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1.
PLoS One ; 16(2): e0246793, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33571300

RESUMEN

BACKGROUND: There is limited evidence on the clinical characteristics of SARS-CoV-2 infection in Latin America. We present findings from a nationwide study in Argentina. RESEARCH QUESTION: What is disease severity measures and risk factors are associated with admission to an intensive care unit and mortality? STUDY DESIGN AND METHODS: Data were extracted from the COVID-19 database of the Integrated Argentina Health Information System, encompassing the period of March 3rd to October 2nd, 2020, using a standardized case report form that included information on contact history, clinical signs and symptoms, and clinical diagnosis. Information was collected at the initial site of care and follow-up conducted through calls by the regional healthcare authorities. A confirmed case of COVID-19 was defined as having a positive result through sequencing or real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. RESULTS: RT-PCR testing was positive in 738,776 cases. Complete datasets were available for analysis in 207,079 cases. Mean age was 42.9±18.8 years, 50.0% were males. Frequent co-existing conditions included hypertension (19.2%), diabetes (9.7%), asthma (6.1%) and obesity (5.2%). Most common symptoms included fever (58.5%), cough (58.0%), headache (45.4%), and sore throat (42.1%). Death or ICU admission were independently associated with older age, male, coma, dyspnea or tachypnea, and seizures, with underlying co-morbidities such as immunodeficiency, chronic renal failure, and liver disease showing the strongest effects. INTERPRETATION: Most cases of COVID-19 diagnosed in Argentina were mild and had a favorable outcome, but fatality rates were relatively elevated. Risk factors for adverse outcome included older age, male sex, coma and seizures, and the concurrent presence of several morbidities. These data may be useful for healthcare providers and healthcare policy makers of low-middle income and Latin American countries to guide decisions toward optimized care during the pandemic.


Asunto(s)
/epidemiología , /fisiopatología , Adulto , Argentina/epidemiología , Asma/epidemiología , Asma/fisiopatología , Comorbilidad , Tos/epidemiología , Tos/fisiopatología , Diabetes Mellitus/epidemiología , Diabetes Mellitus/fisiopatología , Femenino , Fiebre/epidemiología , Fiebre/fisiopatología , Cefalea/epidemiología , Cefalea/fisiopatología , Humanos , Hipertensión/epidemiología , Hipertensión/fisiopatología , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto Joven
2.
Medicine (Baltimore) ; 100(4): e24200, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530212

RESUMEN

BACKGROUND: Diabetic peripheral neuropathy (DPN) is 1 of the most common clinical complications of diabetes, which seriously affects the quality of life of patients and causes a substantial economic burden on diabetes care. The pathogenesis of DPN is complex. There is no targeted treatment method, and mainstream treatment methods have low efficacy and large side effects. Traditional Chinese medicine has rich clinical experience in the prevention and treatment of diabetic peripheral neuropathy, which has dramatically improved the quality of life of patients. It is clinically proven that traditional Chinese medicine fumigants (TCMF) have apparent effects in treating diabetic peripheral neuropathy. Therefore, we aim to systematically review the effectiveness and safety of TCMF for DPN. METHODS: We will search the following databases: PubMed, Embase, Cochrane Library, MEDLINE, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, Cqvip Database, and Wanfang Data. Besides, we will also search for clinical trial registrations, potential grey literature, relevant conference abstracts, and reference lists of established studies. The studies published from the inception of the database to November 2020 will be retrieved. The randomized controlled trials on TCMF for DPN will be included. Also, we will search for clinical trial registrations, potential grey literature, relevant conference abstracts, and reference lists of established studies. The main result is clinical efficacy and nerve conduction velocity. Fasting blood glucose, 2 hours postprandial blood glucose, blood lipid, glycosylated hemoglobin, and adverse events are secondary results. We will perform the analyses using RevMan V.5.3 software. RESULTS: This study will provide a high-quality comprehensive evaluation of the efficacy and safety of TCMF in the treatment of DPN. CONCLUSIONS: This systematic review will evaluate the effectiveness and safety of TCMF in the treatment of DPN, and provide the latest evidence for clinical application. INPLASY REGISTRATION NUMBER: INPLASY2020110137.


Asunto(s)
Neuropatías Diabéticas/terapia , Fumigación/métodos , Medicina China Tradicional/métodos , Enfermedades del Sistema Nervioso Periférico/terapia , Glucemia/análisis , Diabetes Mellitus/sangre , Diabetes Mellitus/fisiopatología , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/etiología , Hemoglobina A Glucada/análisis , Humanos , Metaanálisis como Asunto , Conducción Nerviosa , Enfermedades del Sistema Nervioso Periférico/sangre , Enfermedades del Sistema Nervioso Periférico/etiología , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento
3.
BMC Pregnancy Childbirth ; 21(1): 97, 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-33516185

RESUMEN

BACKGROUND: Maternal mortality is a public health issue, particularly in low- and middle-income countries (LMIC). Sub-Saharan Africa (SSA) is the region most affected worldwide by maternal mortality, and preeclampsia is one of the main causes. We performed a systematic review of observational studies to identify the impact of cardiovascular risk factors on preeclampsia in SSA with a more representative sample. METHODS: Databases: PubMed and Google Scholar were searched to identify published studies. Studies were included if they reported results on the link between at least one cardiovascular risk factor and preeclampsia. Relevant studies quality was assessed with the Newcastle-Ottawa Scale (NOS). Odds ratios and relative risk (RR) were reported with their confidence intervals. RESULTS: Twelve articles (8 case-controls, 3 cohorts, 1 cross-sectional) were included in this review, with a total of 24,369 pregnant women. Cardiovascular risk factors such as chronic hypertension, overweight, obesity, diabetes and alcohol were significantly associated with a high risk of preeclampsia. Very few data were available concerning some risk factors. None of the articles reported tobacco consumption as a preeclampsia risk factor. There is a lack of data from French-speaking SSA countries. CONCLUSION: Cardiovascular risk factors increase the risk of preeclampsia. Our results suggest the need for prospective cohort studies to ascertain this association in order to reduce maternal mortality due to preeclampsia.


Asunto(s)
Diabetes Mellitus/fisiopatología , Hipertensión/fisiopatología , Obesidad/fisiopatología , Sobrepeso/fisiopatología , Preeclampsia/epidemiología , África del Sur del Sahara/epidemiología , Femenino , Humanos , Mortalidad Materna/tendencias , Estudios Observacionales como Asunto , Embarazo
4.
Metabolism ; 116: 154702, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33417895

RESUMEN

N6-methyladenosine (m6A) mRNA methylation has been shown to regulate obesity and type 2 diabetes. However, whether METTL3, the key methyltransferase for m6A mRNA methylation, regulates ß-cell failure in diabetes has not been fully explored. Here, we show that METTL3 is downregulated under the inflammatory and oxidative stress conditions, and islet ß-cell-specific deletion of Mettl3 induces ß-cell failure and hyperglycemia, which is likely due to decreased m6A modification and reduced expression of insulin secretion-related genes. Overall, METTL3 might be a potential drug target for the treatment of ß-cell failure in diabetes.


Asunto(s)
Diabetes Mellitus/genética , Células Secretoras de Insulina/fisiología , Metiltransferasas/fisiología , Animales , Diabetes Mellitus/patología , Diabetes Mellitus/fisiopatología , Islotes Pancreáticos/fisiología , Islotes Pancreáticos/fisiopatología , Metiltransferasas/genética , Ratones , Ratones Noqueados , Enfermedades Pancreáticas/genética , Enfermedades Pancreáticas/patología , Enfermedades Pancreáticas/fisiopatología
5.
Life Sci ; 267: 118881, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33310037

RESUMEN

AIMS: To explore the mechanisms of diabetes mellitus (DM)-induced testicular injury caused by modulation of testicular glycolysis and gut microbiota (GM), and evaluation of the efficacy of catalpol in reversing testicular morbidity. MAIN METHODS: A model of DM-induced testicular injury was established using a high-fat diet in KK-Ay mice. Microbial communities in the feces of mice in normal, model and catalpol (Cat) groups were analyzed by 16S gene sequencing. Correlations between the GM and lactate metabolism levels, lactate dehydrogenase activity, and indicators of testicular injury were analyzed. KEY FINDINGS: Cat significantly reduced general indicators of diabetes in mice with DM-induced reproductive injury, mitigated damage to the testicular tissue, and increased sperm count and motility. Additionally, the levels of products of glycolysis metabolism (e.g. lactate) increased following Cat treatment compared with the Model group. Disorders in the GM were also reversed in the Cat group. SIGNIFICANCE: Cat ameliorated DM-induced testicular injury in KK-Ay mice by increasing the energy available to germ cells through glycolysis, principally through modulation of the GM and a reduction in the quantities of associated pathogenic bacteria.


Asunto(s)
Microbioma Gastrointestinal/efectos de los fármacos , Glucósidos Iridoides/farmacología , Enfermedades Testiculares/metabolismo , Animales , Complicaciones de la Diabetes/fisiopatología , Diabetes Mellitus/fisiopatología , Modelos Animales de Enfermedad , Heces/microbiología , Microbioma Gastrointestinal/fisiología , Glucósidos Iridoides/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Espermatozoides/metabolismo , Enfermedades Testiculares/tratamiento farmacológico , Testículo/metabolismo
6.
Arch Biochem Biophys ; 698: 108743, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33382998

RESUMEN

Hyperglycaemia causes pancreatic ß-cells to release insulin that then attaches to a specific expression of receptor isoform and reverses high glucose concentrations. It is well known that insulin is capable of initiating insulin-receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling pathways in target cells; such as liver, adipose tissues, and muscles. However, recent discoveries indicate that many other pathways, such as the Hedgehog (Hh) and growth factor-stimulating Wingless-related integration (Wnt) signaling pathways; are activated in hyperglycaemia as well. Although these two pathways are traditionally thought to have a decisive role in cellular growth and differentiation only, recent reports show that they are involved in regulating cellular homeostasis and energy balance. While insulin-activated IRS/PI3K/PKB pathway cascades are primarily known to reduce glucose production, it was recently discovered to increase the Hh signaling pathway's stability, thereby activating the PI3K/PKB/mammalian target of rapamycin complex 2 (mTORC2) signaling pathway. The Hh signaling pathway not only plays a role in lipid metabolism, insulin sensitivity, inflammatory response, diabetes-related complications, but crosstalks with the Wnt signaling pathway resulting in improved insulin sensitivity and decrease inflammatory response in diabetes.


Asunto(s)
Diabetes Mellitus/fisiopatología , Proteínas Hedgehog/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Wnt/metabolismo , Vía de Señalización Wnt/fisiología , Animales , Línea Celular , Complicaciones de la Diabetes/fisiopatología , Humanos
7.
Front Public Health ; 8: 593256, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33330336

RESUMEN

Objectives: We aimed to describe the epidemiological and clinical characteristics of patients with COVID-19 in Saudi Arabia in various severity groups. Methods: Data for 485 patients were extracted from the medical records from the infectious disease center of Prince Mohammed bin Abdul Aziz Hospital in Riyadh. Patients' basic information, laboratory test results, signs and symptoms, medication prescribed, other comorbidities, and outcome data were collected and analyzed. Descriptive data were reported to examine the distribution of study variables between the severe and not severe groups. Results: Of 458 included patients, 411 (89.7%) were classified as not severe, 47 (10.3%) as severe. Most (59.1%) patients were aged between 20 and 39 years. Patients with severe conditions were non-Saudi, with a chronic condition history, and tended to have more chronic conditions compared with those without severe disease. Diabetes, hypertension, and thyroid disease were significantly higher in patients with severe disease. Death was reported in only 4.26% of severe patients. Only 16 (34.04%) patients remained in the hospital in the severe group. Conclusions: Severe cases were more likely to have more comorbidities, diabetes, hypertension, and thyroid disorders were most common compared with non-severe cases.


Asunto(s)
/epidemiología , Comorbilidad , Diabetes Mellitus/fisiopatología , Hipertensión/fisiopatología , Índice de Severidad de la Enfermedad , Enfermedades de la Tiroides/fisiopatología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios Transversales , Diabetes Mellitus/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Arabia Saudita/epidemiología , Enfermedades de la Tiroides/epidemiología , Adulto Joven
8.
Pan Afr Med J ; 35(Suppl 2): 139, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33193954

RESUMEN

Thiamine-responsive megaloblastic anaemia (TRMA) is a syndrome associated with megaloblastic anaemia, diabetes mellitus and sensorineural deafness, due to mutations in the SLC19A2gene, which codes for a thiamine carrier protein. Oral thiamine supplementation is the main treatment. We report the case of a 19-year-old man known for TRMA, who presented in the emergency department with bicytopenia (haemoglobin 5,4 g/dL, thrombocytes 38×109/L) revealed by dyspnea and chest pain. Investigations excluded bleeding, hemolysis, coagulopathy and iron deficiencies. A recent infection and an acute coronary syndrome have also been eliminated. We later found out that thiamine treatment had been discontinued three months before, due to general confinement in Tunisia during the COVID-19 pandemic. Parenteral administration of 100 mg of thiamine daily resulted in the recovery of haematopoiesis within three weeks.


Asunto(s)
Anemia Megaloblástica/sangre , Betacoronavirus , Infecciones por Coronavirus/epidemiología , Diabetes Mellitus/sangre , Pérdida Auditiva Sensorineural/sangre , Pandemias , Neumonía Viral/epidemiología , Deficiencia de Tiamina/congénito , Trombocitopenia/etiología , Síndrome Coronario Agudo/diagnóstico , Anemia Megaloblástica/tratamiento farmacológico , Anemia Megaloblástica/fisiopatología , Dolor en el Pecho/etiología , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/fisiopatología , Diagnóstico Diferencial , Hemoglobina A Glucada/análisis , Accesibilidad a los Servicios de Salud , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Sensorineural/fisiopatología , Hemoglobinas/análisis , Humanos , Masculino , Derrame Pericárdico/diagnóstico por imagen , Derrame Pericárdico/etiología , Recurrencia , Tiamina/provisión & distribución , Tiamina/uso terapéutico , Deficiencia de Tiamina/sangre , Deficiencia de Tiamina/tratamiento farmacológico , Deficiencia de Tiamina/fisiopatología , Túnez , Adulto Joven
9.
Clin Sci (Lond) ; 134(21): 2791-2805, 2020 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-33135725

RESUMEN

Angiotensin-converting enzyme II (ACE2) is a homologue of angiotensin-converting enzyme discovered in 2000. From the initial discovery, it was recognized that the kidneys were organs very rich on ACE2. Subsequent studies demonstrated the precise localization of ACE2 within the kidney and the importance of this enzyme in the metabolism of Angiotensin II and the formation of Angiotensin 1-7. With the recognition early in 2020 of ACE2 being the main receptor of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), the interest in this protein has dramatically increased. In this review, we will focus on kidney ACE2; its localization, its alterations in hypertension, diabetes, the effect of ACE inhibitors and angiotensin type 1 receptor blockers (ARBs) on ACE2 and the potential use of ACE2 recombinant proteins therapeutically for kidney disease. We also describe the emerging kidney manifestations of COVID-19, namely the frequent development of acute kidney injury. The possibility that binding of SARS-CoV-2 to kidney ACE2 plays a role in the kidney manifestations is also briefly discussed.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/enzimología , Enfermedades Renales/enzimología , Riñón/enzimología , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/enzimología , Receptores Virales/metabolismo , Lesión Renal Aguda/enzimología , Lesión Renal Aguda/virología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Diabetes Mellitus/enzimología , Diabetes Mellitus/fisiopatología , Historia del Siglo XXI , Interacciones Huésped-Patógeno , Humanos , Hipertensión/enzimología , Hipertensión/fisiopatología , Riñón/fisiopatología , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/fisiopatología , Pandemias , Peptidil-Dipeptidasa A/historia , Peptidil-Dipeptidasa A/uso terapéutico , Neumonía Viral/virología , Receptores Virales/historia
10.
Brasília; CONITEC; nov. 2020.
No convencional en Portugués | BRISA/RedTESA | ID: biblio-1145484

RESUMEN

INTRODUÇÃO: A síndrome coronariana aguda (SCA) é um termo abrangente para: infarto agudo do miocárdio (IAM) com supradesnivelamento do segmento ST, IAM sem supradesnivelamento do segmento ST e angina instável (1,2). A incidência é muito variável entre diferentes países e regiões do mundo (3­8). De acordo com a Organização Mundial da Saúde, doenças isquêmicas do coração foram responsáveis por 12% das mortes observadas em países de média e baixa renda, e aproximadamente 16% das mortes em países da alta renda em 2008 (9). Em particular, pacientes com diabetes mellitus (DM) possuem maior potencial pró-trombótico (3,4) e consequente maior potencial de beneficiarem-se de antiagregantes plaquetários (aspirina, clopidogrel) após uma angioplastia. O prasugrel é um anti-agregante plaquetário da mesma classe do clopidogrel, hoje incorporado ao SUS, e do ticagrelor, cuja incorporação foi rejeitada pela CONITEC. PERGUNTA: O prasugrel é eficaz, seguro e custo-efetivo em relação ao clopidogrel para a redução de eventos cardiovasculares em pacientes com síndrome coronariana aguda (SCA) e diabetes mellitus (DM) que realizaram angioplastia? EVIDÊNCIAS CIENTÍFICAS: Um único ensaio clínico randomizado (TRITON TIMI 38) avaliou prasugrel versus clopidogrel, 23% dos participantes eram diabéticos. Estudo patrocinado pelo demandante. Baixo risco de viés. A análise em pacientes diabéticos é baseada em uma análise de subgrupo. A qualidade da evidência é limitada pois não houve randomização para diabéticos e o estudo não foi controlado para o tipo e gravidade da doença. Ainda, a interação para diabetes não foi significativa (P = 0,09), ou seja, a análise deste subgrupo como um grupo independente não é adequada. A razão de chances, que no estudo pivotal era de 0,76 para redução de infarto foi recalculada para 0,60 no subgrupo de diabéticos. Analisando os resultados do subgrupo de pacientes diabéticos para o desfecho primário composto de morte cardiovascular, infarto e AVC, foram observados eventos em 17,0% no grupo clopidogrel e 12,2% no grupo prasugrel (HR=0,70; IC 0,58 - 0,85). Para morte cardiovascular, 4,2% no grupo clopidogrel e 3,4% no grupo prasugrel (HR=0,85; IC 0,58 - 1,24); IAM não fatal: 13,2% no grupo clopidogrel e 8,2% no grupo prasugrel (HR=0,60; IC 0,48 - 0,76); Trombose de stent: 3,6% no grupo clopidogrel e 2,0% no grupo prasugrel (HR=0,52; IC 0,33 - 0,84). O prasugrel apresentou maior risco de sangramentos não relacionada à cirurgia de revascularização miocárdica: 4,3% no grupo clopidogrel e 5,3% no grupo prasugrel (HR=1,30; IC 0,92 - 1,82). AVALIAÇÃO ECONÔMICA: A avaliação econômica do prasugrel apresentada pelo demandante baseou-se nos resultados do estudo pivotal e em um modelo de custo-efetividade e custo-utilidade utilizado previamente no NICE. Como resultados, prasugrel demonstrou-se ser mais efetivo e com maior custo em relação ao clopidogrel, apresentando uma razão de custo-utilidade incremental (RCEI) de R$ 9.325,00 mil/QALY. O modelo foi refeito pelo parecerista externo, obtendo um novo valor de RCEI de R$ 12.324,53/QALY e com 100% das simulações com valor igual ou inferior a R$ 15.591,13/QALY. RECOMENDAÇÃO PRELIMINAR DA CONITEC: A Conitec, em sua 89ª reunião ordinária, no dia 06 de agosto de 2020, recomendou a não incorporação no SUS de prasugrel para tratamento de pacientes diabéticos com síndrome coronariana aguda pós angioplastia. A recomendação levou em consideração que a população alvo foi mal definida, gerando incertezas no impacto orçamentário e na proposta de redução de preços. A operacionalização da proposta de redução de preços necessita de esclarecimentos. RECOMENDAÇÃO PRELIMINAR DA CONITEC: A Conitec, em sua 89ª reunião ordinária, no dia 06 de agosto de 2020, recomendou a não incorporação no SUS de prasugrel para tratamento de pacientes diabéticos com síndrome coronariana aguda pós angioplastia. A recomendação levou em consideração que a população alvo foi mal definida, gerando incertezas no impacto orçamentário e na proposta de redução de preços. A operacionalização da proposta de redução de preços necessita de esclarecimentos. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da CONITEC presentes na 92ª reunião ordinária, no dia 05 de novembro de 2020, deliberaram por recomendar a não incorporação no SUS do cloridrato de prasugrel para pacientes diabéticos com síndrome coronariana aguda submetidos à angioplastia primária. Os membros presentes entenderam que o medicamento atenderia um subgrupo de pacientes específico e que ainda há incertezas quanto ao seu benefício e segurança. Foi assinado o Registro de Deliberação nº 573.


Asunto(s)
Humanos , Angioplastia/instrumentación , Diabetes Mellitus/fisiopatología , Síndrome Coronario Agudo/fisiopatología , Clorhidrato de Prasugrel/uso terapéutico , Evaluación de la Tecnología Biomédica , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio/economía
11.
Brasília; CONITEC; nov. 2020.
No convencional en Portugués | BRISA/RedTESA | ID: biblio-1145539

RESUMEN

CONTEXTO: O edema macular diabético (EMD) é a principal alteração responsável por perda irreversível de acuidade visual em pacientes com diabetes mellitus (DM) que desenvolveram retinopatia diabética (RD). O EMD é caracterizado por inchaço na região central do olho resultado da ruptura da barreira sanguínea-retiniana e do acúmulo de líquido nas camadas intrarretinianas da mácula. A prevenção primária do EMD é o manejo ideal da doença, considerando a associação direta da prevalência do diabetes e da RD. As estratégias de tratamento consistem inicialmente no controle sistêmico da glicemia, da hemoglobina glicada (HbA1c), de lipídeos séricos, da função renal, estabilização da pressão sanguínea e controle do índice de massa corporal, associado à prática de exercícios físicos e alimentação adequada. O estágio da doença é determinante para a escolha do método de tratamento e o sucesso do tratamento é avaliado pela acuidade visual, pelo estadiamento da classificação da RD e pela análise dos exames complementares. Atualmente a terapia considerada padrão-ouro no tratamento do EMD consiste no uso do fator de crescimento endotelial anti-vascular (antiVEGF), mas em caso de insucesso terapêutico o emprego de corticoides em forma de implantes de liberação controlada tem sido utilizado. Pergunta: O uso do implante biodegradável de dexametasona (Ozurdex®) é eficaz, seguro e custo-efetivo para o tratamento de pacientes adultos com EMD, que falham à terapia com agente anti-VEGF? Evidências científicas: Dez publicações (uma revisão sistemática, dois ensaios clínicos e sete estudos observacionais) foram apresentados no relatório. De acordo com a metanálise, de qualidade metodológica moderada, há um ganho de 20 letras na BCVA (melhor acuidade visual corrigida) de pacientes tratados com o implante biodegradável de dexametasona, após um seguimento médio de avaliação de seis meses. A maioria dos estudos observacionais apontam melhora da BCVA em relação ao baseline do estudo. Os ensaios clínicos apresentaram um risco de viés moderado e um deles descreveu os achados anatômicos do estudo MEAD, avaliando as principais alterações morfológicas em relação ao baseline da ESCR, volume macular, área de espessamento da retina, vazamento macular, perda capilar macular e gravidade da retinopatia diabética. O implante de dexametasona atrasou o tempo de início da progressão do EMD em ± 12 meses, o que ao final do estudo, reduziu a espessura do subcampo central da retina (ESCR) em média 117,3 e 127,8 m nos grupos tratados com dexametasona versus 62,1 m nos olhos tratados com simulação (tratamentos p <0,001 vs, simulação). Entre os desfechos secundários avaliados estão: aumento da PIO, alterações da EFC, ESC e EMC, além de alterações do grau de retinopatia diabética. Os principais eventos adversos relatados em pacientes sob tratamento foram: descolamento de retina, inflamação da câmara anterior; dor ocular; queratite ou opacidade vítrea; e insurgência da catarata. AVALIAÇÃO ECONÔMICA: Foi conduzido um estudo de custo-efetividade e análises de sensibilidade univariada e probabilística. O tratamento com o implante biodegradável de dexametasona foi comparado com um procedimento simulado, ou não tratamento, num horizonte temporal de três anos. Para a indicação proposta, a incorporação da dexametasona resultaria em uma razão de custo-efetividade incremental (RCEI) estimada de R$ 54.568,99 por paciente e inclui custos de aquisição do medicamento, de administração, além de custos com visitas e de avaliação de eventos adversos. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Dois cenários foram avaliados para estimar o impacto orçamentário (AIO) da incorporação da dexametasona. O cenário base foi representado por um impacto total de R$ 1,76 bilhões em uma estimativa epidemiológica e um total de R$ 159,61 milhões em uma estimativa por demanda aferida, enquanto o cenário por protocolo foi representado por uma economia acumulada total de R$ 39,11 milhões em uma estimativa epidemiológica e R$ 3,50 milhões em uma estimativa por demanda aferida, ambos os cenários em um horizonte temporal de 5 anos. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foi detectada uma tecnologia, a fluocinolona acetonida, também um corticoide cuja via de administração é a mesma do implante biodegradável de dexametasona. Os estudos sobre a tecnologia atualmente estão em fase 4. Além disso, foi detectado no horizonte o medicamento aganirsen, um oligonucleotídeo, inibidor do gene IRS1, que está em fase 2 de pesquisa clínica para a indicação. Considerações: A evidência disponível é baseada em estudos clínicos randomizados e estudos observacionais que comparam o período pré-dexametasona e pós-dexametasona. Comparada ao procedimento simulado a dexametasona demonstrou melhora dos desfechos observados (BCVA, EFC, PIO, ESC, EMC, morfologia da retina, alterações no grau de RD e segurança), no entanto, a qualidade das evidências foi considerada baixa. Limitações importantes também foram identificadas na ACE e na AIO, indicando provável superestimação dos valores no âmbito no SUS. DECISÃO PRELIMINAR da Conitec: Diante do exposto, a Conitec, em sua 89ª reunião ordinária, realizada no dia 05 de agosto de 2020, deliberou que a matéria fosse disponibilizada em consulta pública com recomendação preliminar desfavorável à incorporação no SUS do implante biodegradável de dexametasona para tratamento de pacientes com edema macular diabético não responsivos à terapia prévia com anti-VEGF. Considerou-se que as evidências apresentadas são insuficientes para os desfechos analisados, visto baixo nível de certeza apresentado. Além disso, do ponto de vista econômico, o uso de parâmetro inadequado no modelo ocorreu por parte do demandante, pois a dexametasona tem indicação apenas para pacientes não responsivos à terapia prévia com antiangiogênicos, dessa forma não cabe a comparação dos custos com o medicamento aflibercepte, considerando que não são tecnologias substitutas. A matéria foi disponibilizada em consulta pública. CONSULTA PÚBLICA: A Consulta Pública nº 50/2020 foi realizada entre os dias 15/09/2020 a 05/10/2020. Foram recebidas 400 contribuições, sendo 152 pelo formulário para contribuições técnico-científicas e 248 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Dentre as 152 contribuições técnico-científicas, apenas 05 foram analisadas, pois 147 se tratavam de duplicatas, contribuições em branco, desprovidas de teor científico ou que tratavam de experiência ou opinião. As 05 contribuições consideradas para análise discordaram da recomendação preliminar da Conitec, tendo como justificativas: rápida resposta terapêutica da tecnologia, melhor responsividade em comparação à terapia com antiVEGF, bons resultados clínicos em casos de oclusões vasculares, olhos fácicos e uveítes inflamatórias, opção terapêutica em caso de contraindicação aos anti-VEGF ou dificuldade de seguimento. Dentre as 248 contribuições de experiência ou opinião recebidas, apenas 123 foram analisadas, pois 125 se tratavam de duplicatas ou contribuições em branco. Dentre as 123 analisadas, 105 discordaram da recomendação preliminar da Conitec, tendo como argumentações: o implante de dexametasona se trata de única terapia corticoide pós falha terapêutica aos anti-VEGF, pois o aumento de citocinas, em alguns casos, só são controladas pelo corticoide; o implante ser menos oneroso que o custo social quando há perda irreversível de visão dos pacientes; e restrição de uso, no SUS, de um medicamento já disponível no rol de procedimentos da Agência Nacional de Saúde Suplementar (ANS). O demandante e fabricante da tecnologia enviou nova proposta de preço para incorporação com 25% de desconto, junto à nova análise de custo-efetividade e impacto orçamentário, que foram apresentados aos membros do plenário. Além desta, outras contribuições analisadas foram importantes para a complementação do relatório, especialmente por trazer as expectativas de adesão ao procedimento, por profissionais e pacientes. RECOMENDAÇÃO FINAL: Os membros do plenário presentes na 92ª reunião ordinária da Conitec, no dia 04 de novembro de 2020, deliberaram, por unanimidade, recomendar a não incorporação, no SUS, do implante biodegradável de dexametasona para tratamento de pacientes com edema macular diabético não responsivos à terapia prévia com antiVEGF. Foi considerado que ainda há alguns aspectos não esclarecidos sobre a prática clínica no cuidado do EMD, como o limiar de ineficácia ou insucesso terapêutico com anti-VEGF e que faltam evidências científicas que indiquem se a tecnologia avaliada seria substitutiva para os anti-VEGF ou se deveria ser criada uma segunda linha para o cuidado do EMD. Reiterou-se que as evidências avaliadas no relatório técnico não foram consideradas robustas o suficiente para a tomada de decisão em favor da incorporação do implante biodegradavel de dexametasona em casos de ineficácia terapêutica com anti-VEGF, que foi a proposta apresentada pelo demandante. Ademais, não foram adicionadas na CP referências que alterassem a análise das evidências apresentadas no relatório preliminar. Foi assinado o Registro de Deliberação nº 570/2020. DECISÃO: Não incorporar o implante biodegradável de dexametasona no tratamento do edema macular diabético em pacientes não responsivos à terapia prévia com anti-VEGF, no âmbito do Sistema Único de Saúde - SUS, conforme Portaria nº 58, publicada no Diário Oficial da União nº 228, seção 1, página 716, em 1º de dezembro de 2020.


Asunto(s)
Humanos , Dexametasona/uso terapéutico , Edema Macular/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Diabetes Mellitus/fisiopatología , Evaluación de la Tecnología Biomédica , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio/economía
12.
Diabetes Metab J ; 44(5): 737-746, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33115212

RESUMEN

Background: Inconsistent results have been observed regarding the independent effect of diabetes on the severity of coronavirus disease 2019 (COVID-19). We conducted a nationwide population-based cohort study to evaluate the relationship between diabetes and COVID-19 severity in South Korea. METHODS: Patients with laboratory-confirmed COVID-19 aged ≥30 years were enrolled and medical claims data were obtained from the Korean Health Insurance Review and Assessment Service. Hospitalization, oxygen treatment, ventilator application, and mortality were assessed as severity outcomes. Multivariate logistic regression analyses were performed after adjusting for age, sex, and comorbidities. RESULTS: Of 5,307 COVID-19 patients, the mean age was 56.0±14.4 years, 2,043 (38.5%) were male, and 770 (14.5%) had diabetes. The number of patients who were hospitalized, who received oxygen, who required ventilator support, and who died was 4,986 (94.0%), 884 (16.7%), 121 (2.3%), and 211 (4.0%), respectively. The proportion of patients with diabetes in the abovementioned outcome groups was 14.7%, 28.1%, 41.3%, 44.6%, showing an increasing trend according to outcome severity. In multivariate analyses, diabetes was associated with worse outcomes, with an adjusted odds ratio (aOR) of 1.349 (95% confidence interval [CI], 1.099 to 1.656; P=0.004) for oxygen treatment, an aOR of 1.930 (95% CI, 1.276 to 2.915; P<0.001) for ventilator use, and an aOR of 2.659 (95% CI, 1.896 to 3.729; P<0.001) for mortality. CONCLUSION: Diabetes was associated with worse clinical outcomes in Korean patients with COVID-19, independent of other comorbidities. Therefore, patients with diabetes and COVID-19 should be treated with caution.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/mortalidad , Diabetes Mellitus/fisiopatología , Hospitalización/estadística & datos numéricos , Neumonía Viral/epidemiología , Neumonía Viral/mortalidad , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Comorbilidad , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/patología , Neumonía Viral/virología , Pronóstico , República de Corea/epidemiología , Tasa de Supervivencia , Factores de Tiempo
13.
Front Endocrinol (Lausanne) ; 11: 582870, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33042029

RESUMEN

The pandemic of COVID-19, caused by the coronavirus, SARS-CoV-2, has had a global impact not seen for an infectious disease for over a century. This acute pandemic has spread from the East and has been overlaid onto a slow pandemic of metabolic diseases of obesity and diabetes consequent from the increasing adoption of a Western-lifestyle characterized by excess calorie consumption with limited physical activity. It has become clear that these conditions predispose individuals to a more severe COVID-19 with increased morbidity and mortality. There are many features of diabetes and obesity that may accentuate the clinical response to SARS-CoV-2 infection: including an impaired immune response, an atherothrombotic state, accumulation of advanced glycation end products and a chronic inflammatory state. These could prime an exaggerated cytokine response to viral infection, predisposing to the cytokine storm that triggers progression to septic shock, acute respiratory distress syndrome, and multi-organ failure. Infection leads to an inflammatory response and tissue damage resulting in increased metabolic activity and an associated increase in the mechanisms by which cells ingest and degrade tissue debris and foreign materials. It is becoming clear that viruses have acquired an ability to exploit these mechanisms to invade cells and facilitate their own life-cycle. In obesity and diabetes these mechanisms are chronically activated due to the deteriorating metabolic state and this may provide an increased opportunity for a more profound and sustained viral infection.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Diabetes Mellitus/fisiopatología , Estilo de Vida , Obesidad/fisiopatología , Neumonía Viral/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Susceptibilidad a Enfermedades , Humanos , Pandemias , Neumonía Viral/inmunología , Neumonía Viral/virología
14.
PLoS One ; 15(10): e0240394, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33031467

RESUMEN

BACKGROUND: The SARS-CoV-2 pandemic compounds Mexico's pre-existing challenges: very high levels of both non-communicable diseases (NCD) and social inequity. METHODS AND FINDINGS: Using data from national reporting of SARS-CoV-2 tested individuals, we estimated odds of hospitalization, intubation, and death based on pre-existing non-communicable diseases and socioeconomic indicators. We found that obesity, diabetes, and hypertension are positively associated with the three outcomes in a synergistic manner. The municipal poverty level is also positively associated with hospitalization and death. CONCLUSIONS: Mexico's response to COVID-19 is complicated by a synergistic double challenge: raging NCDs and extreme social inequity. The response to the current pandemic must take both into account both to be effective and to ensure that the burden of COVID-19 not falls disproportionately on those who are already disadvantaged.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Adulto , Factores de Edad , Betacoronavirus/fisiología , Comorbilidad , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/terapia , Complicaciones de la Diabetes , Diabetes Mellitus/fisiopatología , Femenino , Hospitalización , Humanos , Hipertensión/fisiopatología , Intubación , Masculino , México/epidemiología , Persona de Mediana Edad , Obesidad/fisiopatología , Pandemias , Neumonía Viral/fisiopatología , Neumonía Viral/terapia , Pobreza , Factores Sexuales , Factores Socioeconómicos
15.
Front Endocrinol (Lausanne) ; 11: 583006, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33101215

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its clinical manifestation (COVID-19; coronavirus disease 2019) have caused a worldwide health crisis. Disruption of epithelial and endothelial barriers is a key clinical turning point that differentiates patients who are likely to develop severe COVID-19 outcomes: it marks a significant escalation in respiratory symptoms, loss of viral containment and a progression toward multi-organ dysfunction. These barrier mechanisms are independently compromised by known COVID-19 risk factors, including diabetes, obesity and aging: thus, a synergism between these underlying conditions and SARS-CoV-2 mechanisms may explain why these risk factors correlate with more severe outcomes. This review examines the key cellular mechanisms that SARS-CoV-2 and its underlying risk factors utilize to disrupt barrier function. As an outlook, we propose that glucagon-like peptide 1 (GLP-1) may be a therapeutic intervention that can slow COVID-19 progression and improve clinical outcome following SARS-CoV-2 infection. GLP-1 signaling activates barrier-promoting processes that directly oppose the pro-inflammatory mechanisms commandeered by SARS-CoV-2 and its underlying risk factors.


Asunto(s)
Envejecimiento/patología , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Diabetes Mellitus/fisiopatología , Péptido 1 Similar al Glucagón/metabolismo , Inflamación/fisiopatología , Obesidad/fisiopatología , Neumonía Viral/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/inmunología , Neumonía Viral/metabolismo , Neumonía Viral/virología
16.
Pan Afr Med J ; 36: 158, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32874422

RESUMEN

Diabetes mellitus is a non-infectious disease and has affected about 425 million adults globally and nearly 15.9 million of them reside in Africa. Moreover, the prevalence of undiagnosed diabetes mellitus is very high in Africa and approximates to around 62%. Nearly 75% of the total deaths due to diabetes are in individuals lesser than 60 years of age. The multifaceted disease of diabetes mellitus produces chronic complications such as, neuropathy, nephropathy, retinopathy, microangiopathy etc. These patients of diabetes mellitus are more susceptible to infections due to compromised immune system. Hence these patients of diabetes mellitus and undiagnosed diabetes mellitus are at greater risk of contracting COVID-19 infections. The dual impact of pathophysiology of COVID-19 infections in diabetes mellitus may increase morbidity and mortality in these patients. Hence there is need of health awareness in diabetics as well in the high-risk group for diabetes such as persons with hypertension and obesity. The scarcity of health resources, shortage of trained medical personnel and disease burden of infectious and non-infectious diseases has laid a heavy impact on the economy in Africa and this has been further strained due to the COVID-19 pandemic. The practice of preventive measures by the risk group of Undiagnosed Diabetes Mellitus patients will prevent them from getting infected by COVID-19 and at the same time decrease mortality rates and hence the undiscovered group that is the patients of undiagnosed diabetes mellitus needs to be vigilant regarding safe preventive practices.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Complicaciones de la Diabetes/epidemiología , Diabetes Mellitus/epidemiología , Neumonía Viral/epidemiología , Adulto , África/epidemiología , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/fisiopatología , Complicaciones de la Diabetes/diagnóstico , Complicaciones de la Diabetes/fisiopatología , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/fisiopatología , Humanos , Pandemias , Neumonía Viral/mortalidad , Neumonía Viral/fisiopatología , Prevalencia , Factores de Riesgo
17.
Am J Physiol Renal Physiol ; 319(4): F712-F728, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32893663

RESUMEN

Inhibitors of proximal tubular Na+-glucose cotransporter 2 (SGLT2) are natriuretic, and they lower blood pressure. There are reports that the activities of SGLT2 and Na+-H+ exchanger 3 (NHE3) are coordinated. If so, then part of the natriuretic response to an SGLT2 inhibitor is mediated by suppressing NHE3. To examine this further, we compared the effects of an SGLT2 inhibitor, empagliflozin, on urine composition and systolic blood pressure (SBP) in nondiabetic mice with tubule-specific NHE3 knockdown (NHE3-ko) and wild-type (WT) littermates. A single dose of empagliflozin, titrated to cause minimal glucosuria, increased urinary excretion of Na+ and bicarbonate and raised urine pH in WT mice but not in NHE3-ko mice. Chronic empagliflozin treatment tended to lower SBP despite higher renal renin mRNA expression and lowered the ratio of SBP to renin mRNA, indicating volume loss. This effect of empagliflozin depended on tubular NHE3. In diabetic Akita mice, chronic empagliflozin enhanced phosphorylation of NHE3 (S552/S605), changes previously linked to lesser NHE3-mediated reabsorption. Chronic empagliflozin also increased expression of genes involved with renal gluconeogenesis, bicarbonate regeneration, and ammonium formation. While this could reflect compensatory responses to acidification of proximal tubular cells resulting from reduced NHE3 activity, these effects were at least in part independent of tubular NHE3 and potentially indicated metabolic adaptations to urinary glucose loss. Moreover, empagliflozin increased luminal α-ketoglutarate, which may serve to stimulate compensatory distal NaCl reabsorption, while cogenerated and excreted ammonium balances urine losses of this "potential bicarbonate." The data implicate NHE3 as a determinant of the natriuretic effect of empagliflozin.


Asunto(s)
Compuestos de Bencidrilo/farmacología , Diabetes Mellitus/tratamiento farmacológico , Glucósidos/farmacología , Túbulos Renales Proximales/efectos de los fármacos , Natriuresis/efectos de los fármacos , Natriuréticos/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Transportador 2 de Sodio-Glucosa/metabolismo , Intercambiador 3 de Sodio-Hidrógeno/metabolismo , Equilibrio Ácido-Base/efectos de los fármacos , Animales , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatología , Modelos Animales de Enfermedad , Glucosuria/metabolismo , Glucosuria/fisiopatología , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/fisiopatología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Fosforilación , Intercambiador 3 de Sodio-Hidrógeno/deficiencia , Intercambiador 3 de Sodio-Hidrógeno/genética
18.
Orv Hetil ; 161(38): 1637-1645, 2020 09.
Artículo en Húngaro | MEDLINE | ID: mdl-32924968

RESUMEN

INTRODUCTION: Intermittent claudication has a significant negative impact on the patients' quality of life. Revascularization procedures and noninvasive medical therapies can improve walking capacity. Cilostazol has IA recommendation for the treatment of intermittent claudication. AIM: The aim of this study was to evaluate the effect of a three-month cilostazol treatment on the health-related quality of life and on the lower-limb functional capacity in diabetic (DM) and non-diabetic patients (NDM) with intermittent claudication in the clinical practice. METHOD: The study was a multicenter, non-interventional trial; 812 patients with peripheral artery disease (Fontaine II stage, mean age: 67.17 years, male/female: 58.25/41.75%, 318 diabetics) were enrolled, who received cilostazol (50 or 100 mg twice a day) for 3 months. The quality of life was evaluated with the EQ-5D-3L questionnaire, the functional capacity with the WELCH questionnaire. Walking distances, ankle-brachial index were measured at baseline and after 3 months. RESULTS: Upon conclusion of the study, the EQ-5D index improved both in non-diabetic and diabetic patients (baseline: NDM -0.45 ± 0.22, DM -0.48 ± 0.23, 3rd month: -0,24 ± 0.18, -0,27 ± 0.19; respectively; p<0.0001) and there was a significant increase in the WELCH score as well (baseline: NDM 20 ± 14, DM 18 ± 14; 3rd month: 33 ± 19, 29 ± 16, respectively; p<0.0001). Both pain-free and maximal walking distance increased by 59.2% (median: 50.0%), 46.58 (median: 40.51%) in NDM and 42.85% (median: 43.33%), 41.61% (median: 34.68%) in DM patients, respectively (p<0.001). CONCLUSIONS: Three months of cilostazol treatment improved the quality of life and lower-limb functional capacity in diabetic and non-diabetic claudicant patients. The WELCH questionnaire is a useful tool in clinical practice for the evaluation of intermittent claudication treatment. Orv Hetil. 2020; 161(38): 1637-1645.


Asunto(s)
Cilostazol/uso terapéutico , Diabetes Mellitus/fisiopatología , Claudicación Intermitente/tratamiento farmacológico , Enfermedad Arterial Periférica/complicaciones , Calidad de Vida/psicología , Tetrazoles/uso terapéutico , Vasodilatadores/uso terapéutico , Anciano , Estudios de Casos y Controles , Complicaciones de la Diabetes , Femenino , Humanos , Claudicación Intermitente/psicología , Extremidad Inferior/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/tratamiento farmacológico , Resultado del Tratamiento , Caminata
19.
Fluids Barriers CNS ; 17(1): 55, 2020 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-32912226

RESUMEN

Human coronaviruses are highly pathogenic viruses that pose a serious threat to human health. Examples include the severe acute respiratory syndrome outbreak of 2003 (SARS-CoV-1), the Middle East Respiratory Syndrome (MERS-CoV) outbreak of 2012, and the current SARS-CoV-2 (COVID-19) pandemic. Herein, we review the neurological manifestations of coronaviruses and discuss the potential pathogenic role of blood-brain barrier dysfunction. We present the hypothesis that pre-existing vascular damage (due to aging, cardiovascular disease, diabetes, hypertension or other conditions) facilitates infiltration of the virus into the central nervous system (CNS), increasing neuro-inflammation and the likelihood of neurological symptoms. We also discuss the role of a neuroinflammatory cytokine profile in both blood-brain barrier dysfunction and macrovascular disease (e.g. ischemic stroke and thromboembolism). Future studies are needed to better understand the involvement of the microvasculature in coronavirus neuropathology, and to test the diagnostic potential of minimally-invasive screening tools (e.g. serum biomarkers, fluorescein retinal angiography and dynamic-contrast MRI).


Asunto(s)
Barrera Hematoencefálica/fisiopatología , Infecciones por Coronavirus/fisiopatología , Inflamación/fisiopatología , Microvasos/fisiopatología , Enfermedades del Sistema Nervioso/fisiopatología , Neumonía Viral/fisiopatología , Betacoronavirus , Barrera Hematoencefálica/inmunología , Barrera Hematoencefálica/virología , Enfermedades Cardiovasculares/fisiopatología , Infecciones por Coronavirus/inmunología , Citocinas/inmunología , Diabetes Mellitus/fisiopatología , Encefalitis/inmunología , Encefalitis/fisiopatología , Humanos , Inflamación/inmunología , Microvasos/inmunología , Enfermedades del Sistema Nervioso/inmunología , Pandemias , Neumonía Viral/inmunología , Convulsiones/inmunología , Convulsiones/fisiopatología , Accidente Cerebrovascular/inmunología , Accidente Cerebrovascular/fisiopatología , Tromboembolia/inmunología , Tromboembolia/fisiopatología
20.
Geriatr Gerontol Int ; 20(10): 980-987, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32886834

RESUMEN

AIMS: Sarcopenia is a serious problem because of its poor prognosis. Growth differentiation factor 15 (GDF15) is associated with mitochondrial dysfunction, inflammation, insulin resistance and oxidative stress, which may play crucial roles for the development of sarcopenia. We aimed to examine whether serum GDF15 level is associated with muscle mass, strength and lower extremity function in older patients with cardiometabolic disease. METHODS: Serum GDF15 levels were measured in 257 patients with cardiometabolic diseases (including 133 patients with diabetes) who had visited the frailty clinic, using a latex turbidimetric immunoassay. Appendicular skeletal muscle index, handgrip strength, timed-up-and-go test and gait speed were evaluated. Power, speed, balance and total scores based on the sit-to-stand test were calculated to assess lower extremity function. RESULTS: The highest tertile of serum GDF15 was independently associated with low handgrip strength, low gait speed, long timed-up-and-go time and scores of lower extremity function but not an appendicular skeletal muscle index in multiple logistic regression analyses after adjustment for covariates. Patients in the highest tertile of GDF15 were at the risk of having three to nine times lower grip strength, three times lower gait speed, five to six times lower mobility and five to 11 times reduction in lower extremity function as compared with those in the lowest GDF15 tertile dependent on the models. CONCLUSIONS: Elevated serum GDF15 level was independently associated with low muscle strength and lower extremity function in older patients with cardiometabolic disease. Serum GDF15 could be one of the biomarkers for muscle weakness and low physical performance. Geriatr Gerontol Int 2020; 20: 980-987.


Asunto(s)
Enfermedades Cardiovasculares/sangre , Diabetes Mellitus/sangre , Factor 15 de Diferenciación de Crecimiento/sangre , Extremidad Inferior/fisiopatología , Fuerza Muscular/fisiología , Sarcopenia/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedades Cardiovasculares/fisiopatología , Diabetes Mellitus/fisiopatología , Femenino , Fragilidad , Fuerza de la Mano , Humanos , Masculino , Músculo Esquelético/fisiopatología , Sarcopenia/fisiopatología , Estudios de Tiempo y Movimiento , Velocidad al Caminar/fisiología
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