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Non-coeliac gluten sensitivity (NCGS) is still a poorly defined clinical condition. This review aims to describe the clinical features of subjects with a symptomatic response to gluten intake, and to estimate the prevalence of NCGS.Literature search was conducted in accordance with PRISMA recommendations. The PubMed database was searched for original articles until 1We identified 30 relevant articles, including 14 studies that investigated NCGS through a double-blind, placebo-controlled crossover trial (DBPCC), and 16 that examined the role of gluten in causing symptoms without a DBPCC. We found that regardless of the diagnostic work up, gluten-sensitive patients were predominately middle-aged females complaining of abdominal pain, bloating and diarrhea. The pooled prevalence of NCGS after DBPCC was 24% (5-34%). Subjects with irritable bowel syndrome or self-reporting gluten intolerance accounted for the vast majority of the patients who did not start a DBPCC. A symptomatic response to a gluten-free diet (GFD) occurred in between 7% and 93% of patients. No data on long-term outcomes of NCGS individuals were reported.Clinical features of NCGS patients did not differ among all the included studies, whereas prevalence figures are rather heterogeneous. Long-term benefit of a GFD on these patients still needs to be ascertained.

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an acute infectious disease that spreads mainly through the respiratory route. Besides interstitial pneumonia, a number of other clinical manifestations were noticed in COVID-19 patients. In particular, liver and spleen dysfunctions have been described both as complications of COVID-19 and as potential predisposing factors for severe COVID-19. Liver damage is rather common in COVID-19 patients, and it is most likely multifactorial, caused by the direct insult of SARS-CoV-2 to the liver by the cytokine storm triggered by the virus, by the use of hepatotoxic drugs, and as a consequence of hypoxia. Although generally mild, liver impairment has been found to be associated with a higher rate of intensive care unit admission. A higher mortality rate was reported among chronic liver disease patients. Instead, spleen impairment in patients with COVID-19 has been poorly described. The main anatomical changes are the architectural derangement of the B cell compartment, white pulp atrophy, and reduction or absence of lymphoid follicles, while, from a functional point of view, the IgM memory B cell pool is markedly depleted. The outcome of COVID-19 in asplenic or hyposplenic patients is yet to be defined. In this review, we will summarise the current knowledge regarding the impact of SARS-CoV-2 on the liver and spleen function, as well as the outcome of patients with a pre-existent liver disease or defective spleen function.

Purpose Insulinomas are rare, functioning pancreatic neuroendocrine neoplasms (pNEN), whose gold standard therapy is surgical resection. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a recent technique that has emerged as minimally invasive therapeutic option for patients with pancreatic lesions not eligible for surgery. In this study, we aimed to describe a series of patients with unresectable pancreatic insulinoma treated with EUS-RFA. Methods This is a single-center, retrospective study including all consecutive patients with functioning pancreatic insulinoma undergoing EUS-RFA for surgical unfitness or surgery refusal, between March 2017 and September 2021. Technical success, radiologic response, and adverse events rate were evaluated. Results A total of 10 patients (mean age: 67.1 ± 10.1 years; F:M 7:3) were enrolled. The mean size of insulinoma was 11.9 ± 3.3 mm. Technical success was achieved in 100% of patients, with an immediate normalization of serum glucose levels. Only one (10%) patient was successfully treated with two RFA sessions. The complete radiologic response within 3 months after EUS-RFA was observed in all patients (100%). Persistent euglycemia was assessed at 6 and 12 months for each treated patient. Three procedure-related early adverse events occurred, including two (20%) cases of mild abdominal pain, and one (10%) case of intraprocedural bleeding with spontaneous hemostasis. No major complications were observed within 48 hours after the procedure. Conclusions Data of this case series suggest that EUS-RFA is a feasible and safe therapeutic approach for unresectable pancreatic insulinomas with long-term efficacy.

ObjectivePeroral endoscopic myotomy (POEM) has become standard treatment for achalasia with comparable efficacy to surgery. In most of published series, the length of myotomy is 12–13 cm. Shorter cuts could have the advantage of shorter procedure time and possibly reduced gastro-oesophageal reflux disease (GORD) rate.DesignThis single-centre, patient-blinded, randomised, non-inferiority clinical trial included 200 patients, who were randomly allocated, to receive either a long-POEM (13 cm; 101 patients) or a short-POEM (8 cm; 99 patients). Primary outcome was defined as an Eckardt symptom score of ≤3 at 24 months after the procedure; a non-inferiority design was chosen with an accepted success range of 6% between the two treatments. Secondary outcomes included operating time, complication rate, postoperative manometry, GORD rate and quality of life.ResultsIn the intention-to-treat analysis, clinical success rates were 89.1% in the long-POEM and 98.0% in the short-POEM group, resulting in an absolute between-group difference of −8.9% (90% CI −14.5 to −3.3).Procedure time was significantly reduced in the short-POEM as compared with the long-POEM group (40 vs 50 min, pNo differences were observed in postoperative GORD: acid exposure >6% on pH monitoring study at 6 months was seen in 34.3% (long-POEM) vs 31.1% (short-POEM), while endoscopic oesophagitis was diagnosed in 37.6% vs 51.5% at 6 months and in 21% vs 24.5% at 24 months. Regular proton pump inhibitor use was not different either (36.8% vs 37.5%).ConclusionsOur study demonstrates non-inferiority of a shorter cut length of POEM as compared with the standard treatment, which saved some procedural time. GORD rate was not reduced by reducing cutting length.Trial registration numberNCT03450928.

The correlation between myocardial injury and clinical outcome in COVID-19 patients is gaining attention in the literature. The aim of the present study was to evaluate the role of cardiac involvement and of respiratory failure in a cohort of COVID-19 patients hospitalized in an academic hospital in Lombardy, one of the most affected Italian (and worldwide) regions by the epidemic. The study included 405 consecutive patients with confirmed COVID-19 admitted to a medical ward from February 25th to March 31st, 2020. Follow-up of surviving patients ended either at hospital discharge or by July 30th, 2020. Myocardial injury was defined on the basis of the presence of blood levels of hs-TnI above the 99th percentile upper reference limit. Respiratory function was assessed as PaO2/FiO2 (P/F) ratio. The primary end-point was death for any cause. During hospitalization, 124 patients died. Death rate increased from 7.9% in patients with normal hs-TnI plasma levels and no cardiac comorbidity to 61.5% in patients with elevated hs-TnI and cardiac involvement (p

COVID-19, caused by SARS-CoV-2, has become a global threat in a matter of months. In particular, Italy has been one of the most affected areas worldwide. Data regarding the clinical picture and clinical course of COVID-19 are still lacking, especially in non-Asian populations. COVID-19 usually causes an influenza-like syndrome, including cough, fever, sore throat, muscle pain, and in some cases a more severe clinical picture, including interstitial pneumonia with acute respiratory distress syndrome, which may be fatal.1 Acute kidney failure has been reported in a substantial proportion of patients with COVID-19,1 2 but little is known regarding the mechanisms leading to kidney injury. Besides fluid depletion, which is expected to be common, a direct damage caused by the virus could be potentially responsible for kidney injury. In fact, as it has been recently hypothesised, SARS-CoV-2 may reach the kidney, as well as other organs, via viral sepsis.3 In turn, this process might be favoured by a defective immune response towards the virus, as in the case of patients treated with immunomodulant drugs, including biological therapies. The impact of COVID-19 in patients suffering from inflammatory bowel disease, particularly those treated with biological agents, is poorly characterised, and data are still emerging. We here describe the unique clinical course of a COVID-19 patient with Crohn’s disease (CD) under biological therapy who was admitted to our internal medicine unit for acute kidney injury. A 25-year-old man has been suffering from CD since the age of 18, when he underwent a colonoscopy that showed multiple ulcers …

BACKGROUND Stigmatization is the separation of an individual from a group due to aspects that make them different. Resilience may in turn influence the perception of stigma. Patients with inflammatory bowel disease (IBD) are susceptible to stigma, although data are very limited. AIM To validate an Italian translation of the IBD perceived stigma scale (PSS) in relation to patients’ resilience. METHODS Consecutive IBD outpatients were prospectively enrolled (December 2018-September 2019) in an Italian, tertiary referral, IBD center. Clinical and demographic data were collected. Stigma and resilience were evaluated through the IBD-PSS and the 25-item Connor-Davidson Resilience Scale, respectively. The International Quality of Life Assessment Project approach was followed to translate the IBD-PSS into Italian and to establish data quality. Higher scores represent greater perceived stigma and resilience. Multivariable analysis for factors associated with greater stigma was computed. RESULTS Overall, 126 IBD patients (mean age 46.1 ± 16.9) were enrolled. The International Quality of Life Assessment criteria for acceptable psychometric properties of the scale were satisfied, with optimal data completeness. There was no ceiling effect, whilst floor effect was present (7.1%). The discriminant validity and the internal consistency reliability were good (Cronbach alpha = 0.87). The overall internal consistency was 95%, and the test-retest reliability was excellent 0.996. The median PSS score was 0.45 (0.20-0.85). Resilience negatively correlated with perceived stigma (Spearman’s correlation = -0.18, 95% confidence intervals: -0.42-0.08, P = 0.03). CONCLUSION We herein validated the Italian translation of the PSS scale, also demonstrating that resilience negatively impacts perceived stigma.

Impaired immune responses have been hypothesised to be a possible trigger of unfavourable outcomes in coronavirus disease 2019 (COVID-19). We aimed to characterise IgM memory B cells in patients with COVID-19 admitted to an internal medicine ward in Northern Italy. Overall, 66 COVID-19 patients (mean age 74 ± 16.6 years; 29 females) were enrolled. Three patients (4.5%; 1 female) had been splenectomised and were excluded from further analyses. Fifty-five patients (87.3%) had IgM memory B cell depletion, and 18 (28.6%) died during hospitalisation (cumulative incidence rate 9.26/100 person-week; 5.8–14.7 95% CI). All patients who died had IgM memory B cell depletion. A superimposed infection was found in 6 patients (9.5%), all of them having IgM memory B cell depletion (cumulative incidence rate 3.08/100 person-week; 1.3–6.8 95% CI). At bivariable analyses, older age, sex, number of comorbidities, and peripheral blood lymphocyte count

Introduction: The Multidimensional Prognostic Index (MPI) is a validated tool for assessing mortality risk in hospitalised patients. We aimed to evaluate whether the MPI predicted mortality and the risk of developing diverticular disease (DD) complications in older patients. Methods: This is a multicentre study conducted in January 2016-March 2018. All patients with DD aged 65 years and older were included. Patients were stratified into three groups according to MPI groups (1, low risk; 2, moderate risk; 3, high risk). Risk of developing DD complications and mortality rate were assessed. Bivariate models were fitted. Results: One hundred hospitalised patients with DD (mean age 77.9 ± 10.6 years, 53 female patients) were included. Patients with higher MPI groups were more likely to develop DD complications. In particular, 12 (46.2%), 21 (52.5%), and 28 (82.4%) patients with complicated DD were distributed to the MPI 1, MPI 2, and MPI 3 groups (p = 0.0063), respectively. Two patients died in the MPI 1, 4 in the MPI 2, and 29 in the MPI 3 group, with mortality rates of 4.0 per 100 person-year (95% confidence interval [CI] 1.0–15.9), 5.6 (95% CI 2.1–15.0), and 89.2 (95% CI 62–130), respectively (log-rank test p < 0.001). In bivariate analysis, after adjustment for age >80 years, Charlson Comorbidity Index >4, DD complications, and the presence of thromboembolism, higher MPI group was independently associated with higher mortality. Those in the MPI 3 group experienced a greater risk of 1-year hospital readmission (p < 0.001). Conclusion: MPI predicted mortality in patients with DD and also correlated with the risk of developing DD complications. Studies focussing on possible pathophysiological mechanisms between DD complications and MPI are needed.

Follow-up modalities for adult coeliac patients remain controversial. Non-invasive markers to identify coeliac patients on a gluten-free diet (GFD) with persistence of villous atrophy (VA) are still lacking. We aim to develop a score to stratify coeliac patients on a GFD according to their risk of having persistent VA and to tailor follow-up modalities accordingly. The clinical notes of over 700 coeliac patients attending our unit (September 1999–November 2018) were retrospectively examined. A total of 273 patients on a GFD with a histological follow-up performed 12–24 months after diagnosis were selected. We developed a bivariable model based on diet adherence and clinical response evaluated by previously validated methods. A four-level score (0·5, 1·5, 3, 4) was obtained. Patients on a strict GFD and with good clinical conditions (score 4) have a very low risk of persistence of VA (2 (95 % CI 1, 5) %). Conversely, the risk is very high (46 (95 % CI 25, 68) %) in patients with poor adherence to a GFD and unsatisfactory clinical response (score 0·5). A score of 1·5 (poor GFD adherence and persistent well-being) is linked with a high risk (23 (95 % CI 14, 36) %). Risk is intermediate (6 (95 % CI 3, 10) %) in patients scoring 3 (strict GFD and no/partial clinical improvement). Three patients who developed complications belonged to this scenario. Patients at low risk of persistent VA can be followed-up non-invasively, whereas a biopsy should be repeated in those at high/very high risk. Case-by-case evaluation is needed in patients at intermediate risk. Studies on a larger sample size are required to confirm these data.

The spectrum of gluten-related disorders (GRD) has emerged as a relevant phenomenon possibly impacting on health care procedures and costs worldwide. Current classification of GRD is mainly based on their pathophysiology, and the following categories can be distinguished: immune-mediated disorders that include coeliac disease (CD), dermatitis herpetiformis (DH), and gluten ataxia (GA); allergic reactions such as wheat allergy (WA); and non-coeliac gluten sensitivity (NCGS), a condition characterized by both gastrointestinal and extra-intestinal symptoms subjectively believed to be induced by the ingestion of gluten/wheat that has recently gained popularity. Although CD, DH, and WA are well-defined clinical entities, whose diagnosis is based on specific diagnostic criteria, a diagnosis of NCGS may on the contrary be considered only after the exclusion of other organic disorders. Neither allergic nor autoimmune mechanisms have been found to be involved in NCGS. Mistakes in the diagnosis of GRD are still a relevant clinical problem that may result in overtreatment of patients being unnecessary started on a gluten-free diet and waste of health-care resources. On the basis of our clinical experience and literature, we aim to identify the main pitfalls in the diagnosis of CD and its complications, DH, and WA. We provide a practical methodological approach to guide clinicians on how to recognize and avoid them.

Objectives Endoscopic sphincterotomy (ES) and papillectomy (EP) are associated with a non-negligible risk of post-procedural bleeding. Despite first-line endoscopic hemostasis being achieved by several methods, patients may experience bleeding persistence or recurrence. In such cases, fibrin glue (FG) injection may be used as a rescue therapy before more invasive approaches. The aim of this study was to evaluate the efficacy and safety of endoscopic FG injection to treat refractory post-ES and post-EP bleeding. Methods Data were collected retrospectively from patients with refractory immediate or delayed bleeding following ES or EP, between October 2007 and November 2019, at a single institution. Clinical success was defined as bleeding control after FG injection. Results Overall, 70 patients were included. Clinical success was reached in 64 (91.4%) patients after one session of FG injection. Of six (8.6%) patients in whom the treatment failed, one required subsequent insertion of a fully covered self-expanding metal stent (FC-SEMS) due to immediate massive bleeding, while five experienced bleeding recurrence. Such events were managed with an additional session of FG injection that failed in two cases. Therefore, one patient underwent FC-SEMS plus selective embolization, whereas the other underwent diagnostic arteriography. No severe periprocedural complications occurred. Two cases of intrabiliary glue migration were treated by endoscopic removal with a retrieval basket. Conclusions Rescue therapy with endoscopic FG injection appears to be effective and safe to treat refractory post-ES and post-EP bleeding. Further studies are required to confirm these preliminary data.