VA Sepulveda Ambulatory Care Center

Emerging observational studies have indicated the association between autism spectrum disorder (ASD) and IBD, including Crohn's disease (CD) and ulcerative colitis (UC), whereas the causality remains unknown. Summary-level data from large-scale genome-wide association (GWAS) studies of IBD and ASD were retrieved. Mendelian randomisation analyses were performed with a series of sensitivity tests. Genetic predisposition to ASD was not associated with the risk of IBD (odds ratio [OR] = 0.99, 95% confidence interval [CI = 0.91-1.06, p = 0.70; OR [95% CI]: 1.03 [0.93-1.13], p = 0.58 for CD; OR [95% CI]: 0.96 [0.87-1.05], p = 0.37 for UC) in the IIBDGC dataset. In the FinnGen dataset, their causal effects were unfounded (OR [95% CI]: 1.04 [0.94-1.15], p = 0.49 for IBD; OR [95% CI]: 1.08 [0.89-1.31], p = 0.42 for CD; OR [95% CI]: 1.00 [0.88-1.13], p = 0.95 for UC). In the meta-analysis of two datasets, the OR was 1.01 (95% CI 0.96-1.07, p = 0.45). For the risk of ASD under genetic liability to IBD, the OR from meta-analysis was 1.03 (95% CI 1.01-1.05, p = 0.01). Our findings indicate genetic predisposition to ASD might not increase the risk of IBD, whereas genetic liability to IBD is associated with an increased risk of ASD. Further investigations using more powerful datasets are warranted.

Abstract Introduction Short sleep duration and obstructive sleep apnea (OSA) are associated with increased rates of cardiovascular disease. Vascular inflammation and endothelial dysfunction are potential mechanisms for this association but can be burdensome or impractical to measure in clinical settings. Other characteristics of sleep health, such as sleep quality, insomnia symptoms, and daytime sleepiness, are infrequently studied in relation to endothelial function. The current study investigated the association between multiple dimensions of sleep health (apnea hypopnea index (AHI), insomnia symptoms, sleep quality, and daytime sleepiness) and endothelial dysfunction using peripheral arterial tonometry (PAT; EndoPAT, Itamar Medical). Methods Participants (N=43) with mild-to-moderate OSA, completed a baseline assessment including demographics, Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). OSA severity was measured with AHI from one night of PSG (home or in-lab). Microvascular endothelial function was assessed using EndoPAT. The hyperemic response was measured following upper arm occlusion and the reactive hyperemia index (RHI) was calculated. Cross-sectional associations of sleep (ISI, PSQI, ESS, AHI), demographic characteristics (age, sex) and BMI with the natural log of RHI (used due to non-normality) were examined using linear regression models. Results In the study sample, mean (SD) age = 54.4 (12.6) years, 63% were female and 77% identified as Black race. Higher AHI (b = -.015. SE = .01, p =.03) and older age (b = -.01. SE = .003, p =.005) were significantly associated with lower RHI, indicating worse endothelial function. ISI, PSQI, ESS, sex, and BMI were not significantly associated with RHI (p’s>.05). Conclusion This study identified an association between OSA severity (higher AHI) and greater endothelial dysfunction, using the novel non-invasive EndoPAT, and null associations with other self-reported sleep characteristics. The study was underpowered to include covariate adjustment or interaction terms, but future studies with larger samples and studies examining potential benefits of OSA treatment on endothelial function are needed. Support (if any) R01HL146059, K24HL143055, K24HL13632. EndoPAT device provided by ZOLL Itimar.

A major obstacle to the implantation of ex vivo engineered tissues is the incorporation of functional vascular supply to support the growth of new tissue and to minimize ischemic injury. Existing prevascularization systems, such as arteriovenous (AV) loop-based systems, require microsurgery, limiting their use to larger animals. We aimed to develop an implantable device that can be prevascularized to enable vascularization of tissues in small rodents, and test its application on the vascularization of embryonic kidneys. Implanting the chamber between the abdominal aorta and the inferior vena cava, we detected endothelial cells and vascular networks after 48 h of implantation. Loading the chamber with collagen I (C), Matrigel (M), or Matrigel + vascular endothelial growth factor) (MV) had a strong influence on vascularization speed: Chambers loaded with C took 7 days to vascularize, 4 days for chambers with M, and 2 days for chambers with MV. Implantation of E12.5 mouse embryonic kidneys into prevascularized chambers (C, MV) was followed with significant growth and ureteric branching over 22 days. In contrast, the growth of kidneys in non-prevascularized chambers was stunted. We concluded that our prevascularized chamber is a valuable tool for vascularizing implanted tissues and tissue-engineered constructs. Further optimization will be necessary to control the directional growth of vascular endothelial cells within the chamber and the vascularization grade. Impact Statement Vascularization of engineered tissue, or organoids, constructs is a major hurdle in tissue engineering. Failure of vascularization is associated with prolonged ischemia time and potential tissue damage due to hypoxic effects. The method presented, demonstrates the use of a novel chamber that allows rapid vascularization of native and engineered tissues. We hope that this technology helps to stimulate research in the field of tissue vascularization and enables researchers to generate larger engineered vascularized tissues.

Introduction: Fatigue has garnered significant attention due to its detrimental effects on overall health and well-being. Fatigue was previously considered as a common symptom of Inflammatory Bowel Disease (IBD). However, approximately 50% of patients with IBD have experienced fatigue before their initial diagnosis. Whether fatigue is the cause or result of IBD remains unknown. Thus, this study was to explore the causal association between fatigue and IBD. Methods: Our observational analysis was based on UK Biobank, a population-based cohort. 478 262 participants aged 37 - 73 were enrolled from 2006 to 2010 with complete information on the frequency of tiredness questionnaire at baseline. We classified the participants into 2 or 4 groups based on the frequency of tiredness. We used Cox proportional hazards models to examine the hazard ratio (HR) and 95% confidence interval (CI) for incident IBD, CD (Crohn's disease) or UC (ulcerative colitis) after adjusting for potential confounders. Participants were categorized into different genetic risk groups, including high, intermediate, and low groups, based on the polygenic risk score (PRS) for IBD, UC and CD for subgroup analysis. Furthermore, Mendelian randomization (MR) study was used to investigate the causality. Results: Among 478 262 participants, 61 007 (12.8%) reported fatigued status at baseline. Compared with unfatigued group, the HRs of multivariable-adjusted models for fatigued groups were 1.28 (95%CI 1.16 to 1.41) for IBD, 1.15 (1.02 to 1.30) for UC and 1.55 (1.32 to 1.56) for CD. The risks of developing IBD, UC, and CD exhibited a stepwise increase with the frequency of tiredness. The results from subgroup analysis, including in high-polygenic risk score groups, were largely consistent. MR showed the significant evidence of casual association between the frequency of tiredness with higher risk of IBD (odds ratio [OR] = 2.15, 95% CI 1.36 to 3.38, P = 0.001), UC (OR 1.88, 95% CI 1.14 to 3.12, P = 0.014) and CD (OR 2.86, 95% CI 1.64 to 4.98, P < 0.001) (Table 1). Conclusion: Our findings suggest the causality between fatigue status and IBD. Participants frequently experienced fatigue are at a higher risk of developing IBD, with a stepwise increase of risk with the frequency of tiredness. A similar association was also observed between fatigue status and risk of CD but not UC. Moreover, such associations persisted in individuals with a higher genetic risk of IBD, CD and UC. Table 1. - Associations of fatigue with the risk of IBD HR (95% CI) HR (95% CI) HR (95% CI) Non-adjusted model P Partially adjusted model P Fully adjusted model P IBD Fatigue status Not fatigued 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) Fatigued 1.49 (1.36,1.63) < 0.001 1.40 (1.28,1.54) < 0.001 1.28 (1.16,1.41) < 0.001 Frequency of tiredness Not at all 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) Several days 1.17 (1.09,1.27) < 0.001 1.19 (1.10,1.28) < 0.001 1.14 (1.05,1.23) 0.001 More than half the days 1.40 (1.22,1.61) < 0.001 1.37 (1.19,1.57) < 0.001 1.26 (1.09,1.45) 0.002 Nearly every day 1.81 (1.60,2.04) < 0.001 1.70 (1.49,1.93) < 0.001 1.50 (1.31,1.71) < 0.001 UC Fatigue status Not fatigued 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) Fatigued 1.28 (1.14,1.43) < 0.001 1.23 (1.09,1.39) < 0.001 1.15 (1.02,1.30) 0.025 Frequency of tiredness Not at all 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) Several days 1.10 (1.00,1.21) 0.040 1.13 (1.03,1.24) 0.009 1.11 (1.01,1.22) 0.033 More than half the days 1.19 (1.00,1.21) 0.051 1.18 (0.99,1.41) 0.060 1.12 (0.94,1.34) 0.206 Nearly every day 1.48 (1.27,1.73) < 0.001 1.44 (1.23,1.69) < 0.001 1.32 (1.12,1.56) 0.001 CD Fatigue status Not fatigued 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) Fatigued 1.98 (1.71,2.30) < 0.001 1.80 (1.53,2.09) < 0.001 1.55 (1.32,1.82) < 0.001 Frequency of tiredness Not at all 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) Several days 1.36 (1.18,1.57) < 0.001 1.33 (1.15,1.54) < 0.001 1.23 (1.07,1.43) 0.005 More than half the days 1.99 (1.59,2.50) < 0.001 1.86 (1.47,2.34) < 0.001 1.63 (1.29,2.06) < 0.001 Nearly every day 2.64 (2.16,3.24) < 0.001 2.34 (1.86,2,84) < 0.001 1.88 (1.51,2.35) < 0.001 IBD: Inflammatory Bowel Disease; UC: Ulcerative Colitis; CD: Crohn's disease; HR: hazard ratio; CI: confidence interval.

The coronavirus disease 2019 (COVID-19) pandemic has led to a fundamental number of morbidity and mortality worldwide. Glucosamine was indicated to help prevent and control RNA virus infection preclinically, while its potential therapeutic effects on COVID-19-related outcomes are largely unknown. To assess the association of habitual glucosamine use with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospital admission, and mortality with COVID-19 in a large population based cohort. Participants from UK Biobank were reinvited between June and September 2021 to have SARS-CoV-2 antibody testing. The associations between glucosamine use and the risk of SARS-CoV-2 infection were estimated by logistic regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) for COVID-19-related outcomes were calculated using COX proportional hazards model. Furthermore, we carried out propensity-score matching (PSM) and stratified analyses. At baseline, 42 673 (20.7%) of the 205 704 participants reported as habitual glucosamine users. During median follow-up of 1.67 years, there were 15 299 cases of SARS-CoV-2 infection, 4214 cases of COVID-19 hospital admission, and 1141 cases of COVID-19 mortality. The fully adjusted odds ratio of SARS-CoV-2 infection with glucosamine use was 0.96 (95% CI: 0.92-1.01). The fully adjusted HR were 0.80 (95% CI: 0.74-0.87) for hospital admission, and 0.81 (95% CI: 0.69-0.95) for mortality. The logistic regression and Cox proportional hazard analyses after PSM yielded consistent results. Our study demonstrated that habitual glucosamine use is associated with reduced risks of hospital admission and death with COVID-19, but not the incidence of SARS-CoV-2 infection.

Abstract BackgroundAnorexia nervosa (AN) is a severe and complex psychiatric disorder with the highest mortality rate of all psychiatric disorders. Previous observational studies have comprehensively indicated an association between inflammatory bowel disease (IBD) and AN, but the causal effect remains unclear. We aimed to test the hypothesis that a causal relationship exists between IBD and the risk of AN.MethodsBased on published open genome-wide association study summary statistics, the single nucleotide polymorphisms (SNPs) of IBD, including ulcerative colitis (UC) and Crohn’s disease (CD), were selected as genetic instrumental variables. Two-sample Mendelian randomization (MR) analyses were conducted to infer the causal relationship between IBD and AN. The methods included inverse variance weighted (IVW), MR-Egger regression, weighted median estimator, weighted mode and MR Pleiotropy RESidual Sum and Outlier (MR-PERSSO). Furthermore, various sensitivity analyses were conducted to assess the robustness of our results.ResultsThe primary analysis IVW suggested that genetically predicted IBD were positively casually associated with AN risk (NSNP= 12, odds ratio [OR]: 1.143, 95% confidence interval [CI]: 1.032-1.266,P= 0.01). In subgroups, consistent positive causal associations with AN risk might show in UC (NSNP= 6, OR: 1.153, 95% CI: 1.022-1.301,P= 0.021), and CD (NSNP= 4, OR: 1.153, 95% CI: 1.008-1.319,P= 0.037). NO heterogeneity and pleiotropy were presented through sensitivity analysis and guaranteed credible and robust estimates.ConclusionOur study identifies that patients diagnosed with IBD, including UC and CD, could be causally associated with an increased risk of AN. It may have clinical benefits for early detection of AN and clinical decisions on management of IBD patients.

Endoscopy featured water-aided colonoscopy (WAC) as novel in the Innovation Forum in 2011. Gastrointestinal Endoscopy published a modified Delphi consensus review (MDCR) that supports WAC for clinical practice in 2021. We tested the hypothesis that experience was an important predictor of WAC use, either as water immersion (WI), water exchange (WE), or a combination of WI and WE. A questionnaire was sent by email to the MDCR authors with an in-depth knowledge of WAC. They responded and also invited colleagues and trainees without in-depth knowledge to respond. Logistic regression analysis was used with the reasons for WAC use treated as the primary outcome. Reports related to WAC post MDCR were identified. Of 100 respondents, >80% indicated willingness to adopt and modify practice to accommodate WAC. Higher adenoma detection rate (ADR) incentivized WE use. Procedure time slots ≤30 and >30min significantly predicted WI and WE use, respectively. Co-authors of the MDCR were significantly more likely to perform WAC (odds ratio [OR]=7.5, P=0.037). Unfamiliarity with (OR=0.11, P=0.02) and absence of good experience (OR=0.019, P=0.002) were associated with colonoscopists less likely to perform WAC. Reports related to WAC post MDCR revealed overall and right colon WE outcomes continued to improve. Network meta-analyses showed that WE was superior to Cap and Endocuff. On-demand sedation with WE shortened nursing recovery time. An important predictor of WAC use was experience. Superior outcomes continued to be reported with WE.