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1.
Actas dermo-sifiliogr. (Ed. impr.) ; 111(8): 629-638, oct. 2020.
Artigo em Espanhol | IBECS | ID: ibc-188364

RESUMO

BACKGROUND AND OBJECTIVES: Spain is in a situation of indefinite lockdown due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is delays in medical and surgical procedures for common diseases. The aim of this study was to model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma (SCC) and melanoma. MATERIAL AND METHODS: Multicenter, retrospective, observational cohort study. We constructed an exponential growth model for both SCC and melanoma to estimate tumor growth between patient-reported onset and surgical excision at different time points. RESULTS: Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter > 4 cm or thickness > 6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (> 6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five-and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months. CONCLUSIONS: In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect tosee to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays


ANTECEDENTES Y OBJETIVOS: La pandemia del coronavirus COVID-19 ha provocado un confinamiento indefinido. Una posible consecuencia de esta situación es un retraso en los procedimientos asistenciales de las patologías comunes. El objetivo de este estudio es estimar el hipotético impacto en la supervivencia que tendría el aumento del tamaño tanto para los carcinomas de células escamosas (CCE) como de los melanomas. MATERIAL Y MÉTODO: Estudio observacional retrospectivo de cohortes multicéntrico. Se desarrolló un modelo de crecimiento exponencial para cada tumor basado en el tiempo de evolución que refiere el paciente. RESULTADOS: Se incluyeron un total de 200 pacientes con CCEs localizados en la cabeza y el cuello y 1000 pacientes con melanoma cutáneo. Se calculó una curva de crecimiento exponencial para cada tumor y se estimó el tamaño del tumor tras 1, 2 y 3 mes tras el diagnóstico. En la muestra, los CCE mayores de 4 cm o > 6 mm de grosor (definidos como T3) pasaron de 83 (41.5%) en el grupo de estudio real a una estimación de 58,5%, 70,5% y 72% tras 1, 2 y 3 meses de retraso quirúrgico estimado. Se estimó una disminución de la supervivencia específica de enfermedad (SEE) de un 6,2%, 8,2% y 5,2% a los 2, 5 y 10 años, respectivamente, tras tres meses de retraso. Para los melanomas, los melanomas ultragruesos (> 6 mm) pasaron del 6,9% en el grupo de estudio al 21,9%, 30,2% y 30,2% tras 1,2 y 3 meses de demora. La SEE a los 5 y 10 años del grupo de estudio descendió un 14,4% en ambos tiempos. CONCLUSIONES: En ausencia de un adecuado diagnóstico y tratamiento de los pacientes con CCE y melanoma en la actual situación de confinamiento en España, podemos llegar a asistir a un considerable aumento de los casos de CCE y melanomas gruesos y de gran tamaño. Se deben fomentar los esfuerzos para promocionar la autoexploración y facilitar el acceso a los dermatólogos para no aumentar la demora de estos pacientes. Palabras clave: melanoma, pronóstico, diagnóstico precoz, carcinoma de células escamosas cutáneo, COVID-19, confinamiento


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Neoplasias de Células Escamosas/mortalidade , Melanoma/mortalidade , Neoplasias Cutâneas/mortalidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Betacoronavirus , Pandemias , Quarentena , Análise de Sobrevida , Estudos Retrospectivos , Estudos de Coortes
2.
Sci Rep ; 10(1): 16496, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020546

RESUMO

This study aimed to analyze aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio in COVID-19 patients. After exclusion, 567 inpatients were included in this study and separated into two groups according to their AST/ALT ratio on admission. Death was regarded as poor prognosis in this study. Of 567 patients, 200 (35.3%) had AST/ALT ≥ 1.38. Of the 200 patients, older age (median age 60 years), myalgia (64 [32%] cases), fatigue (91 [45.5%] cases), some comorbidities and outcomes were significantly different from patients with AST/ALT < 1.38. They also had worse chest computed tomography (CT) findings, laboratory results and severity scores. Levels of platelet count (OR 0.995, 95% CI [0.992-0.998]) and hemoglobin (OR 0.984, 95% CI [0.972-0.995]) were independently associated with AST/ALT ≥ 1.38 on admission. Furthermore, a high AST/ALT ratio on admission was an independent risk factor for poor prognosis (OR 99.9, 95% CI [2.1-4280.5]). In subsequent monitoring, both survivors and non-survivors showed decreased AST/ALT ratio during hospitalization. In conclusion, high AST/ALT ratio might be the indication of worse status and outcomes in COVID-19 patients.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Fadiga/epidemiologia , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Mialgia/epidemiologia , Pandemias , Admissão do Paciente/estatística & dados numéricos , Contagem de Plaquetas , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Análise de Sobrevida
3.
Artigo em Inglês | MEDLINE | ID: mdl-33027393

RESUMO

The Northeast of Brazil has experienced a triple epidemic, with the simultaneous circulation of dengue virus (DENV), chikungunya virus (CHIKV) and Zika virus (ZIKV), which may have contributed to the observed increase across this region of atypical forms of disease and deaths. In view of this fact, non-congenital neurological disorders related to arboviruses were compared with other etiologies, mortality and survival rates of patients admitted to referral neurology hospitals in Pernambuco State, Northeast Brazil, from 2015 to 2018. Blood and cerebrospinal fluid samples were collected and tested using molecular and serological assays. The arbovirus-exposed groups were compared with respect to epidemiological, clinical and neurologic characteristics by using the Pearson's chi-square test. For the survival analysis, the Kaplan-Meier and Hazard Ratio (HR) tests were used, with a 95% confidence interval (CI). Encephalitis and encephalomyelitis were more frequent in arboviruses, while myelitis predominated in the neurological disorders of other etiologies. Guillain-Barré Syndrome (GBS) was similarly distributed amongst the groups. Exposure to one of the arboviruses caused a six-fold increase in the risk of death (HR: 6.37; CI: 2.91 - 13.9). Amongst the arbovirus-exposed groups, infection (DENV/CHIKV) increased nine times the risk of death (HR: 9.07; CI: 3.67 - 22.4). The survival curve indicates that have been exposed to some arbovirus decreased the likelihood of survival compared to those with other etiologies (Log-Rank: p<0.001). Within this scenario, neurologic manifestations of DENV, CHIKV and ZIKV have the potential to increase mortality and decrease survival, and concomitant infection (DENV/CHIKV) is an aggravating factor in reducing the likelihood of survival when compared to monoinfections.


Assuntos
Febre de Chikungunya/diagnóstico , Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Encefalite Viral/epidemiologia , Encefalomielite/virologia , Doenças do Sistema Nervoso/virologia , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Adulto , Brasil , Febre de Chikungunya/complicações , Dengue/complicações , Encefalomielite/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Doenças do Sistema Nervoso/diagnóstico , Análise de Sobrevida , Infecção por Zika virus/complicações
4.
MMWR Morb Mortal Wkly Rep ; 69(41): 1481-1484, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33056954

RESUMO

Breast cancer among males in the United States is rare; approximately 2,300 new cases and 500 associated deaths were reported in 2017, accounting for approximately 1% of all breast cancers.* Risk for male breast cancer increases with increasing age (1), and compared with women, men receive diagnoses later in life and often at a later stage of disease (1). Gradual improvement in breast cancer survival from 1976-1985 to 1996-2005 has been more evident for women than for men (1). Studies examining survival differences among female breast cancer patients observed that non-Hispanic White (White) females had a higher survival than non-Hispanic Black (Black) females (2), but because of the rarity of breast cancer among males, few studies have examined survival differences by race or other factors such as age, stage, and geographic region. CDC's National Program of Cancer Registries (NPCR)† data were used to examine relative survival of males with breast cancer diagnosed during 2007-2016 by race/ethnicity, age group, stage at diagnosis, and U.S. Census region. Among males who received a diagnosis of breast cancer during 2007-2016, 1-year relative survival was 96.1%, and 5-year relative survival was 84.7%. Among characteristics examined, relative survival varied most by stage at diagnosis: the 5-year relative survival for males was higher for cancers diagnosed at localized stage (98.7%) than for those diagnosed at distant stage (25.9%). Evaluation of 1-year and 5-year relative survival among males with breast cancer might help guide health care decisions regarding early detection of male breast cancer and establishing programs to support men at high risk for breast cancer and male breast cancer survivors.


Assuntos
Neoplasias da Mama Masculina/mortalidade , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama Masculina/etnologia , Neoplasias da Mama Masculina/patologia , Grupos de Populações Continentais/estatística & dados numéricos , Grupos Étnicos/estatística & dados numéricos , Geografia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/estatística & dados numéricos , Análise de Sobrevida , Estados Unidos/epidemiologia
5.
MMWR Morb Mortal Wkly Rep ; 69(41): 1473-1480, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33056955

RESUMO

Among U.S. men, prostate cancer is the second leading cause of cancer-related death (1). Past studies documented decreasing incidence of prostate cancer overall since 2000 but increasing incidence of distant stage prostate cancer (i.e., signifying spread to parts of the body remote from the primary tumor) starting in 2010 (2,3). Past studies described disparities in prostate cancer survival by stage, age, and race/ethnicity using data covering ≤80% of the U.S. population (4,5). To provide recent data on incidence and survival of prostate cancer in the United States, CDC analyzed data from population-based cancer registries that contribute to U.S. Cancer Statistics (USCS).* Among 3.1 million new cases of prostate cancer recorded during 2003-2017, localized, regional, distant, and unknown stage prostate cancer accounted for 77%, 11%, 5%, and 7% of cases, respectively, but the incidence of distant stage prostate cancer significantly increased during 2010-2017. During 2001-2016, 10-year relative survival for localized stage prostate cancer was 100%. Overall, 5-year survival for distant stage prostate cancer improved from 28.7% during 2001-2005 to 32.3% during 2011-2016; for the period 2001-2016, 5-year survival was highest among Asian/Pacific Islanders (API) (42.0%), followed by Hispanics (37.2%), American Indian/Alaska Natives (AI/AN) (32.2%), Black men (31.6%), and White men (29.1%). Understanding incidence and survival differences by stage, race/ethnicity, and age can guide public health planning related to screening, treatment, and survivor care. Future research into differences by stage, race/ethnicity, and age could inform interventions aimed at improving disparities in outcomes.


Assuntos
Neoplasias da Próstata/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Grupos de Populações Continentais/estatística & dados numéricos , Grupos Étnicos/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/estatística & dados numéricos , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Análise de Sobrevida , Estados Unidos/epidemiologia
6.
Urol Clin North Am ; 47(4): 419-431, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008493

RESUMO

The management of metastatic renal cell carcinoma (RCC) has evolved rapidly in recent years with several immunotherapy-based combinations of strategies approved as first-line therapies. Targeted strategies, including systemic antiangiogenesis agents and immune checkpoint blockade, form the basis of a therapeutic approach. With rising rates of recurrence after first-line treatment, it is increasingly important to not only adopt a personalized treatment plan with minimal adverse events but also develop predictive biomarkers for response. This review discusses currently available first-line and second-line therapies in RCC and their pivotal data, with specific focus on ongoing clinical trials in the adjuvant setting, including those involving novel agents.


Assuntos
Produtos Biológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Imunoterapia/métodos , Neoplasias Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Quimioterapia Combinada , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Nefrectomia/métodos , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
7.
Urol Clin North Am ; 47(4): 443-456, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008495

RESUMO

Cancer vaccines, cytokines, and checkpoint inhibitors are immunotherapeutic agents that act within the cancer immunity cycle. Prostate cancer has provided unique opportunities for, and challenges to, immunotherapy drug development, including low tumor mutational burdens, limited expression of PD-L1, and minimal T-cell intratumoral infiltrates. Nevertheless, efforts are ongoing to help prime prostate tumors by turning a "cold" prostate cancer "hot" and thus rendering them more susceptible to immunotherapy. Combination treatments, use of molecular biomarkers, and use of new immunotherapeutic agents provide opportunities to enhance the immune response to prostate tumors.


Assuntos
Vacinas Anticâncer/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Idoso , Biomarcadores Tumorais/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/mortalidade , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
8.
Urol Clin North Am ; 47(4): 457-467, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008496

RESUMO

Biochemically recurrent prostate cancer represents a stage of prostate cancer where conventional (continued on next page) computed tomography and technetium Tc 99m bone scan imaging are unable to detect disease after curative intervention despite rising prostate-specific antigen. There is no clear standard of care and no systemic therapy has been shown to improve survival. Immunotherapy-based treatments potentially are attractive options relative to androgen deprivation therapy due to the generally more favorable side-effect profile. Biochemically recurrent prostate cancer patients have a low tumor burden and likely lymph node-based disease, which may make them more likely to respond to immunotherapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Imunoterapia/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/patologia , Idoso , Terapia Combinada , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Seleção de Pacientes , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Medição de Risco , Papel (figurativo) , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
9.
Urol Clin North Am ; 47(4): 469-474, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008497

RESUMO

Multiple immunologic platforms have provided minimal impact in patients with metastatic castration-resistant prostate cancer, necessitating that novel approaches continue to be developed. Although checkpoint inhibitors have been largely ineffective, there remain small cohorts of patients who have durable responses but lack the conventional indicators for response to this class of drugs, that is, high mutational burden or significant genomic alterations, as seen in other solid tumors. This article presents an update on the evolution of immunotherapeutics that target a more lethal form of prostate cancer and provides the groundwork for future considerations as to how this field should proceed.


Assuntos
Quinases Ciclina-Dependentes/genética , Regulação Neoplásica da Expressão Gênica , Imunoterapia/métodos , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/terapia , Idoso , Produtos Biológicos/uso terapêutico , Vacinas Anticâncer/administração & dosagem , Quinases Ciclina-Dependentes/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Fenótipo , Medicina de Precisão/métodos , Prognóstico , Neoplasias de Próstata Resistentes à Castração/patologia , Análise de Sobrevida , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos
10.
BMJ Open Respir Res ; 7(1)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33020114

RESUMO

INTRODUCTION: Smoking causes inflammation of the lung epithelium by releasing cytokines and impairing mucociliary clearance. Some studies have linked smoking with severity of illness of COVID-19 whereas others have found no such association. METHODS: This was a retrospective analysis of all adults hospitalised with COVID-19 from 9 March to 18 May 2020. RESULTS: 1173 patients met the study criteria. 837 patients never smoked whereas 336 patients were either current smokers or past smoker and were grouped together in smokers group. Patients in smokers group were more likely to be male and had higher incidence of underlying chronic obstructive pulmonary disease (19% vs 6%, p<0.001), HIV infection (11% vs 5%,p<0.001), cancer (11% vs 6%, p=0.005), congestive heart failure (15% vs 8%, p<0.001), coronary artery disease (15% vs 9%, p=0.3), chronic kidney disease (11% vs 8%, p=0.037) and end-stage renal disease (10% vs 6%, p=0.009) compared with non-smokers. Outcome analysis showed that smokers were more likely to develop critical illness requiring mechanical ventilation (47% vs 37% p=0.005). Univariate Cox model for survival analysis by smoking status showed that among smokers only current smokers had higher risk of death compared with never smokers (HR 1.61, 95% CI 1.22 to 2.12, p<0.001). In the multivariate approach, Cox model for the survival, female sex, young age, low serum lactate dehydrogenase and systemic steroid use were associated with overall improved survival. CONCLUSION: In our large single-centre retrospective database of patients hospitalised with COVID-19, smoking was associated with development of critical illness and higher likelihood of death.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pacientes Internados/estatística & dados numéricos , Avaliação de Resultados da Assistência ao Paciente , Pneumonia Viral/epidemiologia , Respiração Artificial/estatística & dados numéricos , Fumar/epidemiologia , Idoso , Bases de Dados Factuais , Feminino , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Pandemias , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida
11.
Ann Biol Clin (Paris) ; 78(5): 499-518, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026346

RESUMO

The French society of clinical biology "Biochemical markers of COVID-19" has set up a working group with the primary aim of reviewing, analyzing and monitoring the evolution of biological prescriptions according to the patient's care path and to look for markers of progression and severity of the disease. This study covers all public and private sectors of medical biology located in metropolitan and overseas France and also extends to the French-speaking world. This article presents the testimonies and data obtained for the "Overseas and French-speaking countries" sub-working group made up of 45 volunteer correspondents, located in 20 regions of the world. In view of the delayed spread of the SARS-CoV-2 virus, the overseas regions and the French-speaking regions have benefited from feedback from the first territories confronted with COVID-19. Thus, the entry of the virus or its spread in epidemic form could be avoided, thanks to the rapid closure of borders. The overseas territories depend very strongly on air and/or sea links with the metropolis or with the neighboring continent. The isolation of these countries is responsible for reagent supply difficulties and has necessitated emergency orders and the establishment of stocks lasting several months, in order to avoid shortages and maintain adequate patient care. In addition, in countries located in tropical or intertropical zones, the diagnosis of COVID-19 is complicated by the presence of various zoonoses (dengue, Zika, malaria, leptospirosis, etc.).


Assuntos
Serviços de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Saúde Global/estatística & dados numéricos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Medicina de Viagem/organização & administração , Adulto , África/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Betacoronavirus/fisiologia , Biomarcadores/análise , Biomarcadores/sangue , Camboja/epidemiologia , Criança , Serviços de Laboratório Clínico/organização & administração , Serviços de Laboratório Clínico/estatística & dados numéricos , Busca de Comunicante/métodos , Busca de Comunicante/estatística & dados numéricos , Infecções por Coronavirus/transmissão , Diagnóstico Diferencial , Feminino , França/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Recém-Nascido , Ilhas/epidemiologia , Idioma , Laos/epidemiologia , Louisiana/epidemiologia , Masculino , Pessoal de Laboratório Médico/organização & administração , Pessoal de Laboratório Médico/estatística & dados numéricos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/transmissão , Estudos Retrospectivos , Inquéritos e Questionários , Análise de Sobrevida , Medicina de Viagem/métodos , Medicina de Viagem/estatística & dados numéricos , Doença Relacionada a Viagens , Clima Tropical , Medicina Tropical/métodos , Medicina Tropical/organização & administração , Medicina Tropical/estatística & dados numéricos , Vietnã/epidemiologia
12.
BMC Infect Dis ; 20(1): 728, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028235

RESUMO

BACKGROUND: Late presentation (LP), defined as a CD4 count < 350/mm3 or an AIDS-event at HIV-diagnosis, remains a significant problem across Europe. Linking cohort and surveillance data, we assessed the country-specific burden of LP during 2010-2016 and the occurrence of new AIDS events or deaths within 12 months of HIV-diagnosis believed to be attributable to LP. METHODS: Country-specific percentages of LP and AIDS-events/death rates (assessed with Poisson regression) observed in The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) and EuroSIDA cohorts, were applied to new HIV-diagnoses reported to the European Centre for Disease Prevention and Control. The estimated number of LP in the whole population was then calculated, as was the number of excess AIDS-events/deaths in the first 12 months following HIV-diagnosis assumed to be attributable to LP (difference in estimated events between LP and non-LP). RESULTS: Thirty-nine thousand two hundred four persons were included from the COHERE and EuroSIDA cohorts, of whom 18,967 (48.4%; 95% Confidence Interval [CI] 47.9-48.9) were classified as LP, ranging from 36.9% in Estonia (95%CI 25.2-48.7) and Ukraine (95%CI 30.0-43.8) to 64.2% in Poland (95%CI 57.2-71.3). We estimated a total of > 320,000 LP and 12,050 new AIDS-events/deaths attributable to LP during 2010-2016, with the highest estimated numbers of LP and excess AIDS-events/deaths in Eastern Europe. Country-level estimates of excess events ranged from 17 AIDS-events/deaths (95%CI 0-533) in Denmark to 10,357 (95%CI 7768-147,448) in Russia. CONCLUSIONS: Across countries in Europe, the burden of LP was high, with the highest estimated number of LP and excess AIDS-events/deaths being in Eastern Europe. Effective strategies are needed to reduce LP and the attributable morbidity and mortality that could be potentially avoided.


Assuntos
Infecções por HIV/diagnóstico , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Diagnóstico Tardio , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/mortalidade , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Morbidade , Análise de Sobrevida
13.
Medicine (Baltimore) ; 99(41): e22118, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031259

RESUMO

It is controversial regarding the treatment allocation for patients with stage I hepatocellular carcinoma (SI-HCC). The aim of the present study was to compare the long-term survival in SI-HCC patients undergoing liver transplantation (LT), liver resection (LR), local tumor destruction (LTD), or none. SI-HCC patients diagnosed between 2004 and 2015 were extracted from the SEER 18 registry database. Multivariable Cox models and propensity score matching (PSM) method were used to explore the association between surgical methods and long-term prognosis. A total of 5165 patients with stage I (AJCC, 6th or 7th) HCC were included in the study. Only 36.9% of patients diagnosed with HCC in stage I received surgical therapy. The incidence of LT was decreased over time (P < .001). In the multivariable-adjusted cohort (n = 5165), after adjusting potential confounding factors, a clear prognostic advantage of LT was observed in OS (P < .0001) compared with patients after LR. Patients undergoing LTD had a worse OS in comparison with patients who underwent LR (P < .0001). Patients who received no surgical treatment had the worst OS (P < .0001) among 4 treatment groups. In stratified analyses, the salutary effects of LT vs LR on OS were consistent across all subgroups except for a similar result in the noncirrhotic subgroup (P = .4414). The inferior survival effects of LTD vs LR on OS were consistent across all subgroups, and even in the subgroup with tumor size < 3 cm (P = .0342). In the PSM cohort, patients in LT group showed a better OS (P < .001) than patients in LR group (P < .0001) and patients undergoing LTD had a worse OS compared with patients who underwent LR (P = .00059). In conclusion, LT offered a survival advantage compared with LR among patients with Stage I HCC. LT is the best surgical treatment for stage I HCC in patients with advanced fibrosis, whereas LR provides comparable long-term outcomes to LT in patients without advanced fibrosis and should be considered as the first-line surgical option. LTD can be used as an alternative method when LR and LT are unavailable.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Feminino , Hepatectomia , Humanos , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Programa de SEER , Análise de Sobrevida
14.
Lancet Oncol ; 21(10): 1283-1295, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002436

RESUMO

BACKGROUND: HER2-positive metastatic breast cancer is incurable and new treatments are needed. Addition of atezolizumab to trastuzumab emtansine might potentiate anticancer immunity and enhance the HER2-targeted cytotoxic activity of trastuzumab emtansine. We aimed to test this combination in HER2-positive advanced breast cancer that had progressed after previous treatment with trastuzumab and a taxane. METHODS: The KATE2 study is a randomised, double-blind, placebo-controlled, phase 2 study at 68 centres from nine countries across Asia, Australia, North America, and western Europe. Eligible patients were adults (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and centrally confirmed, measurable, HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane. Patients were randomly assigned (2:1) either trastuzumab emtansine (3·6 mg/kg of bodyweight) plus atezolizumab (1200 mg) or trastuzumab emtansine plus placebo; all study drugs were administered by intravenous infusion every 3 weeks. Randomisation was done via an interactive voice and web response system using a permuted block scheme (block size of six) and was stratified by PD-L1 status, world region, and liver metastases. Patients, investigators, and study team members were masked to treatment allocation. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02924883, and the study has been completed. FINDINGS: Between Sept 26, 2016, and Aug 7, 2017, 330 patients were screened for the study, of whom 202 were randomly allocated either atezolizumab (n=133) or placebo (n=69). At the recommendation of the independent data monitoring committee, treatment assignment was unmasked on Dec 11, 2017, due to futility and the numerically higher frequency of adverse events among patients assigned atezolizumab. This date was set as the clinical cutoff for the primary analysis. Median follow-up was 8·5 months (IQR 6·1-11·5) for patients assigned atezolizumab and 8·4 months (5·3-11·1) for those assigned placebo. Median progression-free survival was 8·2 months (95% CI 5·8-10·7) for patients assigned atezolizumab versus 6·8 months (4·0-11·1) for those assigned placebo (stratified hazard ratio 0·82, 95% CI 0·55-1·23; p=0·33). The most common grade 3 or worse adverse events were thrombocytopenia (17 [13%] among 132 patients who received atezolizumab vs three [4%] among 68 who received placebo), increased aspartate aminotransferase (11 [8%] vs two [3%]), anaemia (seven [5%] vs 0), neutropenia (six [5%] vs three [4%]), and increased alanine aminotransferase (six [5%] vs two [3%]). Serious adverse events occurred in 43 (33%) of 132 patients who received atezolizumab and 13 (19%) of 68 patients who received placebo. One patient who received atezolizumab died due to a treatment-related adverse event (haemophagocytic syndrome). INTERPRETATION: Addition of atezolizumab to trastuzumab emtansine did not show a clinically meaningful improvement in progression-free survival and was associated with more adverse events. Further study of trastuzumab emtansine plus atezolizumab is warranted in a subpopulation of patients with PD-L1-positive, HER2-positive advanced breast cancer. FUNDING: F Hoffman-La Roche.


Assuntos
Ado-Trastuzumab Emtansina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/patologia , Método Duplo-Cego , Resistencia a Medicamentos Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/metabolismo , Análise de Sobrevida , Resultado do Tratamento
15.
Lancet Oncol ; 21(10): 1341-1352, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002438

RESUMO

BACKGROUND: Adjuvant radiotherapy reduces the risk of biochemical progression in prostate cancer patients after radical prostatectomy. We aimed to compare adjuvant versus early salvage radiotherapy after radical prostatectomy, combined with short-term hormonal therapy, in terms of oncological outcomes and tolerance. METHODS: GETUG-AFU 17 was a randomised, open-label, multicentre, phase 3 trial done at 46 French hospitals. Men aged at least 18 years who had an Eastern Cooperative Oncology Group performance status of 1 or less, localised adenocarcinoma of the prostate treated with radical prostatectomy, who had pathologically-staged pT3a, pT3b, or pT4a (with bladder neck invasion), pNx (without pelvic lymph nodes dissection), or pN0 (with negative lymph nodes dissection) disease, and who had positive surgical margins were eligible for inclusion in the study. Eligible patients were randomly assigned (1:1) to either immediate adjuvant radiotherapy or delayed salvage radiotherapy at the time of biochemical relapse. Random assignment, by minimisation, was done using web-based software and stratified by Gleason score, pT stage, and centre. All patients received 6 months of triptorelin (intramuscular injection every 3 months). The primary endpoint was event-free survival. Efficacy and safety analyses were done on the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT00667069. FINDINGS: Between March 7, 2008, and June 23, 2016, 424 patients were enrolled. We planned to enrol 718 patients, with 359 in each study group. However, on May 20, 2016, the independent data monitoring committee recommended early termination of enrolment because of unexpectedly low event rates. At database lock on Dec 19, 2019, the overall median follow-up time from random assignment was 75 months (IQR 50-100), 74 months (47-100) in the adjuvant radiotherapy group and 78 months (52-101) in the salvage radiotherapy group. In the salvage radiotherapy group, 115 (54%) of 212 patients initiated study treatment after biochemical relapse. 205 (97%) of 212 patients started treatment in the adjuvant group. 5-year event-free survival was 92% (95% CI 86-95) in the adjuvant radiotherapy group and 90% (85-94) in the salvage radiotherapy group (HR 0·81, 95% CI 0·48-1·36; log-rank p=0·42). Acute grade 3 or worse toxic effects occurred in six (3%) of 212 patients in the adjuvant radiotherapy group and in four (2%) of 212 patients in the salvage radiotherapy group. Late grade 2 or worse genitourinary toxicities were reported in 125 (59%) of 212 patients in the adjuvant radiotherapy group and 46 (22%) of 212 patients in the salvage radiotherapy group. Late genitourinary adverse events of grade 2 or worse were reported in 58 (27%) of 212 patients in the adjuvant radiotherapy group versus 14 (7%) of 212 patients in the salvage radiotherapy group (p<0·0001). Late erectile dysfunction was grade 2 or worse in 60 (28%) of 212 in the adjuvant radiotherapy group and 17 (8%) of 212 in the salvage radiotherapy group (p<0·0001). INTERPRETATION: Although our analysis lacked statistical power, we found no benefit for event-free survival in patients assigned to adjuvant radiotherapy compared with patients assigned to salvage radiotherapy. Adjuvant radiotherapy increased the risk of genitourinary toxicity and erectile dysfunction. A policy of early salvage radiotherapy could spare men from overtreatment with radiotherapy and the associated adverse events. FUNDING: French Health Ministry and Ipsen.


Assuntos
Adenocarcinoma/radioterapia , Antagonistas de Androgênios/administração & dosagem , Prostatectomia , Neoplasias da Próstata/radioterapia , Terapia de Salvação , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Progressão da Doença , França , Humanos , Masculino , Doenças Urogenitais Masculinas/epidemiologia , Doenças Urogenitais Masculinas/etiologia , Sobremedicalização/prevenção & controle , Pessoa de Meia-Idade , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Radioterapia Adjuvante/efeitos adversos , Terapia de Salvação/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento
16.
Nat Commun ; 11(1): 4627, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009389

RESUMO

Animals have evolved responses to low oxygen conditions to ensure their survival. Here, we have identified the C. elegans zinc finger transcription factor PQM-1 as a regulator of the hypoxic stress response. PQM-1 is required for the longevity of insulin signaling mutants, but surprisingly, loss of PQM-1 increases survival under hypoxic conditions. PQM-1 functions as a metabolic regulator by controlling oxygen consumption rates, suppressing hypoxic glycogen levels, and inhibiting the expression of the sorbitol dehydrogenase-1 SODH-1, a crucial sugar metabolism enzyme. PQM-1 promotes hypoxic fat metabolism by maintaining the expression of the stearoyl-CoA desaturase FAT-7, an oxygen consuming, rate-limiting enzyme in fatty acid biosynthesis. PQM-1 activity positively regulates fat transport to developing oocytes through vitellogenins under hypoxic conditions, thereby increasing survival rates of arrested progeny during hypoxia. Thus, while pqm-1 mutants increase survival of mothers, ultimately this loss is detrimental to progeny survival. Our data support a model in which PQM-1 controls a trade-off between lipid metabolic activity in the mother and her progeny to promote the survival of the species under hypoxic conditions.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Hipóxia/metabolismo , Metabolismo dos Lipídeos , Transativadores/metabolismo , Animais , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Embrião de Mamíferos/metabolismo , Regulação da Expressão Gênica , Glicogênio/metabolismo , Insulina/metabolismo , Larva/metabolismo , Mutação/genética , Consumo de Oxigênio , Transdução de Sinais , Estresse Fisiológico , Análise de Sobrevida , Transativadores/genética , Transcrição Genética , Vitelogeninas/metabolismo
17.
Undersea Hyperb Med ; 47(3): 405-413, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32931666

RESUMO

Objective: Given the high mortality and prolonged duration of mechanical ventilation of COVID-19 patients, we evaluated the safety and efficacy of hyperbaric oxygen for COVID-19 patients with respiratory distress. Methods: This is a single-center clinical trial of COVID-19 patients at NYU Winthrop Hospital from March 31 to April 28, 2020. Patients in this trial received hyperbaric oxygen therapy at 2.0 atmospheres of pressure in monoplace hyperbaric chambers for 90 minutes daily for a maximum of five total treatments. Controls were identified using propensity score matching among COVID-19 patients admitted during the same time period. Using competing-risks survival regression, we analyzed our primary outcome of inpatient mortality and secondary outcome of mechanical ventilation. Results: We treated 20 COVID-19 patients with hyperbaric oxygen. Ages ranged from 30 to 79 years with an oxygen requirement ranging from 2 to 15 liters on hospital days 0 to 14. Of these 20 patients, two (10%) were intubated and died, and none remain hospitalized. Among 60 propensity-matched controls based on age, sex, body mass index, coronary artery disease, troponin, D-dimer, hospital day, and oxygen requirement, 18 (30%) were intubated, 13 (22%) have died, and three (5%) remain hospitalized (with one still requiring mechanical ventilation). Assuming no further deaths among controls, we estimate that the adjusted subdistribution hazard ratios were 0.37 for inpatient mortality (p=0.14) and 0.26 for mechanical ventilation (p=0.046). Conclusion: Though limited by its study design, our results demonstrate the safety of hyperbaric oxygen among COVID-19 patients and strongly suggests the need for a well-designed, multicenter randomized control trial.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Oxigenação Hiperbárica/métodos , Pneumonia Viral/terapia , Pontuação de Propensão , Síndrome do Desconforto Respiratório do Adulto/terapia , Adulto , Idoso , Pressão Atmosférica , Estudos de Casos e Controles , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Oxigenação Hiperbárica/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Respiração Artificial/mortalidade , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Fatores de Risco , Segurança , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
19.
J Int Med Res ; 48(9): 300060520956834, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32967488

RESUMO

PURPOSE: To investigate associations between the clinical characteristics and incubation periods of patients infected with coronavirus disease 2019 (COVID-19) in Wuhan, China. METHODS: Complete clinical and epidemiological data from 149 patients with COVID-19 at a hospital in Hunan Province, China, were collected and retrospectively analyzed. RESULTS: Analysis of the distribution and receiver operator characteristic curve of incubation periods showed that 7 days was the optimal cut-off value to assess differences in disease severity between groups. Patients with shorter (≤7 days) incubation periods (n = 79) had more severe disease, longer durations of hospitalization, longer times from symptom onset to discharge, more abnormal laboratory findings, and more severe radiological findings than patients with longer (>7 days) incubation periods. Regression and correlation analyses also showed that a shorter incubation period was associated with longer times from symptom onset to discharge. CONCLUSION: The associations between the incubation periods and clinical characteristics of COVID-19 patients suggest that the incubation period may be a useful marker of disease severity and prognosis.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Período de Incubação de Doenças Infecciosas , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Adolescente , Adulto , Idoso , Biomarcadores/análise , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Alta do Paciente/estatística & dados numéricos , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida
20.
Zhonghua Zhong Liu Za Zhi ; 42(8): 648-652, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867456

RESUMO

Objective: To investigate the relationship between KDM6A mutation or expression and clinicopathological characteristics of gastric cancer. Methods: Fifty-seven cases of gastric cancer tissues were analyzed by second-generation sequencing, and bioinformation database such as Cbioportal, Kaplan Meier-Plotter, and the Human Protein Atlas were used to analyze the relationship between KDM6A mutation and clinicopathological characteristics of gastric cancer. Results: Among 57 gastric cancer samples, 14 were KDM6A mutation, and the mutation proportion was 24.6%. Compared with the non-mutation group, the Borrmann classification, T stage, TNM stage and tumor diameter of KDM6A mutant group were significantly different (all P<0.05). The median survival time of the KDM6A mutant patients was 53.5 months, significantly shorter than 72.0 months of the KDM6A non-mutation patients (P=0.007). The analysis result of Kaplan Meier-Plotter database showed that, among all of the 875 patients, 655 patients had low KDM6A expression and 220 patients had high expression. The median survival time of patients with low expression was 23.5 months, significantly shorter than 30.8 months of patients with high expression (P=0.002). In male, gastric cancer patients with stage Ⅲ, intestinal type, diffuse type, simple surgical treatment and fluorouracil chemotherapy, the expression of KDM6A is related to the patient's overall survival time (all P<0.05). The analysis result of Cbioportal database showed that, among all of the 1 172 gastric cancer patients, 70 patients with KDM6A mutation, 1100 patients with non-mutation. The median overall survival time of mutant patients was 28.9 months, significantly shorter than 35.9 months of non-mutation patients (P<0.001). The analysis result of Human Protein Atlas database showed that, among all of the 355 gastric cancer patients, 97 patients had high KDM6A expression and 258 patients had low KDM6A expression. The median survival time of patients with low expression was 13.7 months, significantly shorter than 19.8 months of patients with high expression (P=0.022). Conclusions: The survival time of gastric cancer patients with KDM6A mutation or low expression is shorter. The mutation and expression of KDM6A are related to clinical pathological factors, which may become a potential target for the diagnosis and treatment of gastric cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Histona Desmetilases/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Histona Desmetilases/genética , Humanos , Metástase Linfática , Masculino , Mutação/genética , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida
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