Onset Of Diarrhea Research Articles

UJIAKTIVITAS ANTIDIAREEKSTRAKETANOL KULIT BATANGSENGKUANG Dracontomelon dao(Blanco) Merr&RolfeTERHADAP MENCITPUTIH (Mus musculus) JANTAN DENGANMETODEPROTEKSI DIARE

SengkuangorDracontomelon dao(Blanco) Merr & Rolfe.is a plant that has secondary metabolites tannins and flavonoids which are thought to have anti-diarrheal activity. The purpose of this studyisto determine the ethanol extract of the stem bark of Dracontomelon dao(Blanco) Merr & Rolfe hasanantidiarrheal effect and to determine the ethanol extract dose of the stem bark of Dracontomelon dao(Blanco) Merr & Rolfe which has antidiarrheal effect on male white mice (Mus musculus)induced by oleum ricini. The antidiarrheal activity test was carried out using the diarrhea protection method, where micewere induced by0.75 mL of oleum ricini orally, 1 hour later the test solutionwas given i.e. 0.5% Na CMC suspension (negative control), loperamid 0.26 mg/kg bw(positive control), dose of sengkuang stem bark ethanol extract 100 mg/kgbw, 200 mg/ kg bwand 300 mg/kgbw. Then observed the onset of diarrhea, frequency of diarrhea, consistency of diarrhea, duration of diarrhea and weight of diarrhea every 30 minutes for 4 hours. The results of this study arethe ethanol extract of the stem bark Dracontomelon dao(Blanco) Merr & Rolfe at a dose of 100 mg/kgbw, 200 mg/kgbw and 300 mg/kgbw has antidiarrheal activity as indicated by a significant difference in the test group (control positive and all extracts) against the negative control group (p <0.05).

A Significant Role of Rotavirus in Acute Gastroenteritis in Infants and Young Children

A study of the role of rotavirus in acute gastroenteritis in infants and children was conducted in an attempt to find out the magnitude of its problems.
 It was found that the majority of cases with acute diarrhea was caused by rotavirus, only 8% were bacteriial gastroenteritis while the remaining one third of unknown origin.
 The clinical course of rotavirus gastroenteritis seemed to be a dysentery like diarrhea with an acute onset of watery diarrhea, associated with fever and vomiting.
 These findings indicate that a further extensive study is needed and that the regimen of treatment of dysentery-like diarrhea should be reevaluated.

700. Risk Factors and Molecular Epidemiology of Acute and Chronic Norovirus Infection at a Large Tertiary Care Cancer Center

BackgroundNorovirus (NoV) is the leading cause of viral diarrhea in patients with cancer. In this study, we describe risk factors associated with acute and chronic NoV infection in this patient population. MethodsWe identified 132 patients with NoV diarrhea (using stool RT PCR) between 2016-2020 at University of Texas MD Anderson Cancer Center (MDACC). Patient data, including demographics, clinical characteristics, NoV treatments, and complications were retrospectively extracted from charts. Stool samples were analyzed for NoV genogroups and genotypes. We compared characteristics and outcomes of patients with acute diarrhea (< 14day; AD) versus chronic diarrhea ( >14day or recurrences within 12 weeks; CD) and analyzed the data using Pearson Chi square or Fisher’s exact for categorical variables and Wilcoxon rank-sum test for continuous variables. ResultsOf 132 patients identified, 124 had an underlying cancer (39 solid tumor, 85 hematological malignancies, Table 1). On univariate analysis, CD patients were more likely to have a hematological malignancy (p=0.002), be a hematopoietic stem cell recipient (p= 0.013), have a history of gastrointestinal graft versus host disease (p= 0.011), or have received immunosuppressants or steroids in the 90 days before diarrhea onset (p=0.001, Table 2). CD patients had significantly lower white blood cell counts (p=0.038), absolute neutrophil counts (p=0.049), IgG levels (p= 0.001), and serum albumin levels (p=0.002) at the time of NoV diagnosis (Table 3). Patients with CD more often received symptomatic or NoV targeting treatment, including anti-diarrheal (p=0.005), nitazoxanide (p< 0.001), intravenous immune globulin (p=0.017), and oral IgG (p=0.042). CD patients more often had diarrheal recurrence in the first 4 weeks (p=0.001) or the second month (p< 0.001) after initial diagnosis and needed enteral or parenteral nutrition (p=0.004). We genotyped NoV in 67 patients (Figure 1), resulting in identification of the following genogroups: GI (n=9, 13%), GII.4 (n=23, 34%), and other types of GII (n=35, 52%). Genotype diversity was higher in patients with CD than AD (Figure 1). ConclusionIn patients with cancer, CD from NoV is associated with severe immunosuppression, is refractory to therapy and can be caused by a variety of NoV genotypes/genogroups. Disclosures Robert L. Atmar, MD, Takeda Vaccines, Inc. (Grant/Research Support) Mary Estes, PhD, Takeda Vaccines (Consultant, Grant/Research Support) Pablo C. Okhuysen, MD, FACP, FIDSA, Deinove Pharmaceuticals (Grant/Research Support)Ferring Pharmaceuticals (Consultant)Melinta Therapeutics (Grant/Research Support)Merck & Co. (Grant/Research Support)Napo Pharmaceuticals (Consultant, Scientific Research Study Investigator, Research Grant or Support)Singulex (Consultant)Summit Therapeutics (Grant/Research Support)

In vivo anti-diarrheal activity of jujube honey on castor oil-induced diarrhea in mice.

To evaluate the antidiarrheal effect of jujube honey on experimentally castor oil-induced diarrhea in mice by using different testing models (diarrhea, enteropooling and gastrointestinal motility). The mice intragastric administration castor oil was post-treated after 30 min with jujube honey, diluted jujube honey and loperamide or vehicles in different experimental groups. The onset and number of wet defecation on the absorbent paper was recorded for each animal for 4 h. Plasma was examined for C-reactive protein (CRP) and nitric oxide (NO) for clinical inflammation evaluation. The oxidative stress was investigated by superoxide dismutase (SOD) and catalase levels. The diluted jujube honey exhibited an important antidiarrheal activity manifested by significant delay in onset of diarrhea (P < 0.05), loss in number of wet stools (P < 0.001), total number of stools (P < 0.001) and total stool weight of fecal output (P < 0.001) in 4 h in castor oil-induced diarrheal groups. The inhibition of intestinal transit of charcoal meal (P < 0.01) is a most likely mechanism that may account for antidiarrheal effect of jujube honey. It also significantly increased SOD and catalase levels (P < 0.001) and significantly decreased CRP and NO in plasma diarrheic mice (P < 0.01). The results of this research reveal that the jujube honey contains pharmacologically active compounds with antidiarrheal properties. However, diluted honey is more effective in the treatment of diarrhea and imbalance of intestinal motility. In conclusion, these findings illustrated the antidiarrheal activity effect of jujube honey and which has the strongest evidence supporting its use in the treatment of diarrhea in traditional medicine.

Evaluation of Antidiarrheal Activity of 80% Methanolic Extract of the Leaves of Cordia africana (Lamiaceae) in Mice

Background Diarrheal disease is a major cause of morbidity and mortality throughout the world, particularly in developing countries. Currently available drugs are linked with adverse effects, contraindications, and risk of resistance. Traditionally, the leaf concoction of Cordia africana is claimed to be used for diarrhea. However, the safety and efficacy of the leaf extract have not been scientifically approved yet. Therefore, the study was conducted to validate its antidiarrheal activity and safety profile in mice. Method The hydromethanolic extract was obtained by the cold maceration technique in 80% methanol. Phytochemical screening tests were done for secondary metabolites by using standard tests. The antidiarrheal activity of the test extract at the doses of 100, 200, and 400 mg/kg was evaluated by using castor oil-induced diarrheal, gastrointestinal transit, and enteropooling models in mice. Result In an acute toxicity study, there were no visible signs of toxicity and mortality following a single oral administration of 2000 mg/kg. Phytochemical screening tests revealed the presence of alkaloids, saponins, flavonoids, terpenoids, phenols, and tannins. The hydromethanolic extract significantly prolonged the onset of diarrhea and reduced the weight of wet and total feces at 100 (P < 0.01), 200 (P < 0.001), and 400 mg/kg (P < 0.001) in the castor oil-induced diarrheal model. However, in the gastrointestinal transit model, a significant (P < 0.001) reduction in the charcoal meal travel was observed in the middle (200 mg/kg) and higher (400 mg/kg) test doses. Similarly, the extract produced a significant (P < 0.001) reduction in the weight and volume of intestinal contents at the aforementioned doses. Conclusion The study demonstrated that the test extract showed promising antidiarrheal activity. Hence, this study supports its antidiarrheal use in Ethiopian folklore medicine.

Tuberculosis reactivation at ileum following immune checkpoint inhibition with pembrolizumab for metastatic nasopharyngeal carcinoma: a case report

BackgroundTuberculosis (TB) reactivation has been increasingly identified following immune checkpoint inhibitor (ICI) therapy for cancer patients. However there has been no report on TB reactivation in the gastrointestinal tract. In the report, we describe a patient who developed TB ileitis after pembrolizumab for her metastatic nasopharyngeal carcinoma (NPC). Rechallenge with pembrolizumab after its temporary interruption together with anti-TB therapy produced continuous tumor response but without further TB reactivation.Case presentationA 29-year-old lady with metastatic NPC involving the cervical nodes, lungs and bones started pembrolizumab after failure to multiple lines of chemotherapy. She complained of sudden onset of abdominal pain, vomiting and bloody diarrhea with mucus 21 months after pembrolizumab. Colonoscopy revealed terminal ileitis with multiple caseating granulomas with Langerhan cells. Serum interferon gamma release assay was strongly positive. She was treated with anti-TB medication and was later rechallenged with pembrolizumab for her progressive lung metastases without further TB relapse while her lung metastases were brought under control again.ConclusionTo date, this is the first gastrointestinal TB reactivation after ICI therapy for cancer. Guidelines to screen for TB before initiation of ICIs in endemic areas should be established.

Two consecutive attacks of diarrhea in 15 COVID-19 patients: An antibiotic-associated one following the viral one

De los 971 pacientes admitidos en nuestra clínica por sospecha de COVID-19, 15 (1.5%) presentaron dos ataques de diarrea consecutivos. Uno de dichos pacientes (una mujer de 47 años) requirió admisión a la unidad de cuidados intensivos y ventilación mecánica. Murió el 11.o día de hospitalización (18 días de enfermedad). El primer ataque de diarrea en dichos pacientes ocurrió el 6.o (4.o -7.o) día de enfermedad, con una duración de 3 (3-5) días. El segundo ataque de diarrea se desarrolló 11 (8-12) días después del comienzo inicial de diarrea. A pesar de la tendencia existente, la diferencia en la duración de la diarrea y el número máximo de movimientos intestinales por día entre el primer y el segundo ataque no fue estadísticamente significativa (p = 0.130; p = 0.328). Tampoco existió diferencia significativa respecto a los resultados del conteo sanguíneo completo, las pruebas bioquímicas sanguíneas, ni los biomarcadores inflamatorios, entre los pacientes que presentaron un doble ataque de diarrea y los que no presentaron diarrea.

Antidiarrheal activity of Bridelia ferruginea bark methanolic extract involves modulation ATPases in mice and inhibition of muscarinic acetylcholine receptor (M3) and prostaglandin E2 receptor 3 (EP3) in silico.

Diarrhea, an abnormal state in which the individual has about three or more daily bowel movements, is now considered one of the most challenging global public health problems. Using plant products, such as Bridelia ferruginea is an alternative treatment option. The objective of this study was to investigate the antidiarrheal activity of B.ferruginea bark methanolic extract (BfME) and the mechanisms involved. BfME antidiarrheal activity was evaluated in mice model of castor oil-induced diarrhea and enteropooling. To evaluate motility, gastrointestinal transit time was carried out using phenol red meal, while intestinal activities of selected ATPases were also evaluated. Furthermore, the active components in BfME were detected by GC-MS analysis, while molecular docking of the most abundant compounds with muscarinic acetylcholine receptor (M3) and prostaglandin E2 receptor 3 (EP3) were conducted. BfME at 400 and 800mg/kg showed antidiarrheal activity by delaying onset of diarrhea, reduced gastrointestinal transit and increased intestinal activities of Na+ K+-ATPase, Ca2+ Mg2+-ATPase and Mg2+-ATPase. Molecular docking revealed that γ-sitosterol, α-amyrin, and stigmasterol have outstanding binding affinity for M3 and EP3. In view of these results, the observed antidiarrheal activity possibly occurs via the activation of ATPases activities and inhibition of M3 and EP3.

M221 FOOD PROTEIN-INDUCED ENTEROCOLITIS SYNDROME MASQUERADING AS INTUSSUSCEPTION

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food hypersensitivity that typically affects infants. After ingestion of the culprit protein, a delayed onset of vomiting, lethargy, pallor, and bloody diarrhea can occur, which can be life-threatening. The differential diagnosis for acute vomiting in an infant is broad, making this diagnosis challenging. We present a patient in whom FPIES was initially thought to be intussusception, a common cause of childhood bowel obstruction where the intestines telescopes into itself, causing a delay in diagnosis and reoccurrence of symptoms.

UJI EFEKTIVITAS ANTIDIARE EKSTRAK ETANOL DAUN GELUGUR (Garcinia atroviridis Griff ex. T Anderson)TERHADAP TIKUS JANTAN PUTIH (Rattus norvegicus) DENGAN LOPERAMIDE SEBAGAI PEMBANDING

Gelugur leaf (Garcinia atroviridis Griff ex T. Anderson) is a kind of nadir is believed to origanate from the wild forest of Peninsular Malaysia. Gelugur leaves have antidiarrheal compounds in the shapes of tannins and flavonoids to reduce diarrhea. The purpose of this study was to find out the antidiarrheal activity of the ethanolic extract of gelugur leaf in white male rats. The antidiarrheal effect was tested on 15 white male rats with 5 treatment groups, namely, a negative control group of 1% CMC Na, a positive control group of loperamidee hcl, and a treatment group of ethanol extract of gelugur leaves at a dose of 150 miligrams/kgBW, a dose of 300 miligrams/kgBW, and 600 miligrams/kg body weight. Each group was given oral treatment and observations were made on the onset of diarrhea, frequency of diarrhea, and stool consistency. Tests were carried out using an experimental method. The ethanol extract of gelugur leaves was made by maceration method using 96% ethanol. The results of the study on the onset of diarrhea were EEDG 600 miligrams/kgBB (60 minutes), a good decrease in diarrhea frequency was indicated by EEDG 600 miligrams/kgBB (4 times), a good decrease in stool weight was shown by EEDG 600 miligrams/ kgBB (0,7757 grams), good consistency was also shown in the EEDG 600 miligrams/kgBB (soft stools. The data were statistically analyzed using One Way Anova. The results of data analysis from the three EEDG groups affected the decrease in diarrhea because the sig value &lt;0.05 Based on One Way Anova analysis, the five most effective treatments were loperamidee, 600 miligrams/kgBB, EEDG at 300 miligrams/kgBB, EEDG at 150 miligrams/kgBB, and CMC Na 1%. The conclusion in this study is that EEDG 600 miligrams/kgBB has antidiarrheal activity induced by oleum recini when compared with EEDG concentrations of 150 miligrams/kgBB and 300 miligrams/kgBB.

The cost-effectiveness of community health workers delivering free diarrhoea treatment: evidence from Uganda.

Community health workers (CHWs) are a vital part of the health infrastructure in Uganda and in many other low- and middle-income countries. While the need for CHWs is clear, it is less clear how they should dispense health products to maximize the health benefits to their community. In this study, we assess the cost-effectiveness of several competing CHW distribution strategies in the context of treatment for child diarrhoea. We used data from a four-armed cluster-randomized controlled trial to assess the cost-effectiveness of (1) free distribution of oral rehydration salts (ORS) via home deliveries prior to diarrhoea onset (free delivery arm), (2) free distribution via vouchers where households retrieved the treatment from a central location (voucher arm), (3) a door-to-door sales model (home sales arm) and (4) a control arm where CHWs carried out their activities as normal. We assessed the cost-effectiveness from the implementor's perspective and a societal perspective in terms of cost per case treated with ORS and cost per disability-adjusted life year (DALY) averted. Free delivery was the most effective strategy and the cheapest from a societal perspective. Although implementor costs were highest in this arm, cost savings comes from households using fewer resources to seek treatment outside the home (transport, doctor fees and treatment costs). From the implementors' perspective, free delivery costs $2.19 per additional case treated and $56 per DALY averted relative to the control. Free delivery was also extremely cost-effective relative to home sales and vouchers, but there was a large degree of uncertainty around the comparison with vouchers. Free distribution of ORS by CHWs prior to diarrhoea onset is extremely cost-effective compared to other CHW distribution models. Implementers of CHW programmes should consider free home delivery of ORS.

Efficacy of Microencapsulated Probiotic as Adjunct Therapy on Resolution of Diarrhea, Copper-Zinc Homeostasis, Immunoglobulins, and Inflammatory Markers in Serum of Spontaneous Rotavirus-Infected Diarrhoetic Calves.

The objective of this study was to assess the efficacy of a microencapsulated probiotic as an adjunct therapy in rotavirus-positive diarrhea of neonatal calves that received supportive treatment or supportive along with microencapsulated probiotic treatment, for 5days. We examined whether microencapsulated Lactobacillus acidophilus NCDC15 probiotic treatment in rotavirus-infected diarrhoetic calves led to faster resolution of diarrhea, amelioration of zinc-copper imbalance, improved the immunoglobulin A and immunoglobulin G, and decreased the inflammatory markers in serum. Calves with rotavirus-positive diarrhea < 4-week age and fecal scores ≥ 2 were randomly assigned into two groups. The supportive along with microencapsulated probiotic treatment significantly (p < 0.05) increased zinc and immunoglobulin A concentrations and decreased copper, tumor necrosis factor-α, and nitric oxide level in serum on days 3 and 5 from pretreatment values; the immunoglobulin G concentration was elevated (p < 0.05) on day 5. The mean resolution time of abnormal fecal score was 5.3 and 3.3days in supportive treatment and supportive along with microencapsulated probiotic groups, respectively, in log-rank Mantel-Cox test. The calves in the supportive along with microencapsulated probiotic treatment group had faster resolution of diarrhea than supportive treatment group in Dunn's multiple comparisons test. This study demonstrates that supportive treatment along with microencapsulated probiotic administered to naturally rotavirus-infected diarrhoetic calves at onset of diarrhea led to faster resolution of diarrhea, improved zinc and immunoglobulin levels, and decreased the inflammatory parameters in serum of rotavirus-infected diarrhoetic calves.

Antidiarrheal Effect of 80% Methanol Extract and Fractions of Clerodendrum myricoides (Hochst.) Vatke (Lamiaceae) Leaf in Swiss Albino Mice.

Background Diarrhea is one of the tempting symptoms of diseases in the world. In Ethiopian traditional medicine practices, Clerodendrum myricoides is utilized for the treatment of diarrhea without scientific evidence. Objective This study was aimed to evaluate the antidiarrheal activity of 80% methanol extract and fractions of the leaf of Clerodendrum myricoides in mice. Methods The crude extract was prepared by maceration in 80% methanol and then fractionated using hexane, chloroform, and distilled water. Antidiarrheal activity was assessed by castor oil-induced diarrhea, enteropooling, and gastrointestinal motility models using onset of diarrhea, number and weight of feces, volume and weight of intestinal contents, and distance travelled by charcoal meal as main parameters. Negative controls received either distilled water or 2% Tween 80 (10 ml/kg), positive controls received 3 mg/kg loperamide or 1 mg/kg atropine, and the test groups received 100, 200, and 400 mg/kg doses of the extract. Results The crude extract and chloroform fraction significantly prolonged the onset of diarrhea at 200 and 400 mg/kg and decreased the number of wet, total, and weight of fresh feces at all tested doses. Hexane fraction has a significant antidiarrheal effect on the onset, number, and weight of feces at 400 mg/kg. The crude extract and chloroform fraction at all tested doses, as well as aqueous fraction at 200 mg/kg and 100 mg/kg, produced significant reduction in volume and weight of intestinal contents. Additionally, hexane fraction showed significant reduction of volume and weight of the intestinal content at 400 mg/kg. In the gastrointestinal motility test model, both chloroform fraction and crude extract at all tested doses and aqueous fraction at 200 mg/kg and 400 mg/kg showed a significant antidiarrheal effect as compared to the negative control. Conclusion The leaf of Clerodendrum myricoides showed antidiarrheal activity which supports the traditional use.

Relationship between Plasma Concentrations of Afatinib and the Onset of Diarrhea in Patients with Non-Small Cell Lung Cancer.

Simple SummaryHigher afatinib plasma concentrations have been reported to be associated with the severity of diarrhea; however, the specific target plasma concentration of afatinib required to avoid severe diarrhea onset is unclear. We found that an afatinib AUC0–24 of greater than or equal to 823.5 ng·h/mL and C0 of greater than or equal to 28.5 ng/mL may be used as cut-off values for the incidence of afatinib-induced grade 2 diarrhea. A significant correlation between the AUC0–24 and C0 of afatinib was observed (r2 = 0.761; p < 0.001). Therefore, we could use C0 as a marker of therapeutic drug monitoring. In the current study, the median time to the incidence of grade 2 diarrhea in patients with a C0 of more than 28.5 ng/mL was 16 days. Therefore, we recommend monitoring the C0 of afatinib on day 8 after the beginning of afatinib therapy.We evaluated the area under the plasma concentration–time curve (AUC) of afatinib required to avoid the onset of grade 2 or higher diarrhea. The C0 and AUC0–24 of afatinib were significant higher in patients with grade 2 diarrhea than in those with grade 0–1 diarrhea. The areas under the receiver operator curves were 0.795 with the highest sensitivity (89%) and specificity (74%) at an AUC0–24 threshold of 823.5 ng·h/mL, and 0.754 with the highest sensitivity (89%) and specificity (74%) at a C0 threshold of 28.5 ng/mL. In Kaplan–Meier analysis based on these cut-off AUC0–24 and C0 values, the median time to the incidence of grade 2 diarrhea was 16 days. The predicted AUC0–24 of afatinib from the single point of C6 showed the highest correlation with the measured AUC0–24 (r2 = 0.840); however, a significant correlation between the AUC0–24 and C0 was also observed (r2 = 0.761). C0 could be used as a marker of therapeutic drug monitoring because afatinib C0 was related to AUC0–24. Therefore, afatinib C0 should be monitored on day 8 after beginning therapy, and the daily dose of afatinib should be adjusted as an index with a cut-off value of 28.5 ng/mL.

S1960 Acute Pseudomembranous Colitis, Microangiopathic Hemolytic Anemia, and Renal Injury After Pericardiectomy

Introduction: Acute colonic ischemia following surgery is usually a result of colonic hypoperfusion, particularly in watershed regions; however, it is critical to maintain a broad differential diagnosis for alternate etiologies. Case description/methods: A 57-year-old man with lupus on hydroxychloroquine and prednisone underwent elective pericardiectomy for medically refractory constrictive pericarditis. On post-operative day (POD) 3, he developed abdominal pain, nausea, and non-bloody diarrhea. Hematochezia started on POD 4. Computed tomography showed rectosigmoid thickening and perirectal fat stranding (Figure 1A). Sigmoidoscopy revealed edematous, ulcerated, and discolored mucosa from the anal verge to 30 cm proximally that abruptly normalized thereafter (Figure 1B). Sigmoid histology showed lamina propria hemorrhage with crypt withering and focal pseudomembranes (Figure 1C). Clostridioides difficile testing was negative. Colonic ischemia was favored. Given persistent leukocytosis and low fevers, antibiotics were started. From POD 4 to 8, platelets dropped from 142 to 11 × 109/L, and creatinine rose from 1.1 to 2.0 mg/dL (Figure 2). On POD 6, labs showed lactate dehydrogenase 1,107 U/L, indirect bilirubin 2.7 mg/dL, and undetectable haptoglobin, with hemoglobin dropping from 14.0 to 12.9 g/dL from POD 7 to 8. Peripheral smear on POD 8 showed schistocytes (Figure 3). Serum ADAMTS-13, complement levels, and heparin-induced thrombocytopenia panels were normal. Stool PCR detected shiga-toxin producing E. coli and shiga toxin 2, and stool cultures did not grow the 0157:H7 E. coli strain. Antibiotics were stopped due to the diagnosis of shiga-toxin induced hemolytic uremic syndrome (ST-HUS). The hemolysis, thrombocytopenia, and renal injury resolved after one week of supportive measures. Discussion: Infection by shiga-toxin producing E. coli (STEC), especially with shiga toxin 2 (which disrupts protein synthesis, causing apoptosis), presents with hemorrhagic colitis in 80% of cases and ST-HUS in up to 15% of cases. STEC is often acquired from contaminated food/ water. In this case, a hamburger from an external vendor was the suspected source. After a 3-day incubation period, STEC classically presents with abdominal pain and non-bloody diarrhea, followed by bloody diarrhea 1-3 days later. If it occurs, ST-HUS presents 1-2 weeks later from thrombotic microangiopathy. Antibiotics are linked to shiga toxin production by the encoding bacteriophage in the STEC chromosome.Figure 1.: Acute pseudomembranous colitis. A) Rectosigmoid wall thickening (green arrow) and perirectal fat stranding. B) Rectosigmoid colon was edematous, cyanotic, ulcerated, with luminal narrowing by flexible sigmoidoscopy. There was an abrupt transition to normal sigmoid mucosa at 30 cm from anal verge (not shown). C) Pathologic specimens from sigmoid colon showed crypt withering (blue arrow), lamina propria hemorrhage (orange arrow), and pseudomembrane (yellow arrow).Figure 2.: Clinical course of shiga-toxin induced hemolytic uremic syndrome (ST-HUS). Non-bloody diarrhea started on POD 3, followed by bloody diarrhea on POD 4. The patient’s thrombotic microangiopathy, signified by reduction in platelets and renal injury, began 3-4 days later, illustrating the characteristic delay from diarrhea onset and thrombotic microangiopathy in ST-HUS.Figure 3.: Peripheral smear. Peripheral smear was notable for schistocytes (blue arrow), suggestive of hemolysis, and markedly diminished number of platelets (green arrow). The combination of these features was consistent with thrombotic microangiopathy.

S1696 Vedolizumab Treatment of Refractory Immune Checkpoint Inhibitor Colitis

Introduction: Immune checkpoint inhibitors (ICI) are commonly associated with gastrointestinal adverse events including colitis. We present a case of severe immune checkpoint inhibitor colitis managed with vedolizumab after failing standard treatment with steroids and infliximab. Case Description/Methods: A 75-year-old male with metastatic melanoma status post brain tumor resection, radiation therapy and 2 cycles of ipilimumab/nivolumab presented with severe new onset diarrhea 3 weeks after his second cycle of ICI. Given concern for ICI induced colitis, oral prednisone was started with initial improvement of diarrhea. Severe diarrhea recurred with tapering and he was admitted to the hospital. After infectious workup was negative, he received a dose of infliximab for presumed immune-mediated colitis with mild improvement. He was discharged on prednisone 60 mg daily with a rapid 2-week taper before receiving COVID-19 vaccination. He received a second dose of infliximab 2 weeks after the first. However, a week later, he was readmitted to the hospital with grade 3 diarrhea, dehydration, weakness, hypotension, and continued weight loss. Flexible sigmoidoscopy revealed continuous mucosal ulceration with congestion and loss of vascular markings from anus to sigmoid colon (Figure 1). Biopsies showed moderate to severe active colitis with ulceration, increased crypt apoptosis, and crypt dropout-most compatible with immune checkpoint inhibitor colitis. After 1 week of poor response to high dose methylprednisolone, he was given 2 doses of vedolizumab 2 weeks apart which lead to a complete resolution of his GI symptoms. Four months later, he remains asymptomatic with a negative PET scan off vedolizumab and ICI therapy. Discussion: Immune checkpoint inhibitors (ICI) revolutionized therapeutics for malignancy in their enhancement of cytotoxic T cell survival, but the resulting robust immune response engenders adverse gastrointestinal events in 1/3 of patients around 1-2 months after the second or third dose. ICI colitis may result in abscess, perforation, and death, and it is imperative to undergo early endoscopy with biopsy plus initiation of steroids or immunotherapy, especially in severe cases. Our patient presented with grade 3 diarrhea and severe immune-mediated colitis refractory to steroids and infliximab, though vedolizumab was effective in resolution.

SPURIOUS HYPOXEMIA IN A CRITICALLY ILL PATIENT WITH CHRONIC LYMPHOCYTIC LEUKEMIA

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Critically ill patients who require intubation and mechanical ventilation are routinely monitored with arterial blood gas (ABG) analysis to measure arterial oxygen tension (PaO2) as an indicator of adequate gas exchange. The partial pressure of oxygen in an ABG sample can be impacted by many factors including metabolically active cells such as white blood cells or platelets leading to a false measurement of hypoxemia. We report a case of spurious hypoxemia in a critically ill patient due to chronic lymphocytic leukemia. CASE PRESENTATION: 67 year-old male, with no reported past medical history, presented with complaints of acute onset fever, diarrhea and dyspnea. His physical exam was notable for cachexia, tachycardia and tachypnea. On arrival he was hemodynamically unstable and in acute hypoxic respiratory failure, requiring mechanical ventilation. Lab results showed anemia, thrombocytopenia and a leukocyte count of 104,000/mm3. Peripheral blood smear showed large lymphocytes, smudge cells and presence of prolymphocytes. Chest imaging showed left lower lobe pneumonia with emphysematous changes. He was started on broad spectrum antibiotics. Post intubation ABG was notable for PaO2 of 59 but patient's SpO2 was 95%. Repeat ABG showed same results. His vent settings were adjusted including increasing PEEP. His pulse oximetry remained >92% however ABG showed persistent hypoxemia. Patient's PaO2 improved after leukopharesis. However patient succumbed to his clinical condition after family opted for comfort care. DISCUSSION: Spurious hypoxemia occurs when patients with leukocytosis or thrombocytosis have low PaO2 on ABG analysis with a concurrent normal oxygen saturation. It was first described in 1979 as "leukocyte larceny" (1). The pathophysiology is believed to be related to the presence of a high number of metabolically active white blood cells which increase the consumption of the dissolved oxygen in ABG samples (2, 3). The ability to differentiate between true hypoxemia and spurious hypoxemia is important especially when managing critically ill patients with leukocytosis or thrombocytosis. High clinical suspicion for spurious hypoxemia should be considered in patients with white blood cell counts >50,0000/mm3, severe thrombocytosis, high oxygen saturations on pulse oximetry and very low PaO2 on ABG analysis. Some of the methods that have been used to prevent spurious hypoxemia include immediate cooling of ABG samples and rapid analysis of samples, where both methods theoretically slow leukocyte metabolic rate and reduce oxygen consumption. CONCLUSIONS: Early recognition of spurious hypoxemia in patients with leukemia could prevent unnecessary testing and true hypoxemia can be ruled out in the appropriate clinical setting. REFERENCE #1: Hess CE, Nichols AB, Hunt WB, Suratt PM. Pseudohypoxemia secondary to leukemia and thrombocytosis. N Engl J Med. 1979;301(7):361–363. REFERENCE #2: Fox MJ, Brody JS, Weintraub LR. Leukocyte larceny: a cause of spurious hypoxemia. Am J Med 1979;67(5):742–746. REFERENCE #3: Lele A, Mirski M, Stevens R. Spurious hypoxemia. Crit Care Med. 2005;33(8):1854–1856. DISCLOSURES: No relevant relationships by Louis Gerolemou, source=Web Response No relevant relationships by Wael Kalaji, source=Web Response No relevant relationships by Aneeta Kumari, source=Web Response No relevant relationships by Nabil Mesiha, source=Web Response No relevant relationships by Kunal Nangrani, source=Web Response No relevant relationships by Viswanath Vasudevan, source=Web Response

S1965 B Adaptive: A Case of Rituximab-Associated Colitis and SARS-CoV-2 Vaccination

Introduction: Rituximab (RTX) is a monoclonal antibody against the CD20 surface antigen on B-Cell lymphocytes and is used in various hematologic and autoimmune conditions. Our case describes a patient on RTX therapy with pancolitis that coincided with SARS-CoV-2 vaccination (Moderna-mRNA1273). We attempt to explore a potential correlation of mRNA vaccination platforms, RTX therapy and new onset colitis. Case description/methods: A 49 year old male presented with 6 weeks of watery, non-bloody diarrhea, right upper quadrant pain, >10 pound weight loss and fever. History was significant for stage IVa follicular lymphoma in remission on RTX maintenance therapy, splenectomy and SARS-CoV-2 vaccination (Moderna mRNA-1273) 2 days prior to onset of diarrhea. Infectious work up was negative and CT imaging demonstrated diffuse colonic wall thickening with new interval adjacent pancolonic fat stranding. Initial colonoscopy demonstrated diffuse scattered clean based ulcers between 1-8 mm in size throughout the colon and terminal ileum. Biopsies revealed active chronic ileitis with eosinophils, occasional crypt abscess and crypt destruction negative for HSV, CMV or signs of recurrent lymphoma. He was then treated with oral budesonide, bentyl and loperamide but returned 6 weeks later without any relief in abdominal pain or diarrhea. Repeat colonoscopy demonstrated circumferential hyperemia/edema with apthous ulcers throughout the colon. We plan to treat as a Crohn's patient with corticosteroid induction and trial Vedolizumab for maintenance of remission. Discussion: The novel use of mRNA vaccines has been noted to be game changing in its production time as well as its effectiveness at preventing COVID-19 illness. The mechanism of immunity is proposed to be a combination of generation of neutralizing antibodies and T-helper cell activation. To our knowledge, mRNA-1273 has not directly caused colitis. Literature also describes occurrences of fulminant colitis in patients on RTX therapy and is believed to be secondary to dysregulation caused by depletion of CD20+ B cells and upregulation of autoreactive T-cells. While RTX induced colitis may arise de novo, there may be a correlation between the immunogenicity of mRNA vaccines like mRNA-1273 and the induction of colitis in patients while on immunosuppressants. This case demonstrates the increased need for further evaluation of the pathogenesis of RTX induced colitis as well as the immunogenic response seen in COVID-19 vaccination platforms.

Polyphenolic profile and ethno pharmacological activities of Callistemonsubulatus (Cheel) Craven leaves cultivated in Egypt

Ethnopharmacological relevanceThe genus Callistemon (syn. Melaleuca) of the myrtle family (Myrtaceae) has been documented as an integral part in the ethnobotanical system of the indigenous people of Australian mainland and many of its islands. Several Callistemons including the species subulatus were used by aboriginal Australians for making rafts, roofs for shelters, bandages, and food recipes, in addition to the management of wounds, infections, pain, cough, bronchitis, and gastrointestinal tract (GIT) disorders. Aim of the studyThe current study is designed to document the therapeutic effect of the aqueous methanolic extract (AME) of C. sabulatus Chell (syn. M. sabulata) leaves in the management of diarrhea and pain. Also, its influence on additional pharmacological modalities that are related to oxidative stress just as skin aging. Ultimately, the polyphenolic profile of the extract is disclosed and correlated to the aforementioned bioactivities. Materials and methodsThe extract was fractionated using various chromatography techniques and the structures of the isolated compounds were determined based on their chemical and spectral data. The antioxidant activity was assessed using multiple models, including 2,2-diphenyl-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and β-carotene bleaching assays. The anti-skin aging effect was evaluated using different relevant enzymatic assays. The antinociceptive activity was investigated using acetic acid-induced writhing, hot plate test, and formalin-induced paw licking in mice models. The antidiarrheal activity was gauge using the castor oil induced diarrhea, enter pooling and gastrointestinal motility in vivo models. ResultsDiverse polyphenols, including quercetin-3-O-β-D-glucuronopyranoside (1), kaempferol-3-O-β-D-glucuronopyranoside (2), strictinin (3), quercetin-3-O-(2``-O-galloyl)-β-D-glucuronopyranoside (4), afzelin (5), di-galloyl glucose (6), mono-galloyl glucose (7), acacetin (8), apigenin-6,7-dimethyl ether (9), kaempferol trimethyl ether (10), dimethoxy chrysin (11), quercetin (12), kaempferol (13), methyl gallate (14), and gallic acid (15) were identified. The extract exhibited as significant antioxidant activity even better than that of Trolox or BHT. Moreover, it exerts elastase, tyrosinase, and collagenase inhibition activities, in addition to the significant peripheral and central analgesic activity in a dose-dependent manner (P < 0.0001). In castor oil induced diarrhea model, AME significantly prolonged the diarrhea onset, decreased the frequency of defecation, and weight of feces. Likewise, it exhibited a significant reduction in the gastrointestinal motility in charcoal meal model (P < 0.0001) and a considerable inhibitory effect on gastrointestinal transit and peristaltic index with all investigated doses (P < 0.0001). ConclusionEthnobotanicals are versatile resources for the management of various ailments by indigenous people and the experimental research is utmost to validate and uncover their pharmacological relevance. C. sabulatus leaves have strong antioxidant, analgesic, anti-skin aging, and antidiarrheal activities which are validated for the first time by various in vitro and in vivo models. The metabolic profile of the unprecedented AME of C. sabulatus leaves compromises a wide array of bioactive polyphenolic metabolites including, flavonoids, tannins, and phenolic acids that are correlated to the observed bioactivities. Altogether, ethnobotanicals with high and diverse contents of polyphenols are potential candidates for the management of various human aliments including neuropathies, GIT disorders, and skin aging conditions.

Adverse Drug Reactions with HER2-Positive Breast Cancer Treatment: An Analysis from the Italian Pharmacovigilance Database.

BackgroundAnti-HER2 therapy has evolved in the last years and an important role in this transformation was that of monoclonal antibodies and tyrosine kinase inhibitors. Considering their extended use in clinical practice, some toxicity problems have been highlighted around these drugs.ObjectiveTo analyze the onset of adverse drug reactions (ADRs) related to the use of HER2-positive breast cancer treatments through a spontaneous reporting system (SRS) database.MethodsAll ADR reports having as suspected drug trastuzumab, pertuzumab, lapatinib, or trastuzumab emtansine (TDM-1), recorded into the Report Reazioni Avverse dei Medicinali (RAM) system database for national data and into the Italian SRS database for Sicilian data and collected from 2006 to 2020 have been evaluated. A descriptive analysis of basal demographic and drug-related characteristics was performed. A case-by-case methodology was conducted paying particular attention to the serious ADR reports collected in Sicily, focusing on type of seriousness, age, sex, concomitant drugs, comorbidities, time to onset (TTO), and time to resolution (TTR).ResultsOf the 3609 Italian reports, 65.6% were related to trastuzumab (n = 2367), followed by pertuzumab, TDM-1, and lapatinib. Almost all reports occurred in female patients (94.3%) and were most frequent in the age group 18–65 years (69.6%). A higher number of cases were related to general disorders and administration site conditions (n = 1079; 29.9%), gastrointestinal disorders (n = 1037; 28.7%), skin disorders (n = 821; 22.7%), and blood disorders (n = 599; 16.6%). Cases involving trastuzumab and pertuzumab mainly reported general disorders (n = 788; 33.3% and n = 194; 32.1%, respectively) while more than half of the reports associated with lapatinib were related to gastrointestinal (n = 184; 59.7%) and skin diseases (n = 146; 47.4%). Regarding TDM-1, 40% of reports had at least one ADR belonging to blood and lymphatic system disorders. The case-by-case assessment of Sicilian ADR reports showed that 40 cases were serious (33.3%), with a median TTO of 37 (6–97) days. Serious ADR reports mainly involved the onset of thrombocytopenia (n = 8; 20.0%), diarrhea (n = 6; 15.0%), asthenia and cardiac failure (both with n = 5; 12.5%), vomiting, hypersensitivity, and ejection fraction decreased (all with n = 4; 10.0%) and stomatitis (n = 3: 7.5%).ConclusionThis study is fundamentally consistent with results from the literature. Given the serious clinical condition of breast cancer and taking into account the importance of preventing some clinically relevant ADRs related to the use of anti-HER2 therapy, further analyses are essential to better describe the safety profile of these target therapies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-021-00278-z.