Alcohol-related diseases: from metabolism to the main effect on the body.

Alcohol consumption can cause, beyond addiction, roughly 200 different diseases and at least fourteen types of cancer. In 2016 the WHO estimated that 29% of alcohol-related deaths were mainly due to oncological diseases, liver cirrhosis (20%), and cardiovascular disorders (19%). The aim of this review was to focus on the absorption and metabolism of ethanol and discuss the main conditions caused by alcohol consumption (i.e., liver and cardiovascular diseases, and tumors). This narrative review is based on a detailed analysis of the scientific literature published before January 31, 2024 (PubMed, Web of Science, Scopus, Google Scholar). Approximately 90% of the absorbed alcohol reaches the liver where it is metabolized to acetaldehyde, a highly reactive and toxic compound. The excessive use of alcohol causes damage to several organs and systems, mainly the liver (e.g., steatosis, steato-hepatitis, fibrosis, and cirrhosis), cardiovascular system (cardiomyopathy, arrythmias, arterial hypertension, and stroke), and significantly contribute to the onset of neoplastic lesions to various organs including the esophagus, liver and breast. Even moderate drinking appears not to reduce mortality risk. Alcohol intake is one of the main risk factors for several pathological conditions and social problems, thus drastically impacting on public health. Proper awareness of the high risk related to alcohol consumption is of crucial importance to reduce the harm to public health.

Chronic constipation in Parkinson's disease: clinical features and molecular insights on the intestinal epithelial barrier.

Background: Chronic constipation (CC) is a severe symptom in Parkinson's disease (PD), with an unclear pathogenesis. Abnormalities of the enteric nervous system (ENS) and/or intestinal epithelial barrier (IEB) may be pathophysiologically relevant in PD patients with CC. We investigated possible molecular changes of the IEB in PD/CCs compared with CCs and controls. Methods: Twelve PD/CCs (2 female, age range 51-80 years), 20 CCs (15 female, age range 27-78 years), and 23 controls (11 female, age range 32-74 years) were enrolled. Ten PD/CCs and 10 CCs were functionally characterized by anorectal manometry (AM) and transit time (TT). Colon biopsies were obtained and assessed for gene and protein expression, and localization of IEB tight junction markers claudin-4 (CLDN4), occludin-1 (OCCL-1), and zonula occludens-1 (ZO-1) by RT-qPCR, immunoblot and immunofluorescence labeling. Results: PD/CCs were clustered in 2 functional categories: patients with delayed TT and altered AM (60%), and a second group showing only modifications in AM pattern (40%). Gene expression of CLDN4, OCCL-1 and ZO-1 was higher in PD/CCs than controls (P<0.05). Conversely, PD/CCs showed a trend to decrease (P>0.05) in CLDN4 and OCCL-1 protein levels than controls, whereas ZO-1 protein was comparable. In PD/CCs compared with controls, decreasing tendency of vasoactive intestinal polypeptide mRNA, protein and immunoreactive fiber density were observed, although the difference was not statistically significant. Conclusion: Transit and anorectal dysfunctions in PD/CCs are associated with difference in ZO-1, OCCL-1 and CLDN4 expression, thus supporting the role of an altered IEB as a contributory mechanism to possible neuronal abnormalities.

A New Early Predictor of Fatal Outcome for COVID-19 in an Italian Emergency Department: The Modified Quick-SOFA.

Background: Since 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a rapidly spreading pandemic. The present study aims to compare a modified quick SOFA (MqSOFA) score with the NEWS-2 score to predict in-hospital mortality (IHM), 30-days mortality and recovery setting. Methods: All patients admitted from March to October 2020 to the Emergency Department of St. Anna Hospital, Ferrara, Italy with clinically suspected SARS-CoV-2 infection were retrospectively included in this single-centre study and evaluated with the MqSOFA and NEWS-2 scores. Statistical and logistic regression analyses were applied to our database. Results: A total of 3359 individual records were retrieved. Among them, 2716 patients were excluded because of a negative nasopharyngeal swab and 206 for lacking data; thus, 437 patients were eligible. The data showed that the MqSOFA and NEWS-2 scores equally predicted IHM (p < 0.001) and 30-days mortality (p < 0.001). Higher incidences of coronary artery disease, congestive heart failure, cerebrovascular accidents, dementia, chronic kidney disease and cancer were found in the deceased vs. survived group. Conclusions: In this study we confirmed that the MqSOFA score was non-inferior to the NEWS-2 score in predicting IHM and 30-days mortality. Furthermore, the MqSOFA score was easier to use than NEWS-2 and is more suitable for emergency settings. Neither the NEWS-2 nor the MqSOFA scores were able to predict the recovery setting.

Beyond biologics: advanced therapies in inflammatory bowel diseases.

INTRODUCTION: Inflammatory bowel diseases (IBDs) are conditions affecting the gut at different levels characterized by an abnormal activation of the intestinal immune system. In this narrative review, we will provide the reader with an update on the efficacy and safety of new pharmacological strategies to treat IBD patients. EVIDENCE ACQUISITION: We performed a thorough literature review via PubMed, EMBASE, MEDLINE and Science Direct databases addressing studies reporting on new therapies for IBD management published in the last ten years (January 2010-December 2020). Data from pharmaceutical companies and abstracts of conferences/meetings have also been considered. EVIDENCE SYNTHESIS: The discovery of monoclonal antibodies blocking pro-inflammatory cytokines, e.g., tumor necrosis factor-α (TNF-α) radically changed the management of IBDs. Anti-TNF-α agents represent the prototype molecule of "biologics"/"biologicals." These compounds have significantly improved the therapeutic management of IBDs refractory to standard medications as they provide clinical remission, mucosal healing and prevent extra-intestinal manifestations. However, about 50% of patients treated with biologicals experienced drawbacks, including primary failure or loss of response, requiring new effective treatments. Translational studies have identified new strategies, different from the TNF-α blockade, and new molecules, e.g. sphingosine-1-phosphate agonists and the JAK kinase inhibitors, have been proposed as potential therapeutic options for IBDs. CONCLUSIONS: With the availability of novel approaches reviewed in this article, physicians and especially gastroenterologists will increase the therapeutic options to provide a better management of IBD patients, particularly those poorly responsive to biologicals.

Subcutaneous Emphysema as a Life-Threatening Complication of Metastatic Renal Cancer: A Case Report.

Subcutaneous emphysema (SE) could present as an emergency situation requiring appropriate management because of possible serious complications. While the diagnosis can be well established, its classification and treatment are not yet standardized. Herein we report the case of SE occurred in a young man after positioning of a thorax drainage because of a hydro-pneumothorax developed as a consequence of pulmonary metastases from clear cell renal carcinoma. Since there are no data correlating anatomo-clinical categorization with outcome and treatment of patients with SE, a "tailored- treatment" may be considered.

Life-threatening onset of coeliac disease: a case report and literature review.

BACKGROUND: Coeliac disease (CD) results from an immune-mediated reaction to gluten in genetically predisposed individuals. In rare cases CD may occur with acute features deferring the diagnosis and exposing these patients to possible life-threatening complications. Herein we present the case of a young woman with a coeliac crisis, that is, a sudden clinical onset characterised by severe electrolyte imbalance due to an unknown (previously unrecognised) CD. METHODS: This is a case report and literature review revealing that coeliac crisis is under-reported, with a total of 48 adult cases so far published. The diagnosis in our case was established by histopathological analysis of multiple duodenal biopsies. The patient's serum was tested by enzyme-linked immunoassay to detect antitransglutaminase IgA antibodies. RESULTS: In contrast to cases reported in the literature, with male gender predominance and a mean age of 50±17 years, our patient was a young female case of coeliac crisis. However, like in our patient, a higher incidence of coeliac crisis was associated with the human leucocyte antigen (HLA)-DQ2 haplotype, versus HLA-DQ8, and a severe (Marsh-Oberhüber 3c) duodenal mucosa atrophy. Notably, there is no clear correlation between the antitissue transglutaminase 2 IgA antibody titre and coeliac crisis onset/severity, as confirmed by our case report. CONCLUSIONS: The present case highlights that CD may manifest quite abruptly with a severe malabsorption syndrome, that is, electrolyte abnormalities and hypoproteinaemia. Our case should alert physicians, in particular those in the emergency setting, that even a typically chronic disorder, such as CD, may show life-threatening complications requiring urgent management.

Prognosis after pacemaker implantation in extreme elderly.

AIMS: Significant comorbidities may limit the potential benefit of pacemaker (PM) implantation in extreme elderly. A short-term mortality risk prediction score, able to identify high-risk patients, may be a useful tool in this population. METHODS AND RESULTS: We retrospectively analyzed 538 patients aged >80 years at the time of implant who underwent PM implantation. Kaplan-Meier survival and multivariable Cox regression analyses were performed to identify patient, procedural or complication variables predictive of death. The ACP (Aging in Cardiac Pacing) Score was constructed by assigning weighted values to the variables identified by hazard ratios, combined into an additive mortality risk score equation. One, two and three-year overall mortality rate was 11%, 21% and 32% respectively. Renal failure (HR 1.63; CI 1.15-2.31; p = .006), active neoplasia (HR 1.78; CI 1.27-2.51; p = .008), connective tissue disorder (3.07; CI 1.34-7.08; p = .048), cerebrovascular disease (HR 1.75; CI 1.25-2.46; p = .001) and the use of a single lead device (HR 2.27; CI 1.6-3.24; p < .001) were independently associated with worse survival. The ACP Score showed discrete predictive ability (AUC 0,6792 CI 0,63-0,73). Kaplan-Meier survival curves comparing low vs high ACP Scores demonstrated that low ACP scores were associated with reduced mortality rates (p < .001). CONCLUSIONS: Significant comorbidities were associated with worse survival after PM implantation in extreme elderly. The ACP Score is a novel tool that may help to identify patients with high mortality risk after device implantation.