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We aim to estimate the incidence rates (IRs) of SARS-CoV-2 infections stratified by disease severity and comorbidities in pediatric population and to describe the COVID-19 vaccination coverage in children with and without comorbidities. A population-based cohort study was conducted in 6 electronic healthcare records databases from Italy, Spain, and Norway. The study lasted from 1 January 2020 to the latest databases' available data in each site, i.e., in Italian ARS Tuscany and PEDIANET: December 2021, in Spanish BIFAP: February 2022; SIDIAP: June 2022, and VID: December 2021. Finally, in Norwegian Health Registries: December 2021. Children and adolescents were included and stratified into three age categories (< 5, 5- < 12, and 12- < 18 years old). IRs (95% confidence intervals) per 100 person-years (PY) for non-severe (positive SARS-CoV-2 test or diagnosis without hospitalization) and severe COVID-19 (hospitalization, intensive care unit admission, and death after COVID-19) are reported. The cumulative COVID-19 vaccination rollout was stratified by population with and without comorbidities. The study population comprised 5,654,040 individuals < 18 years of age (51% females) across the six European databases (median age: 6 years), with 1.4 to 8.5% of them having at least one at-risk comorbidity for severe COVID-19. Incidence rates of severe COVID-19 were low (0-1 per 100 PY) but 3 to 4 times higher among children and adolescents with comorbidities during Omicron BA.1-2 wave in December 2021-January 2022. Percentages of vaccination rollout in the general population were between 13% in PEDIANET-IT and 64% in BIFAP-ICU-ES. In ARS-IT and SIDIAP-IT, vaccination rate in children with comorbidities was slightly lower than that in the general population., Conclusion: Severe COVID-19 was rare across databases, but up to 3 to 4 times higher in children with comorbidities during the predominance of Omicron BA.1-2 variant in winter 2021-2022. COVID-19 vaccination coverage was slightly lower in children with comorbidities in ARS (Tuscany) and SIDIAP (Catalonia) data sources. Our findings will inform future public policies aimed to protect the pediatric population, both within these countries and globally., What Is Known: • Pediatric population is susceptible to SARS-CoV-2 infection. • COVID-19 severity rates in children vary across study settings and context., What Is New: • This study confirms the low severity rates of COVID-19 in the pediatric population based on a large cohort of children and adolescents residing in Spain, Italy, and Norway. • Incidence of severe COVID-19 in children and adolescents with comorbidities was up to 3 to 4 times higher than in the general pediatric population during the SARS-CoV-2 high transmission wave of Omicron BA.1-2 variant in winter 2021-2022 in Italy and Spain., Competing Interests: Declarations Ethics approval Most data partners that provided data for the herein-presented results had passed the local ethical review process for the whole COVID-19 Vaccine Monitor study (EUPAS42467); Norwegian data (NHR): Regional Committee for Research Ethics (approval number 155294/REK Nord) and the Data Protection Officer at the University of Oslo (approval number 523275); Valencian data (VID): Comité Ético de Investigación con Medicamentos del Hospital General Universitario de Elche (approval number: PI-90/2021); Catalonian data (SIDIAP): Comitè Ètic d'Investigació amb medicaments (CEIm) de l'IDIAP Jordi Gol (approval number: 21/199-PCV); and BIFAP (several Spanish regions): Comité de Ética de la Investigación con Medicamentos del Hospital Universitario de la Princesa and Comité Científico de BIFAP (approval number: CEIm 14/21). There was no need of ethical committee approval for Italian databases (ARS and PEDIANET). This research adhered to the rules and principles of the European Network of Centers of Pharmacoepidemiology and Pharmacovigilance (ENCePP) Code of Conduct. Consent to participate This research was conducted using secondary heathcare data. Informed consent to participate was not obtained. The whole COVID-19 Vaccine Monitor study (EUPAS42467) was conducted following the ENCePP Code of Conduct. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chemoradiation therapy (CRT) is a treatment for muscle-invasive bladder cancer (MIBC). Using a novel transcriptomic profiling panel, we validated prognostic immune biomarkers to CRT using 70 pretreatment tumor samples from prospective trials of MIBC (NRG/RTOG 0524 and 0712). Disease-free survival (DFS) and overall survival (OS) were estimated via the Kaplan-Meier method and stratified by genes correlated with immune cell activation. Cox proportional-hazards models were used to assess group differences. Clustering of gene expression profiles revealed that the cluster with high immune cell content was associated with longer DFS (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.26-1.10; p = 0.071) and OS (HR 0.48, 95% CI 0.24-0.97; p = 0.040) than the cluster with low immune cell content. Higher expression of T-cell infiltration genes (CD8A and ICOS) was associated with longer DFS (HR 0.40, 95% CI 0.21-0.75; p = 0.005) and OS (HR 0.49, 95% CI 0.25-0.94; p = 0.033). Higher IDO1 expression (IFNγ signature) was also associated with longer DFS (HR 0.44, 95% CI 0.24-0.88; p = 0.021) and OS (HR 0.49, 95% CI 0.24-0.99; p = 0.048). These findings should be validated in prospective CRT trials that include biomarkers, particularly for trials incorporating immunotherapy for MIBC. PATIENT SUMMARY: We analyzed patient samples from two clinical trials (NRG/RTOG 0524 and 0712) of chemoradiation for muscle-invasive bladder cancer using a novel method to assess immune cells in the tumor microenvironment. Higher expression of genes associated with immune activation and high overall immune-cell content were associated with better disease-free survival and overall survival for patients treated with chemoradiation., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

We test the robustness of the self-controlled risk interval (SCRI) design in a setting where time between doses may introduce time-varying confounding, using both negative control outcomes (NCOs) and quantitative bias analysis (QBA). All vaccinated cases identified from 5 European databases between 1 September 2020 and end of data availability were included. Exposures were doses 1-3 of the Pfizer, Moderna, AstraZeneca, and Janssen COVID-19 vaccines; outcomes were myocarditis and otitis externa (NCO). The SCRI used a 60-day control window and dose-specific 28-day risk windows, stratified by vaccine brand and adjusted for calendar time. The QBA included two scenarios: (i) baseline probability of the confounder was higher in the control window and (ii) vice versa. The NCO was not associated with any of the COVID-19 vaccine types or doses except Moderna dose 1 (IRR = 1.09, 95%CI 1.01-1.09). The QBA suggested even the strongest literature-reported confounder (COVID-19; RRmyocarditis = 18.3) could only explain away part of the observed effect from IRR = 3 to IRR = 1.40. The SCRI seems robust to unmeasured confounding in the COVID-19 setting, although a strong unmeasured confounder could bias the observed effect upward. Replication of our findings for other safety signals would strengthen this conclusion., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Pasteurellosis, a disease caused by Pasteurella multocida , is responsible for economic losses in rabbit industrial farms due to rhinitis, conjunctivitis, pneumonia, metritis, mastitis, orchitis, subcutaneous abscesses, otitis, encephalitis, and septicaemic forms. Although the occurrence of the disease is conditioned by predisposing factors that affect the rabbit immune response, the strains of P. multocida involved in the infection may have a different pathogenic ability. Therefore, typing of strains spread among the rabbits is important to assess their pathogenic potential. The aim of this study is to investigate the P. multocida strains responsible for disease in rabbit industrial farms. A total of 114 strains identified from different lesions were serotyped. Additionally, the presence of virulence-associated genes was investigated using three PCR (polymerase chain reaction) protocols. Capsular type A was prevalently found in strains from respiratory lesions while types D and F in those from metritis, mastitis, and other lesions. Different associations between some virulence-associated genes and both capsular type and lesions found in rabbits were detected. The presence of 8 virulence-associated genes seems to increase the occurrence of metritis. In addition, strains belonging to capsular type A and responsible for respiratory disorders especially, were found equipped with 10 and 11 virulence-associated genes. Nevertheless, the presence of strains responsible only for rhinitis was also detected among the latter, suggesting that the pathogenic ability of the bacteria depends on the expression rather than the presence of a gene.

Introduction: The aim of this study was to assess the possible extent of bias due to violation of a core assumption (event-dependent exposures) when using self-controlled designs to analyse the association between COVID-19 vaccines and myocarditis., Methods: We used data from five European databases (Spain: BIFAP, FISABIO VID, and SIDIAP; Italy: ARS-Tuscany; England: CPRD Aurum) converted to the ConcePTION Common Data Model. Individuals who experienced both myocarditis and were vaccinated against COVID-19 between 1 September 2020 and the end of data availability in each country were included. We compared a self-controlled risk interval study (SCRI) using a pre-vaccination control window, an SCRI using a post-vaccination control window, a standard SCCS and an extension of the SCCS designed to handle violations of the assumption of event-dependent exposures., Results: We included 1,757 cases of myocarditis. For analyses of the first dose of the Pfizer vaccine, to which all databases contributed information, we found results consistent with a null effect in both of the SCRI and extended SCCS, but some indication of a harmful effect in a standard SCCS. For the second dose, we found evidence of a harmful association for all study designs, with relatively similar effect sizes (SCRI pre = 1.99, 1.40 - 2.82; SCRI post 2.13, 95 %CI - 1.43, 3.18; standard SCCS 1.79, 95 %CI 1.31 - 2.44, extended SCCS 1.52, 95 %CI = 1.08 - 2.15). Adjustment for calendar time did not change these conclusions. Findings using all designs were also consistent with a harmful effect following a second dose of the Moderna vaccine., Conclusions: In the context of the known association between COVID-19 vaccines and myocarditis, we have demonstrated that two forms of SCRI and two forms of SCCS led to largely comparable results, possibly because of limited violation of the assumption of event-dependent exposures., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: University Medical Center Utrecht in collaboration with the Vaccine Monitoring Collaboration for Europe network (VAC4EU). reports financial support was provided by European Medicines Agency. Anna Schultze reports a relationship with GSK that includes: funding grants. Ian Douglas reports a relationship with GSK that includes: equity or stocks and funding grants. Fabio Riefolo reports a relationship with TEAMIT Institute, a research management organisation that participates in financially supported studies for the European Medicines Agency and related healthcare authorities, pharmaceutical companies, and the European Union that includes: employment. Felipe Villalobos, Meritxell Palleja-Millan, Carlo Alberto Bissacco and Elena Segundo reports a relationship with IDIAPJGol, which receives institutional research funding from public and private partners, pharmaceutical companies and regulatory agencies that includes: employment. Miriam Sturkenboom reports a relationship with University Medical Center Utrecht, which conducts studies for the European Medicines Agency, the European Commission and medicine manufacturers, all according to the ENCePP code of conduct that includes: employment. Carlos E. Duran reports a relationship with University Medical Center Utrecht, which receives institutional research funding from pharmaceutical companies and regulatory agencies that includes: employment. Rosa Gini and Davide Messina reports a relationship with ARS Tuscany, which reports funding from the Innovative Medicines Initiative, RTI, PHARMO, University of Southern Denmark, University of Utrecht, Eli Lilly, Pfizer, Novartis, AstraZeneca, Galapagos, and LeoPharma that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier India Pvt Ltd. All rights reserved.)

Background : Adolescent idiopathic scoliosis (AIS) is a spinal pathology affecting 0.47-5.2% of the population, often requiring surgical intervention to control deformity progression. Posterior spinal instrumentation and fusion with pedicle screw fixation are standard procedures for AIS curve correction; however, implant failure remains a significant complication, especially in multi-level fusions. This retrospective cohort study aims to compare the failure rates between conventional pedicle screws (CPSs) and fenestrated pedicle screws (FPSs) in AIS treatment, with a focus on investigating potential causes of these failures. Methods : This study, conducted from January 2016 to December 2020, involves a two-center retrospective analysis of AIS patients undergoing posterior instrumented fusion. Results : Data from a total of 162 patients (122 females and 40 males) revealed a mean age of 14.95 years (range: 11-18). The CPS group consisted of 80 patients (56 females and 24 males), whereas the FPS group consisted of 82 patients (66 females and 16 males) stratified by Risser grade and Lenke Classification. Radiological assessments, clinical outcomes, and SRS-22 scores were evaluated pre-operatively, at 6 months, and post-operatively (minimum follow-up of 2 years). Conclusions : Fenestrated pedicle screws (FPSs) pose concerns due to their lower mechanical strength compared to solid screws. Understanding their limitations and optimizing their application in AIS treatment is essential.

Using 4 data-sources (Spain, Italy, United Kingdom) data and a 1:1 matched cohort study, we aimed to estimate vaccine effectiveness (VE) in preventing SARS-CoV-2 infections with hospitalisations (±30 days) and death (±56 days) in general population and clinical subgroups with homologous/heterologous booster schedules (Comirnaty-BNT and Spikevax-MOD original COVID-19 vaccines) by comparison with unboosted individuals, during Delta and beginning of Omicron variants. Hazard Ratio (HR, by Cox models) and VE ([1-HR]*100) were calculated by inverse probability weights. Between December 2020-February 2022, in adults without prior SARS-CoV-2 infection, we matched 5.5 million people (>1 million with immunodeficiency, 343,727 with cancer) with a booster (3rd) dose by considering doses 1 and 2 vaccine brands and calendar time, age, sex, region, and comorbidities (immunodeficiency, cancer, severe renal disease, transplant recipient, Down Syndrome). We studied booster doses of BNT and MOD administered after doses 1 and 2 with BNT, MOD, or Oxford-AstraZeneca during a median follow-up between 9 and 16 weeks. BNT or MOD showed VE ranging from 70 to 86% across data sources as heterologous 3rd doses, whereas it was 42-88% as homologous 3rd doses. Depending on the severity and available follow-up, 3rd-dose effectiveness lasted between 1 and 5 months. In people with immunodeficiency and cancer, protection across data sources was detected with both heterologous (VE = 54-83%) and homologous (VE = 49-80%) 3rd doses. Overall, both heterologous and homologous 3rd doses with BTN or MOD showed additional protection against the severe effects of SARS-CoV-2 infections for the general population and for patients at potentially high risk of severe COVID-19 (elderly, people with immunodeficiency and cancer) in comparison with two doses schemes during Delta or early Omicron periods. The early VE after vaccination may be due to less testing among vaccinated pairs and unknown confounders, deserving cautious interpretation. The VE wane over time needs further in-depth research to properly envisage when or whether a booster of those vaccines should be administered., Competing Interests: Declaration of Competing Interest All the authors declare financial support was provided by European Medicines Agency and the following financial interests/personal relationships which may be considered as potential competing interests: Elisa Martin Merino (corresponding author): Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) and Agencia Española de Cooperación Internacional para el Desarrollo (AECID) paid a presentation in a course ‘Farmacovigilancia de las vacunas frente a la COVID-19’; Unpaid collaboration in observational studies with Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) for the “Grupo de Trabajo de Efectividad Vacunación COVID-19. Spanish Ministry of Health. ISCIII.CNE. Spanish Agency of Medicines and Medical Devices.” Riefolo Fabio is an employee of TEAMIT Institute, consulting research company that participates in financially supported studies for European Medicines Agency and related healthcare authorities, pharmaceutical companies, and the European Union. Ylenia Ingrasciotta is the CEO of the academic spin-off “INSPIRE srl” of the University of Messina, which has received funding for conducting observational studies from contract research organizations (RTI Health Solutions, Pharmo Institute N.V.) and from pharmaceutical Companies (Chiesi Italia, Kyowa Kirin s.r.l., Daiichi Sankyo Italia S.p.A.). Karin Swart-Polinder is an employee of the PHARMO Institute for Drug Outcomes Research. This independent research institute performs financially supported studies for the government and related healthcare authorities and several pharmaceutical companies., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Childhood obesity is a social health problem in the Western World and an important goal is to analyze and correct risk factors. However, part of the problem could be determined by a different perception of the weight., Material and Methods: In October 2019, we conducted a cross-sectional study in which a questionnaire was administered to the parents of primary and secondary school children in South-East Tuscany, Italy. The aim was to determine the association between children's Body Mass Index (BMI) and the parent's perception., Results: Analysis was carried out on 1,405 complete questionnaires. We found that most parents wrongly perceive the weight of their children. 88.3% of parents with obese children believe that their children are of normal weight or only "a little overweight". 67.6% of parents who have overweight children think that their children are of normal weight (p < 0.001)., Conclusions: Our results show a misperception of the weight of the children in the parents eyes. The acquisition of healthy behaviour during childhood is extremely important for health in adulthood and for avoiding the onset of associated diseases. Therefore, food education becomes a crucial objective. Children and parents need to increase consciousness of the correct weight and diseases resulting from bad nutrition., Competing Interests: sCOOL FOOD program was financed by the Monte dei Paschi Foundation. The authors did not receive any personal funds for the research. Monte dei Paschi Foundation had no role in the test design, data collection or analysis, decision to publish, or preparation and discussion of the test results in the manuscript., (©2023 Pacini Editore SRL, Pisa, Italy.)

Purpose: Trabecular bone score (TBS) is a grey-level textural measurement acquired from dual-energy X-ray absorptiometry lumbar spine images and is a validated index of bone microarchitecture. In 2015, a Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) published a review of the TBS literature, concluding that TBS predicts hip and major osteoporotic fracture, at least partly independent of bone mineral density (BMD) and clinical risk factors. It was also concluded that TBS is potentially amenable to change as a result of pharmacological therapy. Further evidence on the utility of TBS has since accumulated in both primary and secondary osteoporosis, and the introduction of FRAX and BMD T-score adjustment for TBS has accelerated adoption. This position paper therefore presents a review of the updated scientific literature and provides expert consensus statements and corresponding operational guidelines for the use of TBS., Methods: An Expert Working Group was convened by the ESCEO and a systematic review of the evidence undertaken, with defined search strategies for four key topics with respect to the potential use of TBS: (1) fracture prediction in men and women; (2) initiating and monitoring treatment in postmenopausal osteoporosis; (3) fracture prediction in secondary osteoporosis; and (4) treatment monitoring in secondary osteoporosis. Statements to guide the clinical use of TBS were derived from the review and graded by consensus using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach., Results: A total of 96 articles were reviewed and included data on the use of TBS for fracture prediction in men and women, from over 20 countries. The updated evidence shows that TBS enhances fracture risk prediction in both primary and secondary osteoporosis, and can, when taken with BMD and clinical risk factors, inform treatment initiation and the choice of antiosteoporosis treatment. Evidence also indicates that TBS provides useful adjunctive information in monitoring treatment with long-term denosumab and anabolic agents. All expert consensus statements were voted as strongly recommended., Conclusion: The addition of TBS assessment to FRAX and/or BMD enhances fracture risk prediction in primary and secondary osteoporosis, adding useful information for treatment decision-making and monitoring. The expert consensus statements provided in this paper can be used to guide the integration of TBS in clinical practice for the assessment and management of osteoporosis. An example of an operational approach is provided in the appendix. This position paper presents an up-to-date review of the evidence base, synthesised through expert consensus statements, which informs the implementation of Trabecular Bone Score in clinical practice., (© 2023. The Author(s).)

Background: Direct observation is important, yet medical residents are rarely observed. We implemented and evaluated a direct observation program in resident clinics to increase the frequency of observation and feedback and improve perceptions about direct observation., Methods: We assigned faculty as observers in our resident clinics between June 2019 and February 2020. We surveyed residents and faculty before and after the program. Faculty completed a form for each observation performed. We analyzed surveys to examine changes in barriers, frequency and type of observations and feedback, and attitudes toward observation. The analytical sample included 38 and 37 pre- and postresident surveys, respectively, and 20 and 25 pre- and postfaculty surveys, respectively., Results: Resident survey response rates were 32.3% (40/124) pre- and 30.7% (39/127) postintervention. Most residents (76% [pre], 86% [post], P = 0.258) reported being observed in at least one of the four areas: history, examination, counseling, or wrap-up. We received observation tracking forms on 68% of eligible residents. Observed history taking increased from 30% to 79% after the program (P = 0.0010). Survey response rates for faculty were 64.7% (22/34) pre- and 67.5% (25/37) postintervention. Fewer faculty reported time (80% [pre], 52% [post], P = 0.051) and competing demands (65% [pre], 52% [post], P = 0.380) as barriers postintervention. Fewer faculty postintervention viewed observation as a valuable teaching tool (100% [pre], 79% [post], P = 0.0534). All faculty who did not view observation as valuable were the least experienced., Discussion: Assigning faculty as observers can increase observation, especially in history taking, though data suggest an increase in negative perceptions of observation by faculty., (Copyright © 2023 Copyright: © 2023 Education for Health.)

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor alterations. Typical motor symptoms include resting tremors, bradykinesia (hypokinesia or akinesia), muscular stiffness, gait alterations, and postural instability. In this context, neurorehabilitation may have a pivotal role in slowing the progression of PD, using both conventional and innovative rehabilitation approaches. Thirty patients (15 males and 15 females) affected by PD were enrolled in our study. We randomly divided the patients into two groups, an experimental group (EG) and a control group (CG). In particular, the EG performed gait and balance training using the Rysen system, which is an innovative body weight support (BWS) system, whilst the CG received conventional physiotherapy. Both groups underwent 20 sessions, five times weekly, with each session lasting about 40 min. At the end of the training sessions (T1), we found that both groups (EG and CG) achieved clinical improvements, although the EG showed better scores for post-treatment regarding global motor functioning and postural stability compared to the CG. In conclusion, our results suggest that the Rysen system, which is an innovative BWS tool, could be considered a valid device for improving postural control and global motor functions, when compared to conventional gait training, in patients affected by PD.

Background: Human, animal, and environmental health are increasingly threatened by the emergence and spread of antibiotic resistance. Inappropriate use of antibiotic treatments commonly contributes to this threat, but it is also becoming apparent that multiple, interconnected environmental factors can play a significant role. Thus, a One Health approach is required for a comprehensive understanding of the environmental dimensions of antibiotic resistance and inform science-based decisions and actions. The broad and multidisciplinary nature of the problem poses several open questions drawing upon a wide heterogeneous range of studies., Objective: This study seeks to collect and catalogue the evidence of the potential effects of environmental factors on the abundance or detection of antibiotic resistance determinants in the outdoor environment, i.e., antibiotic resistant bacteria and mobile genetic elements carrying antibiotic resistance genes, and the effect on those caused by local environmental conditions of either natural or anthropogenic origin., Methods: Here, we describe the protocol for a systematic evidence map to address this, which will be performed in adherence to best practice guidelines. We will search the literature from 1990 to present, using the following electronic databases: MEDLINE, Embase, and the Web of Science Core Collection as well as the grey literature. We shall include full-text, scientific articles published in English. Reviewers will work in pairs to screen title, abstract and keywords first and then full-text documents. Data extraction will adhere to a code book purposely designed. Risk of bias assessment will not be conducted as part of this SEM. We will combine tables, graphs, and other suitable visualisation techniques to compile a database i) of studies investigating the factors associated with the prevalence of antibiotic resistance in the environment and ii) map the distribution, network, cross-disciplinarity, impact and trends in the literature., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Percutaneous cement discoplasty (PCD) is a minimally invasive surgical procedure that can provide a segmental stabilizing and indirect decompression effect in the case of severely degenerated discs characterized by vacuum phenomenon. This systematic review aims to analyze the available literature relating to correct indications and clinical and radiologic efficacy of PCD in patients affected by advanced degenerative spine conditions., Methods: The search was conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guideline. Comprehensive research of PubMed, Scopus, and OVID databases was made using the following Mesh terms: ((cement) AND (discoplasty) AND ((vertebral) OR (spinal) OR (spine))). Modal distribution was used to assess the most frequent levels of PCD per patient. Quality assessment of each article was performed according to the Oxford Level of Evidence, Methodological Index for Non-Randomized studies, and Risk of Bias in Non-Randomized Studies score by 2 authors., Results: After the databases search, 5 full-text articles were included in the systematic review for a total of 291 patients (218 females and 73 males). Median PCD levels were 2.2. Despite promising clinical results, the methodologic index showed poor Methodological Index for Non-Randomized and Risk of Bias in Non-Randomized Studies scores., Conclusions: PCD provides good clinical results in elderly patients, especially for pain relief. However, the current literature is poor and the article included in the systematic review showed a poor methodologic score, which could affect the conclusions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis. Findings: Over 35 million individuals (49·2% women, median age 39-49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged < 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination. Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bots, Riera-Arnau, Belitser, Messina, Aragón, Alsina, Douglas, Durán, García-Poza, Gini, Herings, Huerta, Sisay, Martín-Pérez, Martin, Overbeek, Paoletti, Pallejà-Millán, Schultze, Souverein, Swart, Villalobos, Klungel and Sturkenboom.)

The ischemia/reperfusion mechanism is believed to be responsible for parenchymal damage caused by temporary hypoperfusion and worsened by the subsequent attempt of reperfusion. This represents a true challenge for physicians of several fields, including neurosurgeons. A limited number of papers have shed the light on a rare pathologic condition that affects patients experiencing an unexplained neurologic deficit after spine surgery, the so-called "white cord syndrome." This entity is believed to be caused by an "ischemia/reperfusion" injury on the spinal cord, documented by a postoperative intramedullary hyperintensity on T2-weighted magnetic resonance imaging sequences. To date, the cases of white cord syndrome reported in literature mostly refer to cervical spine surgery. However, the analysis of several reviews focusing on spine surgery outcome suggests postoperative neurologic deficits of new onset could be charged to a mechanism of ischemia/reperfusion, even if the physiopathology of this event is seldom explored or at least discussed. The same neuroradiologic finding can suggest mechanical damage due to inappropriate surgical manipulation. On this purpose, we performed a systematic review of the literature with the aim to identify and analyze all the factors potentially contributing to ischemic/reperfusion damage of the spinal cord that may potentially complicate any spinal surgery, without distinction between cervical or thoracic segments. Finally, we believe that postoperative neurologic deficit after spinal surgery constituting the "white cord syndrome" could be under-reported; both neurosurgeons and patients should be fully aware of this rare but potentially devasting complication burdening cervical and thoracic spine surgery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Toxoplasma gondii is a major foodborne pathogen capable of infecting all warm-blooded animals, including humans. Although oocyst-associated toxoplasmosis outbreaks have been documented, the relevance of the environmental transmission route remains poorly investigated. Thus, we carried out an extensive systematic review on T. gondii oocyst contamination of soil, water, fresh produce, and mollusk bivalves, following the PRISMA guidelines. Studies published up to the end of 2020 were searched for in public databases and screened. The reference sections of the selected articles were examined to identify additional studies. A total of 102 out of 3201 articles were selected: 34 articles focused on soil, 40 focused on water, 23 focused on fresh produce (vegetables/fruits), and 21 focused on bivalve mollusks. Toxoplasma gondii oocysts were found in all matrices worldwide, with detection rates ranging from 0.09% (1/1109) to 100% (8/8) using bioassay or PCR-based detection methods. There was a high heterogeneity (I 2 = 98.9%), which was influenced by both the sampling strategy (e.g., sampling site and sample type, sample composition, sample origin, season, number of samples, cat presence) and methodology (recovery and detection methods). Harmonized approaches are needed for the detection of T. gondii in different environmental matrices in order to obtain robust and comparable results.

Spine is a frequent site of bone metastases, with a 8.5 months median survival time after diagnosis. In most cases treatment is only palliative. Several advanced techniques can ensure a better Quality of Life (QoL) and increase life expectancy. Radiofrequency ablation (RFA) uses alternating current to produce local heating and necrosis of the spinal lesion, preserving the healthy bone. RFA is supported by vertebral reinforcement through kyphoplasty and vertebroplasty in order to stabilize the fracture with polymethylmethacrylate (PMMA) injection, restoring vertebral body height and reducing the weakness of healthy bone. The aim of this study is to demonstrate the efficacy and advantages of RFA plus vertebral reinforcement through PMMA vertebroplasty and fixation in patients affected by bone spinal metastases. We retrospectively analyzed 54 patients with thoraco-lumbar metastatic vertebral fractures admitted to our Unit between January 2014 and June 2020. Each patient underwent RFA followed by PMMA vertebroplasty and transpedicle fixation. We evaluated pain relief through the Visual Analogue Scale (VAS) Score and PMMA vertebral filling based on the mean Saliou filling score. Analysis of variance (ANOVA) was used to test pain relief with statistical significance for p<0.05. A total of 54 patients (median age 63,44 years; range 34-86 years), with a total of 63 infiltrated vertebrae, were treated with RFA, PMMA vertebroplasty and transpedicular screw fixation; average operative time was 60.4 min (range 51-72). The preoperative average VAS score decreased significantly from 7.81 to 2.50 (p < 0.05) after 12 months. Based on Saliou filling score, filling was satisfactory (12-18) in 20 vertebrae (31,7%), mediocre (6-11) in 33 vertebrae (52,4%), inadequate (0-5) in 10 vertebrae (15,9%). A consistent PMMA filling of vertebral bodies was successfully achieved with significant pain relief. Concomitant RFA, PMMA vertebroplasty and pedicle screw fixation represent a safe and effective technique for the management of spinal metastases, improving clinical outcome and pain control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Giammalva, Costanzo, Paolini, Benigno, Porzio, Brunasso, Basile, Gulì, Pino, Gerardi, Messina, Umana, Palmisciano, Scalia, Graziano, Visocchi, Iacopino and Maugeri.)

Bridges constitute important elements of the transportation network. A vast part of the Italian existing infrastructural system dates to around 60 years ago, which implies that the related bridge structures were constructed according to past design guidelines and underwent a probable state of material deterioration (e.g., steel corrosion, concrete degradation), especially in those cases in which proper maintenance plans have not been periodically performed over the structural lifetime. Consequently, elaborating rapid yet effective safety assessment strategies for existing bridge structures represents a topical research line. This contribution presents a systematic experimental-numerical approach for assessing the load-bearing capacity of existing prestressed concrete (PC) bridge decks. This methodology is applied to the Longano PC viaduct (southern Italy) as a case study. Initially, natural frequencies and mode shapes of the bridge deck are experimentally identified from vibration data collected in situ through Operational Modal Analysis (OMA), based on which a numerical finite element (FE) model is developed and calibrated. In situ static load tests are then carried out to investigate the static deflections under maximum allowed serviceability loads, which are compared to values provided by the FE model for further validation. Since prestressing strands appear corroded in some portions of the main girders, numerical static nonlinear analysis with a concentrated plasticity approach is finally conducted to quantify the effects of various corrosion scenarios on the resulting load-bearing capacity of the bridge at ultimate limit states. The proposed methodology, encompassing both serviceability and ultimate conditions, can be used to identify critical parts of a large infrastructure network prior to performing widespread and expensive material test campaigns, to gain preliminary insight on the structural health of existing bridges and to plan a priority list of possible repairing actions in a reasonable, safe, and costly effective manner.

The laterally positioned flap (LPF) has been proposed as a promising treatment for isolated gingival recessions (GRs) in mandibular incisors. Several modifications have been proposed to reduce the risk of gingival recession (GR) at the donor tooth site. Therefore, the aim of this was to describe a modified one-stage procedure of performing the LPF associated with the subepithelial connective tissue graft (LPF + SCTG) with the modifications for the treatment of deep isolated GR in mandibular incisors. The modified one-stage technique (LPF + SCTG) is unique because it was presented being bilaminar with tunneled connective tissue graft (CTG) in the adjacent tooth and extended to the flap donor site, without a submarginal incision in the adjacent tooth, taking the entire band of the keratinized tissue (KT) into the flap. In addition, 3 clinical cases were described using this surgical technique. Three healthy patients with Cairo RT1 or RT2 GRs on teeth 31 or 41 were treated with the LPF + SCTG technique. Probing depth (PD), clinical attachment level (CAL), complete root coverage (CRC), mean root coverage (MRC), recession depth (RD), and keratinized tissue width (KTW) were assessed at baseline and in the follow-up periods of 18, 24, and 48 months, in the cases 1, 2, and 3, respectively. The LPF + SCTG with the modifications presented is a predictable approach for the treatment of deep isolated RT1 and RT2 GRs in mandibular incisors that are well positioned in the bone envelope with the presence of KTW adjacent to GR and adequate vestibule depth in the donor area of the flap., Competing Interests: The authors have no current or potential conflicts of interest to declare., (Copyright © 2021 Alvaro Francisco Bosco et al.)

Voxel-wise group analysis is presented as a novel feature selection (FS) technique for a deep learning (DL) approach to brain imaging data classification. The method, based on a voxel-wise two-sample t -test and denoted as t -masking, is integrated into the learning procedure as a data-driven FS strategy. t-Masking has been introduced in a convolutional neural network (CNN) for the test bench of binary classification of very-mild Alzheimer's disease vs. normal control, using a structural magnetic resonance imaging dataset of 180 subjects. To better characterize the t -masking impact on CNN classification performance, six different experimental configurations were designed. Moreover, the performances of the presented FS method were compared to those of similar machine learning (ML) models that relied on different FS approaches. Overall, our results show an enhancement of about 6% in performance when t -masking was applied. Moreover, the reported performance enhancement was higher with respect to similar FS-based ML models. In addition, evaluation of the impact of t -masking on various selection rates has been provided, serving as a useful characterization for future insights. The proposed approach is also highly generalizable to other DL architectures, neuroimaging modalities, and brain pathologies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Messina, Borrelli, Russo, Salvatore and Aiello.)

Brain gliomas require a deep knowledge of their effects on brain connectivity. Understanding the complex relationship between tumor and functional brain is the preliminary and fundamental step for the subsequent surgery. The extent of resection (EOR) is an independent variable of surgical effectiveness and it correlates with the overall survival. Until now, great efforts have been made to achieve gross total resection (GTR) as the standard of care of brain tumor patients. However, high and low-grade gliomas have an infiltrative behavior and peritumoral white matter is often infiltrated by tumoral cells. According to these evidences, many efforts have been made to push the boundary of the resection beyond the contrast-enhanced lesion core on T1w MRI, in the so called supratotal resection (SpTR). SpTR is aimed to maximize the extent of resection and thus the overall survival. SpTR of primary brain tumors is a feasible technique and its safety is improved by intraoperative neuromonitoring and advanced neuroimaging. Only transient cognitive impairments have been reported in SpTR patients compared to GTR patients. Moreover, SpTR is related to a longer overall and progression-free survival along with preserving neuro-cognitive functions and quality of life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Giammalva, Brunasso, Costanzo, Paolini, Umana, Scalia, Gagliardo, Gerardi, Basile, Graziano, Gulì, Messina, Pino, Feraco, Tumbiolo, Midiri, Iacopino and Maugeri.)

Transcranial MR-guided Focused ultrasound (tcMRgFUS) is a surgical procedure that adopts focused ultrasounds beam towards a specific therapeutic target through the intact skull. The convergence of focused ultrasound beams onto the target produces tissue effects through released energy. Regarding neurosurgical applications, tcMRgFUS has been successfully adopted as a non-invasive procedure for ablative purposes such as thalamotomy, pallidotomy, and subthalamotomy for movement disorders. Several studies confirmed the effectiveness of tcMRgFUS in the treatment of several neurological conditions, ranging from motor disorders to psychiatric disorders. Moreover, using low-frequencies tcMRgFUS systems temporarily disrupts the blood-brain barrier, making this procedure suitable in neuro-oncology and neurodegenerative disease for controlled drug delivery. Nowadays, tcMRgFUS represents one of the most promising and fascinating technologies in neuroscience. Since it is an emerging technology, tcMRgFUS is still the subject of countless disparate studies, even if its effectiveness has been already proven in many experimental and therapeutic fields. Therefore, although many studies have been carried out, many others are still needed to increase the degree of knowledge of the innumerable potentials of tcMRgFUS and thus expand the future fields of application of this technology.

Objective: in elderly patients reduction and fixation of acetabular fractures showed poor outcomes in fracture patterns where cartilage comminution/impaction and/or femoral head dislocation are present; acute arthroplasty with standard uncemented hemispherical cups and posterior plating has been recently proposed, we report on its safety and effectiveness., Methods: we used this technique to manage 67 displaced acetabular fracture but both column in patients older than 65 years old., Results: fractures of posterior column and/or wall with severe cartilage involvement may be treated safely with acute THA., Conclusions: Good results in complex fracture patterns may also be achieved., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Published by Elsevier B.V. on behalf of Professor P K Surendran Memorial Education Foundation.)

Postoperative rehabilitation after simultaneous anterior cruciate ligament reconstruction and opening wedge high tibial osteotomy is a complex concept. Different osteotomy techniques, extremely selected patients, high expectations in returning to previous sport activities, and the different individual physical profile and performances make traditional chronological criteria impractical and unfeasible. This study presents a novel rehabilitation in which functional objective criteria are considered the key factors for standardizing a 4-step protocol. Each step is "individualized", based on the patient's response to the healing processes and to the different training phases, allowing for a safe return to sports competitions. This definitively implies a strict collaboration between patient, surgeon, physician and physiotherapists, as well as thorough and detailed patient education. Due to the high versatility of these new rehabilitation concepts, the application of the "individualized" steps described in this study may be broadened to include different sports medicine knee injuries that may benefit from a specific, detailed and carefully patient-centered rehabilitation project., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

Periprosthetic osteolysis is still one of the major limitations of prosthetic joints longevity. The process of this "silent" iatrogenic disease involves both mechanical and biological factors that initiate a local immune response in the periprosthetic tissue that eventually lead to implant loosening and failure. There are many causes of the primary aseptic loosening inside the periprosthetic microenvironment, but the most important elements are the wear debris and the cell-particle interactions. Together with implant position, micromotion, bearings, joint fluid pressure, and increased load on the joints drive the pathogenesis of the disease. This narrative review aims to summarise recent studies describing the biological and mechanical factors in the pathogenesis of osteolysis and some of the current pharmacological attempts to "rescue" a failing implant., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures., Introduction: The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach., Methods: Clinical perspective and updated literature search., Results: The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis., Conclusions: A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions.

Preterm infants are at increased risk of micronutrient deficiencies as a result of low body stores, maternal deficiencies, and inadequate supplementations. The aim of this survey was to investigate current vitamin and mineral supplementation practices and compare these with published recommendations and available evidence on dosages and long-term outcomes of supplementations in preterm infants. In 2018, a two-part electronic survey was emailed to 50 Australasian Neonatal Dietitians Network (ANDiN) member and nonmember dietitians working in neonatal units in Australia and New Zealand. For inpatients, all units prescribed between 400 and 500 IU/day vitamin D, compared to a recommended intake range of 400-1000 IU/day. Two units prescribed 900-1000 IU/day at discharge. For iron, 83% of respondents prescribed within the recommended intake range of 2-3 mg/kg/day for inpatients. Up to 10% of units prescribed 6 mg/kg/day for inpatients and at discharge. More than one-third of units reported routine supplementations of other micronutrients, including calcium, phosphate, vitamin E, and folic acid. There was significant variation between neonatal units in vitamin and mineral supplementation practices, which may contribute to certain micronutrient intakes above or below recommended ranges for gestational ages or birth weights. The variations in practice are in part due to differences in recommended vitamin and mineral intakes between expert groups and a lack of evidence supporting the recommendations for supplementations., Competing Interests: All authors are currently working as neonatal dietitians. The Australasian Neonatal Dietitians Network (ANDiN) meeting in 2018, where this survey was pretested, was supported by an unconditional grant from the Nestle Nutrition Institute.

Pneumonia in children due to hydrocarbon aspiration is usually the result of an uncommon accidental event. However, an acute and severe type of pneumonia induced by hydrocarbon aspiration is occasionally experienced by entertainers known as fire-eaters. Different approaches to treat fire-eater's pneumonia appear in the literature. Although there is no consensus regarding the management of this condition, the use of antibiotic therapy is well recognized and recommended by some, whereas others recommend only supportive treatment. Steroids are indicated in severe cases.Here, we report the case of a boy who developed severe pneumonia after inhaling hydrocarbons during an attempt to mimic a fire-eater show. Slow resolution was achieved after broad-spectrum antibiotic therapy in addition to systemic and inhaled steroids and physiotherapy.

Background and Importance: The therapeutic approach for cerebellar damages heavily relies on neurorehabilitation since there are no medications that may improve clinical symptoms mainly those related to cognitive dysfunctions. Nevertheless, neurorehabilitation programs tailored to cerebellar damages have never been validated. Here we describe a new rehabilitation approach based on cooking training (CT). The idea that cooking may stimulate cerebellar activity relies on previous evidence demonstrating the beneficial effect on the executive functions as well as in promoting neural plasticity within the cerebellum. Indeed, CT requires motor/mental coordination, thinking flexibly, planning, implementing strategies, shifting and self-monitoring behaviors, all functions drastically affected in cerebellar disorders., Case Description: A 68-year-old male stroke patient with isolated right cerebellar ischemia in the posterior cerebellum characterized by mild executive dysfunctions. After intensive six weekly two-hour sessions, we found that CT was effective in improving some cognitive abilities in a context of mild motor impairment. In particular, deficits in the execution of the Symbol digit modality test and Wisconsin card-sorting test were recovered., Conclusion: The comparison of our data with those reported in previous studies confirmed the Schmahmann's hypothesis on the effectiveness of neurorehabilitation approaches in cerebellar patients acting as external timekeeping of conscious thoughts., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hepatic ischemia/reperfusion injury (IRI) is a clinical condition that may lead to cellular injury and organ dysfunction that can be observed in different conditions, such as trauma, shock, liver resection, and transplantation. Moderate levels of nitric oxide (NO) produced by the endothelial isoform of the NO synthase protect against liver IRI. GIT-27NO is a NO-derivative of the toll-like receptor 4 antagonist VGX-1027 that has been shown to possess both antineoplastic and immunomodulatory properties in vitro and in vivo. In this study, we have investigated the effects of this compound in vitro, in a model of oxidative stress induced in HepG2 cells by hydrogen peroxide (H 2 O 2 ), and in vivo, in a rat model of IRI of the liver. GIT-27NO significantly counteracted the toxic effects induced by the H 2 O 2 on the HepG2 cells and in vivo, GIT-27NO reduced the transaminase levels and the histological liver injury by reducing necrotic areas with preservation of viable tissue. These effects were almost similar to that of the positive control drug dimethyl fumarate. These data suggest that the beneficial effect of GIT-27NO in the hepatic IRI can be secondary to anti-oxidative effects and hepatocyte necrosis reduction probably mediated by NO release.

A comprehensive description of morbidity and mortality in patients affected by mutations in genes encoding for signal transducers of the RAS-MAPK cascade (RASopathies) was performed in our study recently published in the International Journal of Cardiology. Seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET), collaborated in this multicentric, observational, retrospective data analysis and collection. In this study, clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Cardiac defects, crude mortality, survival rate of patients with 1) hypertrophic cardiomyopathy (HCM) and age <2 years or young adults; 2) individuals with Noonan syndrome and pulmonary stenosis carrying PTPN11 mutations; 3) biventricular obstruction and PTPN11 mutations; 4) Costello syndrome or cardiofaciocutaneous syndrome were analysed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. In particular, with this Data In Brief (DIB) paper, the authors aim to report specific statistic highlights of the multivariable regression analysis that was used to assess the impact of mutated genes on number of interventions and overall prognosis.

Fewer adults meet guidelines for aerobic physical activity, and many report a lack of enjoyment as a barrier. This survey was designed to determine the interest of primary care patients in participating in program designed to maximize enjoyment. Primary care patients (n = 540) in Central Pennsylvania reported their interest in participating in a "a regular fitness program where people your own age played games, such as softball, floor hockey and soccer, that were made to be easier to play and less competitive." Mean age was 58.4 years (SD = 16.5, range = 18-98). More than one-third (37.0%), including 59.6% of those under age 50, were interested in the modified sports fitness program. After adjusting for confounders, patients under age 40 were 5.9 (95% CI: 2.6-13.9) times as interested (v. age > 70) and non-white patients were 3.4 (95% CI: 1.3-8.5) times interested. Female patients and those with hypertension, high cholesterol or obesity were equally interested. A fitness program that consists of modified sports may be of interest to most primary care patients under age 50. Patients' initial interest appears high enough to warrant further development and testing.

Background: RASopathies are developmental disease caused by mutations in genes encoding for signal transducers of the RAS-MAPK cascade. The aim of the present study was to provide a comprehensive description of morbidity and mortality in patients with molecularly confirmed RASopathy., Methods: A multicentric, observational, retrospective study was conducted in seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET). Clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. Multivariable regression analysis was used to assess the impact of mutated genes on number of interventions and overall prognosis., Results: Cardiac defects occurred in 80.3% of cases, almost half of them underwent at least one intervention. Overall, crude mortality was 0.29/100 patients-year. Cumulative survival was 98.8%, 98.2%, 97.7%, 94.3%, at 1, 5, 10, and 20years, respectively. Restricted estimated mean survival at 20years follow-up was 19.6years. Ten patients died (2.7% of the entire cohort; 3.4% of patients with cardiac defect). Patients with hypertrophic cardiomyopathy (HCM) and age <2years or young adults, as well as subjects with biventricular obstruction and PTPN11 mutations had a higher risk of cardiac death., Conclusions: The risk of intervention was higher in individuals with Noonan syndrome and pulmonary stenosis carrying PTPN11 mutations. Overall, mortality was relatively low, even though the specific association between HCM, biventricular outflow tract obstructions and PTPN11 mutations appeared to be associated with early mortality, including immediate post-operative events and sudden death., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Several epidemiological studies have shown that Diabetes Mellitus (DM) or Insulin Resistance (IR) increases the risk of dementia. Besides, some authors suggested that poor glucose control to be associated with worse cognitive function. We aimed to assess cognitive functions and IR-degree over time in diabetic. We also evaluated whether a greater magnitude of cognitive decline could be related with their IR degree. We enrolled 335 diabetic patients and 142 non-diabetic subjects; participants were subdivided into three groups in accordance with their IRdegree assessed by Homa-Index (HI): Normal-HI (non-diabetic NHI < 2,6), Moderate-HI (MHI > 2,6 < 10) and High-HI (HHI > 10). Metabolic status and a comprehensive neuropsycological test battery (MMSE, ADAS-Cog, ACDS-ADL) were assessed at baseline and every 12-months during the follow-up (6,8 years). At the end of the study, the average MMSE decreased significantly in patients of HHI group (P = .001) compared to baseline. MMSE scores were also reduced both in MHI group and in controls, but the difference between two groups was not significant. In HHI group, similar effects were observed for the ADAS-Cog score compared to baseline (P = 0.001); instead, when ACDS-ADL was evaluated, no differences was observed among the three groups. These results remained unchanged also after adjustment for confounding variables (i.e. APOε-status, sex, BMI, education level, heart diseases and HbA1c). We suggest that higher IR-degree is associated with greater cognitive decline in diabetic patients; so we hypothesize that IR degree, more than IR status itself, could be related to the severity of cognitive impairment.

Soft tissue defects are relatively common, yet currently used reconstructive treatments have varying success rates, and serious potential complications such as unpredictable volume loss and reabsorption. Human adipose-derived stem cells (ASCs), isolated from liposuction aspirate have great potential for use in soft tissue regeneration, especially when combined with a supportive scaffold. To design scaffolds that promote differentiation of these cells down an adipogenic lineage, we characterized changes in the surrounding extracellular environment during adipogenic differentiation. We found expression changes in both extracellular matrix proteins, including increases in expression of collagen-IV and vitronectin, as well as changes in the integrin expression profile, with an increase in expression of integrins such as αVβ5 and α1β1. These integrins are known to specifically interact with vitronectin and collagen-IV, respectively, through binding to an Arg-Gly-Asp (RGD) sequence. When three different short RGD-containing peptides were incorporated into three-dimensional (3D) hydrogel cultures, it was found that an RGD-containing peptide derived from vitronectin provided strong initial attachment, maintained the desired morphology, and created optimal conditions for in vitro 3D adipogenic differentiation of ASCs. These results describe a simple, nontoxic encapsulating scaffold, capable of supporting the survival and desired differentiation of ASCs for the treatment of soft tissue defects.

Background: The objective of this study is to evaluate the factors influencing the outcome of back pain and disability in patients operated for lumbar stenosis without instability and deformity using two classical surgical techniques: decompression alone and decompression plus fusion., Methods: This is a retrospective cohort study of patients who underwent lumbar surgery with standard posterior decompression or standard posterior decompression plus pedicle screw fixation for degenerative lumbar stenosis without deformity, spondylolisthesis or instability at our department from June 2010 to January 2014. They were divided into two groups: decompression group (D) and decompression-fusion group (F). We analyzed the following factors: age, gender, levels of stenosis, pre-surgical "micro-instability", and post-surgical "micro-instability"., Results: A total of 174 patients were enrolled in the study. Both Graphic Rating Scale (GRS) and Oswestry Disability Index (ODI) scores were significantly decreased after surgery (P<0.001). Female patients appeared to have lesser improvements from surgery, for both D and F groups. An analysis of variance using the decrease of pain (GRS pre-post) as dependent variable and type of surgery, age, gender and their interaction as factors showed that the main effects of type of surgery and gender were significant. The analysis of variance for the decrease of pain (GRS) and disability (ODI) according to the levels of stenosis showed a significant interaction for GRS scores. Female patients that underwent fixation surgery reported the least improvement in disability. A significant interaction was found on the one-way analysis of variance for the D group without pre-surgical micro-instability using post-surgical micro-instability as factor., Conclusions: Our study supports posterior decompression alone as the gold standard option as treatment for lumbar stenosis without instability and deformity. Additional fusion should be considered only to prevent post-surgical instability. The "micro-instability" is a radiological finding that has its clinical surrogate but is not able to guide the choice of the type of surgery. Moreover the significance of "micro-instability" is still unclear. We suggest a prospective study following patients with asymptomatic micro-instability to definitively understand the clinical history., Competing Interests: The authors have no conflicts of interest to declare.

Background: Stethoscopes are widely used by doctors and nurses. Poor stethoscope hygiene is a potential source of nosocomial infection. This study aimed to propose an innovative solution, based on the latest advances in ultraviolet (UV) light-emitting diodes (LEDs), for disinfecting stethoscope membranes automatically and efficiently., Methods: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Enterococcus faecalis were sown on 28 stethoscope membranes and then transferred to Petri dishes. Treatment involved illuminating exposed Petri dishes with a UVC LED for 1 minute. For each microbe, the number of colony-forming units (cfu) at 36°C was compared in control and treated dishes using the Wilcoxon signed-rank test. The Kruskal-Wallis test was used to assess percent reductions in bacteria. Statistical significance was set at 99%., Results: A significant reduction in cfu counts after UV treatment (P < .01) was found for all bacteria: 85.5% for E faecalis, 87.5% for S aureus, 94.3% for E coli, and 94.9% for P aeruginosa . No significant differences in percent reduction in cfu were found between bacteria (P > .01)., Conclusion: The stethoscope, symbol of medicine and health care professionals, has been demonstrated to be a carrier of microorganisms. The treatment technique was effective and efficient in disinfecting the membranes. These promising results represent a step forward toward eliminating stethoscope membrane contamination with an innovative approach., (Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Mate is the national infusion of Argentina and its properties on human health have not been fully elucidated., Objective: To evaluate changes in lipid profile in dyslipidemic patients supplemented with yerba mate., Methods: 121 dyslipidemic subjects (total cholesterol (TC), LDL cholesterol (LDLC) cholesterol and / or triglycerides (TG) elevated) without lipid-lowering therapy, both sexes (74 women and 47 men) between 40 and 60 years old were studied. After six weeks of mate abstinence, lipid profile and atherogenic index (AI), body composition by anthropometry and recent intake of energy, nutrients and food groups by food frequency questionnaire were analyzed. Daily consumption of mate prepared with 50 g or 100 g of yerba mate was indicated, plus the instruction not to alter eating habits, smoking, medication or exercise. All determinations were repeated after six and twelve weeks. Statistical analysis was performed using Student's T test for paired samples or Wilcoxon test according to normality of the variables (p <0.05)., Results: At the end of twelve weeks, TC fell 9.49% (21.66 mg/dL), LDLC fell 11.95% (17.96 mg/dL) HDLC fell 3.34% (1.65 mg/dL) and AI dropped 6.58% (0.31 points), p <0.001 for all cases. TG decreased 7.02% (10.74 mg/dl; p = 0.029) only in 50 g yerba mate consumers. Anthropometric and nutritional variables did not change significantly., Conclusions: Daily consumption of mate produces a time-dependent decrease in TC and its fractions in dyslipidemic subjects., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Autism spectrum disorder (ASD) results from interactions of genetic and environmental factors. The MET proto-oncogene has been identified as a candidate gene for autism susceptibility, and is implicated in neurodevelopment and social brain circuitry. Here, we describe the first case of a familial mutation of MET, consisting of an interstitial genomic deletion removing exons 12 through 15, causing a frameshift and premature stop codon, with evidence of nonsense-mediated mRNA decay. On the other allele, patients carried the C allele of the MET promoter rs1858830 polymorphism, known to decrease MET expression and previously associated with autism susceptibility. The heterozygous mutation was associated with autism in one patient, and language and social impairment in a sibling. Our observations delineate the phenotypic spectrum associated with a clearly defined, very likely complete loss of function mutation of MET. Incomplete penetrance in this family was consistent with MET as a partial susceptibility gene for ASD. Implication of MET in normal and pathological brain development opens new perspectives for understanding the pathophysiology of autism and for eventual therapeutical clues., (© 2014 International Society for Autism Research, Wiley Periodicals, Inc.)

Objectives: The published Accreditation Council for Graduate Medical Education (ACGME) milestones represent a novel method of evaluation of trainees in graduate medical education. We surveyed agroup of teaching faculty and residents, regarding the new ACGME milestones project. We obtained their input on the expected timeline for the developmental milestones and compared their responses to the ACGME recommendations., Methods: A 42-item survey questionnaire, derived from the original 142 item publication, was completed by 26 internal medicine teaching faculty and 34 internal medicine residents., Results: We found statistically significant differences in the responses given by residents and faculty compared to those in the standard recommendations. The differences were more pronounced with the residents than with the faculty., Conclusions: The results of our survey showed significantly different responses as compared to the standard recommended timelines. Since this is a novel evaluation process, substantial faculty development and resident education regarding the process can help improve its implementation. Future studies should focus on how learners might better understand and refine the milestone evaluation process.

Imaging measurements, such as the ratio of the midsagittal areas of the midbrain and pons (midbrain/pons) and the Magnetic Resonance Parkinsonism Index (MRPI), have been proposed to differentiate progressive supranuclear palsy (PSP) from Parkinson's disease (PD). However, abnormal midbrain/pons values suggestive of PSP have also been reported in elderly individuals and in patients with PD. We investigated the effect of aging on single or combined imaging measurements of the brainstem. We calculated the midbrain/pons and the MRPI (the ratio of the midsagittal areas of the pons and the midbrain multiplied by the ratio of the middle cerebellar peduncle and superior cerebellar peduncle widths) in 152 patients affected by PD, 25 patients with PSP, and a group of 81 age-matched and sex-matched healthy controls using a 3-Tesla magnetic resonance imaging scanner. In healthy controls, aging was negatively correlated with midsagittal area of the midbrain and midbrain/pons values. In patients with PD, in addition to the effect of aging, the disease status further influenced the midbrain/pons values (R(2)  = 0.23; P < 0.001). In both groups, MRPI values were not influenced either by aging or by disease status. No effect of aging on either midbrain/pons or MRPI values was shown in the patients with PSP. Our findings indicated that the MRPI was not significantly influenced by aging or disease-related changes occurring in PD; whereas, in contrast, the midbrain/pons was influenced. Therefore, the MRPI appears to be a more reliable imaging measurement compared with midbrain/pons values for differentiating PSP from PD and controls in an elderly population., (© 2014 International Parkinson and Movement Disorder Society.)

Purpose: To explore the usefulness of histogram analysis of mean diffusivity (MD) derived from diffusion-weighted imaging of large infratentorial structures to distinguish parkinsonian syndromes., Materials and Methods: Local research ethics committee approval and informed consent were obtained. Ten patients with Parkinson disease (PD), nine with the parkinsonian variant of multiple system atrophy (MSA-P), seven with the cerebellar variant of MSA (MSA-C), 17 with progressive supranuclear palsy-Richardson syndrome (PSP-RS), and 10 healthy subjects were recruited. Histograms of MD values were generated for all pixels in the whole infratentorial compartment and separately for the whole brainstem, vermis, and cerebellar hemispheres. To assess the differences in MD values among groups, the Kruskal-Wallis test was used, followed by the Mann-Whitney U test for pairwise comparisons. All P values resulting from pairwise comparisons were corrected with the Bonferroni method., Results: MSA-P and MSA-C groups had higher median MD values (P < .01) in the brainstem and cerebellum when compared with other groups; this finding was in line with the known consistent neurodegenerative damage in posterior cranial fossa structures in these diseases. Median MD values from cerebellar hemispheres were used to discriminate patients with MSA-C and those with MSA-P from patients with PD and those with PSP-RS (P < .01; sensitivity, specificity, and positive predictive value equaled 100%). Furthermore, patients with PSP-RS had significantly higher MD values in the vermis than did healthy subjects (P < .05) and patients with PD (P < .001)., Conclusion: These findings support the clinical usefulness of diffusion imaging in the differential diagnosis of parkinsonism, suggesting that the minimally operator-dependent histogram analysis of the infratentorial structures and particularly of the whole cerebellar hemispheres can be used to distinguish patients with MSA-P and those with MSA-C from patients with PSP-RS and those with PD.