Proximal Gastrointestinal Tract Research Articles

A long journey to the colon: The role of the small intestine microbiota in intestinal disease.

The small intestine represents a complex and understudied gut niche with significant implications for human health. Indeed, many infectious and non-infectious diseases center within the small intestine and present similar clinical manifestations to large intestinal disease, complicating non-invasive diagnosis and treatment. One major neglected aspect of small intestinal diseases is the feedback relationship with the resident collection of commensal organisms, the gut microbiota. Studies focused on microbiota-host interactions in the small intestine in the context of infectious and non-infectious diseases are required to identify potential therapeutic targets dissimilar from those used for large bowel diseases. While sparsely populated, the small intestine represents a stringent commensal bacterial microenvironment the host relies upon for nutrient acquisition and protection against invading pathogens (colonization resistance). Indeed, recent evidence suggests that disruptions to host-microbiota interactions in the small intestine impact enteric bacterial pathogenesis and susceptibility to non-infectious enteric diseases. In this review, we focus on the microbiota's impact on small intestine function and the pathogenesis of infectious and non-infectious diseases of the gastrointestinal (GI) tract. We also discuss gaps in knowledge on the role of commensal microorganisms in proximal GI tract function during health and disease.

Towards an EKG for SBO: A Neural Network for Detection and Characterization of Bowel Obstruction on CT.

A neural network was developed to detect and characterize bowel obstruction, a common cause of acute abdominal pain. In this retrospective study, 202 CT scans of 165 patients with bowel obstruction from March to June 2022 were included and partitioned into training and test data sets. A multi-channel neural network was trained to segment the gastrointestinal tract, and to predict the diameter and the longitudinal position ("longitude") along the gastrointestinal tract using a novel embedding. Its performance was compared to manual segmentations using the Dice score, and to manual measurements of the diameter and longitude using intraclass correlation coefficients (ICC). ROC curves as well as sensitivity and specificity were calculated for diameters above a clinical threshold for obstruction, and for longitudes corresponding to small bowel. In the test data set, Dice score for segmentation of the gastrointestinal tract was 78 ± 8%. ICC between measured and predicted diameters was 0.72, indicating moderate agreement. ICC between measured and predicted longitude was 0.85, indicating good agreement. AUROC was 0.90 for detection of dilated bowel, and was 0.95 and 0.90 for differentiation of the proximal and distal gastrointestinal tract respectively. Overall sensitivity and specificity for dilated small bowel were 0.83 and 0.90. Since obstruction is diagnosed based on the diameter and longitude of the bowel, this neural network and embedding may enable detection and characterization of this important disease on CT.

Short communication: Estimation of ileal digestibility in chickens using single- and dual-tracer methods

Fractionation of digesta, as occurs during gastrointestinal transit in chickens, complicates accurate measurements of ileal digestibility using tracers. Dual-tracer methods using separate tracers for solid and fluid digesta phases may improve the accuracy of digestibility measurements when assumptions of the single tracer method are violated. The aim of the present study was to compare the apparent ileal digestibility (AID) of nutrients calculated with single- and dual-tracer methods in chickens fed diets varying in particle size, anticipating digesta phase separation in the proximal gastrointestinal tract. A total of 112 Dekalb White (BW: 1.53 ± 0.107 kg) and 112 Bovans Black (BW: 1.79 ± 0.127 kg) 29-week-old laying hens were distributed over 32 pens (seven birds/pen). Within breed, pens were randomly assigned to one of two experimental diets (coarse vs fine oat hulls; n = 8 replicate pens per diet/breed combination). Diets were supplemented with TiO2 (3 g/kg) and Co-EDTA (2 g/kg). On days 34, 35, or 36, birds were euthanised and digesta from the ileum was collected for tracer and nutrient analyses. Apparent ileal digestibility was subsequently calculated by single- and dual-tracer methods. Although coarse oat hulls were hypothesised to increase the fractionation of solid and fluid digesta phases, no breed or diet × method interactions were found. Using a single tracer method based on TiO2, AID of nitrogen (N) was overestimated by 3%-units (P < 0.01) compared with the dual-tracer method, whereas AID estimates of DM, starch, fat, and non-starch polysaccharides did not differ (P > 0.09) and precision of all AID estimates was improved. In conclusion, these results show that although from a conceptual perspective, dual-tracer methods are presumed to better account for the variation in flow behaviour of different digesta phases, AID estimates obtained by the commonly used single tracer method using solid-phase tracer TiO2 were more precise and only marginally differed from estimates obtained by a dual-tracer method using distinct tracers for solid (TiO2) and liquid (Co-EDTA) digesta phases. Considering technical and economical constraints, the single tracer method may thus be the method of choice in many situations. Only when digestibility of proteins or amino acids is of specific interest, single tracer methods using a solid-phase tracer may not suffice. Nevertheless, for both single- and dual-tracer methods, tracer selection is critical, and the choice of tracers should depend on the nutrient(s) of interest.

Solubility of lamotrigine in age-specific biorelevant media that simulated the fasted- and fed-conditions of the gastric and intestinal environments in pediatrics and adults: implications for traditional, re-formulated, modified, and new oral formulations

BackgroundLamotrigine is an effective antiseizure medication that can be used in the management of focal and generalized epilepsies in pediatric patients. This study was conducted to quantify and compare the solubility of lamotrigine in age-specific biorelevant media that simulated the fasted and fed conditions of the gastric and intestinal environments in pediatrics and adults. Another aim was to predict how traditional, re-formulated, modified, and new oral formulations would behave in the gastric and intestinal environments across different age groups.MethodsSolubility studies of lamotrigine were conducted in 16 different age-specific biorelevant media over the pH range and temperature specified by the current biopharmaceutical classification system-based criteria. The age-specific biorelevant media simulated the environments in the stomach and proximal gastrointestinal tract in both fasted and fed conditions of adults and pediatric sub-populations. The solubility of lamotrigine was determined using a pre-validated HPLC-UV method.ResultsLamotrigine showed low solubility in the 16 age-specific biorelevant media as indicated by a dose number of > 1. There were significant age-specific variabilities in the solubility of lamotrigine in the different age-specific biorelevant media. Pediatric/adult solubility ratios of lamotrigine fell outside the 80-125% range in 6 (50.0%) and were borderline in 3 (25.0%) out of the 12 compared media. These ratios indicated that the solubility of lamotrigine showed considerable differences in 9 out of the 12 (75.0%) of the compared media.ConclusionFuture studies are still needed to generate more pediatric biopharmaceutical data to help understand the performances of oral dosage forms in pediatric sub-populations.

Effects of dosing non-toxigenic Clostridia on the bacterial populations and immunological responses in the intestinal tract of lactating dairy cows.

Understanding the effects of dosing non-toxigenic Clostridia to cows is rare and has received little attention so far. In the present study, a total of eight lactating dairy cows were divided in two groups: control (n = 4) or Clostridia challenged (oral supplementation of five diverse strains of Paraclostridium bifermentans, n = 4). Bacterial communities were analyzed by qPCR and next-generation sequencing (NGS) in the buccal mucosa as well as digesta and mucosal samples of the gastrointestinal (GI) tract from rumen to rectum (10 compartments), as well as fecal samples. Transcriptomic analysis of barrier and immune-related gene expression was performed on rumen, jejunum, and liver samples. We observed increased microbial populations with the Clostridial challenge in the buccal tissues and the proximal GI tract (forestomach), correlating with Clostridial loads in the feed. Otherwise, there were no significant differences in microbial populations (p > 0.05) throughout the distal part of the GI tract. The NGS approach, however, revealed that the Clostridial challenge changed the relative abundance of gut and fecal microbiota. In particular, in the challenge group, no Bifidobacterium was observed in the mucosa-associated microbiota and abundance of Pseudomonadota increased in the feces. These results indicated potential adverse effects of Clostridia to cow health. In general, immune responses to the Clostridial challenge were weak. However, transcriptional analysis revealed the down-regulation of junction adhesion molecule encoding gene (-1.44 of log2 fold-change), which might impact intestinal permeability.

Prevention of gastrointestinal bleeding in patients operated on the arteries of the lower extremities for critical ischemia

The purpose of the study. To determine the frequency of occurrence and prevention measures of erosive and ulcerative lesions of the proximal gastrointestinal tract in patients operated for critical ischemia with a diagnosis of obliterating atherosclerosis of the arteries of the lower extremities. Materials and methods. The examination included patients with lower limb ischemia - III-IV stage of ischemia according to the Fontaine-Pokrovsky classification. The patients were divided into 2 groups: the control group, where treatment was carried out according to the recommendations: HP diagnosis (express test) was carried out only with an endoscopic picture of gastric ulcer and duodenal ulcer, as well as the main group, in which HP diagnosis was carried out totally with fibrogastroduodenoscopy and a standard three-component eradication scheme was prescribed for at least 14 days when bacterial contamination of the gastric mucosa was detected. Results. In all cases, endoscopic changes characteristic of gastritis were registered in patients of the first group. Of the eight patients (100%), two (25%) were diagnosed with single erosions in the distal parts of the stomach, one patient (12.5%) had atrophic gastritis, and the remaining 5 (62.5%) patients had hyperemia of the antral and prepiloric mucosa. In patients of the second group, there were no changes in FGDS in one patient (25%), foci of mucosal atrophy were diagnosed in two patients (50%), and single erosions in one (25%). Conclusion. Among patients with peripheral artery diseases accompanied by critical ischemia, by the time they seek specialized medical care, there are no healthy or close to such persons with unchanged mucous membrane of the proximal parts. In the high-risk groups for the occurrence of gastrointestinal bleeding, a complex effect on aggression factors is necessary

Inositol pyrophosphate profiling reveals regulatory roles of IP6K2-dependent enhanced IP7 metabolism in the enteric nervous system

Inositol pyrophosphates regulate diverse physiological processes; to better understand their functional roles, assessing their tissue-specific distribution is important. Here, we profiled inositol pyrophosphate levels in mammalian organs using an originally designed liquid chromatography-mass spectrometry (LC-MS) protocol and discovered that the gastrointestinal tract (GIT) contained the highest levels of diphosphoinositol pentakisphosphate (IP7) and its precursor inositol hexakisphosphate (IP6). Although their absolute levels in the GIT are diet dependent, elevated IP7 metabolism still exists under dietary regimens devoid of exogenous IP7. Of the major GIT cells, enteric neurons selectively express the IP7-synthesizing enzyme IP6K2. We found that IP6K2-knockout mice exhibited significantly impaired IP7 metabolism in the various organs including the proximal GIT. In addition, our LC-MS analysis displayed that genetic ablation of IP6K2 significantly impaired IP7 metabolism in the gut and duodenal muscularis externa containing myenteric plexus. Whole transcriptome analysis of duodenal muscularis externa further suggested that IP6K2 inhibition significantly altered expression levels of the gene sets associated with mature neurons, neural progenitor/stem cells, and glial cells, as well as of certain genes modulating neuronal differentiation and functioning, implying critical roles of the IP6K2-IP7 axis in developmental and functional regulation of the enteric nervous system. These results collectively reveal an unexpected role of mammalian IP7-a highly active IP6K2-IP7 pathway is conducive to the enteric nervous system.

Insoluble fibers affect digesta transit behavior in the upper gastrointestinal tract of growing pigs, regardless of particle size.

Physicochemical characteristics of dietary fibers may modulate digesta transit behavior. The present study was conducted to clarify the effect of level and particle size (PS) of insoluble fibers on digesta mean retention time (MRT) in the proximal gastrointestinal tract (mouth-ileocecal junction). Six ileal-cannulated pigs (26.8 ± 2.08 kg) were assigned to 3 dietary treatments in a 3 × 3 replicated Latin-square design. Finely ground (1 mm screen) or coarse (intact) oat husks (OH) and soybean hulls (SBH) were added (50:50, w/w) to a maize-whey protein-wheat-based diet at 50 (low) or 250 g/kg (high) inclusion levels to obtain a low-fine fiber (LF), high-fine fiber (HF), and high-coarse fiber (HC) diet. Markers to follow liquids (Co-EDTA), fine solids (Y3O2), or fibrous particles (Yb-mordanted OH and Cr-mordanted SBH) were given as a single pulse dose and marker concentrations were subsequently measured hourly in digesta for 13 h after administration. Mean retention time values were obtained from the concentration of markers in digesta observed over time by fitting a generalized Michaelis-Menten equation and calculating the time of peak. Fiber addition and fiber particle size neither affected the MRT of liquid nor solid digesta phases (P = 0.903). Segregation between solid and liquid digesta phases was observed for all diets (P < 0.0001), although the extent of segregation was greater for LF compared with HF and HC (P = 0.0220). The MRT of SBH particles, but not of OH-particles was longer for coarse vs fine PS (96 min, P < 0.05). In conclusion, digesta MRT was influenced by the dietary concentration but not by PS of insoluble fibers. The addition of insoluble fibers reduces digesta phase segregation from mouth to distal ileum in growing pigs.

Enzymatic degradation of ochratoxin A in the gastrointestinal tract of piglets.

Animal feeds are often contaminated with ochratoxin A (OTA), a potent natural mycotoxin hazardous to animal and human health that accumulates in blood and tissues. To the best of our knowledge, this study is the first to investigate the in vivo application of an enzyme (OTA amidohydrolase; OAH) that degrades OTA into the nontoxic molecules phenylalanine and ochratoxin α (OTα) in the gastrointestinal tract (GIT) of pigs. Piglets were fed six experimental diets over 14 days, varying in OTA contamination level (50 or 500 μg/kg; OTA50 and OTA500) and presence of OAH; a negative control diet (no OTA added) and a diet containing OTα at 318 µg/kg (OTα318). The absorption of OTA and OTα into the systemic circulation (plasma and dried blood spots, DBS), their accumulation in kidney, liver, and muscle tissues, and excretion through feces and urine were assessed. The efficiency of OTA degradation in the digesta content of the GIT was also estimated. At the end of the trial, accumulation of OTA in blood was significantly higher in OTA groups (OTA50 and OTA500) in comparison to enzyme groups (OAH50 and OAH500, respectively). The supplementation of OAH explicitly reduced the absorption of OTA (P < 0.005) into plasma by 54% and 59% (from 40.53 ± 3.53 to 18.66 ± 2.28 ng/mL in piglets fed the 50 μg OTA/kg diets and from 413.50 ± 71.88 to 168.35 ± 41.02 ng/mL in piglets fed the 500 μg OTA/kg diets, respectively) and in DBS by 50% and 53% (from 22.79 ± 2.63 to 10.67 ± 1.93 ng/mL in piglets fed the 50 μg OTA/kg diets and from 232.85 ± 35.16 to 105.71 ± 24.18 ng/mL in piglets fed the 500 μg OTA/kg diets, respectively). The OTA concentrations in plasma were positively associated with the OTA levels detected in all tissues analyzed; adding OAH reduced OTA levels in the kidney, liver, and muscle (P < 0.005) by 52%, 67%, and 59%, respectively. The analysis of GIT digesta content showed that OAH supplementation led to OTA degradation in the proximal GIT where natural hydrolysis is inefficient. Overall, the data of present in vivo study demonstrated that supplementation of swine feeds with OAH successfully reduced OTA levels in blood (plasma and DBS) as well as in kidney, liver, and muscle tissues. Therefore, an approach to use enzymes as feed additives might be most promising to mitigate the harmful effects of OTA on the productivity and welfare of pigs and at the same time improving the safety of pig-derived food products.

Endoscope-Guided Marble Foreign Body Removal Technique in an Inland Bearded Dragon (Pogona vitticeps)

Abstract A 1-yr-old intact female inland bearded dragon (Pogona vitticeps) was presented approximately 24 h after observed ingestion of a marble. Orthogonal whole-body radiographs with and without contrast revealed a spherical radiopaque foreign body within the gastric lumen and no passage of contrast material beyond the foreign body, suggestive of pyloric outflow obstruction. The complete blood count showed mild basophilia, and plasma biochemical analysis revealed a moderately elevated creatine kinase. The bearded dragon was placed under general anesthesia, and a rigid endoscope was used to visualize the foreign body at the level of the pylorus. The marble foreign body was suctioned and removed orally using a red rubber catheter and a Luer-lock syringe. The patient recovered uneventfully from the procedure and was sent home with sucralfate and omeprazole after 2 days of hospitalization. This report provides a novel, nonsurgical method for removing smooth spherical foreign bodies from the proximal gastrointestinal tract of bearded dragons. The technique may apply to various small-to-medium–sized reptiles or amphibians that present with spherical foreign bodies.

Laparoscopic repair of perforated peptic ulcer - routine procedure or targeted patient selection?

Peptic ulcer is one of the most common diseases of the proximal gastrointestinal tract. Its complications are relatively common, the most serious one being peptic ulcer perforation with the incidence of about 10 cases per 100,000 population per year and the mortality rate of 10-40%. Surgical suture via laparoscopy or laparotomy is the only treatment option. The aim of the study was to compare the short-term results of laparoscopic and open repair of acute peptic ulcer perforation and evaluate the accuracy of the Boey scoring system in the Czech population. Retrospective study conducted at the surgical department of the University Hospital Ostrava. The patients underwent laparoscopic or open repair of perforated peptic ulcer in 2017-2021. The study included 60 patients; laparoscopic repair was performed in 43.3% of the patients, and open repair in 56.7%. Postoperative morbidity was 70.0%, mild complications were reported in 23.3% of the patients, and severe complications in 16.7%. Patients undergoing the laparoscopic repair showed a higher incidence of mild as well as severe complications (26.9% vs 20.6% and 19.2% vs 14.7%) but also a higher incidence of an uncomplicated postoperative course. Overall postoperative mortality was 30.0% (laparoscopy 15.4%, laparotomy 41.2%). The study results confirmed the estimated baseline risk of mortality based on the Boey score. Laparoscopic repair may be the procedure of choice for patients with no or low risk factors. Patients undergoing laparoscopy showed a higher incidence of mild and severe complications. The higher mortality of patients after open repair is related to their worse initial clinical condition. Preoperative determination of mortality risk using the Boey score is accurate and appropriate in terms of choosing the surgical approach.

P137 Lesions of Cytomegalovirus and Epstein Barr virus of the proximal gastrointestinal tract in patients with Inflammatory Bowel Disease after COVID-19

BackgroundThe problem of opportunistic infections in IBD remains one of the most pressing issues in the diagnosis and treatment of this pathology. Particular attention among opportunistic infections in IBD is given to cytomegalovirus infection(CMV), the Epstein-Barr virus(EBV). Aim: To assess the frequency of detection of CMV and EBV in biopsies taken from the mucous membranes of the proximal gastrointestinal tract (GIT) in patients with IBD who underwent COVID-19.Methods72 patients with CD(40 w/32 m) and 69 patients with UC(39 m/30 w) who underwent COVID-19, in whom CMV and EBV were not previously detected, were examined. The age of the patients was from 18 to 62 years(39.4±2.7). All patients(p.) underwent a standard endoscopic examination(EE), disease activity was assessed in accordance with the ECCO regulations; the determination of CMV and EBV was carried out by PCR in biopsies of mucous membranes from the proximal GIT.ResultsEE in 27 p.with CD revealed deeper and more widespread ulcerative lesions of the gastric mucosa(CMV+11 p.40.7%/15.3%;EBV+12 p.44.4%/16.7 %;CMV and EBV+4 p.14.8%/5.5%), in 16 p.similar changes were detected in the esophagus(CMV+7 p.43.7%/9.7%,EBV+6 p.37.5%/8.3%;CMV and EBV+3 p.18.7%/4.2%),in 49 p.in the duodenal region(CMV+17 p.34.7%/23.6 %,EBV+23 p.46.9%/31.9%;CMV and EBV+9 p.18.4%/12.5%).EE with UC revealed deeper and more widespread ulcerative lesions of the gastric mucosa in 29 p. (CMV+12 p.41.4%/17.4%;EBV+13 p.44.8%/18.8%; CMV and EBV+4 p.3.8%/5.8%),in 19 p. similar changes were detected in the esophagus(CMV+9 p.47.7%/13.1%,EBV+6 p.31.6%/8.7%;CMV and EBV+4 p.21.1%/5.8%),in 44 p. in the duodenal region(CMV+17 p.38.6%/24.6%,EBV+23 p. 52.3%/33.3%;CMV and EBV+4 p.9.1%/5.8%).Thus, in patients with CD, when determining CMV in biopsy materials by PCR,an isolated positive result(48.6%) was obtained in 35 cases,for EBV(isolated)-41 cases(56.9%), in 16 pat. a combined lesion of CMV and EBV was revealed(22.2%); the localization of lesions was dominated by the duodenal region(68.1%),the stomach (37.5%)and the esophagus(22.2%). In patients with UC, when determining CMV in biopsy materials by PCR,an isolated positive result(55.1%) was obtained in 38 cases,for EBV(isolated)-42 cases(60.7%),in 12 pat. a combined damage to CMV and EBV(17.4%); the localization of lesions was dominated by the duodenal region(63.8%),the stomach(42%) and the esophagus(27.5%).The clinical and endoscopic picture indicates a more severe course of IBD in the presence of herpes viruses detected by PCR examination of biopsies taken from the mucous membranes of the proximal GIT.ConclusionThe findings allow us to recommend the need for more thorough inspection during endoscopy in patients with IBD who have undergone COVID-19.

P596 Adalimumab use in Paediatric Inflammatory Bowel Disease: A single centre real-life experience

Abstract Background Anti-TNF-α, including infliximab and adalimumab (ADA), plays a crucial role in the treatment of Paediatric Inflammatory Bowel Disease (PIBD). This study evaluates the efficacy of ADA in children ≤ 19 years in a single European centre. Methods A 6-year retrospective analysis of prospectively collected data of PIBD patients treated with ADA (10/2015 onward). Wellbeing, clinical and laboratory findings were assessed at each visit. A mean, median and a standard deviation were calculated were applicable. ANOVA (analysis of variances) was used for evaluation of presence of statistically significant differences and a P-value ≤ 0.05 was regarded as such. Results ADA, all originator, was used in 31 patients. All of them were diagnosed with Crohn’s Disease (CD). The mean age at diagnosis was 14.6±2.8 years (range 6.6–18.2 years). The mean interval from diagnosis till commencement of ADA was 6.9 months (0.25–36 months). Step-up was used 17x and top-down 15x. A top-down approach was indicated in patients with extraintestinal manifestations, fistulizing disease, severe growth impairment and affections of the proximal gastrointestinal tract. Adjacent treatments at the time of commencement of ADA were azathioprine (18/31), CD exclusion diet (7/31), exclusive enteral nutrition (6/31), steroids (4/31), methotrexate and 5-aminosalicylates (both 3/31). Mean CRP at the time of ADA commencement was 8.8 mg/l (1.0–44.4 mg/l), ESR 21 mm/hour (1–66 mm/hour), leukocytes 8.3x109/l (3.3–22.0x109/l), haemoglobin 118.3 g/l (68–150 g/l), platelets 422x109/l (232–828 x109/l) and faecal calprotectin (FC) 901.1 μg/g (95.2–5041.9 μg/g). At the end of induction period, CRP, ESR and FC showed a significant decrease (P&amp;lt; 0.01). Blood count parameters failed to show that (P &amp;gt;0.05). Mean ADA trough levels at the end of induction period were 18.4±2.3 μg/ml. For maintenance of trough levels (≥7.5 μg/ml), weekly administration was required in 5 cases. During the follow-up period, surgical intervention was required 2x (ileocecal resection 1x and stricturoplasty 1x). Adverse side effects consisted of a skin reaction 1x and reversible hair loss 1x. Due to loss of response, 3 patients had to be switched out-of-class to ustekinumab. The mean time to loss of response since ADA commencement was 23.3 months (16–30 months). Antibody formation after 23 months of treatment led to switching one patient to infliximab. One patient was lost to follow-up. Conclusion These data show that ADA is effective in achieving laboratory and clinical remission in PIBD patients. Maintenance of trough levels may sometimes requite weekly administration of ADA. Loss of response may occur. Adverse reactions were minimal.

Bleeding Outcomes in Patients with Gastrointestinal Malignancies Treated with Distally Absorbed Versus Proximally Absorbed Direct Oral Anticoagulants

Introduction: Randomized trials comparing direct oral anticoagulants (DOACs) to low molecular weight heparin demonstrated higher rates of bleeding associated with DOACs, especially in patients with gastrointestinal (GI) malignancies. DOACs differ in location of absorption with apixaban predominately absorbed in the distal small bowel and proximal colon and edoxaban, rivaroxaban and dabigatran absorbed in the proximal GI tract (e.g. stomach and proximal small intestine). No comparative data is available for the DOACs in treatment of cancer-associated thrombosis (CAT). Given the differences in location of absorption, we aimed to assess the association of bleeding in patients with GI malignancy and CAT on apixaban versus those treated with proximally absorbed DOACs (dabigatran, edoxaban, or rivaroxaban).Methods: Using a nationwide cohort of Veterans, we identified patients with active GI malignancy between 2012 and 2018. Using a previously validated algorithm (91% positive predictive value), we identified patients with newly diagnosed VTE. A VTE was considered to occur in the setting of active cancer if the diagnosis occurred (1) within 3 months before cancer diagnosis, (2) within 6 months after cancer diagnosis, or (3) any time after diagnosis of metastatic cancer. We limited the cohort to patients who received at least a 30-day prescription for anticoagulant therapy with apixaban, dabigatran, edoxaban or rivaroxaban. Patients with a prescription for any anticoagulant therapy within 6 months before VTE diagnosis were excluded. We retrospectively followed patients to 30-days after the last DOAC prescription or to death, whichever came first. The primary outcome of interest was clinically significant bleeding while on DOAC therapy. We defined clinically significant bleeding as the presence of an ICD-9 or ICD-10 code for bleeding in any position for an inpatient admission with 3 exceptions: microscopic hematuria, bleeding related to major trauma and metromenorrhgia. We assessed the association between DOAC use and bleeding as a time-to-event outcome while adjusting for the competing risk of non-bleeding related death through the methods of Fine and Gray.Results: Between 2012 and 2018, a total of 215 patients with GI malignancies received a DOAC for treatment of CAT. Eighty-six patients received apixaban and the remaining 129 received a proximally absorbed DOAC with the majority receiving rivaroxaban (80%). Baseline demographics by anticoagulant therapy are listed in Table 1. None of the clinical variables assessed were significantly different between patients on apixaban versus a proximally absorbed DOAC, including variables associated with risk of anticoagulant-related bleeding.Of the 215 patients included, 73% were diagnosed with a distal GI malignancy (colon or lower). During the follow-up period, 43 of 215 patients (20%) experienced a clinically significant bleeding event, 22.1% of patients on apixaban and 18.6% of patients on a proximally absorbed DOAC. Of the 43 bleeding events, 30 were bleeding from the GI tract. In patients on apixaban versus a proximally absorbed DOAC, there was no significant difference in the risk of clinically significant bleeding (hazard ratio (HR) 1.24; 95% confidence interval (CI): 0.67 - 2.21). Similarly, there was no significant difference in the risk of bleeding from the GI tract in patients on apixaban versus a proximally absorbed DOAC (HR 0.90; 95% CI: 0.43 - 1.89).Conclusion: In this study of 215 patients with GI malignancy, we found no significant difference in the risk of bleeding between patients treated with apixaban versus those treated with a proximally absorbed DOAC. The rate of clinically significant bleeding was high (20%) while on DOAC therapy. There is a continued need for future prospective studies evaluating antithrombotic therapy in patients with GI malignancies and CAT. [Display omitted] DisclosuresSanfilippo: AstraZeneca: Research Funding; Atellas Pharma Global: Research Funding. Wang: Servier: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding.

Colonic Volvulus in Children: Surgical Management of a Challenging Condition.

Colonic volvulus (CV) is a rare but potentially life-threatening condition with unclear etiopathogenesis. To date, less than 80 pediatric cases have been described. Hirschsprung’s disease (HD) is associated with CV in 17% of cases, representing a significant risk factor. Non-HD CV is an even more complex entity. The aim of this study is to describe a series of patients with CV to accentuate some peculiar aspects of this disease. We performed a retrospective study (period: 2012–2021) collecting information of patients with CV. Data analyzed included: demographics, medical history, presenting symptoms and radiological and surgical details. Eleven patients (12.5 ± 2.8 years; 7F/4M) had CV (eight sigmoid, two transverse colon, one total colon). Five patients had associated anomalies and three had HD. A two-step approach with volvulus endoscopic/radiological detorsion followed by intestinal resection was attempted in eight cases (one endoscopic approach failed). Three patients required surgery at admission. At follow-up, two patients developed recurrent intestinal obstruction, one of whom also had anastomotic stenosis. Colonic volvulus is a challenging condition that requires prompt patient care. A missed diagnosis could lead to severe complications. The evaluation of the patient should include a careful histological examination (searching for HD and alpha-actin deficiency), immunologic and metabolic screening, neurological tests and detection of chronic intestinal pseudo-obstruction (CIPO). Lifelong follow-up is mandatory for the early recognition and treatment of progressive diseases involving the proximal gastrointestinal tract.

Transplastron Enterocentesis to Manage Buoyancy Disorder in an Adult Loggerhead Sea Turtle (Caretta caretta)

Buoyancy disorder in sea turtles is a common condition that contributes to increased morbidity and mortality in the wild and because of this, is often encountered in rehabilitation facilities. The pathological gas accumulation that is a sequelae of this disorder can create challenges in treatment of this disease, especially when concurrent systemic disease is present. These challenges increase with patient size, as anatomy and location of pathology makes gas evacuation more difficult utilizing conventional methods when medical therapy alone is unsuccessful. This report discusses a novel technique utilizing ultrasonic-guided transplastron enterocentesis of the proximal gastrointestinal tract in an adult loggerhead sea turtle ( Caretta caretta ) with suspected intestinal obstruction. The sea turtle presented with positive buoyancy and routine workup revealed gas accumulation in the gastrointestinal tract, as well as concurrent pneumonia. Medical therapy alone did not diminish the positive buoyancy or gastrointestinal distension. Ultrasonic-guided transplastron enterocentesis was performed via the connective tissue lateral to the 3rd inframarginal scute while the turtle was positioned with its left side raised, allowing any gas-filled intestine to be positioned laterally. Approximately 10.3 L of gas were evacuated from the proximal gastrointestinal lumen and within 15 mins, the turtle was neutrally buoyant. It continued to exhibit normal surfacing, diving, and resting behavior. The turtle was released 111 days after enterocentesis in order to allow treatment of the concurrent pneumonia. The technique discussed in this report has implications for improving treatment of buoyancy disorder in large adult sea turtles and increasing likelihood of release.

Effect of an In Vitro Proximal Gastrointestinal Tract on Viability of Commercially Available Equine Probiotics

Probiotics, by definition, are live micro-organisms and should remain viable when they reach the intended site of action which is typically the cecum and/or colon. In humans, probiotics often need enteric protection to survive transit through the proximal gastrointestinal (GI) tract. Typically, equine probiotics do not advertise enteric protection and to the author's knowledge the viability of equine probiotics after exposure to the proximal GI tract has not been evaluated. The objective of this study was to evaluate the effect of an in vitro simulation of the equine proximal GI tract on probiotic viability. We hypothesized that the simulated proximal GI tract would adversely effect microbial viability and that the adverse effects would be partially ameliorated by increasing the gastric pH to 4. A total of 11 products were evaluated of which six had at least one micro-organism that was adversely effected by exposure to the proximal GI tract and four of which had at least one micro-organism that was adversely affected when the gastric pH was increased to 4.0. Results from this study indicate that some micro-organisms in equine probiotics do not appear to be adversely affected by exposure to the equine proximal GI tract.

Diagnosis and prognosis of epidemic inflammatory bowel disease under convolutional neural network algorithm and nonlinear equation model

this study was to analyze the effect of optimization algorithm based on convolutional neural network (CNN) on the image quality of magnetic resonance enterography (MRE) for small intestine, and explore the diagnosis and prognosis of epidemic inflammation bowel disease (IBD) with the MRE under the optimization algorithm and nonlinear equation model. The residual network structure (RNS) was incorporated into the CNN algorithm to establish an optimization algorithm, which was compared with other algorithms in terms of the peak signal to noise ratio (PSNR), structural similarity (SSIM), and high frequency error norm (HFEN). 392 patients suspected as IBD in the Gastroenterology Department were selected as the research objects. They were divided into a Crohn’s disease (CD) group (243 cases), an ulcerative colitis (UC) group (78 cases), an indeterminate enteritis (IDE) group (49 cases), and a non-IBD group (22 cases). The intestinal manifestations, clinical manifestations, MRE imaging manifestations, and gastrointestinal lesion distribution of patients in different groups were compared to analyze the diagnostic value of MRE for epidemic IBD. It was found that the optimized CNN algorithm showed better PSNR, SSIM, and HFEN than other algorithms. The percentages of patients with diarrhea in the CD group and UC group were 67.90% and 100%, respectively. The pediatric ulcerative colitis activity index (PUCAI) score of patients in the UC group showed that the number of patients with mild activity was at most 40 (51.28%). The Crohn’s disease activity index (CDAI) score showed that there were 197 of patients in the CD group (81.07%) with severe activity. In the CD group, the numbers of patients suffered with lesions in proximal colon, terminal ileum, and upper gastrointestinal tract were 125 (51.44%), 127 (52.26%), and 132 (54.32%), respectively. In the UC group, there were 32 (41.03%), 51 (65.38%), and 25 (32.05%) patients with lesions in the rectum, distal colon, and proximal colon, respectively. The diagnostic sensitivity and specificity of MRE for epidemic IBD was 95.18% and 46.7%, respectively. It indicated that the image quality of the optimization algorithm based on the CNN algorithm was improved greatly. Under the nonlinear equation model, the image characteristics of MRE in patients with different diseases were various, and the diseased parts were greatly different. MRE showed high sensitivity and specificity in the diagnosis of epidemic IBD. This study could provide a reference basis for the clinical diagnosis and prognosis of patients with epidemic IBD.

The Impact of Vitamin D on Response to Anti-tumor Necrosis Factor-α Therapy in Children With Inflammatory Bowel Disease.

Experimental studies have shown that vitamin D has an immunomodulatory effect on the innate and adaptive immune systems. Associations between vitamin D deficiency and development or progression of inflammatory bowel diseases (IBDs) are reported, but a cause-and-effect relationship between pretreatment 25 hydroxyvitamin D [25(OH)D] levels and response to anti-tumor necrosis factor-α (anti-TNF) therapy is not established. This retrospective study evaluated pediatric IBD patients who had 25(OH)D levels drawn within 3 months of initiating infliximab and/or adalimumab treatment. Demographic features, Paris classification, baseline 25(OH)D levels, disease activity, and laboratory results before and after 3 months of anti-TNF therapy were collected. The interaction between vitamin D insufficiency at induction and lack of response to anti-TNF therapy at 3 months was determined. Of the 383 patients, 76 met inclusion criteria. Sixty-five patients (85.5%) had Crohn disease (CD) and 11 (14.5%) had ulcerative colitis. Seven patients had 25(OH)D levels obtained during both infliximab and adalimumab induction; hence 83 subjects were evaluated (infliximab: 70 patients, adalimumab: 13 patients). 25(OH)D <30 ng/mL was found in 55 of 83 (66.3%) subjects. There were no differences in gender, IBD type, disease activity scores between vitamin D-sufficient and vitamin D-insufficient groups. In CD, proximal gastrointestinal tract inflammation was associated with vitamin D insufficiency (P = 0.019), but other Paris classification parameters and laboratory results were similar in 2 groups. Early termination of anti-TNF therapy was significantly higher in patients who had vitamin D insufficiency (14.5% vs 0%, P = 0.034). Vitamin D insufficiency before anti-TNF treatment may result in poor response to induction therapy.

Tropism of Severe Acute Respiratory Syndrome Coronavirus 2 for Barrett’s Esophagus May Increase Susceptibility to Developing Coronavirus Disease 2019

Tropism of Severe Acute Respiratory Syndrome Coronavirus 2 for Barrett’s Esophagus May Increase Susceptibility to Developing Coronavirus Disease 2019