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ObjectiveTo evaluate survival, hospitalisations and surgical procedures for children born with Pierre Robin sequence (PRS) across Europe.DesignMulticentre population-based cohort study.SettingData on 463 live births with PRS from a population of 4 984 793 from 12 EUROCAT congenital anomaly registries.MethodsData on children with PRS born 1995–2014 were linked electronically to data on mortality, hospitalisations and surgical procedures up to 10 years of age. Each registry applied a common data model to standardise the linked data and ran common syntax scripts to produce aggregate tables. Results from each registry were pooled using random-effect meta-analyses.Main outcome measuresProbability of survival, proportion of children hospitalised and undergoing surgery, and median length of hospital stay.ResultsThe majority of deaths occurred in the first year of life with a survival rate of 96.0% (95% CI 93.5% to 98.5%); 95.1% (95% CI 92.7% to 97.7%) survived to age 10. In the first year of life, 99.2% (95% CI 95.0% to 99.9%) of children were hospitalised with a median stay of 21.4 days (95% CI 15.6 to 27.2), and 67.6% (95% CI 46.6% to 81.8%) underwent surgery. In the first 5 years of life, 99.2% of children underwent a median of two surgical procedures. Between ages 5 and 9, 58.3% (95% CI 44.7% to 69.7%) were hospitalised with a median annual stay of 0.3 days.ConclusionsChildren with PRS had high mortality and morbidity with long hospital stays in the first year of life, and almost all had surgery before 5 years of age. Survival improved after infancy with fewer hospitalisations after age 5. This study provides reliable estimates of the survival and morbidity of children with PRS for families and healthcare providers.

To investigate the relationship between prepregnancy maternal body mass index (BMI) and congenital anomalies (CAs).Case-control study on data collected by the registry of CAs of Tuscany (Italy) and birth certificates from 2005 to 2017.Maternal prepregnancy BMI.Any major CAs and groups of organ-specific anomalies. Odds ratios (ORs) were estimated using logistic regression models adjusted for maternal factors.Maternal BMI ≥25 was significantly associated with all nervous system anomalies (OR = 1.61, 95% confidence interval [95% CI] 1.13-2.29) and with neural tube defects (OR = 2.03, 95% CI 1.00-4.12); maternal underweight was significantly associated with orofacial clefts (OR = 1.67, 95% CI 1.12-2.48). After stratification by education, in the low education group, mothers with BMI ≥25 had an increased risk of nervous system anomalies (OR = 2.19, 95% CI 1.01-4.76), whereas underweight mothers had an increased risk of nervous system anomalies (OR = 3.89, 95% CI 1.44-10.53), orofacial clefts (OR = 2.59, 95% CI 1.24-5.42), and urinary anomalies (OR = 1.74, 95% CI 1.07-2.82). In the medium/high education group, the only significantly increased risk was found in mothers with BMI ≥25 for nervous system anomalies (OR = 1.50, 95% CI 1.00-2.25).Main results have shown a positive association of maternal BMI ≥25 with nervous system anomalies and maternal underweight with orofacial clefts. The study has also evidenced the impact of social status and provided clues to the role of maternal ethnic background.

Background Aplasia cutis congenita (ACC) is a rare congenital anomaly characterized by localized or widespread absence of skin at birth, mainly affecting the scalp. Most information about ACC exists as individual case reports and medium-sized studies. Objectives This study aimed to investigate the epidemiology of ACC, using data from a large European network of population-based registries for congenital anomalies (EUROCAT). Methods Twenty-eight EUROCAT population-based registries in 16 European countries were involved. Poisson regression models were exploited to estimate the overall and live birth prevalence, to test time trends in prevalence between four 5-year periods and to evaluate the impact of the change of coding for ACC from the unspecific ICD9-BPA code to the specific ICD10 code. Proportions of ACC cases associated with other anomalies were reported. Results Five hundred cases were identified in the period 1998–2017 (prevalence: 5.10 per 100,000 births). Prevalence across 5-year periods did not differ significantly and no significant differences were evident due to the change from ICD9 to ICD10 in ACC coding. Heterogeneity in prevalence was observed across registries. The scalp was the most common site for ACC (96.4%) and associated congenital anomalies were present in 33.8% of cases. Patau and Adams–Oliver syndromes were the most frequent among the associated chromosomal anomalies (88.3%) and the associated genetic syndromes (57.7%), respectively. 16% of cases were associated with limb anomalies and 15.4% with congenital heart defects. A family history of ACC was found in 2% of cases. Conclusion To our knowledge, this is the only population-based study on ACC. The EUROCAT methodologies provide reliable prevalence estimates and proportions of associated anomalies.

Background: Pierre Robin sequence (PRS) is a rare congenital anomaly. Respiratory disorders and feeding difficulties represent the main burden. Objective: The aim of this study was to investigate the epidemiology of PRS using a cohort of cases from EUROCAT, the European network of population-based registries of congenital anomalies. Methods: We analysed cases of PRS born in the period 1998-2017 collected by 29 population-based congenital anomaly registries in 17 different countries. We calculated prevalence estimates, prenatal detection rate, survival up to 1 week, and proportions of associated anomalies. The effect of maternal age was tested using a Poisson regression model. Results: Out of 11 669 155 surveyed births, a total of 1294 cases of PRS were identified. The estimate of the overall prevalence was 12.0 per 100 000 births (95% CI 9.9, 14.5). There was a total of 882 (68.2%) isolated cases, and the prevalence was 7.8 per 100 000 births (95% CI 6.7, 9.2). A total of 250 cases (19.3%) were associated with other structural congenital anomalies, 77 cases (6.0%) were associated with chromosomal anomalies and 77 (6.0%) with genetic syndromes. The prenatal detection rate in isolated cases was 12.0% (95% CI 9.8, 14.5) and increased to 16.0% (95% CI 12.7, 19.7) in the sub-period 2008-2017. The prevalence rate ratio of non-chromosomal cases with maternal age ≥35 was higher than in cases with maternal age

BACKGROUND: Congenital anomalies are a major cause of perinatal, neonatal and infant mortality.OBJECTIVES: The aim was to investigate temporal changes and geographical variation in survival of children with major congenital anomalies (CA) in different European areas.METHODS: In this population-based linkage cohort study, 17 CA registries members of EUROCAT, the European network for the surveillance of CAs, successfully linked data on 115,219 live births with CAs to mortality records. Registries estimated Kaplan-Meier survival at 28 days and 5 years of age and fitted Cox's proportional hazards models comparing mortality at 1 year and 1-9 years of age for children born during 2005-2014 with those born during 1995-2004. The hazard ratios (HR) from each registry were combined centrally using a random-effects model. The 5-year survival conditional on having survived to 28 days of age was calculated.RESULTS: The overall risk of death by 1 year of age for children born with any major CA in 2005-2014 decreased compared to 1995-2004 (HR 0.68, 95% confidence interval [CI] 0.53, 0.89). Survival at 5 years of age ranged between registries from 97.6% to 87.0%. The lowest survival was observed for the registry of OMNI-Net (Ukraine) (87.0%, 95% CI 86.1, 87.9).CONCLUSIONS: Survival of children with CAs improved for births in 2005-2014 compared with 1995-2004. The use of CA registry data linked to mortality data enables investigation of survival of children with CAs. Factors such as defining major CAs, proportion of terminations of pregnancy for foetal anomaly, source of mortality data and linkage methods are important to consider in the design of future studies and in the interpretation of the results on survival of children with CAs.

SARS-CoV-2, like other coronaviruses, builds a membrane-bound replication organelle (RO) to enable RNA replication(1). The SARS-CoV-2 RO is composed of double membrane vesicles (DMVs) tethered to the endoplasmic reticulum (ER) by thin membrane connectors(2), but the viral proteins and the host factors involved are currently unknown. Here we identify the viral non-structural proteins (NSPs) that generate the SARS-CoV-2 RO. NSP3 and NSP4 generate the DMVs while NSP6, through oligomerization and an amphipathic helix, zippers ER membranes and establishes the connectors. The NSP6ΔSGF mutant, which arose independently in the α, β, γ, η, ι and λ variants of SARS-CoV-2, behaves as a gain-of-function mutant with a higher ER-zippering activity. We identified three main roles for NSP6: to act as a filter in RO-ER communication allowing lipid flow but restricting access of ER luminal proteins to the DMVs, to position and organize DMV clusters, and to mediate contact with lipid droplets (LDs) via the LD-tethering complex DFCP1-Rab18. NSP6 thus acts as an organizer of DMV clusters and can provide a selective track to refurbish them with LD-derived lipids. Importantly, both properly formed NSP6 connectors and LDs are required for SARS-CoV-2 replication. Our findings, uncovering the biological activity of NSP6 of SARS-CoV-2 and of other coronaviruses, have the potential to fuel the search for broad antiviral agents.

ObjectiveTo report and compare the proportion of children with and without congenital anomalies undergoing gastrostomy for tube feeding in their first 5 years.MethodsA European, population-based data-linkage cohort study (EUROlinkCAT). Children up to 5 years of age registered in nine EUROCAT registries (national and regional) in six countries and children without congenital anomalies (reference children) living in the same geographical areas were included. Data on hospitalisation and surgical procedures for all children were obtained by electronic linkage to hospital databases.ResultsThe study included 91 504 EUROCAT children and 1 960 272 reference children. Overall, 1200 (1.3%, 95% CI 1.2% to 1.6%) EUROCAT children and 374 (0.016%, 95% CI 0.009% to 0.026%) reference children had a surgical code for gastrostomy within the first 5 years of life. There were geographical variations across Europe with higher rates in Northern Europe compared with Southern Europe. Around one in four children with Cornelia de Lange syndrome and Wolf-Hirschhorn syndrome had a gastrostomy. Among children with structural anomalies, those with oesophageal atresia had the highest proportion of gastrostomy (15.9%).ConclusionsThis study including almost 2 million reference children in Europe found that only 0.016% of these children had a surgery code for gastrostomy before age 5 years. The children with congenital anomalies were on average 80 times more likely to need a gastrostomy before age 5 years than children without congenital anomalies. More than two-thirds of gastrostomy procedures performed within the first 5 years of life were in children with congenital anomalies.

Aims To identify the most accurate early warning score (EWS) for predicting an adverse outcome in COVID-19 patients admitted to the emergency department (ED). Methods In adult consecutive patients admitted (March 1-April 15, 2020) to the ED of a major referral centre for COVID-19, we retrospectively calculated NEWS, NEWS2, NEWS-C, MEWS, qSOFA, and REMS from physiological variables measured on arrival. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and the area under the receiver operating characteristic (AUROC) curve of each EWS for predicting admission to the intensive care unit (ICU) and death at 48 h and 7 days were calculated. Results We included 334 patients (119 [35.6%] females, median age 66 [54-78] years). At 7 days, the rates of ICU admission and death were 56/334 (17%) and 26/334 (7.8%), respectively. NEWS was the most accurate predictor of ICU admission within 7 days (AUROC 0.783 [95% CI, 0.735-0.826]; sensitivity 71.4 [57.8-82.7]%; NPV 93.1 [89.8-95.3]%), while REMS was the most accurate predictor of death within 7 days (AUROC 0.823 [0.778–0.863]; sensitivity 96.1 [80.4-99.9]%; NPV 99.4[96.2–99.9]%). Similar results were observed for ICU admission and death at 48 h. NEWS and REMS were as accurate as the triage system used in our ED. MEWS and qSOFA had the lowest overall accuracy for both outcomes. Conclusion In our single-centre cohort of COVID-19 patients, NEWS and REMS measured on ED arrival were the most sensitive predictors of 7-day ICU admission or death. EWS could be useful to identify patients with low risk of clinical deterioration.

BackgroundGastroschisis is strongly associated with young maternal age. This association suggests the need for further investigations on non-genetic risk factors. Identifying these risk factors is a public health priority in order to develop prevention strategies aimed at reducing the prevalence and health consequences in offspring.ObjectiveTo systematically assess and quantitatively synthesise the available epidemiological studies to evaluate the association between non-genetic risk factors and gastroschisis.MethodsLiterature from PubMed, EMBASE and Scopus was searched for the period 1990–2018. Epidemiological studies reporting risk estimates between lifestyle and sociodemographic risk factors and gastroschisis were included. Two pairs of reviewers independently extracted information on study characteristics following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and MOOSE (Meta-analysis Of Oservational Studies in Epidemiology) guidelines. Relative risk (RR) estimates were calculated across the studies and meta-analysis was performed using random-effects model.ResultsWe identified 58 studies. Meta-analyses were conducted on 29 studies. Maternal smoking (RR 1.56, 95% CI 1.40 to 1.74), illicit drug use (RR 2.14, 95% CI 1.48 to 3.07) and alcohol consumption (RR 1.40, 95% CI 1.13 to 1.70) were associated with an increased risk of gastroschisis. A decreased risk among black mothers compared with non-Hispanic white mothers (RR 0.49, 95% CI 0.38 to 0.63) was found. For Hispanic mothers no association was observed.ConclusionsExposure to smoking, illicit drugs and alcohol during pregnancy is associated with an increased risk of gastroschisis. A significantly decreased risk for black mothers was observed. Further epidemiological studies to assess the potential role of other environmental factors are strongly recommended.PROSPERO registration numberCRD42018104284.

OBJECTIVES To investigate the survival up to age 10 for children born alive with a major congenital anomaly (CA). METHODS This population-based linked cohort study (EUROlinkCAT) linked data on live births from 2005 to 2014 from 13 European CA registries with mortality data. Pooled Kaplan-Meier survival estimates up to age 10 were calculated for these children (77 054 children with isolated structural anomalies and 4011 children with Down syndrome). RESULTS The highest mortality of children with isolated structural CAs was within infancy, with survival of 97.3% (95% confidence interval [CI]: 96.6%–98.1%) and 96.9% (95% CI: 96.0%–97.7%) at age 1 and 10, respectively. The 10-year survival exceeded 90% for the majority of specific CAs (27 of 32), with considerable variations between CAs of different severity. Survival of children with a specific isolated anomaly was higher than in all children with the same anomaly when those with associated anomalies were included. For children with Down syndrome, the 10-year survival was significantly higher for those without associated cardiac or digestive system anomalies (97.6%; 95% CI: 96.5%–98.7%) compared with children with Down syndrome associated with a cardiac anomaly (92.3%; 95% CI: 89.4%–95.3%), digestive system anomaly (92.8%; 95% CI: 87.7%–98.2%), or both (88.6%; 95% CI: 83.2%–94.3%). CONCLUSIONS Ten-year survival of children born with congenital anomalies in Western Europe from 2005 to 2014 was relatively high. Reliable information on long-term survival of children born with specific CAs is of major importance for parents of these children and for the health care professionals involved in their care.

Patients with rare diseases (RDs) generally have delayed diagnosis and misdiagnosis, which lead to inappropriate care or the need to modify treatment during the course of the disease. The medical care of RD patients can be further complicated by the presence of comorbidities. In this population-based study, we evaluated the prevalence, intensity of use, and consumption of drugs prescribed to RD patients residing in Tuscany (Italy) in the years 2008–2018. Data from the Registry of Rare Diseases of Tuscany were integrated with information retrieved from regional pharmaceutical prescription databases. The overall prevalence of drug use in the RD patients was 85.4%. Drugs for the alimentary tract and metabolism and antiinfectives for systemic use showed the highest prevalence of use, while drugs for the nervous system had the highest intensity of use only in the pediatric patients. The adults exhibited a female preponderance in terms of the prevalence of use and drug consumption in almost all the age groups and therapeutic categories. Conversely, a higher prevalence of use was observed in the male children. These results provide relevant insights into drug profiles in RD patients, representing a first step for future analyses to monitor changes in drug utilization in patients with RDs over time.

Sepsis and septic shock represent a leading cause of mortality in the Emergency Department (ED) and in the Intensive Care Unit (ICU). For these life-threating conditions, different diagnostic and prognostic biomarkers have been studied. Proadrenomedullin (MR-proADM) is a biomarker that can predict organ damage and the risk of imminent death in patients with septic shock, as shown by a large amount of data in the literature. The aim of our narrative review is to evaluate the role of MR-proADM in the context of Emergency Medicine and to summarize the current knowledge of MR-proADM as a serum indicator that is useful in the Emergency Department (ED) to determine an early diagnosis and to predict the long-term mortality of patients with sepsis and septic shock. We performed an electronic literature review to investigate the role of MR-proADM in sepsis and septic shock in the context of ED. We searched papers on PubMed®, Cochrane®, UptoDate®, and Web of Science® that had been published in the last 10 years. Data extracted from this literature review are not conclusive, but they show that MR-proADM may be helpful as a prognostic biomarker to stratify the mortality risk in cases of sepsis and septic shock with different degrees of organ damage, guiding emergency physicians in the diagnosis and the succeeding therapeutic workup. Sepsis and septic shock are conditions of high complexity and have a high risk of mortality. In the ED, early diagnosis is crucial in order to provide an early treatment and to improve patient survival. Diagnosis and prognosis are often the result of a combination of several tests. In our opinion, testing for MR-proADM directly in the ED could contribute to improving the prognostic assessment of patients, facilitating the subsequent clinical management and intensive treatment by the emergency physicians, but more studies are needed to confirm these results.

EUROCAT is a European network of population-based congenital anomaly (CA) registries. Twenty-one registries agreed to participate in the EUROlinkCAT study to determine if reliable information on the survival of children born with a major CA between 1995 and 2014 can be obtained through linkage to national vital statistics or mortality records. Live birth children with a CA could be linked using personal identifiers to either their national vital statistics (including birth records, death records, hospital records) or to mortality records only, depending on the data available within each region. In total, 18 of 21 registries with data on 192,862 children born with congenital anomalies participated in the study. One registry was unable to get ethical approval to participate and linkage was not possible for two registries due to local reasons. Eleven registries linked to vital statistics and seven registries linked to mortality records only; one of the latter only had identification numbers for 78% of cases, hence it was excluded from further analysis. For registries linking to vital statistics: six linked over 95% of their cases for all years and five were unable to link at least 85% of all live born CA children in the earlier years of the study. No estimate of linkage success could be calculated for registries linking to mortality records. Irrespective of linkage method, deaths that occurred during the first week of life were over three times less likely to be linked compared to deaths occurring after the first week of life. Linkage to vital statistics can provide accurate estimates of survival of children with CAs in some European countries. Bias arises when linkage is not successful, as early neonatal deaths were less likely to be linked. Linkage to mortality records only cannot be recommended, as linkage quality, and hence bias, cannot be assessed. publishedVersion

Myopericarditis is an inflammatory heart condition involving the pericardium and myocardium. It can lead to heart failure, dilated cardiomyopathy, arrhythmia and sudden death. Its pathogenesis is mainly mediated by viral infections but also can be induced by bacterial infections, toxic substances and immune mediated disorders. All these conditions can produce severe inflammation and myocardial injury, often associated with a poor prognosis. The specific roles of these different pathogens (in particular viruses), the interaction with the host, the interplay with gut microbiota, and the immune system responses to them are still not completely clear and under investigation. Interestingly, some research has demonstrated the contribution of the gut microbiota, and its related metabolites (some of which can mimic the cardiac myosin), in cardiac inflammation and in the progression of this disease. They can stimulate a continuous and inadequate immune response, with a subsequent myocardial inflammatory damage. The aim of our review is to investigate the role of gut microbiota in myopericarditis, especially for the cardiovascular implications of COVID-19 viral infection, based on the idea that the modulation of gut microbiota can be a new frontier in the cardiological field to prevent or treat inflammatory cardiomyopathies.

Background Rare diseases (RDs) encompass a heterogeneous group of life-threatening or chronically debilitating conditions that individually affect a small number of subjects but overall represent a major public health issue globally. There are still limited data on RD burden due to the paucity of large population-based epidemiological studies. The aim of this research was to provide survival estimates of patients with a RD residing in Tuscany, Italy. Methods Cases collected in the Rare Diseases Registry of Tuscany with diagnosis between 1st January 2000 and 31th December 2018 were linked to the regional health databases in order to retrieve information on mortality of all subjects. Survival at 1, 5 and 10 years from diagnosis with 95% confidence intervals (CI) was estimated by sex, age class, nosological group and subgroup using the Kaplan–Meier method. The effect of sex, age and period of diagnosis (years 2000–2009 or 2010–2018) on survival was estimated using Cox proportional hazards regression. Results Survival at 1, 5 and 10 years from diagnosis was 97.3%, 88.8% and 80.8%, respectively. Respiratory diseases and peripheral and central nervous system disorders were characterized by the lowest survival at 5 and 10 years. Despite a modest higher prevalence of RDs among females (54.0% of the total), male cases had a significant increased risk of death (hazard ratio, HR 1.48, 95% CI 1.38–1.58). Cases diagnosed during 2010–2018 period had a risk of death significantly lower than those diagnosed during 2000–2009 (HR 0.81, 95% CI 0.82–0.96), especially for immune system disorders (HR 0.48, 95% CI 0.26–0.87), circulatory system diseases (HR 0.61, 95% CI 0.45–0.84) and diseases of the musculoskeletal system and connective tissue (HR 0.64, 95% CI 0.49–0.84). Conclusions An earlier diagnosis as well as the improvement in the efficacy of treatment resulted in a decreased risk of death over the years for specific RDs. The linkage between a population-based registry and other regional databases exploited in this study provides a large and accurate mass of data capable of estimating patients’ life-expectancy and increasing knowledge on the collective burden of RDs.

Venditti et al. identify FAPP1 as a new determinant of ER–trans-Golgi network contacts that interacts with the phosphoinositide phosphatase Sac1 and promotes its phosphatase activity. The results suggest that, by controlling PI4P levels, FAPP1 acts as a gatekeeper of cargo Golgi exit., Phosphatidylinositol-4-phosphate (PI4P), a phosphoinositide with key roles in the Golgi complex, is made by Golgi-associated phosphatidylinositol-4 kinases and consumed by the 4-phosphatase Sac1 that, instead, is an ER membrane protein. Here, we show that the contact sites between the ER and the TGN (ERTGoCS) provide a spatial setting suitable for Sac1 to dephosphorylate PI4P at the TGN. The ERTGoCS, though necessary, are not sufficient for the phosphatase activity of Sac1 on TGN PI4P, since this needs the phosphatidyl-four-phosphate-adaptor-protein-1 (FAPP1). FAPP1 localizes at ERTGoCS, interacts with Sac1, and promotes its in-trans phosphatase activity in vitro. We envision that FAPP1, acting as a PI4P detector and adaptor, positions Sac1 close to TGN domains with elevated PI4P concentrations allowing PI4P consumption. Indeed, FAPP1 depletion induces an increase in TGN PI4P that leads to increased secretion of selected cargoes (e.g., ApoB100), indicating that FAPP1, by controlling PI4P levels, acts as a gatekeeper of Golgi exit.

Patients with rare diseases (RDs) need tailored, continuous, and multidisciplinary hospital care. This retrospective cohort study aimed to analyse the healthcare burden of RD patients using a multi-database approach, by linking the data of the Rare Diseases Registry of Tuscany with the regional hospital discharge database. The study population included 21,354 patients diagnosed with a RD between 1 January 2000 and 31 December 2017. The healthcare burden was evaluated for all the RDs during 2009–2018 period. The hospitalisation rate (per 1000) decreased over the years, ranging from 606.9 in 2009 (95% CI: 589.2–625.0) to 443.0 in 2018 (95% CI: 433.2–453.0). A decrease in the average length of stay (LOS) was observed in the earlier years, followed by an increase up to a steady trend (8.3 days in 2018). The patients with RDs of metabolism and the genitourinary system showed the highest hospitalisation rate (903.3 and 644.0 per 1000, respectively). The patients with rare immune system disorders and diseases of the skin and subcutaneous tissue showed the highest LOS (9.7 and 9.5 days, respectively). The methodological approach presented in this population-based study makes it possible to estimate the healthcare burden of RDs, which is crucial in the decision-making and planning aimed at improving patient care.

Background Patients hospitalized with COVID-19 experienced an increased risk of venous thromboembolism. Aims To evaluate the effect of chronic oral anticoagulation (OAC) therapy, both with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), on prognosis of COVID-19 older patients. Methods Single-center prospective study conducted in the Emergency Department (ED) of a teaching hospital, referral center for COVID-19 in central Italy. We evaluated all the patients ≥ 65 years, consecutively admitted to our ED for confirmed COVID-19. We compared the clinical outcome of those who were on chronic OAC at ED admission with those who did not, using a propensity score matched paired cohort of controls. The primary study endpoint was all-cause in-hospital death. Patients were matched for age, sex, clinical comorbidities, and clinical severity at presentation (based on NEWS ≥ 6). Study parameters were assessed for association to all-cause in-hospital death by a multivariate Cox regression analysis to identify independent risk factor for survival. Results Although overall mortality was slightly higher for anticoagulated patients compared to controls (63.3% vs 43.5%, p = 0.012), the multivariate adjusted hazard ratio (HR) for death was not significant (HR = 1.56 [0.78–3.12]; p = 0.208). Both DOACs (HR 1.46 [0.73–2.92]; p = 0.283) and VKAs (HR 1.14 [0.48–2.73]; p = 0.761) alone did not affect overall survival in our cohort. Conclusions Among older patients hospitalized for COVID-19, chronic OAC therapy was not associated with a reduced risk of in-hospital death. Moreover, our data suggest similar outcome both for patients on VKAs or in patients on DOACs. Supplementary Information The online version contains supplementary material available at 10.1007/s40520-021-01924-w.

Introduction : To date, mainly due to age-related vulnerability and to coexisting comorbidities, older patients often face a more severe COVID-19. This study aimed to identify at Emergency Department (ED) admission the predictors of in-hospital mortality and suitable scores for death risk stratification among COVID-19 patients ≥ 80 years old. Methods : Single-centre prospective study conducted in the ED of an university hospital, referral center for COVID-19 in central Italy. We included 239 consecutive patients ≥ 80 years old with laboratory-confirmed COVID-19. The primary study endpoint was all-cause in-hospital mortality. Multivariable Cox regression analysis was performed on significant variables at univariate analysis to identify independent risk factor for death. Overall performance in predicting mortality of WHO severity scale, APACHE II score, NEWS score, and CURB-65 was calculated. Results : Median age was 85 [82-89] and 112 were males (46.9%). Globally, 77 patients (32.2%) deceased. The presence of consolidations at chest x-ray and the hypoxemic respiratory failure were significant predictors of poor prognosis. Moreover, age ≥ 85 years, dependency in activities of daily living (ADL), and dementia were risk factors for death, even after adjusting for clinical covariates and disease severity. All the evaluated scores showed a fairly good predictive value in identifying patients who could experience a worse outcome. Conclusions : Among patients ≥ 80 years old hospitalized with COVID-19, not only a worse clinical and radiological presentation of the disease, but also the increasing age, dementia, and impairment in ADL were strong risk factors for in-hospital death, regardless of disease severity.

Background: In Europe, about 76% of cases of chromosomal anomalies are prenatally diagnosed. Prenatal diagnosis allows more efficient planning of postnatal treatment and helps parents for an informed decision about the continuation of pregnancy. The main aim of this study was to evaluate whether the sociodemographic maternal characteristics affect the probability of prenatal diagnosis of chromosomal anomalies.Methods: Cases of chromosomal anomalies in the period 2005–2017 came from the population-based registry of congenital anomalies of Tuscany (Italy). Differences in the proportion of cases prenatally diagnosed were investigated through the following maternal characteristics: education, geographic origin and occupation. The association between cases of termination of pregnancy after prenatal diagnosis and maternal characteristics was also analysed. Odds Ratios (OR) adjusted by maternal age were calculated using logistic regression models. Results were provided for all cases of chromosomal anomalies and for Down syndrome cases.Results: A total of 1,419 cases were included in the study. Cases prenatally diagnosed were 1,186 (83.6%). We observed a higher proportion of cases not prenatally diagnosed among cases with low maternal education compared to those with high maternal education (OR = 2.16, p < 0.001) and in women from high migratory outflow countries, compared to the Italian ones (OR = 2.85, p < 0.001). For prenatally diagnosed Down syndrome cases, we observed a higher proportion of termination of pregnancy for women with low education level (OR = 4.36, p = 0.023).Conclusions: In our study evidence of differences in the probability of prenatal diagnosis of chromosomal anomalies associated with maternal education and geographic origin was found. Population-based studies investigating sociodemographic disparities can provide essential information for targeted public health programs. Further studies are recommended to monitor the impact of the increasing availability of non-invasive screening tests.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV- 2) is the causative agent of the respiratory disease later named Coronavirus Disease 2019 (COVID-19), remaining a world public health emergency at present...

AIM: The aim of the present study was to describe the clinical presentation of patients aged ≥80 years with coronavirus disease 2019 (COVID-19), and provide insights regarding the prognostic factors and the risk stratification in this population. METHODS: This was a single-center, retrospective, observational study, carried out in a referral center for COVID-19 in central Italy. We reviewed the clinical records of patients consecutively admitted for confirmed COVID-19 over a 1-month period (1-31 March 2020). We excluded asymptomatic discharged patients. We identified risk factors for death, by a uni- and multivariate Cox regression analysis. To improve model fitting and hazard estimation, continuous parameters where dichotomized by using Youden's index. RESULTS: Overall, 69 patients, aged 80-98 years, met the inclusion criteria and were included in the study cohort. The median age was 84 years (82-89 years is interquartile range); 37 patients (53.6%) were men. Globally, 14 patients (20.3%) presented a mild, 30 (43.5%) a severe and 25 (36.2%) a critical COVID-19 disease. A total of 23 (33.3%) patients had died at 30 days' follow up. Multivariate Cox regression analysis showed that severe dementia, pO2 ≤90 at admission and lactate dehydrogenase >464 U/L were independent risk factors for death. CONCLUSIONS: The present data suggest that risk of death could be not age dependent in patients aged ≥80 years, whereas severe dementia emerged is a relevant risk factor in this population. Severe COVID-19, as expressed by elevated lactate dehydrogenase and low oxygen saturation at emergency department admission, is associated with a rapid progression to death in these patients. Geriatr Gerontol Int 2020; ••: ••-••.

Introduction:This study was aimed to assess if combining the evaluation of blood glucose level (BGL) and the Triage Revised Trauma Score (T-RTS) may result in a more accurate prediction of the actual clinical outcome, both in general adult population and in elderly patients with trauma.Methods:This is a retrospective cohort study, conducted in the emergency department (ED) of an urban teaching hospital, with an average ED admission rate of 75,000 patients per year. Those excluded: known diagnosis of diabetes, age Results:Among a total of 68,933 traumas, 9,436 patients (4,407 females) were enrolled, aged from 18 to 103 years; 4,288 were aged ≥65 years. A total of 577 (6.1%) met the primary endpoint: 38 patients died in ED (0.4%) and 539 patients were admitted to ICU. The T-RTS and BGL were independently associated to primary endpoint at multivariate analysis. The cumulative RTS-G score was significantly more accurate than T-RTS and reached the best accuracy in elderly patients. In general population, ROC area under curve (AUC) for T-RTS was 0.671 (95% CI, 0.661 - 0.680) compared to RTS-G ROC AUC 0.743 (95% CI, 0.734 - 0.752); P Conclusions:Results showed RTS-G could be used effectively at ED triage for the risk stratification for death in ED and ICU admission of trauma patients, and it could reduce under-triage of approximately 20% compared to T-RTS. Comparing ROC AUCs, the combined RTS-G score performs significantly better than T-RTS and gives best results in patients ≥65 years.

Background Down syndrome (DS) is the most common autosomal chromosomal anomaly in liveborn infants. About 40% of infants with DS have a major congenital heart defect (CHD). Among them, atrioventricular septal defects (AVSD), atrial septal defects (ASD), ventricular septal defect (VSD) and Tetralogy of Fallot (ToF) are the most common. The aim of this study was to estimate the sex difference in the occurrence of CHD in infants with DS comparing it with non-DS infants. Method Live birth cases of DS diagnosed by the first year of life were extracted from the Registry of Congenital Anomalies of Tuscany (2003–2015 period). CHDs associated with DS were detected both from the registry and the hospital discharge data. Sex differences in total CHDs and ASD, VSD, AVSD, severe CHDs, ToF subgroups were investigated. Relative Risks between males and females (RRMF) with p-values and 95% confidence interval (95% CI) were estimated. RRMF of CHD in infants with DS was compared to RRMF in infants without DS. The ratio between relative risks (RRR) was estimated. Results A total of 230 live birth cases of DS were analyzed, with a prevalence of 5.70 per 10,000 births. Sex ratioMF was 1.3. One hundred and one DS cases (43.9%) were associated with at least one CHD. Among them, CHDs are more frequent in females (total CHD: RRMF = 0.62; 95% CI: 0.46–0.83, ASD: RRMF = 0.40; 95% CI: 0.21–0.77, severe CHD: RRMF = 0.58; 95% CI: 0.35–0.95, AVSD: RRMF = 0.57; 95% CI: 0.32–1.00, VSD: RRMF = 0.59; 95% CI: 0.35–1.00). Four cases of ToF were observed (all males). Sex difference was more evident in DS than in non-DS infants (RRR = 0.63; 95% CI: 0.52–0.77), in particular for severe CHDs (RRR = 0.38; 95% CI: 0.25–0.57). Conclusion The increased sex difference for CHDs in DS suggests a possible role of sex as effect modifier in the association between DS and CHD. The results enforce the evidence on sex differences for CHDs in DS and can stimulate future genetic research activities.

The diagnosis and treatment of sepsis have always been a challenge for the physician, especially in critical care setting such as emergency department (ED), and currently sepsis remains one of the major causes of mortality. Although the traditional definition of sepsis based on systemic inflammatory response syndrome (SIRS) criteria changed in 2016, replaced by the new criteria of SEPSIS-3 based on organ failure evaluation, early identification and consequent early appropriated therapy remain the primary goal of sepsis treatment. Unfortunately, currently there is a lack of a foolproof system for making early sepsis diagnosis because conventional diagnostic tools like cultures take a long time and are often burdened with false negatives, while molecular techniques require specific equipment and have high costs. In this context, biomarkers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT), are very useful tools to distinguish between normal and pathological conditions, graduate the disease severity, guide treatment, monitor therapeutic responses and predict prognosis. Among the new emerging biomarkers of sepsis, Presepsin (P-SEP) appears to be the most promising. Several studies have shown that P-SEP plasma levels increase during bacterial sepsis and decline in response to appropriate therapy, with sensitivity and specificity values comparable to those of PCT. In neonatal sepsis, P-SEP compared to PCT has been shown to be more effective in diagnosing and guiding therapy. Since in sepsis the P-SEP plasma levels increase before those of PCT and since the current methods available allow measurement of P-SEP plasma levels within 17 min, P-SEP appears a sepsis biomarker particularly suited to the emergency department and critical care.

The lack of participatory tools in Health Impact Assessment (HIA) to support decision-makers is a critical factor that negatively affects the impacts of waste policies. This study describes the participatory HIA used in deciding on the possible doubling of the municipal solid waste incinerating plant located near the city of Arezzo, Italy. Within the framework of the new waste management plan, a methodology for the democratic participation of stakeholders was designed adopting the Local Agenda 21 methodology. Communication and participation events with the stakeholders were set up from the plan’s development to its implementation. Eleven different categories of stakeholders including individual citizens were involved in 21 local events, reaching over 500 participants in three years. Actions were performed to build the commitment and ownership of the local administrators. Then, together with the environment and health agencies and a representative from the local committees, the local administrators collaborated with scientists and technicians in the knowledge-building and scoping stages. Focus groups of voluntary citizens worked together with the researchers to provide qualitative and quantitative evidence in the assessment stage. Periodic public forums were held to discuss processes, methods and findings. The local government authority considered the HIA results in the final decision and a new waste strategy was adopted both in the short term (increased curbside collection, waste sustainability program) and in the long term (limited repowering of the incinerator, new targets for separate collection). In conclusion, an effective participatory HIA was carried out at the municipal level to support decision makers in the waste management plan. The HIA21 study contributed to evidence-based decisions and to make a broadly participatory experience. The authors are confident that these achievements may improve the governance of the waste cycle and the trust in the public administration.