Severe Gastrointestinal Research Articles

P49 Belimumab as a potential therapy for lupus enteritis – a case report

Abstract Introduction Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with varied clinical manifestations. Gastrointestinal (GI) complaints are common in 40–60% of SLE patients. Most are mild; however severe life-threatening manifestations may occur. Lupus enteritis (LE) is a rare but severe GI manifestation of SLE, characterised by vasculitis or inflammation of the bowel. Belimumab is a recombinant human monoclonal antibody against the soluble B-lymphocyte stimulator protein (BLyS) and was the first licensed treatment for SLE and lupus nephritis. Herein, we report a case of lupus enteritis that responded well to belimumab therapy. Case description We present a 42-year-old Sri Lankan woman who was diagnosed with SLE in 2015 based on arthritis, Raynaud’s, haemoproteinuria, positive antinuclear antibodies (ANA), anti-double stranded DNA (dsDNA), and anti-Ro antibodies with low complements C3, C4. Renal biopsy confirmed class III a+c lupus nephritis. She was managed with prednisolone, mycophenolate mofetil, hydroxychloroquine and ramipril. She responded well to treatment. She was admitted in August 2018 with recurrent abdominal pains, distension, diarrhoea, nausea, vomiting, 20kg unintentional weight loss, arthritis, lymphadenopathy, and peripheral oedema. Over the last 12 months, she had 5 admissions with similar GI symptoms, which were managed as viral gastroenteritis. Investigations showed nephrotic range proteinuria - urine PCR 330 (0-15 mg/mmol), low albumin = 27 (40-52 g/L), positive anti-dsDNA antibodies = 211 (0-10 IU/ml), CRP 7 (0-4 mg/L), ESR 44 (0-12 mm/hr) with low complements C3 0.36 (0.90-1.80 g/L) and C4 0.07 (0.10-0.40 g/L). Contrast enhanced computed tomography (CECT) scan of the abdomen revealed diffuse oedema of the large bowel extending from the splenic flexure to the rectum, several areas of small bowel thickening, peritoneal enhancement, and moderate volume ascites. Infective causes for colitis were ruled out including abdominal tuberculosis. Sigmoidoscopy and biopsy ruled out inflammatory bowel disease, whereas surgical and gastroenterology reviews ruled out other causes for her presentation. She was diagnosed with lupus enteritis with flare of lupus nephritis and managed with pulsed intravenous methylprednisolone followed by tapering high dose oral prednisolone. Her symptoms gradually improved, and she was discharged. Unfortunately, over the next month, she had recurrent admissions with flares of lupus enteritis requiring further intravenous methylprednisolone. As a result, she was commenced on monthly IV belimumab. Since starting belimumab, she has not had any further flares of lupus enteritis and her anti-dsDNA antibody and complements C3, C4 levels have normalised. Discussion Lupus enteritis (LE) presents with non-specific GI symptoms such as abdominal pain (most common), nausea, vomiting, diarrhoea and ascites. In most cases, it develops months to years after SLE diagnosis but in some cases, may be the presenting feature. Its pathogenesis remains unknown; however, mesenteric vasculitis and/or thromboses are thought to play a role. Contrast enhanced computed tomography (CECT) abdomen is the gold-standard investigation and usually shows bowel wall oedema, dilated bowel loops (>3 cm), bowel wall thickening with peripheral enhancement (“target sign”/”double halo sign”), engorgement of mesenteric vessels with a palisade pattern (“comb-sign”), increased attenuation of mesenteric fat and/or ascites. Laboratory investigations usually reveal markers of active lupus. Significant proteinuria (>0.5 g/24 h) is usually found in around 50% of patients. LE is very steroid responsive, with most patients achieving disease remission with steroids alone. Additional immunosuppression (such as cyclophosphamide, MMF, azathioprine, HCQ or rituximab) may be used concomitantly, for other manifestations of SLE or in those with relapsing or refractory disease. Belimumab has previously been licensed for use in SLE and lupus nephritis; however, there is sparse literature about its use in lupus enteritis. Our patient responded very well to belimumab, with both clinical and immunological remission. Key learning points • Lupus enteritis is a rare but severe gastrointestinal (GI) manifestation of SLE that presents with non-specific GI symptoms such as abdominal pain (most common), nausea, vomiting, diarrhoea and ascites. Clinicians managing SLE patients should have a high index of suspicion regarding the diagnosis, else it may be easily missed leading to recurrent admissions and delayed treatment. • Contrast enhanced CT abdomen is the gold-standard investigation and shows characteristic changes - bowel wall oedema, dilated bowel loops (>3 cm), bowel wall thickening with peripheral enhancement (“target sign”/”double halo sign”), engorgement of mesenteric vessels with a palisade pattern (“comb-sign”), increased attenuation of mesenteric fat and/or ascites • Lupus enteritis is very steroid responsive, with most patients achieving disease remission with steroids alone. Some patients with other SLE manifestations, or relapsing/refractory disease may require additional immunosuppression. Belimumab may be another option to consider in such patients.

Management Effects on Gastrointestinal Disease in Red Wolves (Canis rufus) Under Human Care: A Retrospective Study.

Red wolves (Canis rufus) are the most critically endangered wolf globally, with over 95% of individuals living under human care. Gastrointestinal (GI) disease is one of the leading causes of death among adult red wolves under human care, yet links between management practices and this condition remain unclear. By integrating studbook data, survey-based husbandry information, veterinary records, and necropsy reports, our study explored the relationships between management practices and post-mortem diagnoses of GI mucosal disease among 36 adult red wolves between 2004 and 2022. For final diets fed for a minimum of 4 months before death, we report that wolves fed diets limited to only kibble were more likely to exhibit a greater severity of GI mucosal disease than those fed diets that integrated whole prey or other meat items. In addition, while living at their final facilities for a minimum of 9 months before death, wolves treated with a nonsteroidal anti-inflammatory drug exhibited more severe GI issues than those who were not. Conversely, we found no effect of housing and life history traits on GI health. This study highlights the importance of evaluating management and veterinary protocols on red wolf GI health.

Serum markers of microbial translocation and intestinal damage in assessment of gastrointestinal tract involvement in systemic sclerosis

Gastrointestinal (GI) tract involvement affects up to 90% of Systemic sclerosis (SSc) patients. The presence of GI symptoms is assessed by the University of California, Los Angeles, and Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT 2.0). Microbial translocation (MT) is reported in SSc patients consequently to increased intestinal permeability due to intestinal damage (ID) and dysbiosis. Aim of this study was to assess circulating levels of LBP and EndoCab IgM (markers of MT), IL-6 (marker of inflammation), I-FABP and Zonulin (markers of ID) in a cohort of SSc patients and healthy controls (HC). Moreover, we aimed to correlate these parameters with severity of GI symptoms. UCLA SCTC GIT 2.0 questionnaire was administered to 60 consecutive SSc patients. Markers of MT, inflammation and ID were evaluated in SSc patients and HC. SSc patients had higher median value of markers of MT, inflammation and ID than HC. The logistic regression analysis showed LBP as the only variable associated with an UCLA total score “moderate-to-very severe” [OR 1.001 (CI 95%: 1.001–1.002), p < 0.001]. The logistic regression analysis showed LBP [OR 1.002 (CI 95%: 1.001–1.003), p < 0.01] and disease duration [OR 1.242 (CI 95%: 1.023–1.506), p < 0.05] as variables associated with UCLA distension/bloating “moderate-to-very severe”. The logistic regression analysis showed LBP as the only variable associated with UCLA diarrhea “moderate-to-very severe” [OR 1.002 (CI 95%: 1.001–1.003), p < 0.01]. SSc patients with dysregulation gut mucosal integrity expressed by high levels of MT and ID biomarkers had more severe GI symptoms.

Distinct clinical trajectories of gastrointestinal progression among patients with systemic sclerosis.

Systemic sclerosis (SSc) is heterogeneous in its clinical presentation. Common manifestations cluster together, defining unique subgroups. This investigation aims to characterize gastrointestinal (GI) phenotypes and determine whether they can be distinguished by temporal progression. We examine a well-established SSc patient cohort with a modified Medsger GI severity score measured over time to determine heterogeneity in disease progression. Growth mixture models estimate each patient's phenotype and disease severity trajectory over time. We compare the characteristics of estimated phenotypes using non-parametric statistics and linear and logistic regression to compare patient characteristics between phenotypes while adjusting for disease duration. We examined 2696 SSc patients with at least two Medsger GI scores, identifying four unique phenotypes. The most common phenotype (n = 2325) ("Stable") had an average score of 1 that was consistent over time. Two phenotypes were progressive ["Early Progressive" (n = 142) and "Late Progressive" (n = 115)] with an initial average score of 1. The Early Progressive group increased initially and stabilized, and the Late Progressive group worsened slowly over time. A fourth phenotype ["Early Severe GI"; (n = 114)] had an initial average Medsger GI score just below 3 with high mortality and improving GI severity over time. Clinically distinct GI phenotypes exist among patients with SSc. These phenotypes are not only distinguished by GI and extra-intestinal SSc clinical complications, but they are also temporally distinct. Distinct autoantibody profiles are associated strongly with more severe GI disease.

Severity and organ distribution of graft-versus-host disease with post-transplant cyclophosphamide versus calcineurin inhibitor plus methotrexate/mycophenolate mofetil or sirolimus in allogenic HLA-matched or single-allele mismatched stem cell transplantation.

This retrospective single center study aims to describe changes in the severity and organ-specific distribution of GvHD, by comparing the outcomes of 3 distinct GvHD prophylaxis approaches. Between January 2012 and June 2022, 226 patients underwent allogeneic hematopoietic stem cell transplantation from HLA-matched or 1-allele mismatched related or unrelated donors. Fifty-eight (26%) received prophylaxis with calcineurin inhibitor in combination with mycophenolate mofetil or a short course of methotrexate (Cohort-1), 87 (38%) tacrolimus plus sirolimus (Cohort-2), and 81 (36%) post-transplant cyclophosphamide (PTCy) plus tacrolimus (Cohort-3). The incidence of grade II-IV aGvHD was 69% vs. 41.4% vs. 27.2%; p < .01. The most significant reduction with PTCy was observed in both stage 3-4 skin and lower gastrointestinal (GI) involvement (p < .01). The incidence of moderate-to-severe cGvHD at 12 months was 34.5% vs. 34.5% vs. 6.2%; p < .01. Moderate-to-severe skin and GI cGvHD was less common after PTCy (p < .01). The 1-year GvHD-free/relapse-free survival was higher with PTCy (p < .01). Our study indicates that PTCy-based GvHD prophylaxis reduces the frequency and severity of both acute and chronic GvHD, with a notable decrease in severe GI and cutaneous manifestations. The higher GRFS may result in lower GvHD-related mortality, leading to an improved quality of life among survivors.

Gastrointestinal system involvement in patients with primary immunodeficiency: a single center experience

Aim Primary immunodeficiencies (PIDs) are a heterogeneous disorder group characterized by an impaired immune system, leading to an increased susceptibility to infections and a wide range of clinical manifestations, including gastrointestinal (GI) complications. This study aimed to assess the GI manifestations of PID patients and highlight the significance of atypical gastrointestinal symptoms in the early diagnosis of these patients. Methods A retrospective analysis was conducted on pediatric patients diagnosed with PIDs at Selcuk University Medical Faculty from 2011 to 2021. The study focused on demographic data, clinical presentation, genetic mutations, and GI manifestations, including endoscopic evaluation. Patients were categorized according to the International Union of Immunological Societies (IUIS) PID classifications. Statistical analyses were performed to identify significant associations between PID types and GI manifestations. Results The cohort comprised 101 patients, with 46% presenting with GI symptoms, including malnutrition and chronic diarrhea, as the most common findings. Primary antibody deficiency (PAD) emerged as the most prevalent PID with GI involvement, followed by combined immunodeficiencies (CID) with associated or syndromic features. Endoscopic evaluations revealed inflammatory bowel disease (IBD)-like colitis in a significant subgroup of patients. The analysis showed that some GI symptoms were more common in specific PID categories, highlighting the importance of early gastroenterological assessment in PID patients. Conclusion Recognition of common GI symptoms in pediatric patients with PIDs may facilitate early diagnosis and prompt multidisciplinary management, potentially improving patient outcomes. The study highlights the necessity of considering PIDs in diagnosing persistent or severe GI symptoms in children.

Explorative Characterization of GI Complaints, General Physical and Mental Wellbeing, and Gut Microbiota in Trained Recreative and Competitive Athletes with or without Self-Reported Gastrointestinal Symptoms.

The current state of the literature lacks a clear characterization of gastrointestinal (GI) symptoms, gut microbiota composition, and general physical and mental wellbeing in well-trained athletes. Therefore, this study aimed to characterize differences in self-reported symptoms, gut microbiota composition, and wellbeing (i.e., sleep quality, mood, and physical (PHQ) and mental wellbeing) between athletes with and without GI symptoms. In addition, we assessed the potential impact of a 3-week multi-ingredient fermented whey supplement in the GI complaints group, without a control group, on the gut microbiota and self-reported GI symptoms and wellbeing. A total of 50 athletes (24.7 ± 4.5 years) with GI issues (GI group at baseline, GI-B) and 21 athletes (25.4 ± 5.3 years) without GI issues (non-GI group, NGI) were included. At baseline, there was a significant difference in the total gastrointestinal symptom rating scale (GSRS) score (24.1 ± 8.48 vs. 30.3 ± 8.82, p = 0.008) and a trend difference in PHQ (33.9 ± 10.7 vs. 30.3 ± 8.82, p = 0.081), but no differences (p > 0.05) were seen for other outcomes, including gut microbiota metrics, between groups. After 3-week supplementation, the GI group (GI-S) showed increased Bifidobacterium relative abundance (p < 0.05), reported a lower number of severe GI complaints (from 72% to 54%, p < 0.001), and PHQ declined (p = 0.010). In conclusion, well-trained athletes with GI complaints reported more severe GI symptoms than an athletic reference group, without showing clear differences in wellbeing or microbiota composition. Future controlled research should further investigate the impact of such multi-ingredient supplements on GI complaints and the associated changes in gut health-related markers.

Evaluation of Fluid Loading Protocols for Use Before Returning from Spaceflight

Reductions in plasma volume (PV) during spaceflight contribute to post-spaceflight orthostatic intolerance (OI) during re-exposure to a gravitational environment. Both the National Aeronautics and Space Administration (NASA) and the Russian Space Agency (RSA) utilize fluid loading prior to re-entry to expand PV and mitigate the risk of post flight OI, but the timing of ingestion differs. Before landing NASA crewmembers consume 1-1.5 L of water with salt tablets to produce an isotonic solution in ~1 hour, whereas RSA cosmonauts consume the same, over ~4 hours. Anecdotal reports suggest low palatability and gastrointestinal (GI) distress with salt tablet and water fluid loading. To address this concern, the NASA Space Food Systems Laboratory developed an electrolyte solution. The purpose of this study is to test the effcacy and palatability of the two fluid loading compositions ingested in 1 hour versus 4 hours. Seven participants (2 Female, 39±9 years, 178.2±9.9 cm, 74.9±8.6 kg) completed four randomized visits separated ≥ 48 hours. The four visits were (1) no fluid loading (control), (2) 4 hour ingestion of the electrolyte solution (4hr-Electro), (3) 1 hour ingestion of the electrolyte solution (1hr-Electro), and (4) 4 hour ingestion of salt tablets and water (4hr-Salt). Participants reported to the lab at ~7:00 a.m. fasted, and PV was measured using a carbon monoxide re-breathing technique. During each visit subjects consumed 500 mL of water representing normal daily water intake through the first five hours of the session along with breakfast and lunch meals identical to those provided to astronauts. During the control visit, no other fluid consumption was allowed. During the three fluid loading visits, participants also consumed up to 1.2 L of additional fluid, either water with salt tablets or the electrolyte solution. After completion of the fluid loading protocol no additional fluid was consumed during the final 3.5 hours of the test. Participants remained seated for all portions of the study. Hemoglobin and hematocrit were measured at 0, 1, 2, 3, and 3.5 hours after cessation of food and fluid intake to assess changes in PV. In these preliminary data, PV was not significantly different from baseline at any timepoint during the control and 4hr-Electro sessions ( P&gt;0.20). PV increased from baseline at all timepoints for the 1hr-Electro session ( P&lt;0.003) and at all timepoints, other than 0 ( P=0.17 ), for the 4hr-Salt condition ( P&lt;0.01 ). GI distress was reported by participant during the 4hr-Electro (n=2), 1hr-Electro (n=1), and 4hr-Salt protocols (n=4). No GI distress was reported during the control visit. The most severe GI symptom (18/20) was nausea reported with the 4hr-Salt protocol. These data suggest that both the 4hr-Salt and 1hr-Electro fluid loading protocols successfully expands PV, however the 1hr-Electro results in fewer participants reporting GI symptoms. Supported by Mars Campaign Development - Exploration Capabilities. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

P53 promotes revival stem cells in the regenerating intestine after severe radiation injury

Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused by radiation-induced acute GI syndrome. Through single-cell RNA-sequencing of the irradiated mouse small intestine, we find that p53 target genes are specifically enriched in regenerating epithelial cells that undergo fetal-like reversion, including revival stem cells (revSCs) that promote animal survival after severe damage of the GI tract. Accordingly, in mice with p53 deleted specifically in the GI epithelium, ionizing radiation fails to induce fetal-like revSCs. Using intestinal organoids, we show that transient p53 expression is required for the induction of revival stem cells and is controlled by an Mdm2-mediated negative feedback loop. Together, our findings reveal that p53 suppresses severe radiation-induced GI injury by promoting fetal-like reprogramming of irradiated intestinal epithelial cells.

Gut microbiota profile in CDKL5 deficiency disorder patients

CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by global developmental delay, early-onset seizures, intellectual disability, visual and motor impairments. Unlike Rett Syndrome (RTT), CDD lacks a clear regression period. Patients with CDD frequently encounter gastrointestinal (GI) disturbances and exhibit signs of subclinical immune dysregulation. However, the underlying causes of these conditions remain elusive. Emerging studies indicate a potential connection between neurological disorders and gut microbiota, an area completely unexplored in CDD. We conducted a pioneering study, analyzing fecal microbiota composition in individuals with CDD (n = 17) and their healthy relatives (n = 17). Notably, differences in intestinal bacterial diversity and composition were identified in CDD patients. In particular, at genus level, CDD microbial communities were characterized by an increase in the relative abundance of Clostridium_AQ, Eggerthella, Streptococcus, and Erysipelatoclostridium, and by a decrease in Eubacterium, Dorea, Odoribacter, Intestinomonas, and Gemmiger, pointing toward a dysbiotic profile. We further investigated microbiota changes based on the severity of GI issues, seizure frequency, sleep disorders, food intake type, impairment in neuro-behavioral features and ambulation capacity. Enrichment in Lachnoclostridium and Enterobacteriaceae was observed in the microbiota of patients with more severe GI symptoms, while Clostridiaceae, Peptostreptococcaceae, Coriobacteriaceae, Erysipelotrichaceae, Christensenellaceae, and Ruminococcaceae were enriched in patients experiencing daily epileptic seizures. Our findings suggest a potential connection between CDD, microbiota and symptom severity. This study marks the first exploration of the gut-microbiota-brain axis in subjects with CDD. It adds to the growing body of research emphasizing the role of the gut microbiota in neurodevelopmental disorders and opens doors to potential interventions that target intestinal microbes with the aim of improving the lives of patients with CDD.

Delineating Gastrointestinal Dysfunction Variants in Severe Burn Injury Cases: A Retrospective Case Series with Literature Review

Background: Severe burns can significantly impact various organ systems, including the gastrointestinal (GI) system. GI complications are frequently observed in patients with over 20% total body surface area (TBSA) burn. Objectives: This case series delves into the intricate phenomenology of post-burn GI dysfunction, challenging conventional cause-and-effect paradigms. Our aim is to discern, comprehend, and explore variables influencing positive and negative outcomes, laying the foundation for further research given the current heterogeneity in the literature. Methods: Severe burn patients with GI dysfunction identified between April 1, 2022, and July 31, 2022, from the institutional database are included in this retrospective case-series, and comparisons were made across baseline and treatment conditions across participants. Data were collected on demographics, burn characteristics, complications, and treatment outcomes. Results: We analysed 12 patients with severe burns and GI dysfunction and categorized them into two patterns: Pattern A, characterised by early onset symptoms, gastric and small bowel dilatation, and a relatively benign course with high recovery rates was observed in 6 patients; and Pattern B, characterised by late-onset symptoms, colonic dilatation, shock, and a high mortality rate due to megacolon was seen in 6 patients. Conclusion: The post-burn GI dysfunction observed in our study is a complex interplay of multiple factors. Adequate fluid resuscitation, timely excision of necrotic tissue, staged food ingestion, specific nutrient administration, and appropriate use of antibiotics and judicious use of selective digestive decontamination (SDD) are essential strategies to prevent and treat this syndrome.

Gastric dysrhythmias in patients with early systemic sclerosis: a cross-sectional study.

Gastric involvement in patients with early systemic sclerosis (SSc) has not been previously investigated. We aim to evaluate the association of gastric dysrhythmias with gastrointestinal (GI) symptoms and nailfold video capillaroscopy (NVC). Cross-sectional study. Patients with early SSc, completed the UCLA GIT 2.0 questionnaire, performed an NVC, and a surface Electrogastrography (EGG). Descriptive statistics was used for demographic and clinical characteristics and Fisher and Kendall Tau tests were used for association analysis. 75 patients were screened, 30 patients were consecutively enrolled, 29 performed the EGG and 1 patient had a non-interpretable NVC. 29/30 were female with a mean age of 48.7 years (25-72). The mean disease duration from the first non-RP symptom was 22.6 +/-10.8 months and most of the patients had limited disease (76.6%). Total GIT 2.0 score symptoms were moderate-severe in 63% of the participants and 28/29 had an abnormal EGG. Bradygastria was the most common pattern present in 70% of the participants. NVC patterns: 17% early, 34% active, 28% scleroderma-like, 14% non-specific, and 2 patients had a normal NVC. There was no association between severe GI symptoms or NVC patterns and severely abnormal EGG, but the presence of bradygastria was associated with severe impairment in the social functioning area (p 0.018). Gastric dysmotility is common in early SSc and there is a lack of correlation between GI symptoms and NVC scleroderma patterns. EGG is a sensitive, cheap, and non-invasive exam, that may be an alternative to early diagnosis of GI involvement.

THE ROLE OF ALCOHOL USE IN THE DEVELOPMENT OF CROHN’S DISEASE COMPLICATIONS: A RETROSPECTIVE ANALYSIS

Abstract BACKGROUND Crohn’s disease (CD) is a type of inflammatory bowel disease (IBD) characterized by transmural inflammation that can occur anywhere along the gastrointestinal (GI) tract. Complications of CD include fistulization, abscess formation, and GI bleed. Many social and environmental factors have been associated with CD. The role of alcohol use remains unclear, with some studies suggesting that it may increase the risk of CD and worsen symptoms, and others showing no relationship between alcohol and CD. We aimed to assess the association between alcohol use and the development of CD complications using a large nationwide database. METHODS Patients with a diagnosis of CD were identified using the 2020 Nationwide Inpatient Sample (NIS). Patients were stratified based on whether they had a history of alcohol use. Outcomes included development of fistula, abscess, or bleed. Data were also collected regarding age, gender, race, primary insurance, median income, hospital region, hospital bed size, and comorbidities. The relationship between alcohol use and the development of fistula, abscess, or bleed among patients hospitalized with CD was analyzed using multivariate regression analysis. RESULTS A total of 178,279 patients with a diagnosis of CD were included in the study. Of these, 7,131 (4.0%) had a history of alcohol use. Patients in the alcohol group had lower odds of developing fistula (aOR 0.51, P &amp;lt; 0.001) and abscess (aOR 0.42, P &amp;lt; 0.001). There was no difference in the development of bleed in CD patients with alcohol use compared to without. Patients in the alcohol group had overall lower odds of developing any complication of CD (aOR 0.60, P &amp;lt; 0.001). CONCLUSION CD is a chronic and complex inflammatory disease that can lead to a variety of GI complications including fistula formation, abscess, and bleeding. Many genetic, environmental, social, and immune factors play a role in the disease course. Our study found that alcohol use is associated with a decreased risk of developing CD-related fistula or abscess. Patients with a history of alcohol use have been shown to exhibit earlier and more severe GI symptoms in CD, possibly leading to earlier presentation. Additionally, alcohol use has been found to suppress the immune response, potentially explaining our findings. Further studies are needed to assess the role of alcohol in the pathogenesis and disease course of CD. Inclusion process for the study.

GI Manifestation in Scleroderma

The gastrointestinal (GI) system frequently experiences complications in systemic sclerosis. Pathological changes in the GI system can be revealed from the early onset of the disease, such as esophageal hypomotility, to the late stage of the disease, where severe complications like intestinal pseudo-obstruction may occur. Systemic sclerosis can cause pathological changes throughout the entire gastrointestinal tract. Common symptoms include dysphagia, choking, heartburn, hoarseness, abdominal distension, diarrhea, constipation, and fecal incontinence. Oropharyngeal involvement in systemic sclerosis presents as weakened pharyngeal muscles, leading to oropharyngeal dysphagia, choking, food leakage, and aspiration, attributed to the dysfunction between the pharyngeal muscles and the upper esophageal sphincter due to muscle weakness. However, weak pharyngeal muscles may also be a clinical feature of the systemic sclerosis-polymyositis overlap syndrome. Esophageal involvement is frequently observed, with conditions such as esophageal hypomotility and lower esophageal sphincter incompetence, leading to early symptoms of dysphagia, gastroesophageal reflux, and potential complications such as esophagitis, esophageal stricture, Barrett’s esophagus, and aspiration pneumonia. Furthermore, gastric involvement includes gastric antral vascular ectasia, commonly known as “watermelon stomach,” which leads to gastrointestinal bleeding and chronic anemia. Intestinal manifestations comprise malabsorption, intestinal pseudo-obstruction, and bacterial overgrowth. Additionally, wide-mouthed diverticulosis and fecal incontinence are frequently found. Liver involvement includes primary biliary cirrhosis, most prevalent in limited cutaneous systemic sclerosis or certain overlap syndromes rather than diffuse cutaneous systemic sclerosis. The severity of these changes varies among patients, ranging from asymptomatic to severe conditions, which may result in malnutrition. Severe and chronic GI involvement significantly impacts daily life, making normal eating difficult, diminishing the quality of life, and potentially causing depression. Managing patients with systemic sclerosis who have GI involvement requires a multidisciplinary approach, involving collaboration among rheumatologists, gastroenterologists, nutritionists, surgeons, and possibly psychiatrists. This teamwork is essential to achieve successful patient care outcomes.

Prolonged Gastrointestinal Manifestations After Recovery From COVID-19

Acute enteric infections are well known to result in long-term gastrointestinal (GI) disorders. Although COVID-19 is principally a respiratory illness, it demonstrates significant GI tropism, possibly predisposing to prolonged gut manifestations. We aimed to examine the long-term GI impact of hospitalization with COVID-19. Nested within a large-scale observational cohort study of patients hospitalized with COVID-19 across North America, we performed a follow-up survey of 530 survivors 12-18 months later to assess for persistent GI symptoms and their severity, and for the development of disorders of gut-brain interaction (DGBIs). Eligible patients were identified at the study site level and surveyed electronically. The survey instrument included the Rome IV Diagnostic Questionnaire for DGBI, a rating scale of 24 COVID-related symptoms, the Gastrointestinal Symptoms Rating Scale, and the Impact of Events-Revised trauma symptom questionnaire (a measure of posttraumatic stress associated with the illness experience). A regression analysis was performed to explore the factors associated with GI symptom severity at follow-up. Of the 530 invited patients, 116 responded (52.6% females; mean age, 55.2 years), and 73 of those (60.3%) met criteria for 1 or more Rome IV DGBI at follow-up, higher than the prevalence in the US general population (P < .0001). Among patients who experienced COVID-related GI symptoms during the index hospitalization (abdominal pain, nausea, vomiting, or diarrhea), 42.1% retained at least 1 of these symptoms at follow-up; in comparison, 89.8% of respondents retained any (GI or non-GI) COVID-related symptom. The number of moderate or severe GI symptoms experienced during the initial COVID-19 illness by self-report correlated with the development of DGBI and severity of GI symptoms at follow-up. Posttraumatic stress disorder (Impact of Events-Revised score ≥33) related to the COVID-19 illness experience was identified in 41.4% of respondents and those individuals had higher DGBI prevalence and GI symptom severity. Regression analysis revealed that higher psychological trauma score (Impact of Events-Revised) was the strongest predictor of GI symptom severity at follow-up. In this follow-up survey of patients 12-18 months after hospitalization with COVID-19, there was a high prevalence of DGBIs and persistent GI symptoms. Prolonged GI manifestations were associated with the severity of GI symptoms during hospitalization and with the degree of psychological trauma related to the illness experience.

Comparison of Low Dose Rate and High Dose Rate Brachytherapy Boost Techniques in Prostate Cancer: Evaluation of Toxicity.

The ASCENDE-RT trial has been criticized for higher rates of chronic severe toxicity (18% genitourinary (GU)) than expected with a low dose rate (LDR) boost technique. We compared clinical outcomes of LDR and high dose rate (HDR) boost in the acute and chronic setting from a large single institution experience over a continuous 20-year period, with a focus on GU and gastrointestinal (GI) toxicity during treatment of prostate cancer. We retrospectively reviewed patients treated with LDR boost (2003 - 2013) and HDR boost (2014 - 2018). Clinical and treatment-related prognostic factors including age, stage, androgen deprivation therapy (ADT), dosimetry details, and toxicity data were recorded. Toxicity was scored according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Multi-variable analysis (MVA) was performed to evaluate variables associated with toxicity. A total of 184 men were evaluated (87 LDR and 97 HDR) with a median follow-up of 7.1 years and 4.0 years, respectively. Most patients (92% LDR and 57% HDR) received ADT in addition to BT. The median EBRT dose was 46 Gy for LDR and 45 Gy for HDR (range 25 - 50 Gy). Prostate D90% was similar at 104% and 105% in the LDR and HDR groups, respectively. Urethra D10% and Rectum V100% were both higher with LDR compared to HDR with 155% vs 119% and 0.436% vs 0.073%, respectively. Severe (grade 3+) toxicity was rare (Table 1), with 3.4% of LDR patients experiencing grade 3 chronic GU toxicity. With HDR, 3.1% and 1% of patients experienced acute and chronic grade 3 GU toxicity, respectively. Although non-severe GU toxicity (grade 1-2) was similar between groups (95% LDR vs 89% HDR, p = 0.16), LDR patients experienced more grade 2 GU events (80.5% acute; 82.8% chronic) compared to HDR patients (45.4% acute; 57.7% chronic). There were no severe GI toxicities in the acute or chronic period. Non-severe acute GI toxicity was more common with HDR, while non-severe chronic GI toxicity was more common with LDR. On MVA, acute GU toxicity (any grade) was associated with short term ADT (p = 0.01) and Urethra D10% (p < 0.05); Chronic GU toxicity (any grade) was associated with age (p = 0.09) and Prostate V150cc (p = 0.07) but not BT boost technique. This comparative retrospective analysis of BT boost techniques reveals the overall rate of severe GU and GI toxicity to be low with both LDR and HDR. HDR boost appears to have a slightly more favorable ratio of Grade 1 to Grade 2 GU toxicity and improved urethra/rectum dosimetry. Our analysis suggests that the dosimetric advantages of HDR may deliver small reductions in GU toxicity.

Adaptive Ultra-Hypofractionated Whole-Pelvic Radiotherapy in High-Risk and Very High-Risk Prostate Cancer on 1.5-1.5 MR Linac: The Estimated Delivered Dose and Early Toxicity Results

To study the feasibility and safety for patients with high-risk (HR) and very high-risk (VHR) prostate cancer treated with adaptive ultra-hypofractionated whole-pelvic radiotherapy (UHF-WPRT) on 1.5 magnetic resonance (MR)-Linac. Sevenpatients with clinical stage T3a-4N0-1M0-1c consecutively treated with UHF-WPRT on a 1.5-T MR-Linac were recruited prospectively in a phase II trial (NCT05183074, ChiCTR2000033382). A 36.25 Gy dose in five fractions was delivered every other day with a boost of 40 Gy to the whole prostate, as well as 25 Gy to whole pelvic nodal area with a concomitant boost of 35 Gy to metastatic regional nodes. To estimate the delivered dose, we collected data by 3D-MR for the following stages: pre-MR, position verification-MR (PV-MR) in the Adapt-To-Shape (ATS) workflow, and 3D-MR during the beam-on phase (Bn-MR) and at the end of RT (post-MR). The target and organ-at-risk contours in the PV-MR, Bn-MR, and post-MR stages were projected from the pre-MR data by deformable image registration and manually adapted by the physician, followed by dose recalculation for the ATS plan. The cumulative acute genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated as per NCI-CTCAE 5.0 criteria. The primary endpoints were acute ≥grade 3 genitourinary (GU) and gastrointestinal (GI) toxicities during the first 3 months. Overall, 133 MR scans were collected (35 pre-MR, 35 PV-MR, 31 Bn-MR and 32 post-MR scans). With a median on-couch time of 61 minutes, the mean prostate and pelvic planning target volume (PTV)-V95% of all scans was 96.98 ± 3.06% and 96.44 ± 2.85%, respectively. The corresponding mean prostate clinical target volume (CTV)-V100% was 99.89 ± 0.32%, 98.71 ± 1.90%, 97.77 ± 2.89%, and 98.56 ± 1.72%, and the mean pelvic CTV-V100% was 97.57% ± 3.70%, 96.54 ± 3.80%, 95.43 ± 4.31%, and 94.39 ± 4.47% on pre-MR, PV-MR, Bn-MR and post-MR scans, respectively. For the 4 patients with positive nodes, the mean V100% of metastatic regional nodes was 99.89 ± 0.81%. The median V29 Gy change in the rectal wall was -1% (-18%-20%). The V29 Gy of the rectal wall increased by >15% was observed in one scan. A slight increase in the high dose of bladder wall was noted due to gradual bladder growth during the workflow. With median follow-up time of 7.3 (4.6-12.2) months, all patients were followed-up for more than 3 months. No patient was observed with acute CTCAE grade 2 or more severe GU or GI toxicities (0%). UHF-RT to prostate and pelvic with ATS workflow is well tolerated by patients with HR and VHR prostate cancer, with only mild GU and GI toxicities. The 3D-MR-based dosimetry analysis demonstrated clinically acceptable estimated dose coverage of target volumes during the beam-on period.

Retrospective evaluation of the incidence of gastrointestinal bleeding in dogs receiving ophthalmic nonsteroidal anti-inflammatory drugs.

To report the incidence of gastrointestinal (GI) bleeding and associated risk factors in a population of dogs receiving ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs). Medical records of dogs prescribed ophthalmic NSAIDs (cases), dogs receiving systemic NSAIDs alone and dogs receiving systemic prednisone alone (controls). Data were collected retrospectively from the medical records of 204 dogs prescribed ophthalmic NSAIDs (diclofenac, ketorolac, or flurbiprofen), which were subdivided based on if they received any concurrent systemic NSAIDs or glucocorticoids, 136 dogs receiving a systemic NSAID (carprofen or meloxicam) alone, and 151 dogs receiving a systemic glucocorticoid (prednisone) alone at a referral hospital from 2015 to 2019. Gastrointestinal bleeds developed in 8/79 (10.1%) of topical NSAID-only cases, 10/136 (7.4%) of systemic NSAID controls, and 14/151 (9.3%) of systemic glucocorticoid controls, with no significant difference between the three groups (p = .6103). There were no significant differences in GI bleed rates between cases treated with ketorolac, diclofenac, or flurbiprofen (p = .160), although severe GI bleeding was only seen in ketorolac-treated dogs. Presence of a known concurrent risk factor for GI bleeding was significantly associated with the development of GI bleed in dogs on ophthalmic NSAIDs (p = .032). Dogs treated with ophthalmic NSAIDs developed GI bleeding at a frequency comparable to dogs receiving systemic NSAIDs or systemic glucocorticoids alone, suggesting that dogs receiving ophthalmic NSAIDs may be at increased risk of GI bleeding.

Severe gastrointestinal involvement in pediatric IgA vasculitis: a retrospective single-center cohort study in China.

The study aimed to describe the characteristics of gastrointestinal (GI) involvement in a cohort of hospitalized children with IgA vasculitis (IgAV) in China. We reviewed the records of hospitalized IgAV patients from January 2014 to December 2020 at one tertiary medical center. The patients were divided into the severe GI group and the non-severe GI group according to the presence of massive GI bleeding and complications. The clinical manifestations, laboratory factors, and treatment were analyzed between the two groups. A total of 1,179 patients were hospitalized due to IgAV. GI involvement was noted in 50% (589) of the patients, of whom 288 (48.9%) had severe GI involvement. GI complications were observed in 34 patients with IgAV with GI involvement. Rare onset age (<3 years or within 13-17 years), purpura above the waist, vomiting, high neutrophil-to-lymphocyte ratio, and decreased serum albumin were factors associated with severe GI involvement. Frequencies of renal involvement and biopsy-proven nephritis were higher in the severe GI group. The most commonly used medications were corticosteroids (100.0%) in the severe GI group. The maximum corticosteroid dose was higher (2.9 vs. 2.0 mg/kg), and more second-line therapies were needed (30.9% vs. 16.94%) in the severe GI group. Severe GI involvement in children is common in our center. Rare onset age, purpura above the waist, vomiting, high neutrophil-to-lymphocyte ratio, and decreased serum albumin are associated with severe GI involvement. Patients with severe GI involvement need higher doses of corticosteroids and second-line therapy.

An Exploratory Study Investigating the Prevalence of Gastrointestinal Symptoms in Collegiate Division I American Football Athletes.

Gastrointestinal (GI) symptoms may limit performance, but their prevalence and impact among team sports athletes is not well-documented. The objective of this study was to examine the prevalence of GI symptoms in a small sample of collegiate DI American football athletes, using a survey including the Gastrointestinal Symptoms Ratings Scale (GSRS). Forty-six athletes responded to the survey and reported scores for the 15-question GSRS with additional questions about dietary habits and supplement use. A total of 44 athletes were included in the study (45% of the current roster, age: 20.7 ± 1.7 years, 50% Afro-American or black, 39% skill position, 18% NSAIDs use, and 41% reporting protein supplement use); approximately half of the athletes (52%) reported experiencing GI complaints during exercise. Two-thirds of the athletes (61%) reported at least one or more GI symptoms in general, and 50% reported at least four moderate complaints. Seven athletes (16%) reported ≥2 severe GI symptoms with 5-13 moderate complaints. The most reported symptom was stomach pain (39%, n = 17), followed by hunger pain (36%, n = 16). Athletes reporting the use of protein supplements reported a higher GSRS score (22.0 and interquartile range (IQR) 17.0-31.8) vs. athletes not reporting protein use (15.0 and IQR 15.0-19.3), p = 0.001. Most athletes surveyed reported experiencing GI symptoms. A small group of these athletes reported multiple, varied, and severe symptoms that were associated with self-reported protein supplement use. In conclusion, the number of complaints varied among athletes, confirming the value of integrating the GSRS for screening purposes, and the expected need for individual dietary treatment approaches.