Clinical features of inflammatory bowel disease unclassified: a case-control study.

BACKGROUND: Approximately 10-15% of inflammatory bowel disease (IBD) patients with overlapping features of ulcerative colitis (UC) and Crohn's disease (CD) are termed as inflammatory bowel disease unclassified (IBDU). This study aimed to describe the clinical features of IBDU and evaluate the potential associated factors of reclassification. METHODS: The clinical data of 37 IBDU patients were retrospectively analyzed from November 2012 to November 2020. 74 UC and 74 CD patients were randomly selected and age- and sex-matched with the 37 IBDU patients. Clinical characteristics were compared between the three patient groups. Potential factors associated with the IBDU reclassification were evaluated. RESULTS: 60% of IBDU patients displayed rectal-sparing disease, and 70% of them displayed segmental disease. In comparison to UC and CD, the IBDU group demonstrated higher rates of gastrointestinal bleeding (32.4%), intestinal perforation (13.5%), spontaneous blood on endoscopy (51.4%), and progression (56.8%). The inflammation proceeded relatively slowly, manifesting as chronic alterations like pseudopolyps (78.4%) and haustra blunt or disappearance (56.8%). 60% of IBDU patients exhibited crypt abscess, and 16.7% of them exhibited fissuring ulcers or transmural lymphoid inflammation. The proportions of IBDU patients receiving immunosuppressants, surgery, and infliximab were basically the same as those of CD patients. During the 79 (66, 91) months of follow-up, 24.3% of IBDU patients were reclassified as UC, while 21.6% were reclassified as CD. The presence of intestinal hemorrhaging was associated with CD reclassification, while hypoalbuminemia was associated with UC reclassification. CONCLUSIONS: IBDU may evolve into UC or CD during follow-up, and hemorrhage was associated with CD reclassification. Different from the other two groups, IBDU exhibited a more acute onset and a gradual progression. When an IBD patient presents with transmural inflammation or crypt abscess but lacks transmural lymphoid aggregates or fissuring ulcers, the diagnosis of IBDU should be considered.

Ocular manifestations of mitochondrial neurogastrointestinal encephalomyopathy: A case report and literature review.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive multisystem disorder that often presents with gastrointestinal and neurological symptoms. Here we report a 33-year-old male who presented with a 16-year history of diarrhea with black stool and progressive weight loss. He complained of progressive bilateral blurred vision, upper eyelids heaviness, ocular motility impairment, and color blindness. Peripheral neuropathy, bilateral sensorineural deafness, hyperlactatemia, diabetes mellitus, hepatic steatosis, blood coagulation dysfunction, and diffuse leukoencephalopathy were detected in the systemic evaluation. Based on the novel homozygous pathogenic variant in the TYMP gene (c.1159+1G>A), he was diagnosed with MNGIE. On ophthalmic examinations, the thickness of the inner retina and ganglion cell complex significantly decreased. ERG showed diffusely decreased amplitudes. The electronegative electroretinogram, which was first reported in MNGIE, indicated a more severe inner retina impairment. The bilateral papillomacular bundle defect and central vision loss in MNGIE are consistent with classical mitochondrial optic neuropathies' features. According to the literature, pigmentary retinopathy, optic neuropathy, and abnormal pupillary reflexes are uncommon ocular features of MNGIE. This study contributes to a better understanding of ocular manifestations in MNGIE and demonstrates that MNGIE may have dyschromatopsia and an electronegative electroretinogram.

Malnutrition Defined by the Global Leadership Initiative on Malnutrition (GLIM) Criteria in Hospitalized Patients with Ulcerative Colitis and Its Association with Clinical Outcomes.

(1) Background: The Global Leadership Initiative on Malnutrition (GLIM) was published in 2019, and its application has been explored in several diseases. However, the data on malnutrition based on the GLIM in ulcerative colitis (UC) patients are sparse. (2) Methods: This single-center, retrospective cohort study included 605 hospitalized UC patients. Demographics and clinical data were collected from electronic medical records. Nutritional Risk Screening 2002 (NRS 2002) was used as a screening tool, and malnutrition was diagnosed according to the GLIM criteria. The skeletal muscle area of the third lumber cross-section in abdominal computed tomography was used to evaluate muscle mass within one week before or after admission. (3) Results: The prevalence of malnutrition was 64.1% in this cohort, and the prevalences were 34.2, 57.7, and 86.7% in UC patients with mild, moderate, and severe disease activity, respectively. Malnourished patients tended to need surgical treatment (p = 0.080) and had a 2.4 times greater risk of opportunistic infection. The multivariate logistic regression analysis showed that UC patients with malnutrition had a 1.7-fold increased risk of readmission. (4) Conclusions: Nutritional problems deserve more attention in hospitalized UC patients. Malnutrition identified through the GLIM criteria was associated with opportunistic infection, tended to be associated with surgical treatment, and showed a prognosis value for readmission.

What is the appropriate treatment strategy for cryptogenic multifocal ulcerative stenosing enteritis? A single-center experience from China.

Background: There are few reports on standard treatment and long-term prognosis in patients with cryptogenic multifocal ulcerative stenosing enteritis (CMUSE), particularly in patients in whom remission could not be induced by steroids. The aim of this study was to evaluate the treatment response and progression-free periods of patients with CMUSE and to identify the factors predictive of steroid resistance. Methods: This was a retrospective cohort study that included 25 patients with clinically confirmed CMUSE between 1984 and 2021 from the enteropathy clinic of a tertiary care center. For statistical analyses, chi-square test or Fisher's exact test were used for categorical variables. Survival curves were plotted using the Kaplan-Meier method. Results: The overall median progression-free period was 48 months (range, 1-108 months) after comprehensive therapy, and initial manifestation with severe bleeding rather than ileus was associated with the long-term efficacy. Patients with steroid resistance (N = 10, 55.6%) had poor prognosis, and non-responders had more favorable baseline clinical characteristics, with a higher percentage of female patients (60% vs. 12.5%), earlier disease onset (26.5 years vs. 39 years), rapid progression (42 vs. 108 months), severe anemia (80% vs. 50%), and hypoalbuminemia (50% vs. 0%), in accord with lymphangiectasia or angioectasia identified in pathology. Conclusion: There is no guaranteed treatment strategy in the maintenance of long-term clinical remission for CMUSE patients, particularly in whom with steroid resistance. Female patients with early symptoms onset, severe gastrointestinal hemorrhage and hypoalbuminemia seem to have poor long-term prognosis.

Identification of key genes and biological processes contributing to colitis associated dysplasia in ulcerative colitis.

BACKGROUND: Ulcerative colitis-associated colorectal cancer (UC-CRC) is a life-threatening complication of ulcerative colitis (UC). The mechanisms underlying UC-CRC remain to be elucidated. The purpose of this study was to explore the key genes and biological processes contributing to colitis-associated dysplasia (CAD) or carcinogenesis in UC via database mining, thus offering opportunities for early prediction and intervention of UC-CRC. METHODS: Microarray datasets (GSE47908 and GSE87466) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between groups of GSE47908 were identified using the "limma" R package. Weighted gene co-expression network analysis (WGCNA) based on DEGs between the CAD and control groups was conducted subsequently. Functional enrichment analysis was performed, and hub genes of selected modules were identified using the "clusterProfiler" R package. Single-gene gene set enrichment analysis (GSEA) was conducted to predict significant biological processes and pathways associated with the specified gene. RESULTS: Six functional modules were identified based on 4929 DEGs. Green and blue modules were selected because of their consistent correlation with UC and CAD, and the highest correlation coefficient with the progress of UC-associated carcinogenesis. Functional enrichment analysis revealed that genes of these two modules were significantly enriched in biological processes, including mitochondrial dysfunction, cell-cell junction, and immune responses. However, GSEA based on differential expression analysis between sporadic colorectal cancer (CRC) and normal controls from The Cancer Genome Atlas (TCGA) indicated that mitochondrial dysfunction may not be the major carcinogenic mechanism underlying sporadic CRC. Thirteen hub genes (SLC25A3, ACO2, AIFM1, ATP5A1, DLD, TFE3, UQCRC1, ADIPOR2, SLC35D1, TOR1AIP1, PRR5L, ATOX1, and DTX3) were identified. Their expression trends were validated in UC patients of GSE87466, and their potential carcinogenic effects in UC were supported by their known functions and other relevant studies reported in the literature. Single-gene GSEA indicated that biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to angiogenesis and immune response were positively correlated with the upregulation of TFE3, whereas those related to mitochondrial function and energy metabolism were negatively correlated with the upregulation of TFE3. CONCLUSIONS: Using WGCNA, this study found two gene modules that were significantly correlated with CAD, of which 13 hub genes were identified as the potential key genes. The critical biological processes in which the genes of these two modules were significantly enriched include mitochondrial dysfunction, cell-cell junction, and immune responses. TFE3, a transcription factor related to mitochondrial function and cancers, may play a central role in UC-associated carcinogenesis.

Relationship between clinical features and intestinal microbiota in Chinese patients with ulcerative colitis.

BACKGROUND: Dysbacteriosis may be a crucial environmental factor for ulcerative colitis (UC). Further study is required on microbiota alterations in the gastrointestinal tract of patients with UC for better clinical management and treatment. AIM: To analyze the relationship between different clinical features and the intestinal microbiota, including bacteria and fungi, in Chinese patients with UC. METHODS: Eligible inpatients were enrolled from January 1, 2018 to June 30, 2019, and stool and mucosa samples were collected. UC was diagnosed by endoscopy, pathology, Mayo Score, and Montreal classification. Gene amplicon sequencing of 16S rRNA gene and fungal internal transcribed spacer gene was used to detect the intestinal microbiota composition. Alpha diversity, principal component analysis, similarity analysis, and Metastats analysis were employed to evaluate differences among groups. RESULTS: A total of 89 patients with UC and 33 non-inflammatory bowel disease (IBD) controls were enrolled. For bacterial analysis, 72 stool and 48 mucosa samples were obtained from patients with UC and 21 stool and 12 mucosa samples were obtained from the controls. For fungal analysis, stool samples were obtained from 43 patients with UC and 15 controls. A significant difference existed between the fecal and mucosal bacteria of patients with UC. The α-diversity of intestinal bacteria and the relative abundance of some families, such as Lachnospiraceae and Ruminococcaceae, decreased with the increasing severity of bowel inflammation, while Escherichia-Shigella showed the opposite trend. More intermicrobial correlations in UC in remission than in active patients were observed. The bacteria-fungi correlations became single and uneven in patients with UC. CONCLUSION: The intestinal bacteria flora of patients with UC differs significantly in terms of various sample types and disease activities. The intermicrobial correlations change in patients with UC compared with non-IBD controls.

Advances in the understanding of the intestinal micro-environment and inflammatory bowel disease.

The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes, the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease (IBD). In the past few years, with the advances in the understanding of microbiome, its metabolites and further application of next generation sequencing, analysis of dynamic alteration of gut micro-environment was realized, which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis status. The subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential therapy. In this review, we will summarize the recent knowledge about multi-dimensional dysbiosis, the inter-action between fungus and bacteria under inflamed mucosa, and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD.

Whole Exome Sequencing of Ulcerative Colitis-associated Colorectal Cancer Based on Novel Somatic Mutations Identified in Chinese Patients.

BACKGROUND: Carcinogenesis is a severe consequence of chronic ulcerative colitis. We investigated the somatic mutations and pathway alterations in ulcerative colitis-associated colorectal cancer (CRC) in Chinese patients compared with sporadic CRCs to reveal potential therapeutic targets in ulcerative colitis-associated CRC. METHODS: Whole exome sequencing was performed on archival tumor tissues and paired adjacent nondysplastic mucosa from 10 ulcerative colitis-associated CRC patients at a high risk of carcinogenesis. Genomic alteration profiles from 223 primary CRCs from The Cancer Genome Atlas served as sporadic CRC controls. A meta-analysis was performed to investigate differences in major genetic mutations between ulcerative colitis-associated and Crohn's disease-associated CRCs. RESULTS: We identified 44 nonsilent recurrent somatic mutations via whole exome sequencing, including 25 deleterious mutations involved in apoptosis and the PI3K-Akt pathway (COL6A3, FN1), autophagy (ULK1), cell adhesion (PODXL, PTPRT, ZFHX4), and epigenetic regulation (ARID1A, NCOR2, KMT2D, NCOA6, MECP2, SUPT6H). In total, 11 of the 25 mutated genes significantly differed between ulcerative colitis-associated CRC and sporadic CRC (APC, APOB, MECP2, NCOR2, NTRK2, PODXL, RABGAP1, SIK3, SUPT6H, ULK1, USP48). Somatic TP53 mutations occurred in 33% of ulcerative colitis-associated CRCs. Subsequent meta-analysis revealed distinct mutation profiles for Crohn's disease- and ulcerative colitis-associated CRCs. Mutations involving the NF-kB pathway and epigenetic regulation were more common in ulcerative colitis-associated CRCs than in sporadic CRCs. CONCLUSION: Distinct genomic alteration profiles of deleterious somatic mutations were found in ulcerative colitis-associated and sporadic CRCs. Mutations of epigenetic regulators, such as KMT2D and NCOA6, were common, suggesting an epigenetic pathomechanism for colitis-associated carcinoma in Chinese patients.

Is additional 5-day vasoactive drug therapy necessary for acute variceal bleeding after successful endoscopic hemostasis?: A systematic review and meta-analysis.

BACKGROUND: Vasoactive drugs and endoscopic therapy have been widely used in the management of acute variceal bleeding of cirrhosis patients. The current standard regimen of vasoactive drugs is in combination with endoscopic therapy and continues for up to 5 days; however, the necessity of vasoactive drugs after endoscopic hemostasis was still controversial. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and optimal duration of adjuvant vasoactive drugs after hemorrhage control by endoscopic therapy. METHODS: A search was conducted of PubMed, EMBASE, and Cochrane Library databases until June, 2018. Lan DeMets sequential monitoring boundary was constructed to assess the reliability and conclusiveness of our major results. RESULTS: Seven studies (639 patients) and 4 studies (435 patients) were included in the analyses to evaluate the efficacy and optimal duration of adjuvant vasoactive drugs therapy, respectively. Our analyses showed that adjuvant vasoactive drugs facilitated endoscopic hemostasis and reduced very early re-bleeding rate both in sclerotherapy (risk ratio [RR] 0.51, 95% confidence interval [CI] 0.34-0.78, P = .23, I = 31%) and band ligation (RR 0.48, 95% CI 0.27-0.83, P = .07, I = 62%). However, the 3 to 5-day therapy duration was not superior to a shorter course in very early re-bleeding rate and mortality rate in 42 days (RR 1.77, 95% CI 0.64-4.89, P = .70, I = 0%; RR 0.95, 95% CI 0.43-2.13, P = .81, I = 0%, respectively). CONCLUSION: Additional 5-day vasoactive drug after endoscopic hemostasis may significantly ameliorate very early re-bleeding rate, However, the 3 to 5 days' adjuvant regimen was not superior to a shorter course.