The prevalence of obesity has risen to its highest values over the last two decades. While many studies have either shown brain or microbiome connections to obesity, few have attempted to analyze the brain-gut-microbiome relationship in a large cohort adjusting for cofounders. Therefore, we aim to explore the connection of the brain-gut-microbiome axis to obesity controlling for such cofounders as sex, race, and diet. Whole brain resting state functional MRI was acquired, and connectivity and brain network properties were calculated. Fecal samples were obtained from 287 obese and non-obese participants (males n = 99, females n = 198) for 16s rRNA profiling and fecal metabolites, along with a validated dietary questionnaire. Obesity was associated with alterations in the brain's reward network (nucleus accumbens, brainstem). Microbial diversity (p = .03) and composition (p = .03) differed by obesity independent of sex, race, or diet. Obesity was associated with an increase in Prevotella/Bacteroides (P/B) ratio and a decrease in fecal tryptophan (p = .02). P/B ratio was positively correlated to nucleus accumbens centrality (p = .03) and negatively correlated to fecal tryptophan (p = .004). Being Hispanic, eating a standard American diet, having a high Prevotella/Bacteroides ratio, and a high nucleus accumbens centrality were all independent risk factors for obesity. There are obesity-related signatures in the BGM-axis independent of sex, race, and diet. Race, diet, P/B ratio and increased nucleus accumbens centrality were independent risk factors for obesity. P/B ratio was inversely related to fecal tryptophan, a metabolite related to serotonin biosynthesis, and positively related to nucleus accumbens centrality, a region central to the brain's reward center. These findings may expand the field of therapies for obesity through novel pathways directed at the BGM axis.
Background: Homelessness and substance use are intricately related, and both are prevalent among emergency department (ED) patients. This study examined the longitudinal association of substance use characteristics with future homeless shelter entry among ED patients with any drug use or unhealthy alcohol use. Methods: We present results from a longitudinal cohort study of public hospital ED patients who screened positive for drug use or unhealthy alcohol use and who were not homeless at their baseline (index) ED visit. The primary outcome was homeless shelter entry within 12 months of baseline, ascertained in city homeless shelter administrative data. Primary independent variables of interest were alcohol use severity (AUDIT), drug use severity (DAST-10), and types of drugs used, as reported on baseline survey questionnaires. Results: Analyses included 1,210 ED patients. By 12 months following the baseline ED visit, 114 (9.4%) had entered a homeless shelter. Among patients with the most severe problems related to drug use (DAST-10 score 9-10), 40.9% entered a shelter within 12 months. Past shelter use was the strongest predictor of future shelter entry; once adjusting for historic shelter use the relationship of AUDIT and DAST-10 scores with future shelter entry was no longer statistically significant in multivariable models. Conclusions: ED patients with past year drug use or unhealthy alcohol use had relatively high likelihood of future shelter entry. Risk for homelessness should be addressed in future interventions with this population. Findings illustrate the complexity of relationships between substance use and homelessness.
Background Many institutions are training clinicians in point-of-care ultrasound (POCUS), but few POCUS skills checklists have been developed and validated. We developed a consensus-based multispecialty POCUS skills checklist with anchoring references for basic cardiac, lung, abdominal, and vascular ultrasound, and peripheral intravenous line (PIV) insertion. Methods A POCUS expert panel of 14 physicians specializing in emergency, critical care, and internal/hospital medicine participated in a modified-Delphi approach to develop a basic POCUS skills checklist by group consensus. Three rounds of voting were conducted, and consensus was defined by ≥ 80% agreement. Items achieving < 80% consensus were discussed and considered for up to two additional rounds of voting. Results Thirteen POCUS experts (93%) completed all three rounds of voting. Cardiac, lung, abdominal, and vascular ultrasound checklists included probe location and control, basic machine setup, image quality and optimization, and identification of anatomical structures. PIV insertion included additional items for needle tip tracking. During the first round of voting, 136 (82%) items achieved consensus, and after revision and revoting, an additional 21 items achieved consensus. A total of 153 (92%) items were included in the final checklist. Conclusions We have developed a consensus-based, multispecialty POCUS checklist to evaluate skills in image acquisition and anatomy identification for basic cardiac, lung, abdominal, and vascular ultrasound, and PIV insertion.
Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier : NCT00628745.
Introduction The use of the robot in general surgery has exploded in the last decade. The Veterans Health Administration presents a unique opportunity to study differences between surgical approaches due to the ability to control for health system and insurance variability. This study compares clinical outcomes between robot-assisted and laparoscopic or open techniques for three general surgery procedures. Methods A retrospective observational study using the Veterans Affair Surgical Quality Improvement Program database. Operative time, length of stay, and complications were compared for cholecystectomy (robot-assisted versus laparoscopic), ventral, and inguinal hernia repair (robot-assisted versus laparoscopic or open) from 2015 to 2019. Results More than 80,000 cases were analyzed (21,652 cholecystectomy, 9214 ventral hernia repairs, and 51,324 inguinal hernia repairs). Median operative time was longer for all robot-assisted approaches as compared to laparoscopic or open techniques with the largest difference seen between open and robot-assisted primary ventral hernia repair (unadjusted difference of 93 min, P < 0.001). Median length of stay was between 1 and 4 d and significantly for robot-assisted ventral hernia repairs (versus open, P < 0.01; versus lap for recurrent hernia, P < 0.05). Specific postoperative outcomes of interest were overall low with few differences between techniques. Conclusions While the robotic platform was associated with longer operative time, these findings must be interpreted in the context of a learning curve and indications for use (i.e., use of the robot for technically challenging cases). Our findings suggest that at the Veterans Health Administration, the robot is as safe a platform for common general surgery procedures as traditional approaches. Future studies should focus on patient-centered outcomes including pain and cosmesis.
Background: Falls are common in older adults and can lead to severe injuries. The Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial cluster-randomized 86 primary care practices across 10 health systems to a multifactorial intervention to prevent fall injuries, delivered by registered nurses trained as falls care managers, or enhanced usual care. STRIDE enrolled 5451 community-dwelling older adults age ≥70 at increased fall injury risk. Methods: We assessed fall-related outcomes via telephone interviews of participants (or proxies) every 4 months. At baseline, 12 and 24 months, we assessed health-related quality of life (HRQOL) using the EQ-5D-5L and EQ-VAS. We used Poisson models to assess intervention effects on falls, fall-related fractures, fall injuries leading to hospital admission, and fall injuries leading to medical attention. We used hierarchical longitudinal linear models to assess HRQOL. Results: For recurrent event models, intervention versus control incidence rate ratios were 0.97 (95% confidence interval [CI], 0.93-1.00; p = 0.048) for falls, 0.93 (95% CI, 0.80-1.08; p = 0.337) for self-reported fractures, 0.89 (95% CI, 0.73-1.07; p = 0.205) for adjudicated fractures, 0.91 (95% CI, 0.77-1.07; p = 0.263) for falls leading to hospital admission, and 0.97 (95% CI, 0.89-1.06; p = 0.477) for falls leading to medical attention. Similar effect sizes (non-significant) were obtained for dichotomous outcomes (e.g., participants with ≥1 events). The difference in least square mean change over time in EQ-5D-5L (intervention minus control) was 0.009 (95% CI, -0.002 to 0.019; p = 0.106) at 12 months and 0.005 (95% CI, -0.006 to 0.015; p = 0.384) at 24 months. Conclusions: Across a standard set of outcomes typically reported in fall prevention studies, we observed modest improvements, one of which was statistically significant. Future work should focus on patient-, practice-, and organization-level operational strategies to increase the real-world effectiveness of interventions, and improving the ability to detect small but potentially meaningful clinical effects. Clinicaltrials: gov identifier: NCT02475850.
Background Medication discrepancies can lead to adverse drug events and patient harm. Medication reconciliation is a process intended to reduce medication discrepancies. We developed a Secure Messaging for Medication Reconciliation Tool (SMMRT), integrated into a web-based patient portal, to identify and reconcile medication discrepancies during transitions from hospital to home. Objective We aimed to characterize patients’ perceptions of the ease of use and effectiveness of SMMRT. Methods We recruited 20 participants for semistructured interviews from a sample of patients who had participated in a randomized controlled trial of SMMRT. Interview transcripts were transcribed and then qualitatively analyzed to identify emergent themes. Results Although most patients found SMMRT easy to view at home, many patients struggled to return SMMRT through secure messaging to clinicians due to technology-related barriers. Patients who did use SMMRT indicated that it was time-saving and liked that they could review it at their own pace and in the comfort of their own home. Patients reported SMMRT was effective at clarifying issues related to medication directions or dosages and that SMMRT helped remove medications erroneously listed as active in the patient’s electronic health record. Conclusions Patients viewed SMMRT utilization as a positive experience and endorsed future use of the tool. Veterans reported SMMRT is an effective tool to aid patients with medication reconciliation. Adoption of SMMRT into regular clinical practice could reduce medication discrepancies while increasing accessibility for patients to help manage their medications. Trial Registration ClinicalTrials.gov NCT02482025; https://clinicaltrials.gov/ct2/show/NCT02482025
Importance: Despite longstanding efforts to improve health care quality for patients with complex needs who are at highest risk for hospitalization or death, to our knowledge, no guidance exists on what constitutes measurable high-quality care for this heterogeneous population. Identifying quality measures that are cross-cutting (ie, relevant to multiple chronic conditions and disease states) may enable health care professionals and health care systems to better design and report on quality improvement efforts for this patient population. Objective: To identify quality measures of care and prioritize quality-of-care concepts in the ambulatory primary care setting for patients in the Veterans Health Administration (VHA) who have complex care needs and are at high risk for adverse outcomes, such as hospitalization or death. Evidence review: In this expert panel assessment and prioritization, relevant measure concepts for future quality measure development in 3 care categories (assessment, management, and other features of health care) were extracted from a systematic review, conducted from June 2020 to June 2021, of published studies that suggested, evaluated, or used indicators of quality care for patients at high risk of adverse outcomes. Measure concepts associated with single conditions, surgical or other specialty care settings, and inpatient care were excluded. A panel of 14 experts (10 VHA leaders and staff, 2 non-VHA physician investigators, and 2 veterans) discussed and rated the importance of the remaining set of potentially relevant measure concepts using a modified RAND/UCLA Appropriateness Method on January 15, 2021. Measure concepts were rated on a scale of 1 to 9, with 9 being the highest priority. A median rating of 7.5 or greater was used as the cutoff to identify the highest-priority items. Findings: The systematic review identified 519 measure concepts, from which 15 domains and 49 measure concepts were proposed for expert panel consideration. After panel discussions and changes to measure concepts, the expert panel rated 63 measure concepts in 13 domains. The measure concepts with the highest median ratings focused on caregiver availability and support, COVID-19 vaccination, and pneumonia vaccination (all rated 9.0); housing instability (rated 8.5); and physical function, depression symptoms, cognitive impairment, prescription regimen, primary care follow-up after an emergency department visit or hospitalization, and timely transmission of discharge information to primary care (all rated 8.0). Recommendations to improve care included timely assessment of housing instability, caregiver support, physical function, depression symptoms, and cognitive impairment; annual prescription regimen review; coordinated transitions in care; and preventive care including vaccinations. Conclusions and relevance: The expert panelists identified a parsimonious set of high-priority, evidence-based, cross-cutting quality measure concepts for improving care of patients at high risk for adverse health outcomes in the VHA. These quality measures may inform both future research for patients at high risk and health care system quality improvement.
Background Hepatocellular carcinoma (HCC) is rapidly increasing in the U.S. and is a leading cause of mortality for patients with cirrhosis. Discovering novel biomarkers for risk stratification of HCC is paramount. We examined biomarkers of the gut-liver axis in a prospective multicenter cohort.Methods Patients with cirrhosis without a history of HCC were recruited between May 2015 and March 2020 and prospectively followed at 3 tertiary care hospitals in Los Angeles. Microbiome analysis was performed on duodenal biopsies and metabolomic analysis was performed on serum samples, collected at the time of enrollment. Optimal microbiome-based survival analysis and Cox proportional hazards regression analysis were used to determine microbiota and metabolite associations with HCC development, respectively.ResultsA total of 227 participants with liver cirrhosis contributed a total of 459.58 person-years of follow-up, with 14 incident HCC diagnoses. Male sex (HR = 7.06, 95% CI = 1.02–54.86) and baseline hepatic encephalopathy (HE, HR = 4.65, 95% CI = 1.60–13.52) were associated with developing HCC over follow-up. Adjusting for age, sex, baseline HE, and alkaline phosphatase, an increased risk of HCC were observed for participants with the highest versus lowest three quartiles for duodenal Alloprevotella (HR = 3.22, 95% CI = 1.06–9.73) and serum taurocholic acid (HR = 6.87, 95% CI = 2.32–20.27), methionine (HR = 9.97, 95% CI = 3.02–32.94), and methioninesulfoxide (HR = 5.60, 95% CI = 1.84–17.10). Being in the highest quartile for Alloprevotella or methionine had a sensitivity and specificity for developing HCC of 85.71% and 60.56%, respectively, with an odds ratio of 10.92 (95% CI = 2.23–53.48).Conclusion Alloprevotella and methionine, methioninesulfoxide, and taurocholic acid predicted future HCC development in a high-risk population of participants with liver cirrhosis.
Purpose Early clinical failure criteria (ECFC) were recently introduced to predict unfavorable outcomes in patients with Gram-negative bloodstream infections (BSI). ECFC include hypotension, tachycardia, tachypnea or mechanical ventilation, altered mental status, and leukocytosis evaluated at 72–96 h after BSI. The aim of this retrospective cohort study was to assess performance of ECFC in predicting 28-day mortality in Enterococcus species BSI. Methods Hospitalized adults with Enterococcus species BSI at Prisma Health hospitals from 1 January 2015 to 31 July 2018 were identified. Multivariate logistic regression was used to determine the association between ECFC and 28-day mortality. Area under the receiver operating characteristic (AUROC) curve was used to measure model discrimination. Results Among 157 patients, 28 (18%) died within 28 days of BSI. After adjustments in multivariate model, the risk of 28-day mortality increased in the presence of each additional ECFC (OR 1.6, 95% CI 1.2–2.3, p = 0.005). Infective endocarditis (OR 3.9, 95% CI 1.4–10.7, p = 0.01) was independently associated with 28-day mortality. AUROC curve of ECFC model in predicting 28-day mortality was 0.74 with ECFC of 2 identified as the best breakpoint. Mortality was 8% in patients with ECFC < 2 compared to 33% in those with ECFC ≥ 2 (p < 0.001). Conclusion ECFC had good discrimination in predicting 28-day mortality in patients with Enterococcus species BSI. These criteria may have utility in future clinical investigations.
Diminished social motivation is a core feature of schizophrenia that might reflect disturbances in social reward processing. It is not known whether these disturbances reflect anticipatory (“wanting”) and/or consummatory (“liking”) pleasure deficits. The primary aim of this study was to examine social versus nonsocial reward processing during these temporally distinct substages using event-related potential (ERP) components. Twenty-three schizophrenia participants and 20 healthy participants completed an incentive delay task with social (i.e., smiling expressions) and nonsocial (i.e., money) rewards. We measured two anticipatory ERPs (i.e., “wanting”) (target anticipation: Contingent Negative Variation [CNV]; feedback anticipation: Stimulus Preceding Negativity [SPN]) and one consummatory ERP (i.e., “liking”) (feedback receipt: P300). As a secondary aim, we examined correlations between the ERPs and interview-rated motivational negative symptoms and social functioning. Schizophrenia participants showed overall less target anticipation (blunted CNV) across all trials (social and nonsocial) than healthy participants. Importantly, schizophrenia participants exhibited less anticipation of social rewards relative to nonsocial rewards (SPN), whereas healthy participants showed similar anticipation for both reward types. Both groups showed similar responses to social and nonsocial reward receipt (P300). Furthermore, social reward anticipation during the incentive delay task was associated with more social approach behaviors in the real-world. Together, these findings provide preliminary evidence for intact social reward “liking” and impaired “wanting” in schizophrenia.
Background One year of adjuvant durvalumab following concurrent chemoradiotherapy significantly improves progression-free survival (PFS) and overall survival (OS) for patients with stage III non-small cell lung cancer (NSCLC). However, the optimal length of adjuvant therapy has not been determined. Methods We identified patients with stage III NSCLC treated with definitive chemoradiation and adjuvant durvalumab from November 2017 to April 2021 from the United States Veterans Affairs system. Predictors of early durvalumab discontinuation were evaluated with Cox proportional hazards regression. The effect of differing durations of durvalumab treatment (up to 6, 9, and 12 months) on PFS and OS were compared with a marginal structural model and time-dependent Cox modelling. Results We included 1006 patients with stage III non-small cell lung cancer who received concurrent chemoradiotherapy and at least one dose of adjuvant durvalumab. The median duration of durvalumab treatment was 7 months (interquartile range 2.8–11.5) and 31% completed the intended durvalumab course. The most common reasons for early discontinuation were tumour progression (22%), immune-related adverse events (15%), and non-immune-related toxicity (6.0%), Marginal structural models suggested similar PFS for 9 months versus 12 months of durvalumab treatment and inferior PFS for 6 months versus 12 months. Conclusions A substantial proportion of patients undergoing adjuvant durvalumab discontinue therapy early due to toxicity, and shorter durvalumab treatment durations may provide similar disease control to 12 months of therapy. Prospective randomised controlled studies are needed to characterise the optimal durvalumab treatment duration in locally advanced NSCLC patients.
Event-related potential (ERP) studies of motivated attention in schizophrenia typically show intact sensitivity to affective vs. non-affective images depicting diverse types of content. However, it is not known whether this ERP pattern: 1) extends to images that solely depict social content, (2) applies across a broad sample with diverse psychotic disorders, and (3) relates to self-reported trait social anhedonia. We examined late positive potential (LPP) amplitudes to images involving people that were normatively pleasant (affiliative), unpleasant (threatening), or neutral in 97 stable outpatients with various psychotic disorders and 38 healthy controls. Both groups showed enhanced LPP to pleasant and unpleasant vs. neutral images to a similar degree, despite lower overall LPP in patients. Within the patients, there were no significant LPP differences among subgroups (schizophrenia vs. other psychotic disorders; affective vs. non-affective psychosis) for the valence effect (pleasant/unpleasant vs. neutral). Higher social anhedonia showed a small, significant relation to lower LPP to pleasant images across all groups. These findings suggest intact motivated attention to social images extends across psychotic disorder subgroups. Dimensional transdiagnostic analyses revealed a modest association between self-reported trait social anhedonia and an LPP index of neural sensitivity to pleasant affiliative images.
Nonalcoholic fatty liver disease (NAFLD) has reached pandemic proportions with one of its most consequential complications being hepatocellular carcinoma (HCC). NAFLD-related HCC is becoming the leading indication for liver transplantation in the USA. Given the scarcity of available organs, early detection and prevention remain key in prevention and management of the disease. Over the years, the YAP/TAZ pathway emerged as a key signal transduction pathway in the pathogenesis of HCC. In this review, we explore the interplay between the YAP/TAZ pathway as a point of convergence in HCC pathogenesis. We review the evidence of how lipid reprogramming and key lipid pathways, saturated and monounsaturated fatty acids (through the rate limiting enzyme stearoyl Co-A desaturase), the mevalonic acid pathway (the role of statins) and mTORC1 all play critical roles in intricate and complex network that tightly regulate the YAP/TAZ pro-oncogenic pathway.
Objective To estimate the effectiveness of messenger RNA (mRNA) booster doses during the period of Delta and Omicron variant dominance. Design We conducted a matched test-negative case–control study to estimate the vaccine effectiveness (VE) of three and two doses of mRNA vaccines against infection (regardless of symptoms) and against COVID-19-related hospitalisation and death. Setting Veterans Health Administration. Participants We used electronic health record data from 114 640 veterans who had a SARS-CoV-2 test during November 2021–January 2022. Patients were largely 65 years or older (52%), male (88%) and non-Hispanic white (59%). Main outcome measures First positive result for a SARS-CoV-2 PCR or antigen test. Results Against infection, booster doses had higher estimated VE (64%, 95% CI 63 to 65) than two-dose vaccination (12%, 95% CI 10 to 15) during the Omicron period. For the Delta period, the VE against infection was 90% (95% CI 88 to 92) among boosted vaccinees, higher than the VE among two-dose vaccinees (54%, 95% CI 50 to 57). Against hospitalisation, booster dose VE was 89% (95% CI 88 to 91) during Omicron and 94% (95% CI 90 to 96) during Delta; two-dose VE was 63% (95% CI 58 to 67) during Omicron and 75% (95% CI 69 to 80) during Delta. Against death, the VE with a booster dose was 94% (95% CI 90 to 96) during Omicron and 96% (95% CI 87 to 99) during Delta. Conclusions Among an older, mostly male, population with comorbidities, we found that an mRNA vaccine booster was highly effective against infection, hospitalisation and death. Although the effectiveness of booster vaccination against infection was moderately higher against Delta than against the Omicron SARS-CoV-2 variant, effectiveness against severe disease and death was similarly high against both variants.
Objective To evaluate the effects of interdisciplinary pain management on pain-related disability and opioid reduction in polymorbid pain patients with two or more comorbid psychiatric conditions. Design Two-arm randomized clinical trial testing a three-week intervention with assessments at pre-treatment, post-treatment, 6-month and 12-month follow-up. Setting Department of Veterans Affairs medical facility. Participants 103 military veterans with moderate (or worse) levels of pain-related disability, depression, anxiety, and/or PTSD randomly assigned to usual care (n=53) and interdisciplinary pain management (n=50). All participants reported recent persistent opioid use. Trial participants had high levels of comorbid medical and mental health conditions. Interventions Experimental arm – a three-week, interdisciplinary pain management program guided by a structured manual; Comparison arm – usual care in a large VA medical facility. Main Outcome Measures Oswestry Disability Index (pain disability); Timeline Followback Interview and Medication Event Monitoring System (opioid use). Analysis used generalized linear mixed model with all posttreatment observations (posttreatment, 6-month follow-up, 12-month follow-up) entered simultaneously to create a single posttreatment effect. Results Veterans with polymorbid pain randomized to the interdisciplinary pain program reported significantly greater decreases in pain-related disability compared to veterans randomized to treatment as usual (TAU) at posttreatment, 6-month and 12-month follow-up. Aggregated mean pain disability scores (i.e., a summary effect of all posttreatment observations) for the interdisciplinary pain program were -9.1 (95% CI: -14.4, -3.7, P = .001) points lower than TAU. There was no difference between groups in the proportion of participants who resumed opioid use during trial participation (32% in both arms). Conclusion These findings offer the first evidence of short- and long-term interdisciplinary pain management efficacy in polymorbid pain patients, but more work is needed to examine how to effectively decrease opioid use in this population.
Background and Aims While perceived stress (PS) has been associated with symptomatic flares in inflammatory bowel disease, clinical and physiological measures associated with perceived stress and flare are not known. The aim of this study was to identify physiological factors associated with perceived stress in ulcerative colitis (UC) subjects, and their relationship with flare. Methods UC subjects in clinical remission (Simple Colitis Clinical Activity Index (SCCAI) score< 5) underwent clinical and behavioral assessments, morning salivary cortisol measurements, autonomic nervous system activity testing [heart rate variability(HRV), electrodermal activity(EDA)] at baseline with patient-reported SCCAI every 2 weeks over 1-2 years and fecal calprotectin at time of flare. Clinical flares (SCCAI > 5) and biochemical flares (SCCAI > 5 with fecal calprotectin > 250 μg/g) were evaluated. Results One hundred and ten UC subjects were enrolled with mean follow-up of 65.6 weeks. UC subjects with higher and lower PS were determined. While the high PS group had 3.6 times higher odds of a clinical flare than the low PS group, no significant differences in biochemical flares were observed between the low and high PS groups. The high vs. low PS group differed in tonic sympathetic arousal as indexed by significantly greater baseline EDA [4.3 vs. 3.4 microsiemens(μS); p=0.026] in the high PS group, but not in terms of HRV and morning cortisol levels. Increased fecal calprotectin was associated with cardioautonomic measures suggesting lower parasympathetic activity. Conclusions Increased PS assessed at baseline is associated with tonic sympathetic arousal and greater odds of clinical flares in UC subjects.
It has been well established that traumatic brain injury (TBI) modifies the composition of gut microbiome. Epilepsy, which represents one of the common sequelae of TBI, has been associated with dysbiosis. Earlier study showed that the risk of post-traumatic epilepsy (PTE) after lateral fluid percussion injury (LFPI) in rats can be stratified based on pre-existing (i.e., pre-TBI) gut microbiome profile. In the present study, we examined whether fecal microbiota transfer (FMT) from naïve rats with different prospective histories of PTE would affect the trajectory of PTE in recipients. Fecal samples were collected from naïve adult male Sprague–Dawley rats, followed by LFPI. Seven months later, upon four weeks of vide-EEG monitoring (vEEG), the rats were categorized as those with and without PTE. Recipients were subjected to LFPI, followed by FMT from donors with and without impending PTE. Control groups included auto-FMT and no-FMT subjects. Seven month after LFPI, recipients underwent four-week vEEG to detect spontaneous seizures. After completing vEEG, rats of all groups underwent kindling of basolateral amygdala. Fecal microbiota transfer from donors with impending PTE exerted mild-to-moderate pro-epileptic effects in recipients, evident as marginal increase in multiple spontaneous seizure incidence, and facilitation of kindling. Analysis of fecal samples in selected recipients and their respective donors confirmed that FMT modified microbiota in recipients along the donors’ lines, albeit without full microbiome conversion. The findings provide further evidence that gut microbiome may actively modulate the susceptibility to epilepsy.
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