Colorectal tumor comorbidity is common in patients with duodenal tumors: Exploratory cross-sectional study.

Background and study aims The duodenum and colorectum are target organs for familial colorectal adenomatous polyposis, however, the association of duodenal epithelial tumors (DETs) and colorectal tumors is still controversial. The aim of our study was to elucidate the association between DET and colorectal tumor. Patients and methods This was an exploratory cross-sectional study of patients with DETs treated by endoscopic resection at our hospital, between November 2018 and October 2022. Individuals who underwent colonoscopy as part of the health screening comprised the reference control group for comparison. In both groups, lesions suspected of being tumors were resected. The main outcome was the adenoma detection rate (ADR). Other outcomes were the detection rate for advanced neoplasia (AN) and risk factors for colorectal adenoma and AN, evaluated using univariate and multivariable analyses. Results Analyses were based on data from 163 individuals in the DET group and 177 in the control group. ADR was higher in the DET (63.2%) than in the control (23.6%) group ( P < 0.001). AN and invasive cancer rates were also significantly higher in the DET than in the control group (AN: 20.9% vs 3.4%, respectively, P < 0.001; invasive cancer: 3.1% vs 0%, respectively, P < 0.001). On logistic regression analysis, DET was found to be associated with a 5-fold increase in the detection rate of adenoma and 6-fold increase in AN detection. Conclusions The study revealed significant association between DET and high ADR and a higher frequency of AN and invasive cancer. Screening colonoscopy is suggested for patients with DETs.

Distinctive duodenal microbiomes and bile acid profiles in duodenal tumor patients revealed by prospective observational study.

The incidence of duodenal tumors (DTs) is increasing. However, the mechanisms underlying its development remain unclear. Environmental factors, including the microbiome and bile acids (BAs), are believed to influence tumor development. Therefore, we conducted a single-center, prospective, observational study to investigate the potential differences between patients with DTs and healthy controls (HCs) based on these factors. In addition, the BAs in the duodenal fluid were measured using liquid chromatography-tandem mass spectrometry. We recruited 41 patients and performed 16S rRNA-seq. There was no difference in the observed ASVs or PCoA plot of Bray-Curtis dissimilarity between the DTs and HCs. The lithocholic acid concentration was significantly lower in the DT group than in the control group. The ratio of CDCA to LCA was significantly higher in patients with DTs. No significant differences in microbiota were observed between DTs and HCs. In patients with DTs, the lithocholic acid concentration in duodenal was significantly lower than in HCs.

Novel perfusion system using continuous liquid-suction catheter attachment in colorectal endoscopic submucosal dissection with water pressure method (with video).

Water pressure method (WPM) is useful for colorectal endoscopic submucosal dissection (ESD), characterized not only by underwater conditions but also by active water pressure via the waterjet function. However, the extension of the colorectum by injecting excess water and contaminating the operative field by stool and bleeding have been issues. This study aimed to evaluate the feasibility of a novel perfusion system using a continuous liquid-suction catheter attachment (CLCA) in colorectal ESD with WPM. We retrospectively reviewed cases in which the perfusion system was used in colorectal ESD with WPM between August 2022 and September 2023. We evaluated clinical characteristics, treatment outcomes, volume of injection by the waterjet function, volume of suction by the endoscope and CLCA, and concentration of floating matter in the operative field over time. Thirty-one cases were enrolled. The median lesion size was 30 (range, 15-100) mm. In all cases, en bloc resection was achieved without perforation. The median injection volume was 2312 (range, 1234-13,866) g. The median suction volumes by the endoscope and CLCA were 918 (range, 141-3162) and 1147 (range, 254-11,222) g, respectively. The median concentration of floating matter in the operative field (measured in 15 cases) was 15.3 (range, 7.3-112) mg/mL when the endoscope arrived at the lesion and 8.0 (range, 3.2-16) mg/mL after endoscopically washing at the beginning of the ESD. It ranged from 7.6 to 13.4 mg/dL every 20 min during ESD. This perfusion system could prevent the extension of the lumen and maintain a good field of view in colorectal ESD with WPM.

The tryptophan metabolic pathway of the microbiome and host cells in health and disease.

The intricate and dynamic tryptophan (Trp) metabolic pathway in both the microbiome and host cells highlights its profound implications for health and disease. This pathway involves complex interactions between host cellular and bacteria processes, producing bioactive compounds such as 5-Hydroxytryptamine (5-HT) and kynurenine (Kyn) derivatives. Immune responses to Trp metabolites through specific receptors have been explored, highlighting the role of the aryl hydrocarbon receptor (AHR) in inflammation modulation. Dysregulation of this pathway is implicated in various diseases, such as Alzheimer's and Parkinson's diseases, mood disorders, neuronal diseases, autoimmune diseases such as multiple sclerosis (MS), and cancer. In this article, we describe the impact of the 5-HT, Trp, indole, and Trp metabolites on health and disease. Further, we review the impact of microbiome-derived Trp metabolites that affect immune responses and contribute to maintaining homeostasis, especially in an experimental autoimmune encephalitis (EAE) model of MS.

Unique bile acid profiles in the bile ducts of patients with primary sclerosing cholangitis.

BACKGROUND: The relationship between primary sclerosing cholangitis (PSC) and biliary bile acids (BAs) remains unclear. Although a few studies have compared PSC biliary BAs with other diseases, they did not exclude the influence of cholestasis, which affects the composition of BAs. We compared biliary BAs and microbiota among patients with PSC, controls without cholestasis, and controls with cholestasis, based on the hypothesis that alterations in BAs underlie the pathophysiology of PSC. METHODS: Bile samples were obtained using endoscopic retrograde cholangiopancreatography from patients with PSC (n = 14), non-hepato-pancreato-biliary patients without cholestasis (n = 15), and patients with cholestasis (n = 13). RESULTS: The BA profiles showed that patients with PSC and cholestasis controls had significantly lower secondary BAs than non-cholestasis controls, as expected, whereas the ratio of cholic acid/chenodeoxycholic acid in patients with PSC was significantly lower despite cholestasis, and the ratio of (cholic acid + deoxycholic acid)/(chenodeoxycholic acid + lithocholic acid) in patients with PSC was significantly lower than that in the controls with or without cholestasis. The BA ratio in the bile of patients with PSC showed a similar trend in the serum. Moreover, there were correlations between the alteration of BAs and clinical data that differed from those of the cholestasis controls. Biliary microbiota did not differ among the groups. CONCLUSIONS: Patients with PSC showed characteristic biliary and serum BA compositions that were different from those in other groups. These findings suggest that the BA synthesis system in patients with PSC differs from that in controls and patients with other cholestatic diseases. Our approach to assessing BAs provides insights into the pathophysiology of PSC.

Ulcerative colitis-associated neoplasms often harbor poor prognostic histologic components with low detection by biopsy.

Background/Aims: Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features. Methods: This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component. Results: Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P= 0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%). Conclusions: This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.

Efficacy of Dose Escalation of Oral 5-Aminosalicylic Acid for Ulcerative Colitis With a Mayo Endoscopic Subscore of 1: An Open Label Randomized Controlled Trial.

BACKGROUND: Endoscopic healing is generally defined as Mayo endoscopic subscore (MES) ≤1 in ulcerative colitis (UC). However, patients with an MES of 1 are at higher relapse risk than those with an MES of 0. This study evaluated the therapeutic efficacy of proactive dose escalation of oral 5-aminosalicylic acid (5-ASA) in UC patients with an MES of 1. METHODS: An open-label, randomized controlled trial was conducted in 5 hospitals between 2018 and 2022. Ulcerative colitis patients in clinical remission under oral 5-ASA therapy and diagnosed as having an MES of 1 were enrolled. Patients receiving maintenance therapy other than 5-ASA and immunomodulator were excluded. Patients were randomly assigned in a 1:1 ratio to receive either a dose-escalated (intervention) or constant dose (control) of 5-ASA. Concomitant immunomodulator was used as the stratification factor in the randomization. The primary end point was relapse within 1 year. The subgroup analysis was stratified for the use of immunomodulators. RESULTS: The full analysis set included 79 patients (39 intervention and 40 control). Immunomodulators were used in 20 (25.3%) patients. Relapse was less in the intervention group (15.4%) than the control group (37.5%; P = .026). In the subgroup with concomitant immunomodulators, relapse was also less in the intervention group (10.0%) than the control group (70.0%; P = .020). In patients without immunomodulators, the difference was not significant between 2 groups (intervention, 17.2%; control, 26.7%; P = .53). CONCLUSIONS: Dose escalation of 5-ASA reduced relapse within 1 year in UC patients in clinical remission with an MES of 1.

Dose escalation of 5-aminosalicylic acid for ulcerative colitis reduced relapse rate in patients in clinical remission with a Mayo endoscopic subscore of 1. The therapeutic efficacy was more evident in those whom immunomodulators were used.

Efficacy and safety of the water pressure method for endoscopic submucosal dissection in superficial pharyngeal cancer.

Background and study aims Superficial pharyngeal cancers can be cured with transoral surgery (TOS), which preserves organ function and quality of life. Pharyngeal endoscopic submucosal dissection (ESD) is challenging to perform because of limited maneuverability and complex anatomical features. The water pressure method (WPM) is useful for natural traction techniques during ESD and is potentially useful for pharyngeal ESD. This study aimed to investigate the short-term outcomes of WPM-ESD for pharyngeal lesions. Patients and methods Therapeutic outcomes of patients who underwent WPM-ESD for pharyngeal lesions at Keio University between May 2019 and February 2022 were retrospectively analyzed. Results Twenty-one pharyngeal lesions treated with WPM-ESD were analyzed. Three lesions were located in the oropharynx and 18 in the hypopharynx. All ESD procedures were performed under general anesthesia. The endoscopic en bloc resection rate was 100%. The median procedure time was 15 minutes (range 4-45 minutes). All patients were successfully extubated on the day of ESD. No serious adverse events (AEs) related to WPM-ESDs were observed. None of the patients required nasogastric intubation, percutaneous endoscopic gastrostomy, or tracheotomy. The median fasting time and hospital stay were 2 days (range 2-5 days) and 6 days (range 6-10 days), respectively. All the histological results indicated squamous cell carcinoma. The complete histologic resection rate was 76.2%. Conclusions WPM-ESD achieved a high en bloc resection rate and short procedure time without serious AEs. Thus, it may be a useful treatment for pharyngeal lesions.

Video capsule endoscopy in overt and occult obscure gastrointestinal bleeding: Insights from a single-center, observational study in Japan.

Objective: This study aimed to evaluate the use of video capsule endoscopy (VCE) in patients with obscure gastrointestinal bleeding (OGIB), compare cases of overt and occult OGIB, assess the rates of balloon-assisted enteroscopy (BAE) interventions and rebleeding, and identify predictive markers of positive VCE findings. Methods: Medical records of 430 patients who underwent VCE for OGIB between 2004 and 2022 were analyzed. Occult OGIB was defined as IDA or positive fecal occult blood, whereas overt OGIB was defined as clinically imperceptible bleeding. We retrospectively analyzed demographics, VCE findings based on Saurin classification (P0, P1, and P2), outcome of BAE interventions, and rebleeding rates. Results: A total of 253 patients with overt OGIB and 177 with occult OGIB were included. P1 findings were predominant in both groups, with a similar distribution. The percentage of patients receiving conservative therapy was higher in P1 than in P2 for both overt and occult OGIB. BAE was more frequently performed in P2 than in P1 VCE (83.0% vs. 35.3% in overt OGIB, 84.4% vs. 24.4% in occult OGIB). The percentage of positive findings and intervention in total BAE performed patients were comparable in P1 and P2 of overt OGIB, whereas these percentages in P2 were more than P1 of occult OGIB. Conclusion: VCE effectively identified OGIB lesions requiring intervention, particularly occult OGIB lesions, potentially reducing unnecessary BAE. Rebleeding rates varied according to the VCE findings, emphasizing the importance of follow-up in high-risk patients.

Clinical outcomes of patients with remitting ulcerative colitis after discontinuation of indigo naturalis.

Indigo naturalis is an effective treatment for ulcerative colitis. However, long-term use of indigo naturalis causes adverse events, such as pulmonary hypertension. The natural history of patients with ulcerative colitis who discontinued indigo naturalis after induction therapy is unknown. Moreover, the clinical features of patients who relapsed within 52 weeks after the discontinuation of indigo naturalis are unclear. This study aimed to assess the clinical outcomes of patients with ulcerative colitis after discontinuation of indigo naturalis and to identify potential markers responsible for relapse. This single-center retrospective study investigated the follow-up of 72 patients who achieved a clinical response 8 weeks after indigo naturalis treatment. We observed relapse in patients with ulcerative colitis after the discontinuation of indigo naturalis. We analyzed the factors predicting long-term outcomes after discontinuation of indigo naturalis. Relapse was observed in 24%, 57%, and 71% of patients at 8, 26, and 52 weeks, respectively. There were no predictive markers in patients who relapsed within 52 weeks after the discontinuation of indigo naturalis. The ulcerative colitis relapse rate after indigo naturalis discontinuation was high. Follow-up treatment is required after the discontinuation of indigo naturalis in patients with ulcerative colitis.

Gastrointestinal symptoms in COVID-19 and disease severity: a Japanese registry-based retrospective cohort study.

BACKGROUND: Research on whether gastrointestinal symptoms correlate with the severity of Coronavirus Disease 2019 (COVID-19) has been inconclusive. This study aimed to clarify any associations between gastrointestinal symptoms and the prognosis of COVID-19. METHODS: We collected data from the Japanese nationwide registry for COVID-19 to conduct a retrospective cohort study. Data from 3498 Japanese COVID-19 patients, diagnosed at 74 facilities between February 2020 and August 2022, were analyzed in this study. Hospitalized patients were followed up until discharge or transfer to another hospital. Outpatients were observed until the end of treatment. Associations between gastrointestinal symptoms and clinical outcomes were investigated using multivariable-adjusted logistic regression models. RESULTS: The prevalence of diarrhea, nausea/vomiting, abdominal pain, and melena were 16.6% (581/3498), 8.9% (311/3498), 3.5% (121/3498), and 0.7% (23/3498), respectively. In the univariable analysis, admission to intensive care unit (ICU) and requirement for mechanical ventilation were less common in patients with diarrhea than those without (ICU, 15.7% vs. 20.6% (p = 0.006); mechanical ventilation, 7.9% vs. 11.4% (p = 0.013)). In the multivariable-adjusted analysis, diarrhea was associated with lower likelihood of ICU admission (adjusted odds ratio (aOR), 0.70; 95% confidence interval (CI), 0.53-0.92) and mechanical ventilation (aOR, 0.61; 95% CI, 0.42-0.89). Similar results were obtained in a sensitivity analysis with another logistic regression model that adjusted for 14 possible covariates with diarrhea (ICU; aOR, 0.70; 95% CI, 0.53-0.93; mechanical ventilation; aOR 0.62; 95% CI, 0.42-0.92). CONCLUSIONS: Diarrhea was associated with better clinical outcomes in COVID-19 patients.

Characteristics of flat-type ulcerative colitis-associated neoplasia on chromoendoscopic imaging with indigo carmine dye spraying.

OBJECTIVES: Despite recent advances in endoscopic equipment and diagnostic techniques, early detection of ulcerative colitis-associated neoplasia (UCAN) remains difficult because of the complex background of the inflamed mucosa of ulcerative colitis and the morphologic diversity of the lesions. We aimed to describe the main diagnostic patterns for UCAN in our cohort, including lateral extension surrounding flat lesions. METHODS: Sixty-three lesions in 61 patients with flat-type dysplasia that were imaged with dye chromoendoscopy (DCE) were included in this analysis. These DCE images were analyzed to clarify the dye-chromoendoscopic imaging characteristics of flat dysplasia, and the lesions were broadly classified into dysplastic and nondysplastic mucosal patterns. RESULTS: Dysplastic mucosal patterns were classified into two types: small round patterns with round to roundish structures, and mesh patterns with intricate mesh-like structures. Lesions with a nondysplastic mucosal pattern were divided into two major types: a ripple-like type and a gyrus-like type. Of note, 35 lesions (55.6%) had a small round pattern, and 51 lesions (80.9%) had some type of mesh pattern. About 70% of lesions with small round patterns and 49% of lesions with mesh patterns were diagnosed as high-grade dysplasia or carcinoma, while about 30% of lesions with small round patterns and 51% of lesions with mesh patterns were diagnosed as low-grade dysplasia. CONCLUSION: When a characteristic mucosal pattern, such as a small round or mesh pattern, is found by DCE, the possibility of UCAN should be considered.

Resectability of Small Duodenal Tumors: A Randomized Controlled Trial Comparing Underwater Endoscopic Mucosal Resection and Cold Snare Polypectomy.

INTRODUCTION: Underwater endoscopic mucosal resection (UEMR) and cold snare polypectomy (CSP) are novel endoscopic procedures for superficial nonampullary duodenal epithelial tumors (SNADET). However, consensus on how to use both procedures appropriately has not been established. In this study, we evaluated treatment outcomes of both procedures, including resectability. METHODS: In this single-center randomized controlled study conducted between January 2020 and June 2022, patients with SNADET ≤12 mm were randomly allocated to UEMR and CSP groups. The primary end point was sufficient vertical R0 resection (SVR0), which was defined as R0 resection including a sufficient submucosal layer. We compared treatment outcomes including SVR0 rate between groups. RESULTS: The SVR0 rate was significantly higher in the UEMR group than in the CSP group (65.6% vs 41.5%, P = 0.01). By contrast, the R0 resection rate was not significantly different between study groups (70.3% vs 61.5%, P = 0.29). The submucosal layer thickness was significantly greater in the UEMR group than in the CSP group (median 546 [range, 309-833] µm vs 69 [0-295] µm, P < 0.01). CSP had a shorter total procedure time (median 12 [range, 8-16] min vs 1 [1-3] min, P < 0.01) and fewer total bleeding events (9.4% vs 1.5%, P = 0.06). DISCUSSION: UEMR has superior vertical resectability compared with CSP, but CSP has a shorter procedure time and fewer bleeding events. Although CSP is preferable for most small SNADET, UEMR should be selected for lesions that cannot be definitively diagnosed as mucosal low-grade neoplasias.

Prospective cross-organ analysis for the causes of fever and increased inflammatory response after endoscopic resection.

OBJECTIVES: Fever and increased inflammatory responses sometimes occur following endoscopic resection (ER). However, the differences in causes according to the organ are scarcely understood, and several modified ER techniques have been proposed. Therefore, we conducted a comprehensive prospective study to investigate the cause of fever and increased inflammatory response across multiple organs after ER. METHODS: We included patients who underwent gastrointestinal endoscopic submucosal dissection (ESD) and duodenal endoscopic mucosal resection at our hospital between January 2020 and April 2022. Primary endpoints were fever and increased C-reactive protein (CRP) levels following ER. The secondary endpoints were risk factors for aspiration pneumonia. Blood tests and radiography were performed on the day after ER, and computed tomography was performed if the cause was unknown. RESULTS: Among the 822 patients included, aspiration pneumonia was the most common cause of fever and increased CRP levels after ER of the upper gastrointestinal tract (esophagus, 53%; stomach, 48%; and duodenum, 71%). Post-ER coagulation syndrome was most common after colorectal ESD (38%). On multivariate logistic regression analysis, lesions located in the esophagus (odds ratio [OR] 3.57; P < 0.001) and an amount of irrigation liquid of ≥1 L (OR 3.71; P = 0.003) were independent risk factors for aspiration pneumonia. CONCLUSIONS: Aspiration pneumonia was the most common cause of fever after upper gastrointestinal ER and post-ER coagulation syndrome following colorectal ESD. Lesions in the esophagus and an amount of irrigation liquid of ≥1 L were independent risk factors for aspiration pneumonia.

The gut microbiota-induced kynurenic acid recruits GPR35-positive macrophages to promote experimental encephalitis.

The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities between CD4+ T cells in the spinal cord and their counterparts in the small intestine. Furthermore, we unveil a synergistic relationship between the microbiota, particularly enriched with the tryptophan metabolism gene EC:1.13.11.11, and intestinal cells. This symbiotic collaboration results in the biosynthesis of kynurenic acid (KYNA), which modulates the recruitment and aggregation of GPR35-positive macrophages. Subsequently, a robust T helper 17 (Th17) immune response is activated, ultimately triggering the onset of EAE. Conversely, modulating the KYNA-mediated GPR35 signaling in Cx3cr1+ macrophages leads to a remarkable amelioration of EAE. These findings shed light on the crucial role of microbial-derived tryptophan metabolites in regulating immune responses within extraintestinal tissues.

D-amino Acids Ameliorate Experimental Colitis and Cholangitis by Inhibiting Growth of Proteobacteria: Potential Therapeutic Role in Inflammatory Bowel Disease.

BACKGROUND & AIMS: D-amino acids, the chiral counterparts of protein L-amino acids, were primarily produced and utilized by microbes, including those in the human gut. However, little was known about how orally administered or microbe-derived D-amino acids affected the gut microbial community or gut disease progression. METHODS: The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls. Also, composition of microbe was analyzed from patients with UC. Mice were treated with D-amino acid in dextran sulfate sodium colitis model and liver cholangitis model. RESULTS: The ratio of D- to L-amino acids was lower in the feces of patients with UC than that of healthy controls. Supplementation of D-amino acids ameliorated UC-related experimental colitis and liver cholangitis by inhibiting growth of Proteobacteria. Addition of D-alanine, a major building block for bacterial cell wall formation, to culture medium inhibited expression of the ftsZ gene required for cell fission in the Proteobacteria Escherichia coli and Klebsiella pneumoniae, thereby inhibiting growth. Overexpression of ftsZ restored growth of E. coli even when D-alanine was present. We found that D-alanine not only inhibited invasion of pathological K. pneumoniae into the host via pore formation in intestinal epithelial cells but also inhibited growth of E. coli and generation of antibiotic-resistant strains. CONCLUSIONS: D-amino acids might have potential for use in novel therapeutic approaches targeting Proteobacteria-associated dysbiosis and antibiotic-resistant bacterial diseases by means of their effects on the intestinal microbiota community.

Downregulation of chemokine receptor 9 facilitates CD4+CD8αα+ intraepithelial lymphocyte development.

Intestinal intraepithelial lymphocytes (IELs) reside in the gut epithelial layer, where they help in maintaining intestinal homeostasis. Peripheral CD4+ T cells can develop into CD4+CD8αα+ IELs upon arrival at the gut epithelium via the lamina propria (LP). Although this specific differentiation of T cells is well established, the mechanisms preventing it from occurring in the LP remain unclear. Here, we show that chemokine receptor 9 (CCR9) expression is low in epithelial CD4+CD8αα+ IELs, but CCR9 deficiency results in CD4+CD8αα+ over-differentiation in both the epithelium and the LP. Single-cell RNA sequencing shows an enriched precursor cell cluster for CD4+CD8αα+ IELs in Ccr9-/- mice. CD4+ T cells isolated from the epithelium of Ccr9-/- mice also display increased expression of Cbfß2, and the genomic occupancy modification of Cbfß2 expression reveals its important function in CD4+CD8αα+ differentiation. These results implicate a link between CCR9 downregulation and Cbfb2 splicing upregulation to enhance CD4+CD8αα+ IEL differentiation.

A Roadmap for the Human Gut Cell Atlas.

The number of studies investigating the human gastrointestinal tract using various single-cell profiling methods has increased substantially in the past few years. Although this increase provides a unique opportunity for the generation of the first comprehensive Human Gut Cell Atlas (HGCA), there remains a range of major challenges ahead. Above all, the ultimate success will largely depend on a structured and coordinated approach that aligns global efforts undertaken by a large number of research groups. In this Roadmap, we discuss a comprehensive forward-thinking direction for the generation of the HGCA on behalf of the Gut Biological Network of the Human Cell Atlas. Based on the consensus opinion of experts from across the globe, we outline the main requirements for the first complete HGCA by summarizing existing data sets and highlighting anatomical regions and/or tissues with limited coverage. We provide recommendations for future studies and discuss key methodologies and the importance of integrating the healthy gut atlas with related diseases and gut organoids. Importantly, we critically overview the computational tools available and provide recommendations to overcome key challenges.

Risk of venous thromboembolism with a central venous catheter in hospitalized Japanese patients with inflammatory bowel disease: a propensity score-matched cohort study.

BACKGROUND/AIMS: Thromboprophylaxis is recommended for hospitalized patients with inflammatory bowel disease (IBD) in Western countries, although it is selectively administered to high-risk patients in East Asia. A central venous catheter (CVC) is commonly placed in patients with IBD. Although CVC placement is considered a risk factor for venous thromboembolism (VTE), the degree of increased risk in patients with IBD is uncertain. This study aimed to identify the risk of VTE with CVC placement in hospitalized Japanese patients with IBD without thromboprophylaxis. METHODS: This retrospective cohort study included patients with ulcerative colitis or Crohn's disease who were admitted for disease flares at Keio University Hospital between January 2016 and December 2020. Patients who already had thrombosis or were administered any antithrombotic treatment on admission were excluded. VTE development during the hospitalization was surveyed, and VTE risk associated with CVC indwelling was estimated using propensity score matching and inverse probability of treatment weighting analyses. RESULTS: Altogether, 497 hospitalized patients with IBD (ulcerative colitis, 327; Crohn's disease, 170) were enrolled. VTE developed in 9.30% (12/129) of catheterized patients and in 0.82% (3/368) of non-catheterized patients. The propensity score matching yielded 127 matched pairs of patients. The catheterized group demonstrated higher odds for VTE than the non-catheterized group (odds ratio, 13.15; 95% confidence interval, 1.68-102.70). A similar result was obtained in the inverse probability of treatment weighting analysis (odds ratio, 11.02; 95% confidence interval, 2.64-46.10). CONCLUSIONS: CVC placement is a major risk factor for VTE among hospitalized Japanese patients with IBD without thromboprophylaxis.