Onset Of Diarrhea Research Articles

Using digital engagement to proactively manage symptoms in patients on capecitabine.

12079 Background: Adherence to oral chemotherapy is a challenge due to the toxic adverse events (AEs) patients’ experience. Capecitabine (CAP) may cause patients to experience AEs such as diarrhea and hand and foot syndrome (HFS), leading to therapy non-adherence. Digital patient engagement has successfully improved patient adherence and has been used to monitor AEs in a variety of cancer types. We used proprietary secure messaging to engage specialty patients receiving CAP and to message them at the expected onset of diarrhea and HFS; nurse care management was deployed for patients reporting an AE. The objective of this study was to determine whether nurse engagement using digital tools to manage oncology AEs resulted in improved medication adherence. Methods: CAP patients were sent outgoing SMS branching logic messages during November 2019, and respondents reporting AEs were engaged by nurses using a proprietary secure messaging platform. Nurses made clinical interventions in these patients by either making a pharmacologic or non-pharmacologic recommendation or referring the patient to an oncologist. The number of patients responding to outgoing SMS and secure messaging, nurse interventions, and medication fill history were measured. We compared 30-day post-intervention proportion of days covered (PDC) in the intervention group (those that engaged with nurses and received digital adherence and clinical messages) to standard of care (those who received digital adherence and clinical messages but did not engage) using the Student’s t-test. Results: 1,421 outgoing messages were sent to utilizers of CAP; 95 patients replied indicating the occurrence of either diarrhea or HFS. Nurse care managers reached 49 (52%) unique patients resulting in 54 interventions where care coordination was provided. The majority of engaged patients reached (74%) had symptom resolution as a result of nurse intervention. PDC was 79.3% in the intervention group and 68.8% (p = 0.038) in the standard of care group. Conclusions: SMS and secure messaging patients with AEs on CAP resulted in clinical interventions by nurse care managers. Nurse intervention resulted in the majority of patients having symptomatic resolution and therapy continuation. PDC indicated greater medication adherence in the engaged group. These results for one drug suggest that nurse digital engagement can be effective in increasing adherence for patients treated with oral oncolytics suffering from AEs. Proactive symptom tracking supports the early identification of potential AEs and effective nurse care coordination.

Management of adverse events in patients with HER2+ metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine (HER2CLIMB).

1043 Background: Tucatinib (TUC) is an investigational TKI, highly selective for HER2 without significant inhibition of EGFR. HER2CLIMB is a randomized trial of TUC vs placebo in combination with trastuzumab and capecitabine in patients (pts) with HER2+ breast cancer (NCT02614794, Murthy NEJM 2019). The most common G ≥3 adverse events (AEs) with higher incidence on the TUC arm (diarrhea, palmar-plantar erythrodysesthesia syndrome [PPE], and elevated liver enzymes) are described herein. Methods: Given that pts on the TUC arm had a longer duration of tx than those on the control arm, time-at-risk exposure-adjusted incidence rates of diarrhea, AST, ALT, and PPE were calculated as the number of pts with an event divided by the total exposure time-at-risk of an initial occurrence of the event among pts in the tx group. Time-to-event analyses were conducted for AST/ALT/bilirubin (in aggregate), diarrhea, and PPE. Results: Diarrhea and elevated AST/ALT/bilirubin on both the TUC and control arms were primarily G1/2 and manageable with dose modifications, and in some cases of diarrhea, with antidiarrheal tx. Median time to diarrhea onset was shorter on the TUC arm compared to control. For AST/ALT/bilirubin and PPE, median time to first onset was Cycles 1 and 2. On the TUC arm, antidiarrheals were used in 49.7% of cycles in which diarrhea was reported (39.8% on the control arm), and when used, the median duration of use on each arm was 3 days per cycle. Prophylactic antidiarrheals were not required per protocol. When adjusted for exposure (time-at-risk exposure-adjusted incidence rate per 100 person-years), the difference in G ≥3 events between tx arms becomes similar for diarrhea and PPE (21 vs 17 and 21 vs 19). The difference in G ≥3 events between arms is reduced for AST and ALT (7 vs 1 and 8 vs 1). Conclusions: TUC with trastuzumab and capecitabine was well-tolerated. Rates of G ≥3 diarrhea and PPE were similar between tx arms. Elevated liver enzymes were higher on the TUC arm, but were transient and reversible. Discontinuation of TUC due to AEs was rare. Clinical trial information: NCT02614794 . [Table: see text]

SAT-509 Sudden Onset of Malabsorption

Celiac disease (CD) is an immune-mediated enteropathy caused by a reaction to gliadin which responds to a restriction to dietary gluten. It has been traditionally recognized in children and young adults, although, recently, detection in the elderly population has increased. CD occurs in 2–5% of patients with autoimmune hypothyroidism, and is more prevalent in this group than in the general populationAn 82-year-old Caucasian woman with primary hypothyroidism and a BMI of 16 is referred to our endocrinology clinic for help with the management of hypothyroidism. She had a history of well controlled hypothyroidism on weight-dosed levothyroxine for many years until several months prior when she developed sudden onset of diarrhea and weight loss. Since then, her thyroid function tests showed an elevated TSH despite medication adherence. Her levothyroxine dose was steadily increased to 300 mcg daily and yet, her TSH still remained elevated. Laboratory work up was done which revealed elevated transglutaminase antibodies, suggesting the diagnosis of CD. The patient refused an endoscopy for a tissue diagnosis. Even though the patient has been diagnosed with CD, she has trouble following a gluten free diet and still has intermittent diarrhea and high levothyroxine requirements.Although lack of medication adherence is common, it is important to exclude gastric or intestinal causes of malabsorption in patients with high thyroid replacement requirements. Elderly patients often have paucity of symptoms, so high clinical suspicion is necessary to diagnose these patients.

Is It Crohn’s Disease?

Question: An otherwise healthy 22-year-old woman was admitted to a hospital for persistent diarrhea, abdominal cramps, and weight loss over the previous weeks. Laboratory findings showed a C-reactive protein of 5.58 mg/dL (reference value, <0.80 mg/dL), white blood cell count of 7350/μL, hemoglobin of 12.5 g/dL, and calprotectin of 22 μg/g (reference value, <50 μg/g); the remaining values were unremarkable. Stool cultures excluded common bacterial and protozoal pathogens, including Clostridium difficile. Abdominal ultrasound examination showed concentric thickening of the last ileal loop extending 7 cm proximal to the ileocecal valve. A colonoscopy revealed an inflamed mucosa in the distal 15 cm of the ileum with edema and aphthous erosions; colonic examination was normal. Biopsies were taken in all tracts from distal ileum to the rectum and the histopathological examination was suggestive of active ileal Crohn’s disease. During hospitalization, the patient was treated with a single course of oral steroids and received a 5-day course of levofloxacin 500 mg once daily. She had a rapid clinical response and oral steroids were tapered within 8 weeks, after which she maintained clinical remission for 3 more months. In March 2020, the patient was referred to the outpatient clinic of our center, complaining of worsening fatigue and recent onset of diarrhea, with 3–4 nonbloody bowel movements per day. Suspecting a Crohn’s disease exacerbation, a contrast-enhanced intestinal magnetic resonance imaging was performed. Radiologic examination showed regular distention of the intestine, no significant thickening of bowel walls, and no enhancement in the distal ileum (Figure A). Other abdominal findings were normal, thus making a Crohn’s flare improbable. Incidentally, on the cranial scans bilateral consolidations in peripheral pulmonary parenchyma were noticed in T2 sequences (white arrow in Figure B) and T1 sequences after gadolinium infusion (white arrow in Figure C and Figure D). On the basis of the history, the clinical presentation and the radiologic findings, what is your diagnostic suspicion? Look on page 1246 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Finally, a nasopharyngeal swab tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The patient did not meet the criteria for hospitalization or treatment. She was therefore discharged at home, with instructions to self-isolate, report to the hospital any change in symptoms or oxygen saturation, and wait 2 weeks before repeating virus testing. At 2 weeks follow-up she repeated 2nasopharyngeal SARS-CoV-2 swabs that were both negative and she was thus declared virus free. Diarrhea resolved spontaneously few days after the first virus test, along with an improvement of fatigue. At a follow-up visit, she reported feeling well and was not experiencing gastrointestinal or respiratory symptoms. Gastrointestinal symptoms are common among patients with coronavirus disease-19 (COVID-19), although their timing in the history of infection is yet to be clarified. In particular, diarrhea has been reported in ≤50.5% of patients alongside nausea and vomiting, which have been found in 1.0%–17.3% of patients.1D’Amico F. Baumgart D.C. Danese S. et al.Diarrhea during COVID-19 infection: pathogenesis, epidemiology, prevention and management.Clin Gastroenterol Hepatol. 2020; 18: 1663-1672Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar Like in the case described, these symptoms can be the main clinical manifestation of COVID-19 and, owing to their nonspecific nature, can mimic several gastrointestinal conditions. In a recent case series from Spain, COVID-19 presented in patients with inflammatory bowel disease (IBD) with pneumonia and fever as most common symptoms, as well as diarrhea in 21%.2Rodríguez-Lago I. Ramírez de la Piscina P. Elorza A. et al.Characteristics and prognosis of patients with inflammatory bowel disease during the SARS-CoV-2 pandemic in the Basque Country (Spain).Gastroenterology. 2020; 159: 781-783Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Hence, in the midst of COVID-19 outbreak, SARS-CoV-2 infection should be ruled out in the assessment of any IBD exacerbation. In conclusion, we recommend considering COVID-19 in the differential diagnosis of any gastrointestinal condition presenting with diarrhea among its main manifestation. Generally, treatment for IBD, including biologics and JAK inhibitors, should not be suspended during COVID-19 pandemic as recently recommended by the International Organization for the Study of IBD (www.ioibd.org/ioibd-update-on-covid19-for-patients-with-crohns-disease-and-ulcerative-colitis/).3Rubin D.T. Feuerstein J.D. Wang A.Y. et al.AGA Clinical Practice Update on Management of Inflammatory Bowel Disease During the COVID-19 Pandemic: Expert Commentary.Gastroenterology. 2020; 159: 350-357Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar Our described case was reported on SECURE IBD (Surveillance Epidemiology of Coronavirus Under Research Exclusion – IBD, https://covidibd.org/), an international registry aimed at monitor and report outcomes of confirmed COVID-19 occurring in IBD patients. We encourage all physicians caring for patients with IBD to contribute to it.

Preliminary Evaluation of the Antidiarrheal Effects of Ethanol Leaf Extract and Fractions of &lt;i&gt;Rauwolfia vomitoria&lt;/i&gt; Afzel. (Apocynaceae)

Context: Diarrhea, a major leading cause of death among under-five children in developing countries is still ravaging the society today due to limitations associated with conventional treatment approaches. The leaf of Rauwofia vomitoria (R. vomitoria) is used by the locals in Nigeria for the treatment of diarrhea. Aim: This study evaluated the anti-diarrheal activity of the leaf extract and fractions of R. vomitoria using animal models. Methods: Phytochemical screening of the extract was carried out. The extracts and fractions of R. vomitoria were screened using castor-oil induced diarrhea, castor-oil induced enteropooling, charcoal meal test and ex-vivo anti-spasmomodic models. The tests groups received 400 mg/kg of the extract, n-hexane, ethyl acetate and water fractions based on the result of preliminary study. The Negative control (5 ml/kg of 5% Tween-80) and Positive control (Loperamide, 2 mg/kg and atropine sulphate, 10 mg/kg) were used. Ex-vivo anti-spasmodic test was carried out using isolated guinea pig ileum. Results: Phytochemical test revealed the presence of alkaloids, saponins, tannins, flavonoids, cardiac glycoside, terpenoids and steroids. In castor oil-induced diarrhea model, 400 mg/kg of the extract and fractions significantly (p≤0.05) prolonged diarrhea onset, decreased frequency of defecation, weight of feces, and volume of intestinal content. The extract and n-hexane fraction produced more significant (p&lt;0.05) antidiarrheal activity in castor oil –induced enteropooling and charcoal meal test models. The extract exhibited a dose dependent inhibition of acetylcholine induced contraction of isolated ileum. Conclusion: Results obtained from this study validate the folkloric use of R. vomitoria leaf extract in the treatment of diarrhea.

Evaluation of Antidiarrheal Activity of the Ethanol Extract Leucaena leucocephala (Lam) de Wit Seed

BACKGROUND: Leucaena leucocephala belongs to the Leguminosae/Fabaceae family. L. leucocephala seeds contain alkaloids, flavonoids, and tannins which according to the previous research have antidiarrhea activity.&#x0D; AIM: This study was investigate the antidiarrheal activity of the ethanol extracts of Leucaena leucocephala (Lam) de Wit seeds induced by oleum ricini and intestinal transit methods for rats.&#x0D; MATERIALS AND METHODS: L. leucocephala seeds were extracted by maceration with 80% ethanol. Evaluation of antidiarrheal extract activity was performed by induction of oleum ricini and intestinal transit methods. The extract at dose doses of 50, 100, 200, and 400 mg/kg BW was orally administered to the animals 1 h after induction by oleum ricini. Then diarrhea time, frequency, consistency, stool weight, and duration of diarrhea were observed every 30 min for 6 h. In determining the intestinal transit method, a percentage of the distance of the Chinese ink determined. This study was used positive control as Loperamide (1 mg/kg BW) and 0.5% Na-CMC as a negative control.&#x0D; RESULT: In diarrhea induced by castor oil, L. leucocephala seed extract at doses of 100, 200, and 400 mg/kg bw has been shown to significantly delay the onset of diarrhea, reduce diarrhea frequency, stool weight and duration of diarrhea compared with Na CMC as a negative control (p &lt; 0.05). The extract at a dose of 400 mg/kg bw did not differ significantly from loperamide as positive control (p &gt; 0.05). In this study, L. leucocephala extract reduced the distance traveled by Chinese ink in the intestine but only at a dose of 400 mg/kg bw which has a comparable activity with loperamide significantly . The antidiarrheal activity of extract showed at a dose dependent manner.&#x0D; CONCLUSION: The ethanol extract of L. leucocephala seeds has antidiarrheal activity which supports its use in folk medicines.

Antidiarrheal Activity of n-Hexane Fraction Seeds of Leucaenae leucocephala (Lam) de Wit on Rat

Objective: To evaluate the antidiarrheal activity of the n-hexane fraction of L. leucocephala (Lam) de Wit seeds induced by castor oil and intestinal motility methods for rats.&#x0D; Method: L.leucochepala seeds simplicia powder extracted by maceration with 80% ethanol. Ethanol extract was fractionated with n-hexane solvent. Investigating of antidiarrheal activity of L.leucocephala fraction by induction of castor oil and intestinal motility methods.&#x0D; Result: The n-hexane L.leucocephala fraction reduced diarrhea based on observations of the onset of diarrhea, frequency, consistency, weight of stool and duration of diarrhea compared with negative controls. The n-hexane L.leucocephala fraction showed antidiarrheal activity at doses of 200 and 400 mg/kg bw (P &lt;0.05) but differed significantly from loperamide (P &lt;0.05). In the intestinal motility method of the n-hexane fraction doses of 200 and 400 mg/kg bw the activity in inhibiting intestinal motility was significantly different from 0.5% CMC Na (P &lt;0.05).&#x0D; Conclusion: Then-hexane fraction of L. leucocephala seeds based on antidiarrheal activity testing has the ability to reduce diarrhea.&#x0D; &#x0D;

開腹手術で確定診断と治療を行った後腹膜膿瘍を合併した十二指腸水平脚潰瘍穿孔の1例(A case of perforated ulcer in third portion of duodenum with retroperitoneal abscess, which was diagnosed and treated by laparotomy)

要旨 60歳の男性。腹痛・下痢・嘔吐出現3日目に前医受診し原因不明のイレウスと診断され保存的加療が行われた。症状出現9日目のCT検査で後腹膜膿瘍形成を指摘され，加療目的で当院に転院となった。同日，虫垂穿孔または十二指腸穿孔による後腹膜膿瘍を疑い開腹手術を施行し，約1cm大の十二指腸水平脚後壁穿孔を認めた。十二指腸穿孔部位は炎症性に肥厚し脆弱で，単純縫合や被覆は困難と判断し，十二指腸水平脚部分切除および十二指腸下行脚−空腸吻合をOverlap法で行った。術後経過は良好で，約8か月後の上部消化管内視鏡検査で十二指腸に発赤・びらんのみ認め，切除検体の病理学的な特記所見はなく，十二指腸水平脚潰瘍穿孔と診断した。十二指腸水平脚穿孔は頻度が低く，特異的所見に乏しいが，後腹膜膿瘍形成前の発症早期に穿孔部位の縫合閉鎖手術を行うことが望ましい。後腹膜膿瘍を合併した症例では，ドレナージ・外科手術による治療を状況に応じて行うべきであると考えられた。

Association between Vitamin D Deficiency and Recurrent Acute Diarrhea in Children

Background: Vitamin D deficiency is highly prevalent among children worldwide. It causes impairment of the immune response to infection and decreased activity of gut antimicrobial peptides. The impact of vitamin D deficiency on the severity of acute diarrhea among children may be helpful for diarrheal management. Objective: To assess vitamin D deficiency and its correlation with recurrent acute diarrhea in children. Subjects and Methods: This study included 60 children, (1 to 5 years old) suffering from recurrent acute diarrhea more than 6 times per last year. They were subjected to complete history, clinical examination laboratory investigation and supplementation of vitamin D for three months for children who had vitamin D deficiency or insufficiency. Results: Vitamin D deficiency was found in 56.7%, insufficient in 21.7%, and sufficient in 21.7% in children with recurrent acute diarrhea. There was a statistical difference as regards the number of acute diarrhea attacks and vitamin D deficiency. Hemoglobin level was decreased below normal in (55%) of children with deficiency. Stool examination detected Enterobius vermicularis, Giardia lamblia, Entamoeba histolytica, and Ascaris lumbricoides in (26.7%, 8.3%and 3.3%, and 1.7%) respectively. Seventy-five percent of the studied children were supplemented with vitamin D which significantly decreases the number of diarrheal attacks. Conclusion: This study pay attention to the role of vitamin D in the susceptibility to infection-related illness in children. There is a positive correlation between vitamin D deficiency and iron-deficiency anemia. A significant decrease in the number of attacks of acute diarrhea after vitamin D supplementation was noted.

Milk consumption monitoring as a farmer friendly indicator for advanced treatment in limited fed calves with neonatal diarrhoea syndrome

The purpose of this study was to investigate whether milk consumption (MC) could be used as a simple farmer-friendly indicator for providing advanced treatment to limited fed diarrhoeic neonatal calves. Complementarily, it was evaluated whether the standard indications for veterinary care (severe dehydration and/or acidosis-septicaemia) are associated with different patterns in MC. The MC and health records of 103 calves with diarrhoeathat were fed a milk replacer at the volume of 10% of their body weight were used in the study. The MC reduction rate (MCRR) was calculated after each feeding (MC&lt;sub&gt;t&lt;/sub&gt;) during the diarrhoea course, based on the MC prior to the diarrhoea onset for each calf (MC&lt;sub&gt;0&lt;/sub&gt;) using the formula MCRR = 100 × (MC&lt;sub&gt;0&lt;/sub&gt; − MC&lt;sub&gt;t&lt;/sub&gt;)/MC&lt;sub&gt;0&lt;/sub&gt;. The calves were assigned into the ST group (n = 58) if they only received the standard treatment (oral rehydration solutions between milk feedings) until recovery, and into the advanced treatment (VT) group (n = 45) if they needed advanced treatment (i.v. fluids ± antibiotics) directly or after the standard treatment. The calves in the VT group that only had dehydration, were further assigned into the DH subgroup (n = 22) and those with signs of acidosis-septicaemia with or without dehydration were assigned into the ASD subgroup (n = 23). The MC was practically stable in the ST group throughout the diarrhoea course. In the VT group, the MC was significantly reduced during the last 36 hours prior to the advanced treatment administration. This reduction was significantly higher in the ASD subgroup than the DH subgroup. The MCRR on the last meal prior to treatment administration was proven to be a very reliable indicator for the detection of diarrhoeic calves needing advanced treatment (cut-off: ≥ 24.5%; sensitivity: 95.6%; specificity: 98.7%) and of those with acidosis-septicaemia (cut-off: ≥ 29.6%; sensitivity: 91.7%; specificity: 99.1%). The results of the study show thatfarmers employing this feeding regimen should seek veterinary assistance when the milk consumption of calves is reduced by ≥ 24.5%.

Safety and Tolerability of Two Different Formulations of Mycophenolate (Mycophenolate Mofetil and Mycophenolate Sodium) among Patient with Connective Tissue Disease Associated Interstitial Lung Disease (CTD-ILD) in a Tertiary Care Hospital

Background: One of the leading cause of mortality in various connective tissue diseases(CTD) like systemicsclerosis(SSc)is Interstitial lung disease(ILD). The various CTD which may present as ILD include systemicsclerosis (SSc), rheumatoid arthritis(RA),dermatomyositis (DM), primary Sjogren’s syndrome(pSS), mixtedconnective tissue disease(MCTD) and systemic lupus erythematosus (SLE).Objective: To compare the safety and tolerability of two salts of mycophenolate,i.e. mycophenolate mofetiland mycophenolate sodium in our patients with CTD-ILD.Patients and Method: Ourstudy was retrospective observational study; involving 70 patients diagnosedwith CTD-ILD and was treated with two formulations of Mycophenolate (Mofetil and Sodium) minimumfor six months with at least one follow-up during the period of May 2013 to April 2017 at tertiary carehospital from India. Fifty-six patients received MPS and fourteen patients received MMF. The details ofpatients obtained from case records were recorded in a proforma. Statistical analysis was performed usingGraph pad for frequency, mean and percentages.Results: In our study,most of the patients receivedMycophenolate sodium (n=56) with the BD dose regimenof 720 mg (n=36), 540 mg (n=18) and 180 mg (n=2). Patients treated with MMF 1000 mg (n=12) and 750mg (n=2) as BD dose regimen.The adverse events reported in this study were GI (diarrhoea), herpes zosterinfection, cytopenia, malignancies or any other infections. The incidence of diarrhea is most commonlyobserved in this study population. Out of 26 reported cases, 14 patients had an episode of diarrhea at leastonce and 12 patients had diarrhea attack twice the preceding year.Conclusions: Both formulations of Mycophenolate were tolerated well, and have low-dose corticosteroiduse with no discontinuation of therapy.

Protective effect of SKB_Gutbiotic against castor oil and E.coli induced diarrhea in laboratory animals

The aim of this study is to evaluate antidiarrheal activity of SKB_Gutbiotic against Castor oil and E.coli induced diarrhea in Swiss albino mice and Sprague Dawley rats. In present study three doses of SKB_Gutbiotic were tested against castor oil induced diarrhea in mice. Its effect on co-administration with l-arginine was studied. SKB_Gutbiotic delayed onset of diarrhea, reduced fecal output and fecal weight. In Gastrointestinal transit time and Castor oil induced enteropooling, SKB_Gutbiotic significantly reduced peristaltic index and volume of intestinal content respectively. In E.coli induced diarrhea model, E.coli suspension was administered for 3 days for inducing diarrhea. SKB_Gutbiotic significantly and dose dependently reduced fecal output, improved fecal consistency, reduced fecal water content and improved WBC count. Histopathological images showed improvement in damage caused to the mucosal epithelium due to E.coli and also improved complete crypt cell architecture and integrity of goblet cells. These results indicated that SKB_Gutbiotic can be used as an antidiarrheal agent against castor oil and E.coli induced diarrhea. It inhibits colonization of E.coli bacteria on colonic epithelium which results into decreased intestinal hypersecretion and motility which is very useful in the management of infectious diarrhea. Thus SKB_Gutbiotic could be an effective alternative to standard antidiarrheal drugs.

A257 NEW ONSET ULCERATIVE COLITIS IN A PATIENT WITH KNOWN AUTOIMMUNE HEPATITIS TYPE 1

Abstract Background Elevated transaminases can occur in up to 17 per cent of cases of Inflammatory Bowel Disease (IBD)1, with many cases related to concurrent autoimmune conditions of the liver. Primary Sclerosing Cholangitis (PSC) is the most common autoimmune disease of the liver that is associated with IBD. Other causes of liver inflammation in patients with IBD can include Autoimmune Hepatitis (AIH). Aims We aim to report a case of new onset ulcerative colitis in a patient with autoimmune hepatitis type 1 in the absence of concomitant PSC. Methods Case report and review of literature. Results A 25-year-old male with painless jaundice and was found to have Autoimmune hepatitis type 1 with typical morphological changes, positive Antinuclear antibodies and elevated IgG levels. Histopathological exam of the liver did not show any direct changes to the bile ducts to suggest PSC. The patient was started on steroids and Mycophenolate Mofetil (MMF) and developed new onset diarrhea. Colonoscopy was performed and both endoscopic and pathological findings were suggestive of likely inflammatory bowel disease, although drug induced colitis (MMF) could not be excluded. Conclusions We conclude that there is a link between autoimmune hepatitis with IBD, in absence of concomitant PSC. Funding Agencies None

Abstract OT2-02-09: Phase II study of trimebutine maleate and probiotics for abemaciclib-induced diarrhea in patients with ER-positive and HER2-negative advanced breast cancer (MERMAID) WJOG11318B

Abstract Background: The standard treatment for estrogen receptor-positive, HER2-negative inoperable and/or recurrent breast cancers is a combination of endocrine therapy and a CDK4/6 inhibitor (abemaciclib). When abemaciclib is administered, 80%-90% of patients experience diarrhea, resulting in the reduction of patient QOL and compliance. Loperamide is recommended for abemaciclib-induced diarrhea as well as chemotherapy induced diarrhea. However, previous reports showed that approximately 40% patients had constipation due to supportive treatment of loperamide. Moreover, the side effects of molecular targeted drugs, including abemaciclib, are not clear in the mechanism, and the effectiveness of coping therapy similar to chemotherapy and the treatment for side effects have not been clearly established. Thus developing new measures to effectively manage abemaciclib-induced diarrhea is an important clinical task, especially prevention of diarrhea without increasing adverse events such as constipation will be important to maintain QOL of patients receiving abemaciclib. Trial Design: This is a multicenter, randomized, open-label Phase II study to evaluate the efficacy and safety of probiotics (bifidobacterial formulation) and trimebutine maleate in treatment of abemaciclib-induced diarrhea. Both Arms A and B will receive hormone therapies (selected by physician in charge*) as directed along with abemaciclib 150 mg bid over the course of 28 days, and simultaneously to initiation of abemaciclib administration, will be given two pills of Biofermin® tid in Both Arms. Once patients experience diarrhea that is grade 6 or greater on the Bristol scale (higher grade than loose stool), salvage therapy using loperamide will be administered in Arm A. In contrast, participants from Arm B will be administered 100 mg trimebutine maleate. Thereafter, following meals, trimebutine maleate tid will be given throughout the trial period of 28 days. Eligibility Criteria: Key eligibility criteria for this trial are: Histologically diagnosed estrogen receptor-positive, HER2-negative breast cancer. Stage IIIB/IIIC breast cancer that is not subjected to surgery for curative intent, Stage IV breast cancer suitable for endocrine therapy. No prior treatment with CDK 4/6 inhibitors, and any type and number of previous treatments will be allowed in the selection criteria except CDK4/6 inhibitors. Specific Aims: The primary endpoint is the percentage of patients who experienced Grade 2 or greater diarrhea during the trial duration of 28 days and key secondary endpoints include safety, frequency and duration of all-grade diarrhea, frequency of emesis and constipation, comparative usage of loperamide in Arms A and B, and QOL/PRO in the 28-day study duration Statistical Design: By using the 40% threshold as the null hypothesis, appropriate statistical analysis will be performed based on a binomial distribution. The significance level will be 2.5%, determined using a one-tailed test. Interval estimation will be appropriately deduced from a binomial distribution. If either arm shows a significant reduction compared with the threshold value, as secondary validation, intergroup comparison of the primary endpoint percentage of diarrhea onset will be performed. In this case, the significance level will be 10%, determined using a two-tailed test. Target Accrual: A total of 50 patients will be enrolled and duration of enrollment will be 1 year. This trial will open to accrual in September 2019. Contact Information: Hiroko Masuda, Showa University Hospital, Tokyo, Japan, hmasuda@med.showa-u.ac.jp Citation Format: Hiroko Masuda, Tsutomu Iwasa, Toru Mukohara, Shinya Tokunaga, Koji Matsumoto, Naoki Niikura, Yasuaki Sagara, Yasuo Miyoshi, Akihiko Shimomura, Masato Takahashi, Takeshi Nagashima, Mihoko Doi, Manabu Futamura, Kenichi Yoshimura, Toshimi Takano, Junji Tsurutani. Phase II study of trimebutine maleate and probiotics for abemaciclib-induced diarrhea in patients with ER-positive and HER2-negative advanced breast cancer (MERMAID) WJOG11318B [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-02-09.

Which probiotic has the best effect on preventing Clostridium difficile-associated diarrhea? A systematic review and network meta-analysis.

Clostridium difficile-associated diarrhea (CDAD) accounts for up to 25% of patients with antibiotic-associated diarrhea (AAD). We aimed to determine which probiotic is most effective in preventing CDAD using a network meta-analysis. Studies were identified by searching PubMed, EMBASE and the Cochrane Library databases for randomized controlled trials (RCTs) that evaluated the efficacy of probiotic interventions for CDAD. Primary outcomes were the incidence rates of AAD and CDAD, and secondary outcomes were the duration of diarrhea and the time until onset of diarrhea. The PROSPERO registered number of this study is CRD42018106115. Ten RCTs including 11 analyses and including 4 692 patients were identified. Compared with the control group, probiotic intervention reduced the incidence rates of CDAD (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.17-0.61) and AAD (OR 0.39, 95% CI 0.23-0.66). Similar results were observed regarding the duration of diarrhea and the time until onset of diarrhea. Meta-regression analysis showed a correlation between the type of probiotic used and the incidence of CDAD and AAD. All nine kinds of probiotic interventions were statistically more effective than the placebo, with Lactobacillus casei ranking as the best intervention (OR 0.19, 95% credible interval [CrI] 0.06-0.63) for decreasing the incidence rate of CDAD. L. casei also ranked the highest in reducing the incidence rate of AAD (OR 0.32, 95% CrI 0.14-0.74). Lactobacilli strains, especially L. casei, have a good effect on the prevention of CDAD and AAD.

Intestinal Rupture Due to a Non-Perforating Foreign Body

Background: Intestinal obstruction by a foreign body is a common occurrence in domestic animals, needing the attention of veterinarians and owners, given that a serious complication of this condition is intestinal rupture, with consequent peritonitis. Perforating objects are the ones most often associated with rupture, but any object that obstructs the intestinal tract, if not removed properly, can lead to intestinal rupture, generating a poor prognosis. This article reports a case of intestinal rupture caused by a non-perforating foreign body in a dog. Case: A 1-year-old Chow-Chow dog was taken by its owner to the Portal Pet private clinic, with a history of foreign body ingestion and emesis. The owner reported that he took the animal to veterinary care in another establishment on the day he noticed vomiting, with no other abnormality being detected. An injectable medication was administered, but the owner did not know what it was, and the dog was discharged. After 15 days, the owner sought care at the clinic initially mentioned, due to the persistence of emesis, in addition to the onset of diarrhea and apparent apathy. On physical examination, the dog was apathetic, with pale mucosa and pain on abdominal palpation. A firm structure was felt, located in the epigastric region, compatible with a foreign body. The dog was referred for hospitalization and an abdominal ultrasound was requested, in addition to blood samples for hematological and serum biochemical tests (urea, creatinine, alanine aminotransferase, and alkaline phosphatase). Serology for parvovirus was also performed. The blood count revealed leukopenia (4,800 thousand/mm3) and biochemical analysis showed an increase in alkaline phosphatase (895.5 U/l). The results for parvovirus were negative. Ultrasonography confirmed the presence of a foreign body. The animal was referred for exploratory laparotomy, in which the foreign body was found in the abdominal cavity as a result of intestinal rupture, and peritonitis was observed. The foreign body was removed, the abdominal cavity washed, intestinal raffia made, and an abdominal drain inserted. The foreign body was identified as a silicone makeup sponge. Three days later, the drain was removed. The patient had good post-surgical clinical evolution and was discharged. The prescription given was as follows: omeprazole 1 mg/kg (VO, every 24 h in the morning, for 2 weeks); dipyrone25 mg/kg (VO, TID, for 4 days); cephalexin 25 mg/kg (VO, BID, for 10 days); mineral vitamin supplement based on probiotics and prebiotics 1 tablet/10 kg (VO, every 24 h, for 10 days); vermifuge based on milbemycin oxime and praziquantel 5-25 mg (VO, in a single dose, with repetition after 15 days); enrofloxacin 50 mg 10 mg/kg (VO, every 24 h, for 7 days); immunoglobulinbased on blood plasma, vitamins and minerals 1 tablet/10 kg (VO, BID, until new recommendations); and metronidazole 40 mg/mL oral solution at a dose of 25 mg/kg (VO, BID, for 7 days). As topical treatment, an antiseptic spraybased on laurel, diethylene glycol ether, sodium sulfate, and povidine iodinewas prescribed for surgical wound cleansing, until the suture removal, and the use of a surgical collar was requested. A reassessment was scheduled after 10 days, during which the suture was removed. At this point the dog had fully recovered.Discussion: Intestinal obstruction by a foreign body is a common cause of veterinary emergencies. As observed in the reported case, rupture of the intestinal wall and peritonitis can result. Although the prognosis of the affected animals is guarded, diagnosis prior to the worsening of septicemia as well as immediate surgical intervention were essential for recovery.

Thrombocytopenia and endocarditis in a patient with Whipple\u2019s disease: case report

BackgroundWhipple’s disease (WD) is a rare multisystem infectious disorder that is caused by the actinomycete Tropheryma whipplei. It presents with joint pain followed by abdominal pain, diarrhea, malabsorption and finally failure to thrive. Diagnosis requires tissue sampling and histology with periodic acid-Schiff [PAS] staining. Thrombocytopenia associated with endocarditis associated with WD has been reported twice.Case presentationA 56 year old Caucasian male presented with years of steroid treated joint pain and recent onset diarrhea, weight loss and abdominal pain. Ultimately he was found to have a platelet count of 4000 with concomitant endocarditis and embolic stroke. Small bowel biopsy confirmed the diagnosis of WD approximately 1 year after his first visit. His platelets improved with antibiotic treatment but he eventually expired 16 months after his initial consult and 5 months after his definitive diagnosis.ConclusionWD can remain undiagnosed and untreated until late in the course of the illness. A high index of suspicion is recognized as necessary for early diagnosis to begin treatment. Critical thrombocytopenia associated with endocarditis is a rare and potentially poor prognostic sign in late stage Whipple’s disease.

A double-blind placebo-controlled trial of azithromycin to reduce mortality and improve growth in high-risk young children with non-bloody diarrhoea in low resource settings: the Antibiotics for Children with Diarrhoea (ABCD) trial protocol

BackgroundAcute diarrhoea is a common cause of illness and death among children in low- to middle-income settings. World Health Organization guidelines for the clinical management of acute watery diarrhoea in children focus on oral rehydration, supplemental zinc and feeding advice. Routine use of antibiotics is not recommended except when diarrhoea is bloody or cholera is suspected. Young children who are undernourished or have a dehydrating diarrhoea are more susceptible to death at 90 days after onset of diarrhoea. Given the mortality risk associated with diarrhoea in children with malnutrition or dehydrating diarrhoea, expanding the use of antibiotics for this subset of children could be an important intervention to reduce diarrhoea-associated mortality and morbidity. We designed the Antibiotics for Childhood Diarrhoea (ABCD) trial to test this intervention.MethodsABCD is a double-blind, randomised trial recruiting 11,500 children aged 2–23 months presenting with acute non-bloody diarrhoea who are dehydrated and/or undernourished (i.e. have a high risk for mortality). Enrolled children in Bangladesh, India, Kenya, Malawi, Mali, Pakistan and Tanzania are randomised (1:1) to oral azithromycin 10 mg/kg or placebo once daily for 3 days and followed-up for 180 days. Primary efficacy endpoints are all-cause mortality during the 180 days post-enrolment and change in linear growth 90 days post-enrolment.DiscussionExpanding the treatment of acute watery diarrhoea in high-risk children to include an antibiotic may offer an opportunity to reduce deaths. These benefits may result from direct antimicrobial effects on pathogens or other incompletely understood mechanisms including improved nutrition, alterations in immune responsiveness or improved enteric function. The expansion of indications for antibiotic use raises concerns about the emergence of antimicrobial resistance both within treated children and the communities in which they live. ABCD will monitor antimicrobial resistance. The ABCD trial has important policy implications. If the trial shows significant benefits of azithromycin use, this may provide evidence to support reconsideration of antibiotic indications in the present World Health Organization diarrhoea management guidelines. Conversely, if there is no evidence of benefit, these results will support the current avoidance of antibiotics except in dysentery or cholera, thereby avoiding inappropriate use of antibiotics and reaffirming the current guidelines.Trial registrationClinicaltrials.gov, NCT03130114. Registered on April 26 2017.

Differences in time-to-testing and time-to-isolation between community-onset and hospital-onset Clostridioides difficile cases at a tertiary care VA medical center

Delayed identification and isolation of patients with Clostridiodies difficile infection (CDI) may contribute to in-hospital transmission and delay appropriate therapy. To assess potential points for intervention, we conducted a retrospective cohort study to determine differences in time-to-testing and time-to-isolation among community-onset (CO), community-onset healthcare facility-associated (CO-HCFA), and hospital-onset (HO) CDI. We compared clinical and demographic data of all CO, CO-HCFA, and HO CDI patients at our institution between October 2011 and September 2015. We then performed bivariable analysis on our cohorts to identify differences in time-to-testing and time-to-isolation for CO versus CO-HCFA versus HO CDI patients. 355 patients with CDI were hospitalized during the study; 138 (38.9%) with CO CDI, 52 (14.6%) with CO-HCFA CDI, and 165 (46.5%) with HO CDI. 117 (84.8%) CO CDI patients were tested within 1 day of diarrhea onset compared to 41 (78.8%) of CO-HCFA and 113 (68.5%) of HO CDI patients (P < .01). 51 CO CDI patients (36.7%) were placed on empirical isolation precautions at the time of diarrhea onset compared to 22 (43.1%) of CO-HCFA CDI patients and 32 (19.4%) of HO CDI patients (P < .01). CO CDI patients are more likely to be isolated empirically and tested earlier than HO CDI patients. Further attention should be paid to isolating hospitalized patients who develop diarrhea as an inpatient.

Evaluation of the antidiarrhoeal activity of Careya arborea leaves extract

Aim: To evaluate the antidiarrhoeal activity of Careya arborea leaves extract. Methods: Antidiarrhoeal activity of the methanol extract of Careyaarborea leaves (MECAL) was investigated using different animal models of diarrhea in rats. Results: The antidiarrhoeal activity demonstrated by MECAL was found to be dose-dependent at different doses in the castor oil-induced diarrhea model. Graded doses viz 125, 250 and 500 mg/kg produced a significant decrease in mean fecal drops, the weight of feces onset of diarrhea as compared with control. The % protection was found to be 35%, 40% and 51% at graded doses of extract respectively. In MgSO4 induced diarrhea model, test extract demonstrated dose-dependent antidiarrhoeal potential which was evident by monitoring significant delay in the onset of diarrhea and decrease in No. of fecal dropping and weight of stool when compared to the control group. The higher dose (500 mg/kg) of test extract produced 33 % protection of diarrhea which was found to be less potent than standard. Conclusion: The results of the present investigation concluded that the methanolic extract of Careyaarborea leaves (MECAL) demonstrated dose-dependent antidiarrhoeal activity due to the presence of pharmacologically effective component(s).