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Abstract Background Over the past two decades there has been a remarkable advance in the management of juvenile idiopathic arthritis (JIA), which has led to considerable improvement in prognosis. In 2018, the introduction of the treat-to-target (T2T) strategy in JIA has been advocated to further ameliorate disease outcome. To provide a benchmark for comparing future outcomes in the “T2T era”, this study investigates the percentage of JIA patients who achieved clinical inactive disease (CID) in the decade that preceded the publication of the T2T recommendations in JIA. Methods The clinical charts of all JIA patients followed at the study center between 2007 and 2017 who were first seen within 6 months after disease onset and had a minimum of 6-month follow-up information available were reviewed retrospectively. The attainment of CID, defined by 2004 Wallace criteria, was assessed cross-sectionally at 6, 12, 24, and 60 months after first observation. Results A total of 394 patients were included. Patients were classified into four “functional phenotypes”: systemic arthritis (7.1%), oligoarthritis (48.2%), polyarthritis (40.4%), and other arthritis (4.3%). The overall frequency of CID was 25.1% at 6 months, 34.5% at 12 months, 44.6% at 24 months, and 49.1% at 60 months. The systemic and oligoarticular subgroups had the highest rates of CID at 6 months (32.1% and 29.5%, respectively) and at 12 months (40% and 41.1%, respectively). At the 60-month evaluation, which was available for 226 out of 394 patients (57.4%), the frequency of CID among patients still followed at study center was 42.9%, 51.7%, 46.7%, and 45.5% for the systemic, oligoarticular, polyarticular, and other arthritis phenotypes, respectively. Conclusion A sizeable proportion of patients treated in the decade preceding the beginning of the “T2T era” and on continued follow-up did not achieve or maintain the state of CID over the long term. Future studies will determine whether the application of the T2T strategy increases the ability to achieve sustained disease quiescence in patients who respond suboptimally to the conventional therapeutic regimens.

OBJETIVO: O objetivo geral deste estudo é avaliar o impacto na qualidade de vida das famílias de pacientes com DA e determinar se há uma relação com a gravidade da doença. MÉTODOS: Estudo individual, observacional e transversal que inclui 20 pacientes pediátricos com idades entre 1 e 12 anos e seus cuidadores. Serão realizados dois momentos de avaliação (A1 e A2), nos quais o SCORAD do paciente será avaliado e o DFI será aplicado ao membro da família. RESULTADOS: Ao comparar A1 e A2, o SCORAD demonstrou um escore z de 2,76 (p=0,0058), enquanto o DFI mostrou um escore z de 2,52 (p=0,0119). O coeficiente de correlação de Spearman demonstrou uma correlação positiva com significância estatística (rs = 0,74, p = 0,0002). CONCLUSÕES: Quando os pacientes experimentaram uma diminuição nos escores do SCORAD, a qualidade de vida de seus membros familiares melhorou, como evidenciado por uma diminuição nos escores do DFI. Além disso, na análise de cada consulta individual, também observamos que escores mais altos do SCORAD em pacientes estavam associados a escores mais altos do DFI. Os resultados deste estudo reforçam o que foi previamente demonstrado em outros estudos: o impacto negativo da DA não apenas nos pacientes, mas principalmente em seus cuidadores. Além disso, observamos que quanto mais grave a doença, maior o impacto na família.

Objective: To assess the risk of recurrent preterm birth following spontaneous extreme preterm birth between 16+0 - 27+6 weeks. Methods: A nationwide retrospective cohort study was conducted with data from the Perinatal Registry of the Netherlands. We included nulliparous women with a singleton pregnancy that ended in spontaneous preterm birth between 16+0 and 27+6 weeks of gestation without congenital anomalies or antenatal death between 2010–2014 and had a subsequent pregnancy in the 5 years following (2010–2019). The primary outcome of this study was recurrent preterm birth

Objective: In 2019 the Dutch national prevention of preterm birth (PTB) protocol was adjusted to withhold tocolysis for threatened PTB above 30 weeks of gestation due to insufficient evidence regarding its effectiveness on improving perinatal outcomes. The aim of this study is to evaluate neonatal outcomes of children born in the Netherlands between 30 and 32 weeks of gestation before and after the national protocol change. Study design: We performed a nationwide retrospective cohort study comparing outcomes of births in the years 2018 (tocolysis) and 2020 (no tocolysis). Tocolytic therapy consisted of either nifedipine or atosiban. Data were extracted from the national Perinatal Registry (PERINED). Women with a spontaneous PTB from 30 + 0 to 31 + 6 weeks of gestation were included. The primary outcome was a composite of mortality, severe intraventricular hemorrhage, severe necrotizing enterocolitis, cystic periventricular leukomalacia, and retinopathy of prematurity needing therapy. Secondary outcomes included additional neonatal outcomes. The odds ratio (OR) with corresponding 95 % confidence interval (CI) was calculated by logistic regression analysis for the year 2020 compared with 2018. Results: Composite neonatal outcome did not differ between 2018 compared to 2020 (8.4 % (18/215) vs 8.2 % (25/306), OR 0.95; 95 % CI 0.51–1.77). No difference in composite neonatal outcome was found when analyzing groups as singletons (7.1 % vs 9.3 %, OR 1.35; 95 % CI 0.64–2.87), and multiples (13.3 % vs 5.9 %, OR 0.41; 95 % CI 0.13–1.26). Conclusion: There was no significant difference in composite neonatal outcome in pregnancies resulting in spontaneous PTB between 30 and 32 weeks of gestation in 2018 (with tocolysis) compared to 2020 (no tocolysis). These results support the protocol adjustment to withhold tocolytic treatment in women with threatened PTB above 30 weeks of gestation.

Recent data shows that alterations in the expression and/or activation of the vascular endothelial growth factor receptor 2 (VEGFR2) in high grade serous ovarian cancer (HGSOC) modulate tumor progression. However, controversial results have been obtained, showing that in some cases VEGFR2 inhibition can promote tumorigenesis and metastasis. Thus, it is urgent to better define the role of the VEGF/VEGFR2 system to understand/predict the effects of its inhibitors administered as anti-angiogenic in HGSOC. Here, we modulated the expression levels of VEGFR2 and analyzed the effects in two cellular models of HGSOC. VEGFR2 silencing (or its pharmacological inhibition) promote the growth and invasive potential of OVCAR3 cells in vitro and in vivo. Consistent with this, the low levels of VEGFR2 in OV7 cells are associated with more pronounced proliferative and motile phenotypes when compared to OVCAR3 cells, and VEGFR2 overexpression in OV7 cells inhibits cell growth. In vitro data confirmed that VEGFR2 silencing in OVCAR3 cells favors the acquisition of an invasive phenotype by loosening cell-ECM contacts, reducing the size and the signaling of focal adhesion contacts (FAs). This is translated into a reduced FAK activity at FAs, ECM-dependent alterations of mechanical forces through FAs and YAP nuclear translocation. Together, the data show that low expression, silencing or inhibition of VEGFR2 in HGSOC cells alter mechanotransduction and lead to the acquisition of a pro-proliferative/invasive phenotype which explains the need for a more cautious use of anti-VEGFR2 drugs in ovarian cancer.

Introdução: Desde 2022, foi identificado surto multinacional da mpox, infecção causada pelo Monkeypoxvirus (MPXV). O Brasil apresentou inúmeros casos, com 11.212 confirmados até 30/01/2024, afetando desproporcionalmente homens que fazem sexo com homens (HSH). A evolução clínica da mpox cursa geralmente com síndrome febril aguda e lesões mucocutâneas. Geralmente tem evolução autolimitada, mas pode complicar com infecção secundária e acometimento de tecidos profundos. A transmissão por contato sexual foi mais descrita no surto de 2022/2023, podendo ocorrer pelo contato direto ou indireto com lesões, fluidos corporais e gotículas respiratórias de pessoas com mpox. Relato de caso: Mulher cisgênero, 28 anos, com epilepsia controlada, sem outras comorbidades, trabalha como vendedora em praça pública, internada em 04/2024 em unidade hospitalar externa devido à lesão pustular fronto-temporal direita, evolução de 2 dias, que progrediu com sinais de infecção secundária e celulite periorbitária. Esta regrediu completamente com antibioticoterapia, porém houve progressão da lesão primária associada a vesículas em dedos e região perianal. Aventada hipótese de mpox, foi transferida para este centro, onde se observou lesão vegetante e crostosa em fronte, duas lesões vesiculares em região metacarpofalangeana e uma em região interfalangeana distal, além de lesão em linha média torácica e outra em região perianal, ambas de centro ulcerado e indolores. A paciente negou contato com pessoas com quadro semelhante e exposição sexual nos últimos 3 anos. O rastreio infeccioso foi negativo para infecções fúngicas e ISTs. PCR MPXV foi detectável em swabs coletados em todas as lesões e PCR para varicela zoster foi não detectável. Recebeu suporte clínico e orientações de isolamento domiciliar e encaminhada para seguimento ambulatorial. Comentários: O relato aponta diagnóstico de mpox em mulher cis, com lesão inicial extragenital, sem contato sexual e provável aquisição comunitária (já que trabalha em praça pública). Desde 10/2023, o Rio de Janeiro apresenta transmissão sustentada de mpox, e profissionais de saúde precisam estar atentos para evoluções atípicas e oligossintomáticas, possibilitando identificação e diagnóstico adequados. Medidas de prevenção, como campanhas de vacinação, precisam ser implementadas sobretudo para as populações mais vulnerabilizadas. Palavras-chave: Mpox, Transmissão, Comunitária. Conflitos de interesse: Informo que não possuo conflitos de interesses relacionados a este trabalho. Ética e financiamentos: Declarações de interesse: nenhuma. Declarações de interesse: Nenhum.

Aims: Evaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression. Methods: 56 patients were treated for 702 BMs with 197 (range 2–8) HyperArc courses in case of exclusive intracranial progression. Primary end-point was the overall survival (OS), secondary end-points were intracranial progression-free survival (iPFS), toxicity, local control (LC), neurological death (ND), and whole-brain RT (WBRT)-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.). Results: The 1-year OS was 70 %, and the median was 20.8 months (17–36). At the univariate analysis (UVA) biological equivalent dose (BED) > 51.3 Gy and non-melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1-year iPFS was 15 %. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 96.4 % of them occurred within the isodoses range 0–7 Gy as follows: 26.6 % (0 Gy), 16.5 % (1 Gy), 16.5 % (2 Gy), 20.1 % (3 Gy), 13.1 % (5 Gy), 3.4 % (7 Gy) (p = 0.00). Radionecrosis occurred in 2 metastases (0.28 %). No clinical toxicity of grade 3 or higher occurred during follow-up. One- and 2-year LC was 90 % and 79 %, respectively. At the UVA BED > 70 Gy and non-melanoma histology were significant predictors of higher LC. The 2-year WBRT-free survival was 70 %. After a median follow-up of 17.4 months, 12 patients deceased by ND. Conclusion: Intracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV. Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival.

ABSTRACT Proteins encoded by the ESX-1 genes of interest are essential for full virulence in all Mycobacterium tuberculosis complex (Mtbc) lineages, the pathogens causing the highest mortality worldwide. Identifying critical regions in these ESX-1-related proteins could provide preventive or therapeutic targets for Mtb infection, the game changer needed for tuberculosis control. We analyzed a compendium of whole genome sequences of clinical Mtb isolates from all lineages from >32,000 patients and identified single nucleotide polymorphisms. When mutations corresponding to all non-synonymous single nucleotide polymorphisms were mapped on structural models of the ESX-1 proteins, fully conserved regions emerged. Some could be assigned to known quaternary structures, whereas others could be predicted to be involved in yet-to-be-discovered interactions. Some mutants had clonally expanded (found in >1% of the isolates); these mutants were mostly located at the surface of globular domains, remote from known intra- and inter-molecular protein–protein interactions. Fully conserved intrinsically disordered regions of proteins were found, suggesting that these regions are crucial for the pathogenicity of the Mtbc. Altogether, our findings highlight fully conserved regions of proteins as attractive vaccine antigens and drug targets to control Mtb virulence. Extending this approach to the whole Mtb genome as well as other microorganisms will enhance vaccine development for various pathogens.IMPORTANCEWe mapped all non-synonymous single nucleotide polymorphisms onto each of the experimental and predicted ESX-1 proteins’ structural models and inspected their placement. Varying sizes of conserved regions were found. Next, we analyzed predicted intrinsically disordered regions within our set of proteins, finding two putative long stretches that are fully conserved, and discussed their potential essential role in immunological recognition. Combined, our findings highlight new targets for interfering with Mycobacterium tuberculosis complex virulence.

Background and objectives: Anorexia of aging (AoA) is a prevalent geriatric syndrome characterized by a multifactorial decline in appetite and reduced food intake associated with the aging process. This systematic review aims to investigate the use and outcomes of cannabinoids in addressing AoA, with the goal of providing a comprehensive understanding and discussing their potential integration into daily clinical practice. Methods: A thorough search of databases (Embase Ovid, Scopus, PubMed, Cochrane Library, and Web of Science) identified 6100 studies. After eliminating duplicates and screening titles and abstracts, 25 studies underwent full appraisal. Two reviewers assessed inclusion suitability, and study methodologies were evaluated using the Newcastle-Ottawa Scale (NOS) for observational studies and the modified Jadad Scoring Scale for randomized controlled trials. Ultimately, six studies published between 2002 and 2019, involving 869 participants, were included in the review. Results: Out of the 6 fin. l papers selected, 5 were randomized trials, and 1 was a prospective study. Megestrol acetate (800 mg/d) proved to be more effective than dronabinol 2.5 mg twice a day in increasing appetite. Nabilone (at a dosage of 0.5 mg per day) did not show superiority over placebo in alleviating symptoms such as pain, nausea, loss of appetite, and weight. However, with a double dosage followed by 1.0 mg/6 weeks, after eight weeks of treatment, patients recorded a significant increase in calorie intake and carbohydrate consumption compared to the placebo group, with some patients also experiencing substantial weight gain. Regarding delta-9-tetrahydrocannabinol (THC), a weight increase of ≥10% was observed in 17.6% of patients with doses of 5 mg or 10 mg capsules daily, without significant side effects. Additionally, patients treated with THC 2.5 mg reported improved chemosensory perception and increased appetite before meals compared to placebo. No significant side effects were reported in older adults taking cannabinoids. Conclusions: Cannabinoids offer promise in enhancing the quality of life for older individuals with active neoplastic disease. However, to establish comprehensive guidelines, further research with larger sample sizes is essential. Only through this approach can we fully grasp the potential and application of cannabinoids in addressing the nutritional concerns associated with neoplastic diseases.

BackgroundObesity prevalence in youth with spina bifida is higher than in their typically developing peers. Obesity is associated with lifelong medical, psychological, and economic burdens. Successful prevention or treatment of obesity in individuals with spina bifida is compromised by (1) the lack of valid and reliable methods to identify body fat in a clinical setting and (2) limited data on energy expenditure that are necessary to provide daily caloric recommendations. ObjectiveThe objectives of this study will be to develop 2 algorithms for use in youth with spina bifida in a clinical setting, one to model body fat and one to predict total daily energy expenditure. In addition, physical activity and dietary intake will be described for the sample. MethodsThis multisite, prospective, national clinical study will enroll 232 youth with myelomeningocele aged 5 to 18 years (stratified by age and mobility). Participants will be enrolled for 1 week. Data obtained include 4 measures of body composition, up to 5 height measures, a ramped activity protocol, and a nutrition and physical activity screener. Participants will wear an accelerometer for the week. On the final study day, 2 samples of urine or saliva, which complete the doubly labeled water protocol, will be obtained. The analysis will include descriptive statistics, Bland-Altman plots, concordance correlation, and regression analysis. ResultsThe study received extramural federal funding in July 2019. Data collection was initiated in March 2020. As of April 2024, a total of 143 (female participants: n=76, 53.1%; male participants: n=67, 46.9%) out of 232 participants have been enrolled. Data collection is expected to continue throughout 2024. A no-cost extension until November 2025 will be requested for data analysis and dissemination of findings. ConclusionsThis study furthers previous pilot work that confirmed the acceptability and feasibility of obtaining alternate height, body composition, and energy expenditure measures. The findings from this study will enhance screening, prevention, and treatment of abnormal weight status by facilitating the accurate identification of youths’ weight status category and recommendations of daily caloric needs for this population that is at higher risk of obesity. Furthermore, the findings have the potential to impact outcomes for youth diagnosed with disabilities other than spina bifida who experience similar challenges related to alterations in body composition or fat distribution or measurement challenges secondary to mobility issues or musculoskeletal problems. International Registered Report Identifier (IRRID)DERR1-10.2196/52779

BackgroundFederated learning (FL) is a technique for learning prediction models without sharing records between hospitals. Compared to centralized training approaches, the adoption of FL could negatively impact model performance.AimThis study aimed to evaluate four types of multicenter model development strategies for predicting 30-day mortality for patients undergoing transcatheter aortic valve implantation (TAVI): (1) central, learning one model from a centralized dataset of all hospitals; (2) local, learning one model per hospital; (3) federated averaging (FedAvg), averaging of local model coefficients; and (4) ensemble, aggregating local model predictions.MethodsData from all 16 Dutch TAVI hospitals from 2013 to 2021 in the Netherlands Heart Registration (NHR) were used. All approaches were internally validated. For the central and federated approaches, external geographic validation was also performed. Predictive performance in terms of discrimination [the area under the ROC curve (AUC-ROC, hereafter referred to as AUC)] and calibration (intercept and slope, and calibration graph) was measured.ResultsThe dataset comprised 16,661 TAVI records with a 30-day mortality rate of 3.4%. In internal validation the AUCs of central, local, FedAvg, and ensemble models were 0.68, 0.65, 0.67, and 0.67, respectively. The central and local models were miscalibrated by slope, while the FedAvg and ensemble models were miscalibrated by intercept. During external geographic validation, central, FedAvg, and ensemble all achieved a mean AUC of 0.68. Miscalibration was observed for the central, FedAvg, and ensemble models in 44%, 44%, and 38% of the hospitals, respectively.ConclusionCompared to centralized training approaches, FL techniques such as FedAvg and ensemble demonstrated comparable AUC and calibration. The use of FL techniques should be considered a viable option for clinical prediction model development.

Objetivo: Descrever o processo de construção do material didático “Meu plano de aleitamento materno” para educação, apoio e promoção do aleitamento materno para gestantes e pessoas lactantes. Método: Este é um estudo metodológico realizado em três fases: diagnóstico situacional, revisão de literatura e contextualização da prática profissional, e construção da tecnologia educacional baseada em políticas públicas e programas de aleitamento materno brasileiros. O estudo ocorreu de março de 2022 a outubro de 2023 e utilizou-se o software Canva para construção do produto. Resultados: Desenvolveu-se uma tecnologia inédita a nível nacional que integra educação e cuidado em saúde por meio do plano de aleitamento materno. Considerações finais: Considera-se que o material didático intitulado “Meu plano de aleitamento materno” é um recurso eficaz para promover a autonomia da mulher no ciclo gravídico-puerperal e pode ser utilizado na enfermagem para educar, promover e apoiar o aleitamento materno em diversos níveis de atenção à saúde.

BackgroundGNAO1-related disorders (GNAO1-RD) encompass a diverse spectrum of neurodevelopmental and movement disorders arising from variants in the GNAO1 gene. Dyskinetic crises, marked by sudden and intense exacerbations of abnormal involuntary movements, present a significant challenge in GNAO1-RD.ObjectivesThis study aimed to establish a standardized framework for understanding dyskinetic crises, addressing crucial aspects such as definition, triggers, diagnostic criteria, complications, and management strategies.MethodsA Delphi consensus process was conducted involving international experts in GNAO1-RD. The panel of thirteen experts participated in three voting rounds, discussing 90 statements generated through a literature review and clinical expertise.ResultsConsensus was achieved on 31 statements, defining dyskinetic crises as abrupt, paroxysmal episodes involving distinct abnormal movements in multiple body regions, triggered by emotional stress or infections. Dyskinetic crises may lead to functional impairment and complications, emphasizing the need for prompt recognition. While individualized pharmacological recommendations were not provided, benzodiazepines and clonidine were suggested for acute crisis management. Chronic treatment options included tetrabenazine, benzodiazepines, gabapentin, and clonidine. Deep brain stimulation should be considered early in the treatment of refractory or prolonged dyskinetic crisis.ConclusionThis consensus provides a foundation for understanding and managing dyskinetic crises in GNAO1-RD for clinicians, caregivers, and researchers. The study emphasizes the importance of targeted parental and caregiver education, which enables early recognition and intervention, thereby potentially minimizing both short- and long-term complications. Future research should concentrate on differentiating dyskinetic crises from other neurological events and investigating potential risk factors that influence their occurrence and nature. The proposed standardized framework improves clinical management, stakeholder communication, and future GNAO1-RD research.

During COVID-19 pandemic pediatricians have been challenged by the occurrence of the multisystem inflammatory syndrome in children (MIS-C). This condition displays some features similar to those of Kawasaki disease (KD), but was is characterized by clinical signs and symptoms that are infrequent in this illness, such as diarrhea, abdominal pain, neurologic dysfunction and cardiac involvement, especially myocarditis. Many children with MIS-C necessitated ICU admission due to development of multiorgan failure and circulatory shock, usually of myocardial origin. Management is based on the administration of intravenous immunoglobulin, glucocorticoids and, in the most severe forms, anakinra. The clinical similarities between MIS-C and KD have raised an intense debate about whether they represent different illnesses with overlapping clinical features or are part of the same disease spectrum. Most authorities favor the assumption that MIS-C is distinct from KD, based on epidemiological, clinical and immunological differences between the two entities. Others argue that the two disorders may represent a continuum, with some differences in phenotype and severity being related to viral load or strain or magnitude or kinetics of immune response. The present article is aimed to analyze critically the rationale and evidence in favor of the second hypothesis.

A presente pesquisa tem por objetivo principal discutir a atuação profissional e educativa com pessoas idosas na Educação de Jovens e Adultos (EJA) em favor dos interesses das classes populares. De modo específico, caracterizar a sociedade contemporânea e o processo formativo de pessoas idosas que estudam ou estudaram na EJA à luz dos conceitos de cidadania e humanização, principalmente por considerar que na sociedade capitalista há um processo que caminha para a formação desumana, desigual e preconceituosa. Há, ainda, a situação permeada por sentimentos de angústia diante o “fracasso escolar”, consideravelmente no que tange o processo de rompimento das barreiras para “vencer” o “cotidiano” que impõe toda a espécie de obstáculos e estigmatizações. Por este motivo, faz-se necessária a intervenção do Estado, primeiramente, com políticas educacionais capazes de proporcionar uma vida digna a todos, de forma a promover o acesso a uma educação inclusiva, a partir da relação estabelecida entre equipe escolar e educandos, de maneira efetiva à luz dos direitos sobre os educandos, conforme previsto na Constituição Federal (1988), na Lei de Diretrizes e Bases da Educação (1996), no Estatuto da Pessoa Idosa, e na Declaração dos Direitos Humanos.