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Our international team highlights issues with efficacy reports in several studies on DMG with the new drug ONC201.
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OBJECTIVES: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome. STUDY DESIGN: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1-4, 5-11, 12-16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified. RESULTS: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes. CONCLUSIONS: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities.
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Edad de Inicio , COVID-19 , Sistema de Registros , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica , Humanos , Niño , COVID-19/epidemiología , COVID-19/mortalidad , COVID-19/complicaciones , Preescolar , Femenino , Masculino , Lactante , Adolescente , Estudios Retrospectivos , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Europa (Continente)/epidemiología , Recién NacidoRESUMEN
Objective: Virtual care for chronic conditions has seen uptake due to COVID-19. Evaluation of virtual models is important to ensure evidence-based practice. There is a paucity of research in the use of virtual care for management of chronic back disorders. The objective of this study was to evaluate effectiveness of a team-based virtual care model for back disorder assessment where a physical therapist uses virtual care to join a nurse practitioner and patient in a rural Saskatchewan, Canada community. Methods: Sixty-four rural adults with chronic back disorders were randomly allocated to receive either: (1) team-based virtual care (n = 24); (2) care from an urban physical therapist travelling to community (n = 20); or (3) care from a rural nurse practitioner (n = 20). The team-based care group involved a nurse practitioner located with a rural patient, and a physical therapist joining using virtual care. The physical therapist alone and the nurse practitioner alone groups received in-person assessments. Groups with a physical therapist involved had follow-up treatments by in-person physical therapy. Outcomes over six months included pain, disability, back beliefs, satisfaction, quality-adjusted health status and management-related costs. Results: There were no significant differences for pain, disability, back beliefs and satisfaction between groups. The average cost per patient for implementing in-person physical therapist assessment ($135) was higher compared with the team over virtual care ($118) and NP care ($59). Conclusion: Primary outcomes were not different by group. Physical therapist alone was more costly than other groups. Future research should include more participants, longer follow-up time and refined cost parameters. Trial Registration: ClinicalTrials.gov NCT02225535; https://clinicaltrials.gov/ct2/show/NCT02225535 (Archived by WebCite at http://www.webcitation.org/6lqLTCNF7).
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Introduction: We explored trajectories of pain intensity and depressive symptoms over the first 24 months of the pandemic in people with low back pain. Methods: This longitudinal study was conducted alongside the Quebec Low Back Pain Study. Starting in April 2020 and every 3 months until July 2022, 291 participants completed an online survey. Group-based trajectory modeling was used to identify patterns of pain intensity and depressive symptoms. Onset outbreak characteristics were then put in relation with trajectory groups using multivariate logistic regression. Results: The analysis revealed 5 trajectories of pain intensity and depressive symptoms, respectively. The pain trajectories were stable mild (n = 17, 5.8%); stable moderate (n = 103, 35.4%); stable severe (n = 81, 27.8%); U-shape (n = 24, 8.3%), and inverted U-shape (n = 66, 22.7%). The trajectories of depressive symptoms were stable none (n = 58, 19.9%); stable very mild (n = 61, 21.0%); stable mild (n = 85, 29.2%); stable moderate (n = 59, 21.7%); and severe slightly improving (n = 24, 8.3%). Pre-COVID everyday/nearly everyday pain, average pain intensity, and widespread bodily pain were predictive of pain trajectory groups. Higher pre-COVID depression, acute stress disorder, and lockdown measures-related stress were associated with moderate/severe depressive trajectories. Discussion: Our findings indicated relative stability of pain and depressive symptoms among participants during the COVID-19 pandemic but also highlighted subgroups of people who experienced temporary deterioration or improvement over the first months of the pandemic that then reverted back to baseline levels. Modifiable risk factors were identified before the onset of the pandemic, which could give preventive measures in targeted populations.
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INTRODUCTION: Focused ultrasound (FUS) is an innovative and emerging technology for the treatment of adult and pediatric brain tumors and illustrates the intersection of various specialized fields, including neurosurgery, neuro-oncology, radiation oncology, and biomedical engineering. OBJECTIVE: The authors provide a comprehensive overview of the application and implications of FUS in treating pediatric brain tumors, with a special focus on pediatric low-grade gliomas (pLGGs) and the evolving landscape of this technology and its clinical utility. METHODS: The fundamental principles of FUS include its ability to induce thermal ablation or enhance drug delivery through transient blood-brain barrier (BBB) disruption, emphasizing the adaptability of high-intensity focused ultrasound (HIFU) and low-intensity focused ultrasound (LIFU) applications. RESULTS: Several ongoing clinical trials explore the potential of FUS in offering alternative therapeutic strategies for pathologies where conventional treatments fall short, specifically centrally-located benign CNS tumors and diffuse intrinsic pontine glioma (DIPG). A case illustration involving the use of HIFU for pilocytic astrocytoma is presented. CONCLUSION: Discussions regarding future applications of FUS for the treatment of gliomas include improved drug delivery, immunomodulation, radiosensitization, and other technological advancements.
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Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/diagnóstico por imagen , Niño , Glioma/terapia , Glioma/diagnóstico por imagen , Terapia por Ultrasonido/métodosRESUMEN
Hemophagocytic lymphohistiocytosis (HLH) is a rare genetic hyperinflammatory syndrome that occurs early in life. Macrophage activation syndrome (MAS) usually refers to a secondary form of HLH associated with autoimmunity, although there are other causes of secondary HLH, such as infections and malignancy. In this article, we reviewed the concepts, epidemiology, clinical and laboratory features, diagnosis, differential diagnosis, prognosis, and treatment of HLH and MAS. We also reviewed the presence of MAS in the most common autoimmune diseases that affect children. Both are severe diseases that require prompt diagnosis and treatment to avoid morbidity and mortality.
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Enfermedades Autoinmunes , Linfohistiocitosis Hemofagocítica , Síndrome de Activación Macrofágica , Niño , Humanos , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/etiología , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/complicaciones , Enfermedades Autoinmunes/complicaciones , Diagnóstico DiferencialRESUMEN
Although the effectiveness of cardiac rehabilitation (CR) programs in secondary prevention is well-recognized, there is a lack of studies exploring the potential of mobile health to enhance educational interventions within CR. The objective is to assess the impact of a structured WhatsApp-assisted health educational intervention, in conjunction with the usual care, compared to the usual care alone among participants enrolled in a CR program. The trial will recruit 32 participants enrolled in a CR program, who will be randomly assigned to a structured WhatsApp-assisted health educational intervention plus usual care or usual care alone group. The intervention will span 4 weeks, with assessments at baseline, 4 weeks, and 3, 6, and 12 months. The primary outcome measure is the cardiovascular risk factors knowledge score. Secondary outcomes include physical activity levels, anxiety and depression, and quality of life. Expected results include improved knowledge of cardiovascular risk factors, increased physical activity levels, and better mental health outcomes in the intervention group. Additionally, an enhancement in the overall quality of life is anticipated. These findings are expected to underscore the value of integrating mHealth with traditional CR methods, potentially shaping future approaches in chronic disease management and prevention.
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BACKGROUND: Diffuse midline glioma (DMG) is a pediatric tumor with dismal prognosis. Systemic strategies have been unsuccessful and radiotherapy (RT) remains the standard-of-care. A central impediment to treatment is the blood-brain barrier (BBB), which precludes drug delivery to the central nervous system (CNS). Focused ultrasound (FUS) with microbubbles can transiently and non-invasively disrupt the BBB to enhance drug delivery. This study aimed to determine the feasibility of brainstem FUS in combination with clinical doses of RT. We hypothesized that FUS-mediated BBB-opening (BBBO) is safe and feasible with 39 Gy RT. METHODS: To establish a safety timeline, we administered FUS to the brainstem of non-tumor bearing mice concurrent with or adjuvant to RT; our findings were validated in a syngeneic brainstem murine model of DMG receiving repeated sonication concurrent with RT. The brainstems of male B6 (Cg)-Tyrc-2J/J albino mice were intracranially injected with mouse DMG cells (PDGFB+, H3.3K27M, p53-/-). A clinical RT dose of 39 Gy in 13 fractions (39 Gy/13fx) was delivered using the Small Animal Radiation Research Platform (SARRP) or XRAD-320 irradiator. FUS was administered via a 0.5 MHz transducer, with BBBO and tumor volume monitored by magnetic resonance imaging (MRI). RESULTS: FUS-mediated BBBO did not affect cardiorespiratory rate, motor function, or tissue integrity in non-tumor bearing mice receiving RT. Tumor-bearing mice tolerated repeated brainstem BBBO concurrent with RT. 39 Gy/13fx offered local control, though disease progression occurred 3-4 weeks post-RT. CONCLUSION: Repeated FUS-mediated BBBO is safe and feasible concurrent with RT. In our syngeneic DMG murine model, progression occurs, serving as an ideal model for future combination testing with RT and FUS-mediated drug delivery.
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Barrera Hematoencefálica , Glioma , Humanos , Ratas , Niño , Masculino , Ratones , Animales , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Tronco Encefálico , Sistemas de Liberación de Medicamentos/métodos , Imagen por Resonancia Magnética , Glioma/radioterapia , Microburbujas , EncéfaloRESUMEN
Pediatric intracranial sarcomas are rare, aggressive tumors with a poor prognosis in general. Here we report the case of a child who was initially diagnosed with a primary intracranial sarcoma, DICER1-mutant; subsequent genetic analyses confirmed a pathogenic germline DICER1 mutation. She received multimodal standard treatments consisting of surgery, radiotherapy and chemotherapy. The tumor recurred 2.5 years later within the surgical cavity. Following the gross tumor resection of this new lesion, the same multimodal standard approach was used. From a molecular perspective, evidence of hyperactivation of the MAPK-kinase pathway with a pathogenic KRAS mutation at both diagnosis and recurrence was present. The patient is currently in remission, 18 months post-end of treatment.
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Neoplasias Encefálicas , ARN Helicasas DEAD-box , Recurrencia Local de Neoplasia , Ribonucleasa III , Sarcoma , Humanos , Ribonucleasa III/genética , ARN Helicasas DEAD-box/genética , Femenino , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico por imagen , Recurrencia Local de Neoplasia/genética , Sarcoma/genética , Mutación/genética , NiñoRESUMEN
OBJECTIVE: To describe the current state of the art in the therapeutic administration of botulinum toxin with indications, efficacy, and safety profile for children and adolescents with cerebral palsy. DATA SOURCE: An integrative review was conducted. The MEDLINE/PubMed database was searched twice within the last decade using distinct terms, and only studies written in the English language were included. The study population was limited to those aged 0-18 years. Articles that were duplicates or lacked sufficient methodology information were excluded. DATA SYNTHESIS: We found 256 articles, of which 105 were included. Among the included studies, most were conducted in developed countries. Botulinum toxin demonstrated good safety and efficacy in reducing spasticity, particularly when administered by a multidisciplinary rehabilitation team. It is primarily utilized to improve gait and upper limb function, facilitate hygiene care, reduce pain, prevent musculoskeletal deformities, and even decrease sialorrhea in patients without a functional prognosis for walking. CONCLUSIONS: The administration of botulinum toxin is safe and efficacious, especially when combined with a multi-professional rehabilitation team approach, which increases the probability of functional improvement. It can also be beneficial for patients with significant functional impairments to help with daily care tasks, such as hygiene, dressing, and reducing sialorrhea. Pediatricians must be familiar with this treatment and its indications to attend to and refer patients promptly when necessary, and to exploit their neuroplasticity. Further research on this topic is required in developing countries.
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Toxinas Botulínicas , Parálisis Cerebral , Fármacos Neuromusculares , Sialorrea , Niño , Adolescente , Humanos , Toxinas Botulínicas/uso terapéutico , Sialorrea/tratamiento farmacológico , Fármacos Neuromusculares/uso terapéutico , Parálisis Cerebral/tratamiento farmacológico , Espasticidad Muscular/tratamiento farmacológicoRESUMEN
Acute coronary syndrome (ACS) remains a significant global health concern, with a growing recognition of its impact on young adults, particularly young female adults. Although gender-related factors, defined as a social construct that encompasses 4 distinct dimensions (gender roles, gender identity, gender relations, and institutionalized gender) are undoubtedly relevant across age groups, young female patients with ACS face specific challenges and disparities in outcomes, compared to other populations. This narrative review examines the role of gender-related factors-specifically, gender roles, gender identity, gender relations, and institutionalized gender-in influencing objective and subjective ACS outcomes in young female patients. In the 5 articles identified, the objective outcomes included hospital readmission, "door-to-electrocardiography" time, and coronary atherosclerosis progression. Subjective outcomes, such as physical and mental functional status, quality of life, physical limitations, and vital exhaustion, were also examined. Being employed, which is a gender role, emerged as a protective factor against hospital readmission. Gender identity factors such as depression and stress were correlated with negative outcomes, and anxiety influenced "door-to-electrocardiography" times. Institutional factors, including income disparities, affected readmission likelihood. Strong social support decreased physical limitations post-ACS, whereas financial challenges and lower education negatively impacted quality of life and vital exhaustion. These findings underscore the intricate interplay of gender dimensions in shaping ACS outcomes among young female patients. Integrating these insights into clinical practice and research can enhance care, mitigate disparities, and foster improved cardiovascular health in this vulnerable population.
Le syndrome coronarien aigu (SCA) demeure un problème de santé préoccupant à l'échelle mondiale, avec une reconnaissance croissante de ses conséquences chez les jeunes adultes, plus particulièrement les jeunes femmes adultes. Les facteurs liés au genre, définis comme un construit social à quatre dimensions distinctes (les rôles liés au genre, l'identité de genre, les relations de genre et le genre institutionnalisé) sont indéniablement d'une grande importance dans tous les groupes d'âge, mais les jeunes patientes atteintes d'un SCA font face à des disparités et des défis particuliers à l'égard des résultats de santé par rapport à d'autres populations. La présente synthèse narrative propose un examen de l'influence des facteurs liés au genre (plus particulièrement les rôles liés au genre, l'identité de genre, les relations de genre et le genre institutionnalisé) sur les issues objectives et subjectives du SCA chez les jeunes patientes. Dans les 5 articles retenus, les issues objectives incluaient la réadmission à l'hôpital, le temps écoulé entre l'arrivée à l'hôpital et la réalisation de l'électrocardiographie et l'évolution de l'athérosclérose coronarienne. Les issues subjectives, comme le statut fonctionnel physique et mental, la qualité de vie, les limitations physiques et le syndrome d'épuisement, ont également été examinées. Être employé, qui est un rôle de genre, est apparu comme facteur de protection contre la réadmission à l'hôpital. Des facteurs liés à l'identité de genre, comme la dépression et le stress, étaient corrélés à des issues négatives et l'anxiété était liée au temps écoulé entre l'arrivée à l'hôpital et la réalisation de l'électrocardiographie. Les facteurs liés aux institutions, y compris les disparités de revenus, influençaient la probabilité de réadmission à l'hôpital. La présence d'un bon réseau social était associée à de plus faibles limitations physiques après le SCA, alors que les problèmes financiers et un faible niveau d'éducation avaient une influence néfaste sur la qualité de vie et le syndrome d'épuisement. Ces résultats font ressortir les interactions complexes entre les différentes dimensions du genre qui façonnent les issues du SCA chez les jeunes patientes. L'intégration de ces renseignements dans la pratique clinique et dans la recherche scientifique pourrait permettre d'améliorer les soins, de limiter les disparités auxquelles font face ces patientes et de favoriser une meilleure santé cardiovasculaire au sein de cette population vulnérable.
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PURPOSE: This study aimed to identify opioid consumption trajectories among persons living with chronic pain (CP) and put them in relation to patient-reported outcomes 6 months after initiating multidisciplinary pain treatment. METHODS: This study used data from the Quebec Pain Registry (2008-2014) linked to longitudinal Quebec health insurance databases. We included adults diagnosed with CP and covered by the Quebec public prescription drug insurance plan. The daily cumulative opioid doses in the first 6 months after initiating multidisciplinary pain treatment were transformed into morphine milligram equivalents. An individual-centered approach involving principal factor and cluster analyses applied to longitudinal statistical indicators of opioid use was conducted to classify trajectories. Multivariate regression models were applied to evaluate the associations between trajectory group membership and outcomes at 6-month follow-up (pain intensity, pain interference, depression, and physical and mental health-related quality of life). RESULTS: We identified three trajectories of opioid consumption: "no or very low and stable" opioid consumption (n = 2067, 96.3%), "increasing" opioid consumption (n = 40, 1.9%), and "decreasing" opioid consumption (n = 39, 1.8%). Patients in the "no or very low and stable" trajectory were less likely to be current smokers, experience polypharmacy, use opioids or benzodiazepine preceding their first visit, or experience pain interference at treatment initiation. Patients in the "increasing" opioid consumption group had significantly greater depression scores at 6-month compared to patients in the "no or very low and stable" trajectory group. CONCLUSION: Opioid consumption trajectories do not seem to be important determinants of most PROs 6 months after initiating multidisciplinary pain treatment.
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Dolor Crónico , Trastornos Relacionados con Opioides , Adulto , Humanos , Analgésicos Opioides/uso terapéutico , Calidad de Vida , Trastornos Relacionados con Opioides/tratamiento farmacológico , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/epidemiología , Medición de Resultados Informados por el PacienteRESUMEN
BACKGROUND: Sex differences exist in the likelihood of cognitive decline. The age at hypertension diagnosis is a unique contributor to brain structural changes associated with cerebral small vessel disease. However, whether this relationship differs between sexes remains unclear. Therefore, our objective was to evaluate sex differences in the association between the age at hypertension diagnosis and cerebral small vessel disease-related brain structural changes. METHODS: We used data from the UK Biobank to select participants with a known age at hypertension diagnosis and brain magnetic resonance imaging (n=9430) and stratified them by sex and age at hypertension diagnosis. Control participants with magnetic resonance imaging scans but no hypertension were chosen at random matched by using propensity score matching. For morphological brain structural changes, generalized linear models were used while adjusting for other vascular risk factors. For the assessment of white matter microstructure, principal component analysis led to a reduction in the number of fractional anisotropy variables, followed by regression analysis with major principal components as outcomes. RESULTS: Males but not females with a younger age at hypertension diagnosis exhibited lower brain gray and white matter volume compared with normotensive controls. The volume of white matter hyperintensities was greater in both males and females with hypertension than normotensive controls, significantly higher in older females with hypertension. Compared with normotensive controls, white matter microstructural integrity was lower in individuals with hypertension, which became more prominent with increasing age. CONCLUSIONS: Our study demonstrates that the effect of hypertension on cerebral small vessel disease-related brain structure differs by sex and by age at hypertension diagnosis.
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Enfermedades de los Pequeños Vasos Cerebrales , Hipertensión , Sustancia Blanca , Humanos , Masculino , Femenino , Anciano , Caracteres Sexuales , Encéfalo , Imagen por Resonancia Magnética , Hipertensión/diagnóstico por imagen , Hipertensión/complicaciones , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/complicacionesRESUMEN
Abstract Hemophagocytic lymphohistiocytosis (HLH) is a rare genetic hyperinflammatory syndrome that occurs early in life. Macrophage activation syndrome (MAS) usually refers to a secondary form of HLH associated with autoimmunity, although there are other causes of secondary HLH, such as infections and malignancy. In this article, we reviewed the concepts, epidemiology, clinical and laboratory features, diagnosis, differential diagnosis, prognosis, and treatment of HLH and MAS. We also reviewed the presence of MAS in the most common autoimmune diseases that affect children. Both are severe diseases that require prompt diagnosis and treatment to avoid morbidity and mortality.
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Abstract Biological invasions are one of the major threats to biodiversity and good quality of life, resulting from the translocation of species by human action. There are more than 500 alien species currently invading ecosystems in Brazil, particularly plants and fishes, while little is known about invasive microorganisms. Although invasive alien species are present in all ecosystems in the country, most have been recorded in habitats with greater human interference, such as urban and peri-urban areas, farmland, dams, reservoirs, ports, and canals. Historically, the southern and southeastern regions of Brazil have had more invasive alien species, but there has been an increase in the number of invasive alien species in the central-western and northern regions in recent decades. The ornamental trade of plants and fishes as well as the illegal pet trade of wild mammals and reptiles are some of the main pathways for invasive species introduction and spread in Brazil. Breeding and cultivation systems that allow escape to natural areas are a relevant route of species introductions in freshwater ecosystems, while unintentional introductions from shipping and infrastructure are of extreme concern in marine ecosystems. The negative impacts of invasive alien species on the biota mainly include changes in community structure and local decrease in native species richness, mediated by predation, competition, and ecosystem changes. Most negative impacts are recorded for intentionally introduced species, such as fishes and plants, but unintentional introductions have led to impacts on good quality of life, with associated costs and impacts on human health. The management of biological invasions faces challenges that need to be overcome, such as the lack of public knowledge about the impact of invasive alien species, the popular appeal of charismatic invasive species or those used by humans, and the use of controversial control techniques. However, successful experiences of eradication and control in terrestrial and marine ecosystems have been recorded, some of them involving public engagement in management actions. Recognizing the issue as a cross-cutting public policy and developing ongoing governance experiences are fundamental goals for the management of invasive alien species in Brazil.
Resumo Invasões biológicas são uma das maiores ameaças à biodiversidade e à boa qualidade de vida, ocorrendo a partir da translocação de espécies por ação humana. Existem mais de 500 espécies exóticas invadindo ecossistemas atualmente no Brasil, com destaque para plantas e peixes. Pouco se sabe sobre microrganismos invasores. Apesar de existirem espécies exóticas invasoras em todos os ecossistemas no país, a maior parte dos registros foi feita em hábitats com maior interferência humana, como áreas urbanas, periurbanas, terras cultivadas, represas, reservatórios, portos e canais. Historicamente, as regiões sul e sudeste do Brasil apresentam mais espécies exóticas invasoras, mas nas últimas décadas se tem observado um aumento no número de espécies exóticas invasoras nas regiões centro-oeste e norte. O comércio de plantas e peixes ornamentais, assim como o comércio ilegal de mamíferos e répteis silvestres como animais de estimação são algumas das principais vias de introdução e disseminação de espécies exóticas invasoras no Brasil. Sistemas de criação e cultivo que possibilitam o escape para áreas naturais são uma relevante via de introdução em ecossistemas de águas continentais, enquanto introduções não intencionais a partir de navegação e de infraestrutura são de extrema preocupação em ecossistemas marinhos. Os impactos negativos de espécies exóticas invasoras sobre a biota incluem principalmente alterações na estrutura de comunidades e diminuição local da riqueza de espécies nativas, mediados por predação, competição e modificações ecossistêmicas. A maior parte dos impactos negativos registrados ocorreram para espécies introduzidas intencionalmente, como peixes e plantas, mas introduções não intencionais têm levado a impactos na boa qualidade de vida, com custos associados e impactos sobre a saúde humana. A gestão de invasões biológicas esbarra em desafios a serem superados, tais como a falta de conhecimento do público sobre o impacto de espécies exóticas invasoras, o apelo popular de espécies invasoras carismáticas ou utilizadas por humanos e o emprego de técnicas controversas de controle. Entretanto, experiências bem-sucedidas de erradicação e controle em ecossistemas terrestres e marinhos têm sido registrados, alguns deles envolvendo engajamento público nas ações de manejo. Reconhecer o tema como uma política pública transversal e desenvolver experiências continuadas de governança são metas fundamentais para a gestão e o manejo de espécies exóticas invasoras no Brasil.
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ABSTRACT Objective: To conduct a bibliographic review on tuberculosis (TB) disease in children and adolescents with rheumatic diseases, being managed with biologic therapy. Data source: An integrative review with a search in the U.S. National Library of Medicine and the National Institutes of Health (PubMed) using the following descriptors and Boolean operators: (["tuberculosis"] AND (["children"] OR ["adolescent"]) AND ["rheumatic diseases"] AND (["tumor necrosis factor-alpha"] OR ["etanercept"] OR ["adalimumab"] OR ["infliximab"] OR ["biological drugs"] OR ["rituximab"] OR ["belimumab"] OR ["tocilizumab"] OR ["canakinumab"] OR ["golimumab"] OR ["secukinumab"] OR ["ustekinumab"] OR ["tofacitinib"] OR ["baricitinib"] OR ["anakinra"] OR ["rilonacept"] OR ["abatacept"]), between January 2010 and October 2021. Data synthesis: Thirty-seven articles were included, with the total number of 36,198 patients. There were 81 cases of latent tuberculosis infection (LTBI), 80 cases of pulmonary tuberculosis (PTB), and four of extrapulmonary tuberculosis (EPTB). The main rheumatic disease was juvenile idiopathic arthritis. Among LTBI cases, most were diagnosed at screening and none progressed to TB disease during follow-up. Of the TB cases using biologics, most used tumor necrosis factor-alpha inhibitors (anti-TNFα) drugs. There was only one death. Conclusions: The study revealed a low rate of active TB in pediatric patients using biologic therapy. Screening for LTBI before initiating biologics should be done in all patients, and treatment, in cases of positive screening, plays a critical role in preventing progression to TB disease.
RESUMO Objetivo: Fazer um levantamento bibliográfico referente à tuberculose (TB) em crianças e adolescentes com doenças reumáticas, em uso de imunobiológicos. Fonte de dados: Revisão integrativa com busca na base United States National Library of Medicine (PubMed) utilizando os descritores e operadores booleanos: (["tuberculosis"] AND (["children"] OR ["adolescent"]) AND ["rheumatic diseases"] AND (["tumor necrosis fator-alpha"] OR ["etanercept"] OR ["adalimumab"] OR ["infliximab"] OR ["biological drugs"] OR ["rituximab"] OR ["belimumab"] OR ["tocilizumab"] OR ["canakinumab"] OR ["golimumab"] OR ["secukinumab"] OR ["ustekinumab"] OR ["tofacitinib"] OR ["baricitinib"] OR ["anakinra"] OR ["rilonacept"] OR ["abatacept"]), entre janeiro de 2010 e outubro de 2021. Síntese de dados: Trinta e sete artigos foram incluídos, com o total de 36.198 pacientes. Houve 81 casos de tuberculose latente (ILTB), 80 casos de tuberculose pulmonar (TBP) e quatro casos de tuberculose extrapulmonar (TBEP). A principal doença reumática foi a artrite idiopática juvenil. Entre os casos de ILTB, a maioria foi diagnosticada no rastreio e nenhum evoluiu para a TB. Dos casos de TB em uso de imunobiológicos, a maioria utilizava fármacos antiTNFα. Houve somente um caso de óbito. Conclusões: O estudo demonstrou baixa taxa de TB nos pacientes pediátricos em uso de imunobiológicos. O rastreio para ILTB antes do início da terapia com agentes biológicos deve ser realizado em todos os pacientes, e o tratamento, nos casos de rastreio positivo, é importante para evitar a progressão para TB doença.
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ABSTRACT Objective: To describe the current state of the art in the therapeutic administration of botulinum toxin with indications, efficacy, and safety profile for children and adolescents with cerebral palsy. Data source: An integrative review was conducted. The MEDLINE/PubMed database was searched twice within the last decade using distinct terms, and only studies written in the English language were included. The study population was limited to those aged 0-18 years. Articles that were duplicates or lacked sufficient methodology information were excluded. Data synthesis: We found 256 articles, of which 105 were included. Among the included studies, most were conducted in developed countries. Botulinum toxin demonstrated good safety and efficacy in reducing spasticity, particularly when administered by a multidisciplinary rehabilitation team. It is primarily utilized to improve gait and upper limb function, facilitate hygiene care, reduce pain, prevent musculoskeletal deformities, and even decrease sialorrhea in patients without a functional prognosis for walking. Conclusions: The administration of botulinum toxin is safe and efficacious, especially when combined with a multi-professional rehabilitation team approach, which increases the probability of functional improvement. It can also be beneficial for patients with significant functional impairments to help with daily care tasks, such as hygiene, dressing, and reducing sialorrhea. Pediatricians must be familiar with this treatment and its indications to attend to and refer patients promptly when necessary, and to exploit their neuroplasticity. Further research on this topic is required in developing countries.
RESUMO Objetivo: Descrever o estado da arte em aplicação terapêutica de toxina botulínica com indicações, eficácia e perfil de segurança em crianças e adolescentes com paralisia cerebral. Fontes de dados: Realizada revisão integrativa através de busca na base de dados MEDLINE/PubMed em dois momentos nos últimos 10 anos, e termos distintos, em inglês, numa população entre 0 e 18 anos de idade. Excluiu-se artigos duplicados ou com informações insuficientes de metodologia. Síntese dos dados: 256 artigos foram encontrados e 105 foram incluídos, sendo a maior parte realizados em países desenvolvidos. A toxina botulínica mostrou boa segurança e efetividade na redução da espasticidade, especialmente administrada por uma equipe de reabilitação multiprofissional, usada principalmente para: melhora da marcha e da função dos membros superiores, facilitação dos cuidados de higiene, analgesia e prevenção de deformidades musculoesqueléticas, além de redução da sialorreia, inclusive em pacientes sem prognóstico funcional de marcha. Conclusões: A aplicação de toxina botulínica foi efetiva e segura, principalmente quando atrelada a uma abordagem por equipe de reabilitação multiprofissional, o que aumenta as chances de melhora funcional. Mostrou-se benéfica também para pacientes com grandes comprometimentos funcionais para facilitar os seus cuidados diários em relação à higiene, colocar e tirar roupas e redução da sialorreia. O pediatra deve estar familiarizado com esse tratamento e suas indicações para atender e direcionar pacientes o mais breve possível quando indicado e aproveitar o máximo de neuroplasticidade. Há necessidade de investimentos em mais pesquisas sobre este tema em países em desenvolvimento.
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BACKGROUND: Rheumatic patients have a higher frequency of tuberculosis(TB) than the general population. This study aimed to describe children and adolescents with TB and rheumatic diseases(RD) who were being treated in a reference center. METHODS: A series of TB cases were investigated in a reference center for childhood TB in Rio de Janeiro, Brazil, from 1995 to 2022. RESULTS: Fifteen patients with underlying RD and TB were included with 8(53%) being female. The mean age at RD diagnosis was 7.10years (SD ± 0,57 years), and the mean age at TB diagnosis was 9.81 years(SD ± 0.88 years). A total of 9 cases of pulmonary TB(PTB) and 6 cases of extrapulmonary TB-pleural(2), joint/osteoarticular(1), cutaneous(1), ocular(1), and peritoneal(1)- were described. The RD observed in the 15 patients included juvenile idiopathic arthritis(9), juvenile systemic lupus erythematosus(3), juvenile dermatomyositis(1), polyarteritis nodosa(1), and pyoderma gangrenosum(1). Among the immunosuppressants/immunobiologics, methotrexate(8) was the most commonly used, followed by corticosteroids(6), etanercept(2), mycophenolate mofetil(1), cyclosporine A(1), adalimumab(1), and tocilizumab(1). The most common symptoms were fever and weight loss, and a predominance of PTB cases was noted. GeneXpert MTB/RIF® was performed in six patients and was detectable in two without rifampicin resistance; Xpert Ultra® was performed in five patients, and traces with indeterminate rifampicin resistance were detected in three. One female patient discontinued treatment, and another passed away. CONCLUSIONS: The case series demonstrated the importance of suspecting and investigating TB in RD affected patients who are using immunosuppressants/ immunobiologics, particularly in countries with high rates of TB such as Brazil.
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Mycobacterium tuberculosis , Enfermedades Reumáticas , Tuberculosis , Humanos , Niño , Femenino , Adolescente , Masculino , Rifampin , Sensibilidad y Especificidad , Brasil/epidemiología , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Inmunosupresores/uso terapéuticoRESUMEN
Objective: The purpose of this study was to map and describe the studies that have investigated therapeutic alternatives for the management of paediatric multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Considering the origin of the studies performed (low-, middle- and high-income countries), a systematic scoping review was conducted with primary studies that reported the use of medications for the treatment of patients with MIS-C. Sources: The searches were performed in MEDLINE, Embase, Lilacs, Epistemonikos, CINAHL, and CENTRAL, in the grey literature (theses and dissertations from CAPES, ProQuest, and PROSPERO) and in clinical trial databases until May 2022. The selection and extraction of studies were performed independently by two reviewers. Summary of the findings: A total of 173 studies were included, most of which were published as case reports or series. No randomized controlled clinical trials (RCTs) were identified. The investigated drugs were immunoglobulins, glucocorticoids, monoclonal antibodies, anticoagulants, and antiplatelet agents. Conclusion: The dosages, when reported, were heterogeneous among the studies. The ethnicity and comorbidity of the participants were poorly reported. Monoclonal antibodies, drugs with higher costs, were mostly described in studies of high-income countries.
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Mutations in genes coding for proteasome subunits and/or proteasome assembly helpers typically cause recurring autoinflammation referred to as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE) or proteasome-associated autoinflammatory syndrome (PRAAS). Patients with CANDLE/PRAAS present with mostly chronically elevated type I interferon scores that emerge as a consequence of increased proteotoxic stress by mechanisms that are not fully understood. Here, we report on five unrelated patients with CANDLE/PRAAS carrying novel inherited proteasome missense and/or nonsense variants. Four patients were compound heterozygous for novel pathogenic variants in the known CANDLE/PRAAS associated genes, PSMB8 and PSMB10, whereas one patient showed additive loss-of-function mutations in PSMB8. Variants in two previously not associated proteasome genes, PSMA5 and PSMC5, were found in a patient who also carried the PSMB8 founder mutation, p.T75M. All newly identified mutations substantially impact the steady-state expression of the affected proteasome subunits and/or their incorporation into mature 26S proteasomes. Our observations expand the spectrum of PRAAS-associated genetic variants and improve a molecular diagnosis and genetic counseling of patients with sterile autoinflammation.