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Gastric cancer (GC) is a relevant public health issue as its incidence and mortality rates are growing worldwide. There are recognized carcinogen agents, such as obesity, tobacco, meat, alcohol consumption and some dietary protective factors. Strategies of early diagnosis through population-based surveillance programs have been demonstrated to be effective in lowering the morbidity and mortality related to GC in some countries. Indeed, the detection of early lesions is very important in order to offer minimally invasive treatments. Endoscopic resection is the gold standard for lesions with a low risk of lymph node metastasis, whereas surgical mini-invasive approaches can be considered in early lesions when endoscopy is not curative. This review outlines the role of lifestyle and prevention strategies for GC, in order to reduce the patients’ risk factors, implement the surveillance of precancerous conditions and, therefore, improve the diagnosis of early lesions. Furthermore, we summarize the available treatments for early gastric cancer.

DOCK8 deficiency is a combined immunodeficiency due to biallelic variants in dedicator of cytokinesis 8 (DOCK8) gene. The disease has a wide clinical spectrum encompassing recurrent infections (candidiasis, viral and bacterial infections), virally driven malignancies and immune dysregulatory features, including autoimmune (cytopenia and vasculitis) as well as allergic disorders (eczema, asthma, and food allergy). Hypomorphic function and somatic reversion of DOCK8 has been reported to result in incomplete phenotype without IgE overproduction. Here we describe a case of DOCK8 deficiency in a 8-year-old Caucasian girl. The patient’s disease was initially classified as autoimmune thrombocytopenia, which then evolved toward a combined immunodeficiency phenotype with recurrent infections, persistent EBV infection and lymphoproliferation. Two novel variants (one deletion and one premature stop codon) were characterized, resulting in markedly reduced, but not absent, DOCK8 expression. Somatic reversion of the DOCK8 deletion was identified in T cells. Hypomorphic function and somatic reversion were associated with restricted T cell repertoire, decreased STAT5 phosphorylation and impaired immune synapse functioning in T cells. Although the patient presented with incomplete phenotype (absence of markedly increase IgE and eosinophil count), sclerosing cholangitis was incidentally detected, thus indicating that hypomorphic function and somatic reversion of DOCK8 may delay disease progression but do not necessarily prevent from severe complications.

Coronavirus disease 2019 (COVID-19) is a major worldwide threat caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly spreading to a global pandemic. As of May 11, 2020, 4,176,346 cases have been reported worldwide, 219,814 in Italy, and of them, 81,871 occurred in the Lombardy region.1 Although the respiratory manifestations of COVID-19 have been widely described, the impact on the gastrointestinal (GI) system remains less clear. The reported prevalence of digestive symptoms ranges from 3% to 79%, depending on the setting,2–5 but data on GI endoscopic and histologic findings in COVID-19 patients are lacking. Therefore, the aim of this study is to describe the GI endoscopic and histologic findings in COVID-19 patients.

Purpose: Whether deferring surgery after endoscopic self-expandable metal stent (SEMS) placement for neoplastic stricture, and operating patients in a quasi-elective situation, may result in similar oncologic outcomes to elective operations is unclear. This study aimed to evaluate the disease-free survival (DFS) rates of patients who underwent an interval colon resection after SEMS placement or an elective operation with comparable cancer stages. Methods: From a prospective dataset, we retrospectively selected patients with the following characteristics: (1) left-sided colon cancer and (2) cancer stage I to III. Exclusion criteria were as follows: (1) palliative surgery and (2) emergency operation. Then we stratified patients into two groups: (A) full-elective left colon resection and (B) quasi-elective left colon resection, defined as surgery performed after SEMS placement for obstructive colon cancer. DFS function was studied by the Kaplan-Meier method. Results: After 1:2 matching based on cancer stage, 106 patients of the group A were compared with 53 patients of group B. In each group, there were 9.4% of stage I, 39.4% of stage II, and 50.9% of stage III patients. The rate of technical failure in SEMS placement was 3.8%. After a mean follow-up of 54 months, 16 (15.1%) patients in the full-elective groups and 10 (18.9%) in the quasi-elective group experience cancer recurrence (log rank = 0.588). DFS curve did not reach the median value. Conclusions: SEMS placement with interval colon resection for obstructive neoplastic strictures seems to provide similar long-term oncologic outcomes to operations performed in an elective setting when a low rate of technical failure is achieved.

Goals: The present survey from the Italian Society of Digestive Endoscopy (SIED-Società Italiana di Endoscopia Digestiva) was aimed at reporting infection control practice and outcomes at Digestive Endoscopy Units in a high-incidence area. Background: Lombardy was the Italian region with the highest coronavirus disease-2019 (COVID-19) prevalence, at the end of March 2020 accounting for 20% of all worldwide deaths. Joint Gastro-Intestinal societies released recommendations for Endoscopy Units to reduce the risk of the contagion. However, there are few data from high-prevalence areas on adherence to these recommendations and on their efficacy. Methods: A survey was designed by the Lombardy section of SIED to analyze (a) changes in activity and organization, (b) adherence to recommendations, (c) rate of health care professionals' (HCP) infection during the COVID-19 outbreak. Results: In total, 35/61 invited centers (57.4%) participated; most modified activities were according to recommendations and had filtering face piece 2/filtering face piece 3 and water-repellent gowns available, but few had negative-pressure rooms or provided telephonic follow-up; 15% of HCPs called in sick and 6% had confirmed COVID-19. There was a trend (P = 0.07) toward different confirmed COVID-19 rates among endoscopists (7.9%), nurses (6.6%), intermediate-care technicians (3.4%), and administrative personnel (2.2%). There was no correlation between the rate of sick HCPs and COVID-19 incidence in the provinces and personal protective equipment availability and use, whereas an inverse correlation with hospital volume was found. Conclusions: Adherence to recommendations was rather good, though a minority were able to follow all recommendations. Confirmed COVID-19 seemed higher among endoscopists and nurses, suggesting that activities in the endoscopy rooms are at considerable viral spread risk.

Up to 20% of health care personnel (HCP) were found to be infected with coronavirus disease (COVID-19)1 in the outbreak in northern Italy.2 Recommendations on patient and HCP protection have been made, such as postponing procedures, triage, use of personal protective equipment (PPE), and creation of differentiated in-hospital pathways.3,4 However, several barriers against the adoption of these strategies exist, including cultural factors and shortages of medical resources; therefore, there are few reports of real-world experiences and outcomes with their adoption.5 The aim of this survey was to investigate the burden of COVID-19 on endoscopic activity in a high-risk area of COVID-19 outbreak, approaches to evaluating patients, adoption and compliance of HCP with protective measures, and initial possible viral transmission outcomes from endoscopy units within a large, community-based setting (both between patients and HCP and between HCP).

Cornelia de Lange syndrome (CdLS) is a rare genetic condition related to mutation of various cohesion complex related genes. Its natural history is quite well characterized as regard pediatric age. Relatively little information is available regarding the evolution of the disease in young-adult age. In medical literature, only one specific study has been published on this topic. We report on our experience on 73 Italian CdLS patients (40 males and 33 females) with and age range from 15 to 49 years. Our results confirm the previous study indicating that gastroesophageal reflux disease (GERD) is the main medical problem of these patients in childhood and young-adult age. Other medical features that should be considered in the medical follow-up are tendency to overweight/frank obesity, constipation, discrepancy of limbs’ length, epilepsy, hearing, and visual problems. Behavioral problems are particularly frequent as well. For this reason, every source of hidden pain should be actively searched for in evaluating a patient showing such a disorder. Finally, recommendations for medical follow-up in adult age are discussed. © 2016 Wiley Periodicals, Inc.

Background: The incidence of biliary tract pathology is growing with an age-related trend, and progresses as the population ages. Endoscopic Retrograde Cholangiopancreatography (ERCP) represents the gold standard for treatment in these cases, but evidence about its safety in the elderly is still debated. Methods: We retrospectively analyzed the clinical records of all patients aged ≥65 undergoing ERCP between July 2013 and July 2015. Of 387 ERCP cases, 363 (~ 94%) were completed entirely. The mean age of the study population (n = 363) was 79.9 years old (range 70-95), with 190 subjects aged 70-79 and 173 older than 80. We recorded demographics, Charlson Comorbidity index (CCI), American Society of Anesthesiologists (ASA) physical status classification score, indication for the use of the ERCP procedure, and clinical outcomes. Then, we tested all variables to identify the potential risk factors for complications associated with the procedure. Results: The older group (those ≥80 years old) showed significantly more patients with ASA Classes III-IV than the younger one (those ≤79 years old). Interestingly, the CCI was higher in the younger group (p = 0.009). The overall complication rate was 17.3% without inter-group differences. Older age, sex, CCI and intra-ERCP procedures were not related to a higher risk of complications, and the multivariate regression did not identify any of the considered variables to be an independent risk factor for complications. Conclusion: ERCP appears as safe in the patients aged 80 years and older, as it is in those aged 70-79 years old in our study, however, a selection bias may affect these findings. A study including a comprehensive geriatric assessment will contribute to shedding light on this issue.

Background: Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug–drug interactions. Methods: In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other QTc-prolonging risk factors. We concurrently considered administered drug doses and pharmacokinetic interactions modulating drug clearance to calculate individual weights of relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we estimated individual drug exposure with these drugs and included this information as weights in weighted regression analyses. Results: Drugs attributing a ‘known’ risk for clinical consequences were associated with the largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with 95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for the ‘conditional’ risk class increased upon refinement with relative drug exposure and co-administration of a ‘known’ risk drug as a further risk factor. Conclusions: These observations indicate that indiscriminate combinations of QTc-prolonging drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation caused by drug combinations strongly depends on the nature of the combination partners and individual drug exposure.

BACKGROUND: The efficacy and safety of self-expandable metallic stent (SEMS) placement as a bridge to elective surgery or definitive palliation versus emergency operation to treat colorectal obstruction is debated. This study aimed to evaluate the outcomes of patients with colorectal obstruction treated using different strategies. METHODS: Subjects admitted to the authors' department with colorectal obstruction (n = 134) were studied prospectively. They underwent endoscopic stenting as a bridge to elective surgery (SEMS group: n = 49) or for definitive palliation (n = 34). A total of 51 patients underwent immediate surgery without stenting (NO-SEMS). Treatment was decided by the senior on-call surgeon. RESULTS: Placement of SEMS was technically successful in 95.3 % and clinically successful in 98.7 % of cases. The short-term complications in the SEMS group were perforation (n = 1, 1.2 %), migration (n = 4, 4.9 %), occlusion (n = 4, 4.9 %), colon bleeding (n = 3, 3.7 %), and abdominal pain (n = 6, 7.4 %). The postoperative complication rate was 32.7 % in the SEMS group versus 60.8 % in the NO-SEMS group (P = 0.005), with a significant reduction in wound infections (26.5 vs 54.9 %; P = 0.004), abdominal abscess (14.3 vs 39.2 %; P = 0.006), respiratory morbidity (10.2 vs 37.3 %; P = 0.002), and intensive care treatment (10.2 vs 33.3 %; P = 0.007). The median postoperative hospital stay was 10 versus 15 days (P = 0.001). The in-hospital mortality rate in both groups was 2 %. Long-term follow-up evaluation showed less incisional hernia (6.3 vs 22.0 %; P = 0.04) and definitive stoma formation (6.3 vs 26.0 %; P = 0.01) in the SEMS group than in the NO-SEMS group, respectively. Kaplan-Meier survival curves showed a benefit for the SEMS group (log-rank test, 0.004). The long-term SEMS-related complication rate for the palliative patients was 43.8 %. The hospital readmission rate for SEMS complications was 34.4 %. Overall clinical success was 81.2 %. CONCLUSIONS: In case of c

Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a crosssectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.

Aims. In recent years several warnings have been issued by regulatory authorities on the risk of electrocardiogram abnormalities in individuals exposed to psychotropic drugs. As a consequence of these warnings, monitoring of the QT interval corrected for heart rate (QTc) has become increasingly common. This study was conducted to measure the frequency of QTc prolongation in unselected psychiatric patients, and to document the associated factors using a cross-sectional approach. Method. The study was carried out in 35 Italian psychiatric services that are part of the STAR (Servizi Territoriali Associati per la Ricerca) Network, a research group established to produce scientific knowledge by collecting data under ordinary circumstances. During a three-month period, a consecutive unselected series of both in- and out-patients were enrolled if they performed an ECG during the recruitment period and were receiving psychotropic drugs on the day ECG was recorded. Results. During the recruitment period a total of 2411 patients were included in the study. The prevalence of QTc prolongation ranged from 14.7% (men) and 18.6% (women) for the cut-off of 450 ms, to 1.26% (men) and 1.01% (women) for the cut-off of 500 ms. In the multivariate model conducted in the whole sample of patients exposed to psychotropic drugs, female sex, age, heart rate, alcohol and/or substance abuse, cardiovascular diseases and cardiovascular drug treatment, and drug overdose were significantly associated with QTc prolongation. In patients exposed to antipsychotic drugs, polypharmacy was positively associated with QTc prolongation, whereas use of aripiprazole decreased the risk. In patients exposed to antidepressant drugs, use of citalopram, citalopram dose and use of haloperidol in addition to antidepressant drugs, were all positively associated with QTc prolongation. Conclusions. The confirmation of a link between antipsychotic polypharmacy and QTc prolongation supports the current guidelines that re

Celiac disease is an intestinal disease which shows different symptoms and clinical manifestations among pediatric and adult patients. These variations could be imputable to age-related changes in gut architecture and intestinal immune system, which could be characterized by gene expression differences possibly regulated by miRNAs. We analyzed a panel of miRNAs and their target genes in duodenal biopsies of Marsh 3AB and 3C pediatric celiac patients, compared to controls. Moreover, to assess variation of expression in plasma samples, we evaluated circulating miRNA levels in controls and patients at diagnosis or on gluten-free diet. We detected a decreased miR-192-5p expression in celiac patients, but no variations in NOD2 and CXCL2, targets previously identified in adults. Conversely, we detected a significant increase in mRNA and protein levels of another target, MAD2L1, protein related to cell cycle control. miR-31-5p and miR-338-3p were down-regulated and their respective targets, FOXP3 and RUNX1, involved in Treg function, resulted up-regulated in celiac patients. Finally, we detected, in celiac patients, an increased expression of miR-21-5p, possibly caused by a regulatory loop with its putative target STAT3, which showed an increased activation in Marsh 3C patients. The analysis of plasma revealed a trend similar to that observed in biopsies, but in presence of gluten-free diet we could not detect circulating miRNAs values comparable to controls. miRNAs and their gene targets showed an altered expression in duodenal mucosa and plasma of celiac disease pediatric patients, and these alterations could be different from adult ones.