A "tailored" interventional and surgical management for moderate to critical acute pancreatitis in late phase: a cohort study.

PURPOSE: Several interventional procedures are available to treat moderate-to-critical acute pancreatitis (AP) in its late phase. The ongoing debate on these options, together with the scarcity of reported quality of life (QoL) information in the Literature, prompted us to conduct a review of our experience. METHODS: All the patients treated at our referral Center for moderate-to-critical AP according to Determinant-Based Classification (DBC) were retrospectively reviewed. Patients treated conservatively or operated within 4 weeks were excluded. The included patients were managed following a "tailored" interventional-surgical approach, which did not exclude the possibility to skip one or more steps of the classic "step-up" approach, based on the patient's clinical course, and divided into four groups, according to the first procedure performed: percutaneous drainage (PD), endoscopic approach (END), internal derivation (INT), and necrosectomy (NE). In-hospital and mid-term follow-up variables were analyzed. RESULTS: The study sample consisted in 47 patients: 11 patients were treated by PD, 11 by END, 13 by INT, and 12 by NE. A significant distribution of the DBC severity (p = 0.029) was registered among the four groups. Moreover, the NE group had statistically significant reduced SF-36 scores in the domain of social functioning at 3 months (p = 0.011), at 1 year (p = 0.002), and at 2 years (p = 0.001); role limitations due to physical health at 6 months (p = 0.027); and role limitations due to emotional problems at 1 year (p = 0.020). CONCLUSIONS: In the "late phase" of moderate to critical AP requiring an invasive management, PD, END, INT, and NE are all effective options, depending on patents' status and necrosis location. A "tailored" interventional-surgical management could be pursued, but up-front more invasive approaches are at higher risk of worse QoL. TRIAL REGISTRATION: The manuscript was registered at clinicaltrials.gov in 04/2021 and identified with NCT04870268.

Artificial Intelligence in the Diagnosis of Upper Gastrointestinal Diseases.

Artificial intelligence (AI) has enormous potential to support clinical routine workflows and therefore is gaining increasing popularity among medical professionals. In the field of gastroenterology, investigations on AI and computer-aided diagnosis (CAD) systems have mainly focused on the lower gastrointestinal (GI) tract. However, numerous CAD tools have been tested also in upper GI disorders showing encouraging results. The main application of AI in the upper GI tract is endoscopy; however, the need to analyze increasing loads of numerical and categorical data in short times has pushed researchers to investigate applications of AI systems in other upper GI settings, including gastroesophageal reflux disease, eosinophilic esophagitis, and motility disorders. AI and CAD systems will be increasingly incorporated into daily clinical practice in the coming years, thus at least basic notions will be soon required among physicians. For noninsiders, the working principles and potential of AI may be as fascinating as obscure. Accordingly, we reviewed systematic reviews, meta-analyses, randomized controlled trials, and original research articles regarding the performance of AI in the diagnosis of both malignant and benign esophageal and gastric diseases, also discussing essential characteristics of AI.

Therapeutic drug monitoring in Crohn's disease patients treated with anti-TNF: a comparison of two techniques.

BACKGROUND: Therapeutic drug monitoring is a useful clinical decision aid in managing patients with inflammatory bowel disease treated with anti-tumor necrosis factor (anti-TNF). Various techniques are available to evaluate drug trough levels, and among these a point-of-care (POC) method has been proposed to overcome the limitations inherent to other methodologies. In this study we aimed to evaluate the capability of POC to discriminate between relapse and remission disease phases, and to assess the concordance of the POC and homogeneous mobility shift assay (HMSA) results. METHODS: Drug trough level of 46 Crohn's disease patients treated with either adalimumab or infliximab were evaluated with both a POC technique and an HMSA at various time points (week-16 and -48) during anti-TNF treatment. RESULTS: Median adalimumab trough level of patients in remission were significantly higher as compared to relapsing patients using both HMSA (week 16, P = 0.0001; week48, P = 0.001) and POC (week 16, P = 0.0003; week 48, P = 0.0012), and similar results were observed with infliximab trough level at week 16 (HMSA, P = 0.019; POC, P = 0.0072). Overall, we observed a good correlation between the techniques for both infliximab (r = 0.76; P < 0.0001) and adalimumab (r = 0.75; P < 0.0001), with no difference in discriminatory accuracy between assays (infliximab: HMSA versus POC c-index, 0.921 versus 0.895, P =0.149; adalimumab: HMSA versus POC c-index, 0.817 versus 0.850, P = 0.197). CONCLUSION: Both POC and HMSA assays are able to reliably differentiate relapse and remission phases in Crohn's disease patients treated with anti-TNF. These techniques showed good concordance and we feel that their preferential use should be based on local accessibility, physicians' experience and preference, and the need for timeliness availability of results.

Eosinophilic esophagitis: novel concepts regarding pathogenesis and clinical manifestations.

Eosinophilic esophagitis is a chronic disease whose incidence and prevalence are increasing, based on a genetic-driven interaction between environment and immune system. Several gene loci involved in the development of the disease have been identified. A two-step mechanism has been hypothesized: a thymic stromal lymphopoietin-induced allergic sensitization followed by upregulation of CAPN14-related esophageal-specific pathways. Environment seems to have a larger effect than genetic variants. Factors that could play a role are allergens, drugs, colonizing bacteria and possibly Helicobacter Pylori infection. Acting on these modifiable risk factors may be a tool to prevent the disease. EoE is characterized by a typical eosinophilic infiltrate limited to the esophageal epithelium, supported by a Th2-mediated immune response, found in other atopic conditions. The key of the pathogenesis is the disfunction of the epithelial barrier which allow the interaction between allergens and inflammatory cells. Eosinophilic-predominant inflammation leads to the typical wall remodeling, histologically characterized by epithelial and smooth muscle hyperplasia, lamina propria fibrosis and neo-angiogenesis. These alterations find their clinical expression in the pattern of symptoms: dysphagia, food impaction, chest pain, heartburn.

Refractory Gastroesophageal Reflux Disease: A Management Update.

Gastroesophageal reflux disease (GERD) is one of the most frequent gastrointestinal disorders. Proton pump inhibitors (PPIs) are effective in healing lesions and improving symptoms in most cases, although up to 40% of GERD patients do not respond adequately to PPI therapy. Refractory GERD (rGERD) is one of the most challenging problems, given its impact on the quality of life and consumption of health care resources. The definition of rGERD is a controversial topic as it has not been unequivocally established. Indeed, some patients unresponsive to PPIs who experience symptoms potentially related to GERD may not have GERD; in this case the definition could be replaced with "reflux-like PPI-refractory symptoms." Patients with persistent reflux-like symptoms should undergo a diagnostic workup aimed at finding objective evidence of GERD through endoscopic and pH-impedance investigations. The management strategies regarding rGERD, apart from a careful check of patient's compliance with PPIs, a possible change in the timing of their administration and the choice of a PPI with a different metabolic pathway, include other pharmacologic treatments. These include histamine-2 receptor antagonists (H2RAs), alginates, antacids and mucosal protective agents, potassium competitive acid blockers (PCABs), prokinetics, gamma aminobutyric acid-B (GABA-B) receptor agonists and metabotropic glutamate receptor-5 (mGluR5) antagonists, and pain modulators. If there is no benefit from medical therapy, but there is objective evidence of GERD, invasive antireflux options should be evaluated after having carefully explained the risks and benefits to the patient. The most widely performed invasive antireflux option remains laparoscopic antireflux surgery (LARS), even if other, less invasive, interventions have been suggested in the last few decades, including endoscopic transoral incisionless fundoplication (TIF), magnetic sphincter augmentation (LINX) or radiofrequency therapy (Stretta). Due to the different mechanisms underlying rGERD, the most effective strategy can vary, and it should be tailored to each patient. The aim of this paper is to review the different management options available to successfully deal with rGERD.

Chronic Constipation: Is a Nutritional Approach Reasonable?

Chronic constipation (CC) is one of the most common gastroenterological diagnoses in clinical practice. Treatment includes several steps, depending on the severity of symptoms. Lifestyle modifications and increased intake of fiber and water are suggested by most health professionals. Unfortunately, the recommendations in this regard are the most varied, often conflicting with each other and not always based on solid scientific arguments. This paper aims to clarify this topic by providing practical indications for the management of these patients in every day clinical practice. The literature available on this topic is scarce, and dietary studies have important methodological biases. However, fiber, mainly by binding water and acting as bulking agents and/or as prebiotics for the intestinal microbiota, and mineral water, especially if rich in magnesium and/or bicarbonate, are useful tools. An adequate, well-designed diet should be a cornerstone of any effective treatment for chronic constipation. High-quality studies on larger samples are mandatory to give scientific validity to the role of the food in CC therapy and to enable professionals to choose the best approach for their patients, combining nutritional and pharmacological agents.

Modern Diagnosis of Early Esophageal Cancer: From Blood Biomarkers to Advanced Endoscopy and Artificial Intelligence.

Esophageal cancer (EC) is the seventh most common cancer and the sixth cause of cancer death worldwide. Histologically, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) account for up to 90% and 20% of all ECs, respectively. Clinical symptoms such as dysphagia, odynophagia, and bolus impaction occur late in the natural history of the disease, and the diagnosis is often delayed. The prognosis of ESCC and EAC is poor in advanced stages, being survival rates less than 20% at five years. However, when the diagnosis is achieved early, curative treatment is possible, and survival exceeds 80%. For these reasons, mass screening strategies for EC are highly desirable, and several options are currently under investigation. Blood biomarkers offer an inexpensive, non-invasive screening strategy for cancers, and novel technologies have allowed the identification of candidate markers for EC. The esophagus is easily accessible via endoscopy, and endoscopic imaging represents the gold standard for cancer surveillance. However, lesion recognition during endoscopic procedures is hampered by interobserver variability. To fill this gap, artificial intelligence (AI) has recently been explored and provided encouraging results. In this review, we provide a summary of currently available options to achieve early diagnosis of EC, focusing on blood biomarkers, advanced endoscopy, and AI.

Irritable Bowel Syndrome prevalence and work ability in a sample of healthcare workers exposed to occupational stress.

OBJECTIVE: Occupational stress represents a significant precipitating factor in different diseases but its role in Irritable Bowel Syndrome (IBS) needs to be clarified. The present cross-sectional study aimed at investigating the prevalence of IBS diagnosis in a sample of health workers and exploring the potential relationships between IBS, work-related stress levels and work ability. METHODS: 653 health workers undergoing periodical occupational health surveillance at the Occupational and Preventive Medicine Unit of a major University Hospital in central Italy, were consecutively recruited and screened for IBS diagnosis, according to ROMA IV criteria. The rating scales IBS Severity Scoring System (IBS-SSS), Demand-Control-Support Questionnaire (DCSQ) and Work Ability Index (WAI) were used to assess respectively IBS severity, occupational stress and work ability levels. RESULTS: IBS prevalence in the sample was 16.8%. Participants suffering from IBS were characterized by a higher prevalence of psychiatric diagnosis and sleep disturbances, higher levels of job strain and isostrain as well as by lower levels of work ability compared to non affected subjects. Moreover, the severity of IBS correlated positively with occupational stress and both were negatively associated with work ability. CONCLUSIONS: The present results suggest the need for preventive, organizational and management strategies at workplace aimed at protecting the health and well-being but also productivity of the worker with IBS.

Dietary Management of Eosinophilic Esophagitis: Tailoring the Approach.

Eosinophilic esophagitis (EoE) is a unique form of non-immunoglobulin E-mediated food allergy, restricted to the esophagus, characterized by esophageal eosinophil-predominant inflammation and dysfunction. The diagnosis requires an esophago-gastroduodenoscopy with esophageal biopsies demonstrating active eosinophilic inflammation with 15 or more eosinophils/high-power field, following the exclusion of alternative causes of eosinophilia. Food allergens trigger the disease, withdairy/milk, wheat/gluten, egg, soy/legumes, and seafood the most common. Therapeutic strategies comprise dietary restrictions, proton pump inhibitors, topical corticosteroids, biologic agents, and esophageal dilation when strictures are present. However, avoidance of trigger foods remains the only option targeting the cause, and not the effect, of the disease. Because EoE relapses when treatment is withdrawn, dietary therapy offers a long-term, drug-free alternative to patients who wish to remain off drugs and still be in remission. There are currently multiple dietary management strategies to choose from, each having its specific efficacy, advantages, and disadvantages that both clinicians and patients should acknowledge. In addition, dietary regimens should be tailored around each individual patient to increase the chance of tolerability and long-term adherence. In general, liquid elemental diets devoid of antigens and elimination diets restricting causative foods are valuable options. Designing diets on the basis of food allergy skin tests results is not reliable and should be avoided. This review summarizes the most recent knowledge regarding the clinical use of dietary measures in EoE. We discussed endpoints, rationale, advantages and disadvantages, and tailoring of diets, as well as currently available dietary regimens for EoE.

Raising Children on a Vegan Diet: Parents' Opinion on Problems in Everyday Life.

A growing number of Italian families are adopting a vegan diet (VD) for their offspring from infancy for various reasons, with health benefits and ethics being the most common reasons. Barriers to effective communication with primary care pediatricians (PCPs) are perceived by many parents and, depending on the actors involved and the environment, a VD may affect social interactions in everyday life. A national cross-sectional survey was conducted between July and September 2020. Parents of children following a VD completed an online questionnaire. Data from 176 Italian parents were collected. About 72% (71.8%) of the children included in this study had been on a VD since weaning. Parents did not inform their primary care pediatricians (PCP) about the VD in 36.2% of the cases. In 70.8% of the cases, PCPs were perceived as skeptical or against a VD. About 70% (71.2%) of the parents relied on medical dietitians, and 28.2% on nutritionists/dietitians for dietary counseling. Parents administered an individual B12 supplement in 87.2% of the cases. To the best of our knowledge, this survey is the first which explores the relationship between vegan parents and their PCPs, the parental management of their children's diet and problems regarding the implementation of a VD in everyday life.

Ig Glycosylation in Ulcerative Colitis: It's Time for New Biomarkers.

Background: Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to monitor the disease and to predict therapeutic outcome. Methods: We enrolled consecutive UC patients treated with anti-TNF, naïve to biologic drugs. Therapeutic outcome was evaluated after 54 weeks of treatment in terms of clinical remission (Partial Mayo Score -PMS- <2) and mucosal healing (Mayo Endoscopic Score <2). On serum samples collected at baseline and after 54 weeks of treatment, a Lectin-based ELISA assay was performed, and specific glycosylation patterns were evaluated by biotin-labelled lectins. We have also collected 21 healthy controls (NHS) samples, age and sex-matched. Results: Out of 44 UC patients enrolled, 22 achieved clinical remission and mucosal healing after 54 weeks. At baseline, when Protein A was used as coating, UC patients non-responders showed a reduced reactivity to Jacalin (JAC) in comparison with NHS (p = 0.04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline (p = 0.04). When JAC binding was tested selecting IgG by means of Fab anti-IgG Fab, UC patients displayed an increased reactivity after anti-TNF therapy (p < 0,0001 vs controls). At baseline, PMS inversely correlates with JAC binding when Fab anti-IgG Fab was used in solid phase (r 2 = 0,2211; p = 0,0033). Patients with higher PMS at baseline (PMS ≥5) presented lower binding capacity for JAC in comparison with NHS and with lower PMS patients (p = 0,0135 and p = 0,0089, respectively). Conclusion: Ig glycosylation was correlated with clinical and endoscopic activity in patients with UC. JAC protein A-selected Ig showed a possible role in predicting therapeutic effectiveness. If these data would be confirmed, Ig glycosylation could be used as biomarker in UC.

Oral Sucrosomial Iron Is as Effective as Intravenous Ferric Carboxy-Maltose in Treating Anemia in Patients with Ulcerative Colitis.

Anemia is a frequent complication of ulcerative colitis, and is frequently caused by iron deficiency. Oral iron supplementation displays high rates of gastrointestinal adverse effects. However, the formulation of sucrosomial iron (SI) has shown higher tolerability. We performed a prospective study to compare the effectiveness and tolerability of oral SI and intravenous ferric carboxy-maltose (FCM) in patients with ulcerative colitis in remission and mild-to-moderate anemia. Patients were randomized 1:1 to receive 60 mg/day for 8 weeks and then 30 mg/day for 4 weeks of oral SI or intravenous 1000 mg of FCM at baseline. Hemoglobin and serum levels of iron and ferritin were assessed after 4, 8, and 12 weeks from baseline. Hemoglobin and serum iron increased in both groups after 4 weeks of therapy, and remained stable during follow up, without significant treatment or treatment-by-time interactions (p = 0.25 and p = 0.46 for hemoglobin, respectively; p = 0.25 and p = 0.26 for iron, respectively). Serum ferritin did not increase over time during SI supplementation, while it increased in patients treated with FCM (treatment effect, p = 0.0004; treatment-by-time interaction effect, p = 0.0002). Overall, this study showed that SI and FCM displayed similar effectiveness and tolerability for treatment of mild-to-moderate anemia in patients with ulcerative colitis under remission.

Eosinophilic esophagitis: clinical, endoscopic, histologic and therapeutic differences and similarities between children and adults.

In the absence of secondary causes, eosinophilic esophagitis (EoE) is a chronic, local, progressive, T-helper type 2 immune-mediated disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. In the last 20 years, the incidence and prevalence of EoE have risen sharply, and the chances of encountering affected patients in clinics and endoscopy rooms have increased. Nevertheless, it is estimated that the mean diagnostic delay of EoE is 4-6 years in both children and adults. Unfortunately, the longer the disease stays unrecognized, the likelier it is for the patient to have persistent or increased esophageal eosinophilic inflammation, to complain of non-resolving symptoms, and to develop fibrotic complications. Early detection depends on the recognition of initial clinical manifestations that vary from childhood to adulthood and even among patients of the same age. The disease phenotype also influences therapeutic approaches that include drugs, dietary interventions, and esophageal dilation. We have herein reviewed epidemiologic, clinical, endoscopic, and histologic features and therapeutic options of EoE focusing on differences and similarities between children and adults that may certainly serve in daily clinical practice.

Serum triiodothyronine-to-thyroxine (T3/T4) ratio predicts therapeutic outcome to biological therapies in elderly IBD patients.

INTRODUCTION: Rates of elderly patients with inflammatory bowel diseases (IBDs) are increasing, and biomarkers are needed to optimise their therapies. Serum triiodothyronine-to-thyroxine (T3/T4) ratio has been correlated with geriatric patient frailty. AIM: To assess the suitability of T3/T4 ratio as a response marker to biologics in elderly patients with IBD. METHODS: Patients with IBD over 60 years old were enrolled, when starting biological therapy. Therapeutic outcome was assessed after 54 weeks of treatment as mucosal healing (Mayo endoscopic score < 2 for ulcerative colitis; ulcer disappearance for Crohn's disease) and clinical remission (Partial Mayo Score < 2 for ulcerative colitis; Harvey-Bradshaw Index < 5 for Crohn's disease). T3/T4 ratio was evaluated at baseline, and its association with therapeutic outcomes was tested by multivariable logistic regression and receiver operating characteristic (ROC). RESULTS: We enrolled 80 patients; 44 achieved clinical remission and 36 mucosal healing. Baseline T3/T4 ratio was higher in patients with mucosal healing, as compared with those without mucosal healing (P < 0.0001), regardless of the disease type or biological drug (OR 6.4 [2.9-14.3] for each T3/T4 unit increase, P < 0.0001). A cut point of 3.3 was identified as the optimal threshold of baseline T3/T4 ratio for predicting mucosal healing, providing 78% sensitivity and 89% specificity (area under the ROC curve 0.88 [0.79-0.94]; positive and negative likelihood ratios 6.8 [2.9-15.9] and 0.3 [0.1-0.5] respectively). CONCLUSIONS: T3/T4 ratio seems a reliable tool for predicting therapeutic outcome of biological therapy in elderly patients with IBD. If validated, the assessment of this parameter before starting biological treatment might be suggested.

Is Gluten the Only Culprit for Non-Celiac Gluten/Wheat Sensitivity?

The gluten-free diet (GFD) has gained increasing popularity in recent years, supported by marketing campaigns, media messages and social networks. Nevertheless, real knowledge of gluten and GF-related implications for health is still poor among the general population. The GFD has also been suggested for non-celiac gluten/wheat sensitivity (NCG/WS), a clinical entity characterized by intestinal and extraintestinal symptoms induced by gluten ingestion in the absence of celiac disease (CD) or wheat allergy (WA). NCG/WS should be regarded as an "umbrella term" including a variety of different conditions where gluten is likely not the only factor responsible for triggering symptoms. Other compounds aside from gluten may be involved in the pathogenesis of NCG/WS. These include fructans, which are part of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), amylase trypsin inhibitors (ATIs), wheat germ agglutinin (WGA) and glyphosate. The GFD might be an appropriate dietary approach for patients with self-reported gluten/wheat-dependent symptoms. A low-FODMAP diet (LFD) should be the first dietary option for patients referring symptoms more related to FODMAPs than gluten/wheat and the second-line treatment for those with self-reported gluten/wheat-related symptoms not responding to the GFD. A personalized approach, regular follow-up and the help of a skilled dietician are mandatory.

Low Fermentable Oligo- Di- and Mono-Saccharides and Polyols (FODMAPs) or Gluten Free Diet: What Is Best for Irritable Bowel Syndrome?

Irritable Bowel Syndrome (IBS) is a very common functional gastrointestinal disease. Its pathogenesis is multifactorial and not yet clearly defined, and hence, its therapy mainly relies on symptomatic treatments. Changes in lifestyle and dietary behavior are usually the first step, but unfortunately, there is little high-quality scientific evidence regarding a dietary approach. This is due to the difficulty in setting up randomized double-blind controlled trials which objectively evaluate efficacy without the risk of a placebo effect. However, a Low Fermentable Oligo-, Di- and Mono-saccharides And Polyols (FODMAP) Diet (LFD) and Gluten Free Diet (GFD) are among the most frequently suggested diets. This paper aims to evaluate their possible role in IBS management. A GFD is less restrictive and easier to implement in everyday life and can be suggested for patients who clearly recognize gluten as a trigger of their symptoms. An LFD, being more restrictive and less easy to learn and to follow, needs the close supervision of a skilled nutritionist and should be reserved for patients who recognize that the trigger of their symptoms is not, or not only, gluten. Even if the evidence is of very low-quality for both diets, the LFD is the most effective among the dietary interventions suggested for treating IBS, and it is included in the most updated guidelines.

A Low-FODMAP Diet for Irritable Bowel Syndrome: Some Answers to the Doubts from a Long-Term Follow-Up.

A low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet (LFD) is a possible therapy for irritable bowel syndrome (IBS). This study investigates the short- and long-term efficacy and nutritional adequacy of an LFD and the patients' long-term acceptability. Patients' adherence and ability to perceive the "trigger" foods were also evaluated. Seventy-three IBS patients were given an LFD (T0) and after 2 months (T1), 68 started the reintroduction phase. At the end of this period (T2), 59 were advised to go on an Adapted Low-FODMAP Diet (AdLFD) and 41 were evaluated again after a 6-24 month follow-up (T3). At each time, questionnaires and Biolectrical Impedance Vector Analysis (BIVA) were performed. The LFD was effective in controlling digestive symptoms both in the short- and long-term, and in improving quality of life, anxiety and depression, even if some problems regarding acceptability were reported and adherence decreased in the long term. The LFD improved the food-related quality of life without affecting nutritional adequacy. When data collected at T0 were compared with those collected at T2, the perception of trigger foods was quite different. Even if some problems of acceptability and adherence are reported, an LFD is nutritionally adequate and effective in improving IBS symptoms also in the long term.

Fecal Calprotectin Predicts Mucosal Healing in Patients With Ulcerative Colitis Treated With Biological Therapies: A Prospective Study.

INTRODUCTION: Biological therapies are widely used for the treatment of ulcerative colitis. However, only a low proportion of patients achieve clinical remission and even less mucosal healing. There is currently scarce knowledge about the early markers of therapeutic response, with particular regard to mucosal healing. The aim of this prospective study was to evaluate the role of fecal calprotectin (FC) as early predictor of mucosal healing. METHODS: A prospective observational study was conducted on patients with ulcerative colitis, who started biological therapy with infliximab, adalimumab, golimumab, or vedolizumab at our center. All patients underwent colonoscopy, performed by 2 blinded operators, at baseline and week 54 or in case of therapy discontinuation because of loss of response. FC was assessed at baseline and week 8 and evaluated as putative predictor of mucosal healing at week 54. RESULTS: We enrolled 109 patients, and 97 were included in the analysis. Twenty-six patients (27%) experienced loss of response. Over 71 patients (73%) with clinical response at week 54, clinical remission was obtained in 60 patients (61.9%) and mucosal healing in 45 patients (46.4%). After 8 weeks of treatment, FC predicted mucosal healing at week 54 (P < 0.0001). Sensitivity, specificity, positive predictive value, and negative predictive value were estimated to be 75%, 88.9%, 86.6%, and 75.5%, respectively, based on a cutoff of 157.5 mg/kg. DISCUSSION: The present study suggests that FC assessment after 8 weeks of treatment with all the biological drugs could represent a promising early marker of response to therapy in terms of mucosal healing.

Serum oncostatin M at baseline predicts mucosal healing in Crohn's disease patients treated with infliximab.

BACKGROUND: Oncostatin M is upregulated in Crohn's disease inflamed intestinal mucosa, and has been suggested as a promising biomarker to predict responsiveness to anti-TNF therapy in patients with inflammatory bowel diseases. AIM: To evaluate the suitability of serum oncostatin M as a predictive marker of response to infliximab in Crohn's disease. METHODS: We included patients treated with infliximab monotherapy. All patients underwent colonoscopy at week 54 to evaluate mucosal healing. Serum oncostatin M and faecal calprotectin were measured at baseline and after 14 weeks of treatment. Mann-Whitney test was used to evaluate correlation of oncostatin M and faecal calprotectin at baseline and week 14 with mucosal healing at week 54. Their accuracy in predicting mucosal healing was assessed by area under the curve (AUC). RESULTS: In a cohort of 45 included patients, 27 displayed mucosal healing. At both baseline and week 14, oncostatin M levels were significantly lower in patients with mucosal healing than in patients not achieving this endpoint (P < 0.001). Faecal calprotectin levels at week 14 were lower also in responders than nonresponders (P < 0.001). Oncostatin M values at baseline and week 14 were significantly associated (Spearman correlation = 0.92, P < 0.001). The diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing (AUC = 0.91) was greater than faecal calprotectin (AUC = 0.51, P < 0.001). CONCLUSION: These results suggest that oncostatin M can predict the outcome of infliximab treatment. Compared with faecal calprotectin, the predictive capability of oncostatin M was appreciable at baseline, thus indicating oncostatin M as a promising biomarker for driving therapeutic choices in Crohn's disease.

Bile reflux in patients with nerd is associated with more severe heartburn and lower values of mean nocturnal baseline impedance and chemical clearance.

BACKGROUND: Mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave (PSPW) index are novel impedance-based markers of reflux, but the effect of bile reflux on these metrics is unknown. The aim of this study was to evaluate bile reflux, MNBI, and PSPW index in patients with endoscopy-negative GERD partially responsive to PPI therapy. METHODS: All patients underwent off-PPI endoscopy, esophageal manometry, multichannel intraluminal impedance pH (MII-pH), and bile reflux monitoring. Abnormal esophageal acid exposure time (AET) was required for inclusion. Symptom intensity (using 10-cm visual analog scales), and conventional and novel MII-pH metrics were compared between patients with and without abnormal bile reflux. KEY RESULTS: We evaluated 42 NERD patients (29 males, mean age: 53.4 ± 13. years), mean AET 6.1 ± 2%, of which 21 had abnormal bile reflux (Group A, 10.2 ± 4.9%), and 21 had normal bile reflux (Group B, 0.4 ± 0.1%, P < .05 compared with Group A). Heartburn reporting on PPI was higher in Group A (7.2 ± 2.1 vs 5.8 ± 0.9; P = .002), but AET, number of reflux events (acidic and weakly acidic), did not differ between the two groups. However, both PSPW index and MNBI were lower in Group A (P < .001). A strong inverse linear correlation was found between bile reflux and both MNBI (Pearson's test; R = -0.714; P < .001) and PSPW index (R = -0.722; P < .001). CONCLUSIONS AND INFERENCES: Compared to acid reflux alone, the presence of bile in an acidic esophageal environment is associated with more severe heartburn, lesser relief from PPI therapy, higher impairment of esophageal mucosal integrity and less effective chemical clearance.