Gastrointestinal Injury Research Articles

Acute Hemorrhage Related Colonic Injury Misdiagnosed as Signet-Ring Cell Carcinoma

Abstract Introduction/Objective Hypovolemic shock/hypoperfusion-related gastrointestinal injury is an unusual event in the practice of oncological pathology. The histologic findings can be ambiguous, potentially masquerading other entities, especially epithelial neoplasms. One needs to pay close attention to the subtle microscopic features and the associated sudden clinical event(s). Concordant hypovolemic history will help decision-making but can be overlooked or unaware of. Methods/Case Report A 72-year-old gentleman with prostate hypertrophy, rheumatoid arthritis, and hypertension presented to the emergency room with palpitation, dizziness, and dyspnea. He was diagnosed with atrial fibrillation and started on anticoagulation. Unexpectedly, the patient returned 3 days later with sudden gastrointestinal hemorrhage and severe anemia (hemoglobin 2.7). Emergency colonoscopy identified mucosal hemorrhage, erosion, and a friable, mass-like area in the sigmoid colon; the corresponding biopsy was called signet-ring cell carcinoma. Subsequently, the patient was referred to our institution for consultation. Results (if a Case Study enter NA) The provided biopsy showed multiple clusters of signet-ring-like cells with extravasated mucin, detached or distributed within edematous colonic fragments, resembling signet-ring cell carcinoma. However, no overt cytologic or architecture atypia or mitosis was appreciated; instead, microscopic hemorrhage, capillary thrombi, withering and distorted crypts, and mucosal necrotic sloughing were present, worse on the luminal surface. Furthermore, no background dysplasia or adenoma was identified. These findings uncovered an originally misdiagnosed acute colitis due to hypoperfusion. Subsequent imaging studies detected no gastrointestinal mass/lesion. 22-months later, the patient’s clinical follow-up was unremarkable. Conclusion Severe hemorrhage/hypoperfusion-induced colitis may pose a dilemma clinically and histopathologically when the contributing event is underrecognized. Detailed history and laboratory review and astute microscopic inspection are warranted.

An Interesting Case of Acute Colitis Possibly Associated with Deposition of Pharmaceutical Fillers

Abstract Introduction/Objective Crospovidone and microcrystalline cellulose, known as pharmaceutical fillers, are nonabsorbable and insoluble white powders. They are widely used in the pharmaceutical and food industries to facilitate the delivery of consumed substances and can be identified in pathological specimens from the gastrointestinal tract. Here, we report a case of diarrhea and colonic inflammation associated with extensive deposition of crospovidone and microcrystalline cellulose within the colonic mucosa. Methods/Case Report A 49-year-old male with no significant past medical history presented with abdominal pain and diarrhea for 3 weeks. CT abdomen showed wall thickening and inflammatory stranding throughout the colon, and area with possible pneumatosis coli versus pseudo-pneumatosis. Colonoscopy revealed segmental involvement with congested, erythematous and friable mucosa confined to hepatic flexure, transverse colon and splenic flexure. The biopsies of these areas showed colonic mucosa with chronic and acute inflammation, architectural distortion of the glands, melanosis coli, and extensive deposition of foreign body material within the mucosa. Closer microscopic examination of the foreign body material revealed an aggregate of coral-shaped particles with a pink center and purple periphery, which were non-birefringent under polarized light, consistent with crospovidone. Also, there was an extensive deposition of aggregates of polygonal, transparent fragments which appeared brightly birefringent under polarized light, consistent with microcrystalline cellulose. The patient denied the usage of laxatives. Results (if a Case Study enter NA) NA. Conclusion Although the data does not suggest an association between the presence of pharmaceutical fillers within the gastrointestinal tract and mucosal injury, our case suggests the possibility of associated colitis. Here, extensive mucosal deposition of crospovidone and microcrystalline cellulose shows possible association with endoscopic findings of congested and inflamed colonic mucosa, supported by microscopic examination of the sampled tissue. Hence, more investigation of iatrogenic foreign body materials, such as pharmaceutical fillers is required for optimal patient care.

Acute gastrointestinal failure is associated with worse hemodynamic and perfusion parameters over 48 h after admission in patients with septic shock: Retrospective cohort study.

This study aimed to investigate the relationship between acute gastrointestinal injury (AGI) and hemodynamic and perfusion parameters in the first week of intensive care unit (ICU) admission and evaluate the association of AGI with ICU and hospital outcomes in patients with septic shock undergoing mechanical ventilation. This retrospective cohort study applied the criteria proposed by the European Society of Intensive Medicine to classify the participants into risk/dysfunction group (AGI grade I and II) and failure group (AGI grade III and IV). Hemodynamic and perfusion parameters data previously collected in the first 48 h after ICU admission (admission, 12, 24, 48 h) were analyzed. A total of 163 were included and classified into AGI grades I (n = 79), II (n = 64), III (n = 20), and IV (none). Groups consisted of AGI risk/dysfunction (n = 143, 87.8%) and AGI failure (n = 20, 12.2%) patients. Patients with AGI failure had higher heart rate and mottling score (MS) at admission, lower mean arterial pressure, and an oliguria incidence at 12 h compared with those without AGI failure. Skin MS and abdominal primary site of infection were risk factors for AGI failure. AGI failure tended to be a risk factor for ICU mortality (risk ratio [95% CI]: 1.37 [0.99-1.89]; P = 0.053). AGI was frequently observed in patients with septic shock in the first week of ICU admission. Higher heart rate and MS and lower mean arterial pressure and incidence of oliguria were identified in patients with AGI failure compared with those without. AGI failure was associated with ICU mortality.

AGI grade-guided chaiqin chengqi decoction treatment for predicted moderately severe and severe acute pancreatitis (CAP trial): study protocol of a randomised, double-blind, placebo-controlled, parallel-group, pragmatic clinical trial

BackgroundAcute pancreatitis (AP) is a common digestive disease with increased incidence globally but without internationally licenced pharmacological therapy. Moderately severe and severe acute pancreatitis (MSAP/SAP) contributes predominately for its morbidities and mortality and has been managed in West China Hospital for decades using the traditional Chinese medicinal formula chaiqin chengqi decoction (CQCQD). The current study tests whether the early administration of CQCQD will result in improved clinical outcomes in predicted MSAP/SAP patients.MethodsThis is a single-centre, randomised, controlled, double-blind pragmatic clinical trial. AP patients aged 18–75 admitted within 72 h of onset will be assessed at admission for enrolment. We excluded the predicted mild acute pancreatitis (Harmless Acute Pancreatitis Score > 2 at admission) and severe organ failure (Sequential Organ Failure Assessment [SOFA] score of respiratory, cardiovascular, or renal systems > 3) at admission. Eligible patients will be randomly allocated on a 1:1 basis to CQCQD or placebo control administration based on conventional therapy. The administration of CQCQD and placebo is guided by the Acute Gastrointestinal Injury grade-based algorithm. The primary outcome measure will be the duration of respiratory failure (SOFA score of respiratory system ≥ 2) within 28 days after onset. Secondary outcome measures include occurrence of new-onset any organ failure (SOFA score of respiratory, cardiovascular, or renal system ≥ 2) and new-onset persistent organ failure (organ failure lasts > 48 h), dynamic surrogate biochemical markers and clinical severity scores, gut-centred treatment modalities, local complications status, intensive care need and duration, surgical interventions, mortality, and length of hospital stay. Follow-up will be scheduled on 6, 12, and 26 weeks after enrolment to assess AP recurrence, local complications, the requirement for surgical interventions, all-cause mortality, and patient-reported outcomes.DiscussionThe results of this study will provide high-quality evidence to appraise the efficacy of CQCQD for the early management of AP patients.Trial registrationChictr.org.cn Registry (ChiCTR2000034325). Registered on 2 July, 2020.

Establishment and evaluation of a prediction model for acute gastrointestinal injury in patients with prolonged disorder of consciousness

ObjectiveTo establish a prediction model for acute gastrointestinal injury (AGI) in patients with prolonged disorder of consciousness (pDOC) and to evaluate and apply the prediction model. MethodsThe clinical data of 165 patients with pDOC admitted to the hyperbaric oxygen department from January 2021 to December 2021 were retrospectively reviewed, and the patients were divided into an AGI group (n = 91) and an N-AGI group (n = 74) according to whether AGI occurred. A prediction model was built by fitting multiple independent influencing factors through logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the model, the Hosmer–Lemeshow (H–L) test was used to evaluate the goodness-of-fit of the model, and the ROC curve and calibration curve were drawn to evaluate the predictive performance. A nomogram was plotted to visualize the prediction model.ResultsAccording to the multivariate logistic regression analysis results, the prediction model was finally constructed with the CRS-R score, DAO, PCT, ALB, and I-FABP, and a nomogram was generated. The area under the ROC curve (AUC) of the prediction model was 0.931, the sensitivity was 83.5%, and the specificity was 93.2%. The data were divided into 5 groups for the H–L test (χ2 = 2.54, P = 0.468 > 0.05) and into 10 groups for the H–L test (χ2 = 9.98, P = 0.267 > 0.05). A calibration curve was drawn based on the test results, indicating that the prediction model has a good goodness-of-fit and good prediction stability.ConclusionThe prediction model for AGI in pDOC patients constructed in this study can be used in clinical practice and is helpful to predict the occurrence of AGI in pDOC patients.

Severe gastrointestinal injury associated with SARS-CoV-2 infection: Thrombosis or Inflammation?: A retrospective case series study.

Objectives:Acute gastrointestinal injury (AGI) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a low incidence of complications in patients admitted to the intensive care unit (ICU). Pathophysiological knowledge related to AGI is limited, as few studies have been published on this topic. Therefore, this study was carried out to identify the clinical and histopathological features of patients with SARS-CoV-2 infection and grade IV AGI.Methods:This is a retrospective case study of fifteen patients with SARS-CoV-2 infection and grade IV AGI who underwent emergency surgery.Results:This study revealed a mortality rate of 62.5%. The most frequent gastrointestinal symptoms were abdominal distension (100%) and increased gastric residual volume (93.3%). Distended bowel loops on plain abdominal radiography (90%) and intestinal pneumatosis on computed tomography (50%) were the most frequent imaging findings. Surgical exploration revealed intestinal ischemia (66.6%) and necrosis (46.6%), and histopathology showed ischemic and liquefactive necrosis with mixed inflammatory involvement and absence of thrombosis as the cause of AGI.Conclusions:AGI associated with severe SARS-CoV-2 infection has a high mortality rate and poses a diagnostic challenge in the ICU. The complex pathophysiology and histopathological findings indicate an associated inflammatory phenomenon as the main alteration in the absence of thrombosis, as per the intestinal biopsies of the cases studied. Further clinical studies are required to gain a better understanding of this pathology.

PERFORATION OF THE SIGMOID COLON AFTER INGESTA OF A FOREIGN BODY.

Introduction: The ingestion of a foreign body (FB) is uncommon, yet important cause of gastrointestinal injury; it has more incidence in the pediatric population. Less than 1 % of the FB is associated with complications, particularly gastrointestinal perforations. We present the case of a 76 years old Case report: female, who refers lower quadrant abdominal pain of 48 hours of evolution, with gradually exacerbation over 1 day, The CT Findings reveal the presences of pneumoperitoneum and a high-density FB in the architecture of rectosigmoid colon, she underwent exploratory laparotomy with trans -surgical ndings: Perforation of 0.5 cm in rectosigmoid union, with the protrusion of a bone with perilesional edema. Treated with suturing in two planes, with good evolution. Most ingest Discussion and conclusions: ed FB pass through the GI tract uneventfully within 1 week, and is more common among children and older individuals. Patients with dentures, alcoholics and psychiatric patients are at high risk of FB ingestions. In the case of perforation due to foreign body, different techniques can be performed; the most common are: In the stomach, primary suture, in the small bowel, primary suture or segmental resection with anastomosis, and in the colon, sigmoid and rectum, primary suture, wound eversion by colostomy, segmental resection with anastomosis, and segmental resection with proximal colostomy.

Upregulation of claudin‑4 by Chinese traditional medicine Shenfu attenuates lung tissue damage by acute lung injury aggravated by acute gastrointestinal injury

Context Many studies have explored new methods to cure acute lung injury (ALI); however, none of those methods could significantly change the high mortality rate of ALI. Shenfu is a Chinese traditional medicine that might be effective against ALI. Objective Our study explores the therapeutic potential of Shenfu in ALI. Materials and methods Male C57BL/6 mice were assigned to control, lipopolysaccharide (LPS) (500 µg/100 μL per mouse), and LPS + Shenfu (30 mL/kg) groups. Shenfu (10 µL/mL) was added to LPS (10 µg/mL) treated MLE-12 cells for 48 h in vitro. Male C57BL/6 mice were divided into four groups: LPS, LPS + 3% dextran sulphate sodium (DSS), 3% DSS + Shenfu, and LPS + 3% DSS + Shenfu. Results Compared with the ALI group, Shenfu reduced wet/dry weight ratio (19.8%, 36.2%), and reduced the IL-2 (40.9%, 61.6%), IFN-γ (43.5%, 53.3%) TNF-α (54.1%, 42.1%), IL-6 (54.8%,70%), and IL-1β (39.9%, 65.1%), reduced serum uric acid (18.8%, 48.7%) and creatinine (17.4%, 41.1%). Moreover, Shenfu enhanced cell viability (17.2%, 59.9%) and inhibited cell apoptosis (63.0%) and p38/ERK phosphorylation in in vitro cultured epithelial cells with LPS stimulation. Mechanistically, Shenfu mediated the protective effect by upregulating claudin-4 expression. In addition, Shenfu could protect against both lung and intestinal epithelial damage in acute gastrointestinal injury-exacerbated ALI. Discussion and conclusions Taken together, the results revealed the therapeutic effect and the underlying mechanism of Shenfu injection in an ALI in mouse model, indicating its clinical potential to treat patients with ALI.

P-Selectin is a Critical Factor for Platelet-Mediated Protection on Restraint Stress-Induced Gastrointestinal Injury in Mice.

Psychological stress is associated with increased risk of gastrointestinal (GI) tract diseases. Evidence indicated that platelets facilitate GI tissue repair in intestinal anastomosis models. However, whether platelets are involved in native mechanism of the rescue of stress-induced GI injury for maintaining the GI homeostasis remains elusive. Because P-selectin-deficient (Selp−/−) mice displayed higher stress-induced GI injury compared to the wild-type (Selp+/+) mice, and P-selectin is specifically expressed in platelets, we hypothesize that P-selectin-expressing platelets play a protective role in the rescue of stress-induced GI injury. Our goal is to clarify the putative protective role of platelets in a GI system, thereby develop a feasible intervention strategy, such as platelet transfer, to overcome stress-induced GI injury. Through monitoring the plasma levels of GI-nonabsorbable Evans blue dye to reveal the progression course of GI injury in live mice, we found that intravenous treatments of purified platelets ameliorated stress-induced GI leakage. The transfer of platelets from wild-type mice was more potent than from Selp−/− mice in the rescue of stress-induced-GI leakage in the recipients. As such, platelet transfer-mediated rescue was conducted in a P-selectin dependent manner. Additionally, platelet-mediated protection is associated with corrections of stress-induced aberrant GI mRNA expressions, including tight junctions claudin 3 and occludin, as well as stress-induced genes activating transcription factor 3 and AMP-activated protein kinase, after the transfer of wild-type platelets into wild-type and Selp−/− mice. Furthermore, the stress-induced apoptosis of CD326+ GI epithelial cells was rescued by the transfer of wild type, but not P-selectin-deficient platelets. These results suggest that platelet plays a protective role for maintaining the GI homeostasis during stress in vivo, and that P-selectin is a molecular target for managing stress-induced GI tract injury.

Seat belt injuries and external markings at autopsy in cases of lethal vehicle crashes.

A study was undertaken to determine what injuries are associated with the wearing of seat belts and if the presence of cutaneous seat belt markings observed on victims of lethal vehicle crashes increased the likelihood of underlying injury. Autopsy reports from the files at Forensic Science South Australia were reviewed for all fatal motor vehicle crashes from January 2014 to December 2018. A total of 173 cases were included for analysis with 127 occupants wearing seat belts at the time of impact (73.4%) (age range = 18-93; mean = 45 M:F = 81:46). Of these, only 38 had external seat belt markings (29.9%) (age range = 19-83; mean = 49 M:F = 20:18). Logistic regression modelling showed that occupants who were wearing seat belts were more likely to experience closed head injury without skull fractures in addition to mesenteric and gastrointestinal injury. Increasing body mass index increased the incidence of seat belt markings (p < 0.01) and markings were more likely to be found in the presence of bilateral pelvic fractures. Thus, external seat belt markings were observed in only a minority of seatbelt wearers, and more often in individuals with higher BMIs and with bilateral pelvic fractures (possibly associated with greater momentum and impact force).

Adverse reaction signals mining and hemorrhagic signals comparison of ticagrelor and clopidogrel: A pharmacovigilance study based on FAERS.

Background: Ticagrelor and clopidogrel are commonly used antiplatelet agents, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to provide a reference for safe and reasonable clinical use. Methods: Data were collected in FAERS from 2012 Q1 to 2022 Q2 for data cleaning. We used system organ classes (SOCs) and prefer terms (PTs) from the Medical Dictionary of Regulatory Activity (MedDRA version 25.1). Adverse event reports were retrieved at the PT level. Adverse reaction (ADR) signals of ticagrelor and clopidogrel were mined by calculating reporting odds ratios (ROR), proportional reporting ratios (PRR), information component (IC) and empirical Bayesian geometric mean (EBGM). After that, further analysis of the hemorrhagic signals and their clinical information were performed. Results: The number of ADR reports where the primary suspect (PS) drugs were 15,133 for ticagrelor and 23,860 for clopidogrel. Significant ADR signals were identified by the SOC analysis for ticagrelor including cardiac disorders (ROR 4.87, PRR 4.46), respiratory disorders (ROR 2.45, PRR 2.28), and vascular disorders (ROR 2.22, PRR 2.16). Clopidogrel included blood disorders (ROR 2.86, PRR 2.77), vascular disorders (ROR 2.71, PRR 2.61), and cardiac disorders (ROR 2.29, PRR 2.22). At the PT level, the more frequent ADR signals for ticagrelor were dyspnoea, contusion, and haemorrhage, while clopidogrel were gastrointestinal haemorrhage, anaemia, and drug interaction. The hemorrhagic signals of both were mainly focused on the SOC level of gastrointestinal disorders, injury disorders and vascular disorders and nervous system disorders. The death and life-threatening rate of ticagrelor was 7.76 percentage higher than that of clopidogrel. Conclusion: Clinicians need to pay attention to not only common ADRs but also be alert to new ADR signals when choosing to use ticagrelor and clopidogrel. This study provides a reference for the reasonable and safe clinical use of ticagrelor and clopidogrel.

S2567 Vaping-Induced Duodenal Ulcer

Introduction: Vaping, or electronic cigarette use has tremendously increased. It is estimated a population of five million is involved in vaping each year. While lung injury associated with vaping has gained national attention, the systemic burden of vaping has not been established. To date, there is no current report on the prevalence of gastrointestinal symptoms alone in association with vaping, yet it has been reported that 90% of patients who present with lung injury also have gastrointestinal symptoms. This raises the concern that vaping may also result in gastrointestinal injury such as seen with tobacco smoking and use of nicotine products. To our knowledge, vaping has not been shown to be associated with gastrointestinal ulcers or peptic ulcer disease. Case Description/Methods: We report a case of a 19-year-old male who was admitted to the intensive care unit for concern of hemorrhagic shock after presenting with hematemesis from a duodenal ulcer. The patient had no other medical history or known risk factors for peptic ulcer disease. However, he did report a seven-month history of vaping marijuana and THC products through a vaping pen for several hours per day prior to his onset of gastrointestinal symptoms and eventual hematemesis. Patient gastrin levels were normal. Gastric biopsies were negative for H Pylori. He denied using NSAIDS, including BC powders and goody powders. Discussion: This case emphasizes the need for clinicians to obtain a medical history of vaping when assessing patients with gastrointestinal symptoms. Future research in vaping should evaluate if the various compounds in vaping products or if the different methods of vaping can cause adverse gastrointestinal side effects such as ulcers.

S2126 Sevelamer-Induced Colitis

Introduction: Drug-induced Gastrointestinal (GI) injury has been well established throughout the literature and continues to prevail with the ever-growing expansion of pharmaceutical drug development. Mucosal injuries due to medications ranging from common over-the-counter drugs to novel chemotherapeutics, have been one of the more common findings seen both endoscopically and histologically in drug-induced GI injury. Though frequently seen with NSAIDs, iron pills, and bisphosphonates, lately, resin-based binders like Sevelamer have shown an increased incidence of GI mucosal injuries. Sevelamer is an oral phosphate binder widely used to treat hyperphosphatemia in patients with chronic kidney disease. Here we present a case of Sevelamer induced colitis in a patient on Sevelamer Carbonate therapy for hyperphosphatemia secondary to acute kidney injury. Case Description/Methods: 34 year old male with history of hypertension, obesity class III status post sleeve gastrectomy, OSA, congestive heart failure, and a recent diagnosis of COVID-19 was admitted to the MICU for acute hypoxemic respiratory failure requiring intubation. His hospital course was complicated by worsening renal function and oliguria with creatinine 8.9 and phosphorus 6.4. He was started on hemodialysis (HD), followed by Sevelamer Carbonate 0.8 g TID then increased to 1.6 g TID. Weeks after initiating HD, he developed bright red blood per rectum requiring intermittent transfusions. CT abdomen pelvis and mesenteric angiogram were unremarkable. Upper GI endoscopy showed a Forest Class III duodenal ulcer. Colonoscopy showed localized severe friable ulcerated mucosa with loss of vascular pattern in the cecum and ascending colon. Biopsy at these sites revealed mucosal ulcerations with granulation tissue with Sevelamer crystal deposits. Hematochezia improved on discontinuing Sevelamer (Figure). Discussion: Sevelamer is a calcium-free oral phosphate binder that has replaced calcium-based binders to treat hyperphosphatemia. Common side effects include nausea, vomiting, and diarrhea. GI mucosal injury from resin-based binders has been reported, although colitis induced by Sevelamer crystal deposition is rare. Previous literature shows a wide range of presentations, including ulcerations, GI bleeding, and colonic strictures. As with prior reports, we show similar endoscopic and histological findings from our patient consistent with this rare entity.Figure 1.: A, Colonoscopic finding showing erythematous ulcerated mucosa in the proximal ascending colon. B, Biopsy from proximal ascending colon site showing granulation tissue with ulceration. The black arrow indicates the Sevelamer Crystal deposition, showing the characteristic “Fish Scale” pattern.

S152 Gastrointestinal Tract Injuries Associated With Sevelamer: A Systematic Review

Introduction: Sevelamer is a phosphate binder that is used to treat hyperphosphatemia in patients with chronic kidney disease. Sevelamer is known to cause multiple gastrointestinal side effects including nausea, vomiting, constipation, and abdominal pain. However, sevelamer crystals were observed in rare cases in the gastrointestinal tract (GIT) with associated serious injuries including inflammation, ulceration, ischemia, and perforation. In this study, we conducted a systematic review to investigate the association of sevelamer with GIT injuries. Methods: We conducted a systematic search in MEDLINE, EMBASE, Scopus, and Cochrane Central Register of Controlled Trials to identify eligible reports of sevelamer-associated gastrointestinal tract injuries. The bibliographies of identified articles, Goggle scholars, and websites of relevant professional associations were also searched for relevant studies. Two independent reviewers identified eligible studies and data were extracted in Excel. Only studies that had sevelamer crystals seen in the histopathological exams were included. (Table) Results: We included 58 studies describing a total of 77 patients with a mean age of 58.8 years. Diabetes was present in 27% of cases and at least one risk factor to have slow GIT motility was identified in 63.3% of patients. Both sevelamer carbonate and sevelamer hydrochloride were reported to be associated with GIT injury. Gastrointestinal bleeding (44.2 %) and abdominal pain (37.7 %) were the most common presenting symptoms. The large intestines were the most common area of involvement (74 %), especially in the rectosigmoid area (36.4 %). Ulceration (52 %) and inflammation (48.1 %) were the most common histopathological findings. Stopping sevelamer was the most common pharmacological intervention. 20.8% of patients required surgical intervention, while 6.5% had an endoscopic intervention. Full recovery was reported in 45.5% while 6.5% of patients died. Conclusion: While sevelamer crystals can be found incidentally in the mucosa of the GIT, there is growing evidence that sevelamer use can be associated with GIT injury. Slow GIT motility can be an important risk factor to develop sevelamer-associated GIT injury. If a GIT injury was found during endoscopy and sevelamer crystals were identified on histopathological exam, discontinuing sevelamer and using an alternative phosphate binder should be considered. Further studies are needed to identify risk factors and the best approaches for primary and secondary prevention. Table 1. - Characteristics of included studies GIT: gastrointestinal tract, GIB: Gastrointestinal bleeding Demographics Age (years)Malesfemales 58.88 ± 10.934 (44.2 %)35 (44.5 %) Comorbidities DiabetesConstipationPrevious abdominal surgeryBlood thinnersPossible Slow GIT motility 27 (35.5 %)4 (5.2 %)15 (19.5 %)16 (20.8 %)49 (63.3%) Sevelamer treatment Sevelamer carbonateSevelamer hydrochlorideBothAverage doseMedian doseDuration 16 (20.8 %)12 (15.6 %)1 (1.3%)4,176.29 mg3,200.00 mg5 days – 7 years Symptoms GIBAbdominal painDiarrheaNausea/vomitingEsophageal dysphagia 34 (44.2 %)29 (37.7 %)12 (15.6 %)10 (13%)1 (1.3%) Location of GIT injury EsophagusStomachSmall IntestinesIleocecal valveLarge intestinesCecum and/or ascending colonTransverse ColonDescending colonRectosigmoidDiffuse colonic or unspecifiedAppendix 8 (10.4 %)8 (10.4 %)3 (3.9 %)3 (3.9 %)57 (74 %)8 (10.4 %)7 (9.1 %)1 (1.3%)28 (36.4 %)15 (19.5 %)2 (2.6 %) Histopathological abnormalities* UlcerationInflammationPerforationNecrosisIschemiaStrictureInflammatory polyp 40 (52 %)37 (48.1 %)14 (18.2 %)11 (14.3 %)6 (7.8 %)3 (3.9 %)3 (3.9 %) Pharmacological interventions Stopped SevelamerDecreased sevelamer doseContinued Sevelamer 35 (45.5 %)1 (1.3 %)1 (1.3 %) Procedural interventions Surgical interventionEndoscopic treatmentEndovascular intervention 16 (20.8)5 (6.5 %)1 (1.3 %) Outcomes RecoveredDeathNot reported 35 (45.5 %)5 (6.5 %)37 (48.1 %) *Includes both microscopic and macroscopic findings.

S2521 Sevelamer: An Underreported Cause of Enteritis and Colitis

Introduction: Hyperphosphatemia is a common metabolic derangement in patients with end-stage renal disease (ESRD). In addition to dietary constraints, phosphate binders are needed to treat hyperphosphatemia. Sevelamer is the most used resin-based phosphate binder and can crystallize to form concretions. Crystals formed by other resin-based binders such as polystyrene sulfonate (kayexalate) are a well-known cause of gastrointestinal (GI) mucosal injury. However, sevelamer is an underreported culprit. Here, we describe a case of ileitis and colitis caused by sevelamer crystals. Case Description/Methods: A 65-year-old male veteran with ESRD, secondary hyperparathyroidism treated with sevelamer, and cocaine abuse was admitted for abdominal pain and bloody diarrhea for 3 days. CT scan of the abdomen and pelvis revealed inflammation of the ileum and rectosigmoid. He was started on ciprofloxacin and metronidazole. Stool studies were negative. A colonoscopy revealed an ulcerated and erythematous terminal ileum (TI) between 15cm and 7cm proximal to the ileocecal valve. There was mild ulceration and erythema in the ascending colon. The worst ulceration was between 40cm to 30cm from the anal verge with additional ulceration seen in the rectosigmoid. The colonic mucosa between the ulcerations were normal appearing. Biopsies taken from the TI, ascending colon, and descending colon revealed chronic ileitis and colitis with ulceration, granulation tissue associated crystals, crypt abscess, and fibrinopurulent debris and negative for infection or malignancy. A review the medication reconciliation confirmed no exposure to kayexalate and, thus, concluded that sevelamer was the cause. The patient was advised to stop taking sevelamer. A follow up colonoscopy 6 months later revealed complete mucosal healing (Figure). Discussion: GI mucosal injury is a rare and underrecognized adverse effect of sevelamer. A limited number of reported cases describe a range of symptoms such as nausea, vomiting, constipation, dysentery, and acute abdomen requiring surgery. The enteritis and colitis caused by sevelamer can be overlooked and presumed to be infectious or ischemic etiology. The pathology can also be missed because of misidentification or failure to identify crystals on histology. Increased awareness of this underreported complication of sevelamer is important for these reasons and for directing appropriate therapy with cessation of this medication in the setting of enteritis or colitis.Figure 1.: H&E stain showing fibrinopurulent exudate (ischemic /acute erosive pattern colitis) and the presence of Sevelamer crystals.

Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model.

Exposure to high doses of radiation, accidental or therapeutic, often results in gastrointestinal (GI) injury. To date, there are no therapies available to mitigate GI injury after radiation exposure. Gamma-tocotrienol (GT3) is a promising radioprotector under investigation in nonhuman primates (NHP). We have shown that GT3 has radioprotective function in intestinal epithelial and crypt cells in NHPs exposed to 12 Gy total-body irradiation (TBI). Here, we determined GT3 potential in accelerating the GI recovery in partial-body irradiated (PBI) NHPs using X-rays, sparing 5% bone marrow. Sixteen rhesus macaques were treated with either vehicle or GT3 24 h prior to 12 Gy PBI. Structural injuries and crypt survival were examined in proximal jejunum on days 4 and 7. Plasma citrulline was assessed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Crypt cell proliferation and apoptotic cell death were evaluated using Ki-67 and TUNEL staining. PBI significantly decreased mucosal surface area and reduced villous height. Interestingly, GT3 increased crypt survival and enhanced stem cell proliferation at day 4; however, the effects seemed to be minimized by day 7. GT3 did not ameliorate a radiation-induced decrease in citrulline levels. These data suggest that X-rays induce severe intestinal injury post-PBI and that GT3 has minimal radioprotective effect in this novel model.

Clinical efficacy of combined use of Xuebijing and mild hypothermia therapy for the treatment of severe traumatic brain injury, and its effect on patient mortality and complications

Purpose: To investigate the clinical efficacy of combined use of Xuebijing and mild hypothermia therapy in severe traumatic brain injury (TBI), and its effect on mortality and incidence of complications.&#x0D; Methods: Eighty-six severe TBI patients admitted to The Fourth People's Hospital of Chongqing were selected. Patients were randomly and equally assigned to control group (COG) who received conventional treatment, and study group (EXG) given a combination of Xuebijing and mild hypothermia therapy. Relevant clinical indicators and therapeutic effects were compared.&#x0D; Results: Post-treatment levels of inflammatory indices, including procalcitonin (PCT), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly reduced, with lower levels in EXG (p &lt; 0.05). Between-group differences were seen in human leukocyte antigen-DR isotype (HLA-DR), CD3+, CD4+, CD8+, and C3 indicators (p &lt; 0.05). EXG had significantly lower protein expression levels of neuron-specific enolase (NSE) and S100 beta than COG (p &lt; 0.05). After treatment, plasma protein levels of coagulation indices, viz, prothrombin time (PT) and activated partial thromboplastin time (APTT) were lower than pre-treatment levels, with even much lower levels in EXG (p &lt; 0.05). There were reduced incidence of lung infection, acute gastrointestinal injury, acute respiratory distress syndrome (ARDS) and hypernatremia (p &lt; 0.05). More patients had better recovery in EXG (p &lt; 0.05) than in control group.&#x0D; Conclusion: The combined therapy improves the prognosis of severe TBI, lowers the levels of inflammatory factors, ameliorates plasma coagulation, and enhances immunity with a high degree of safety. However, further clinical trials should be undertaken prior to application in clinical practice

602. LONG-TERM OUTCOME OF COLON INTERPOSITION IN SEVERE CORROSIVE UPPER DIGESTIVE TRACT INJURY

Abstract Long-term outcome of colonic interposition in patients with severe corrosive upper gastrointestinal tract injury is less known. Patients diagnosed of severe corrosive upper digestive tract injury were included. Patients with full-thickness organ necrosis underwent emergent surgical resection without primary reconstruction. Subsequent esophageal reconstruction with substernal colonic interposition approximately 6 months after the ingestion was undertaken in physically and mentally fit patients. Esophageal dilatation program was applied as first line treatment in all patients with esophageal stricture at a median duration of 5 weeks after the injury. Esophageal replacement procedure was offered to the patients who had failed dilatation. Late complications, swallow function, nutritional autonomy and overall survival in patients who underwent colonic interposition were evaluated. There were 70 patients undergoing colonic interposition. Of 70 patients, 50 (71%) had cervical pharyngo-colonic and 20 had cervical esophago-colonic anastomoses. There was one (1.4%) 90-day hospital mortality. Anastomosis leakage was 8%. At median follow up of 58 months, late deaths were observed in 6 patients causing by nesidioblastosis (2), resuicidal attempt (2) and intestinal volvulus (2). Adhesive small intestinal obstruction requiring laparotomy was observed in 7(10%). Nutritional autonomy was achieved in 55 of 60 (92%) patients. Strictures were developed in 10 (16%) and dumping syndrome in 20 (30%) patients. Five- and ten-year overall survival were 72% and 61%, respectively. Colonic interposition in patients with severe corrosive upper digestive tract injury was safe and effective. Long-term survival, function and nutritional outcome are good regardless of the proximal level of cervical anastomosis. However, the late negative impact of the reconstructive procedure on metabolic derangement and small intestinal obstruction cannot be overemphasized.

Ameliorative effect of the probiotic peptide against benzo(α)pyrene-induced inflammatory damages in enterocytes

Probiotics are living bacteria that provide health benefits to the host when consumed in sufficient quantities. However, the protective effect of the bioactive peptides isolated from the probiotics against benzo(α)pyrene (BaP) induced gastrointestinal injury has never been investigated. The current work used a bio-assay guided technique to identify-four new cyclic peptides in BaP-induced Caco-2 cell culture and mouse colitis model. Lactobacillus rhamnosus cycle (Thr-His-Ala-Trp) peptide-1 (LRCP-1) effectively inhibited BaP-induced epithelial cytokine over-release and intracellular ROS over-production. Simultaneously, LRCP-1 attenuated BaP-induced NAD (P)H: oxidases (NOXs), Matrix metalloproteinases (MMPs) over-expression, respectively. Furthermore, increased NAD (P)H: quinone oxidoreductase 1 (NQO1)/heme oxygenase-1 (HO-1)/nuclear factor E2-related factor 2 (Nrf2) expression and aryl hydrocarbon receptor (AhR) pathway activation induced by the BaP-exposure were also inhibited after the LRCP-1 treatment. Notably, LRCP-1 is a promising agent protecting gastrointestinal epithelial cells from BaP-induced inflammatory and oxidative damages.

Network pharmacology and experimental verification-based strategy to explore the underlying mechanism of Liu Jun An Wei formula in the treatment of gastrointestinal reactions caused by chemotherapy for colorectal cancer.

Background: Liu Jun An Wei formula (LJAW), derived from “Liu Jun Zi Decoction”, is a classical prescription of Tradition Chinese Medicine and has been used for the treatment of gastrointestinal reactions caused by chemotherapy for colorectal cancer (CRC) for many years. Its molecular mechanism remains to be further explored. Objective: To clarify the mechanism of LJAW in attenuating gastrointestinal reactions caused by chemotherapy for CRC. Methods: The 5-fluorouracil (5-FU) induced mouse and intestine organoid models were established to observe the effect of LJAW. The ingredients of LJAW were analyzed and identified by UPLC-Q-TOF-MS technology. Targets of LJAW and chemotherapy-induced gastrointestinal reactions were collected from several databases. “Ingredient-target” network and protein-protein interaction network were constructed based on network pharmacology. Then, gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Subsequently, molecular docking method was used to verify the interaction between the core ingredients and key targets. The results were validated by both in vivo experiments and organoid experiments. Western Blot was used to analyze the influence of LJAW on key targets including PI3K, AKT1, MAPK1, MAPK14 proteins and their phosphorylated proteins. RT-qPCR and Western Blot were used to detect the mRNA and protein levels of apoptosis-related gene PUMA. Results: Compared with the 5-FU group, the LJAW group had better morphology in mouse small intestine and intestine organoids. In total, 18 core ingredients and 19 key targets were obtained from 97 ingredients and 169 common targets. KEGG analysis showed that the common targets were involved in PI3K/Akt, MAPK, apoptosis and other signal pathways, which are closely related to gastrointestinal injury. Experiments confirmed that LJAW lowered the expressions of phosphorylated proteins including p-PI3K, p-AKT1, p-MAPK1, and p-MAPK14 and reduced the mRNA and protein levels of PUMA. Conclusion: LJAW shows protective effect on 5-FU induced small intestine and intestinal organoids injury. LJAW attenuates gastrointestinal reactions caused by chemotherapy for CRC probably by regulating apoptosis-related genes through PI3K/AKT and MAPK signaling pathways.