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PURPOSE Accurate risk assessment is essential for the success of population screening programs in breast cancer. Models with high sensitivity and specificity would enable programs to target more elaborate screening efforts to high-risk populations, while minimizing overtreatment for the rest. Artificial intelligence (AI)-based risk models have demonstrated a significant advance over risk models used today in clinical practice. However, the responsible deployment of novel AI requires careful validation across diverse populations. To this end, we validate our AI-based model, Mirai, across globally diverse screening populations. METHODS We collected screening mammograms and pathology-confirmed breast cancer outcomes from Massachusetts General Hospital, USA; Novant, USA; Emory, USA; Maccabi-Assuta, Israel; Karolinska, Sweden; Chang Gung Memorial Hospital, Taiwan; and Barretos, Brazil. We evaluated Uno's concordance index for Mirai in predicting risk of breast cancer at one to five years from the mammogram. RESULTS A total of 128,793 mammograms from 62,185 patients were collected across the seven sites, of which 3,815 were followed by a cancer diagnosis within 5 years. Mirai obtained concordance indices of 0.75 (95% CI, 0.72 to 0.78), 0.75 (95% CI, 0.70 to 0.80), 0.77 (95% CI, 0.75 to 0.79), 0.77 (95% CI, 0.73 to 0.81), 0.81 (95% CI, 0.79 to 0.82), 0.79 (95% CI, 0.76 to 0.83), and 0.84 (95% CI, 0.81 to 0.88) at Massachusetts General Hospital, Novant, Emory, Maccabi-Assuta, Karolinska, Chang Gung Memorial Hospital, and Barretos, respectively. CONCLUSION Mirai, a mammography-based risk model, maintained its accuracy across globally diverse test sets from seven hospitals across five countries. This is the broadest validation to date of an AI-based breast cancer model and suggests that the technology can offer broad and equitable improvements in care.

Introduction and objectives Pregnancy in women with Marfan syndrome (MS) is associated with an increased risk of aortic events. The clinical evidence on pregnant patients with MS is limited and there is no specific consensus on their optimal management. We report our multicenter experience. Methods From January 2004 to January 2020, 632 patients with MS underwent periodic monitoring in Marfan units. During this period, we identified all pregnant women with MS and analyzed the incidence of aortic events during pregnancy and puerperium. Results There were 133 pregnancies in 89 women with MS (8 women with prior aortic surgery). There were no maternal deaths, but 5 women had aortic events during the third trimester and puerperium (type A dissections in 2, type B dissection in 1, and significant [≥ 3 mm] aortic growth in 2). The aortic event rate was 3.7%. Pregestational aortic diameter ≥ 40 mm showed a nonsignificant association with aortic events (P = .058). Fetal mortality was 3% and 37.6% of births were cesarean deliveries. Conclusions Women with MS have an increased risk of aortic events during pregnancy, especially in the third trimester and postpartum period. Patients with MS and aortic diameters ≥ 40 mm should be assessed in experienced centers for prophylactic aortic surgery before pregnancy. It is important to provide early diagnosis, prepregnancy study of the aorta, beta-blocker administration, and close monitoring during pregnancy, especially during the last trimester and postpartum.

Resumen Introduccion y objetivos El embarazo en el sindrome de Marfan (SM) incrementa el riesgo de eventos aorticos. La evidencia clinica actual es escasa y no existe un consenso especifico sobre el tratamiento optimo de estas pacientes. Se presenta nuestra experiencia multicentrica. Metodos Entre enero de 2004 y enero de 2020, 632 pacientes con SM mantuvieron revisiones periodicas en unidades de Marfan. Durante este periodo se identifico a todas las mujeres gestantes y se analizo la incidencia de eventos aorticos durante el embarazo y el puerperio. Resultados Se hallaron 133 embarazos de 89 mujeres (8 con cirugia de aorta previa). No hubo mortalidad materna. Cinco mujeres sufrieron eventos aorticos durante el tercer trimestre del embarazo y el puerperio (2 disecciones tipo A, 1 diseccion tipo B y 2 crecimientos significativos de la aorta (≥ 3 mm). La incidencia de eventos aorticos fue del 3,7%. Se evidencio una mayor tendencia a eventos con diametros aorticos pregestacionales ≥ 40 mm (p = 0,058). La mortalidad fetal fue del 3%. El 37,6% de los partos se realizaron mediante cesarea. Conclusiones Las mujeres con SM tienen un incremento del riesgo de eventos aorticos en el embarazo, especialmente durante el tercer trimestre y el periodo posparto. Se deberia valorar, en centros de referencia, la cirugia aortica profilactica pregestacional con diametros aorticos ≥ 40 mm. Es importante un diagnostico precoz, un estudio pregestacional de toda la aorta, la administracion de bloqueadores beta y un estrecho seguimiento durante el embarazo, especialmente durante el ultimo trimestre y el posparto.

Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated., Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.

Hepatitis D virus (HDV) is a defective liver-tropic virus that needs the helper function of hepatitis B virus (HBV) to infect humans and replicate. HDV is transmitted sexually or by a parenteral route, in co-infection with HBV or by super-infection in HBV chronic carriers. HDV infection causes acute hepatitis that may progress to a fulminant form (7%-14% by super-infection and 2%-3% by HBV/HDV co-infection) or to chronic hepatitis (90% by HDV super-infection and 2%-5% by HBV/HDV co-infection), frequently and rapidly progressing to cirrhosis or hepatocellular carcinoma (HCC). Peg-interferon alfa the only recommended therapy, clears HDV in only 10%-20% of cases and, consequently, new treatment strategies are being explored. HDV endemicity progressively decreased over the 50 years from the identification of the virus, due to improved population lifestyles and economic levels, to the use of HBV nuclei(t)side analogues to suppress HBV replication and to the application of universal HBV vaccination programs. Further changes are expected during the severe acute respiratory syndrome coronavirus-2 pandemic, unfortunately towards increased endemicity due to the focus of healthcare towards coronavirus disease 2019 and the consequently lower possibility of screening and access to treatments, lower care for patients with severe liver diseases and a reduced impulse to the HBV vaccination policy.

Background/objectives: To compare the number of eye surgical procedures performed in Italy in the 2 months following the beginning of lockdown (study period) because of COVID-19 epidemic with those performed in the two earlier months of the same year (intra-year control) and in the period of 2019 corresponding to the lockdown (inter-year control). Methods: Retrospective analysis of surgical procedures carried out at 39 Academic hospitals. A distinction was made between elective and urgent procedures. Intravitreal injections were also considered. Percentages for all surgical procedures and incidence rate ratios (IRR) for rhegmatogenous retinal detachment (RRD) events were calculated. A p value Results: A total of 20,886 versus 55,259 and 56,640 patients underwent surgery during the lockdown versus intra-and inter-year control periods, respectively. During the lockdown, only 70% of patients for whom an operation/intravitreal injection was recommended, finally underwent surgery; the remaining patients did not attend because afraid of getting infected at the hospital (23%), taking public transportation (6.5%), or unavailable swabs (0.5%). Elective surgeries were reduced by 96.2% and 96.4%, urgent surgeries by 49.7% and 50.2%, and intravitreal injections by 48.5% and 48.6% in the lockdown period in comparison to intra-year and inter-year control periods, respectively. IRRs for RRDs during lockdown dropped significantly in comparison with intra- and inter-year control periods (CI: 0.65–0.80 and 0.61–0.75, respectively, p Conclusion: This study provides a quantitative analysis of the reduction of eye surgical procedures performed in Italy because of the COVID-19 epidemic.

International audience; Objective: This multilanguage study used simple speech recording and high-end pattern analysis to provide sensitive and reliable noninvasive biomarkers of prodromal versus manifest α-synucleinopathy in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and early-stage Parkinson disease (PD).Methods: We performed a multicenter study across the Czech, English, German, French, and Italian languages at 7 centers in Europe and North America. A total of 448 participants (337 males), including 150 with iRBD (mean duration of iRBD across language groups 0.5-3.4 years), 149 with PD (mean duration of disease across language groups 1.7-2.5 years), and 149 healthy controls were recorded; 350 of the participants completed the 12-month follow-up. We developed a fully automated acoustic quantitative assessment approach for the 7 distinctive patterns of hypokinetic dysarthria.Results: No differences in language that impacted clinical parkinsonian phenotypes were found. Compared with the controls, we found significant abnormalities of an overall acoustic speech severity measure via composite dysarthria index for both iRBD (p = 0.002) and PD (p < 0.001). However, only PD (p < 0.001) was perceptually distinct in a blinded subjective analysis. We found significant group differences between PD and controls for monopitch (p < 0.001), prolonged pauses (p < 0.001), and imprecise consonants (p = 0.03); only monopitch was able to differentiate iRBD patients from controls (p = 0.004). At the 12-month follow-up, a slight progression of overall acoustic speech impairment was noted for the iRBD (p = 0.04) and PD (p = 0.03) groups.Interpretation: Automated speech analysis might provide a useful additional biomarker of parkinsonism for the assessment of disease progression and therapeutic interventions. ANN NEUROL 2021;90:62-75.

Low back pain (LBP) is a common reason for adults to seek medical care and is associated with important functional limitation and patient burden. Yet, heterogeneity in the causes and presentation of LBP and a lack of standardization in its management impede effective prevention and treatment. We conducted a modified Delphi study to generate consensus statements for the diagnosis, management, and prognosis of LBP. A panel of five experts proposed 19 statements that were subsequently evaluated by physicians who treat LBP in their everyday clinical practice. Physicians were asked to validate statements in the form of a web survey assessing level of agreement on a five-point Likert-like scale. Consensus (≥ 70% agreement) was obtained for all 19 statements. Strength of agreement and physician comments highlighted the importance of pain management, but also strategies to ameliorate functional limitation and prevent future LBP episodes. Respondents favored multidisciplinary approaches and multimodal management for LBP, although there was some ambiguity as to how multidisciplinary strategies could be feasibly incorporated into daily practice. Finally, the results indicated some conflict regarding the use of imaging for the diagnosis of LBP and how to classify LBP for targeted treatment. The results of this study provide a summary of favored clinical practice for the management of chronic LBP. While the consensus statements were generally agreeable to survey respondents, some areas of ambiguity, including how to increase the feasibility of multidisciplinary strategies, when and how to use diagnostic imaging in LBP, and LBP classification, necessitate clarification in future studies and guidelines.

PubMed, Scopus, and ISI Web of Knowledge databases were searched to identify studies published up to December 2020 on the involvement of urinary and male genital systems in COVID-19. Sixteen studies involving a total of 575 patients (538 males and 37 females) were included in this systematic review. The COVID-19 phase was available for 479 patients: 426 in the acute and 53 in the recovery phase. De novo lower urinary tract symptoms (LUTS) were observed in 43 patients and deterioration of preexisting LUTS in 7. Bladder hemorrhage was observed in 3 patients and acute urinary retention in one. Regarding male genital system, scrotal discomfort was observed in 8 patients, swelling in 14, pain in 16, and erythema in one; low flow priapism was observed in 2 patients. Ultrasound examination identified acute orchitis in 10 patients, acute epididymitis in 7, and acute epididymo-orchitis in 16. A case-control study reported that patients with moderate COVID-19 show a significant reduction in sperm concertation, total number of sperms per ejaculate, progressive motility, and complete motility. Contrary to what known from the first studies on the subject, this review also including subsequent studies give evidence of an involvement of lower urinary tract and male genital system in COVID-19. This article is protected by copyright. All rights reserved.

Objetivo: analisar, por meio da literatura, as contribuições da assistência de enfermagem no contexto das pandemias. Método: revisão integrativa da literatura realizada na Biblioteca Virtual em Saúde (BVS) e Scientific Eletronic Library Online (SciELO) e PubMed com os Descritores em Ciências da Saúde (DeCS) "assistência integral í saúde"; "cuidados de Enfermagem" e "pandemias". Os critérios de inclusão foram: texto em português e inglês e de exclusão foram desconsiderados artigos em formatos de textos, que não passaram por processos rigorosos de avaliação. Resultados: A primeira categoria mostra os profissionais da enfermagem superam desafios em saúde por intermédio da assistência qualificada, o cuidado holí­stico e o plano de cuidados desses profissionais refletiram na recuperação. A segunda categoria enfatiza que as teorias de enfermagem implementadas no contexto histórico da enfermagem moderna no cenário atual. Conclusão: As contribuição da assistência de enfermagem quanto as pandemias vivenciadas, coloca a enfermagem como protagonista.

Objective To evaluate factors impacting survival outcomes in patients with uterine serous carcinoma (USC). Methods Data of consecutive patients diagnosed with USC undergoing surgery between 2000 and 2020 at Fondazione IRCCS Istituto Nazionale Tumori of Milan (Italy) were reviewed. Progression-free (PFS) and overall survival (OS) outcomes were evaluated using Kaplan-Meier and Cox proportional hazard models. Results Records of 147 consecutive patients meeting the inclusion criteria were analyzed. Stage distribution was: 67 (45.6%) patients with early-stage with uterine confined disease and 80 (54.4%) with advanced stages disease. Minimally invasive surgery was performed in 43 patients (29.5%). The median follow-up period was 78.6 months (IQ range = 35.7–117.3 months). The overall recurrence rate was 41% (60 patients): 19/67 patients (28.4%) with early-stage disease and 41/80 patients (51.3%) with advanced stage. The 5-year PFS rate was 35.0% (95% confidence interval [CI]: 27.5–44.7%). In multivariate analysis, age, BMI, depth of myometrial invasion, cytology, and optimal cytoreduction with postoperative residual tumor absent significantly impacted on PFS. The 5-year OS rates were 46.5% (95% CI: 38.1–56.8). The result of multivariate analysis showed that there was significant difference in OS based only on optimal cytoreduction and accuracy of retroperitoneal surgery. Conclusions In apparent early-stage USC, peritoneal and retroperitoneal staging allows to identify patients with disease harboring outside the uterus. Optimal cytoreduction is the most significant prognostic factor. Further collaborative studies are warranted in order to improve outcomes of USC patients.

Our aim was to analyze outcomes of patients aged 70 years or above presenting with type A acute aortic dissection (TAAAD) and cerebrovascular accident (CVA). A retrospective analysis of the International Registry of Acute Aortic Dissection (IRAD) was conducted. Patients aged 70 years or above (n = 1449) were stratified according to presence or absence of CVA before surgery (CVA: n = 110, 7.6%). In-hospital outcomes and mortality up to 5 years were analyzed. Additionally, in-hospital outcomes of patients who received medical management were described. No patient presenting with CVA over the age of 87 years underwent surgery. The rates of in-hospital mortality and post-operative CVA were significantly higher in patients presenting with CVA (in-hospital mortality: 32.7% vs 21.7%, P = 0.008; post-operative CVA: 23.4% vs 8.3%, P0.001). Presence of CVA was independently associated with significantly increased in-hospital mortality (odds ratio 2.99, 95% confidence interval 1.35 - 6.60, P = 0.007). In survivors of the hospital stay, presenting CVA had no independent influence on mortality up to 5 years (hazard ratio 1.52, 95% confidence interval 0.99 - 2.31, P = 0.54). In medically managed patients, exceedingly high rates of in-hospital mortality (71.4%) and CVA (90.9%) were noted. Patients presenting with TAAAD and CVA at ≥ 70 years of age are at significantly increased risk of in-hospital mortality, although long-term mortality is not affected in hospital survivors. Medical management is associated with poor outcomes. We believe that surgical management should be offered after critical assessment of comorbidities.

This study sought to assess the predictive value of wall shear stress (WSS) for colocalized ascending aorta (AAo) growth rate (GR) in patients with bicuspid aortic valve (BAV).BAV is associated with AAo dilation, but there is limited knowledge about possible predictors of aortic dilation in patients with BAV. An increased WSS has been related to aortic wall damage in patients with BAV, but no previous prospective study tested its predictive value for dilation rate. Recently, a registration-based technique for the semiautomatic mapping of aortic GR has been presented and validated.Forty-seven patients with BAV free from valvular dysfunction prospectively underwent 4-dimensional flow cardiac magnetic resonance to compute WSS and subsequent follow-up with 2 electrocardiogram-gated high-resolution contrast-enhanced computed tomography angiograms for GR assessment.During a median follow-up duration of 43 months, mid AAo GR was 0.24 mm/year. WSS and its circumferential component showed statistically significant association with mid AAo GR in bivariate (P = 0.049 and P = 0.014, respectively) and in multivariate analysis corrected for stroke volume and either baseline AAo diameter (P = 0.046 and P = 0.014, respectively) or z-score (P = 0.036 and P = 0.012, respectively). GR mapping further detailed that GR was heterogeneous in the AAo and that circumferential WSS, but not WSS magnitude, showed statistically significant positive associations with GR in the regions with the fastest growth.4D flow cardiac magnetic resonance-derived WSS and, in particular, its circumferential component predict progressive dilation of the ascending aorta in patients with BAV. Thus, the assessment of WSS may be considered in the follow-up of these patients.

Objetivo: O objetivo do presente estudo foi analisar como o treinamento de restrição de fluxo sanguíneo (RFS) tem sido utilizado por profissionais no Brasil, com foco no perfil do usuário, controle de variáveis de treinamento e taxa de ocorrência de efeitos adversos. Métodos: Oitenta e seis profissionais de saúde com experiência em treinamento de RFS foram entrevistados por meio de um questionário digital elaborado pelos autores, contendo 17 perguntas sobre as características do uso do método. Resultados: O treinamento em RFS tem sido utilizado no Brasil nos últimos 5 anos, principalmente por profissionais de Educação Física que atendem principalmente adultos, atletas e idosos saudáveis, com diversos objetivos. A maioria dos profissionais parece seguir recomendações científicas específicas para a prescrição do treinamento de RFS, com exceção de uma pequena parcela dos participantes, principalmente no que se refere ao controle da pressão no RFS. Efeitos adversos imediatos de baixa gravidade associados ao método foram observados a taxas razoáveis e nenhum efeito sério foi relatado. Conclusão: Como um pequeno número de profissionais relatou desatenção às recomendações científicas para o controle dessa variável, esses efeitos adversos podem estar associados ao controle inadequado da pressão de oclusão vascular.

Aims This study aimed to explore factors related to non-adherence to exergaming in patients with heart failure. Methods and results Data from patients in the exergame group in the HF-Wii trial were used. Adherence to exergaming was defined as playing 80% or more of the recommended time. Data on adherence and reasons for not exergaming at all were collected during phone calls after 2, 4, 8, and 12 weeks. Logistic regression was performed between patients who were adherent and patients who were non-adherent. Secondly, a logistic regression was performed between patients who not exergamed at all and patients who were adherent to exergaming. Finally, we analysed the reasons for not exergaming at all with manifest content analysis. Almost half of the patients were adherent to exergaming. Patients who were adherent had lower social motivation [odds ratio (OR) 0.072; 95% confidence interval (CI) 0.054-0.095], fewer sleeping problems (OR 0.84; 95% CI 0.76-0.092), and higher exercise capacity (OR 1.003; 95% CI 1.001-1.005) compared with patients who were non-adherent. Patients who not exergamed at all had lower cognition (OR 1.18; 95% CI 1.06-1.31) and more often suffered from peripheral vascular disease (OR 3.74; 95% CI 1.01-13.83) compared with patients who were adherent to exergaming. Patients most often cited disease-specific barriers as a reason for not exergaming at all. Conclusions A thorough baseline assessment of physical function and cognition is needed before beginning an exergame intervention. It is important to offer the possibility to exergame with others, to be able to adapt the intensity of physical activity. Funding Agencies|Swedish National Science Council [K2013-69X-22302-01-3, 2016-01390]; Swedish National Science Council/the Swedish Research Council for Health, Working Life and Welfare, VR-FORTE [2014-4100]; Swedish Heart and Lung Association [Hjart-Lungfonden] [E085/12]; Swedish Heart and Lung Foundation (Hjart-Lungfonden) [20130340, 20160439]; Vardal Foundation (Vardalstiftelsen) [2014-0018]; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [FORSS 474681]

Evaluate the effect of 12 wks of concurrent training (CT) in the extracellular matrix (ECM) of subcutaneous adipose tissue (SAT) in people living with HIV/AIDS (PLWHA). In the non-randomized clinical trial, 19 participants, 11 healthy (HIV–) and 18 PLWHA under the use of highly active antiretroviral therapy (HAART) for at least 1 year (HIV+). All participants engaged in a moderate-intensity CT program for 12 weeks, 3 times a week. Before and after CT, aerobic and strength performance were assessed, as well as anthropometric and biochemical blood profiles. In addition, SAT biopsies were performed for histologic and morphometric analyses. Statistical analysis was carried out with R Studio, using descriptive and inferential analysis, ANOVA test, and mixed-effect model (P < 0.05). HIV+ showed higher levels of very-low-density lipoproteins and triglycerides and lower levels of high-density lipoproteins at baseline than HIV– (P < 0.05). All groups showed improved aerobic and strength performances (P < 0.05). Both groups showed reduced adipocyte sizes after CT (P < 0.05). Lastly, HIV+ presented smaller adipocytes and higher elastic fiber deposition at baseline and decreased after training only in HIV+, similar to the HIV group. Thus, CT in PLWHA promoted a decrease in the size heterogeneity of adipocytes and elastic fiber deposition, remodeling the ECM, and improving the SAT fibrosis profile. Brazilian Clinical Trials Registry (ensaiosclinicos.gov.br – UTN: U1111-1214-3022).Novelty: Adipose tissue fibrosis is improved by training in people living with HIV. Concurrent training remodels adipose tissue extracellular matrix.

Background and aims Monitoring the immune response against SARS-CoV-2 is pivotal in the evaluation of long-term vaccine efficacy. Immunoglobulin G (IgG) antibodies represent an advisable tool to reach this goal, especially for the still poorly defined antibody trend induced by the new class of mRNA vaccines against SARS-CoV-2. Materials and methods Anti-Spike RBD IgG antibodies were monitored in a cohort of healthcare workers at CRO Aviano, National Cancer Institute, through MAGLUMI® chemiluminescence assay, at 1 and 4 months after full-schedule of BNT162b2 or mRNA-1273 vaccination. Results At 1 month after vaccination, 99.9% of 767 healthcare workers showed a reactive antibody response, which was inversely correlated with age, and positively associated with a previous history of COVID-19, and mRNA-1273 vaccination. Serological response was maintained in 99.6% of the 516 subjects monitored also at follow-up. An antibody decay from 559.8 AU/mL (IQR 359.7–845.7) to 92.7 AU/mL (IQR 65.1–148.6; p

Data on the prevalence and mortality of paediatric sepsis in resource-poor settings are scarce. We aimed to assess the prevalence and in-hospital mortality of severe sepsis and septic shock treated in paediatric intensive care units (PICUs) in Brazil, and risk factors for mortality.We performed a nationwide, 1-day, prospective point prevalence study with follow-up of patients with severe sepsis and septic shock, using a stratified random sample of all PICUs in Brazil. Patients were enrolled at each participating PICU on a single day between March 25 and 29, 2019. All patients occupying a bed at the PICU on the study day (either admitted previously or on that day) were included if they were aged 28 days to 18 years and met the criteria for severe sepsis or septic shock at any time during hospitalisation. Patients were followed up until hospital discharge or death, censored at 60 days. Risk factors for mortality were assessed using a Poisson regression model. We used prevalence to generate national estimates.Of 241 PICUs invited to participate, 144 PICUs (capacity of 1242 beds) included patients in the study. On the day of the study, 1122 children were admitted to the participating PICUs, of whom 280 met the criteria for severe sepsis or septic shock during hospitalisation, resulting in a prevalence of 25·0% (95% CI 21·6-28·8), with a mortality rate of 19·8% (15·4-25·2; 50 of 252 patients with complete clinical data). Increased risk of mortality was associated with higher Pediatric Sequential Organ Failure Assessment score (relative risk per point increase 1·21, 95% CI 1·14-1·29, p0·0001), unknown vaccination status (2·57, 1·26-5·24; p=0·011), incomplete vaccination status (2·16, 1·19-3·92; p=0·012), health care-associated infection (2·12, 1·23-3·64, p=0·0073), and compliance with antibiotics (2·38, 1·46-3·86, p=0·0007). The estimated incidence of PICU-treated sepsis was 74·6 cases per 100 000 paediatric population (95% CI 61·5-90·5), which translates to 42 374 cases per year (34 940-51 443) in Brazil, with an estimated mortality of 8305 (6848-10 083).In this representative sample of PICUs in a middle-income country, the prevalences of severe sepsis or septic shock and in-hospital mortality were high. Modifiable factors, such as incomplete vaccination and health care-associated infections, were associated with greater risk of in-hospital mortality.Fundação de Amparo à Pesquisa do Estado de São Paulo and Conselho Nacional de Desenvolvimento Científico e Tecnológico.For the Portuguese translation of the abstract see Supplementary Materials section.

STUDY OBJECTIVES: To assess the responsiveness of the Idiopathic Hypersomnia Severity Scale (IHSS) to medications and estimate the minimum clinically important difference, to report clinically relevant score ranges, and to confirm its psychometric properties and whether items need to be weighted in drug-free and treated patients with idiopathic hypersomnia (IH). METHODS: Two-hundred twenty-six (166 drug-free and 60 treated) patients with IH (cross-sectional sample) completed the 14-item IHSS to quantify the severity of the 3 major IH symptoms (excessive daytime sleepiness, prolonged nighttime sleep, and sleep inertia) and consequences; 77 untreated patients were evaluated again after treatment (longitudinal sample). Patients filled in the Epworth Sleepiness Scale, Beck Depression Inventory II, and European Quality of Life questionnaires. RESULTS: The IHSS confirmed adequate psychometric properties with a factor analysis indicating a 3-component solution. IHSS total score was lower in treated than untreated patients, with a mean difference of 4–5 points in the cross-sectional and longitudinal samples. Distribution-based methods were used to estimate that 4 points represented the minimum clinically important difference. Four severity levels were defined with between-group differences related to treatment. The probability of having severe sleepiness, depressive symptoms, and low quality of life increased with the severity level. Our results showed that IHSS item-weighting was not necessary. CONCLUSIONS: The IHSS is a valid and reliable tool to quantify IH symptoms, with 4 severity score levels of clinical importance. The IHSS has adequate psychometric properties and can detect symptom changes after treatment. These findings should stimulate its use in clinical settings and in research studies. CITATION: Rassu AL, Evangelista E, Barateau L, et al. Idiopathic Hypersomnia Severity Scale to better quantify symptoms severity and their consequences in idiopathic hypersomnia. J Clin Sleep Med. 2022;18(2):617–629.

Bicuspid aortic valve (BAV) patients are at high risk of developing progressive aortic valve dysfunction and ascending aorta dilation. However, the progression of the disease is not well defined. We aimed to assess mid-long-term aorta dilation and valve dysfunction progression and their predictors. Patients were referred from cardiac outpatient clinics to the echocardiographic laboratories of 10 tertiary hospitals and followed clinically and by echocardiography for &gt, 5 years. Seven hundred and eighteen patients with BAV (median age 47.8 years [IQR 33–62], 69.2% male) were recruited. BAV without raphe was observed in 11.3%. After a median follow-up of 7.2 years [IQR5–8], mean aortic root growth rate was 0.23 ± 0.15 mm/year. On multivariate analysis, rapid aortic root dilation (&gt, 0.35 mm/year) was associated with male sex, hypertension, presence of raphe and aortic regurgitation. Annual ascending aorta growth rate was 0.43 ± 0.32 mm/year. Rapid ascending aorta dilation was related only to hypertension. Variables associated with aortic stenosis and regurgitation progression, adjusted by follow-up time, were presence of raphe, hypertension and dyslipidemia and basal valvular dysfunction, respectively. Intrinsic BAV characteristics and cardiovascular risk factors were associated with aorta dilation and valvular dysfunction progression, taking into account the inherent limitations of our study-design. Strict and early control of cardiovascular risk factors is mandatory in BAV patients.

This International Consensus Classification and Nomenclature for the congenital bicuspid aortic valve condition recognizes 3 types of bicuspid valves: 1. The fused type (right-left cusp fusion, right-non-coronary cusp fusion and left-non-coronary cusp fusion phenotypes); 2. The 2-sinus type (latero-lateral and antero-posterior phenotypes); and 3. The partial-fusion (forme fruste) type. The presence of raphe and the symmetry of the fused type phenotypes are critical aspects to describe. The International Consensus also recognizes 3 types of bicuspid valve-associated aortopathy: 1. The ascending phenotype; 2. The root phenotype; and 3. Extended phenotypes. © 2021 Jointly between the RSNA, the European Association for Cardio-Thoracic Surgery, The Society of Thoracic Surgeons, and the American Association for Thoracic Surgery. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. All rights reserved. Keywords: Bicuspid Aortic Valve, Aortopathy, Nomenclature, Classification.

Bisphosphonates are the first-choice treatment of osteoporosis and Paget’s disease of bone. Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. This pathway regulates cholesterol and glucose homeostasis and is a target for statins. In this retrospective cohort study, we evaluated the effects of an intravenous infusion of zoledronic acid (5 mg) or clodronic acid (1500 mg) on blood lipid (i.e. total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides) and glucose levels in patients with osteoporosis and Paget’s disease of bone. All patients were evaluated before, 1 and 6 months after bisphosphonate treatment. Pagetic and osteoporotic patients treated with zoledronic acid showed a significant reduction in glucose and atherogenic lipids during follow-up whereas these phenomena were not observed after clodronic treatment. The effect on circulating lipid levels was similar in naïve and re-treated Pagetic patients. Zoledronic acid treatment was associated with a reduction in blood glucose and atherogenic lipids in patients with metabolic bone disorders. The extent of change was similar to that obtained with the regular assumption of a low-intensity statin. Further studies are warranted to better evaluate the clinical implications of these observations. Supplementary Information The online version of this article (10.1007/s00223-021-00811-w) contains supplementary material, which is available to authorized users.

Rare genetic neurological disorders (RND; ORPHA:71859) are a heterogeneous group of disorders comprising >1700 distinct genetic disease entities. However, genetic discoveries have not yet translated into dramatic increases of diagnostic yield and indeed rates of molecular genetic diagnoses have been stuck at about 30–50% across NGS modalities and RND phenotypes [1, 2]. Existence of yet unknown disease genes as well as shortcomings of commonly employed NGS technologies and analysis pipelines in detecting certain variant types are typically cited to explain the low diagnosis rates. To increase the diagnostic yield in RNDs - one of the four focus disease groups in Solve-RD - we follow two major approaches, that we will here present and exemplify: (i) systematic state-of the art re-analysis of large cohorts of unsolved whole-exome/genome sequencing (WES/WGS) RND datasets; and (ii) novel-omics approaches. Based on the way Solve-RD systematically organizes researchers’ expertise to channel this approach [3], the European Reference Network for Rare Neurological Diseases (ERN-RND) has established its own Data Interpretation Task Force (DITF) within SOLVE-RD, which is currently composed of clinical and genetic experts from 29 sites in 15 European countries. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 779257. Data were analysed using the RD‐Connect Genome‐Phenome Analysis Platform, which received funding from EU projects RD‐Connect, Solve-RD and EJP-RD (Grant Numbers FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (Grant Numbers PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinformática, INB) and ELIXIR Implementation Studies. The study was further funded by the Federal Ministry of Education and Research, Germany, through the TreatHSP network (01GM1905 to RS and LS), the National Institute of Neurological Diseases and Stroke (R01NS072248 to SZ and RS), the European Joint Program on Rare Diseases-EJP-RD COFUND-EJP N° 825575 through funding for the PROSPAX consortium (441409627 to MS, RS and BvW). CW was supported by the PATE program of the Medical Faculty, University of Tübingen. CEE received support from the Dutch Princess Beatrix Muscle Fund and the Dutch Spieren voor Spieren Muscle fund. Authors on this paper are members of the European Reference Network for Rare Neurological Diseases (ERN-RND, Project ID 739510)

Purpose: Osteoporosis (Op) and metabolic syndrome (MetS) are two common disorders showing common pathogenic patterns. This cross-sectional study was performed to evaluate if MetS and its constitutive elements are associated to an increased risk of low bone mineral density (BMD) in free-living women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. Methods: 13,182 free-living Caucasian women referring to “COMEGEN” general practitioners cooperative operating in Naples, Italy, performed a contextual evaluation of BMD by DXA and all MetS constitutive elements (systolic and diastolic blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose) between June 1st 2008 and May 31st 2018. Subjects aged less than 40 years or with signs or symptoms suggestive of secondary Op were excluded from the study. Results: MetS is associated to an increased risk of low BMD (Odds Ratio 1.19; 95% Confidence Interval 1.08–1.31). Among MetS constitutive elements, hypertension was associated to increased risk of low BMD, whereas high fasting glucose level/diabetes were associated to reduced risk of low BMD. Conclusions: The significant association between Op and MetS in free-living women examined by DXA for suspected Op suggests the advisability of a contextual evaluation of both disorders in this setting.

PURPOSE: To study whether a new combination of different warming kits is clinically effective for vitrified human blastocysts. METHODS: This is a longitudinal cohort study analysing two hundred fifty-five blastocysts warming cycles performed between January and October 2018. Embryos were vitrified using only one brand of ready-to-use kits (Kitazato), whereas the warming procedure was performed with three of the most widely used vitrification/warming kits (Kitazato, Sage and Irvine) after patient stratification for oocyte source. The primary endpoint was survival rate, while the secondary endpoints were clinical pregnancy, live birth and miscarriage rates. RESULTS: We observed a comparable survival rate across all groups of 100% (47/47) in KK, 97.6% (49/50) in KS, 97.6% (41/42) in KI, 100% (38/38) in dKK, 100% (35/35) in dKS and 100% (43/43) in dKI. Clinical pregnancy rates were also comparable: 38.3% (18/47) in KK, 49% (24/49) in KS, 56.1% (23/ 41) in KI, 47.4% (18/38) in dKK, 31.4% (11/35) in dKS and 48.8% (21/ 43) in dKI. Finally, live birth rates were 29.8% (14/47) in KK, 36.7% (18/49) in KS, 46.3% (19/41) in KI, 36.8% (14/38) in dKK, 25.7% (9/35) in dKS and 41.9% (18/43) in dKI, showing no significant differences. CONCLUSION: This study confirmed the efficacy of applying a single warming protocol, despite what the “industry” has led us to believe, supporting the idea that it is time to proceed in the cryopreservation field and encouraging embryologists worldwide to come out and reveal that such a procedure is possible and safe.

INTRODUÇÃO: A fibrose cística (FC) ou mucoviscidose é uma doença genética de caráter autossômico recessivo e multissistêmico causada devido a um desequilíbrio do transporte iônico. A ventilação mecânica não invasiva (VNI) é uma técnica que utiliza pressão positiva para proporcionar auxílio ventilatório sem necessidade de prótese endotraqueal ou traqueostomia, melhorando, assim, o conforto do paciente. OBJETIVO: Avaliar a efetividade da ventilação não invasiva (VNI) em pacientes com fibrose cística, visando responder à pergunta norteadora: “Qual efetividade da VNI no tratamento do paciente com Fibrose Cística? ”. METODOLOGIA: Foi realizada uma revisão sistemática de caráter quantitativo de artigos a partir da pesquisa nas bases de dado Pubmed, PEDro, Scielo e Lilacs, em outubro de 2021, utilizando os descritores “non-invasive ventilation” e “cystic fibrosis”. Foram selecionados 9 artigos após serem incluídos estudos apresentando texto completo, sendo ensaio clínico, randomizado e pesquisa com humanos, deixando livre idioma e ano de publicação, e excluídos estudos que não abordavam a temática proposta e estudos duplicados. RESULTADO E DISCUSSÃO: Os estudos finais foram expostos em três tabelas contanto com artigos encontrados em cada base de dado pesquisada, pontuação dos artigos quanto a escala PeDro e uma tabela expositiva contendo dados referentes a cada pesquisa. Dentre os expostos foi possível analisar que a VNI pode ser usada em pacientes com FC, comprovando melhora significativamente a expectoração de muco, a fadiga muscular, a desobstrução das vias aéreas e a melhora dos sintomas torácicos. CONCLUSÃO: A ventilação mecânica não invasiva apresenta ação benéfica em pacientes com fibrose cística, entretanto mais estudos são necessários para análise de suas ações, de forma individual ou conjugada.

To review the existing literature on PET/MR for musculoskeletal malignancies. PubMed (MEDLINE) was searched through July 2021. The search strategy focused on the keywords “PET/CT”, “PET/MR”, “MRI”, “attenuation correction”, “sarcoma”, “skeletal”, “metastases”, “myeloma”, “FDG”, “Sodium fluoride”, “PSMA”, “DOTATATE”, “fluciclovine”, and “FAPI”. 97 relevant papers were considered for review. Studies selected were primarily retrospective and prospective cohort studies. There is limited literature comparing PET/CT to PET/MR for evaluation of primary musculoskeletal malignancies and musculoskeletal metastatic disease. Most studies involve relatively small numbers of patients. Despite limited evidence and the lack of widespread application, PET/MR is a promising imaging technique for evaluating musculoskeletal malignancies. This is owing primarily to the strength of its constituent modalities. PET permits for acquisition of metabolic information using a variety of emerging novel radiopharmaceuticals. MR allows for assessment of bone marrow and for identification and characterization of soft-tissue lesions. Selection of appropriate radiopharmaceutical and MR protocol parameters is key for optimal evaluation. Although PET/MR has shown promise in evaluation of musculoskeletal involvement of multiple malignancies, it has not yet demonstrated broad superior to PET/CT. More research is needed to understand its value in the care of patients with such diseases.

Liver cancer is the fourth leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 80% of all liver cancers. The serum concentration of alpha-fetoprotein (AFP) is the only validated biomarker for HCC diagnosis. MicroRNAs (miRNAs) are small non-coding RNAs of 21–30 nucleotides playing a critical role in human carcinogenesis, with types of miRNAs with oncogenic (oncomiRs) or tumor suppressor features. The altered expression of miRNAs in HCC is associated with many pathological processes, such as cancer initiation, tumor growth, apoptosis escape, promotion of migration and invasion. Moreover, circulating miRNAs have been increasingly investigated as non-invasive biomarkers for HCC diagnosis. MiRNAs’ expression patterns are altered in HCC and several single miRNAs or miRNAs panels have been found significantly up or downregulated in HCC with respect to healthy controls or non-oncological patients (cirrhotic or with viral hepatitis). However, any of the investigated miRNAs or miRNAs panels has entered clinical practice so far. This has mostly to do with lack of protocols standardization, small sample size and discrepancies in the measurement techniques. This review summarizes the major findings regarding the diagnostic role of miRNAs in HCC and their possible use together with standard biomarkers in order to obtain an early diagnosis and easier differential diagnosis from non-cancerous liver disease.

Background Coronavirus disease-19 (COVID-19) due to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the largest emergency that humanity had to be dealing with in the last century. During the last months, different types of vaccines have been designed to contain the ongoing SARS-CoV-2 pandemic, with successful results in many countries. Comirnaty (Pfizer/BioNtech) COVID-19 vaccine is a lipid nanoparticle-formulated, nucleoside mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2. Although vaccines have an undeniable efficacy, they can also present several neurological side effects, including headache. According to ICHD-3 Classification, status migrainosus (SMg) is described as a debilitating migraine attack lasting for more than 72 h. Symptoms of SMg can be very severe, preventing the normal daily activities of the individual. Case presentation In the present report, we describe a case of SMg that lasted 11 days, time correlated with the second dose of COVID-19 vaccine (Pfizer/Comirnaty) in a 37-year-old woman with a history of migraine without aura. Conclusions In patients with a history of migraine, COVID-19 vaccination could lead to a worsening of headache and, in rare cases, to the development of a SMg. This may be related to the inflammatory response that occurs after vaccination. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-021-05741-x.

Objective Thoracic endovascular aortic repair (TEVAR) is widely used for the treatment of patients with blunt traumatic thoracic aortic injury (BTAI). However, aortic haemodynamic and biomechanical implications of this intervention are poorly investigated. This study aimed to assess whether patients treated by TEVAR following BTAI have thoracic aortic abnormalities in geometry, stiffness, and haemodynamics. Methods Patients with BTAI treated by TEVAR at Vall d’Hebron Hospital between 1999 and 2019 were compared with propensity score matched healthy volunteers (HVs). All subjects underwent cardiovascular magnetic resonance (CMR) comprising a 4D flow CMR sequence. Spatially resolved aortic diameter, length, volume, and curvature were assessed. Pulse wave velocity, distensibility, and longitudinal strain (all measurements of aortic stiffness) were determined regionally. Moreover, advanced haemodynamic descriptors were quantified: systolic flow reversal ratio (SFRR), quantifying backward flow during systole, and in plane rotational flow (IRF), measuring in plane strength of helical flow. Results Twenty-six BTAI patients treated by TEVAR were included and matched with 26 HVs. They did not differ in terms of age, sex, and body surface area. Patients with TEVAR had a larger and longer ascending aorta (AAo) and marked abnormalities in local curvature. Aortic stiffness was greater in the aortic segments proximal and distal to TEVAR compared with controls. Moreover, TEVAR patients presented strongly altered flow dynamics compared with controls: a reduced IRF from the distal AAo to the proximal descending aorta and an increased SFRR in the whole thoracic aorta. These differences persisted adjusting for cardiovascular risk factors and were independent of time elapsed since TEVAR implantation. Conclusion At long term follow up, previously healthy patients who underwent TEVAR implantation following BTAI had increased diameter, length and volume of the ascending aorta, and increased aortic stiffness and abnormal flow patterns in the whole thoracic aorta compared with matched controls. Further studies should address whether these alterations have clinical implications.

Whole blood transfusion (WBT) began in 1667 as a treatment for mental illness, with predictably poor results. Its therapeutic utility and widespread use were initially limited by deficiencies in transfusion science and antisepsis. James Blundell, a British obstetrician, was recognized for the first allotransfusion in 1825. However, WBT did not become safe and therapeutic until the early 20(th) century, with the advent of reliable equipment, sterilization, and blood typing. The discovery of citrate preservation in World War I allowed a separation of donor from recipient and introduced the practice of blood banking. During World War II, Elliott and Strumia were the first to separate whole blood into blood component therapy (BCT), producing dried plasma as a resuscitative product for “traumatic shock.” During the 1970s, infectious disease, blood fractionation, and financial opportunities further drove the change from WBT to BCT, with few supporting data. Following a period of high-volume crystalloid and BCT resuscitation well into the early 2000s, measures to avoid the resulting iatrogenic resuscitation injury were developed under the concept of damage control resuscitation. Modern transfusion strategies for hemorrhagic shock target balanced BCT to reapproximate whole blood. Contemporary research has expanded the role of WBT to therapy for the acute coagulopathy of trauma and the damaged endothelium. Many US trauma centers are now using WBT as a front-line treatment in tandem with BCT for patients suffering hemorrhagic shock. Looking ahead, it is likely that WBT will once again be the resuscitative fluid of choice for patients in hemorrhagic shock.

Introduction: The use of whole body electromyostimulation (WB-EMS) has been shown to be an efficient method for inducing significant improvements in muscle strength and performance outcomes. Hypothetically, WB-EMS had been considered an enhancer of energy expenditure in the session, but this remains unclear. Objective: In view of the lack of information, this study aims to evaluate the energy expenditure of WB-EMS associated with whole body High-Intensity Interval Training (HIIT). Methods: Fourteen male participants were submitted into two randomized exercise sessions: HIIT (whole body weight exercises without WB-EMS) and HIIT+WB-EMS (whole body weight exercises associated with WB-EMS). For both exercise conditions, the subjects performed whole body HIIT according to the following protocol: 3 minutes of warm-up followed by 4 exercises (30 seconds of stimulus) organized in 2 blocks, with 3 sets in each exercise, a rest period of 15 seconds between sets, and 180 seconds between blocks. The following exercises were performed: jumping jacks, squat and thrusts, burpees, and spider plank. Results: Significant differences were found in the absolute VO2 (HIIT:2.18±0.34, HIIT+WB-EMS:2.32±0.36 L.min−1) and relative VO2 (HIIT:26.30±3.77, HIIT+WB-EMS:28.02± 3.74 ml.kg.min−1), MET (HIIT:7.51±1.07, HIIT+WB-EMS:8.00±1.07), lactate concentration (HIIT:11.59±2.16, HIIT+WB-EMS: 12.64±1.99 mmol.L−1) and total energy expenditure (HIIT: 249.6± 45.04 Kcal, HIIT+ WB-EMS: 268.9±40.67 Kcal; 7.46 ± 5.31%). Conclusion: Our data indicate that the use of WB-EMS associated with HIIT generated a slightly higher metabolic demand than that of the control. However, the absolute differences do not allow us to indicate the superiority of WB-EMS, and future trials should be designed to determine the long-term effects. RESUMEN Introducción: Se ha demostrado que el uso de la electroestimulación de cuerpo entero (WB-EMS) es un método eficaz para inducir mejoras significativas en la fuerza muscular y los resultados de rendimiento. Hipotéticamente, la práctica de WB-EMS se consideró un potenciador del gasto calórico en la sesión, pero esto aún no está claro. Objetivo: el objetivo del estudio fue evaluar el gasto energético del WB-EMS asociado al HIIT con el peso corporal. Métodos: Se asignaron al azar catorce participantes masculinos a dos sesiones de ejercicio: HIIT (ejercicios de peso corporal total sin WB-EMS) y HIIT + WB-EMS (ejercicios de peso corporal total asociados con WB-EMS). Para ambas condiciones de ejercicio, los sujetos realizaron HIIT con peso corporal según el siguiente protocolo: 3 minutos de calentamiento seguido de 4 ejercicios (30 segundos de estímulo) organizados en 2 bloques con 3 series en cada ejercicio y 15 segundos entre series y ejercicios y 180 segundos entre bloques de descanso pasivo con los siguientes ejercicios realizados: jump jack, squat and thrust, burpee y spider plank. Resultados: Se encontraron diferencias significativas en el consumo de VO2 absoluto (HIIT: 2,18 ± 0,34, HIIT + WB-EMS: 2,32 ± 0,36 L.min−1) y relativo (HIIT: 26,30 ± 3,77, HIIT + WB-EMS: 28,02 ± 3,74 ml.kg.min1), MET (HIIT: 7,51 ± 1,07, HIIT + WB-EMS: 8,00 ± 1, 07), concentración de lactato (HIIT: 11,59 ± 2,16, HIIT + WB-EMS: 12,64 ± 1,99 mmol.L−1) y gasto energetico total (HIIT: 231,5±36,38Kcal, HIIT + WB-EMS:246,9± 38,76Kcal; 6,14± 5,61%). Conclusión: Nuestros datos indican que el uso de WB-EMS asociado a HIIT generó, en una de manera sutil, una mayor respuesta a la demanda metabólica que la situación de control. Sin embargo, las diferencias absolutas no permiten indicar la superioridad del WB-EMS con estudios futuros y deben planificarse. RESUMO Introdução: O uso da eletromioestimulação de corpo inteiro (whole body electromyostimulation - WB-EMS) tem mostrado ser um método eficiente para induzir melhora significativa da força muscular e do desempenho. Hipoteticamente, a prática de WB-EMS foi considerada potencializadora do gasto energético na sessão, mas isso ainda não está claro. Objetivo: Diante da escassez de informações, o objetivo deste estudo foi avaliar o gasto energético da WB-EMS associada ao treinamento intervalado de alta intensidade (HIIT) com o peso corporal. Métodos: Quatorze participantes do sexo masculino foram submetidos a duas sessões de exercícios randomizadas: HIIT (exercícios com peso corporal sem WB-EMS) e HIIT + WB-EMS (exercícios com peso corporal associados a WB-EMS). Para ambas as condições de exercício, os indivíduos realizaram HIIT com peso corporal, de acordo com o seguinte protocolo: 3 minutos de aquecimento seguidos de 4 exercícios (30 segundos de estímulo), organizados em 2 blocos com 3 séries em cada exercício, com 15 segundos de descanso passivo entre as séries e 180 segundos entre os blocos, com os seguintes exercícios realizados: jumping jack (polichinelo), squat and thrust, burpee e spider plank. Resultados: Diferenças significativas foram encontradas no consumo de VO2 absoluto (HIIT: 2,18 ± 0,34, HIIT + WB-EMS: 2,32 ± 0,36; L.min−1) e VO2 relativo (HIIT: 26,30 ± 3,77, HIIT + WB-EMS: 28,02 ± 3,74; ml.kg.min−1), MET (HIIT: 7,51 ± 1,07, HIIT + WB-EMS: 8,00 ± 1,07), concentração no sangue de lactato (HIIT: 11,59 ± 2,16, HIIT + WB- EMS: 12,64 ± 1,99 mmol.L−1) e gasto energético total (HIIT: 249,6± 45,04 Kcal, HIIT+ WB-EMS: 268,9± 40,67 Kcal; 7,46 ± 5,31%). Conclusão: Nossos dados indicam que o uso de WB-EMS associado ao HIIT gerou demanda metabólica ligeiramente superior à do controle. Entretanto, as diferenças absolutas não permitem indicar superioridade do WB-EMS, e estudos futuros devem ser planejados de modo a determinar os efeitos a longo prazo. Nível de evidência II.

OBJECTIVES To evaluate if the topical application of Otosporin® before in-office bleaching with a 35% hydrogen peroxide (HP) gel reduces the risk and intensity of tooth sensitivity (TS), as well as the bleaching effectiveness. MATERIALS AND METHODS Twenty participants were selected for this split mouth, triple-blind, multicenter randomized clinical trial. Before each bleaching session, the placebo was applied in the patient's hemi-arch and the other half received the Otosporin®, according to the randomization procedure. Both products were applied topically for 10 min. The 35% HP was applied in two sessions with a 1-week interval. The risk and intensity of TS were assessed using the Numerical Scale (NRS) and the Visual Analog Scale (VAS). The bleaching effectiveness were evaluated with the visual scales and with a digital spectrophotometer. The absolute risk of TS was compared by McNemar's test. To compare the intensity of TS, the Wilcoxon signed-rank test was used to evaluate the NRS, while the paired t test was used to evaluate VAS. Bleaching effectiveness (ΔSGUs and ΔEab, ΔE00, and ΔWID) was compared between groups using the paired t-test (α = 0.05). RESULTS No significant difference at risk (p = 1.0) and intensity of TS (p > 0.59; VAS and p = 1.00 for NRS) was detected between groups. For both groups, a significant bleaching was observed after 30 days of evaluation (p

The aim of the present study was to explore the prognostic role of 2- deoxy-2-[18F]fluoro-D-glucose PET (FDG PET)/CT in recurrent luminal A and luminal B breast cancer.From two institutional databases, we retrospectively retrieved data about breast cancer patients undergoing FDG PET/CT between 2011 and 2018 for the assessment of recurrency. Molecular subtypes of breast cancer were defined based on the expression of estrogen, progesterone, human epidermal growth factor receptor 2 (HER2)-b receptors and proliferation index. Overall survival (OS, intended as the time from PET/CT and the time of death) was registered for each patient, by checking the medical charts. Parametric and survival analyses were computed.Data of 179 patients were retrieved. Sixty-three patients had luminal A, 88 luminal B and 28 luminal B/He breast cancer. At the time of PET/CT scan, cancer antigen (CA) 15.3 levels was within the normal range in 119 patients, whereas it was increased in 60 patients. FDG PET/CT results were suggestive for disease recurrence in 114 (63.7%) patients. The median time lapse from the FDG PET/CT scan to the last clinical follow-up visit was 51 months (1-192 months). Patients with evidence of a PET/CT scan suggestive for disease recurrence showed a significantly shorter OS (P 0.001) compared to patients with no PET/CT evidence of recurrence, in each subset of luminal breast cancer. Moreover, PET/CT was able to stratify the prognosis of patients independently from the level of tumor marker.These data suggest that FDG PET/CT may be an attractive prognostic tool in recurrent breast cancer. Our study supports its prognostic role both in luminal A and B-type molecular subtypes, regardless of the CA 15.3 levels.

Acute Kidney Injury (AKI) can be defined as a spectrum of diseases associated with a sudden onset of a renal failure status, the feline patient has azotemia, the disorder in fractional electrolyte excretion (FE), and shedding of epithelial cells from renal tubular segments observed in the urinary sediment. Thus, the objective of the present study was to evaluate the FE, plasma and urinary osmolality, and urinary specific gravity (USG) in cats that spontaneously developed AKI due to urethral obstruction (UO) and healthy cats. Blood and urine samples were collected from a group of 20 cats diagnosed with AKI secondary to urethral obstruction (GAKI; n=20) and clinically healthy cats (GC; n=15). The serum creatinine (sCre) and urinary creatinine (uCre), were measured by spectrophotometry, serum and urinary analyzes of sodium, potassium and chloride by ion selective electrode device and serum and urinary osmolarity by osmometer. The GAKI results were statistically compared with those of the CG using Student's t tests to assess normal data, while the Maan-Whitney test was used for non-normal data. A significant increase in the sCr, sK, FENa, FECl and RFI parameters of the GAKI cats when compared to the GC (p < 0.05). The sCl, USG, uCr, uK and uOSM parameters decreased significantly when compared between the two groups. Thus, given the established methodology and the results found, it is possible to infer that an increase in EFNa, EFCl in addition to the RFI and a decrease in USG and uOSM were associated with cats with AKI and can serve as markers of kidney damage, as well as monitoring the prognosis.

Made available in DSpace on 2022-04-28T19:46:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-05 The most common testicular neoplasms in dogs are seminoma, leydigocytoma and sertolioma, affecting middle-aged and elderly dogs, where cryptorchidism is a predisposing factor, as well as some breeds. It can occur alone or, less frenquently, concurrently, generally affecting the same testicle. This study aimed to report the case of a non-cryptorchid 14-year-old mixed breed dog diagnosed with seminoma and sertolioma, each in a testicle. The animal showed an increase in scrotal volume, with no changes in other clinical parameters on physical examination. On ultrasound examination, it was possible to observe alterations suggestive of neoplasia in both testicles and prostatic alteration suggestive of benign prostatic hyperplasia. Complementary blood count and biochemical tests were performed and, as treatment, orchiectomy was performed. Fragments were collected from both testicles and sent for histopathological examination. Microscopy of the left testicle showed the presence of round cells, multiple and evident nucleoli, cells in different phases of mitosis and binucleation, these changes being compatible with seminoma. In contrast, in the right testicle, spindle and elongated cells (pseudo-lobular) were observed, presence of long cytoplasmic projections with rounded ovoid nucleus, spindle cells and degeneration of seminiferous tubules, compatible with sertolioma. It was observed that physical examination associated with ultrasound was efficient to detect the presence of neoplasms, being validated by histopathological examination. Orchiectomy was an assertive treatment indicated for this case. UNINGÁ - Ingá University Center, PR Mineiros University Center, GO São Paulo State University, SP Federal University of the Valleys of Jequitinhonha and Mucuri, MG São Paulo State University, SP

Status epilepticus (SE) is associated with high morbidity and mortality. This multicenter retrospective cohort study aims to identify the factors associated with the occurrence of SE and the predictors of its recurrence in patients with adult-onset seizures.We retrospectively analyzed data of 1115 patients with seizure onset18 years, observed from 1983 to 2020 in 7 Italian Centers (median follow-up 2.1 years). Data were collected from the databases of the Centers. Patients with SE were consecutively recruited, and patients without SE history were randomly selected in a 2:1 ratio. To assess determinants of SE, different clinical-demographic variables were evaluated and included in univariate and multivariate logistic regression model.Three hundred forty-seven patients had a SE history, whereas the remaining 768 patients had either isolated seizures or epilepsy without SE history. The occurrence of SE was independently associated with increasing age at onset of disease (OR 1.02, 95% CI 1.01--1.03, p0.001), female sex (OR 1.39, 95% CI 1.05--1.83, p=0.02) and known etiology (OR 3.58, 95% CI 2.61--4.93, p0.001). SE recurred in 21% of patients with adult-onset SE and recurrence was associated with increasing number of anti-seizure medications taken at last follow-up (OR 1.88, 95% CI 1.31--2.71, p0.001).In patients with adult-onset seizures, SE occurrence is associated with known etiologies, advanced age and female sex. Patients with recurrent SE are likely to have a refractory epilepsy, deserving careful treatment to prevent potentially fatal events.

Background: in Italy, Hepatitis-B-vaccine is advised and provided free-of-charge for subjects with chronic liver disease (CLD), including liver cirrhosis. Aims: to evaluate HB-vaccine-coverage and variables associated with lack of vaccination in cirrhotic patients with particular attention to cirrhosis' etiology. Methods: cirrhotic patients of any etiology (excluding HBsAg+) referring to 8 tertiary-centers were prospectively enrolled for a-six-months-period in 2019. Subjects were asked if they received HB-vaccine previously. Multiple-logistic-regression-analysis was performed to identify independent predictors of lack of vaccination. Results: 731 cases were recruited. Overall-vaccine-coverage was 16.3% (23.7% in those younger than 65y, 10.0% in those older than 64y; p64 y (OR: 4.27; CI 95%: 2.52-7.24), educational level

Background The incidence of social isolation among older adults is on the rise in today's health care climate. Consequently, preventing or ameliorating social isolation through technology in this age group is now being discussed as a significant social and health issue. Aim The purpose of the opinion paper is to clarify social transformation through technology and shed light on a new reality for older adults in situations of social isolation. Our goal is to persuade the reader that our position on this topic is a valid one. We support our claims with practice-based evidence and published research studies. Methods To do so, we checked the most recent literature, most of which came from the last decade. Our literature survey focused primarily on what is known about technology and how technology can affect social transformation and perceptions of social isolation. Findings Two dominant transformative realities became the focal points: the precarious implications of loneliness for older adults and the emerging reality of social change through digital technology central to eHealth and mHealth. Discussion To benefit from new technologies and reduce the detrimental effects of social isolation, we must engage older adults in a meaningful way and adapt the system of smart devices to reflect the specific physiological and psychological characteristics of the ageing population. Conclusion Older adults need to comprehend the meanings of their social experiences to preserve their active lifestyle. Human interactions may be desirable, but technological dominance may also minimize the adverse effects of social isolation.

Spray drying is a rapid, continuous, cost-effective, reproducible, and scalable process for reducing the moisture content of a fluid material into a solid powder. To improve this process in juice powder production, automation can be applied to increase efficiency and productivity. Hence, fuzzy logic is used in this study as a control system in the spray-drying process of concentrated liquid bignay juice into juice powder, where the inlet temperature and carrier agent concentrations affecting the properties of the juice powder, such as moisture content and product yield, are considered. The proposed fuzzy system can provide feedback to the control variables, inlet temperature, and carrier agent concentration based on the moisture content and product yield of the juice powder.

PURPOSE OF REVIEW To review the recent literature on indications for and functional outcomes following laryngectomy for severe laryngeal dysfunction. RECENT FINDINGS The use of functional laryngectomy as a definitive treatment for severe laryngeal dysfunction is increasing as more patients with head and neck cancer are treated with definitive chemoradiotherapy. Data are emerging on the efficacy of this technique as measured by aspiration, recurrent pneumonias, enteral tube feeding dependence, and surgical complication rates. Though most patients have marked improvement in aspiration and oral intake, difficulties in swallowing and voicing functions may persist. SUMMARY Functional laryngectomy is an effective treatment for end-stage laryngeal dysfunction. There is a clear benefit with regard to prevention of aspiration and alleviation of nothing by mouth status. However, qualitative speech and swallowing outcomes are less well studied, though available data suggest that many patients still suffer some degree of continued chronic impairment. More research is needed on these outcomes in order to appropriately counsel patients regarding long-term functional outcomes.

Facial expressions of pain have been identified in several animal species. The aim of this systematic review was to provide evidence on the measurement properties of grimace scales for pain assessment. The protocol was registered (SyRF#21-Nov-2019) and the study is reported according to the PRISMA guidelines. Studies reporting the development, validation, and the assessment of measurement properties of grimace scales were included. Data extraction and assessment were performed by two investigators, following the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines. Six categories of measurement properties were assessed: internal consistency, reliability, measurement error, criterion and construct validity, and responsiveness. Overall strength of evidence (high, moderate, low) of each instrument was based on methodological quality, number of studies and studies' findings. Twelve scales for nine species were included (mice, rats, rabbits, horses, piglets, sheep/lamb, ferrets, cats and donkeys). Considerable variability regarding their development and measurement properties was observed. The Mouse, Rat, Horse and Feline Grimace Scales exhibited high level of evidence. The Rabbit, Lamb, Piglet and Ferret Grimace Scales and Sheep Pain Facial Expression Scale exhibited moderate level of evidence. The Sheep Grimace Scale, EQUUS-FAP and EQUUS-Donkey-FAP exhibited low level of evidence for measurement properties. Construct validity was the most reported measurement property. Reliability and other forms of validity have been understudied. This systematic review identified gaps in knowledge on the measurement properties of grimace scales. Further studies should focus on improving psychometric testing, instrument refinement and the use of grimace scales for pain assessment in non-human mammals.

Aims To determine if adapting the ablation index (AI) to the left atrial wall thickness (LAWT), which is a determinant of lesion transmurality, is feasible, effective, and safe during paroxysmal atrial fibrillation (PAF) ablation. Methods and results Consecutive patients referred for PAF first ablation. Left atrial wall thickness three-dimensional maps were obtained from multidetector computed tomography and integrated into the CARTO navigation system. Left atrial wall thickness was categorized into 1 mm layers and AI was titrated to the LAWT. The ablation line was personalized to avoid thicker regions. Primary endpoints were acute efficacy and safety, and freedom from atrial fibrillation (AF) recurrences. Follow-up (FU) was scheduled at 1, 3, 6, and every 6 months thereafter. Ninety patients [60 (67%) male, age 58 ± 13 years] were included. Mean LAWT was 1.25 ± 0.62 mm. Mean AI was 366 ± 26 on the right pulmonary veins with a first-pass isolation in 84 (93%) patients and 380 ± 42 on the left pulmonary veins with first-pass in 87 (97%). Procedure time was 59 min (49–66); radiofrequency (RF) time 14 min (12.5–16); and fluoroscopy time 0.7 min (0.5–1.4). No major complication occurred. Eighty-four out of 90 (93.3%) patients were free of recurrence after a mean FU of 16 ± 4 months. Conclusion Personalized AF ablation, adapting the AI to LAWT allowed pulmonary vein isolation with low RF delivery, fluoroscopy, and procedure time while obtaining a high rate of first-pass isolation, in this patient population. Freedom from AF recurrences was as high as in more demanding ablation protocols. A multicentre trial is ongoing to evaluate reproducibility of these results.

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BACKGROUND: Weight telemonitoring may be an effective way to improve patients' ability to manage heart failure and prevent unnecessary utilization of health services. However, the effectiveness of such interventions is dependent upon patient adherence. OBJECTIVE: The purpose of this study was to determine how adherence to weight telemonitoring changes in response to 2 types of events: hospital readmissions and emergency department visits. METHODS: The Better Effectiveness After Transition–Heart Failure trial examined the effectiveness of a remote telemonitoring intervention compared with usual care for patients discharged to home after hospitalization for decompensated heart failure. Participants were followed for 180 days and were instructed to transmit weight readings daily. We used Poisson regression to determine the within-person effects of events on subsequent adherence. RESULTS: A total of 625 events took place during the study period. Most of these events were rehospitalizations (78.7%). After controlling for the number of previous events and discharge to a skilled nursing facility, the rate for adherence decreased by nearly 20% in the 2 weeks after a hospitalization compared with the 2 weeks before (adjusted rate ratio, 0.81; 95% confidence interval: 0.77–0.86; P < .001). CONCLUSIONS: Experiencing a rehospitalization had the effect of diminishing adherence to daily weighing. Providers using telemonitoring to monitor decompensation and manage medications should take advantage of the potential “teachable moment” during hospitalization to reinforce the importance of adherence.

Objectives The authors explored the development and validation of machine-learning models for augmenting the echocardiographic grading of aortic stenosis (AS) severity. Background In AS, symptoms and adverse events develop secondarily to valvular obstruction and left ventricular decompensation. The current echocardiographic grading of AS severity focuses on the valve and is limited by diagnostic uncertainty. Methods Using echocardiography (ECHO) measurements (ECHO cohort, n = 1,052), we performed patient similarity analysis to derive high-severity and low-severity phenogroups of AS. We subsequently developed a supervised machine-learning classifier and validated its performance with independent markers of disease severity obtained using computed tomography (CT) (CT cohort, n = 752) and cardiovascular magnetic resonance (CMR) imaging (CMR cohort, n = 160). The classifier’s prognostic value was further validated using clinical outcomes (aortic valve replacement [AVR] and death) observed in the ECHO and CMR cohorts. Results In 1,964 patients from the 3 multi-institutional cohorts, 1,346 (68%) subjects had either nonsevere or discordant AS severity. Machine learning identified 1,117 (57%) patients as having high-severity and 847 (43%) as having low-severity AS. High-severity patients in CT and CMR cohorts had higher valve calcium scores and left ventricular mass and fibrosis, respectively than the low-severity group. In the ECHO cohort, progression to AVR and progression to death in patients who did not receive AVR was faster in the high-severity group. Compared with the conventional classification of disease severity, machine-learning–based severity classification improved discrimination (integrated discrimination improvement: 0.07; 95% confidence interval: 0.02 to 0.12) and reclassification (net reclassification improvement: 0.17; 95% confidence interval: 0.11 to 0.23) for the outcome of AVR at 5 years. For both ECHO and CMR cohorts, we observed prognostic value of the machine-learning classifications for subgroups with asymptomatic, nonsevere or discordant AS. Conclusions Machine learning can integrate ECHO measurements to augment the classification of disease severity in most patients with AS, with major potential to optimize the timing of AVR.

Background Recent studies have shown that the serum uric acid/creatinine ratio (SUA/SCr) is a better predictor of chronic kidney disease (CKD) than serum uric acid (SUA) isolated. The aim of the present study was to evaluate the association of isolated SUA and the SUA/SCr with CKD in hypertensive patients. Methods Cross-sectional study conducted with hypertensive patients followed-up by the Primary Health Care Service (PHC). Sociodemographic, economic, lifestyle, clinical, anthropometric, and biochemical variables were evaluated. The association between SUA parameters (quartiles of SUA and quartiles of SUA/SCr) and CKD was evaluated by bivariate and multivariate logistic regression. The association between SUA parameters (SUA and SUA/SCr) and estimated glomerular filtration rate (eGFR) was evaluated by linear regression. The analyses were performed considering four adjustment models. SUA and SUA/SCr were compared by receiver operating characteristic (ROC) curve. Results In the fully adjusted model, SUA was positively associated with the presence of CKD (OR = 6.72 [95 % CI 1.96–22.96]) and inversely associated with eGFR (β Coef. = -2.41 [95 % CI -3.44; -1.39]). SUA/SCr was positively associated with eGFR (β Coef. = 2.39 [1.42; 3.36]). According to the ROC curve, the SUA is a better predictor of CKD than the SUA/SCr. Conclusions Elevated levels of isolated SUA were associated with CKD and eGFR. However, the SUA/SCr was not associated with CKD. We do not recommend using the SUA/SCr to predict CKD in hypertensive patients.

The increase in inflammatory cytokines associated with a reduction in the bioavailability of zinc has been used as a marker for inflammation. Despite the high inflammatory state found in institutionalized older individuals, few studies have proposed verifying the factors associated with this condition in this population. To verify the factors associated with inflamm-aging in institutionalized older people. A total of 178 older people (≥ 60 years old) living in nursing homes in Natal/RN were included in the study. Cluster analysis was used to identify three groups according to their inflammatory state. Analysis anthropometric, biochemical, sociodemographic, and health-related variables was carried out. In sequence, an ordinal logistic regression was performed for a confidence level of 95% in those variables with p