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Scores in upper GI bleeding (UGIB) are used to stratify death risk and need for hospitalization at admission, but a tool that incorporates dynamic changes during the hospital stay is lacking. We aimed to develop a death risk score that considers changes in clinical status during hospitalization and compare its performance with existing ones.A multicenter cohort study enrolling patients with UGIB in 50 Italian hospitals from January 2014 to December 2015 was conducted. Data were collected and used to develop a risk score using logistic regression analyses. Performance curves (area under the receiver-operating characteristic [AUROC] curves), sensitivities, specificities, positive and negative predictive values, and outcomes classified as low, intermediate, and high death risk were calculated. The score's performance was externally validated and then compared with other scores.We included 1852 patients with nonvariceal UGIB in the development cohort and 912 in the validation cohorts. The new score, which we named the Re.Co.De (rebleeding-comorbidities-deteriorating) score, included 10 variables depicting the changes in clinical conditions while in the hospital. The mortality AUROC curves were .93 (95% confidence interval, .91-.96) in the derivation cohort and .94 (95% confidence interval, .91-.98) in validation cohort. In a comparison of AUROC curves with other scores, the new score showed a significant performance compared with pre- and postendoscopy scores. Patients with low and high scores had 30-day mortality rates of .001% and 48.2%, respectively.The Re.Co.De score has a higher performance for predicting mortality in patients with UGIB compared with other scores, correctly identifying patients at low and high death risk while in the hospital through a dynamic re-evaluation of clinical status.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord.This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV).We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days.Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.

Background: the lack of standardized pathways for patients with gastrointestinal bleeding may have led to differences in their management and inequity to medical care access. The "Hub & Spoke" model was adopted to fill this gap in many disciplines, but, to our knowledge, no data exist on its efficacy on mortality in GI bleeding. We aimed to evaluate if the "Hub & Spoke" organizational model has an impact on mortality risk from UGIB. Methods: from January 2014 to December 2015, 3324 consecutive patients admitted for UGIB in 50 Italian hospitals were enrolled (1977 patients in hospitals within the "Hub & Spoke" network for digestive hemorrhagic emergency and 1347 in hospitals outside the "Hub & Spoke" network). Clinical, endoscopic and organizational data were recorded. Results: we observed no differences in mortality between patients admitted to hospitals included or not included in the "Hub & Spoke" network (5.2% vs 6.1%, p = 0.3). On multivariate analysis, admission in gastroenterology wards (OR 0.61, p = 0.001) or an academic hospital (OR 0.65, p < 0.056) were independent protective factors while being in "Hub & Spoke" organization system did not affect mortality (OR 1.09, p = 0.57). Conclusion: the "Hub & Spoke" model per sé does not impact on mortality while being treated in academic hospital or gastroenterology wards improved survival.

Hydrogen peroxide (H2O2) is an essential second intracellular messenger. To reach its targets in the cytosol, H2O2 must cross a membrane, a feat that requires aquaporins (AQP) endowed with ‘peroxiporin’ activity (AQP3, AQP8, AQP9). Here, we exploit different organelle-targeted H2O2-sensitive probes to show that also AQP11 efficiently conduits H2O2. Unlike other peroxiporins, AQP11 is localized in the endoplasmic reticulum (ER), accumulating partly in mitochondrial-associated ER membranes (MAM). Its downregulation severely perturbs the flux of H2O2 through the ER, but not through the mitochondrial or plasma membranes. These properties make AQP11 a potential regulator of ER redox homeostasis and signaling., Graphical abstract Image 1, Highlights • AQP11 is an endoplasmic reticulum (ER)-resident peroxiporin. • AQP11 allows H2O2 fluxes across the ER membrane. • Its levels impact ER redox homeostasis.