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Identifying patients at risk for mortality from COVID-19 is crucial to triage, clinical decision-making, and the allocation of scarce hospital resources. The 4C Mortality Score effectively predicts COVID-19 mortality, but it has not been validated in a United States (U.S.) population. The purpose of this study is to determine whether the 4C Mortality Score accurately predicts COVID-19 mortality in an urban U.S. adult inpatient population.This retrospective cohort study included adult patients admitted to a single-center, tertiary care hospital (Philadelphia, PA) with a positive SARS-CoV-2 PCR from 3/01/2020 to 6/06/2020. Variables were extracted through a combination of automated export and manual chart review. The outcome of interest was mortality during hospital admission or within 30 days of discharge.This study included 426 patients; mean age was 64.4 years, 43.4% were female, and 54.5% self-identified as Black or African American. All-cause mortality was observed in 71 patients (16.7%). The area under the receiver operator characteristic curve of the 4C Mortality Score was 0.85 (95% confidence interval, 0.79-0.89).Clinicians may use the 4C Mortality Score in an urban, majority Black, U.S. inpatient population. The derivation and validation cohorts were treated in the pre-vaccine era so the 4C Score may over-predict mortality in current patient populations. With stubbornly high inpatient mortality rates, however, the 4C Score remains one of the best tools available to date to inform thoughtful triage and treatment allocation.

Background and Aims Lumen-apposing metal stents (LAMSs) provide an endoscopic method for management of walled-off necrosis (WON) and a gateway for the performance of endoscopic necrosectomy (EN). However, bleeding may occur in up to 20% of EN procedures. Predictive factors for bleeding in this patient population are unknown, and there is no agreed-upon algorithm for management of bleeding. The aim of this study was to evaluate preprocedural risk factors for bleeding in patients undergoing endoscopic drainage or EN for WON. Methods A retrospective cohort of patients undergoing EN for WON was reviewed. Demographics, comorbidities, concurrent medications, and etiology of pancreatitis were recorded. Pre-, peri-, and postprocedural clinical variables were compared using Chi-squared test and independent t-test. Results Between June 2014 and October 2020, 536 EN were performed in 151 patients. Intraprocedural bleeding occurred during 28 procedures (5.2%) in 18 patients (11.9%.) Endoscopic hemostasis was attempted in 8 patients (10 procedures). Eight patients (10 procedures) in total were treated by IR. Thrombocytopenia (p = 0.006) and cirrhosis (p = 0.049) were associated with intraprocedural bleeding, although thrombocytopenia was present in only one patient. Identification of a vessel within the cavity endoscopically was also associated with bleeding (p Conclusions EN for WON was associated with a 5.2% per procedure risk of bleeding and an 11.9% per-patient bleeding risk. Identification of a vessel within the cavity during endoscopy is predictive of bleeding during EN. Patients who require more transfusions before endoscopy may require earlier intervention by IR.

BACKGROUND International Statistical Classification of Disease and Related Health Problems, 10th Revision codes (ICD-10) are used to characterize cohort comorbidities. Recent literature does not demonstrate standardized extraction methods. OBJECTIVE Compare COVID-19 cohort manual-chart-review and ICD-10-based comorbidity data; characterize the accuracy of different methods of extracting ICD-10-code-based comorbidity, including the temporal accuracy with respect to critical time points such as day of admission. METHODS Design: Retrospective cross-sectional study. MEASUREMENTS ICD-10-based-data performance characteristics relative to manual-chart-review. RESULTS Discharge billing diagnoses had a sensitivity of 0.82 (95% Confidence Interval [CI]: 0.79-0.85; comorbidity range 0.35-0.96). The past medical history table had a sensitivity of 0.72 (95% CI: 0.69-0.76; range 0.44-0.87). The active problem list had a sensitivity of 0.67 (95% CI: 0.63-0.71; range 0.47-0.71). On day of admission, the active problem list had a sensitivity of 0.58 (95% CI: 0.54-0.63; range 0.30-0.68) and past medical history table had a sensitivity of 0.48 (95% CI: 0.43-0.53; range 0.30-0.56). CONCLUSIONS AND RELEVANCE ICD-10-based comorbidity data performance varies depending on comorbidity, data source, and time of retrieval; there are notable opportunities for improvement. Future researchers should clearly outline comorbidity data source and validate against manual-chart-review. This article is protected by copyright. All rights reserved.

Objective COVID-19 has disproportionately affected low-income communities and people of color. Previous studies demonstrated that race/ethnicity and socioeconomic status (SES) are not independently correlated with COVID-19 mortality. The purpose of our study is to determine the effect of race/ethnicity and SES on COVID-19 30-day mortality in a diverse, Philadelphian population. Methods This is a retrospective cohort study in a single center tertiary care hospital in Philadelphia, PA. The study includes adult patients hospitalized with polymerase-chain-reaction-confirmed COVID-19 between March 1st , 2020 and June 6th , 2020. The primary outcome was a composite of COVID-19 death or hospice discharge within 30 days of discharge. The secondary outcome was intensive care unit (ICU) admission. Results The study included 426 patients. 16.7% died, 3.3% were discharged to hospice, and 20.0% were admitted to the ICU. Using multivariable analysis, race/ethnicity was not associated with the primary nor secondary outcome. In Model 4, age greater than 75 (Odds Ratio [OR], 11.01; 95% confidence interval [CI], 1.96 to 61.97) and renal disease (OR 2.78; 95% CI, 1.31 to 5.90) were associated with higher odds of the composite primary outcome. "Very-low-income area" (OR 0.29; 95% CI, 0.12 to 0.71) and BMI 30-35 (OR 0.24; 95% CI, 0.08 to 0.69) were associated with lower odds of the primary outcome. Conclusions When controlling for demographics, SES, and comorbidities, race/ethnicity was not independently associated with the composite primary outcome. Very-low SES, as extrapolated from census-tract-level income data, were associated with lower odds of the composite primary outcome. This article is protected by copyright. All rights reserved.

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation as the result of immunosuppressant medications. Epstein-Barr virus (EBV) has been implicated in most of these cases, specifically with B-cell predominant lymphoma. This case report describes a 24-year-old female who presented with recurrent GI bleed within 6 months post-orthostatic heart transplant. Endoscopic evaluations including video capsule study, push enteroscopy, and colonoscopy revealed multiple ulcerated lesions in duodenum, jejunum, and colon secondary to Epstein-Barr Virus-associated monomorphic PTLD. Despite continuation of rituximab after discharge, she returned to the hospital for recurrent GI bleed requiring additional endoscopic intervention. PTLD is a devastating disease of the post-transplant population. Due to a high risk of recurrent GI bleeding, patients with PTLD may benefit from careful monitoring by gastroenterology as an outpatient with a low threshold for repeat endoscopic evaluation despite being on immunotherapy or chemotherapy.

Backgrounds Endoscopic ultrasound (EUS)-guided placement of lumen-apposing metal stents (LAMSs) has gained popularity for the treatment of pancreatic walled-off necrosis (WON). We compared the 20-mm and 15-mm LAMSs for the treatment of symptomatic WON in terms of clinical success and adverse events. Methods We conducted a retrospective, case-matched study of 306 adults at 22 tertiary centers from 04/2014 to 10/2018. A total of 102 patients with symptomatic WON who underwent drainage with 20-mm LAMS (cases) and 204 patients who underwent drainage with 15-mm LAMS (controls) were matched by age, sex, and drainage approach. Conditional logistic regression analysis was performed to compare clinical success (resolution of WON on follow-up imaging without reintervention) and adverse events (according to American Society for Gastrointestinal Endoscopy criteria). Results Clinical success was achieved in 92.2 % of patients with 20-mm LAMS and 91.7 % of patients with 15-mm LAMS (odds ratio 0.92; P = 0.91). Patients with 20-mm LAMS underwent fewer direct endoscopic necrosectomy (DEN) sessions (mean 1.3 vs. 2.1; P Conclusions The 20-mm LAMS showed comparable clinical success and safety profile to the 15-mm LAMS, with the need for fewer DEN sessions for WON resolution.

Background Vitamin D plays a protective role in ulcerative colitis (UC) patients through unclear mechanisms. Cathelicidin is an antimicrobial peptide induced by 1,25(OH)D2. Our goal was to evaluate the link between cathelicidin and vitamin D–associated clinical outcomes in UC patients, explore vitamin D induction of cathelicidin in human colon cells, and evaluate the effects of intrarectal human cathelicidin on a murine model of colitis. Methods Serum and colonic cathelicidin levels were measured in UC patients and correlated with clinical and histologic outcomes. Human colon cells were treated with 1,25(OH)2D and production of cathelicidin and cytokines were quantified. Antimicrobial activity against Escherichia coli from cell culture supernatants was measured. Mice were treated with intrarectal cathelicidin, and its effects on DSS colitis and intestinal microbiota were evaluated. Results In UC patients, serum 25(OH)D positively correlated with serum and colonic cathelicidin. Higher serum cathelicidin is associated with decreased risk of histologic inflammation and clinical relapse but not independent of 25(OH)D or baseline inflammation. The 1,25(OH)2D treatment of colon cells induced cathelicidin and IL-10, repressed TNF-α, and suppressed Escherichia coli growth. This antimicrobial effect was attenuated with siRNA-cathelicidin transfection. Intrarectal cathelicidin reduced the severity of DSS colitis but did not mitigate the impact of colitis on microbial composition. Conclusions Cathelicidin plays a protective role in 25(OH)D-associated UC histologic outcomes and murine colitis. Cathelicidin is induced by vitamin D in human colonic epithelial cells and promotes antimicrobial activity against E. coli. Our study provides insights into the vitamin D–cathelicidin pathway as a potential therapeutic target.

BACKGROUND Bladder injuries often occur in the setting of polytrauma, and if severe, may require open surgical repairs. We assess the role of urologists and general surgeons (GS) in the open surgical management of bladder injuries and their outcomes in a traumatic setting. METHODS Patients who underwent open bladder injury repair secondary to trauma from 2000 to 2017 by urology or GS were identified in the Pennsylvania Trauma Outcome Study database by International Classification of Diseases-9th Rev.-Clinical Modification procedure codes (57.19-57.93). Patient demographics, initial trauma assessment, length of hospital stay, associated complications, and mortality were evaluated. Urology management of a bladder injury was defined by documentation of a urologist in the operating room or urological consultation during the hospital stay. GS management was defined by documented bladder repair without urology involvement as described previously. RESULTS Of 624,504 patients in the database, 701 met inclusion criteria (419 managed by urology, 282 by GS). The most commonly performed procedure was suturing of bladder lacerations (80.5%). On univariate analysis, GS was more likely to manage patients with penetrating injuries and those who required exploratory laparotomy less than 2 hours upon arrival. Urology was more likely to manage patients with concomitant pelvic fractures and higher Injury Severity Score (ISS). On multivariate analysis, higher ISS was predictive of urology management (odds ratio, 1.83; 95% confidence interval, 1.17-2.87, p = 0.008), while patients who required urgent exploratory laparotomy was predictive of GS management (odds ratio, 0.34; 95% confidence interval, 0.21-0.55, p < 0.001). Patients with concomitant pelvic fractures (n = 318) were also more likely to have higher ISS (p < 0.001) and were more likely to be managed by urology (odds ratio, 1.52; 95% confidence interval, 1.01-2.30, p = 0.046). Mortality, length of hospital stay, and complication rates were not significantly different between the two specialties and among individual procedures. CONCLUSION Our study describes the landscape of traumatic bladder repairs between urology and GS. GS may maintain similar patient outcomes when managing select cases of traumatic bladder injuries in the absence of urologists. LEVEL OF EVIDENCE Therapeutic, level IV.

Background Patients with depression frequently seek care in the emergency department (ED), especially in the context of suicidal ideation (SI) and self-harm (SH). However, the prevalence and trends in the United States (US) of ED visits for depression have not yet been characterized using a nationally representative sample. This study evaluates ED trends for depression in the US from 2006 to 2014. Methods Data was obtained from the Nationwide Emergency Department Sample (NEDS) in 2006 and 2014 using a primary ICD-9 diagnosis of depression or a primary diagnosis of suicidal ideation (SI) and a secondary diagnosis of depression. Results Between 2006 and 2014, there was a 25.9% increase in visits to the ED for depression, which was higher than the 14.8% increase in total ED visits during this time period. The mean inflation adjusted charges associated with depression-related ED visits increased by 107.7%, which was higher than the increase in mean charges for all ED visits in the same time period (40.47%). Visit rates were bimodally distributed with respect to age, with peaks in adolescence and middle age. Notably there was a 61.3% increase in ED visits for depression in individuals younger than 20 between 2006 and 2014. Over half of patients were admitted for inpatient care with a mean length of stay of 5.6 days in both years. Inpatient charges increased 71.8% between 2006 and 2014. Conclusions ED visits for depression in the United States rose 25.9% between 2006 and 2014, which was higher than the 14.8% increase in total ED visits during this time period. Over half of ED depression visits were admitted to inpatient stay (mean 5.6 days both years).

BACKGROUND & AIMS: Vitamin D has immune modulating effects on cytokines. Serum vitamin D levels are associated with the risk of relapse in patients with ulcerative colitis (UC), through unknown mechanisms. We tested the hypothesis that this beneficial role of vitamin D on UC is mediated through anti-inflammatory serum cytokine profiles. METHODS: Serum samples from a prospective cohort of seventy UC patients in clinical remission were collected and baseline histological and endoscopic scores were recorded at enrollment. Clinical relapse events were recorded over the 12-month follow-up period. Serum vitamin D and cytokines levels (IL-6, IL-8, IL-17A, TNF-α, IFN-γ, IL-4, IL-10) were quantified using ELISA. Linear regression was used to determine correlation between vitamin D and cytokine profiles. Logistic regression models were used to determine the association between serum cytokine profiles and baseline histologic mucosal healing and clinical relapse. RESULTS: Higher serum vitamin D levels positively correlated with higher ratios of IL-4+IL-10/IL-17A+TNF-α (r= 0.37, P

Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) are cell surface-located transmembrane ecto-enzymes of the CD39 superfamily which regulate inflammation and tissue repair by catalyzing the phosphohydrolysis of extracellular nucleotides and modulating purinergic signaling. In the liver, NTPDase2 is reportedly expressed on portal fibroblasts, but its functional role in regulating tissue regeneration and fibrosis is incompletely understood. Here, we studied the role of NTPDase2 in several models of liver injury using global knockout mice. Liver regeneration and severity of fibrosis were analyzed at different time points after exposure to carbon tetrachloride (CCl4) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or partial hepatectomy in C57BL/6 wild-type and globally NTPDase2-deficient (Entpd2 null) mice. After chronic CCl4 intoxication, Entpd2 null mice exhibit significantly more severe liver fibrosis, as assessed by collagen content and histology. In contrast, deletion of NTPDase2 does not have a substantial effect on biliary-type fibrosis in the setting of DDC feeding. In injured livers, NTPDase2 expression extends from the portal areas to fibrotic septae in pan-lobular (CCl4-induced) liver fibrosis; the same pattern was observed, albeit to a lesser extent in biliary-type (DDC-induced) fibrosis. Liver regeneration after partial hepatectomy is not substantively impaired in global Entpd2 null mice. NTPDase2 protects from liver fibrosis resulting from hepatocellular injury induced by CCl4. In contrast, Entpd2 deletion does not significantly impact fibrosis secondary to DDC injury or liver regeneration after partial hepatectomy. Our observations highlight mechanisms relating to purinergic signaling in the liver and indicate possible therapeutic avenues and new cellular targets to test in the management of hepatic fibrosis.

Cd39 scavenges extracellular ATP and ADP, ultimately generating adenosine, a nucleoside, which has anti-inflammatory effects in the vasculature. We have evaluated the role of Cd39 in the development of atherosclerosis in hyperlipidemic mice. ApoE KO (Cd39+/+/ApoE−/−) and Cd39/ApoE double KO (DKO) (Cd39−/−/ApoE−/−) mice were maintained on chow or Western diet for up to 20 weeks before evaluation of atherosclerotic lesions. We found that DKO mice exhibited significantly fewer atherosclerotic lesions than ApoE KO mice, irrespective of diet. Analyses of plaque composition revealed diminished foam cells in the fatty streaks and smaller necrotic cores in advanced lesions of DKO mice, when compared with those in ApoE KO mice. This atheroprotective phenotype was associated with impaired platelet reactivity to ADP in vitro and prolonged platelet survival, suggesting decreased platelet activation in vivo. Further studies with either genetic deletion or pharmacological inhibition of Cd39 in macrophages revealed increased cholesterol efflux mediated via ABCA1 to ApoA1. This phenomenon was associated with elevated plasma HDL levels in DKO mice. Our findings indicate that complete deletion of Cd39 paradoxically attenuates development of atherosclerosis in hyperlipidemic mice. We propose that this phenotype occurs, at least in part, from diminished platelet activation, increased plasma HDL levels, and enhanced cholesterol efflux and indicates the complexity of purinergic signaling in atherosclerosis.

Background Ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3), also known as CD39L3, is the dominant ectonucleotidase expressed by beta cells in the islet of Langerhans and on nerves. NTPDase3 catalyzes the conversion of extracellular ATP and ADP to AMP and modulates purinergic signaling. Previous studies have shown that NTPDase3 decreases insulin release from beta-cells in vitro. This study aims to determine the impact of NTPDase3 in diet-induced obesity (DIO) and metabolism in vivo. Methods We developed global NTPDase3 deficient (Entpd3−/−) and islet beta-cell-specific NTPDase-3 deficient mice (Entpd3flox/flox,InsCre) using Ins1-Cre targeted gene editing to compare metabolic phenotypes with wildtype (WT) mice on a high-fat diet (HFD). Results Entpd3−/− mice exhibited similar growth rates compared to WT on chow diet. When fed HFD, Entpd3−/− mice demonstrated significant resistance to DIO. Entpd3−/− mice consumed more calories daily and exhibited less fecal calorie loss. Although Entpd3−/− mice had no increases in locomotor activity, the mice exhibited a significant increase in basal metabolic rate when on the HFD. This beneficial phenotype was associated with improved glucose tolerance, but not higher insulin secretion. In fact, Entpd3flox/flox,InsCre mice demonstrated similar metabolic phenotypes and insulin secretion compared to matched controls, suggesting that the expression of NTPDase3 in beta-cells was not the primary protective factor. Instead, we observed a higher expression of uncoupling protein 1 (UCP-1) in brown adipose tissue and an augmented browning in inguinal white adipose tissue with upregulation of UCP-1 and related genes involved in thermogenesis in Entpd3−/− mice. Conclusions Global NTPDase3 deletion in mice is associated with resistance to DIO and obesity-associated glucose intolerance. This outcome is not driven by the expression of NTPDase3 in pancreatic beta-cells, but rather likely mediated through metabolic changes in adipocytes.

Diabetic individuals commonly report disordered bowel habits. This study aims to report the prevalence and associated factors of chronic diarrhea (CD) and chronic constipation (CC) in diabetics using a nationally representative sample of US adults. Analyses were performed using data from subjects in the 2009–2010 National Health and Nutrition Examination Survey (NHANES) dataset who completed the Bowel Health Questionnaire. The NHANES dataset provides medical comorbidities, demographics, and dietary habits of a nationally representative group of adult survey participants in the United States. CC and CD were defined by Bristol Stool Form Scale (BSFS) Types 1 & 2 and BSFS Types 6 & 7 as the “usual or most common stool type,” respectively, and frequent laxative users were also defined as having CC. Co-variables for all subjects included demographic and lifestyle factors, and co-variables evaluated only in diabetics included treatment and severity markers for diabetes. We identified 661 diabetic subjects and 4488 non-diabetic subjects. Diabetic subjects (25.8%) reported disordered bowel habits. In unadjusted analysis, CD was more prevalent in diabetics than in non-diabetics (11.2% vs. 6.0%; p

Background & Aims Fecal urgency is a common symptom among patients with gastrointestinal disorders, but can also occur in healthy individuals with normal bowel habits. There have been few studies of fecal urgency in the general population. We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) to analyze the prevalence of and risk factors for this symptom. Methods We analyzed data from 4676 persons who completed the Bowel Health Questionnaire from the NHANES, from 2009 through 2010. The NHANES sampled a nationally representative group of adults in the United States and provides information on demographics, medical comorbidities, and dietary habits of survey participants. The Bowel Health Questionnaire provided additional information about bowel symptoms such as urgency, incontinence, constipation, and diarrhea. We identified individuals with fecal urgency and calculated differences in fecal urgency among subgroups using chi-squared analysis. We used logistic regression to identify factors associated with urgency. Results In our study population, the prevalence of fecal urgency was 3.3%; 29.5% of individuals with fecal urgency had diarrhea. The prevalence of fecal urgency was significantly higher in individuals who had diarrhea (14.8%) than in individuals without diarrhea (3.1%). Older age, female sex, poverty, urinary urge incontinence, diarrhea, and increased stool frequency were all associated with fecal urgency on multivariable analysis. Decreased fiber intake and increased carbohydrate intake were associated with urgency among individuals with diarrhea. Conclusions In an analysis of data from 4676 individuals who completed a Bowel Health Questionnaire from the NHANES, we found a significantly higher proportion of individuals with diarrhea to have fecal urgency. However, most individuals with fecal urgency do not have diarrhea. Factors associated with fecal urgency vary among individuals with and without diarrhea.

No studies to date estimate the prevalence of chronic diarrhea in the United States using the Bristol stool form scale (BSFS). This study aims to report the prevalence and associated factors of chronic diarrhea using BSFS scores in a nationally representative sample of US adults.We identified 5,246 adult participants (age ≥20 years) who completed the bowel health questionnaire in the National Health and Nutrition Examination Survey 2009-2010 data set. Chronic diarrhea was defined as type 6 or 7 rating on the BSFS (mushy or liquid consistency) as the "usual or the most common stool type." Co-variables included age, race, education, poverty income ratio, body mass index, number of medications, feeling depressed, physical activity, and dietary intake. Prevalence estimates and prevalence odds ratios (PORs) were analyzed in adjusted multivariable models using appropriate sampling weights.We found a prevalence of chronic diarrhea of 6.6% (95% confidence interval (CI) 5.8, 7.4) in the nationally representative data set. High daily carbohydrate intake (POR 1.56, 95% CI 1.02, 2.40), obesity (POR 2.04, 95% CI 1.44, 2.89), feeling depressed (POR 1.84, 95% CI 1.21, 2.80), older age (POR 1.02, 95% CI 1.01, 1.02), and female sex (POR 1.68, 95% CI 1.28, 2.21) were positively correlated with chronic diarrhea. Non-Hispanic White race (POR 0.49, 95% CI 0.29, 0.81) and higher education (POR 0.60, 95% CI 0.43, 0.83) were negatively correlated with chronic diarrhea.In a nationally representative sample of the US adults, the prevalence of chronic diarrhea was 6.6%. We identified demographic, lifestyle, and dietary factors associated with chronic diarrhea.

Unconjugated bilirubin (UCB), a product of heme oxidation, has known immunosuppressant properties but the molecular mechanisms, other than antioxidant effects, remain largely unexplored. We note that UCB modulates T helper type 17 (Th17) immune responses, in a manner dependent upon heightened expression of CD39 ectonucleotidase. UCB has protective effects in experimental colitis, where it enhances recovery after injury and preferentially boosts IL-10 production by colonic intraepithelial CD4+ cells. In vitro, UCB confers immunoregulatory properties on human control Th17 cells, as reflected by increased levels of FOXP3 and CD39 with heightened cellular suppressor ability. Upregulation of CD39 by Th17 cells is dependent upon ligation of the aryl hydrocarbon receptor (AHR) by UCB. Genetic deletion of CD39, as in Entpd1–/– mice, or dysfunction of AHR, as in Ahrd mice, abrogates these UCB salutary effects in experimental colitis. However, in inflammatory bowel disease (IBD) samples, UCB fails to confer substantive immunosuppressive properties upon Th17 cells, because of decreased AHR levels under the conditions tested in vitro. Immunosuppressive effects of UCB are mediated by AHR resulting in CD39 upregulation by Th17. Boosting downstream effects of AHR via UCB or enhancing CD39-mediated ectoenzymatic activity might provide therapeutic options to address development of Th17 dysfunction in IBD.

Objective Recent studies have suggested that the enteric nervous system can modulate gut immunity. Ecto-nucleoside triphosphate diphosphohydrolases [E-NTPDases] regulate purinergic signalling by sequential phosphohydrolysis of pro-inflammatory extracellular adenosine 5'-triphosphate [ATP]. Herein, we test the hypothesis that E-NTPDases modulate gut inflammation via neuro-immune crosstalk. Design We determined expression patterns of NTPDase2 and NTPDase3 in murine and human colon. Experimental colitis was induced by dextran sodium sulphate [DSS] in genetically engineered mice deficient in NTPDase2 or NTPDase3. We compared plasma adenosine diphosphatase [ADPase] activity from Crohn's patients and healthy controls, and linked the enzyme activity to Crohn's disease activity. Results NTPDase2 and -3 were chiefly expressed in cells of the enteric nervous system in both murine and human colon. When compared with wild type, DSS-induced colitis was exacerbated in Entpd2, and to a lesser extent, Entpd3 null mice as measured by disease activity score and histology, and marked anaemia was seen in both. Colonic macrophages isolated from Entpd2 null mice displayed a pro-inflammatory phenotype compared with wild type. In human plasma, Crohn's patients had decreases in ADPase activity when compared with healthy controls. The drop in ADPase activity was likely associated with changes in NTPDase2 and -3, as suggested by inhibitor studies, and were correlated with Crohn's disease activity. Conclusions NTPDase2 and -3 are ecto-enzymes expressed in the enteric nervous system. Both enzymes confer protection against gut inflammation in experimental colitis and exhibit alterations in Crohn's disease. These observations suggest that purinergic signalling modulated by E-NTPDases governs neuro-immune interactions that are relevant in Crohn's disease.

Our current understanding of normal bowel patterns in the United States (US) is limited. Available studies have included individuals with both normal and abnormal bowel patterns, making it difficult to characterize normal bowel patterns in the US. The current study aims to (1) examine frequency and consistency in individuals with self-reported normal bowel habits and (2) determine demographic factors associated with self-reported normalcy.This study used data from adult participants who completed bowel health questions as part of the National Health and Nutrition Examination Survey (NHANES) in 2009-2010 and who reported normal bowel patterns (N=4,775). Data regarding self-perceived bowel health; stool frequency; stool consistency (using the Bristol Stool Form Scale (BSFS)); and demographic factors were analyzed.95.9% of the sample reported between 3 and 21 BMs per week. Among men, 90% reported a BSFS between 3 and 5, while for women it was 2-6. After controlling for age, the following demographic variables were associated with normalcy: male sex, higher education, higher income,2 daily medications, and high daily fiber intake. Hispanic ethnicity was significantly associated with abnormal self-reported bowel habits.This is the first study to evaluate normal bowel frequency and consistency in a representative sample of adults in the US. The current findings bolster the common "3 and 3" metric of normal frequency (3 BMs/day to 3 BMs/week) while also suggesting different criteria for normal consistency for men and women. Finally, this study provides novel information about demographic factors associated with normal frequency and consistency.