Resolution Of Diarrhea Research Articles

Efficacy of GV-1 Aqua-acupuncture for Acute Diarrhea in Dogs: A Controlled, Randomized Clinical Study

The objective of this randomized controlled study was to determine whether integrating GV-1 aqua-acupuncture (aqua-AP) and conventional therapy can accelerate the resolution of acute diarrhea in dogs. A total of 39 client-owned dogs experiencing acute diarrhea of less than 5 days duration were enrolled and randomly assigned to Group A, conventionally treated control (no aqua-AP); Group B, conventionally treated control plus sham aqua-AP (subcutaneous injection of vitamin B12 at a non-acupuncture point); or Group C, conventionally treated plus aqua-AP at GV-1 (vitamin B12 injected at GV-1 acupuncture point). Conventional treatment, uniformly applied to all patients, consisted of a bland diet, metronidazole and probiotics. Each owner, blinded to the group assignment of their dog, reported the time duration from the start of the treatment to the first observed normal stool (denoted as Tns). Study results revealed a significant difference among the Tns values of the 3 study groups. The meanSD Tns in Group A was 68.059.5 hours and 59.541.6 hours in Group B. Group C was 22.628.6 hours, which was more than 50% shorter than each of the other 2 groups. Furthermore, the proportion of subjects in Group C, whose first stool after treatment initiation was normal, was significantly greater than the other groups (A: 7.7%; B: 7.7%, and C 46.2%; p = 0.029). These findings suggest that aqua-AP at GV-1 can be an effective integrated treatment with conventional therapy for resolving acute diarrhea in dogs. Further studies with a larger sample size, and comparisons with other conventional treatments are warranted.

Donor, patient age and exposure to antibiotics are associated with the outcome of faecal microbiota transplantation for recurrent Clostridioides difficile infection: A prospective cohort study.

Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI), but its effect varies inexplicably. To optimise the effectiveness of FMT for rCDI and validate determinants for effect METHODS: We conducted a cohort study, including all patients treated with FMT for rCDI between October 2018 and June 2020. Statistical process control was used to evaluate the impact of prospective quality improvement on the effect of single FMT treatments per 10-11 patients. Targeting an 80% effect, optimisations included changes to processing procedures, preparation and clinical application of FMT. The primary outcome was the resolution of Clostridioides difficile-associated diarrhoea at week 8. If CDI recurred, FMT was repeated. All patients were followed for 8 weeks after their latest FMT. 183 patients with rCDI received 290 FMT treatments. A single FMT achieved resolution at week 8 in 127 (69%, 95% CI: 62%-76%), while repeated FMT cumulatively achieved resolution in 167/183 (91%, 95% CI: 86%-95%). The single FMT effect varied between 36% and 100% over time. In a mixed-effect model, patient age above 65 years, non-rCDI antibiotics at week 1 post-FMT, and donor were associated with effect. Neither increasing the dosages of faecal microbes nor standardising the processing improved outcomes. FMT has a high cumulative effectiveness in patients with rCDI following multiple administrations, but the single FMT effect is variable and may be optimised using statistical process control. Optimising FMT by considering patient age, post-FMT antibiotics, donor and multiple administrations may improve the treatment outcomes. gov (Study identifier: NCT03712722).

Emergence of canine hookworm treatment resistance: Novel detection of Ancylostoma caninum anthelmintic resistance markers by fecal PCR in 11 dogs from Canada.

To describe dogs with detected Ancylostoma caninum anthelmintic treatment resistance markers in Canada. 11 client-owned dogs with fecal quantitative PCR (qPCR) assay detected A caninum with benzimidazole (BZ) resistance genotypic markers. Signalment, presenting concern, duration of clinical signs, fecal testing, treatment, and outcomes were obtained. Where available, follow-up data were collected via telephone or email with the primary veterinarian. Ancylostoma spp was detected from 184/32,205 dog fecal samples by reference laboratory qPCR surveillance, between May 15, 2022, and April 26, 2023. 11 of these 184 samples had A caninum with genetic BZ F167Y resistance marker detection. 4 dogs had not traveled outside Canada, 6 had been imported from the US, and the travel history was unclear in 1 dog. 7 of the dogs had gastro-intestinal signs (diarrhea or soft stool) on initial presentation. Clinical improvement was reported in 6 of these dogs (resolution of diarrhea and soft stool), with 1 dog lost to follow-up. All 11 dogs received anthelmintic treatment (varied drugs and duration). Identification of genetic markers of BZ resistance raises concerns about the potential animal and human impacts of resistant hookworms. 4 dogs lacked an origin from or travel history to the US, indicating true emergence and/or novel spread within Canada, not just importation from an area where resistance has been reported. Fecal surveillance was performed with a qPCR test incorporating treatment (BZ) resistance markers. There is a need to raise clinician awareness around treatment-resistant hookworm in dogs and the capability of fecal surveillance for genotypic and phenotypic resistance.

Comparison of Outcome of Lactose-Free Formula Milk with Yogurt in Children with Acute Diarrhea

Background: Diarrhea is one of the most common problems in Pakistan where Khyber Pakhtunkhwa has the maximum prevalence i.e, 28% followed by Sindh (23%), Punjab (22%), and Baluchistan (12%). According to WHO every year 1.5 million children under 5 years, die just because of diarrhea. Therefore, this study aimed to look at the effect of lactose-free formula milk versus homemade plain yogurt in children with acute diarrhea. Methods: A randomized controlled trial was carried out on 60 children of age 4-24 months, 30 in each group in the Department of Pediatrics, Services Hospital Lahore. Group 1 was given yogurt while lactose-free milk was given to group 2. The duration of resolution of diarrhea was noted in hours and data was statistically analyzed using SPSS version 20. Practical Implication: The practical implication of comparing lactose-free formula milk with yogurt as a dietary intervention for children with acute diarrhea involves several considerations. Firstly, the severity and duration of diarrhea should be evaluated to determine the appropriate intervention. Secondly, the age and nutritional needs of the child should be taken into account. Thirdly, the availability and acceptance of lactose-free formula milk and yogurt in the local context should be considered. Additionally, the potential benefits and drawbacks of each option, such as the nutritional content, ease of digestion, and probiotic properties of yogurt, need to be assessed. It is important to consult with healthcare professionals and make an informed decision based on the specific circumstances to promote optimal outcomes in managing acute diarrhea in children. Results: Out of 60 children, 26 (43.33%) were male and 34 (56.67%) were female. In groups 1 and 2, the mean duration of resolution of diarrhea (outcome) was 43.9 ± 7.30 hours and 71.57 ± 12.92 hours respectively. Group 1 patients’ treatment showed a significant difference in the outcome than group 2 patients (P value= 0.00). However, the treatment effect on gender was found non-significant (P value= 0.48). The outcome in females was 43.6 ± 7.5 hours with yogurt and 70.6 ± 8.4 hours with lactose-free milk while in males the outcome was 44.3 ± 8.6 hours with yogurt and 73.1 ± 9.1 hours with lactose-free milk. Conclusion: The use of yogurt is better than lactose-free formula milk for the resolution of diarrhea. Keywords: Lactose-free formula milk, homemade plain yogurt, diarrhea.

Chronic inflammatory enteropathy: faecal microbiota transplantation in clinical practice

Chronic inflammatory enteropathy is an umbrella term that encompasses various inflammatory disorders of the gastrointestinal tract. In the absence of identifiable underlying infectious, neoplastic or metabolic causes, chronic or recurrent signs of gastrointestinal disease and histopathological evidence of mucosal inflammation are the hallmarks of chronic inflammatory enteropathy. Subgroups of chronic inflammatory enteropathy are retrospectively categorised as food-responsive, immunosuppression-responsive, small intestinal dysbiosis or non-responsive based on the selective response to therapeutic trials. Small intestinal dysbiosis is an overarching term used to describe derangement of the small intestinal microbiota caused by an abnormal proliferation of bacteria and/or change in bacterial species present in the small intestinal lumen. The pathogenesis of chronic inflammatory enteropathy remains elusive, although current hypotheses emphasise the role of adverse immune responses to dietary and microbial antigens thought to arise from immune system dysregulation, genetic susceptibility and intestinal dysbiosis. The gastrointestinal tract of dogs is colonised by a vast population of microorganisms, known as the intestinal microbiota, which is composed of viruses, fungi, bacteria and protozoa. Clinical use of faecal microbiota transplantation in promoting normobiosis has been gaining popularity within the field of canine gastroenterology. This modifies the intestinal bacterial microbiota and has shown promise as an adjunctive treatment of enteric disease, associated with a faster resolution of diarrhoea and enhanced clinical recovery.

Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing

Bile acid sequestrants (BAS) may be a treatment in microscopic colitis (MC), but efficacy data are limited. We evaluated the effectiveness of BAS in MC and assessed the utility of bile acid testing to predict response. Adults with MC treated with BAS (2010-2020) at Mayo Clinic were identified. Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing using previously validated cutoffs. Response was defined at 12 +/- 4 weeks after BAS initiation as: complete (resolution of diarrhea), partial (≥50% improvement in diarrhea), nonresponse (<50% improvement), and intolerance (discontinuation due to side-effects). Logistic regression was used to identify predictors of response to BAS. We identified 282 patients [median age 59 (20-87) years; 88.3% women] with median follow-up 4.5 (0.4-9.1) years. Patients were treated with the following BAS: 64.9% cholestyramine, 21.6% colesevelam, and 13.5% colestipol. Clinical outcomes were: 49.3% complete response, 16.3% partial response, 24.8% nonresponse, and 9.6% intolerance. There were no differences in outcomes between those on BAS alone or BAS combined with other medications (p=0.98). The dose of BAS was not associated with response (p=0.51). Bile acid testing was done in 31.9% and 56.7% were positive. No predictors of response to BAS were identified. After BAS discontinuation, 41.6% had recurrence at a median of 21 (1-172) weeks. In one of the largest cohorts evaluating BAS treatment in MC, nearly two-thirds had a partial or complete response. Additional research is needed to determine the role of BAS and bile acid malabsorption in MC.

Post-infectious vasculitis secondary to Campylobacter coli infection

•Vascular inflammation may be linked to Campylobacter coli infection.•Post-infectious vasculitis may cause relapsing fever after an acute infection.•18F-fluorodeoxyglucose positron emission tomography/computed tomography may be helpful for the diagnosis of post-infectious vasculitis. A 56-year-old male with no comorbidity was admitted for relapsing fever at 40°C with diarrhea and night sweats, 3 weeks after initial onset without microbiological screening in December 2020. Blood analysis showed C-reactive protein of 251.5 mg/l and negative cultures. A 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) revealed hypermetabolism highly suggestive of vasculitis affecting large and medium size arteries from upper and lower limbs, associated with highly hypermetabolic pan-colitis (Figure 1a). Stool culture was positive for Campylobacter coli. Temporal artery biopsy showed lymphocytic arteritis associated with eosinophils infiltrate, without any granuloma. A single dose of azithromycin allowed diarrhea resolution in 2 days and the inflammatory syndrome decreased after introduction of corticosteroids. The patient was treated for over 1 year, without relapse. FDG-PET/CT control after 2 years showed clear hypermetabolism regression (Figure 1b). Vascular involvements are rarely described in Campylobacter species infection but need specific follow-up to detect secondary aneurysm or stenosis. To our knowledge, diffuse vasculitis has never been previously described with Campylobacter coli [1Boissonneau S Graillon T Meyer M Brunel H Fuentes S Dufour H. Intracranial giant mycotic aneurysm without endocarditis and vasculitis: report of rare entity and review of literature.World Neurosurg. 2018; 119: 353-357https://doi.org/10.1016/j.wneu.2018.08.086Crossref PubMed Scopus (4) Google Scholar, 2Charbonnel A Carmoi T Lecoules S Bonnefoy S Algayres JP. Vascular manifestations due to Campylobacter fetus subsp. fetus infection: report of two cases.Rev Med Interne. 2012; 33: 643-645https://doi.org/10.1016/j.revmed.2012.08.011Crossref Scopus (2) Google Scholar, 3Torphy DE Bond WW. Campylobacter fetus infections in children.Pediatrics. 1979; 64: 898-903https://doi.org/10.1542/peds.64.6.898Crossref PubMed Google Scholar]. Clinical and histological findings were not suggestive of giant cell arteritis, the main differential diagnosis for large size vessels vasculitis after 50 years. FDG-PET/CT may help diagnose post-infectious vasculitis in case of relapsing fever after an acute infection. The authors have no competing interests to declare.

Nitazoxanide in Acute Rotavirus Diarrhea- A Randomized Controlled Trial Study in a Tertiary Care Hospital in Bangladesh

Background: Acute rotavirus diarrhea is one of the leading cause of morbidity and mortality in children younger than 5 years. Nitazoxanide, an antiparasitic agent, acts by inhibiting the maturation of rotavirus viral protein 7 thus interferes with viral morphogenesis. Aim of the study: was to evaluate the role of nitazoxanide in the treatment of acute rotavirus diarrhea in 6 months to 2 years aged children. Methods: This randomized controlled trial was conducted at Bangladesh Shishu Hospital &amp; Institute, Dhaka, Bangladesh from June 2018 to July 2020. A total of 70 children with acute onset diarrhea of &lt;48 hours. duration was included in this study. All the studied patients were divided into two equal groups (group I and group II) by lottery, each comprising 35 children. The groupI represented the study group who received standard treatment of diarrhea plus oral nitazoxanide (15mg/kg/day) twice daily for 3 days and the group II is the control group received standard treatment only. Results: Study demonstrated that maximum number of patients 22 (31.4%) were between 14-17 months of age group and 36% patients came from rural, 64% from urban areas. Study showed before commencement of treatment most of the patients in both groups experienced some dehydration, vomiting, fever, &amp; abdominal distension. At 48 hours’ improvement was observed in both groups, comparatively higher in group I. Difference of some dehydration and vomiting improvement between two groups were statistically significant (p &lt;0.05). After 3 days’ treatment normal stool consistency was found in 24(68.5%) patients in group I &amp; 10 (28.5%) in group II patients. The difference was also statistically significant (p=&lt;0.05). Mean time of resolution of diarrhea 62.5 hours in Group-I and 96.5 hours in group-II. Compared to the group II, group I showed decrease in mean time of resolution of diarrhea (p= 0.001). The mean duration of hospital stay was prolonged in group-II (86.5 hours vs. 102.5 hours in group I &amp; II respectively), the difference was statistically significant (p˂0.05). Conclusion: In the present study, oral nitazoxanide was found effective in the treatment of acute rotavirus diarrhea in 6 months to 2 years old children.

Short- and long-term follow-up after fecal microbiota transplantation as treatment for recurrent Clostridioides difficile infection in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at an increased risk of developing Clostridioides difficile infection (CDI). Treatment of CDI in patients with IBD is challenging due to higher failure rates and concomitant IBD activity. We performed a multicentre cohort study in patients with IBD who received fecal microbiota transplantation (FMT) for recurrent CDI (rCDI), to further investigate factors that influence the clinical outcome and course of both rCDI and IBD. This is a multicentre cohort study conducted in five European FMT centres. Adult IBD patients treated with FMT for rCDI were studied. Cure was defined as clinical resolution of diarrhoea or diarrhoea with a negative C. difficile test. The definition of an IBD flare was record based. Long-term follow-up data were collected including new episodes of CDI, IBD flares, infections, hospital admissions, and death. In total, 113 IBD patients underwent FMT because of rCDI. Mean age of the patients was 48 years; 64% had ulcerative colitis. Concomitant rCDI was associated with an IBD flare in 54%, of whom 63% had received IBD remission-induction therapy prior to FMT. All FMT procedures were preceded by vancomycin treatment, 40% of patients received FMT via colonoscopy. CDI cure rate was 71%. Long-term follow-up data were available in 90 patients with a median follow-up of 784 days (402-1251). IBD activity decreased in 39% of patients who had active IBD at baseline, whereas an IBD flare occurred in only 5%. During follow-up of up to 2 years, 27% of the patients had infections, 39% were hospitalized, 5% underwent colectomy, and 10% died (median age of these latter patients: 72 years). FMT for rCDI in IBD patients is safe and effective, and IBD exacerbation after FMT is infrequent. Further studies should investigate the effects on IBD course following FMT.

Characterization and management of adverse events observed with mobocertinib (TAK-788) treatment for EGFR exon 20 insertion–positive non–small cell lung cancer

ABSTRACT Background Mobocertinib has demonstrated durable clinical benefit in platinum-pretreated patients (PPP) with epidermal growth factor receptor exon 20 insertion–positive non–small cell lung cancer (NSCLC). Research design and methods Pooled safety analysis of two studies included patients with NSCLC (N = 257) treated with the recommended phase 2 dose (RP2D) of mobocertinib (160 mg once daily). We report overall safety (treatment-emergent adverse events [TEAEs]) in the RP2D population; characterization of GI and skin-related events in 114 PPP from a phase 1/2 study (NCT02716116); and clinical activity in PPP with and without dose reductions due to TEAEs. Results In the RP2D population (N = 257), the most common TEAEs were diarrhea (93%), nausea (47%), rash (38%), and vomiting (37%). In PPP (N = 114), median times to diarrhea onset and resolution were 5 and 2 days, respectively. Median times to onset and resolution of skin-related events were 9 and 78 days, respectively. Among PPP with (n = 29) or without (n = 85) dose reductions due to TEAEs, overall response rates were 21% and 31% and median durations of response were 5.7 and 17.5 months, respectively. Conclusions GItaiwan and skin-related events are common with mobocertinib; minimizing dose reductions with proactive management may improve clinical outcomes. Trial Registration NCT02716116; NCT03807778

383. Assessing the 2021 IDSA Treatment Clostridioides difficile Guidelines in a Small, Community Hospital

Abstract Background Cambridge Health Alliance (CHA) is an academic healthcare system in the greater Boston area that includes two acute care, community hospitals. Oral vancomycin has been the first line treatment option for initial C. difficile infection (CDI). In 2021, IDSA updated its guidelines to recommend fidaxomicin as the preferred treatment for initial episodes. At our institution, fidaxomicin is restricted to infectious diseases approval.The objective of this evaluation was to assess CDI recurrence rate and to identify a target population within our organization who may benefit from fidaxomicin as initial CDI treatment. Methods A retrospective chart review of all inpatients ordered for oral vancomycin or fidaxomicin from January 2021 to February 2022 was conducted to assess treatment success, failure, and 60 day recurrence rate of CDI at two community teaching hospitals. Treatment success was defined as resolution of diarrhea or absence of diarrhea for two consecutive days after completion of therapy. Treatment failure was defined as continuation of symptoms for greater than 6 days after treatment initiation. Risk factors for recurrence evaluated were age &amp;gt; 65 years, immunocompromised status, fulminant infection, and use of vancomycin versus fidaxomicin. Results A total of 47 patients administered oral vancomycin or fidaxomicin for CDI treatment between January 2021 and February 2022 were included in the analysis. Only one patient received fidaxomicin. The median age was 66 years and 55.3% female. Four patients were immunocompromised. Only one immunocompromised patient over 65 years had CDI recurrence. In our population, oral vancomycin had a treatment success rate of 85.1% and a recurrence rate of 2%. The one patient who received fidaxomicin did not have recurrence. Given the low recurrence rate, we were unable to identify significant risk factors associated with CDI recurrence in our population. Conclusion In our population, oral vancomycin had a high treatment success rate, which correlates with current literature. Limitations of our analysis include its retrospective design, small sample size, and inclusion of few immunocompromised patients. Oral vancomycin remains the preferred treatment for an initial CDI episode in our population, as recurrence rate is low. Disclosures All Authors: No reported disclosures.

Noroviral diarrhea in solid organ transplant recipients: An analysis of interventions and outcomes.

Noroviral infection can lead to chronic diarrhea in solid organ transplant (SOT) recipients with significant morbidity and mortality. Existing literature has described a wide spectrum of illness and has not come to a consensus on the optimal management of this condition. We undertook a retrospective review of all adult SOT recipients between 1/1/2018 and 12/31/2020 who were diagnosed with their first episode of noroviral diarrhea (NVD). Demographic, clinical interventions, and outcomes within 6months of diagnosis were recorded. Patients' outcomes were classified as either resolved, improved or persistent at 6months. Seventy-nine SOT recipients were included. Thirty-eight patients (48%) had chronic diarrhea at baseline (CDB). Thirty-two patients (40%) received nitazoxanide, 28 patients (35%) had their immunosuppression adjusted and seven patients (9%) received intravenous immunoglobulin. Diarrhea improved or resolved in 68 patients (85%). Improvement or resolution of diarrhea was observed in 98% of those who did not have history of chronic diarrhea versus 74% in those who did (p=.002). NVD improved in all 12 patients who had mycophenolate discontinued, although this was not statistically significant (p=.131). CDB was associated with worse outcomes regardless of intervention. A low threshold to test for NVD in SOT recipients with chronic diarrhea is prudent to prevent delayed diagnosis.

Evaluating the effectiveness of colostrum as a therapy for diarrhea in preweaned calves.

Diarrhea is the primary cause of morbidity and mortality in dairy calves. Many cases of diarrhea in calves are treated with antimicrobials, increasing the risk of antimicrobial resistance, therefore, creating a need for alternative therapies. The objective of this study was to evaluate the effects of feeding spray-dried maternal derived bovine colostrum replacer at the onset of diarrhea on calf growth and duration and severity of the disease in preweaning dairy calves. At a calf-raising facility in southern Ontario, calves were scored for fecal consistency twice daily on a scale of 0 to 3 and enrolled into the trial when they had 2 consecutive fecal scores of 2 (runny or spreads readily) or one fecal score of 3 (liquid consistency, splatters). Calves were then randomly allocated to receive one of the following 3 treatments: (1) control (CON; n = 35): 8 feedings over 4 d of 2.5 L of milk replacer at a concentration of 130 g/L (26% crude protein and 17% fat); (2) short-term colostrum supplementation (STC; n = 35): 4 feedings over the first 2 d of 2.5 L of a mixture of milk replacer at 65 g/L and bovine colostrum replacer at 65 g/L (26% IgG and 14.5% fat) followed by 4 feedings over 2 d of 2.5 L of milk replacer at a concentration of 130 g/L; or (3) long-term colostrum supplementation (LTC; n = 38): 8 feedings over 4 d of 2.5 L of a mixture of milk replacer at 65 g/L and bovine colostrum replacer at 65 g/L. Serum IgG was determined at arrival to the facility and body weight, days to enrollment since facility arrival, and severity of diarrhea were recorded at enrollment. Daily health exams evaluating fecal consistency were performed for 28 consecutive days after enrollment and body weight was measured at d 0, 1, 2, 3, 4, 7, 14, 21, 28, 42 and 56 after enrollment. The median days to resolution of a case of diarrhea was 3.5 d (range: 0.5-11.5 d), 2.75 d (range: 0.5-11.0 d), and 2.75 d (range: 0.5-7.0 d) in CON, STC, and LTC, respectively. Using a Cox proportional hazards model, it was found that calves in LTC group had faster resolution of diarrhea compared with calves in the CON group. In addition, there was an association between both days to enrollment since facility arrival and body weight and resolution of diarrhea, where calves who were at the facility longer before enrollment and heavier at the onset of diarrhea, resolved diarrhea quicker. In addition, calves with a fecal score of 3 at enrollment took longer to resolve their case of diarrhea. With respect to body weight, a linear regression model was built and found that over the 56 d following enrollment calves in the LTC treatment grew 98 g/d more than calves in the CON group. These results suggest that bovine colostrum may be an effective therapy for diarrhea in preweaning calves.

UNEXPECTED DIAGNOSIS FOLLOWING IMMUNODEFICIENCY WORK-UP

<h3>Introduction</h3> A 15-month-old infant with severe recurrent sinopulmonary infections was evaluated for a primary immunodeficiency. Investigation resulted in a diagnosis that initially wasn't suspected. <h3>Case Description</h3> Our patient was born at term and had no medical concerns until 10-months-old when she developed recurrent otitis accompanied by fevers, diarrhea, and failure to gain weight appropriately. Within five months she was diagnosed with four separate ear infections, each requiring multiple rounds of antibiotics to treat. She was also diagnosed with anemia, splenomegaly, and two episodes of pneumonia. She was hospitalized for one episode of pneumonia and staphylococcus aureus was isolated from a bronchopulmonary lavage. An extensive immunodeficiency laboratory investigation revealed a borderline abnormal oxidative burst test and selective IgA deficiency. Genetic testing for chronic granulomatous disease was negative. Celiac testing was inconclusive based on her IgA deficiency, so an upper GI endoscopy was completed to rule out this condition. She was ultimately diagnosed with eosinophilic esophagitis based on esophageal biopsies. <h3>Discussion</h3> Eosinophilic esophagitis was not considered in the initial differential diagnosis as this typically does not result in recurrent infections. This case demonstrates the important link between malnutrition and immune dysregulation; poor nutrition can lead to secondary immune dysfunction. Recent studies have postulated a correlation between IgA deficiency and eosinophilic esophagitis, this case adds data to that observation. After appropriate treatment, this patient's symptoms dramatically improved with no continued infections, appropriate weight gain, and resolution of diarrhea and splenomegaly.

RF11 | PSAT273 RET Gene Fusion In a Putative Case of Medullary Thyroid Cancer

Abstract Background Oncogenic RET gene fusions have been identified in non-small cell lung cancer and non-medullary thyroid cancers, whereas RET point mutations are the key genetic finding in both inherited and sporadic medullary thyroid cancer (MTC). The presence of a RET gene fusion provides a target for selective RET inhibitor drugs. We describe an unusual patient with suspected MTC and a positive RET gene fusion, with excellent response to targeted therapy. Clinical Case A 50-year-old male presented to our institution with cough, fatigue, heat intolerance, and flushing. His only remarkable history was stage IIIBS Hodgkin lymphoma treated with chemotherapy, in remission for approximately 6 years. CT chest revealed new bulky mediastinal and hilar adenopathy with bulky cervical nodes. VATS biopsy of a mediastinal node showed metastatic neuroendocrine neoplasm with plasmacytoid features that was immunoreactive for calcitonin, CEA and cytokeratin, but negative for TTF1 and PAX-8. The differential diagnosis included MTC or metastatic atypical carcinoid tumor. Next Generation Sequencing was negative, including RET and RAS point mutations. Subsequent testing for re-arrangements showed a KIF5B-RET gene fusion, an oncogene identified in lung adenocarcinoma. Biochemical findings showed a calcitonin level of 16,033 (normal &amp;lt; 10 pg/mL) and CEA 6.9 (normal &amp;lt; 4.7 ng/mL). Chromogranin A was 146.6 (normal &amp;lt; 101.16 ng/mL). ACTH and cortisol were normal. Neck US revealed a calcified 5 mm right upper pole thyroid nodule and extensive bilateral cervical nodes. A provisional diagnosis was made of MTC. Vandetanib was started. Two months later, he reported worsening orthopnea, diarrhea, and weight loss. CT chest showed marked worsening with enlarging mediastinal hilar and supraclavicular adenopathy with new moderate sized pericardial and pleural effusion. Vandetanib was discontinued and Selpercatinib started, following FDA approval. He reported prompt resolution of dyspnea and diarrhea and improved weight and energy. Calcitonin declined to &amp;lt;2 pg/mL, and CEA to1.6 ng/mL four months into treatment. CT neck showed marked shrinkage of lymph nodes with a persistent calcified thyroid nodule. CT chest showed marked shrinkage of mediastinal and hilar masses, with resolution of bronchial narrowing and right pleural effusion. Nine months after presentation, there were no chest symptoms and biochemical markers and imaging remained stable. Conclusion Approximately 25% of MTC tumors lack activating point mutations in RET or RAS genes. Analysis of actionable fusion mutations should be considered if there is metastatic disease. High serum calcitonin levels are not pathognomonic for MTC and tumor histology may overlap with neuroendocrine lung cancers, creating a diagnostic challenge. Depending on whether this patient's tumor originated in the thyroid gland, it may represent an unusual case of RET gene fusion in MTC. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m.

Chronic diarrhea secondary to canine leishmaniosis: Case series

Chronic diarrhea is a clinical sign associated with canine leishmaniosis, varying from 3 % to 30 % of prevalence. However, its occurrence in dogs has been mostly associated with chronic kidney or liver disease. Leishmania organisms can cause inflammation of the digestive tract with chronic diarrhea as the only clinical manifestation, although it has been poorly documented in dogs. The aim of this retrospective observational study was to describe dogs with chronic diarrhea as the main clinical sign associated with leishmaniosis. All cases had a complete blood count, biochemistry, urinalyses, and diagnostic tests for leishmaniosis. Exclusion criteria included renal or hepatic disease and/or previous diagnosis of gastrointestinal disease. Twenty-three dogs were included. Small bowel diarrhea was present in 7/23 (30.4 %), large bowel diarrhea in 9/23 (39.2 %) and mixed diarrhea in 7/23 (30.4 %). Gastrointestinal biopsies were performed in 8/23 dogs and Leishmania amastigotes were found in all of them. In the others, leishmaniosis was diagnosed by serology in 10/15 dogs (66.7 %), serology plus blood PCR in 3/15 (20.0 %), lymph node cytology in 1/15 (6.7 %), and blood PCR in 1/15 (6.7 %). All dogs treated had a complete resolution of diarrhea with specific treatment for leishmaniosis alone, based on meglumine antimoniate (75–100 mg/kg SID SC for 1 month) plus allopurinol (10 mg/kg BID PO ≥ 6 months). This study suggests that leishmaniosis should be also included in the differential diagnosis of dogs from endemic areas presenting with the primary problem of large-bowel, small-bowel, or mixed-bowel chronic diarrhea.

S135 Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing

Introduction: Bile acid sequestrants (BAS) may be an effective non-corticosteroid treatment in patients with microscopic colitis (MC), but data are lacking. We evaluated the effectiveness of BAS therapy in MC and assessed the utility of bile acid testing to predict response. Methods: Adults diagnosed with MC and treated with BAS at Mayo Clinic Rochester (1/1/2010 - 12/31/2020) were identified. Response was assessed at 12 +/- 4 weeks after initiation of BAS therapy and defined as: complete (resolution of diarrhea), partial (≥50% improvement in number of bowel movements), nonresponse (< 50% improvement), and intolerance (discontinuation due to side-effects). Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing using previously validated cutoffs (total bile acids (BA) >2,337 μmol/48 hours, primary BA >10%, or primary BA >4% with total BA >1,000 μmol/48 hours). Univariate and multivariable logistic regression was used to identify predictors of response to BAS. Results: A total of 282 patients were identified [median age 59 (20-87) years; 88.3% women] with a median duration of follow-up of 4.5 (0.4-9.1) years (Table). Prior to BAS therapy, 278 (98.6%) were treated with another medication (loperamide, budesonide, bismuth subsalicylate, or mesalamine) for MC. Patients were treated with the following BAS: 183 (64.9%) cholestyramine, 61 (21.6%) colesevelam, and 38 (13.5%) colestipol. Clinical outcomes with BAS were: 139 (49.3%) complete response, 46 (16.3%) partial response, 70 (24.8%) no response, and 27 (9.6%) intolerance. In patients with complete or partial response to BAS, 65/185 (35.1%) were on a concomitant medication for MC. The dose of BAS did not vary between response and non-response groups (p=0.51). A total of 90/282 (31.9%) had bile acid testing and 51/90 (56.7%) had a positive test. Age at MC diagnosis, smoking history, baseline diarrhea severity, history of cholecystectomy, use of prior MC medications, and abnormalities on bile acid testing did not predict response to BAS. After BAS discontinuation, 77/185 (41.6%) responders had recurrence at a median of 21 (1-172) weeks. Conclusion: In one of the largest cohorts evaluating BAS treatment in MC, we demonstrate that nearly two-thirds had a partial or complete response to these agents. Additional research is needed to determine the role of bile acid malabsoprtion in MC, as well as the subset of patients that are most likely to benefit from BAS therapy. Table 1. - Baseline Characteristics in Microscopic Colitis Patients With and Without Bile Acid Testing Median (range) or n (%) Characteristics All Patients(n = 282) Bile Acid Testing Performed(n = 90) No Bile Acid Testing Performed(n = 192) p-value Age 59 (20-87) 57 (23-87) 60 (20-87) 0.35 Sex, female 249 (88.3%) 82 (91.1%) 167 (87.0%) 0.31 Race, white 276 (97.9%) 89 (98.9%) 187 (97.4%) 0.53 Subtype, lymphocytic colitis 139 (49.3%) 52 (57.8%) 87 (45.3%) 0.06 Bowel movements, number 6 (3-20) 6 (3-20) 5 (3-15) 0.45 Body mass index (kg/m2) 25.4 (16.2-47.0) 24.5 (16.2-47.0) 25.7 (16.7-46.4) 0.21 Smoking history 95 (33.7%) 37 (41.1%) 58 (30.2%) 0.17 Cholecystectomy 69 (24.5%) 28 (31.1%) 41 (21.4%) 0.08 Celiac disease 20 (7.1 %) 5 (5.6%) 15 (7.8%) 0.39 Previous medications* 278 (98.6%) 88 (97.8%) 190 (98.9%) 0.44 *Medications for microscopic colitis prior to bile acid sequestrant treatment.

CT-207 Protracted Diarrhea from High-Dose Melphalan in Autologous Hematopoietic Transplantation: Response to Short Course of Oral Budesonide

Approximately, 40% of patients receiving high dose melphalan (HDM) develop grade III or IV diarrhea (CTCAE 5.0) that promptly improves upon neutrophilic engraftment. Persistence of grade III diarrhea beyond 72 hours post-engraftment, though uncommon results in significant morbidity and prolongs hospitalization. Enlighten by a histopathologic finding of crypt inflammation, we utilized a short course of oral budesonide in a patient resulting in rapid resolution of diarrhea. We herein document 3 such cases and discuss their role in reducing morbidity and duration of hospitalization. All patients (age 44, 63 and 65, 2 female) received melphalan 200 mg/m2. Neutrophilic engraftment occurred on day +11 in 2 patients and day +12 in 1. Persistent grade III diarrhea 72 hours after neutrophil engraftment is defined as protracted diarrhea from melphalan. Infectious workup included stool examination for salmonella, shigella, rotavirus, cryptosporidium, and clostridium difficile we negative. Colonoscopy in one patient confirmed patchy crypt apoptosis and crypt abscess formation. Standard supportive care including antidiarrheals offered no improvement. Oral budesonide (BUD)was introduced at 5, 7- and 16-days post-engraftment (day + 17, +18 and +27 of ASCT). The dose of BUD comprised 6 mg/day in 2 while one patient received a 9 mg/day dose. Two patients had rapid resolution of diarrhea within 48 hours, while the third patient improved in 7 days. Total duration of BUD was 2, 2, and 26 days. Patients received a total cumulative dose of 12 mg, 15 mg, and 117 mg. Time to discharge from BUD initiation was 2, 2, and 7 days. A translational model of melphalan-induced gut toxicity reveals drug-host-microbe interaction that drives tissue injury and inflammation. Palifermin, a recombinant human keratinocyte growth factor is effective in reducing diarrhea of HDM. However, its cost is prohibitive. While newer melphalan preparations are available and prevention of melphalan-induced GI toxicity is being studied (Uproleselan), a short course of oral budesonide provided rapid resolution and facilitated patient discharge. Oral BUD results in rapid resolution of lower GI toxicity of HDM and potentially lowers the cost of hospitalization.

P32 Therapeutic dilemma due to gut complications with spondyloarthritis

Introduction/BackgroundTumor necrosis factor (TNF) inhibitor therapy is one of the primary modalities of treating spondyloarthritis. However, infections secondary to biologic use is a common complication. Clostridium difficile is a gut colonizer which may become pathogenic in the presence of dysbiosis and antibiotic use. Symptomatic clostridium difficile infection(CDI) due to adalimumab(ADA) use causing lymphocytic colitis(LC) is rarely reported. We present a case of axial plus peripheral spondyloarthritis on adalimumab who developed CDI and presented a therapy related dilemma.Description/MethodWe present a case of a 52-year-old lady who was diagnosed as HLAB27 positive axial spondyloarthritis with bilateral sacroiliitis on MRI bilateral sacroiliac joint in 2016. She failed two non-steroidal antinflammatory drugs (NSAID) with high disease activity scores(BASDAI 8.6, BASFI 6.2, Spinal VAS 9). She was eventually initiated on injection adalimumab in 2017. There was clinical improvement after 6 months of initiating ADA. Repeat MRI spine and SI joint showed resolution of inflammatory changes with adalimumab. Sulfasalazine was added in the treatment protocol due to peripheral arthralgia, however she developed a drug rash to it and it was stopped. In September 2021, she developed recurrent non-bloody watery diarrhoeal episodes. Adalimumab was stopped and she tested positive for Clostridium difficile on three occasions. She received multiple courses of vancomycin, fidoxamycin and metronidazole with partial resolution of diarrhoea. Adalimumab was rechallended in January 2022 since her disease activity was worsening in the absence of NSAID and biologic use. However, it was paused again due to worsening of diarrhoea. Gastroenterology conducted a Colonoscopy and biopsy of colonic polyps which showed increased number of intraepithelial lymphocytes with no thickening of subepithelial collagen plate suggestive of lymphocytic colitis (LC). It was postulated that CDI may have been the trigger for her LC. She has been started on local corticosteroid therapy(budesonide) for her LC. At this junction, we were faced with the decision of restarting adalimumab for her which may have been the original cause of her CDI.Discussion/ResultsWe present this case in view of a dilemma regarding which problem occurred first Did immunosuppression due to adalimumab lead to CDI? Literature is not suggestive of increased risk of CDI with adalimumab, especially in a non-inflammatory bowel disease (IBD) background. Was the lymphocytic colitis triggered by the CDI or was clostridium difficile just incidentally detected on a background of LC? There is a well documented associated of LC with autoimmune conditions and use of NSAIDs along with proton pump inhibitor is another trigger for it. TNF alpha inhibitor is one of the treatment modalities of refractory LC. Would it be appropriate to restart ADA for her since she responded well despite there being a risk of recurrence of a CDI? Finally, what is the role of gut dysbiosis in the role of CDI and LC in this situation. Presently, she is planned to be treated with local steroid therapy for her LC. ADA will be rechallenged once her gut has responded to the steroid course. In the event of her gut worsening on a rechallenge, she will be given a trial of Infliximab.Key learning points/ConclusionThe case highlights the crucial point of thinking of causes of diarrhea apart from well documented conditions of ulcerative colitis/Crohn’s disease in an immunosuppressed spondyloarthritis patient. A detailed stool examination including bacterial and parasitic examination is crucial in recurrent diarrhea. The threshold for colonoscopy should be low when episodes are refractory to treatment. The case-based conference gives us an opportunity to receive feedback regarding further management approaches in this case.

Digestive tolerability and acceptability of Fibersol-2 in healthy and diarrheal children 1-3 years old at a rural facility, Bangladesh: Results from a four arm exploratory study.

Fibersol-2 has some beneficial effects on human health. We aimed to evaluate the digestive tolerability and acceptability of Fibersol-2 in healthy and diarrheal children, as well as improvement in stool consistencies in young diarrheal children. Sixty children of either sex, aged 1-3 years having four groups (healthy children/low dose, healthy children/high dose, children with diarrhea/low dose and children with diarrhea/high dose) were enrolled into this exploratory study between 1st August to 23rd October 2017. Two presumptive doses, low (2.5g) and high (5g), twice daily with 50 ml drinking water for seven days were the interventions. Outcomes were to observe the development of possible abdominal symptoms, such as pain, distension, rumbling, and bloating during the intervention and post-intervention periods in healthy and diarrheal children as well as improvement in stool consistencies in diarrheal children. Among the diarrheal children, the median (IQR) duration of resolution of diarrhea was 3.9 (2.9, 5.1) days vs. 3.5 (2.0, 8.0) days, p = 0.885; in low dose and high dose groups, respectively. Significant difference was observed in terms of abdominal pain (27% vs. 7%, p = 0.038) and distension (40% vs. 0%, p<0.001) in diarrheal children, compared to healthy children during the pre-intervention period. We also observed significant difference in respect of abdominal distension (23% vs. 0%, p = 0.011), rumbling (27% vs. 0%, p = 0.005) and bloating (43% vs. 3%, p = 0.001) in diarrheal children, compared to healthy children during the intervention period. However, no significant difference was observed in relation to abdominal pain (p = 0.347) and distension (p = 0.165) during the pre-intervention period, compared to the intervention period in diarrheal children. Moreover, no significant difference was observed during the post-intervention period for the diarrheal and healthy children. Fibersol-2 was found to be well tolerated in healthy and diarrheal children aged 1-3 years. This study was registered as part of a randomized trial at ClinicalTrials.gov, number NCT03565393. The authors confirmed that all ongoing and related trials for this drug/intervention were registered.