Fecal Leukocytes Research Articles

Key Focus Areas in Pouchitis Therapeutic Status: A Narrative Review.

Pouchitis, as the most common complication after ileal pouch-anal anastomosis (IPAA), has an incidence from 7% to 46%. Pouchitis treatment still represents one of the biggest gaps of knowledge in the treatment of diseases. This review has focused on achievements and challenges in the treatment of pouchitis. A combined assessment of symptoms, endoscopic findings, histologic results, quick biomarkers, and fecal calprotectin test were determined to be valuable diagnostic criteria. Conventional therapy was described as a modification of bacterial flora, mainly with antibiotics and more recently with probiotics such as bifidobacteria, lactobacilli, and streptococci. Other therapeutic approaches such as anti-tumor necrosis factor, infliximab, adalimumab, vedolizumab, ustekinumab, tacrolimus, tofacitinib, thiopurines, corticosteroids, prolyl hydroxylase-containing enzymes, povidone-iodine, dextrose spray, fecal microbiota transplantation, herbal medicines, and leukocyte apheresis have been discussed. Changes in dietary components, and administration of complementary and alternative medicine, probiotics, and fecal transplantation in addition to conventional therapies were also shown to affect the outcome of disease. Due to the potential significant impairment in quality of life caused by pouchitis, it is essential to address the gaps in knowledge for both patients and physicians in its treatment. Therefore, well-designed and adequately powered studies should assess the optimal treatment for pouchitis.

Evaluation of Fecal Inflammatory Biomarkers to Identify Bacterial Diarrhea Episodes: Systematic Review and Protocol for the Enterics for Global Health Shigella Surveillance Study.

The measurement of fecal inflammatory biomarkers among individuals presenting to care with diarrhea could improve the identification of bacterial diarrheal episodes that would benefit from antibiotic therapy. We reviewed prior literature in this area and describe our proposed methods to evaluate 4 biomarkers in the Enterics for Global Health (EFGH) Shigella surveillance study. We systematically reviewed studies since 1970 from PubMed and Embase that assessed the diagnostic characteristics of inflammatory biomarkers to identify bacterial diarrhea episodes. We extracted sensitivity and specificity and summarized the evidence by biomarker and diarrhea etiology. In EFGH, we propose using commercial enzyme-linked immunosorbent assays to test for myeloperoxidase, calprotectin, lipocalin-2, and hemoglobin in stored whole stool samples collected within 24 hours of enrollment from participants in the Bangladesh, Kenya, Malawi, Pakistan, Peru, and The Gambia sites. We will develop clinical prediction scores that incorporate the inflammatory biomarkers and evaluate their ability to identify Shigella and other bacterial etiologies of diarrhea as determined by quantitative polymerase chain reaction (qPCR). Forty-nine studies that assessed fecal leukocytes (n = 39), red blood cells (n = 26), lactoferrin (n = 13), calprotectin (n = 8), and myeloperoxidase (n = 1) were included in the systematic review. Sensitivities were high for identifying Shigella, moderate for identifying any bacteria, and comparable across biomarkers. Specificities varied depending on the outcomes assessed. Prior studies were generally small, identified red and white blood cells by microscopy, and used insensitive gold standard diagnostics, such as conventional bacteriological culture for pathogen detection. Our evaluation of inflammatory biomarkers to distinguish diarrhea etiologies as determined by qPCR will provide an important addition to the prior literature, which was likely biased by the limited sensitivity of the gold standard diagnostics used. We will determine whether point-of-care biomarker tests could be a viable strategy to inform treatment decision making and increase appropriate targeting of antibiotic treatment to bacterial diarrhea episodes.

Fecal leukocyte frequency in children with acute viral gastroenteritis: a single-center experience.

Our objective was to determine the frequency of rotavirus, adenovirus, and rota-adenovirus co-infections and investigate the fecal leukocyte rate associated with these infections in patients with gastroenteritis. This is a retrospective study. We identified patients who were admitted to the pediatric emergency department with acute gastroenteritis and had their stool samples tested for rotavirus and/or adenovirus antigens. Among them, we determined the individuals who underwent stool microscopy tests on the same day and recorded their results. A total of 1,577 patients who underwent testing for rotavirus and/or adenovirus antigens in their stool samples were identified. Among these patients, 583 individuals had concurrent fecal microscopy results. The prevalence of solely rotavirus antigen positivity was 16.4%, solely adenovirus antigen positivity was 2.9%, and rota-adenovirus co-infections were detected in 1.8% of the children. The fecal leukocyte rates in children infected with rotavirus, adenovirus, and rota-adenovirus co-infections were 4.8, 13.3, and 88.9%, respectively. The presence of fecal leukocytes was detected at a high rate in cases of viral gastroenteritis, especially in rota-adenovirus co-infections. Therefore, clinicians should not consider only bacterial pathogens in the presence of fecal leukocytes.

Clinical factors predicting rotavirus diarrhea in children: A cross-sectional study from two hospitals.

Rotavirus is still a significant contributing morbidity and mortality in pediatric patients. To look at clinical signs and symptoms and laboratory findings that can predict rotavirus gastroenteritis compared to non-rotavirus gastroenteritis. This was a cross-sectional study with medical records obtained from December 2015 to December 2019. Inclusion criteria for this study include all hospitalised pediatric patients (0-18 years old) diagnosed with suspected rotavirus diarrhea. The receiver operating curve and Hosmer-Lemeshow test would be used to assess the final prediction findings' calibration (goodness of fit) and discrimination performance. This study included 267 participants with 187 (70%) rotavirus-diarrhea cases. The patients were primarily male in both rotavirus (65.2%) and non-rotavirus (62.5%) groups. The median age is 1.33 years old (0.08-17.67 years old). Multivariate analysis shows that wet season (ORadj = 2.5; 95%CI: 1.3-4.8, Padj = 0.006), length of stay (LOS) ≥ 3 days (ORadj = 5.1; 95%CI: 1.4-4.8, Padj = 0.015), presence of abdominal pain (ORadj = 3.0; 95%CI: 1.3-6.8, Padj = 0.007), severe dehydration (ORadj = 2.9; 95%CI: 1.1-7.9, Padj = 0.034), abnormal white blood cell counts (ORadj = 2.8; 95%CI: 1.3-6.0, Padj = 0.006), abnormal random blood glucose (ORadj = 2.3; 95%CI: 1.2-4.4, Padj = 0.018) and presence of fecal leukocytes (ORadj = 4.1, 95%CI: 1.7-9.5, Padj = 0.001) are predictors of rotavirus diarrhea. The area under the curve for this model is 0.819 (95%CI: 0.746-0.878, P value < 0.001), which shows that this model has good discrimination. Wet season, LOS ≥ 3 d, presence of abdominal pain, severe dehydration, abnormal white blood cell counts, abnormal random blood glucose, and presence of fecal leukocytes predict rotavirus diarrhea.

Relationship of Salmonella isolation with different serum and inflammatory intestinal parameters in natural fowl typhoid outbreaks from laying hens

Our study was undertaken to determine the best samples and selective-differential plating media to be used for Salmonella spp. isolation. We also compared hematological and serum biochemical values, Salmonella biovar Gallinarum (SG) detection (isolation and serological test), and inflammatory intestinal response (fecal leukocyte) in laying hens with naturally occurring fowl typhoid outbreaks. Furthermore, we looked for a biomarker of SG infection. Spleen, liver, ovarian follicle content, and bone marrow were found to be the best samples for SG isolation and the agreement between MacConkey-Salmonella Shigella agar was slight to excellent. The laying hens with SG isolation and rapid serum plate agglutination positive results showed a higher percentage of heterophils, heterophil/lymphocyte ratio and total white blood cells, and a lower percentage of lymphocytes than those with negative results. Furthermore, the positive fecal leukocyte samples had a higher percentage of heterophils, gamma-glutamyl transferase, total protein and globulin values than negative samples. Five biomarkers’ cut-offs are proposed to distinguish between laying hens positive and negative to SG isolation.

Factors associated with stunting: gut inflammation and child and maternal-related contributors among under-five children in Hawassa City, Sidama Region, Ethiopia

BackgroundUnder-nutrition remains a major global public health challenge, particularly among children under the age of five. Among the manifestations of under-nutrition, stunting accounts for the larger proportion, which is associated with multiple factors. In Ethiopia, however, the link between intestinal inflammation and childhood stunting was not well investigated. Therefore, the present study aimed to determine the association between gut inflammation and childhood stunting.MethodA community-based cross-sectional study was conducted and a total of 82 children were included in the study. Anthropometric data were collected by measuring weight in underwear and without shoes with an electronic scale to the nearest 0.1 kg and their height in the Frankfort plane with a telescopic height instrument. Environmental risk factors for enteric bacterial exposure, access to improved sources of drinking water, and the presence of facilities for hygiene and sanitation conditions were assessed using a questionnaire. Gut inflammation was tested through fecal leukocyte count and each sample was stained with methylene blue. Stool samples were inoculated on MacConkey agar, Salmonella-Shigella agar, and Xylose Lysine Deoxycholate agar after enrichment with Selenite cystine broth and incubated at 37 °C for 18–24 h. Binary and multiple logistic regressions and Chi-square models were used to analyze the data.ResultData from the current study revealed that gut inflammation was (AOR: 5.28, 95% CI: 1.32–22.25) associated with stunting. On the other hand, children with reported diarrhea within the last week were 6 times more likely for the probability of being stunted (AOR: 6.21, 95% CI: 2.68–26.83). The findings of this study also demonstrated that children from a household with a family size of more than 5 members were three times more likely to be stunted than their counterparts (AOR: 3.21, 95% CI: 1.20 -10.13). Facts of the current study demonstrated that breastfeeding for 24 months and below was negatively associated (AOR: 0.3; 95% CI: -0.46-0.89) with gut inflammation. Detection of E.coli and Shigella species in the stool samples of children and Menaheria residents were positively associated with gut inflammation (AOR: 5.4, 95% CI: 1.32–22.25; AOR: 5, 95% CI: 1.47–24.21), respectively.ConclusionTherefore, there was a strong correlation between stunting and gastrointestinal inflammation. Moreover, stunting was associated with diarrhea, breastfeeding duration, residence, and family size. Similarly, intestinal inflammation was linked to residence, breastfeeding duration, and the prevalence of bacterial infections such as E. coli and Shigella species.

S2157 Vibrio Species Infection Followed by New Onset Lymphocytic Colitis: Cause or Coincidence?

Introduction: The pathophysiology and epidemiology of lymphocytic colitis (LC), a form of microscopic colitis, is not well understood. The incidence of this disorder in some populations has increased over time, nearing that of inflammatory bowel disease (IBD). Medications, autoimmune conditions, infectious etiologies, and genetics have been proposed as predisposing to or triggering LC. Of the reported bacterial pathogens, Vibrio species has not yet been linked to LC. We report a case of LC diagnosed post-infection with Vibrio spp. Case Description/Methods: A 68-year-old male with a past medical history of Gilbert syndrome, remote tobacco use, GERD, anxiety and hyperlipidemia presented with 8-12 episodes daily of watery diarrhea for 16 days. The diarrhea, associated with fecal incontinence and abdominal cramping, began after consumption of raw clams and oysters. The patient’s abdominal exam was without tenderness to palpation, masses, or organomegaly. Initial labs showed no leukocytosis and electrolytes were normal. Stool studies demonstrated a positive fecal leukocyte stain. A stool PCR was positive for Vibrio cholerae/parahaemolyticus. He was treated with tetracycline, though his symptoms did not completely relent. Repeat stool cultures were negative despite residual loose stools. Further workup included a negative stool C. Diff toxin and excluded celiac disease. Postinfectious IBD was suspected, and he was started on a FODMAP diet and dicyclomine. Despite reported compliance, his symptoms did not improve. Subsequent colonoscopy revealed a grossly normal ileum and colon. Colonic biopsies depicted colonic mucosa with mildly increased intraepithelial lymphocytes, consistent with LC. Treatment was initiated with oral budesonide and tapered. Diarrhea resolved after 2 weeks of treatment. Discussion: The temporal nature of Vibrio spp. infection raises the question of causality of LC. H. Pylori, Yersinia, and C. Diff have been linked to collagenous colitis. Thus far, LC has only been linked to Campylobacter jejuni. Statins, PPIs, and SSRIs have also been associated with LC. PPI use may predispose to Vibrio infection due to hypochlorhydria. Consideration of post-infectious IBD and new onset LC raises an interesting point, as the conditions are clinically similar. While the exact mechanism of post-infectious LC is unknown, upregulation of nitric oxide synthase is seen in both infection with Vibrio and LC. Further metabolic clarification and investigation are yet required to define the pathogenesis of this disorder.

S2079 Not Just Another Case of Diarrhea: A Case of Vibrio Cholera During COVID-19 Era

Introduction: Vibrio cholerae is a gram negative, comma-shaped, toxin producing bacteria, which causes large volumes of watery stool leading to dehydration, hypovolemic shock, and metabolic acidosis. Stool culture with PCR is the gold standard for diagnosis. It is pertinent that if cholera is a differential, treatment with isotonic oral rehydration and antibiotics are not delayed. When traveling to endemic or epidemic areas vaccination should be considered. Here we discuss a case of Vibrio cholera infection diagnosed in Farmington, Connecticut in a patient with recent travel back from Pakistan in mid-April 2022. Case Description/Methods: 61-year-old female with no relevant past medical history presented to the hospital complaining of fatigue and 3 days of profuse, watery, dark diarrhea occurring 8 times daily, starting the day she returned home to Connecticut after traveling in Pakistan. She drank primarily store-bought bottled water but reported some cooking with tap water. She was lethargic and hypovolemic with a diffusely tender abdomen and hyperactive bowel sounds. Lab work was pertinent for leukocytosis, AKI, hypokalemia, and mild metabolic acidosis. Hemoccult stool, Clostridium difficile toxins A&B, Salmonella, Shigella, and fecal leukocyte count were negative. Her course was complicated by altered mental status, worsening AKI, hypokalemia, and metabolic acidosis requiring a bicarbonate drip. Eight days into her admission stool study resulted positive for cholera (Figure 1). Her metabolic derangements were aggressively treated, and her symptoms improved. Discussion: During the COVID-19 pandemic and ongoing travel restrictions, cholera is not typically the first infection thought of for patients with diarrhea and fatigue. Still, we are seeing cases rise in locations where cholera case-fatality rates were previously dropping in a pre-pandemic COVID-era, thought to be from reduced health promotion activities.1 In 2019, the Center for Disease Control and Prevention reported a total of 14 cases of Vibrio cholera within the United States,2 most from overseas travel. Thus, it is important to keep a broad differential diagnosis regardless of location even during a time of travel restrictions.Figure 1.: Vibrio culture on thiosulfate-citrate-bile salts-sucrose (TCBS) agar (left) and on blood agar (right).

A98 FECAL LEUKOCYTE ESTERASE: AN ALTERNATIVE BIOMARKER TO FECAL CALPROTECTIN IN INFLAMMATORY BOWEL DISEASE

BackgroundFecal calprotectin (FC) is a non-invasive biomarker used in inflammatory bowel disease (IBD) management and risk stratification of non-specific gastrointestinal symptoms. Leukocyte esterase is an inexpensive and widely available point-of-care inflammatory marker present on urinalysis test strips.AimsWe aim to assess the diagnostic accuracy of fecal leukocyte esterase (FLE) relative to FC and endoscopy and demonstrate its use as an alternative biomarker for IBD.MethodsIn this prospective cohort study, 70 patients who had FC ordered as part of standard clinical care also received FLE testing. FLE levels were compared to various FC cut-off values, endoscopy and pathology findings as gold standard.ResultsAs the FC cut-off increased from 50 to 500 μg/g, FLE sensitivity increased from 67% to 95% while the specificity decreased from 86% to 76%. The area under the receiver operating characteristic (AUROC) increased from 0.79 to 0.90. An FLE of ≥1+ had the best test characteristics. Amongst patients who underwent endoscopic evaluation, FLE demonstrated an identical sensitivity (75%) and specificity (86%) to FC in predicting endoscopic inflammation. AUROC was 0.80 for FLE and 0.85 for FC with an optimal cut-off of ≥2+ and 301 μg/g, respectively. When used to distinguish between active IBD and no/inactive IBD patients, FLE had a sensitivity of 84% and specificity of 90%, comparable to the 84% and 83%, respectively, of FC. AUROC was 0.88 for FLE and 0.91 for FC with an optimal cut-off of ≥2+ and 145 μg/g, respectivelyConclusionsFLE demonstrates adequate correlation and comparable accuracy to FC in predicting endoscopic inflammation and distinguishing between patients with active versus inactive IBD. Funding AgenciesNone

Fecal Leukocyte Esterase, an Alternative Biomarker to Fecal Calprotectin in Inflammatory Bowel Disease: A Pilot Series.

Fecal calprotectin (FC) is a noninvasive biomarker used in inflammatory bowel disease (IBD) management and risk stratification of nonspecific gastrointestinal symptoms. Leukocyte esterase is an inexpensive and widely available point-of-care inflammatory marker present on urinalysis test strips. We aim to assess the diagnostic accuracy of fecal leukocyte esterase (FLE) relative to FC and endoscopy and demonstrate its use as an alternative biomarker for IBD. In this prospective cohort study, 70 patients who had FC ordered as part of standard clinical care also received FLE testing. FLE levels were compared with various FC cutoff values and endoscopy and pathology findings as the gold standard. As the FC cutoff increased from 50 to 500 μg/g, FLE sensitivity increased from 67% to 95% while the specificity decreased from 86% to 76%. The area under the receiver operating characteristic (AUROC) curve increased from 0.79 to 0.90. An FLE of ≥1+ had the best test characteristics. Among patients who underwent endoscopic evaluation, FLE demonstrated an identical sensitivity (75%) and specificity (86%) to FC in predicting endoscopic inflammation. AUROC was 0.80 for FLE and 0.85 for FC with an optimal cutoff of ≥2+ and 301 μg/g, respectively. When used to distinguish between patients with active IBD and no/inactive IBD, FLE had a sensitivity of 84% and specificity of 90%, comparable with the 84% and 83%, respectively, of FC. AUROC was 0.88 for FLE and 0.91 for FC with an optimal cutoff of ≥2+ and 145 μg/g, respectively. FLE demonstrates adequate correlation and comparable accuracy with FC in predicting endoscopic inflammation and distinguishing between patients with active vs inactive IBD.

S2471 Life Savers or Colon Killers? A Peculiar Case of Excessive Sucralose Ingestion Preceding the Development of Inflammatory Bowel Disease

Introduction: Inflammatory bowel disease (IBD) is characterized by chronic recurrent intestinal inflammation thought to result from host-microbial interactions and ill-defined environmental triggers in a genetically susceptible individual. We present a case of IBD temporally associated with the excessive ingestion of sucralose, the primary artificial sweetener in sugar free “Life Savers”. Case Description/Methods: A 65-year-old male was admitted with a one-week history of abdominal bloating, nausea, vomiting, and significant bloody diarrhea. He denied recent travel, sick contacts, dietary changes, NSAID or antibiotic use, but mentioned consuming approximately 50 “life savers” daily for the past month. On exam, vitals were normal and physical exam showed mild abdominal tenderness. Initial workup showed mild anemia, leukocytosis, acute kidney injury, elevated C-reactive protein, positive fecal leukocytes, and pancolitis on CT imaging. He was empirically started on ceftriaxone and metronidazole for possible infectious colitis, but he remained symptomatic. Evaluation showed no growth on stool culture, negative ova and parasites, and negative C. Diff. Colonoscopy was done which showed diffuse severe pan-colitis characterized by cobble-stoning and deep ulcerations most severe in ascending and descending colon. The sigmoid colon and rectum had milder involvement; terminal ileum was normal. Pathology showed markedly active chronic colitis with normal ileal mucosa and no sign of CMV. Intravenous methylprednisolone was initiated for suspected IBD. His diarrhea greatly improved. Patient was started on infliximab for likely Crohn’s colitis (given characteristic cobble-stoning), transitioned to oral steroids, and discharged home. At follow up, he remained clinically improved and steroid taper was initiated. Additional history revealed the patient had similar symptoms a year ago after a month of heavy Life Saver consumption. Discussion: This case adds to a growing body of literature temporally linking the consumption of sucralose with an increased incidence of IBD. It has been hypothesized these compounds inhibit gut flora through the inactivation of digestive proteases leading to accelerated degradation of the mucous layer and underlying endothelium. This exposes multiple immunogenic antigens and particles from the gut lumen which can cause dysregulated immune activation and development of IBD. Our case provides a dramatic example of such a toxicity given the excessive sucralose consumed and clear temporal association.Figure 1.: Patient colonoscopy showing active colitis.

Microbiome diversity declines while distinct expansions of Th17, iNKT, and dendritic cell subpopulations emerge after anastomosis surgery

BackgroundAnastomotic failure causes morbidity and mortality even in technically correct anastomoses. Initial leaks must be prevented by mucosal reapproximation across the anastomosis. Healing is a concerted effort between intestinal epithelial cells (IECs), immune cells, and commensal bacteria. IEC TLR4 activation and signaling is required for mucosal healing, leading to inflammatory factor release that recruits immune cells to limit bacteria invasion. TLR4 absence leads to mucosal damage from loss in epithelial proliferation, attenuated inflammatory response, and bacteria translocation. We hypothesize after anastomosis, an imbalance in microbiota will occur due to a decrease in TLR4 expression and will lead to changes in the immune milieu.ResultsWe isolated fecal content and small intestinal leukocytes from murine, Roux-en-Y and end-to-end anastomoses, to identify microbiome changes and subsequent alterations in the regulatory and pro-inflammatory immune cells 3 days post-operative. TLR4+ IECs were impaired after anastomosis. Microbiome diversity was reduced, with Firmicutes, Bacteroidetes, and Saccharibacteria decreased and Proteobacteria increased. A distinct TCRβhi CD4+ T cells subset after anastomosis was 10–20-fold greater than in control mice. 84% were Th17 IL-17A/F+ IL-22+ and/or TNFα+. iNKT cells were increased and TCRβhi. 75% were iNKT IL-10+ and 13% iNKTh17 IL-22+. Additionally, Treg IL-10+ and IL-22+ cells were increased. A novel dendritic cell subset was identified in anastomotic regions that was CD11bhi CD103mid and was 93% IL-10+.ConclusionsThis anastomotic study demonstrated a decrease in IEC TLR4 expression and microbiome diversity which then coincided with increased expansion of regulatory and pro-inflammatory immune cells and cytokines. Defining the anastomotic mucosal environment could help inform innovative therapeutics to target excessive pro-inflammatory invasion and microbiome imbalance.

A20 DIAGNOSTIC ACCURACY OF A LOW COST, WIDELY AVAILABLE TEST STRIP FOR PREDICTING A POSITIVE FECAL CALPROTECTIN TEST

Abstract Background Fecal calprotectin is a non-invasive test of colonic inflammation used for monitoring inflammatory bowel disease activity and for risk stratifying non-specific colonic symptoms. Calprotectin is a leukocyte specific enzyme. A similar test, leukocyte esterase is used to detect leukocytes in urine and is widely available as a low-cost point-of-care test strip. We hypothesize that an unmodified version of the urine test strip would be highly accurate in predicting a positive fecal calprotectin test in a real world sample of patients. Aims To explore a low cost, rapid alternative to the fecal calprotectin test Methods All inpatient and outpatient stool samples tested for calprotectin by the Vancouver General Hospital laboratory from February 2020 to November 2020 were included prospectively. Samples were simultaneously tested for fecal leukocyte esterase using an unmodified Roche Cobas Chemstrip urinalysis test strip by central lab personnel. An identical aliquot was sent to LifeLabs for calprotectin as per standard protocol. All samples were suspended in buffer using established laboratory protocols prior to testing. Fecal leukocyte esterase results were reported as 0–4+ based on visual interpretation, calprotectin results were reported as mcg/g of stool. REB review and approval was obtained prior to data collection. Sensitivity, Specificity and AUROC were calculated using Microsoft Excel and JROCFIT. Results 26 samples were collected. Using a fecal calprotectin greater than 120 mcg/g as a gold standard an AUROC of 0.89 (SE= .06) was calculated. A leukocyte esterase reading of 2+ or greater had the best test characteristics based on ROC curve analysis. Using this cutoff, 21/26 samples were concordant, giving an accuracy of 80.8%, sensitivity of 90.9% and specificity of 73.3%. Positive likelihood ratio was 8.07 and negative likelihood ratio was 0.29. Assuming an AUROC of 0.8, the sample size N=26 is 90% powered (β=0.9) to predict the true AUROC within 0.1 with a type I error rate of .05 (α&amp;lt;.05). Conclusions This study suggests application of a prepared stool sample to a urinalysis test strip gives a result highly predictive of a positive fecal calprotectin test. Further results are being collected prospectively to improve the robustness of these preliminary data. Secondary outcomes including comparison to endoscopy and biopsy results where available are planned if an adequate sample size can be accrued. Future studies justifying independent clinical use of leukocyte esterase would require a common gold standard comparator such as endoscopy. Fecal calprotectin testing is not universally insured and is not available as a rapid test strip. Use of fecal leukocyte esterase may reduce costs and shorten time to results if proven to be independently reliable. Funding Agencies None

S3554 Tissue Diagnosis of Cryptosporidiosis in an Immunosuppressed Patient With Persistent Diarrhea

INTRODUCTION: Immunosuppressed patients are at high risk for severe gastrointestinal infections including a broad array of typical and opportunistic infections. Cryptosporidium usually cause self-limited diarrhea in immunocompetent hosts, but life-threatening diarrhea in immunocompromised patients. We here report an interesting case of tissue-diagnosed cryptosporidiosis in an immunosuppressed patient with persistent diarrhea. CASE DESCRIPTION/METHODS: A 29-year-old immunosuppressed female with bilateral lung transplantation due to surfactant C deficiency presented with one month of worsening watery diarrhea, nausea, vomiting, and abdominal cramping. She denied any hematochezia, hematemesis, suspicious food intake, recent sick contact, or family history of inflammatory bowel disease. Her medications included tacrolimus, mycophenolate, and low dose prednisone. Physical examination was unremarkable. Serologic tests were notable for mild transaminitis and normal Tacrolimus level. Stool tests including examination for ova and parasites, culture, C-diff toxin PCR, Shiga toxins 1-2, Giardia antigen, fecal leukocytes, and pancreatic fecal elastase were normal. EGD and colonoscopy had normal endoscopic findings. Terminal ileum’s biopsies revealed many mucosal apical basophilic circular-shaped organisms with epicellular invasion and marked lymphoplasmacytic infiltrate in the lamina propria consistent with cryptosporidiosis (Figures A, B). Stool immunofluorescent assays for cryptosporidium oocysts later confirmed the diagnosis and patient had resolution of symptoms following treatment with nitazoxanide and azithromycin. DISCUSSION: Cryptosporidiosis causes a combination of malabsorption and secretory diarrhea secondary to mucosal attachment, villus architecture distortion, epicellular invasion, inflammatory response, and cellular apoptosis. Cryptosporidium can also involve the biliary system by spreading through the intestinal lumen. Direct immunofluorescence and PCR testing are the most sensitive and specific diagnostic tests for cryptosporidiosis. Although stool examination for ova and parasites remains the simplest and widely available test, limiting factors include low oocysts shedding and variable microscopic expertise. Direct visualization on intestinal biopsies is limited by patchy infection; it was the key to diagnosis in our case. Therapy in non-HIV immunocompromised patients involves reducing the dosage of immunosuppressive therapy and initiation of dual antibiotics.Figure AFigure B

S2919 Atypical Presentation odslrf Cryptosporidiosis in an Immunocompetent Female

INTRODUCTION: Cryptosporidiosis is an opportunistic diarrheal infection caused by Cryptosporidium, an intracellular protozoan, prevalent mostly in immunocompromised individuals. We report a rare case of extensive cryptosporidiosis of the upper gastrointestinal (UGI) tract in an immunocompetent individual. CASE DESCRIPTION/METHODS: A 77 year-old female with history of cholecystectomy presented to the clinic with 2-months history of nausea and chronic epigastric pain. Her symptoms were aggravated by spicy foods and not relieved with omeprazole and sucralfate. She did not have any diarrhea, fever or chills. She was a retired nurse and denied any sick contacts, contact with farm animals or a travel history. She denied any animal bites. She consumed only bottled water for drinking. Her workup was unremarkable for anemia or leukocytosis and normal liver enzymes. She had mild delayed gastric emptying and a positive glucose breath test for small bowel bacterial overgrowth (SIBO). She received Reglan and Doxycycline with no significant improvement. Her esophagogastroduodenoscopy (EGD) showed esophagitis and antral erosions. Biopsy report by local pathologist showed esophagitis, chronic inactive gastritis and duodenitis. A secondary review by our GI pathologist confirmed prior findings but also reported cryptosporidium in the esophageal, gastric and duodenal biospies. Giemsa stain was negative for helicobacter pylori. Her HIV antibody was negative and IgA levels were normal. She was treated with a 3-day course of Nitazoxanide 500 mg twice daily with improvement in her symptoms. A repeat EGD after 4 months showed no inflammation and absence of cryptosporidium suggesting successful eradication. DISCUSSION: Cryptosporidiosis presents commonly as secretory diarrhea, malaise and cramping abdominal pain with or without biliary involvement (10–30%). Asymptomatic cases have been reported in immunocompetent hosts especially in children. Fecal leukocytes are rare unless co-infected with another enteric pathogen. We report an atypical presentation of non-diarrheal cryptosporidiosis associated with biopsy-proven inflammation in UGI tract that responded to Nitazoxanide. The patient likely contracted the parasite from an untraceable contaminated water source. Clinically, a high level of suspicion should be exercised in patients with refractory UGI symptoms to look for infectious causes. It is also important to consider an expert GI pathologist’s review of the histopathology in cases with an unclear diagnosis.Figure 1.: A. Low power photomicrograph of the stomach demonstrates only mild reactive change.Figure 2.: B. At high power, numerous organisms similar to those seen in B are noted in adherent mucus.Figure 3.: C. High power image of duodenum highlights numerous small (1-2 micron) basophilic “beads” seemingly adherent to the brush border.

Microscopic Examination of Fecal Leukocytes as a Simple Method to Detect Infective Colitis in Children

Background: Various pathogenic bacteria are reported as the cause of infectious colitis in children. Infectious colitis does not have a specific sign, therefore an accurate examination is required. The implementation of fecal cultures accompanied with drug resistance tests often have constraints, beside the relatively expensive costs, longer times are needed, and not all health care facilities have required instruments. On the other hand, this condition requires an immediate antibiotic therapy, so that the infection should not be continued. In daily practice, it is not uncommon to find diarrhea with the amount of fecal leukocyte 10/hpf with pathogenic bacteria on the examination of the fecal culture.Method: Cross-sectional study was conducted to observe the pattern of bacterial distribution in children’s fecal who have acute diarrhea and the correlation between the existence of pathogenic bacteria and the number of leukocytes in the fecal, as well as antibiotic resistance patterns. The population of this study is children with age of 6 months old - 18 years old who were suffering from acute diarrhea with the amount of fecal leucocyte ≥ 5/hpf, who recruited from polyclinic or patient admitted at Cipto Mangunkusumo Hospital and Fatmawati General Hospital, Jakarta.Results: Based on examinations of fecal cultures and PCR, Salmonella sp and C. dificille were found subsequently in 2 children (33.3%), Enterophatogenic E. Coli(EPEC) and Shigella were found subsequently in 1 child (16.7%). Based on the ROC curve, it was found that there was no intersection of maximum and minimal leukocyte value with the midline, whereas the best sensitivity and specificity value was found at the cut-off point of 8.5, hence the cut-off point of leukocytes was determined at 8 and 8. The sensitivity value was 83.3% and the specificity value was 45.1%.Conclusion: The antibiotic sensitivity test showed that one child infected by EPEC was sensitive to ciprofloxacin. Two children infected by Salmonella, were still sensitive to chloramphenicol, cotrimoxazole, cefixime, and ceftriaxone. Two children infected by C. Difficile were sensitive to ceftriaxone, and 1 child infected by Shigella was sensitive to cefixime, ceftriaxone and ciprofloksazine.

Fecal Calprotectin, CRP and Leucocytes in IBD Patients: Comparison of Biomarkers With Biopsy Results.

BackgroundThis study aimed to compare fecal calprotectin (FC) levels with other commonly used parameters as part of patient care during evaluation for inflammatory bowel disease (IBD).MethodsWe recruited adult IBD patients with ulcerative colitis (UC) and Crohn’s disease (CD) and compared the results of the patient’s biopsy results (i.e., inflamed versus noninflamed) for six sites (i.e., ileum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum) with concentrations of C-reactive protein (CRP), total leucocytes and fecal calprotectin (FC).ResultsWe found that FC was significantly elevated in a concentration-dependent manner that correlated with the number of active inflammation sites reported in biopsy. Although CRP and leucocyte measurements trended upwards in line with inflammation reported from biopsy, the results were highly variable and highlighted poor reliability of these biomarkers for indicating IBD inflammation.ConclusionsThese results strongly suggest that FC correlates best with biopsy reports and is a superior marker than CRP and leucocytes.

Manifestations of digestive system of hospitalized patients with coronavirus disease 2019 in Wuhan, China: a single-center descriptive study

Objective To study the manifestations of digestive system of hospitalized patients with coronavirus disease 2019 (COVID-19) in Wuhan, China, and to provide a reference for disease control and treatment. Methods The data of hospitalized patients with COVID-19 in the Sino-French Branch of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 27 to February 14, 2020 were retrospectively analyzed, which included general information, positive rate of nucleic acid test, severity of disease, incubation period, initial symptoms and manifestations of digestive system. The general information, positive rate of nucleic acid detection, and manifestations of digestive system were compared between critical patients who required non-invasive or invasive assisted ventilation (critical group) and non-critical patients without assisted ventilation (non-critical group). Continuous corrected Chi-square test and independent sample median Chi-square test were used for statistical analysis. Results Among the 305 patients, there were 146 males (47.9%) and 159 females (52.1%), and the median age was 57 years old. Nucleic acid assay of nasopharyngeal swabs or pharyngeal swabs were positive in 84.1% (228/271) patients including 46 patients (15.1%) of critical group and 259 patients (84.9%) of non-critical group. The incubation period was one to fifteen days, and the median period was six days. The initial symptoms were mainly fever (81.1%, 163/201), cough (39.3%, 79/201), fatigue (54.7%, 110/201), and loss of appetite (50.2%, 101/201). In one to ten days after the disease onset, 79.1% (159/201) of patients developed gastrointestinal symptoms including nausea (29.4%, 59/201), vomiting (15.9%, 32/201), or abdominal pain (6.0%, 12/201). 49.5% (146/295) of patients had diarrhea, with a median time of 3.3 days, (3.3±1.6) times per day, and a duration of (4.1±2.5) days. After excluding possible drug-related diarrhea, the incidence of diarrhea was still 22.2%. Only 6.9% (4/58) of patients had positive fecal leukocytes or fecal occult blood test. Alanine aminotrans ferase (ALT), aspartate aminotransferase (AST), or total bilirubin (TBil) increased in 39.1% (119/304) of patients on admission. Patients with ALT or AST ≥ 80 U/L only accounted for 7.9% (24/304) and 6.3% (19/304), respectively. About 2.0% (6/304) of patients also had increased TBil level, and the average level was (37.4±21.1) μmol/L. The median age of critical group was older than that of non-critical group (65 years vs. 56 years), the proportion of patients with abnormal liver function and slightly increased AST (40- 0.05). Conclusions The manifestation of digestive system of hospitalized COVID-19 patients in Wuhan is significant, the proportion of patients with diarrhea and abnormal aminotransferase level is high. And on admission the proportion of patients with abnormal liver function of critical group is higher than that of non-critical group, which will provide reference for the prevention and treatment of COVID-19. Key words: 2019-nCoV; COVID-19; Diarrhea; Liver function; Gastrointestinal tract

3058 An Unusual Case of Ischemic Colitis

INTRODUCTION: 48-year-old obese (BMI: 40) female, G0P0A0 LMP 1 year ago, with hypertension and hypercholesterolemia who presented with sudden left lower abdominal cramping pain associated with bloody diarrhea of one day duration. Denied associated systemic symptoms. She was using aspirin, simvastatin, metoprolol and had a progestin-only intrauterine device (IUD) placed 2 years ago. Physical examination with tenderness at the left lower quadrant. Digital rectal examination unremarkable. Laboratories with leukocytosis, lactatemia and positive fecal leukocytes. Abdominopelvic CT with IV contrast revealed left-sided peri-colonic and colonic inflammatory changes. CASE DESCRIPTION/METHODS: Gastroenterology service consulted due to non-specific colitis and there was concern for ischemic colitis as CT revealed inflammation in a watershed area. Colonoscopy showed edematous mucosa from the splenic flexure to the sigmoid colon associated with multiple large longitudinal ulcers. Biopsies revealed mucosal hemorrhage and neutrophil infiltration, suggestive of ischemic injury. Etiology of ischemia not clear given no obvious risk factors. Cardiovascular, myeloproliferative and prothrombotic workups were negative. The last piece of the puzzle rested on the IUD which was removed by the OBGYN service. A few days later, a follow up CT showed marked inflammation improvement. DISCUSSION: Ischemic colitis is generally considered a disease of the elderly. The most common causes include low-flow states due to cardiac dysfunction and hypovolemia. However, in younger patients, hypercoagulable states and drugs are the most common etiologies. In our patient, it was hard to initially find a reasonable cause of ischemia but, after excluding all etiologies, patient's IUD was the most likely cause of bowel ischemia. Combination contraceptives are a well-known risk factor for venous thromboembolism (VTE). However, few data have been published regarding whether the risk of VTE increases with progestin-only contraceptives (1). Mechanism is unclear, although it is hypothesized that protein concentrations influenced by hormones affect coagulation homeostasis (2). This risk appears to increase if additional VTE risk factors are present such in our patient with an elevated BMI (3). This rare case proves the importance of acquiring a detailed medical history including the use of contraceptives. Moreover, awareness of this diagnosis is essential so that early recognition can lead to individualized treatment decision and better patient's outcome.

Epidemiological and Molecular Investigations on Salmonella Responsible for Gastrointestinal Infections in the Southwest of Shanghai From 1998 to 2017.

PurposeTo investigate the characteristics of gastrointestinal infections in Southwest Shanghai.MethodsClinical and epidemiological characteristics of patients with Salmonella infections between 1998 and 2017 admitted to the Jinshan Hospital in the Southwest of Shanghai were retrospectively analyzed. A total of 565 isolated Salmonella strains were classified by serotyping and pulsed field gel electrophoresis (PFGE).ResultsFrom 1998 to 2006, diarrhea was mainly caused by Vibrio parahaemolyticus followed by Shigella and Salmonella. From 2007 to 2010, Vibrio parahaemolyticus infection was the major cause of diarrhea followed by Salmonella and Shigella. From 2011 to 2017, Salmonella infections became the main cause of diarrhea after Vibrio parahaemolyticus. Salmonella infections increased from 2006 on and peaked between May and October, accounting for 82.48% of yearly infections. Patients with Salmonella infections (90.5%) had a history of eating unclean food, abdominal pain (58.05%), diarrhea ≥5 times a day (50.44%), moderate fever (24.96%) and increased fecal leukocytes (41.42%). From 1998 to 2017, infected specimens from clinical cases were dominated by Salmonella enterica serovar Typhimurium (S. Typhimurium) (21.59%) followed by Salmonella enterica serovar Enteritis (S. Enteritidis) (16.81%), Salmonella enterica serotype London (6.55%) and Salmonella group B (13.10%). Other species included Salmonella enterica serovar Thompson, Salmonella enterica serovar Saintpaul, Salmonella group D, Salmonella group C, Salmonella enterica serovar Choleraesuis and Salmonella enterica serovar Aberdeen. The PFGE classification of Salmonella serovars in 2008–2017 demonstrated that S. Enteritidis had 9 PFGE banding patterns and S. Typhimurium 16 with varying degrees of similarity among S. Enteritidis and S. Typhimurium. The results of antibiotic susceptibility tests for the 330 Salmonella strains revealed that fosfomycin had the highest sensitivity rate (97.5%) followed by levofloxacin and ceftriaxone (81%), and ampicillin/sulbactam (78.2%). The resistance to piperacillin and ciprofloxacin was 60.9 and 50.61%, respectively.ConclusionThe features of onset, epidemiological characteristics and molecular subtyping of Salmonella were conducive to clinical diagnosis, rational use of antibiotics and improved therapeutic efficacy.