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Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common but potentially severe adverse event associated with chimeric antigen receptor T-cell (CART) therapy characterized by the development of acute neurologic symptoms following CART infusion. ICANS encompasses a wide clinical spectrum typified by mild to severe encephalopathy, seizures and/or cerebral edema. As more patients have been treated with CART new ICANS phenomenology has emerged. We present the clinical course of five children who developed acute onset of quadriparesis or paraparesis associated with abnormal brain and/or spine neuroimaging after infusion of CD19 or CD22-directed CART, adverse events not previously reported in children. Orthogonal data from autopsy studies, cerebrospinal fluid (CSF) flow cytometry and CSF proteomics/cytokine profiling demonstrated chronic white matter destruction, but a notable lack of inflammatory pathologic changes and cell populations. Instead, children with quadriparesis or paraparesis post-CART therapy had lower levels of pro-inflammatory cytokines such as interferon gamma (IFNï§), CCL17, CCL23, and CXCL10 than those who did not develop quadriparesis or paraparesis. Taken together, these findings imply a non-inflammatory source of this newly described ICANS phenomenon in children. The pathophysiology of some neurologic symptoms following CART may therefore have a more complex etiology than exclusive T-cell activation and excessive cytokine production.
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This review aimed to update the clinical practice guidelines for managing children and adolescents with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society, the international scientific organization studying chromosome 22q11.2 differences and related conditions, recruited expert clinicians worldwide to revise the original 2011 pediatric clinical practice guidelines in a stepwise process: (1) a systematic literature search (1992-2021), (2) study selection and data extraction by clinical experts from 9 different countries, covering 24 subspecialties, and (3) creation of a draft consensus document based on the literature and expert opinion, which was further shaped by survey results from family support organizations regarding perceived needs. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text reviews, including 1545 meeting criteria for potential relevance to clinical care of children and adolescents. Informed by the available literature, recommendations were formulated. Given evidence base limitations, multidisciplinary recommendations represent consensus statements of good practice for this evolving field. These recommendations provide contemporary guidance for evaluation, surveillance, and management of the many 22q11.2DS-associated physical, cognitive, behavioral, and psychiatric morbidities while addressing important genetic counseling and psychosocial issues.
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Síndrome de DiGeorge , Adolescente , Humanos , Criança , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/terapia , Aconselhamento Genético , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition. STUDY DESIGN: This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition. RESULTS: In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.7%) and/or the patient was not referred for acute care (n = 90; 51.4%) at the initial clinical encounter, and this did not improve over time. Although many features of the presentation were similar in those initially diagnosed with AFM and those who were not; preceding illness, constipation, and reflexes differed significantly between the 2 groups. Patients with a non-AFM initial diagnosis more often required ventilatory support (26.2% vs 12.2%; OR, 0.4; 95% CI, 0.2-1.0; P = .05). These patients received immunomodulatory treatment later (3 days vs 2 days after neurologic symptom onset; 95% CI, -2 to 0; P = .05), particularly intravenous immunoglobulin (5 days vs 2 days; 95% CI, -4 to -2; P < .001). CONCLUSIONS: Delayed recognition of AFM is concerning because of the risk for respiratory decompensation and need for intensive care monitoring. A non-AFM initial diagnosis was associated with delayed treatment that could have a clinical impact, particularly as new treatment options emerge.
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Viroses do Sistema Nervoso Central , Infecções por Enterovirus , Mielite , Doenças Neuromusculares , Criança , Humanos , Mielite/diagnóstico , Mielite/terapia , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/terapia , Viroses do Sistema Nervoso Central/diagnóstico , Viroses do Sistema Nervoso Central/terapia , Estudos Retrospectivos , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/terapiaRESUMO
Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare disorder that causes significant neurodevelopmental sequelae in children. Approximately half of pediatric OMAS cases are paraneoplastic, typically associated with localized neuroblastic tumors. Since early persistence or relapse of OMAS symptoms is common even after tumor resection, OMAS relapses may not routinely prompt reevaluation for recurrent tumors. We report a 12-year-old girl with neuroblastic tumor recurrence associated with OMAS relapse a decade after initial treatment. Providers should be aware of tumor recurrence as a trigger for distant OMAS relapse, raising intriguing questions about the role of immune surveillance and control of neuroblastic tumors.
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Síndrome de Opsoclonia-Mioclonia , Feminino , Humanos , Criança , Síndrome de Opsoclonia-Mioclonia/etiologia , Síndrome de Opsoclonia-Mioclonia/terapia , Recidiva Local de Neoplasia , Ataxia/terapia , Ataxia/complicaçõesRESUMO
OBJECTIVES: We developed a group-based program (My Healthy Brain, MHB) to engage older adults at-risk for dementia in healthy lifestyles. We report on a two-part study to adapt MHB by incorporating mindfulness skills, using mobile health technology to monitor and reinforce behaviors, and delivering it via live video. METHODS: Participants were older adults (age ≥ 60) with subjective cognitive decline (SCD) and at least one lifestyle risk factor. In Aim 1 (n = 11, 2 groups), we conducted focus groups to obtain qualitative feedback on proposed adaptations. In Aim 2 (n = 10), we conducted a virtual open pilot with exit interviews to explore the feasibility and outcomes of the adapted MHB. RESULTS: Thematic analysis revealed: (1) barriers and facilitators to healthy lifestyles, (2) positive impressions of MHB, (3) interest in mindfulness skills, and (4) openness to study technologies. MHB met a-priori feasibility benchmarks and was associated with improvements in cognition, lifestyle (e.g. physical function), and proposed mechanisms (e.g. mindfulness). Exit interviews confirmed high feasibility and satisfaction. CONCLUSION: The integration of mindfulness, live video, and mobile health technologies was feasible and promising for improving healthier lifestyles. The results inform the next feasibility RCT of MHB to prepare for efficacy testing.Supplemental data for this article is available online at http://dx.doi.org/10.1080/13607863.2022.2032600.
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Demência , Atenção Plena , Humanos , Idoso , Atenção Plena/métodos , Estudos de Viabilidade , Estilo de Vida , Fatores de Risco , Demência/prevenção & controleRESUMO
Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.
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Viroses do Sistema Nervoso Central/diagnóstico por imagem , Viroses do Sistema Nervoso Central/reabilitação , Infecções por Enterovirus/epidemiologia , Hipotonia Muscular , Debilidade Muscular , Mielite/diagnóstico por imagem , Mielite/reabilitação , Doenças Neuromusculares/diagnóstico por imagem , Doenças Neuromusculares/reabilitação , Viroses do Sistema Nervoso Central/líquido cefalorraquidiano , Viroses do Sistema Nervoso Central/virologia , Criança , Infecções por Enterovirus/líquido cefalorraquidiano , Infecções por Enterovirus/complicações , Saúde Global , Humanos , Imageamento por Ressonância Magnética , Hipotonia Muscular/etiologia , Debilidade Muscular/etiologia , Mielite/líquido cefalorraquidiano , Mielite/virologia , Doenças Neuromusculares/líquido cefalorraquidiano , Doenças Neuromusculares/virologia , Avaliação de Resultados da Assistência ao PacienteRESUMO
OBJECTIVES: We sought to characterize psychosocial profiles of adaptation to neurofibromatosis (NF). METHODS: Participants (N = 224) completed self-report measures of psychosocial functioning, including risk (i.e., perceived stress, depression, anxiety) and resiliency (i.e., gratitude, optimism, coping, social support, mindfulness, empathy). We used a TwoStep hierarchical cluster analysis to determine clusters reflecting adaptation to NF. RESULTS: The analysis revealed two distinct groups, with the "Low Adaptation" group defined by high emotional distress and low resiliency (n = 130; 57% of participants), and the "High Adaptation" group defined by low emotional distress and high resiliency (n = 85; 37% of participants). Clusters differed significantly across nearly all criterion variables, as well as quality of life and pain interference. CONCLUSION: Both risk and resiliency factors are important for understanding psychosocial adaptation to NF. Findings suggest that clinical providers should prioritize screening and intervention methods targeting these variables to promote positive adaptation to NF. TRIAL REGISTRATION: ClinicalTrials.gov NCT03406208; https://clinicaltrials.gov/ct2/show/NCT03406208 (Archived by WebCite at http://www.webcitation.org/72ZoTDQ6h ).
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Adaptação Psicológica , Neurofibromatoses , Humanos , Neurofibromatoses/psicologia , Resiliência Psicológica , RiscoRESUMO
AIMS: GSK3358699 is a mononuclear myeloid-targeted bromodomain and extra-terminal domain (BET) family inhibitor which demonstrates immunomodulatory effects in vitro. This phase 1, randomized, first-in-human study evaluated the safety, pharmacokinetics, and pharmacodynamics of GSK3358699 in healthy male participants (NCT03426995). METHODS: Part A (N = 23) included three dose-escalating periods of 1-40 mg of GSK3358699 or placebo in two cohorts in a single ascending-dose crossover design. Part C (N = 25) was planned as an initial dose of 10 mg of GSK3358699 or placebo daily for 14 days followed by selected doses in four sequential cohorts. RESULTS: In part A, exposure to GSK3358699 and its metabolite GSK3206944 generally increased with increasing doses. The median initial half-life ranged from 0.7 to 1.1 (GSK3358699) and 2.1 to 2.9 (GSK3206944) hours after a single dose of 1-40 mg. GSK3206944 concentrations in monocytes were quantifiable at 1-hour post-dose following 10 mg of GSK3358699 and 1 and 4 hours post-dose following 20-40 mg. Mean predicted percentage inhibition of ex vivo lipopolysaccharide-induced monocyte chemoattractant protein (MCP)-1 reached 75% with 40 mg of GSK3358699. GSK3358699 did not inhibit interleukin (IL)-6 and tumour necrosis factor (TNF). The most common adverse event (AE) was headache. Four AEs of nonsustained ventricular tachycardia were observed across parts A and C. One serious AE of atrial fibrillation (part C) required hospitalization. CONCLUSIONS: Single doses of GSK3358699 are generally well tolerated with significant metabolite concentrations detected in target cells. A complete assessment of pharmacodynamics was limited by assay variability. A causal relationship could not be excluded for cardiac-related AEs, resulting in an inability to identify a suitable repeat-dose regimen and study termination.
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Relação Dose-Resposta a Droga , Área Sob a Curva , Estudos Cross-Over , Método Duplo-Cego , Voluntários Saudáveis , Humanos , MasculinoRESUMO
OBJECTIVES: uncertainty pervades the complex illness trajectories experienced by older adults with multimorbidity. Uncertainty is experienced by older people, their informal carers and professionals providing care, yet is incompletely understood. We aimed to identify and synthesise systematically the experience of uncertainty in advanced multimorbidity from patient, carer and professional perspectives. DESIGN: systematic literature review of published and grey qualitative literature from 9 databases (Prospero CRD 42021227480). PARTICIPANTS: older people with advanced multimorbidity, and informal carers/professionals providing care to this group. Exclusion criteria: early multimorbidity, insufficient focus on uncertainty. ANALYSIS: weight-of-evidence assessment was used to appraise included articles. We undertook thematic synthesis of multi-perspective experiences and response to uncertainty. RESULTS: from 4,738 unique search results, we included 44 articles relating to 40 studies. 22 focused on patient experiences of uncertainty (n = 460), 15 on carer experiences (n = 197), and 19 on health professional experiences (n = 490), with 10 exploring multiple perspectives. We identified a shared experience of 'Total Uncertainty' across five domains: 'appraising and managing multiple illnesses'; 'fragmented care and communication'; 'feeling overwhelmed'; 'uncertainty of others' and 'continual change'. Participants responded to uncertainty by either active (addressing, avoiding) or passive (accepting) means. CONCLUSIONS: the novel concept of 'Total Uncertainty' represents a step change in our understanding of illness experience in advanced multimorbidity. Patients, carers and health professionals experienced uncertainty in similar domains, suggesting a shared understanding is feasible. The domains of total uncertainty form a useful organising framework for health professionals caring for older adults with multimorbidity.
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Cuidadores , Multimorbidade , Idoso , Comunicação , Pessoal de Saúde , Humanos , Pesquisa Qualitativa , IncertezaRESUMO
BACKGROUND: The number of young people in New Zealand (Aotearoa) who experience mental health challenges is increasing. As those in Aotearoa went into the initial COVID-19 lockdown, an ongoing digital mental health project was adapted and underwent rapid content authoring to create the Aroha chatbot. This dynamic digital support was designed with and for young people to help manage pandemic-related worry. OBJECTIVE: Aroha was developed to provide practical evidence-based tools for anxiety management using cognitive behavioral therapy and positive psychology. The chatbot included practical ideas to maintain social and cultural connection, and to stay active and well. METHODS: Stay-at-home orders under Aotearoa's lockdown commenced on March 20, 2020. By leveraging previously developed chatbot technology and broader existing online trial infrastructure, the Aroha chatbot was launched promptly on April 7, 2020. Dissemination of the chatbot for an open trial was via a URL, and feedback on the experience of the lockdown and the experience of Aroha was gathered via online questionnaires and a focus group, and from community members. RESULTS: In the 2 weeks following the launch of the chatbot, there were 393 registrations, and 238 users logged into the chatbot, of whom 127 were in the target age range (13-24 years). Feedback guided iterative and responsive content authoring to suit the dynamic situation and motivated engineering to dynamically detect and react to a range of conversational intents. CONCLUSIONS: The experience of the implementation of the Aroha chatbot highlights the feasibility of providing timely event-specific digital mental health support and the technology requirements for a flexible and enabling chatbot architectural framework.
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COVID-19 , Transtornos Mentais , Adolescente , Humanos , Adulto Jovem , Controle de Doenças Transmissíveis , COVID-19/epidemiologia , COVID-19/prevenção & controle , Nova Zelândia/epidemiologia , Pandemias , Transtornos Mentais/prevenção & controleRESUMO
Importance: The administration of a high fraction of oxygen following return of spontaneous circulation in out-of-hospital cardiac arrest may increase reperfusion brain injury. Objective: To determine whether targeting a lower oxygen saturation in the early phase of postresuscitation care for out-of-hospital cardiac arrest improves survival at hospital discharge. Design, Setting, and Participants: This multicenter, parallel-group, randomized clinical trial included unconscious adults with return of spontaneous circulation and a peripheral oxygen saturation (Spo2) of at least 95% while receiving 100% oxygen. The trial was conducted in 2 emergency medical services and 15 hospitals in Victoria and South Australia, Australia, between December 11, 2017, and August 11, 2020, with data collection from ambulance and hospital medical records (final follow-up date, August 25, 2021). The trial enrolled 428 of a planned 1416 patients. Interventions: Patients were randomized by paramedics to receive oxygen titration to achieve an oxygen saturation of either 90% to 94% (intervention; n = 216) or 98% to 100% (standard care; n = 212) until arrival in the intensive care unit. Main Outcomes and Measures: The primary outcome was survival to hospital discharge. There were 9 secondary outcomes collected, including hypoxic episodes (Spo2 <90%) and prespecified serious adverse events, which included hypoxia with rearrest. Results: The trial was stopped early due to the COVID-19 pandemic. Of the 428 patients who were randomized, 425 were included in the primary analysis (median age, 65.5 years; 100 [23.5%] women) and all completed the trial. Overall, 82 of 214 patients (38.3%) in the intervention group survived to hospital discharge compared with 101 of 211 (47.9%) in the standard care group (difference, -9.6% [95% CI, -18.9% to -0.2%]; unadjusted odds ratio, 0.68 [95% CI, 0.46-1.00]; P = .05). Of the 9 prespecified secondary outcomes collected during hospital stay, 8 showed no significant difference. A hypoxic episode prior to intensive care was observed in 31.3% (n = 67) of participants in the intervention group and 16.1% (n = 34) in the standard care group (difference, 15.2% [95% CI, 7.2%-23.1%]; OR, 2.37 [95% CI, 1.49-3.79]; P < .001). Conclusions and Relevance: Among patients achieving return of spontaneous circulation after out-of-hospital cardiac arrest, targeting an oxygen saturation of 90% to 94%, compared with 98% to 100%, until admission to the intensive care unit did not significantly improve survival to hospital discharge. Although the trial is limited by early termination due to the COVID-19 pandemic, the findings do not support use of an oxygen saturation target of 90% to 94% in the out-of-hospital setting after resuscitation from cardiac arrest. Trial Registration: ClinicalTrials.gov Identifier: NCT03138005.
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COVID-19 , Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Feminino , Idoso , Masculino , Parada Cardíaca Extra-Hospitalar/mortalidade , Alta do Paciente , Oxigênio , Pandemias , Saturação de Oxigênio , Oxigenoterapia , Hospitais , VitóriaRESUMO
Nearly half of dementia cases may be explained by modifiable lifestyle risk factors. Multidomain interventions are needed to bypass cognitive decline (CD) and aging-related barriers to sustained healthy lifestyles in at-risk older adults. We iteratively developed My Healthy Brain, a group-based lifestyle program (8 weeks, 90 min sessions) delivered via live video that applies behavioral principles to target multiple risk factors for dementia. We describe the program structure, virtual delivery, and outcomes for a group of older adults with subjective CD or mild cognitive impairment and lifestyle risk factors (e.g., sedentary, poor sleep or diet). We also conducted a group exit interview to qualitatively assess participant experiences and elicit feedback to improve My Healthy Brain. This case report demonstrates that delivering evidence-based brain health education and behavior change skills in a group setting via live video is feasible, acceptable, and has the potential to improve lifestyle, cognitive, and psychosocial outcomes in older adults with CD.
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Demência , Humanos , Idoso , Demência/psicologia , Estilo de Vida , Fatores de Risco , Encéfalo , DietaRESUMO
Mendelian disorders of cholesterol biosynthesis typically result in multi-system clinical phenotypes, underlining the importance of cholesterol in embryogenesis and development. FDFT1 encodes for an evolutionarily conserved enzyme, squalene synthase (SS, farnesyl-pyrophosphate farnesyl-transferase 1), which catalyzes the first committed step in cholesterol biosynthesis. We report three individuals with profound developmental delay, brain abnormalities, 2-3 syndactyly of the toes, and facial dysmorphisms, resembling Smith-Lemli-Opitz syndrome, the most common cholesterol biogenesis defect. The metabolite profile in plasma and urine suggested that their defect was at the level of squalene synthase. Whole-exome sequencing was used to identify recessive disease-causing variants in FDFT1. Functional characterization of one variant demonstrated a partial splicing defect and altered promoter and/or enhancer activity, reflecting essential mechanisms for regulating cholesterol biosynthesis/uptake in steady state.
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Colesterol/genética , Farnesil-Difosfato Farnesiltransferase/genética , Anormalidades Musculoesqueléticas/genética , Criança , Pré-Escolar , Elementos Facilitadores Genéticos/genética , Feminino , Humanos , Lactente , Masculino , Regiões Promotoras Genéticas/genética , Splicing de RNA/genética , Síndrome de Smith-Lemli-Opitz/genética , Sequenciamento do Exoma/métodosRESUMO
BACKGROUND: Two evidence-based practice projects and an innovative model provided best evidence and a framework for the implementation and sustainment of a bedside shift report (BSR) quality improvement project. PROBLEM: Without a standardized BSR process, there was a lack of Veteran involvement in care planning decisions and nurse dissatisfaction related to missed communication of pertinent patient information. APPROACH: Facilitators and barriers were identified and addressed during planning. Key elements of BSR were incorporated. After approval by shared governance, unit-based champions and leaders supported the change. Implementation began every 2 weeks on a different unit. OUTCOMES: Implementation was completed in 4 months for 11 units. After 15 months, there was consistent BSR on 82% of the units and improved patient satisfaction with nurses taking time to listen. CONCLUSIONS: Best evidence, unit-based champions, leadership support, project coordinators, and persistence are critical to implementing and sustaining practice change.
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Assistência Centrada no Paciente , Melhoria de Qualidade , Comunicação , Humanos , Liderança , Satisfação do PacienteRESUMO
The pandemic is creating unprecedented demand for mental health support for young people. While schools often facilitate mental health support for their students, the demands for online teaching and the uncertainty created by the pandemic make traditional delivery of support through schools challenging. Technology provides a potential way forward. We have developed a digital ecosystem, HABITS, that can be integrated into school and healthcare systems. This has allowed us to deploy specific evidence-based interventions directly, and through schools, to students and to parents in New Zealand during the current pandemic. Chatbot architecture is particularly suited to rapid iteration to provide specific information while apps can provide more generalised support. While technology can provide some solutions, it is important to be aware of the potential to increase current inequities, with those facing the greatest challenges to health and well-being, also least able to afford the resources to access digital interventions. Development of an integrated and equitable digital system will take time and collaboration.
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Serviços de Saúde da Criança/organização & administração , Infecções por Coronavirus , Serviços de Saúde Mental/organização & administração , Saúde Mental , Pandemias , Pneumonia Viral , Serviços de Saúde Escolar/organização & administração , Estudantes/psicologia , Adolescente , COVID-19 , Criança , Computadores , Ecossistema , Humanos , Nova Zelândia , TelecomunicaçõesRESUMO
Acute flaccid myelitis (AFM) is a polio-like disease that results in paralysis in previously healthy persons. Although the definitive cause of AFM remains unconfirmed, enterovirus D68 (EV-D68) is suspected based on 2014 data demonstrating an increase in AFM cases concomitant with an EV-D68 outbreak. We examined the prevalence in children and the molecular evolution of EV-D68 for 2009-2018 in Philadelphia, Pennsylvania, USA. We detected widespread EV-D68 circulation in 2009, rare detections in 2010 and 2011, and then biennial circulation, only in even years, during 2012-2018. Prevalence of EV-D68 significantly correlated with AFM cases during this period. Finally, whole-genome sequencing revealed early detection of the B1 clade in 2009 and continued evolution of the B3 clade from 2016 to 2018. These data reinforce the need to improve surveillance programs for nonpolio enterovirus to identify possible AFM triggers and predict disease prevalence to better prepare for future outbreaks.
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Viroses do Sistema Nervoso Central/epidemiologia , Surtos de Doenças , Enterovirus Humano D/isolamento & purificação , Infecções por Enterovirus/epidemiologia , Mielite/epidemiologia , Doenças Neuromusculares/epidemiologia , Viroses do Sistema Nervoso Central/virologia , Criança , Infecções por Enterovirus/virologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Mielite/virologia , Doenças Neuromusculares/virologia , Philadelphia/epidemiologia , Estudos RetrospectivosRESUMO
Acute flaccid myelitis (AFM) is a rare condition associated with spinal cord gray matter abnormalities and frequent persistent motor deficits in the limbs. We present our experience with the diagnosis, management, and outcomes of affected children in 2014 and 2016, emphasizing features that should trigger early consideration of AFM. Early viral testing may increase the rate of detecting associated viruses.
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Viroses do Sistema Nervoso Central/diagnóstico , Viroses do Sistema Nervoso Central/terapia , Mielite/diagnóstico , Mielite/terapia , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/terapia , Encéfalo/diagnóstico por imagem , Viroses do Sistema Nervoso Central/virologia , Criança , Pré-Escolar , DNA Viral , Erros de Diagnóstico/estatística & dados numéricos , Enterovirus/genética , Enterovirus/isolamento & purificação , Feminino , Fluoxetina/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Imageamento por Ressonância Magnética , Masculino , Metilprednisolona/uso terapêutico , Mielite/virologia , Doenças Neuromusculares/virologia , Troca Plasmática , Reação em Cadeia da Polimerase , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medula Espinal/diagnóstico por imagemAssuntos
Planejamento Antecipado de Cuidados , Idoso Fragilizado , Fragilidade , Humanos , Idoso , Fragilidade/terapia , IncertezaRESUMO
Children with 22q11.2 deletion syndrome often come to medical attention due to signs and symptoms of neurologic dysfunction. It is imperative to understand the expected neurologic development of patients with this diagnosis in order to be alert for the potential neurologic complications, including cortical malformations, tethered cord, epilepsy, and movement disorders. We present an update of brain imaging findings from the CHOP 22q and You Center, a review of the current literature, and our current management practices for neurological issues.
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Síndrome de DiGeorge/fisiopatologia , Doenças do Sistema Nervoso/genética , Síndrome de DiGeorge/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/fisiopatologiaRESUMO
22q11.2 deletion syndrome (22q11.2DS) is a disorder caused by recurrent, chromosome-specific, low copy repeat (LCR)-mediated copy-number losses of chromosome 22q11. The Children's Hospital of Philadelphia has been involved in the clinical care of individuals with what is now known as 22q11.2DS since our initial report of the association with DiGeorge syndrome in 1982. We reviewed the medical records on our continuously growing longitudinal cohort of 1,421 patients with molecularly confirmed 22q11.2DS from 1992 to 2018. Most individuals are Caucasian and older than 8 years. The mean age at diagnosis was 3.9 years. The majority of patients (85%) had typical LCR22A-LCR22D deletions, and only 7% of these typical deletions were inherited from a parent harboring the deletion constitutionally. However, 6% of individuals harbored other nested deletions that would not be identified by traditional 22q11.2 FISH, thus requiring an orthogonal technology to diagnose. Major medical problems included immune dysfunction or allergies (77%), palatal abnormalities (67%), congenital heart disease (64%), gastrointestinal difficulties (65%), endocrine dysfunction (>50%), scoliosis (50%), renal anomalies (16%), and airway abnormalities. Median full-scale intelligence quotient was 76, with no significant difference between individuals with and without congenital heart disease or hypocalcemia. Characteristic dysmorphic facial features were present in most individuals, but dermatoglyphic patterns of our cohort are similar to normal controls. This is the largest longitudinal study of patients with 22q11.2DS, helping to further describe the condition and aid in diagnosis and management. Further surveillance will likely elucidate additional clinically relevant findings as they age.