Non-steroidal Anti-inflammatory Enteropathy Research Articles

A dual role of lysophosphatidic acid type 2 receptor (LPAR2) in nonsteroidal anti-inflammatory drug-induced mouse enteropathy

Lysophosphatidic acid (LPA) is a bioactive phospholipid mediator that has been found to ameliorate nonsteroidal anti-inflammatory drug (NSAID)-induced gastric injury by acting on lysophosphatidic acid type 2 receptor (LPAR2). In this study, we investigated whether LPAR2 signaling was implicated in the development of NSAID-induced small intestinal injury (enteropathy), another major complication of NSAID use. Wild-type (WT) and Lpar2 deficient (Lpar2−/−) mice were treated with a single, large dose (20 or 30 mg/kg, i.g.) of indomethacin (IND). The mice were euthanized at 6 or 24 h after IND treatment. We showed that IND-induced mucosal enteropathy and neutrophil recruitment occurred much earlier (at 6 h after IND treatment) in Lpar2−/− mice compared to WT mice, but the tissue levels of inflammatory mediators (IL-1β, TNF-α, inducible COX-2, CAMP) remained at much lower levels. Administration of a selective LPAR2 agonist DBIBB (1, 10 mg/kg, i.g., twice at 24 h and 30 min before IND treatment) dose-dependently reduced mucosal injury and neutrophil activation in enteropathy, but it also enhanced IND-induced elevation of several proinflammatory chemokines and cytokines. By assessing caspase-3 activation, we found significantly increased intestinal apoptosis in IND-treated Lpar2−/− mice, but it was attenuated after DBIBB administration, especially in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Finally, we showed that IND treatment reduced the plasma activity and expression of autotaxin (ATX), the main LPA-producing enzyme, and also reduced the intestinal expression of Lpar2 mRNA, which preceded the development of mucosal damage. We conclude that LPAR2 has a dual role in NSAID enteropathy, as it contributes to the maintenance of mucosal integrity after NSAID exposure, but also orchestrates the inflammatory responses associated with ulceration. Our study suggests that IND-induced inhibition of the ATX-LPAR2 axis is an early event in the pathogenesis of enteropathy.

Protective effects of Saccharomyces boulardii CNCM I-745 in an experimental model of NSAID-induced enteropathy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce a broad spectrum of gastro-intestinal adverse effects, including ulceration and bleeding. The pathophysiology of NSAID enteropathy is complex and incompletely understood, but some evidence showed that NSAIDs impair the intestinal barrier and cause a gut dysbiosis. Identifying new treatments aiming to reverse or attenuate NSAID-induced adverse effects would have a significant impact on a high number of patients. The aim of this work is to assess the effects of the probiotic yeast Saccharomyces boulardii CNCM I-745 (Sb) on a model of NSAID-induced enteropathy. Four groups of mice were tested: Control, Indomethacin, Sb, and Sb + Indomethacin. A clinical score was evaluated throughout the experiment. Faecal calprotectin, microbiota and haemoglobin analyses were performed. At the end of the treatments, the small intestine, colon, and caecum lengths, and intestinal permeability were measured. Sections of ileum and jejunum were observed to assess a histological score and ileal cytokines were measured by immunoassay. Indomethacin-treated animals showed an increase in their clinical scores, reflecting a worsening of their general state. Mice co-treated with Sb and indomethacin displayed an improvement of their clinical score in comparison with mice treated with indomethacin alone. Sb prevented the indomethacin-induced shortening of the small intestine and caecum, and significantly attenuated the severity of intestinal lesions. Sb also prevented the increase in faecal calprotectin, reduced faecal haemoglobin, and prevented the increase of intestinal permeability in mice treated with indomethacin. Sb also counteracted the increase of faecal bacteria associated with the pathogenesis of NSAID-enteropathy. In conclusion, our results show a protective effect of Sb in a model of indomethacin-induced enteropathy. Sb improved the intestinal barrier function and exerted a positive action on gut microbiota composition.

Lafutidine Ameliorates Indomethacin-Induced Small Intestinal Damage in Rats by Modifying the Intestinal Mucosal Barrier, Inflammation, and Microbiota

Introduction: Nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage is a serious and escalating clinical problem without effective treatment. Lafutidine (LAF) is a novel histamine H2 receptor antagonist with a mucosal protective action. This study aimed to investigate the protective effect of LAF on indomethacin (IND)-induced enteropathy in rats. Methods: Rats were treated with LAF for 10 days with concomitant IND treatment on the final 5 days. Changes in metabolism and hematological and biochemical parameters were measured, and intestinal damage was blindly scored. Intestinal mucosal tissue and luminal contents were collected for transcriptome and microbiota sequencing. Intestinal inflammation and barrier function were also evaluated. Results: LAF treatment prevented anorexia and weight loss in rats and ameliorated reductions in hemoglobin, hematocrit, total protein, and albumin levels. LAF reduced the severity of IND-induced intestinal damage including macroscopic and histopathological damage score. Transcriptome sequencing results indicated that LAF might have positive effects on intestinal inflammation and the intestinal mucosal barrier. Further research revealed that LAF decreased neutrophil infiltration, and IL-1β and TNF-α expression in intestinal tissue. Besides, the treatment increased mucus secretion, MUC2, Occludin, and ZO-1 expression, and decreased serum D-lactate levels. LAF treatment also ameliorates microbial dysbiosis in small intestine induced by IND and increased the abundance of Lactobacillus acidophilus. Conclusion: LAF may protect against NSAID enteropathy via enhancing the intestinal mucosal barrier, inhibiting inflammation, and regulating microbiota.

Indication, Location of the Lesion, Diagnostic Yield, and Therapeutic Yield of Double-Balloon Enteroscopy: Seventeen Years of Experience.

Double-balloon enteroscopy (DBE) has become one of the standard methods in the diagnosis and treatment of small bowel (SB) disease. However, previous studies for DBE have limitations due to heterogeneity of indications and operators. The aim was to investigate the indication, location of the lesion, diagnostic yield, and therapeutic yield of DBE based on long-term data from a single operator. A retrospective study was performed by reviewing medical records of subjects who had received DBE at our unit in the past 17 years. Overall diagnostic yield was 78.7% (210/267). The diagnostic yield for obscure gastrointestinal bleeding (OGIB) was 68.3% (84/123). The diagnostic yield for OGIB was significantly lower (p < 0.001) than that for other indications. Therapeutic yield was 24.7% (66/267). Complications occurred in 7 (2.6%). Crohn’s disease, intestinal tuberculosis, nonsteroidal anti-inflammatory drug enteropathy, and diverticular lesions were mainly found in the ileum. Vascular lesions, non-specific inflammation, and neoplastic lesions were found more frequently in the jejunum. DBE is an excellent and safe endoscopic method for the diagnosis and treatment of SB lesions. DBE has a lower diagnostic rate for OGIB than for other indications. The location where a lesion is commonly found depends on the type of the lesion.

Comprehensive Evaluation and Unique Morphologic Features of Nonsteroidal Anti-Inflammatory Drug (NSAID) Enteropathy in the Terminal Ileum.

Differentiating NSAID enteropathy from Crohn disease can be challenging on terminal ileum biopsy. It is important to distinguish these two entities for management. In this study, clinical, radiographic, endoscopic, and histologic features of 30 patients diagnosed with NSAID enteropathy and 30 patients diagnosed with Crohn disease on terminal ileal biopsy were compared. None of the patients in the NSAID cohort demonstrated significant changes on imaging performed prior to biopsy. Depending on disease severity, patients with Crohn disease showed imaging findings ranging from minimal changes to significant bowel wall and/or luminal changes. Endoscopically, erythema, erosions, and/or ulcers in the terminal ileum were observed in a majority of NSAID cases. Patients with active Crohn disease were noted to have erythema, ulcers, strictures, and/or visible inflammation throughout the distal ileum and colon. Histologically, at least 80% of cases in each cohort showed ulceration/erosion and cryptitis/crypt abscesses. The Crohn disease cohort had significantly higher degree of lymphoplasmacytic inflammation in the lamina propria compared to the NSAID cohort. In contrast, a significantly higher percentage of the NSAID cohort had gland/crypt atrophy. A decrease in number of Paneth cells was found in the NSAID cohort. Decreased lamina propria lymphoplasmacytic inflammation was the most specific and the presence of gland atrophy the most sensitive feature favoring NSAID enteropathy. In summary, the combination of gland/crypt/Paneth cell atrophy with decreased lamina propria lymphoplasmacytic inflammation can aid in differentiating NSAID enteropathy from Crohn disease in terminal ileal biopsies; however, correlation with clinical, radiographic, and endoscopic findings is still required.

Gut Microbiota in NSAID Enteropathy: New Insights From Inside.

As a class of the commonly used drugs in clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) can cause a series of adverse events including gastrointestinal injuries. Besides upper gastrointestinal injuries, NSAID enteropathy also attracts attention with the introduction of capsule endoscopy and double balloon enteroscopy. However, the pathogenesis of NSAID enteropathy remains to be entirely clarified. Growing evidence from basic and clinical studies presents that gut microbiota is a critical factor in NSAID enteropathy progress. We have reviewed the recent data about the interplay between gut microbiota dysbiosis and NSAID enteropathy. The chronic medication of NSAIDs could change the composition of the intestinal bacteria and aggravate bile acids cytotoxicity. Meanwhile, NSAIDs impair the intestinal barrier by inhibiting cyclooxygenase and destroying mitochondria. Subsequently, intestinal bacteria translocate into the mucosa, and then lipopolysaccharide released from gut microbiota combines to Toll-like receptor 4 and induce excessive production of nitric oxide and pro-inflammatory cytokines. Intestinal injuries present in the condition of intestinal inflammation and oxidative stress. In this paper, we also have reviewed the possible strategies of regulating gut microbiota for the management of NSAID enteropathy, including antibiotics, probiotics, prebiotics, mucosal protective agents, and fecal microbiota transplant, and we emphasized the adverse effects of proton pump inhibitors on NSAID enteropathy. Therefore, this review will provide new insights into a better understanding of gut microbiota in NSAID enteropathy.

Colostrum Therapy for Human Gastrointestinal Health and Disease.

There is increasing awareness that a broad range of gastrointestinal diseases, and some systemic diseases, are characterized by failure of the mucosal barrier. Bovine colostrum is a complex biological fluid replete with growth factors, nutrients, hormones, and paracrine factors which have a range of properties likely to contribute to mucosal healing in a wide range of infective, inflammatory, and injury conditions. In this review, we describe the anatomy and physiology of the intestinal barrier and how it may fail. We survey selected diseases in which disordered barrier function contributes to disease pathogenesis or progression, and review the evidence for or against efficacy of bovine colostrum in management. These disorders include enteropathy due to non-steroidal anti-inflammatory drugs (NSAIDs), inflammatory bowel disease (IBD), necrotizing enterocolitis, infectious diarrhea, intestinal failure, and damage due to cancer therapy. In animal models, bovine colostrum benefits NSAID enteropathy, IBD, and intestinal failure. In human trials, there is substantial evidence of efficacy of bovine colostrum in inflammatory bowel disease and in infectious diarrhea. Given the robust scientific rationale for using bovine colostrum as a promoter of mucosal healing, further work is needed to define its role in therapy.

SHORT- AND LONG-TERM EFFECTS OF NSAIDS ON THE GASTROINTESTINAL MUCOSA: COMPLEX ANALYSIS OF BENEFITS AND COMPLICATIONS PREVENTION

The aim: To analyse data from recent studies, dedicated to the use of non-steroidal anti-inflammatory drugs (NSAIDs); to evaluate the best clinical practice in the use of NSAIDs in order to prevent side effects (SEs) in different clinical scenarios; to optimise treatment of patients at risk of NSAIDs-related SEs. Materials and methods: A comprehensive bibliographic search was performed using the keywords "NSAIDs", "NSAID gastropathy", "NSAID enteropathy", "complications of NSAID therapy", "cardiovascular disease", "cardiovascular risk" in the PubMed, Web of Science, Cochrane Library, Google Academy databases. Conclusions: NSAID-induced gastrointestinal lesions are а relevant problem of internal medicine, this is due to the fact that the pathogenic mechanisms of this process are still unclear. All the gastrointestinal tract (GIT) related risk factors(RFs) for gastro- and enterocolonopathies associated with the use of NSAIDs should be taken into consideration by physicians of all specialties. The examination and diagnostic of the GIT should be performed regularly to prevent complications. Uncontrolled, long-lasting, unprescribed NSAID usage should draw the attention of doctors, especially in patients with comorbid states.

Role of proteinase-activated receptors 1 and 2 in nonsteroidal anti-inflammatory drug enteropathy.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can promote lower gastrointestinal detrimental effects. Proteinase-activated receptors 1 (PAR1) and PAR2 are involved in the pathophysiology of several digestive disorders. This study examines the contribution of PAR1 and PAR2 in NSAID-induced small intestinal injury, and to investigate the underlying mechanisms. Male Wistar rats (40weeks old) were treated with indomethacin (1.5mg/kg BID) for 14days. Subgroups of animals were treated intraperitoneally with TFFLR-NH2 (PAR1 agonist), AC55541 (PAR2 agonist), SCH79797 (PAR1 antagonist) or ENMD-1068 (PAR2 antagonist). After treatments, blood and feces were collected for the assessment of hemoglobin and calprotectin, respectively. The ileum was processed for the evaluation of myeloperoxidase (MPO), malondialdehyde (MDA), and the protein expression of occludin and activated caspase-3. Indomethacin elicited a significant intestinal damage, associated with a decrease in blood hemoglobin and an increase in tissue MPO, MDA and fecal calprotectin. In this setting, either the PAR1 agonist or PAR2 antagonist counteracted these changes, with the exception of MDA, which was unaffected. By contrast, the PAR1 antagonist or PAR2 agonist did not exert any effect on all the parameters. Indomethacin also decreased occludin and increased activated caspase-3 expression in ileal tissues. The PAR1 agonist or PAR2 antagonist prevented the reduced occludin expression, while the PAR2 antagonist also decreased the levels of activated caspase-3. PAR2 is involved in the pathogenesis of indomethacin enteropathy, through pro-inflammatory mechanisms and an impairment of the intestinal epithelial barrier. PAR1 activation and PAR2 inhibition could represent suitable strategies for the prevention of NSAID enteropathy.

Modern opportunities for treatment and prevention of NSAID-induced enteropathies

Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently actively used in real clinical practice and everyday life with a wide range of pathological conditions and diseases, and are part of the medicinal arsenal of doctors of various specialties. Along with high pharmacotherapeutic efficacy according to the main indications, a whole range of various complications is associated with the use of NSAIDs. Of particular relevance is the negative specific effect of NSAIDs on the mucous membrane of the gastrointestinal tract. The problem of NSAID gastropathy is widely discussed in the literature, which is largely due to the possibilities of its prevention and treatment using proton pump inhibitors. For a long time, much less attention was paid to the issues of NSAID-dependent bowel damage, which may be associated with less instrumental diagnostic capabilities of these lesions and the lack of effective means for their prevention and treatment. The review presented addresses the pathogenesis, clinical features and diagnosis of NSAID enteropathy. Proton pump inhibitors effectively prevent the development of dyspepsia, erosion and ulcers, as well as gastrointestinal bleeding when taking NSAIDs at the level of the upper gastrointestinal tract, but they are ineffective in preventing and treating NSAID enteropathy. A new approach is the use of rebamipide, which has proven its clinical effectiveness in the prevention of NSAID-mediated Lesions in the upper and Lower gastrointestinal tract. Currently, rebamipid is included in the recommendations of the leading specialized communities in Russia and is recommended not only for the prevention and treatment of NSAIDs induced gastrointestinal lesions, but also as part of the complex therapy of peptic ulcer and anti-heLicobacter therapy. The review reviewed studies showing the efficacy and safety of rebamipide for the treatment and prevention of NSAID enteropathy.

Glycomacropeptide Ameliorates Indomethacin-Induced Enteropathy in Rats by Modifying Intestinal Inflammation and Oxidative Stress.

Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is considered a serious and increasing clinical problem without available treatment. Glycomacropeptide (GMP) is a 64-amino acid peptide derived from milk κ-casein with numerous biological activities. The aim of this study was to investigate the protective effect of GMP on NSAID enteropathy in rats. Enteropathy was induced by seven days oral indomethacin administration. Rats were orally GMP treated from seven days previous and during the establishment of the enteropathy model. Changes in metabolism, hematological and biochemical blood alterations, intestinal inflammation and oxidative damage were analyzed. Integrity barrier markers, macroscopic intestinal damage and survival rate were also evaluated. GMP treatment prevented anorexia and weight loss in animals. Furthermore, prophylaxis with GMP ameliorated the decline in hemoglobin, hematocrit, albumin and total protein levels. The treatment had no therapeutic efficacy on the decrease of occludin and mucin (MUC)-2 expression in intestinal tissue. However, GMP markedly decreased neutrophil infiltration, and CXCL1, interleukin-1β and inducible nitric oxide synthase expression. Nitric oxide production and lipid hydroperoxide level in the small intestine were also diminished. These beneficial effects were mirrored by preventing ulcer development and increasing animal survival. These results suggest that GMP may protect against NSAID enteropathy through anti-inflammatory and antioxidant properties.

NSAID enteropathy

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used drugs in the world, and their side effects are very high. First of all, these are NSAID gastropathy, but in the long term, 5070% of NSAIDs cause damage to the small intestine (NSAID enteropathy), sometimes with serious consequences. To date, no drugs have been proposed with proven effectiveness to prevent this side effect. Apparently, this is not due to the fully clarified mechanism of pathogenesis. The most promising is the hypothesis of the participation of individual representatives of microflora in the development of enteropathy. Therefore, modulating the intestinal flora with the help of probiotics can be the basic therapeutic strategy for the prevention and treatment of such damage.

Small intestinal damage associated with the use of nonsteroidal anti-inflammatory drugs

The use of nonsteroidal anti-inflammatory drugs (NSAID), even if short-term, may be associated to small intestinal complications, such as erosions, ulcers and chronic mucosal inflammation. Video capsule endoscopy allows for identification of such lesions in 20 to 55% of the patients who have taken nonselective NSAID for 2 to 4 weeks. The pathophysiology of NSAID-induced enteropathy is related to a reduced reparative potential of the mucosa and abnormalities of the microbial balance in the small intestine. In real world practice, NSAID enteropathy is commonly asymptomatic, and its manifestations, such as bleeding, perforation and ileus, are quite rare (about 0.3 episodes per 100 patient-years). The main manifestation of NSAID enteropathy is chronic iron deficient anemia. The use of rebamipide, sulfasalazine, mesalazine, and rifaximin has been discussed in the treatment of NSAID enteropathy, whereas its prevention implies preferential administration of coxibs, the use of rebamipide and probiotics.

Drug-Induced Small Bowel Injury: a Challenging and Often Forgotten Clinical Condition.

Most drugs are given by the oral route. Oral intake allows direct contact between the drug and the entire GI tract mucosa, exposing it to potential topical damage until absorption. Medication-induced GI symptoms and lesions are therefore commonly encountered in clinical practice. This review will examine the most common drugs or classes of drugs affecting small bowel function and/or structure. Since non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medicines, NSAID enteropathy is highly prevalent and brings about considerable morbidity. Antimicrobials and proton-pump inhibitors profoundly modify intestinal microbiota, affecting gut sensory and motor functions, while other drugs (like iron and gold derivatives) impair intestinal permeability. Olmesartan (and likely ACE inhibitors) induce villous atrophy and consequent malabsorption. Mycophenolate mofetil, cancer chemotherapeutic agents, and immune checkpoint inhibitors cause intestinal inflammation, abdominal pain, and diarrhea. Potassium chloride supplements may induce small bowel ulceration, stenosis, and perforation while the cotraceptive pill and anticoagulants are associated with intestinal ischemia and spontaneous intramural hematoma, respectively. In clinical practice, a deep knowledge of clinical pharmacology and toxicology and a high degree of suspicion of drug-related adverse events are mandatory. Only then, the practicing physician will be able to diagnose medication-induced small bowel lesions correctly and will implement the best strategies to treat them.

NSAIDs disrupt intestinal homeostasis by suppressing macroautophagy in intestinal epithelial cells

Small intestinal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs) remains an under-recognized clinical disorder. The incomplete understanding of the pathophysiology has hampered the development of prevention and treatment strategies leading to the high morbidity and mortality rates. NSAIDs are known to modulate macroautophagy, a process indispensable for intestinal homeostasis. Whether NSAIDs stimulate or repress macroautophagy and how this correlates with the clinical manifestations of NSAID enteropathy, however, remains unknown. The objectives of this study were to determine whether NSAIDs impaired macroautophagy and how this affects macroautophagy-regulated intestinal epithelial cell (IEC) processes essential for intestinal homeostasis (i.e., clearance of invading pathogens, secretion and composition of mucus building blocks, and inflammatory response). We show that NSAID treatment of IECs inhibits macroautophagy in vitro and in vivo. This inhibition was likely attributed to a reduction in the area and/or distribution of lysosomes available for degradation of macroautophagy-targeted cargo. Importantly, IEC regulatory processes necessary for intestinal homeostasis and dependent on macroautophagy were dysfunctional in the presence of NSAIDs. Since macroautophagy is essential for gastrointestinal health, NSAID-induced inhibition of macroautophagy might contribute to the severity of intestinal injury by compromising the integrity of the mucosal barrier, preventing the clearance of invading microbes, and exacerbating the inflammatory response.

Activation of intestinal GR-FXR and PPARα-UGT signaling exacerbates ibuprofen-induced enteropathy in mice.

Nonsteroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal injury (enteropathy) occurs in about two-thirds of regular NSAID users. To date, there is no proven-effective treatment for NSAID enteropathy, and its underlying mechanism remains obscure. The present study showed that glucocorticoids are an important determinant of NSAID enteropathy. High dose dexamethasone (DEX, 75mg/kg) markedly exacerbated the acute toxicity of ibuprofen (IBU, 200mg/kg) in the small intestine of mice, which was not due to the pregnane-X-receptor pathway. Instead, glucocorticoid receptor (GR) mediated the effect of DEX (5mg/kg) on both the acute (200mg/kg) and 7-day repeated-dose (50mg/kg) toxicity of IBU in the small intestine. Combined treatment of DEX (5mg/kg) and IBU (50mg/kg) synergistically repressed the intestinal farnesoid X receptor (FXR)-cystathionine-γ-lyase signaling, which was accompanied with an elevation in the biliary excretion of bile acids, especially the FXR antagonist tauro-β-muricholic acid. DEX (5mg/kg) also activated intestinal peroxisome proliferator-activated receptor α (PPARα)-UDP-glucuronosyltransferase (UGT) pathway, which increased the formation and enterohepatic circulation of IBU-acyl glucuronide. Furthermore, DEX (5mg/kg) and IBU (50mg/kg) altered the intestinal microbial composition, characterized with a marked decrease in Actinobacteria. To conclude, the present study for the first time suggests that glucocorticoids play vital roles in control of IBU enteropathy via intestinal GR-FXR and PPARα-UGT signaling.

Characteristics of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)-Induced Small Bowel Injury Identified by Single-Balloon Endoscopy or Capsule Endoscopy.

BackgroundThe special features of nonsteroidal anti-inflammatory drugs (NSAIDs) enteropathy were partially clarified by single-balloon endoscopy(SBE).We aimed to investigate the characteristics of NSAIDs injuries that were differ from other ulcer diseases and efficacy of SBE compared with capsule endoscopy(CE).Material/Methods1,644 symptomatic patients (221 patients taking NSAIDs) hospitalized between January 2006 and March 2016 were recruited and underwent SBE and/or CE.ResultsNSAIDs damages were identified in 110 patients (49.77%). The special features of NSAIDs lesions included: variform, superficial, multiple and irregular arrangement; <1 cm in diameter (67.27%); the location in jejunum and ileum was similar; ileocecal valve was rarely influenced (20.91%). The specificity and positive predictive value of SBE for diagnosing NSAIDs breaks were higher than CE (95.74% vs. 80.00%; 95.45% vs. 81.63%, p<0.05). There were no differences in the detection rate and the diagnostic accuracy rate of small bowel diseases between SBE and CE in the NSAIDs group (69.4% vs. 66.3% and 83.58% vs. 80.65%, p>0.05 respectively). The consistency in diagnosing NSAIDs breaks for the 2 methods was 82.61%. More tiny lesions at the distal ileum were detected by SBE. Four patients misdiagnosed by CE got accurate diagnose through biopsy by SBE. Three patients with active bleeding caused by NSAIDs-induced ulcers underwent hemostasis successfully by SBE.ConclusionsNSAIDs injuries might be distinguished from other diseases by endoscopic features and biopsy through SBE, which appeared to be an effective method for diagnosis and treatment.

The non-invasive exfoliated transcriptome (exfoliome) reflects the tissue-level transcriptome in a mouse model of NSAID enteropathy

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used classes of medications in the world, yet they induce an enteropathy that is associated with high morbidity and mortality. A major limitation to better understanding the pathophysiology and diagnosis of this enteropathy is the difficulty of obtaining information about the primary site of injury, namely the distal small intestine. We investigated the utility of using mRNA from exfoliated cells in stool as a means to surveil the distal small intestine in a murine model of NSAID enteropathy. Specifically, we performed RNA-Seq on exfoliated cells found in feces and compared these data to RNA-Seq from both the small intestinal mucosa and colonic mucosa of healthy control mice or those exhibiting NSAID-induced enteropathy. Global gene expression analysis, data intersection, pathway analysis, and computational approaches including linear discriminant analysis (LDA) and sparse canonical correlation analysis (CCA) were used to assess the inter-relatedness of tissue (invasive) and stool (noninvasive) datasets. These analyses revealed that the exfoliated cell transcriptome closely mirrored the transcriptome of the small intestinal mucosa. Thus, the exfoliome may serve as a non-invasive means of detecting and monitoring NSAID enteropathy (and possibly other gastrointestinal mucosal inflammatory diseases).

Video Capsule Endoscopy and Deep Enteroscopy

Until 2001, the nonsurgical evaluation of the small intestine was largely limited to the use of radiologic imaging (e.g., small bowel follow-through or enteroclysis). With the now widespread availability of video capsule endoscopy and deep enteroscopy since 2001, we are now able to visualize the length and most of the mucosa of the small intestine and manage small bowel lesions that were previously inaccessible except by surgical intervention. This review serves as an overview for these two procedures, detailing the indications and contraindications, proper timing of the procedure, technical aspects of the devices themselves, possible complications, and outcomes. Figures show endoscopic images that demonstrate multiple angioectasias, bleeding during capsule endoscopy, active Crohn disease of the small bowel, severe mucosal scalloping, small bowel carcinoid tumor, small bowel polyp associated with Peutz-Jeghers syndrome, and nonsteroidal antiinflammatory drug enteropathy; serial x-rays of a patient with a patency capsule retained inside the small intestine; a computer image showing the distribution of small bowel tumors; and a pie chart displaying the breakdown of the distribution of benign and malignant tumors that can be found in the small intestine. Videos show multiple angioectasias, bleeding during capsule endoscopy, active Crohn disease of the small bowel, small bowel carcinoid tumor, and small bowel polyp associated with Peutz-Jeghers syndrome. This review contains 10 highly rendered figures, 5 videos, and 50 references.

Circumferential Jejunal Ulcers: An Unusual Manifestation of Nonsteroidal Anti-Inflammatory Drug Enteropathy

Circumferential Jejunal Ulcers: An Unusual Manifestation of Nonsteroidal Anti-Inflammatory Drug Enteropathy