Clinical and Experimental Gastroenterology最新文献

Background: Patients requiring hospitalization to critical care units are at a higher risk for gastrointestinal (GI) bleeding. Although severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection is predominantly a pulmonary disease, other serious manifestations including thromboembolic phenomenon are reported. Acute respiratory distress syndrome (ARDS) requiring mechanical ventilation, use of steroids and anticoagulation are all known to increase the risk of GI bleeding significantly.

Aim: To study the incidence of GI bleeding and its impact on mortality in patients admitted with SARS-CoV-2.

Methods: We retrospectively reviewed all patients admitted with SARS-CoV-2 from February 1, 2020 to April 15, 2020. We collected data including demographics, comorbid conditions, laboratory parameters, steroid and anticoagulant use. Coffee ground emesis, hematemesis, melena and hematochezia were defined as GI bleeding. All-cause mortality was reviewed for all patients included in the study. The relationship between GI bleeding and mortality was studied using logistic regression.

Results: We had a total of 1206 patients hospitalized with SARS-CoV-2 infection with an all-cause mortality of 34% (n = 411). The overall incidence of GI bleeding was 3.1% (n = 37) with no significant difference between the patients who survived versus died during hospitalization (1.3% vs 1.5%, p = 0.77). Logistic regression analysis did not identify GI bleeding as an independent predictor of mortality. Therapeutic doses of anticoagulation were administered in 13.3% (n = 161) of patients, of which 6.8% (n = 11) developed GI bleeding. Patients were more likely to develop GI bleeding with use of therapeutic doses of anticoagulation (29.7% vs 12.8%, p = 0.003), steroids (37.8% vs 18.5%, p = 0.003) and mechanical ventilation (48.6% vs 30.4%, p = 0.018).

Conclusion: Patients hospitalized with SARS-CoV-2 infection are at risk of gastrointestinal bleeding. Therapeutic doses of anticoagulation, mechanical ventilation and steroid use are significant risk factors for GI bleeding. However, GI bleeding did not significantly alter the mortality rates in SARS-CoV-2-infected patients.

Background: In the anal sphincter complex, the intersphincteric space between the internal and external sphincters is the only conventionally recognized pathway for the spread of sepsis. However, there is another unrecognized space discovered on MRI, the "outer-sphincteric space", between the external anal sphincter and its lateral fascia along which pus can spread. An abscess in the intersphincteric space is easily drained into the rectum via the transanal route and is more likely to spread into the supralevator space. Conversely, an abscess in the outer-sphincteric space is difficult to drain transanally into the rectum and is more likely to become a transsphincteric abscess/fistula.

Methods: The MRIs of anal fistula patients operated over four years on intersphincteric abscesses were analyzed. The pattern of spread into the ischiorectal fossa and/or supralevator space and ease of drainage into the rectum through the transanal route were studied.

Results: Thirty-six patients were operated on to drain their intersphincteric abscesses through the anal canal. Two distinct patterns were noted. Twenty patients had abscesses in the intersphincteric space, which were easily drained into the rectum. Of them, 6/20 had supralevator extension, while only 1/20 had spread to the ischiorectal fossa. In 16/36 patients, the abscess was in the outer-sphincteric space and could not be drained into the rectum. In 9/16 of these patients, pus spread into the ischiorectal fossa but supralevator spread did not happen in any patient.

Conclusion: Apart from the intersphincteric space, there is perhaps another unrecognized anatomical space - the outer-sphincteric space - discovered on MRI, through which pus can spread in anal fistulas or abscesses.

The hepatorenal syndrome type of acute kidney injury (HRS-AKI), formerly known as type 1 hepatorenal syndrome, is a rapidly progressing renal failure that occurs in many patients with advanced cirrhosis and ascites. Accumulating evidence has led to a recent evolution of diagnostic criteria for this serious complication of end-stage liver disease. The aim of this review is to provide an overview of disease-related characteristics and therapeutic management of patients with HRS-AKI. Relevant literature was compiled to support discussion of the pathophysiology, diagnosis, prognosis, associated conditions, prevention, treatment, and management of HRS-AKI. Onset of HRS-AKI is characterized by sudden severe renal vasoconstriction, leading to an acute reduction in glomerular filtration rate and rapid, potentially life-threatening, renal deterioration. Although our understanding of disease pathophysiology continues to evolve, etiology of HRS-AKI likely involves systemic hemodynamic changes caused by liver disease, inflammation, and damage to renal parenchyma. There is currently no gold standard for diagnosis, which typically involves a clinical workup, abdominal imaging, and laboratory assessments. The current consensus definition of HRS-AKI includes proposed diagnostic criteria based on changes in serum creatinine levels tailored for high sensitivity, and rapid detection to accelerate diagnosis and treatment initiation. The only potential cure for HRS-AKI is liver transplantation; however, vasoconstrictive agents and other supportive measures are used as needed to help maintain survival for patients who are awaiting or are ineligible for transplantation. The severity of HRS-AKI, complex pathology, limited treatment options, and range of associated conditions pose significant challenges for both patients and care providers.

Overview: The purpose of this review is to introduce options for dietary therapies and supplements for the treatment of irritable bowel syndrome (IBS). IBS is a common condition with heterogeneity in pathogenesis and clinical presentation. Current treatment options are targeted at symptom relief with medications. Patients naturally pursue dietary modifications when dealing with symptoms. Dietary therapy for IBS has been poorly studied in the past; however, newer evidence suggests the use of certain diets, such as the low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, as an intervention in patients with IBS for symptom improvement. Exclusion strategies are frequently tried, such as gluten restriction or lactose avoidance, but lack quality evidence behind their use. Additionally, supplements, such as fiber, probiotics, and peppermint oil, have also been used for IBS with more recent data suggesting the use of these supplements with specific caveats.

Purpose: A novel experimental model based on a 3D reconstructed human oesophageal epithelium model (HO2E) has been developed to investigate the structural and functional changes of the oesophageal epithelium following exposure to a solution of HCl 0.1 N (pH = 1.2) mirroring GERD microenvironment condition.

Methods: The barrier structure modification after the exposure to the acid solution on HO2E tissues was investigated immediately after damage induction and after 1 hour post incubation and compared to HO2E tissues exposed to phosphate buffered saline solution. Immunofluorescence (IF) was applied to quantify the expression and localization of barrier function proteins: Claudin-1 (CLDN-1), Claudin-4 (CLDN-4), Zonulin-1 (ZO-1), E-Cadherin and Mucin-1 (MUC1). Barrier functionality was measured by TEER.

Results: In the acidic microenvironment, TEER measurement has shown some limitations and results were not applicable, whereas the evaluation of protein localization and quantification provided clear and robust evidence of the damage which occurred to the epithelium barrier structure. CLDN-4 expression significantly decreased after exposure to acid. ZO-1 protein appeared upregulated immediately after exposure to HCl and was mainly localized in the cytoplasm and not on the cell membrane. This different localization was also observed for CLND-1. CLDN-1, MUC1 and, to a lower extent, ZO-1 expression increased during the post-incubation period.

Conclusion: The relevant tissue biomarkers identified, CLDN-1 and MUC1, can be used to monitor TJ structure and epithelial barrier recovery after acid-induced damage which, in our experimental conditions, were non-destructive and suitable for recovery studies. The established model can be useful to investigate the mechanism of action of formulations acting on this specific pathophysiological condition and/or designed to potentiate the physiological defense mechanisms of oesophageal mucosa.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The need for increased patient survival has not been met for PDAC. The addition of mannose to conventional chemotherapy leads to accumulation of mannose metabolite in cancer cells and increases subsequent cell death. This susceptibility to mannose depends on the levels of phosphomannose isomerase (PMI). The cancer cells with lower levels of PMI are more sensitive to mannose than cells with higher levels. In this study, we investigated the association of PMI expression with clinical and pathological features of PDAC cases.

Methods: PMI antibody immunohistochemistry (AbCam) was performed on tissue microarrays from 235 PDAC by a standard protocol on Ventana automated immunostainer. The PMI intensity was graded (0-3) and the proportion of positivity was scored. Correlation of PMI expression with staging and survival was analyzed.

Results: Of the 235 cases, 51.5% (n=121) cases demonstrated grade 2 intensity with 90.1% of these (n=109) showing positivity in ≥70% of tumor cells. Ninety-eight (41.7%) cases exhibited grade 3 intensity with 94.9% (n=93) of these cases showing ≥70% reactivity. Sixteen cases (6.8%) were nonreactive (intensity grade 0-1). Intensity of PMI expression was associated with significantly better prognosis as assessed by median survival in months (M): grade 0-1 intensity group: 11.2 M; grade 2 intensity group: 25.2 M; and grade 3 intensity group: 33.2 M (p=0.03). A minority (6.8%) of PDACs show non-high PMI expression with poorer prognosis.

Discussion: Mannose may be a particularly useful adjunct with chemotherapy to treat this aggressive subgroup. PMI expression is also a potential biomarker to predict the prognosis of PDAC.

Ulcerative colitis (UC) is a chronic inflammatory disorder that requires sustained treatment for optimal outcomes. The 5-aminosalicylate (5-ASA) class of medications are first-line for the treatment of mild-to-moderate UC but suffer from suboptimal adherence rates in real-world settings. This review summarizes the literature on adherence and patient preference to 5-ASA in patients with UC. We begin by highlighting key studies that measure real-world adherence rates, as well as some of the pitfalls associated with certain techniques. We examine the data on the consequences of non-adherence, which range from decreased quality of life and higher risk of colorectal cancer at the individual level to increased costs to the overall healthcare system. We then turn to the reasons and risk factors for non-adherence and summarize the current understanding of the barriers towards adherence. Afterwards, we describe the research on patient preferences between 5-ASA formulations and dosing regimen. Finally, we summarize the evidence regarding interventions to improve 5-ASA adherence. While adherence remains a challenge in practice, understanding the current state of the field can better inform future efforts towards increasing adherence, and thus clinical outcomes, in UC.

Leukocyte trafficking to the gastrointestinal tract is recognized to play a role in the pathogenesis of inflammatory bowel disease (IBD). Integrins are expressed on immune cells and interact with cell adhesion molecules (CAM) to mediate leukocyte trafficking. Blockade of the gut-tropic integrin α4β7 and its subunits has been exploited as a therapeutic target in IBD. Natalizumab (anti-α4) is approved for moderate to severe Crohn's disease (CD), but its use is limited due to potential risk of progressive multifocal leukoencephalopathy. Vedolizumab (anti-α4β7) is approved for the treatment of ulcerative colitis (UC) and CD. It is the most widely used anti-integrin therapy in IBD and has been shown to be effective in both induction and maintenance therapy, with a favorable safety profile. Several models incorporating clinical, genetic, immune, gut microbial, and vitamin D markers to predict response to vedolizumab in IBD have been developed. Etrolizumab (anti-β7) blocks leukocyte trafficking via α4β7 and cell adhesion via αEβ7 integrins. Large phase 3 clinical trials evaluating efficacy of etrolizumab in the induction and maintenance of patients with IBD are underway. Other investigational anti-integrin therapies include abrilumab (anti-α4β7 IgG2), PN-943 (orally administered and gut-restricted α4β7 antagonist peptide), AJM300 (orally active small molecule inhibitor of α4), and ontamalimab (anti-MAdCAM-1 IgG).