrence. Several aspects including patients’ past and present features are important in making the right decision in the surgical management of CD. Adequate preparation of the nutritional status, correction of anemia, optimization of medical therapy and anatomic mapping of the small bowel and colon with imaging tests are essential for the definition of best timing and type of surgery in abdominal resections in CD patients. This fact demonstrates the specific need for a multidisciplinary team in the management of CD surgical patients. A pesar de los avances significativos en la terapia médica, particularmente de los agentes biológicos, aún un número significativo de pacientes con enfermedad de Crohn (EC) necesitará de la cirugía como una importante estrategia terapéutica. El papel del coloproctólogo en el equipo multidisciplinario de enfermedad inflamatoria intestinal es fundamental. La discusión con gastroenterólogos, radiólogos y nutriólogos para definir el mejor momento de la cirugía post optimización y la mejor estrategia quirúrgica que se utilizará, impactará en mejores resultados postoperatorios en pacientes con EC. En esta revisión, discutimos importantes aspectos relacionados con las estrategias quirúrgicas del manejo multidisciplinario de la EC, incluyendo el manejo preoperatorio y optimización, la definición del enfoque y la técnica más adecuada de acuerdo a la ubicación de la enfermedad y la prevención más apropiada para el manejo de la recurrencia postoperatoria. Otras variables tales como los antecedentes y las características actuales del paciente, son importantes para tomar la decisión correcta en el tratamiento quirúrgico de la EC. La adecuada preparación del estado nutricional, la corrección de la anemia, la optimización de la terapia médica y la evaluación del intestino delgado y del colon a través de estudios de imágenes son esenciales para definir el mejor momento y el tipo de cirugía en las resecciones intestinales en pacientes con EC. Este hecho muestra la necesidad de un equipo multidisciplinario especializado en el manejo de pacientes quirúrgicos con EC.

Fecal microbiota transplant for Crohn disease: A study evaluating safety, efficacy, and microbiome profile.

Emerging trials suggest fecal microbiota transplantation (FMT) is a promising treatment for ulcerative colitis; however, there is a paucity of data in Crohn disease (CD). The objectives of this article are to determine whether single-dose FMT improves clinical and endoscopic outcomes in CD patients and to identify meaningful changes in the microbiome in response to FMT. We performed a prospective, open-label, single-center study. Ten CD patients underwent FMT and were evaluated for clinical response (defined as decrease in Harvey-Bradshaw Index score ≥3 at one month post-FMT) and microbiome profile (16S ribosomal RNA sequencing) at one month post-FMT. Three of 10 patients responded to FMT. Two of 10 patients had significant adverse events requiring escalation of therapy. On microbiome analysis, bacterial communities of responders had increased relative abundance of bacteria commonly found in donor gut microbiota. Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm. Responders tended to have lower baseline alpha diversity, suggesting baseline perturbation of microbiota may be an indicator of potential responders to FMT in this patient population. Controlled trials are needed to further assess the efficacy and safety of FMT in CD and determine whether FMT is a viable option in this patient population.Clinicaltrials.gov number: NCT02460705.

One-year clinical outcomes with biologics in Crohn's disease: transmural healing compared with mucosal or no healing.

While mucosal healing has been proved to predict relevant clinical outcomes in Crohn's disease (CD), little is known about the long-term significance of transmural healing. To prospectively assess the 1-year clinical outcomes in CD patients achieving transmural healing following treatment with biologics, and to compare them with those in patients reaching only mucosal healing or no healing. Observational longitudinal study, evaluating 1-year outcomes in terms of steroid-free clinical remission, rate of hospitalisation and need for surgery in a group of CD patients treated with anti-tumour necrosis factor (TNF) alpha for 2years. Bowel sonography was used in all patients to determine transmural healing. Of 218 patients who completed a 2-year treatment course with anti-TNF alpha, 68 (31.2%) presented transmural (plus mucosal) healing (bowel wall thickness ≤3mm at bowel sonography), 60 (27.5%) mucosal healing only, and 90 (41.3%) did not achieve any intestinal healing. Transmural healing was associated with a higher rate of steroid-free clinical remission (95.6%), lower rates of hospitalisation (8.8%) and need for surgery (0%) at 1year compared to mucosal (75%, 28.3% and 10%, respectively) and no healing (41%, 66.6% and 35.5%, respectively) (P<0.001). Furthermore, transmural healing was associated with longer intervals until clinical relapse (HR, hazard ratio 0.87, P=0.01), hospitalisation (HR 0.88, P=0.002) and surgery (HR 0.94, P=0.008) than mucosal healing. Also among patients discontinuing treatment with biologics, transmural healing predicted better clinical outcomes at 1 year than mucosal healing (P=0.01). Transmural healing is an ambitious and powerful treatment goal associated, to a greater extent than mucosal healing, with improvement of all clinical outcomes. Additionally, transmural healing is associated with better long-term clinical outcomes than mucosal healing also after discontinuation of biologics.

Long-term prognosis of Japanese patients with biologic-naïve Crohn's disease treated with anti-tumor necrosis factor-α antibodies.

Background/AimsFew reports have described the long-term treatment outcomes of the anti-tumor necrosis factor-α antibody for Japanese Crohn’s disease (CD) patients. The aim of this study was to evaluate them and clarify the clinical factors that affect the long-term prognosis of the anti-tumor necrosis factor-α treatments.MethodsThis was a retrospective, observational, single-center cohort study. Japanese CD patients treated with either infliximab or adalimumab as a first-line therapy were analyzed. The cumulative retention rates of the biologics, relapse-free survival, and surgery-free survival were analyzed using Kaplan-Meier methods. The clinical factors associated with the long-term outcomes were estimated by both the log-rank test and Cox proportional hazard model.ResultsThe cumulative retention rate was significantly higher in the group with a concomitant elemental diet of ≥900 kcal/day, baseline C-reactive protein (CRP) levels <2.6 mg/dL, and baseline serum albumin levels ≥3.5 g/dL, respectively. The baseline serum albumin levels were also associated with both relapse-free and surgery-free survival. The lack of concomitant use of an elemental diet ≥900 kcal/day was identified as the only independent risk factor for the withdrawal of the biologics.ConclusionsBaseline CRP levels and serum albumin levels could affect the long-term outcomes in CD patients. Concomitant elemental diet of ≥900 kcal/day could have a positive influence on clinical treatment course.

Post-operative abdominal complications in Crohn's disease in the biological era: Systematic review and meta-analysis.

To perform a systematic review and meta-analysis on post-operative complications after surgery for Crohn's disease (CD) comparing biological with no therapy. PubMed, Medline and Embase databases were searched to identify studies comparing post-operative outcomes in CD patients receiving biological therapy and those who did not. A meta-analysis with a random-effects model was used to calculate pooled odds ratios (OR) and confidence intervals (CI) for each outcome measure of interest. A total of 14 studies were included for meta-analysis, comprising a total of 5425 patients with CD 1024 (biological treatment, 4401 control group). After biological therapy there was an increased risk of total infectious complications (OR = 1.52; 95%CI: 1.14-2.03, 8 studies) and wound infection (OR = 1.73; 95%CI: 1.12-2.67; P = 0.01, 7 studies). There was no increased risk for other complications including anastomotic leak (OR = 1.19; 95%CI: 0.82-1.71; P = 0.26), abdominal sepsis (OR = 1.22; 95%CI: 0.87-1.72; P = 0.25) and re-operation (OR = 1.12; 95%CI: 0.81-1.54; P = 0.46) in patients receiving biological therapy. Pre-operative use of anti-TNF-α therapy may increase risk of post-operative infectious complications after surgery for CD and in particular wound related infections.

Intestinal healing after anti-TNF induction therapy predicts long-term response to one-year treatment in patients with ileocolonic Crohn's disease naive to anti-TNF agents.

IntroductionObjective assessment of Crohn’s disease (CD) activity in patients treated with anti-tumour necrosis factor (anti-TNF) antibodies is crucial for the prediction of its long-term results. Mucosal healing estimated endoscopically has a strong predictive value; however, only combined assessment together with transmural healing in magnetic resonance enterography (MRE) gives full information about the whole spectrum of inflammatory lesions in CD.AimTo assess the usefulness of intestinal healing phenomenon in CD, defined as improvement both in endoscopy and MRE, after anti-TNF induction therapy, in predicting long-term results of 1-year treatment.Material and methodsTwenty-six patients with ileocolonic CD were enrolled into the study. In this group a parallel assessment of disease activity was estimated before and after induction doses of anti-TNF antibodies with ileocolonoscopy and MRE by using appropriate scores. Subsequently the patients were treated until 12 months and then followed-up. The associations between intestinal healing (assessed in MRE and endoscopy), and mucosal and transmural healing with long-term results of 1-year anti-TNF therapy were analysed statistically.ResultsThe median time of follow-up was 29 months (interquartile range – IQR: 14–46). Intestinal healing was significantly associated with favourable therapeutic outcomes (p = 0.02) and had 75% (IQR: 35–97%) sensitivity and 72% (IQR: 46–90%) specificity in predicting long-term remission. Other parameters were not useful (transmural healing) or their usefulness was of borderline significance (mucosal healing).ConclusionsDynamic assessment of intestinal healing is an accurate method in predicting long-term outcomes in CD patients responding to 1-year anti-TNF therapy.

CONSORT: Different End-Points of Preoperative Nutrition and Outcome of Bowel Resection of Crohn Disease: A Randomized Clinical Trial.

Nutritional therapy cannot only improve nutritional status but also reduce bowel inflammation in Crohn disease (CD). The benefits of preoperative nutritional therapy on outcomes of surgery for CD have been demonstrated. However, the ideal end-points of preoperative nutrition in CD remain elusive. We conducted this study to figure out whether improvement of malnutrition or reduction of inflammation is the better end-point of preoperative nutrition for CD.This was a prospective, randomized study. All patients enrolled received preoperative nutrition with different end-points (improvement of malnutrition, IOM, or reduction of inflammation, ROI). The end-points were defined using serum albumin and body weight gain, and serum C-reactive protein (CRP), respectively. Postoperative complications, rate of fecal diversion, and postoperative recurrence of the disease were compared.A total of 108 patients were randomized and 91 patients (44 in IOM group and 47 in ROI group) completed this study. It took 25.57 ± 11.68 days to achieve ROI and 45.29 ± 18.47 days for IOM (P = 0.0023). After nutritional therapy, serum CRP, CDAI, and serum albumin in both groups improved significantly. But patients in the IOM group had a higher albumin level and body weight gain compared with ROI group (P = 0.0026, P < 0.0001). When comparing postoperative complications, rate of fecal diversion, and postoperative recurrence, no significant differences were noted.Compared with IOM, ROI as the end-point of preoperative nutrition had the same benefits on operative outcomes in CD patients undergoing resection, but could be achieved in a shorter time (NCT01540942).