Sledding injuries: is safety in this winter pastime overlooked? A three-year survey in South-Tyrol

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Sledding is a popular traditional pastime in northern countries. However it is only rarely thought as a potentially dangerous activity even though serious injuries and deaths do occur. The purpose of this study was to calculate the incidence, the severity and the pattern of sleddingrelated injuries in our area, in order to set up possible preventive measures. Results: In three consecutive winter seasons (Dec.–Apr.,2002–2005). 356 patients (182 males, 174 females, mean age 26.9 years, range 2 to 81) were referred directly to our ED after a sledding injury. One patient (male, age 21 years) was transferred from a community hospital and died on the following day. Two patients (males, age 47 and 28 years) were declared dead on the scene. In the majority of the cases the accident was due to a fall and collision with the ground or a standing object. The number of injuries showed a progressive increase during the observed seasons and all deadly accidents were observed in the last season. Injuries were divided into three severity classes: minor (ISS ≤ 3), intermediate (ISS ≥ 4 < 15), severe (ISS ≥ 15). Minor and intermediate injuries were equally distributed between males and females, whereas all severe and deadly accidents occurre

Loss of miR-204 expression is a key event in melanoma

Cutaneous melanoma (CM) is a malignancy with increasing occurrence. Its microRNA repertoire has been defined in a number studies, leading to candidates for biological and clinical relevance: miR-200a/b/c, miR-203, miR-205, miR-204, miR-211, miR-23b and miR-26a/b. Our work was aimed to validate the role of these candidate miRNAs in melanoma, using additional patients cohorts and in vitro cultures. miR-26a, miR-204 and miR-211 were more expressed in normal melanocytes, while miR-23b, miR-200b/c, miR-203 and miR-205 in epidermis and keratinocytes. None of the keratinocyte-related miRNAs was associated with any known mutation or with clinical covariates in melanoma. On the other hand, the loss of miR-204 was enriched in melanomas with NRAS sole mutation (Fisher exact test, P = 0.001, Log Odds = 1.67), and less frequent than expected in those harbouring CDKN2A mutations (Fisher exact test, P = 0.001, Log Odds − 1.09). Additionally, miR-204 was associated with better prognosis in two independent melanoma cohorts and its exogenous expression led to growth impairment in melanoma cell lines. Thus, miR-204 represents a relevant mechanism in melanoma, with potential prognostic value and its loss seems to act in the CDKN2A pathway, in cooperation with NRAS

ERS statement on standardisation of cardiopulmonary exercise testing in chronic lung diseases

The objective of this document was to standardise published cardiopulmonary exercise testing (CPET) protocols for improved interpretation in clinical settings and multicentre research projects. This document: 1) summarises the protocols and procedures used in published studies focusing on incremental CPET in chronic lung conditions; 2) presents standard incremental protocols for CPET on a stationary cycle ergometer and a treadmill; and 3) provides patients’ perspectives on CPET obtained through an online survey supported by the European Lung Foundation. We systematically reviewed published studies obtained from EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects were included. The literature supports a test protocol with a resting phase lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental phase with work rate increased linearly at least every minute, followed by a recovery phase of at least 2–3 min. Patients responding to the survey (n=295) perceived CPET as highly beneficial for their diagnostic assessment and informed the Task Force consensus. Future research should focus on the individualised estimation of optimal work rate increments across different lung diseases, and the collection of robust normative data.The document facilitates standardisation of conducting, reporting and interpreting cardiopulmonary exercise tests in chronic lung diseases for comparison of reference data, multi-centre studies and assessment of interventional efficacy. http://bit.ly/31SXeB

Improving prehospital trauma management for skiers and snowboarders - need for on-slope triage?

Background Injuries from skiing and snowboarding became a major challenge for emergency care providers in Switzerland. In the alpine setting, early assessment of injury and health status is essential for the initiation of adequate means of care and transport. Nevertheless, validated standardized protocols for on-slope triage are missing. This article can assist in understanding the characteristics of injured winter sportsmen and exigencies for future on-slope triage protocols. Methods Six-year review of trauma cases in a tertiary trauma centre. Consecutive inclusion of all injured skiers and snowboarders aged >15 (total sample) years with predefined, severe injury to the head, spine, chest, pelvis or abdomen (study sample) presenting at or being transferred to the study hospital. Descriptive analysis of age, gender and injury pattern. Results Amongst 729 subjects (total sample) injured from skiing or snowboarding, 401 (55%, 54% of skiers and 58% of snowboarders) suffered from isolated limb injury. Amongst the remaining 328 subjects (study sample), the majority (78%) presented with monotrauma. In the study sample, injury to the head (52%) and spine (43%) was more frequent than injury to the chest (21%), pelvis (8%), and abdomen (5%). The three most frequent injury combinations were head/spine (10% of study sample), head/thorax (9%), and spine/thorax (6%). Fisher's exact test demonstrated an association for injury combinations of head/thorax (p < 0.001), head/abdomen (p = 0.019), and thorax/abdomen (p < 0.001). Conclusion The data presented and the findings from previous investigations indicate the need for development of dedicated on-slope triage protocols. Future research must address the validity and practicality of diagnostic on-slope tests for rapid decision making by both professional and lay first responders. Thus, large-scale and detailed injury surveillance is the future research priority

European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part I

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients’ autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the ‘Cicatrising Conjunctivitis Assessment Tool’ and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course

European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part II

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10–25% of patients laminin 332 is recognized. In 25–30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials

Exploring the Prognostic Performance of MECKI Score in Heart Failure Patients with Non-Valvular Atrial Fibrillation Treated with Edoxaban

Introduction: Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF. Materials and Methods: This study included consecutive outpatients with HF and NVAF treated with edoxaban (n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation. Results: Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations’ survival appeared non-significantly different at the 2-year follow-up. Conclusions: this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients

Multiparametric prognostic scores in chronic heart failure with reduced ejection fraction: a long-term comparison

Aims: Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction. Methods and results: We collected data on 6112 HF patients and compared the prognostic accuracy of MECKI score, HFSS, and SHFM at 2- and 4-year follow-up for the combined endpoint of cardiovascular death, urgent cardiac transplantation, or ventricular assist device implantation. Patients were followed up for a median of 3.67 years, and 931 cardiovascular deaths, 160 urgent heart transplantations, and 12 ventricular assist device implantations were recorded. At 2-year follow-up, the prognostic accuracy of MECKI score was significantly superior [area under the curve (AUC) 0.781] to that of SHFM (AUC 0.739) and HFSS (AUC 0.723), and this relationship was also confirmed at 4 years (AUC 0.764, 0.725, and 0.720, respectively). Conclusion: In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2- and 4-year follow-up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed

The satisfactory growth and development at 2 years of age of the INTERGROWTH-21st Fetal Growth Standards cohort support its appropriateness for constructing international standards.

BACKGROUND: The World Health Organization recommends that human growth should be monitored with the use of international standards. However, in obstetric practice, we continue to monitor fetal growth using numerous local charts or equations that are based on different populations for each body structure. Consistent with World Health Organization recommendations, the INTERGROWTH-21st Project has produced the first set of international standards to date pregnancies; to monitor fetal growth, estimated fetal weight, Doppler measures, and brain structures; to measure uterine growth, maternal nutrition, newborn infant size, and body composition; and to assess the postnatal growth of preterm babies. All these standards are based on the same healthy pregnancy cohort. Recognizing the importance of demonstrating that, postnatally, this cohort still adhered to the World Health Organization prescriptive approach, we followed their growth and development to the key milestone of 2 years of age. OBJECTIVE: The purpose of this study was to determine whether the babies in the INTERGROWTH-21st Project maintained optimal growth and development in childhood. STUDY DESIGN: In the Infant Follow-up Study of the INTERGROWTH-21st Project, we evaluated postnatal growth, nutrition, morbidity, and motor development up to 2 years of age in the children who contributed data to the construction of the international fetal growth, newborn infant size and body composition at birth, and preterm postnatal growth standards. Clinical care, feeding practices, anthropometric measures, and assessment of morbidity were standardized across study sites and documented at 1 and 2 years of age. Weight, length, and head circumference age- and sex-specific z-scores and percentiles and motor development milestones were estimated with the use of the World Health Organization Child Growth Standards and World Health Organization milestone distributions, respectively. For the preterm infants, corrected age was used. Variance components analysis was used to estimate the percentage variability among individuals within a study site compared with that among study sites. RESULTS: There were 3711 eligible singleton live births; 3042 children (82%) were evaluated at 2 years of age. There were no substantive differences between the included group and the lost-to-follow up group. Infant mortality rate was 3 per 1000; neonatal mortality rate was 1.6 per 1000. At the 2-year visit, the children included in the INTERGROWTH-21st Fetal Growth Standards were at the 49th percentile for length, 50th percentile for head circumference, and 58th percentile for weight of the World Health Organization Child Growth Standards. Similar results were seen for the preterm subgroup that was included in the INTERGROWTH-21st Preterm Postnatal Growth Standards. The cohort overlapped between the 3rd and 97th percentiles of the World Health Organization motor development milestones. We estimated that the variance among study sites explains only 5.5% of the total variability in the length of the children between birth and 2 years of age, although the variance among individuals within a study site explains 42.9% (ie, 8 times the amount explained by the variation among sites). An increase of 8.9 cm in adult height over mean parental height is estimated to occur in the cohort from low-middle income countries, provided that children continue to have adequate health, environmental, and nutritional conditions. CONCLUSION: The cohort enrolled in the INTERGROWTH-21st standards remained healthy with adequate growth and motor development up to 2 years of age, which supports its appropriateness for the construction of international fetal and preterm postnatal growth standards

EMERGENCY PLANNING IN CASE OF CBRN EVENTS: AN INNOVATIVE METHODOLOGY TO IMPROVE THE SAFETY KNOWLEDGE OF ADVISORS AND FIRST RESPONDERS BY A MULTIDISCIPLINARY TABLE TOP EXERCISE.

ABSTRACT Nowadays Chemical-Biological-Radiological-Nuclear (CRBN) risks are one of the main safety concern. The radiological disasters of Fukushima and Chernobyl, the chemical events of Seveso or the release of Sarin in the Tokio Subway,and the biological emergencies such as the H1N1 flue represent few examples of a dreadful evidence: : CBRNe risks are a real and global threat around us. A CBRNe event can be either of an intentional and un-intentional nature and it is important to have highly specialized advisors that can support decision makers and first responders to face this threat. The University of Rome Tor Vergata, in collaboration with the most important Italian and International Bodies that work in the field of CBRN safety and security and supported by NATO and OPCW, organized two International Master Courses in Protection against CBRN events. In this context, a Table Top Exercise (TTX) was organized, in collaboration with the Ministry of Interior and Ministry of Defence, taking into account that, in each country, the system response to CBRNe events strongly depends also on law and procedures, that enforce the advisors and first responders to rely with different skills and roles in function of the administration of origin. The organized TTX was aimed to test the level preparation of the Master students and experts working in Italy in the field of CBRN events and to test the emergency planning preparation. In particular, a radiological release was simulated in a Harbour facility in Urban Area. The students were divided in multidisciplinary groups with heterogeneous competences. Each group was supported by CBRNì experts and was stressed by the injects from a Command and Operative Centre. Responsiveness to the injects and to the stress together with the ability to organize and manage safety and security operations, but also to interpret each role in the team according to according to national laws, were evaluated for each group. The scenario, the logistic organization, on-going adjustments during the exercise and the outcomes will be presented and analyzed by the authors in this paper. PRELIMINARY INDEX 1. Abstract 2. Introduction 3. Table Top Exercise (TTX) 3.1 What is a TTX 3.2 How the TTX is organized 3.3 Scenario and injects 3.4 Organizational and technical solutions 4. Dat