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1.
Nat Med ; 28(9): 1813-1822, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36064599

RESUMO

Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3-5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation.


Assuntos
Esclerose Lateral Amiotrófica , Células-Tronco Neurais , Esclerose Lateral Amiotrófica/terapia , Animais , Modelos Animais de Doenças , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Humanos , Medula Espinal , Superóxido Dismutase
2.
J Alzheimers Dis ; 77(2): 459-504, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32925078

RESUMO

COVID-19 is a severe infectious disease that has claimed >150,000 lives and infected millions in the United States thus far, especially the elderly population. Emerging evidence has shown the virus to cause hemorrhagic and immunologic responses, which impact all organs, including lungs, kidneys, and the brain, as well as extremities. SARS-CoV-2 also affects patients', families', and society's mental health at large. There is growing evidence of re-infection in some patients. The goal of this paper is to provide a comprehensive review of SARS-CoV-2-induced disease, its mechanism of infection, diagnostics, therapeutics, and treatment strategies, while also focusing on less attended aspects by previous studies, including nutritional support, psychological, and rehabilitation of the pandemic and its management. We performed a systematic review of >1,000 articles and included 425 references from online databases, including, PubMed, Google Scholar, and California Baptist University's library. COVID-19 patients go through acute respiratory distress syndrome, cytokine storm, acute hypercoagulable state, and autonomic dysfunction, which must be managed by a multidisciplinary team including nursing, nutrition, and rehabilitation. The elderly population and those who are suffering from Alzheimer's disease and dementia related illnesses seem to be at the higher risk. There are 28 vaccines under development, and new treatment strategies/protocols are being investigated. The future management for COVID-19 should include B-cell and T-cell immunotherapy in combination with emerging prophylaxis. The mental health and illness aspect of COVID-19 are among the most important side effects of this pandemic which requires a national plan for prevention, diagnosis and treatment.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/psicologia , Infecções por Coronavirus/terapia , Humanos , Imunoterapia , Saúde Mental , Apoio Nutricional , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/psicologia , Pneumonia Viral/terapia , Tratamento Farmacológico da COVID-19
3.
Hosp Pract (1995) ; 37(1): 40-50, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20877170

RESUMO

BACKGROUND: Intensivists have been associated with decreased mortality in several studies, but in one major study, centers with intensivist-staffed units reported increased mortality compared with controls. We hypothesized that a closed unit, in which a unit-based intensivist directly provides and coordinates care on all cases, has improved mortality and utilization compared with an open unit, in which individual attendings and consultants provide care, while intensivists serve as supervising consultants. METHODS: We undertook the retrospective study of outcomes in 2 intensive care units (ICUs)-a traditional open unit managed by faculty intensivists and a second closed unit overseen by the same faculty intensivists who coordinated the care on all patients in a large community hospital. PRIMARY OUTCOME: In-hospital mortality. SECONDARY OUTCOMES: Hospital length of stay (LOS), ICU LOS, and relative costs of hospitalization. RESULTS: From January 2006 to December 2007, we identified 2602 consecutive admissions to the 2 medical ICUs. Of all patients admitted to the closed and open units, 19.2% and 24.7%, respectively, did not survive (P < 0.001, adjusted for severity). Median hospital LOS was 10 days for the closed unit and 12 days for the open unit (P < 0.001). Median ICU LOS was 2.2 days for the closed unit and 2.4 days for the open unit (P = NS). The unadjusted cost index for the open unit was 1.11 relative to the closed unit (1.0) (P < 0.001). However, after adjusting for disease severity, cost differences were not significantly different. CONCLUSIONS: We observed significant reductions in mortality and hospital LOS for patients initially admitted to a closed ICU versus an open unit. We did not observe a significant difference in ICU LOS or total cost after adjustment for severity.


Assuntos
Cuidados Críticos/organização & administração , Mortalidade Hospitalar , Médicos Hospitalares/organização & administração , Unidades de Terapia Intensiva/organização & administração , Tempo de Internação/estatística & dados numéricos , Avaliação de Processos e Resultados em Cuidados de Saúde , Equipe de Assistência ao Paciente/organização & administração , Centros Médicos Acadêmicos/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Custos de Cuidados de Saúde , Humanos , Pacientes Internados/estatística & dados numéricos , Unidades de Terapia Intensiva/economia , Masculino , Pessoa de Meia-Idade , Modelos Organizacionais , Estudos Retrospectivos , Índice de Gravidade de Doença , Estados Unidos
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