Constructing a molecular subtype model of colon cancer using machine learning.

Background: Colon cancer (CRC) is one of the malignant tumors with a high incidence in the world. Many previous studies on CRC have focused on clinical research. With the in-depth study of CRC, the role of molecular mechanisms in CRC has become increasingly important. Currently, machine learning is widely used in medicine. By combining machine learning with molecular mechanisms, we can better understand CRC's pathogenesis and develop new treatments for it. Methods and materials: We used the R language to construct molecular subtypes of colon cancer and subsequently explored prognostic genes with GEPIA2. Enrichment analysis is used by WebGestalt to obtain differential genes. Protein-protein interaction networks of differential genes were constructed using the STRING database and the Cytoscape tool. TIMER2.0 and TISIDB databases were used to investigate the correlation of these genes with immune-infiltrating cells and immune targets. The cBioportal database was used to explore genomic alterations. Results: In our study, the molecular prognostic model of CRC was constructed to study the prognostic factors of CRC, and finally, it was found that Charcot-Leyden crystal galectin (CLC), zymogen granule protein 16 (ZG16), leucine-rich repeat-containing protein 26 (LRRC26), intelectin 1 (ITLN1), UDP-GlcNAc: betaGal beta-1,3-N-acetylglucosaminyltransferase 6 (B3GNT6), chloride channel accessory 1 (CLCA1), growth factor independent 1 transcriptional repressor (GFI1), aquaporin 8 (AQP8), HEPACAM family member 2 (HEPACAM2), and UDP glucuronosyltransferase family 2 member B15 (UGT2B15) were correlated with the subtype model of CRC prognosis. Enrichment analysis shows that differential genes were mainly associated with immune-inflammatory pathways. GFI1 and CLC were associated with immune cells, immunoinhibitors, and immunostimulator. Genomic analysis shows that there were no significant changes in differential genes. Conclusion: By constructing molecular subtypes of colon cancer, we discovered new colon cancer prognostic markers, which can provide direction for new treatments in the future.

A Comprehensive Pan-Cancer Analysis of the Tumorigenic Effect of Leucine-Zipper-Like Transcription Regulator (LZTR1) in Human Cancer.

The elucidation of the action site, mechanism of Leucine-Zipper-like Transcription Regulator-1 (LZTR1) and its relationship with RAS-MAPK signaling pathway attracts more and more scholars to focus on the researches of LZTR1 and its role in tumorigenesis. However, there was no pan-cancer analysis between LZTR1 and human tumors reported before. Therefore, we are the first to investigate the potential oncogenic roles of LZTR1 across all tumor types based on the datasets of TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus). LZTR1 plays a double-edged role in tumor development and prognosis. We found that the high expression of LZTR1 brings better outcomes in esophageal carcinoma (ESCA) and head and neck squamous cell carcinoma (HNSC) but brings worth outcomes in uveal melanoma (UVM), adrenocortical carcinoma (ACC), liver hepatocellular carcinoma (LIHC), and prostate adenocarcinoma (PRAD). Moreover, the expression of LZTR1 also strongly associated with pathological in ACC and bladder urothelial carcinoma (BLCA). We also found that the LZTR1 expression was associated with some immune cell infiltration including endothelial cells, regulatory T cells (Tregs), T cell CD8+, natural killer cells (NK cell), macrophages, neutrophil granulocyte, and cancer-associated fibroblasts in different cancers. Missense mutation in LZTR1 was detected in most cancers from TCGA datasets. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Body (GO) method was used to explain the pathogenesis of LZTR1. Our pan-cancer study provides a relatively comprehensive understanding of the carcinogenic role of LZTR1 in human tumors.

A pan-cancer bioinformatic analysis of the carcinogenic role of SMARCA1 in human carcinomas.

SMARCA1is a mammalian imitation switch (ISWI) gene that encodes for SNF2L. SNF2L is involved in regulating cell transition from a committed progenitor state to a differentiated state. Although many papers have detailed the correlation between SMARCA1 and different cancers, no pan-cancer analysis has been conducted to date. We started by exploring the potential carcinogenic role of SMARCA1 across 33 carcinomas using the cancer genome atlas (TCGA) and the genotype-tissue expression (GTEx) databases. The expression of SMARCA1 was significantly elevated in some tumor types but not in others. There was a distinct relationship between SMARCA1 expression and patient prognosis. S116 phosphorylation levels were up-regulated in both lung adenocarcinoma and uterine corpus endometrial carcinoma. The expression level of SMARCA1 was positively correlated with cancer-associated fibroblasts infiltration in a number of tumors, such as colon adenocarcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma. It was also associated with CD8+ T-cell infiltration in head and neck squamous cell carcinoma and lung adenocarcinoma. Furthermore, SMARCA1 is involved in chromatin remodeling and protein processing-associated mechanisms. Our study presents an initial assessment and illustration of the carcinogenic role of SMARCA1 in different carcinomas.

Gallbladder neuroendocrine carcinoma diagnosis, treatment and prognosis based on the SEER database: A literature review.

BACKGROUND: Gallbladder neuroendocrine carcinoma (GB-NEC) has a low incidence rate; therefore, its clinical characteristics, diagnosis, treatment and prognosis are not well explored. AIM: To review recent research and analyze corresponding data in the Surveillance Epidemiology and End Results (SEER) database. METHODS: Data of GB-NEC (n = 287) and gallbladder adenocarcinoma (GB-ADC) (n = 19 484) patients from 1975 to 2016 were extracted from the SEER database. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards regression. P < 0.05 was considered statistically significant. We also reviewed 108 studies retrieved from PubMed and Reference Citation Analysis (https://www.referencecitationanalysis.com/). The keywords used for the search were: "(Carcinoma, Neuroendocrine) AND (Gallbladder Neoplasms)". RESULTS: The GB-NEC incidence rate was 1.6% (of all gallbladder carcinomas), male to female ratio was 1:2 and the median survival time was 7 mo. The 1-, 2-, 3- and 5-year overall survival (OS) was 36.6%, 17.8%, 13.2% and 7.3% respectively. Serum chromogranin A levels may be a specific tumor marker for the diagnosis of GB-NEC. Elevated carcinoembryonic antigen, carbohydrate antigen (CA)-19-9 and CA-125 levels were associated with poor prognosis. Age [hazard ratio (HR) = 1.027, 95% confidence interval (CI): 1.006-1.047, P = 0.01] and liver metastasis (HR = 3.055, 95% CI: 1.839-5.075, P < 0.001) are independent prognostic risk factors for OS. Patients with advanced GB-NEC treated with surgical resection combined with radiotherapy and/or chemotherapy may have a better prognosis than those treated with surgical resection alone. There was no significant difference in OS between GB-NEC and GB-ADC. CONCLUSION: The clinical manifestations and prognosis of GB-NEC are similar to GB-ADC, but the treatment is completely different. Early diagnosis and treatment are the top priorities.

Comprehensive bioinformatic analysis of MMP1 in hepatocellular carcinoma and establishment of relevant prognostic model.

Matrix metalloproteinase 1 (MMP1) encodes endopeptidases associated with degradation of multiple components of the extracellular matrix. This function has increasingly been considered to play a major proteolysis role in tumor invasion and metastasis. However, the relationship between MMP1 gene expression, tumor-immune microenvironment and prognosis in hepatocellular carcinoma patients remains mostly unclear. This study focused on a comprehensive analysis of MMP1 in hepatocellular carcinoma, specifically the prognosis and tumor-immune microenvironment. MMP1 expression was analyzed using TCGA database and clinical samples. MMP1 associated mechanisms, pathways, mutations and prognosis in hepatocellular carcinoma were evaluated. We also analyzed the tumor-immune microenvironment and corresponding treatments. Our research demonstrated that MMP1 expression was upregulated in patients with hepatocellular carcinoma and correlated with poor survival. A prognostic model was established and its performance evaluated. We also found and report various correlations between MMP1 and immune-related cells/genes, as well the potential therapeutic agents. These findings indicate that MMP1 can potentially be a promising prognostic biomarker and indicator of the tumor-immune microenvironment status in hepatocellular carcinoma.

Pancreatic adenocarcinoma associated immune-gene signature as a novo risk factor for clinical prognosis prediction in hepatocellular carcinoma.

Pancreatic adenocarcinoma (PAAD) has high mortality and a very poor prognosis. Both surgery and chemotherapy have a suboptimal therapeutic effect, and this caused a need to find new approaches such as immunotherapy. Therefore, it is essential to develop a new model to predict patient prognosis and facilitate early intervention. Our study screened out and validated the target molecules based on the TCGA-PAAD dataset. We established the risk signature using univariate and multivariate Cox regression analysis and used GSE62452 and GSE28735 to verify the accuracy and reliability of the model. Expanded application of PAAD-immune-related genes signature (-IRGS) on other datasets was conducted, and the corresponding nomograms were constructed. We also analyzed the correlation between immune-related cells/genes and potential treatments. Our research demonstrated that a high riskscore of PAAD-IRGS in patients with PAAD was correlated with poor overall survival, disease-specific survival and progression free interval. The same results were observed in patients with LIHC. The models constructed were confirmed to be accurate and reliable. We found various correlations between PAAD-IRGS and immune-related cells/genes, and the potential therapeutic agents. These findings indicate that PAAD-IRGS may be a promising indicator for prognosis and of the tumor-immune microenvironment status in PAAD.

Transarterial chemoembolization versus surgical resection for giant hepatocellular carcinoma under the different status of capsule: a retrospective study.

Background: As an independent risk factor for the recurrence of hepatocellular carcinoma (HCC), the capsule has not been investigated in giant HCC (HCC ≥10 cm in diameter). In addition, whether the first line treatment for giant HCC should be surgery or transarterial chemoembolization (TACE) remains controversial. The aim of this study was to investigate the influence of tumor capsule on the prognosis of patients with giant HCC, and to compare the prognosis between surgical resection and TACE in giant HCC patients under different status of capsule to better inform surgeons. Methods: A retrospective review was conducted of all patients (n=83) who had been diagnosed with giant HCC and undergone surgical resection or TACE in the Affiliated Lihuili Hospital, Ningbo University, from January 2012 to December 2020. Among those who underwent surgical resection, overall survival (OS) and progression-free survival (PFS) were compared between patients with a complete capsule and with either an incomplete or no capsule. In patients with an incomplete/no capsule, survival outcomes were also compared between surgical resection and TACE. Prognostic factors for OS and PFS were analyzed in patients who underwent surgical resection. Results: In our study, 30 surgical patients had a complete capsule (Group 1), 33 surgical patients had an incomplete/no capsule (Group 2); 20 patients who had undergone TACE had an incomplete/no capsule (Group 3). The patient demographics were comparable, expect for liver segment invasion and tumor number, which suggested these 2 factors were related with capsule. Median OS was 39 months in Group 1, 27 months in Group 2, and 10 months in Group 3. Median PFS was 17 months in Group 1, 17 months in Group 2, and 7.5 in Group 3. There were significant statistical differences in OS and PFS between Group 1 and Group 2 (P=0.036; P=0.025). In patients who underwent surgical resection surgical time, liver segments invasion, and capsule were the independent risk factor for OS. Conclusions: In giant HCC patients, complete tumor capsule could take a better long-term outcomes than incomplete or no tumor capsule. In addition, if possible, such patients should opt for surgical resection to obtain a better prognosis.

Therapeutic effectiveness and safety of sintilimab-dominated triple therapy in unresectable hepatocellular carcinoma.

Immune checkpoint inhibitor therapy has shown promising results in patients with unresectable hepatocellular carcinoma. This study aimed to evaluate the effectiveness and safety of sintilimab, a programmed cell death protein-1 (PD-1) blockade, combined with sorafenib and transhepatic arterial chemotherapy and embolization in this patient population, compared with sintilimab monotherapy and sintilimab-sorafenib duotherapy. This was a 22 months single center retrospective cohort study in China. 80 patients with unresectable hepatocellular carcinoma were included, with diagnosis confirmed by either histologic, cytologic or diagnostic imaging analysis. The patients were divided into three groups based on therapeutic regimen: sintilimab monotherapy (sintilimab group, n = 22), sintilimab-sorafenib duotherapy (duplex group, n = 23), sintilimab-sorafenib and transcatheter arterial chemoembolization combined therapy (triple group, n = 35). The principal evaluation criteria were overall survival and progression free survival in the population, assessed according to response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1). Secondary evaluation criteria were safety, objective response rate and disease control rate. From March 1st, 2019 to December 31, 2020, 80 patients with unresectable hepatocellular carcinoma were included and divided into three treatment groups (22 received sintilimab monotherapy, 23 received sintilimab-sorafenib duotherapy, and 35 received sintilimab-sorafenib combined with transcatheter arterial chemoembolization). The median overall survival of all patients was 11.0 months (95% CI 7.7-14.3). Median overall survival was 13.0 months (95% CI NE-NE), 9.0 months(95% CI 6.3-11.7)and 3.0 months (95% CI 1.9-4.1, p < 0.0001) in the triple therapy, duplex and sintilimab groups respectively, while the corresponding median progression-free survival were 5.0 months (95% CI 2.9-7.1, p < 0.001), 4.0 months (95% CI 2.8-5.2) and 2.0 months (95% CI 1.7-2.3). Disease control and clinical benefits rates were higher in the triple therapy group (80%, 95% CI 63.1-91.6, p < 0.001; 54.3%, 95% CI 36.6-71.2, p < 0.01) compared to the sintilimab group. Median duration of disease control was 4.0 months (95% CI NE-NE, p < 0.01) in the triple therapy group, longer than that of the duplex group (2.0 months, 95% CI 0.9-3.1) and sintilimab group (2.0 months, 95% CI 0.8-3.2). Grade 3 or 4 treatment-related adverse events occurred in 26.3% of 80 patients with hypertension was the most common event observed (38, 47.5%), however, other severe toxic effects were infrequent. Sintilimab combined with sorafenib and transcatheter arterial chemoembolization might have more beneficial effects on overall and progression-free survival and on the duration of disease control outcomes than both sintilimab monotherapy and sintilimab-sorafenib duotherapy in patients with unresectable hepatocellular carcinoma. This triple therapy model might represent an innovative and effective option for inoperable liver cancer.

Mesenteric Adipose Tissue Alterations in Crohn's Disease Are Associated With the Lymphatic System.

Background: Mesenteric fat wrapping and thickening are typical characteristics of Crohn's disease (CD). The purpose of this study was to explore the cause of mesenteric adipose hypertrophy and analyze the role of lymphatic vessels in mesenteric adipose tissue in CD. Methods: Twenty-three CD patients who underwent ileocolonic resection were included. In CD patients, specimens were obtained from hypertrophic mesenteric adipose tissue (htMAT) next to the diseased ileum. The mesenteric lymphatic vessels in mesenteric adipose tissue were separated under stereoscope microscope. Transmission electron microscopy and immunofluorescence were used to observe the structure of mesenteric lymphatic vessels. The NF-κB signaling pathway in mesenteric adipose tissue was detected in CD specimens using Western blotting. Results: Electron microscopy showed that the structure of mesenteric lymphatic vessel was discontinuous, and the microstructure of lymphatic endothelial cells appeared ruptured and incomplete. Through an immunofluorescence technique, we found that the surface of lymphatic endothelial cells lacked tight junction protein staining in CD. Also, the expression of claudin-1, occludin, and ZO-1 in the mesenteric lymphatic vessel of htMAT was significantly lower than that of control. These results indicated that the structure of the mesenteric lymphatic vessel in htMAT was mispatterned and ruptured, which could lead to lymph leakage. Leaky lymph factors could stimulate adipose tissue to proliferate. Antigens that leaked into the mesenteric adipose tissue could effectively elicit an immune response. The levels of cytokines (TNF-a, IL-1ß, IL-6) was increased in the htMAT of CD patients by activated NF-κB signaling pathway. Conclusions: Our findings demonstrated that the hypertrophy of mesenteric adipose tissue may result from mispatterned and ruptured lymphatic vessels. Alteration of mesenteric adipose tissue was associated with activated NF-κB signaling pathway. This study enhances support for elucidating the importance of mesenteric lymphatic vessels and adipose tissue in CD.

Thickness of Subcutaneous Fat Is a Predictive Factor of Incisional Surgical Site Infection in Crohn's Disease Surgery: A Retrospective Study.

BACKGROUND: Incisional surgical site infection (iSSI) is a frequent postoperative complication of abdominal surgeries in patients with Crohn's disease (CD). In this study, we investigated the association between thickness of subcutaneous fat (TSF) and iSSI in patients with CD undergoing intestinal resections. PATIENTS AND METHODS: Patients with CD who had undergone abdominal surgery from January 2014 to January 2017 were included in this retrospective study. Patients' TSF and other possible predictors of iSSI, including clinical characteristics, preoperative medications, hematological index, surgery-related data, and postoperative outcomes, were collected. Univariate and multivariate statistical analyses were used to examine the potential factors. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of factors. RESULTS: The patient cohort comprised 246 patients (167 male (67.9%); mean age 35.7 ± 12.4 years; mean disease duration 69.6 ± 60.8 months). The incidence of iSSI was 24.8% (61/246). TSF was a significant predictor of iSSI (OR 1.079, 95% CIs (1.020, 1.142), P = 0.008), being 13.7 mm in patients with iSSI and 9.9 mm in those without iSSI (P < 0.001). Additionally, C-reactive protein (CRP) concentrations (OR 1.059, P = 0.003) were also possible predictors of iSSI, as indicated by both univariate and multivariate analysis. A model of iSSI comprising TSF and CRP concentrations was moderately accurate (AUC 0.827, CIs (0.766, 0.888)). CONCLUSIONS: Preoperative TSF and CRP independently affect iSSI in patients with CD undergoing intestinal resections.

Let-7b ameliorates Crohn's disease-associated adherent-invasive E coli induced intestinal inflammation via modulating Toll-Like Receptor 4 expression in intestinal epithelial cells.

Crohn's disease (CD)-associated adherent invasive Escherichia coli (AIEC) has been implicated as a causative or contributory factor in CD pathology. MicroRNA let-7b/Toll-like receptor 4 (TLR-4) signaling pathways may play an important role in microbiota-mucosa interactions. We aimed to investigate whether AIEC influences IECs' function of expressing TLR4, and the potential role of let-7b in regulating AIEC induced gut inflammation. Wild type (WT) and interleukin-10 knockout (IL-10 KO) mice in specific pathogen free (SPF) housing were infected by AIEC LF82, and IL-10 KO mice were treated with pre-let7b or anti-let-7b. Besides, T84 cells were infected by AIEC LF82 or E. coli K-12, and treated with let-7b mimics or inhibitor. let-7b/TLR4 signaling pathway was investigated and the therapeutic effects of let-7b treatment on colitis in IL-10-mice and on cytokines release in T84 were assessed. We found AIEC elicited/exacerbated colitis in WT/IL-10 KO mice, and promoted proinflammatory cytokines release in T84 cells that correlated with increased TLR4 expression and decreased let-7b. Overexpression of let-7b significantly ameliorated the severity of colitis in AIEC infected IL-10 KO mice, and reduced secretion of cytokines in AIEC-infected T84 cells via regulating TLR4 expression. Besides, overexpression of TLR4 caused by inhibition of let-7b led to increased proinflammatory cytokines release in K-12 infected T84 cells. These results suggest AIEC instigates excessive mucosal immune response against gut microbiota via let-7b/TLR4 signaling pathway. Let-7b may be a potential therapeutic target of CD, especially for CD with AIEC infection.

Decreased Expression of Prox1 Is Associated With Postoperative Recurrence in Crohn's Disease.

BACKGROUND: Prox1 is a transcription factor necessary for lymphangiogenesis and lymphatic function. The aim of the study was to assess the correlation between the expression of Prox1 and postoperative recurrence in Crohn's disease [CD]. METHODS: Forty CD patients who underwent ileo-colonic resection were included. Expression levels of Prox1 and D2-40 were detected using immunohistochemistry. Expression levels of Prox1, VEGFR3, and VEGFC protein were also detected in fresh CD specimens using western blotting and quantitative polymerase chain reaction [Q-PCR]. Endoscopic recurrence was used as the endpoint. Patients comprised two groups: endoscopic recurrence [Group R+] and no endoscopic recurrence [Group R-]. RESULTS: Prox1 protein expression was significantly higher in CD than in normal tissues [p <0.05], as detected using both immunohistochemistry and western blotting. Analysis of inter-relationships revealed significant correlation between Prox1 expression and lymphatic vessel density [p <0.001, r = 0.823]. There was also significant correlation between Prox1 expression and the visceral fat area [VFA] [p = 0.002, r = -0.469]. The Group R- patients had significantly higher Prox1 expression than the Group R+ patients [21.08 ± 1.61 versus 15.64 ± 1.17, p = 0.011]. Also, the lymphatic vessel density value was lower in Group R+ than in Group R- patients [6.02 ± 0.39 versus 8.13 ± 0.59, p = 0.004]. Moreover, there was a significant difference in the VFA between Group R- and Group R+ patients [64.43 ± 7.76 versus 90.44 ± 6.11, p = 0.016]. In addition to Prox1, VEGFC/VEGFR3 was found to increase, which was further confirmed using Q-PCR. CONCLUSIONS: Prox1 expression could be useful as a protective factor against recurrence in CD patients. The therapeutic role of Prox1 may lead to improved treatments.

Intraoperative inspection alone is a reliable guide to the choice of surgical procedure for enteroenteric fistulas in Crohn's disease.

BACKGROUND/AIMS: Resection of the diseased segment and suture of the victim segment is recommended for enteroenteric fistula in Crohn's disease (CD). The main difficulty in this procedure remains reliable diagnosis of the victim segment, especially for fistulas found intraoperatively and inaccessible on endoscopic examination. We aimed to explore whether intraoperative inspection alone is reliable. METHODS: Patients undergoing conservative surgery between 2011 and 2016 for enteroenteric fistulas complicating CD were identified from a prospectively maintained database. Patients were divided according to whether the victim segment was evaluated by preoperative endoscopy + intraoperative inspection (PI group) or by intraoperative inspection alone (I group). Outcomes were compared. RESULTS: Of 65 patients eligible for the study, 37 were in in the PI group and 28 were in the I group. The baseline characteristics were similar between the groups, except for the rate of emergency surgery (0/37 in PI group vs. 5/28 in I group, P=0.012). Fistulas involved more small intestines (4/37 in PI group vs. 15/28 in I group, P<0.001) and fewer sigmoid colons (17/37 in PI group vs. 4/28 in I group, P=0.008) in I group due to accessibility with endoscopy. No difference was found in postoperative complications, stoma rates, postoperative recurrence, or disease at the repair site between the 2 groups (P>0.05). CONCLUSIONS: For fistulas found intraoperatively and inaccessible on endoscopic examination, intraoperative inspection was a reliable guide when choosing between en bloc resection and a conservative procedure.

Visceral Fat Is Associated With Mucosal Healing of Infliximab Treatment in Crohn's Disease.

BACKGROUND: Visceral fat is the pathogenesis of Crohn's disease and is associated with disease status. OBJECTIVE: This study aimed to evaluate the effect of the visceral fat on mucosal healing in patients with Crohn's disease after infliximab induction therapy DESIGN:: This was a retrospective study. SETTINGS: The study was conducted in a tertiary referral hospital. PATIENTS: Between 2011 and 2017, 97 patients with Crohn's disease with the presence of ulcers underwent infliximab therapy. MAIN OUTCOME MEASURES: We studied them retrospectively. Mucosal healing was the end point. Patients composed 2 groups: mucosal healing and no mucosal healing. Univariate, multivariate, and receiver operating characteristic curve analyses determined the predictive value of the visceral fat area. RESULTS: Univariate analysis showed a statistically significant difference in the smoking history between the groups. Mucosal healing rates after infliximab were lower among active smokers (p = 0.022). Healed patients had significantly less visceral fat area before therapy (47.76 ± 4.94 vs 75.88 ± 5.55; p = 0.000) and a lower mesenteric fat index (0.52 ± 0.04 vs 0.89 ± 0.07; p = 0.000). There was no significant difference in the subcutaneous fat area (87.39 ± 5.01 vs 93.31 ± 6.95; p = 0.500). Multivariate analysis showed that only visceral fat area (OR = 0.978 (95% CI, 0.964-0.992); p = 0.002) and smoking history (OR = 0.305 (95% CI, 0.089-0.996); p = 0.041) were independent factors for mucosal healing. Receiver operating characteristic curve analysis showed predictive cutoff values of 61.5 cm and 0.62 for visceral fat area and mesenteric fat index. LIMITATIONS: This was a retrospective study. CONCLUSIONS: There was an association between increased visceral fat area and attenuated mucosal healing after infliximab therapy in biologically naive patients with Crohn's disease, indicating a need for earlier increased infliximab doses among patients with increased visceral fat. See Video Abstract at http://links.lww.com/DCR/A590.