Clinical and Experimental Gastroenterology最新文献

Introduction: Celiac disease (CeD) diagnosis has worldwide shared protocols. Conversely, follow-up of patients is still an object of study. Gluten immunogenic peptide detection in the urine (GIP) appears to be a new and efficient method for dietary gluten control of patients. The present study aims to assess the clinical usefulness of the GIP point-of-care urine test in the follow-up of symptomatic and asymptomatic patients with CeD before and during the COVID-19 lockdown in Italy.

Methods: Thirty adult CeD patients on a gluten-free diet (GFD) were enrolled before and during the COVID-19 lockdown through follow-up visits or remote consultation. Patients underwent anthropometrical evaluation, dietetic interview, and State-Trait Anxiety Inventory (STAI). Then, two groups were formed: symptomatic and worried about gluten contamination. Each patient received 5 GIP point-of-care tests to perform a maximum of 5 times in the following 5 weeks in case of symptoms or anxiety state due to hypothesized gluten contamination.

Results: Sixteen symptomatic patients and 14 patients with concerns related to gluten contamination were included. There were no differences in age, BMI, compliance to GFD and GIP positive tests between the two groups. Worried group showed a borderline higher level of anxiety than symptomatic group (p = 0.06), with a significant minor percentage of patients reporting "no or low anxiety" (14.3% vs 50% p = 0.03). The symptomatic patients showed a higher rate of diarrhea than worried group (25% vs 0%, p = 0.04). Gluten in urine samples was globally found in 8 out of 30 cases (26.6%).

Conclusion: The GIP test is a tool that can be used as a point of care test to assess adequate compliance with GFD and reassure symptomatic CeD patients from the feeling of anxiety for gluten contamination, especially during the COVID-19 pandemic.

Introduction: In non-alcoholic fatty liver disease (NAFLD), neutrophils in liver infiltrates are activated, which may contribute to disease progression towards non-alcoholic steatohepatitis (NASH). However, the functional status of the blood neutrophils remains unknown and their role in the disease mechanisms is thus uncertain. We therefore characterized activation and function of blood neutrophils in patients with NAFLD in relation to clinical disease markers and the NAFLD plasma milieu.

Methods: We studied 20 patients with NAFLD, among these 6 patients with NASH, and 14 healthy persons. Neutrophil activation, interleukin (IL)-8 production and oxidative burst were measured by flow cytometry on participants´ neutrophils and on healthy neutrophils exposed in vitro to plasma from the study participants.

Results: Blood neutrophils from the NASH patients showed a doubling in their expression of the activation marker CD62L. Also, all NAFLD patients had 50-100% increased expression of CD11b. Functionally, NASH neutrophils had 30% elevated IL-8 production and more than doubled spontaneous oxidative burst. In all NAFLD patients, higher spontaneous oxidative burst was associated with worse liver function. Incubation of healthy neutrophils with NAFLD plasma paradoxically slightly reduced CD62L and CD11b expression, and NASH plasma also reduced the frequency of IL-8-producing neutrophils.

Conclusion: In NAFLD, blood neutrophils are activated, and in NASH also functionally primed. This suggests a progressive neutrophil aggressiveness already present with liver fat infiltration. However, NAFLD plasma in vitro, if anything, had the opposite effect on the healthy neutrophils so the NAFLD-related neutrophil activation cannot be attributed to humoral factors and remains unexplained.

Background: The pathophysiology of inflammatory bowel diseases remains poorly understood and treatment remains suboptimal for many patients. We hypothesize that the inflammatory milieu secondarily prolongs the injury and attenuates healing. We propose primary or adjuvant therapy with biocompatible adhesives to restore a barrier to protect submucosal structures, particularly stem cells.

Methods: We used the well-described mouse dextran sodium sulfate (DSS) model of colitis resembling human ulcerative colitis to test the therapeutic efficacy of intrarectal administration of the tamarind plant-derived xyloglucan (TXG) polymer adhesive which underwent extensive analytic characterization. Mice in control, DSS-only, TXG-only, and DSS + TXG groups were studied for gross (weight, blood in stool, length of colon) and multiple histologic parameters.

Results: Compared to DSS-only mice, TXG prevented the weight loss, occurrence of blood in the stool and colon shortening, with all those parameters not being statistically different from treatment naïve animals. Histologically, there was dramatic and highly statistically significant reduction in the total inflammatory index and protection from goblet cell loss, cellular infiltration, crypt abscess formation, epithelial erosion, granulation tissue, epithelial hyperplasia crypt irregularity and crypt loss. The TXG purity and characterization were established by nuclear magnetic resonance, infrared spectroscopy, differential scanning calorimetry, and texture analysis.

Conclusion: The striking attenuation of disease severity by intrarectal TXG use warrants future investigations of natural bioadhesives with well-established high safety profiles, and which could potentially be derivatized to include therapeutically active moieties for local drug delivery.

Chronic idiopathic constipation (CIC) is a common functional bowel disorder characterized by difficult, infrequent, and/or incomplete defecation. It has a great impact on the quality of life and on health care system and represents a heavy economic burden. The diagnosis is based on symptoms, classified by the Rome IV criteria. The aim of this review was to evaluate the current therapeutic guidelines for adult CIC and highlight new emerging treatments. In detail, European, French, Spanish and Korean guidelines have been identified and compared. Osmotic laxatives, and in particular polyethylene glycol, represent the first-line therapeutic approach. Stimulant laxatives are recommended as a second-line therapy. Pelvic floor rehabilitation is recommended in patients with ano-rectal dyssynergia. In patients who fail to improve with pharmacological therapies sacral nerve stimulation is considered as last chance before surgery. Surgical approach has however limited indications in selected cases. Inertia coli refractory to any approach and obstructed defecation are two subtypes which can benefit from surgery. Among emerging agents, prucalopride, a prokinetic agent, is recommended as a second-line treatment in refractory CIC patients. In addition, the secretagogues linaclotide and plecanatide and the bile acid transported inhibitor elobixibat can be effective in patients not responsive to a second-line therapeutic regimen, although they are not worldwide commercially available.

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.