RESUMO
OBJECTIVES: We sought to characterise the outcomes of patients with haematological malignancy and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hospital in our regional network of 7 hospitals. METHODS: Consecutive hospitalised patients with haematological malignancy and SARS-CoV-2 infection were identified from 01/03/2020 to 06/05/2020. Outcomes were categorised as death, resolved or ongoing. The primary outcome was preliminary case fatality rate (pCFR), defined as the number of cases resulting in death as a proportion of all diagnosed cases. Analysis was primarily descriptive. RESULTS: 66 Patients were included, overall pCFR was 51.5%. Patients ≥ 70 years accounted for the majority of hospitalised cases (42, 63%) and fatalities (25, 74%). Mortality was similar between females (52%) and males (51%). Immunosuppressive or cytotoxic treatment within 3 months of the diagnosis of SARS-CoV-2 infection was associated with a significantly higher pCFR of 70%, compared with 28% in those not on active treatment (P = .0013, 2 proportions z test). CONCLUSIONS: Mortality rates in patients with haematological malignancy and SARS-CoV-2 infection in hospital are high supporting measures to minimise the risk of infection in this population.
Assuntos
COVID-19/complicações , Neoplasias Hematológicas/complicações , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , COVID-19/mortalidade , COVID-19/prevenção & controle , Citotoxinas/efeitos adversos , Feminino , Neoplasias Hematológicas/terapia , Hospitalização , Humanos , Terapia de Imunossupressão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , SARS-CoV-2 , Reino Unido/epidemiologiaAssuntos
Formação de Anticorpos/efeitos dos fármacos , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , SARS-CoV-2/imunologia , Vacinação , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacina BNT162 , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , ChAdOx1 nCoV-19 , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mielogênica Crônica BCR-ABL Positiva/virologia , Masculino , Pessoa de Meia-IdadeAssuntos
Síndromes Mielodisplásicas/terapia , Adulto , Anemia/complicações , Anemia/terapia , Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Transfusão de Sangue/métodos , Decitabina/uso terapêutico , Gerenciamento Clínico , Hematínicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Hemorragia/complicações , Hemorragia/terapia , Humanos , Quelantes de Ferro/uso terapêutico , Síndromes Mielodisplásicas/complicações , Neutropenia/complicações , Neutropenia/terapia , Trombocitopenia/complicações , Trombocitopenia/terapiaRESUMO
Myelodysplastic syndromes (MDS) are a heterogeneous group of chronic hematological malignancies characterized by dysplasia, ineffective hematopoiesis and a variable risk of progression to acute myeloid leukemia. Sequencing of MDS genomes has identified mutations in genes implicated in RNA splicing, DNA modification, chromatin regulation, and cell signaling. We sequenced 111 genes across 738 patients with MDS or closely related neoplasms (including chronic myelomonocytic leukemia and MDS-myeloproliferative neoplasms) to explore the role of acquired mutations in MDS biology and clinical phenotype. Seventy-eight percent of patients had 1 or more oncogenic mutations. We identify complex patterns of pairwise association between genes, indicative of epistatic interactions involving components of the spliceosome machinery and epigenetic modifiers. Coupled with inferences on subclonal mutations, these data suggest a hypothesis of genetic "predestination," in which early driver mutations, typically affecting genes involved in RNA splicing, dictate future trajectories of disease evolution with distinct clinical phenotypes. Driver mutations had equivalent prognostic significance, whether clonal or subclonal, and leukemia-free survival deteriorated steadily as numbers of driver mutations increased. Thus, analysis of oncogenic mutations in large, well-characterized cohorts of patients illustrates the interconnections between the cancer genome and disease biology, with considerable potential for clinical application.
Assuntos
Mutação , Síndromes Mielodisplásicas/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Progressão da Doença , Epistasia Genética , Feminino , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mielomonocítica Crônica/genética , Masculino , Pessoa de Meia-Idade , Doenças Mieloproliferativas-Mielodisplásicas/genética , Oncogenes , Prognóstico , Splicing de RNA/genética , Spliceossomos/genéticaRESUMO
In this review, we present an overview of the role of exercise in neuromuscular disease (NMD). We demonstrate that despite the different pathologies in NMDs, exercise is beneficial, whether aerobic/endurance or strength/resistive training, and we explore whether this benefit has a similar mechanism to that of healthy subjects. We discuss further areas for study, incorporating imaginative and novel approaches to training and its assessment in NMD. We conclude by suggesting ways to improve future trials by avoiding previous methodological flaws and drawbacks in this field.
Assuntos
Terapia por Exercício/métodos , Exercício Físico/fisiologia , Força Muscular/fisiologia , Doenças Neuromusculares/terapia , Treinamento Resistido/métodos , Animais , Ensaios Clínicos como Assunto/métodos , Humanos , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/fisiopatologia , Resistência Física/fisiologiaRESUMO
BACKGROUND: In children and adolescents, obesity increases the risk of metabolic syndrome (MS). OBJECTIVE: We examined the prevalence of MS among obese and morbidly obese children and adolescents referred to an obesity clinic in a university-based hospital center. DESIGN/METHODS: A total of 194 obese (BMI > 95%) children and adolescents were evaluated. Fasting glucose, insulin, lipid panel, BMI, blood pressures were obtained. Main outcome measures were prevalence of components of MS by modified National Cholesterol Education Program (NCEP or Adult Treatment Panel 111 (ATP 111), with MS defined as > or = 3 components. RESULTS: There were 113 females (58%) and 81 males (42%); mean age of the cohort was 11.9 years (range: 3.4-18.8 years). One hundred seventy four (90%) of the cohort were African-American, 14 (7%) were Hispanic and 6 (3%) were others. Mean BMI z- score was 2.5 and ranged from 1.7 to 4.8. Thirty five percent of the total cohort had MS. Among the morbidly obese patients (BMI z-score > 2.5), the prevalence of the MS increased to 44%. Impaired fasting glucose (5.8 %), impaired glucose tolerance (6.5%) and silent diabetes mellitus (2.4%) were also identified. CONCLUSIONS: One third of obese patients referred to a hospital-based obesity center had the MS and nearly half of morbidly obese children and adolescents had MS.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Síndrome Metabólica/etnologia , Obesidade Mórbida/etnologia , População Urbana/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Cidade de Nova Iorque/epidemiologia , Prevalência , Distribuição por SexoRESUMO
Although obesity affects all cultures, ethnic groups and social strata, this disorder affects African Americans, Hispanics and the poor at a disproportionate rate. The Downstart Pediatric Healthy Lifestyle Program was developed to provide a multi-disciplinary behavioral modification program for inner city families in Brooklyn, New York interested in leading a healthier, more active lifestyle. The Downstart Program uses a four-pronged approach of medical evaluation, exercise, nutritional education and lifestyle modification. A psychological evaluation is performed to determine the individual's ability and readiness to participate in group activities. Baseline physical fitness, flexibility and muscle strength are measured, followed by a twice-weekly karate/martial arts/dance program, incorporating principles established by the President's Council on Exercise. Nutritional and behavioral modification aspects of the program consist of weekly education about food groups, portion control, goal setting and appropriate rewards for attaining goals. Our preliminary results indicate that the Downstart Program may be a viable intervention for weight loss. Further study is needed to improve strategies for motivating patients and means and criteria for assessing long-term effects on health and lifestyle.
Assuntos
Exercício Físico , Promoção da Saúde/organização & administração , Obesidade Mórbida/terapia , Pediatria/organização & administração , Comportamento de Redução do Risco , Negro ou Afro-Americano , Idoso , Hispânico ou Latino , Hospitais Urbanos/organização & administração , Humanos , Cidade de Nova Iorque , Obesidade Mórbida/etnologia , Obesidade Mórbida/psicologia , Avaliação de Programas e Projetos de Saúde , Redução de PesoRESUMO
Trisomy 21 [Down's syndrome (DS)] and mutations in transcription factor GATA1 predispose neonates to a transient myeloproliferative disorder (TMD) and/or acute megakaryocytic leukaemia (AMKL). The role of trisomy 21 in their pathogenesis is unclear. We previously reported two rare neonates without DS who had TMD, one of whom progressed to AMKL. Trisomy 21 was detected only in blood cells at presentation with TMD/AMKL and disappeared with disease resolution. We now show that the blood cells at presentation of TMD harboured GATA1 genomic DNA mutations, suggesting a requirement for trisomy 21 in haematopoietic cells, rather than other cell types, for development of TMD/AMKL.