RESUMO
Capillary Refill Time (CRT) assesses peripheral perfusion in resource-limited settings. However, the repeatability and reproducibility of CRT measurements are limited for individuals with darker skin. This paper presents quantitative CRT measurements demonstrating good performance and repeatability across all Fitzpatrick skin phototypes. The study involved 22 volunteers and utilized controlled compression at 7 kPa, an RGB video camera, and cocircular polarized white LED light. CRT was determined by calculating the time constant of an exponential regression applied to the mean pixel intensity of the green (G) channel. An adaptive algorithm identifies the optimal regression region for noise reduction, and flags inappropriate readings. The results indicate that 80% of the CRT readings fell within a 20% range of the expected CRT value. The repetition standard deviation was 17%. These findings suggest the potential for developing reliable and reproducible quantitative CRT methods for robust measurements in patient triage, monitoring, and telehealth applications.
Assuntos
Hemodinâmica , Pele , Humanos , Reprodutibilidade dos Testes , Pele/irrigação sanguínea , Pressão , CapilaresRESUMO
ABSTRACT: Vaccine strategies for cancer differ from infectious disease in focusing mainly on clearing rather than preventing disease. Here we survey general vaccine strategies and combination therapy concepts being investigated for cancer treatment, with a focus on tumor antigens rather than cancer-inducing viruses or microorganisms. Many tumor antigens are "altered-self" and tend to arouse weaker immune responses than "foreign" antigens expressed by infectious agents. Further, unlike an infectious disease patient, a cancer patient's immune system is damaged, suppressed, or senescent and mainly tolerant of their disease. Thus, vaccine efficacy in a cancer patient will rely upon adjuvant or combination treatments that correct the inflammatory tumor microenvironment and degrade tumoral immunosuppression that dominates patient immunity. This brief overview is aimed at new researchers in cancer immunology seeking an overview of vaccine concepts to eradicate malignancy by provoking a selective immune attack.
Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Vacinas Anticâncer/uso terapêutico , Neoplasias/terapia , Antígenos de Neoplasias , Microambiente TumoralRESUMO
IDO2 is one of two closely related tryptophan catabolizing enzymes induced under inflammatory conditions. In contrast to the immunoregulatory role defined for IDO1 in cancer models, IDO2 has a proinflammatory function in models of autoimmunity and contact hypersensitivity. In humans, two common single-nucleotide polymorphisms have been identified that severely impair IDO2 enzymatic function, such that <25% of individuals express IDO2 with full catalytic potential. This, together with IDO2's relatively weak enzymatic activity, suggests that IDO2 may have a role outside of its function in tryptophan catabolism. To determine whether the enzymatic activity of IDO2 is required for its proinflammatory function, we used newly generated catalytically inactive IDO2 knock-in mice together with established models of contact hypersensitivity and autoimmune arthritis. Contact hypersensitivity was attenuated in catalytically inactive IDO2 knock-in mice. In contrast, induction of autoimmune arthritis was unaffected by the absence of IDO2 enzymatic activity. In pursuing this nonenzymatic IDO2 function, we identified GAPDH, Runx1, RANbp10, and Mgea5 as IDO2-binding proteins that do not interact with IDO1, implicating them as potential mediators of IDO2-specific function. Taken together, our findings identify a novel function for IDO2, independent of its tryptophan catabolizing activity, and suggest that this nonenzymatic function could involve multiple signaling pathways. These data show that the enzymatic activity of IDO2 is required only for some inflammatory immune responses and provide, to our knowledge, the first evidence of a nonenzymatic role for IDO2 in mediating autoimmune disease.
Assuntos
Artrite/imunologia , Autoimunidade/imunologia , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Animais , Antígenos de Neoplasias/metabolismo , Linhagem Celular , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Técnicas de Introdução de Genes , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Células HEK293 , Humanos , Inflamação/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
OBJECTIVES: To assess the rate of spontaneous closure and the incidence of adverse events in infants discharged home with a patent ductus arteriosus. STUDY DESIGN: In a prospective multicenter study, we enrolled 201 premature infants (gestational age of 23-32 weeks at birth) discharged home with a persistently patent ductus arteriosus (PDA) and followed their PDA status at 6-month intervals through 18 months of age. The primary study outcome was the rate and timing of spontaneous ductal closure. Secondary outcomes included rate of assisted closure and the incidence of serious adverse events. RESULTS: Spontaneous ductal closure occurred in 95 infants (47%) at 12 months and 117 infants (58%) by 18 months. Seventeen infants (8.4%) received assisted closure with surgical ligation or device assisted occlusion. Three infants died (1.5%). Although infants with spontaneous closure had a higher mean birth weight and gestational age compared with infants with a persistent PDA or assisted closure, we did not identify other factors predictive of spontaneous closure. CONCLUSIONS: Spontaneous closure of the PDA occurred in slightly less than one-half of premature infants discharged with a patent ductus by 1 year, lower than prior published reports. The high rate of assisted closure and/or adverse events in this population warrants close surveillance following discharge. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02750228.
Assuntos
Permeabilidade do Canal Arterial , Permeabilidade do Canal Arterial/cirurgia , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Alta do Paciente , Estudos ProspectivosRESUMO
Physical exercise has profound effects on quality of life and susceptibility to chronic disease; however, the regulation of skeletal muscle function at the molecular level after exercise remains unclear. We tested the hypothesis that the benefits of exercise on muscle function are linked partly to microtraumatic events that result in accumulation of circulating heme. Effective metabolism of heme is controlled by Heme Oxygenase-1 (HO-1, Hmox1), and we find that mouse skeletal muscle-specific HO-1 deletion (Tam-Cre-HSA-Hmox1fl/fl) shifts the proportion of muscle fibers from type IIA to type IIB concomitant with a disruption in mitochondrial content and function. In addition to a significant impairment in running performance and response to exercise training, Tam-Cre-HSA-Hmox1fl/fl mice show remarkable muscle atrophy compared to Hmox1fl/fl controls. Collectively, these data define a role for heme and HO-1 as central regulators in the physiologic response of skeletal muscle to exercise.
Assuntos
Heme Oxigenase-1/genética , Heme/metabolismo , Proteínas de Membrana/genética , Fibras Musculares Esqueléticas/metabolismo , Atrofia Muscular/genética , Condicionamento Físico Animal/fisiologia , 5-Aminolevulinato Sintetase/genética , 5-Aminolevulinato Sintetase/metabolismo , Animais , Ferroquelatase/genética , Ferroquelatase/metabolismo , Regulação da Expressão Gênica , Heme Oxigenase-1/deficiência , Isoenzimas/genética , Isoenzimas/metabolismo , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Masculino , Proteínas de Membrana/deficiência , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/fisiopatologia , Proteína MyoD/genética , Proteína MyoD/metabolismo , Fator de Transcrição PAX7/genética , Fator de Transcrição PAX7/metabolismo , Transdução de Sinais , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Resumo Introdução e objetivos: Stents Coated with the Biodegradable Polymer on their Abluminal Faces and Elution of Sirolimus Versus Biolimus Elution for the Treatment of de Novo Coronary Lesions (Destiny Trial) é um estudo randomizado de não inferioridade que comparou o stent farmacológico eluído com Sirolimus Inspiron® (SES) ao controle o stent Biomatrix® Flex eluído com biolimus (BES). Relatórios dentro do primeiro ano mostraram resultados semelhantes para ambos os stents, em seguimento clínico, angiográfico e também em análise de tomografia de coerência ótica e ultrassom intracoronário. A presente análise tem como objetivo comparar o desempenho clínico desses dois stents farmacológicos com polímeros biodegradáveis após cinco anos do procedimento índice. Métodos: Foram randomizados 170 pacientes (194 lesões) em uma proporção de 2:1 para trata mento com SES ou BES, respetivamente. O desfecho primário para o presente estudo foi a taxa em cinco anos de eventos cardíacos adversos maiores combinados, definida como morte cardíaca, infarto do miocárdio ou revascularização da lesão-alvo. Resultados: Em cinco anos, o desfecho primário ocorreu em 12,5% e 17,9% para o grupo SES e BES, respectivamente (p=0,4). Não houve trombose de stent definitiva ou provável entre os pacientes tratados com o novo SES durante os cinco anos de seguimento e ausência de trombose de stent após o primeiro ano no grupo BES. Conclusões: O novo stent Inspiron® apresentou uma boa e semelhante performance clínica no seguimento em longo prazo, quando comparado com o controle o stent de última geração Biomatrix® Flex.
Assuntos
Ultrassonografia de Intervenção , Tomografia de Coerência Óptica , Stents Farmacológicos , TromboseRESUMO
INTRODUCTION AND OBJECTIVES: The Stents Coated With the Biodegradable Polymer on Their Abluminal Faces and Elution of Sirolimus Versus Biolimus Elution for the Treatment of de Novo Coronary Lesions - DESTINY Trial is a non-inferiority randomized study that compared the Inspiron™ sirolimus-eluting stent (SES) with the control Biomatrix™ Flex biolimus-eluting stent (BES). Previous reports in the first year showed similar outcomes for both stents, in clinical, angiographic, optical coherence tomography, and intravascular ultrasound assessments. The present analysis aims to compare the clinical performance of these two biodegradable polymer drug-eluting stents five years after the index procedure. METHODS: A total of 170 patients (194 lesions) were randomized in a 2:1 ratio for treatment with SES or BES, respectively. The primary endpoint for the present study was the five-year rate of combined major adverse cardiac events, defined as cardiac death, myocardial infarction, or target lesion revascularization. RESULTS: At five years, the primary endpoint occurred in 12.5% and 17.9% of the SES and BES groups, respectively (p=0.4). There was no definite or probable stent thrombosis among patients treated with the novel SES stent during the five years of follow-up, and no stent thrombosis after the first year in the BES group. CONCLUSIONS: The novel Inspiron™ stent had similar good clinical performance in long-term follow-up when compared head-to-head with the control latest-generation Biomatrix™ Flex biolimus-eluting stent.
Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Implantes Absorvíveis , Doença da Artéria Coronariana/cirurgia , Humanos , Polímeros , Desenho de Prótese , Resultado do TratamentoRESUMO
The mechanical properties of biological tissues are fingerprints of certain pathologic processes. Ultrasound systems have been used as a non-invasive technique to both induce kilohertz-frequency mechanical vibrations and detect waves resulting from interactions with biological structures. However, existing methodologies to produce kilohertz-frequency mechanical vibrations using ultrasound require the use of variable-frequency, dual-frequency and high-power systems. Here, we propose and demonstrate the use of bursts of megahertz- frequency acoustic radiation to observe kilohertz-frequency mechanical responses in biological tissues. Femoral bones were obtained from 10 healthy mice and 10 mice in which osteoporosis had been induced. The bones' porosity, trabecular number, trabecular spacing, connectivity and connectivity density were determined using micro-computed tomography (µCT). The samples were irradiated with short, focused acoustic radiation pulses (fâ¯=â¯3.1 MHz, tâ¯=â¯15 µs), and the low-frequency acoustic response (1-100 kHz) was acquired using a dedicated hydrophone. A strong correlation between the spectral maps of the acquired signals and the µCT data was found. In a subsequent evaluation, soft tissue stiffness measurements were performed with a gel wax-based tissue-mimicking phantom containing three spherical inclusions of the same type of gel but different densities and Young's moduli, yet with approximately the same echogenicity. Conventional B-mode ultrasound was unable to image the inclusions, while the novel technique proposed here showed good image contrast.
Assuntos
Fêmur/diagnóstico por imagem , Osteoporose/diagnóstico por imagem , Ondas Ultrassônicas , Ultrassonografia/métodos , Animais , Osso Esponjoso/diagnóstico por imagem , Módulo de Elasticidade , Camundongos , Imagens de Fantasmas , Porosidade , Som , Microtomografia por Raio-XRESUMO
BACKGROUND: Record linkage is the process of identifying and combining records about the same individual from two or more different datasets. While there are many open source and commercial data linkage tools, the volume and complexity of currently available datasets for linkage pose a huge challenge; hence, designing an efficient linkage tool with reasonable accuracy and scalability is required. METHODS: We developed CIDACS-RL (Centre for Data and Knowledge Integration for Health - Record Linkage), a novel iterative deterministic record linkage algorithm based on a combination of indexing search and scoring algorithms (provided by Apache Lucene). We described how the algorithm works and compared its performance with four open source linkage tools (AtyImo, Febrl, FRIL and RecLink) in terms of sensitivity and positive predictive value using gold standard dataset. We also evaluated its accuracy and scalability using a case-study and its scalability and execution time using a simulated cohort in serial (single core) and multi-core (eight core) computation settings. RESULTS: Overall, CIDACS-RL algorithm had a superior performance: positive predictive value (99.93% versus AtyImo 99.30%, RecLink 99.5%, Febrl 98.86%, and FRIL 96.17%) and sensitivity (99.87% versus AtyImo 98.91%, RecLink 73.75%, Febrl 90.58%, and FRIL 74.66%). In the case study, using a ROC curve to choose the most appropriate cut-off value (0.896), the obtained metrics were: sensitivity = 92.5% (95% CI 92.07-92.99), specificity = 93.5% (95% CI 93.08-93.8) and area under the curve (AUC) = 97% (95% CI 96.97-97.35). The multi-core computation was about four times faster (150 seconds) than the serial setting (550 seconds) when using a dataset of 20 million records. CONCLUSION: CIDACS-RL algorithm is an innovative linkage tool for huge datasets, with higher accuracy, improved scalability, and substantially shorter execution time compared to other existing linkage tools. In addition, CIDACS-RL can be deployed on standard computers without the need for high-speed processors and distributed infrastructures.
Assuntos
Conjuntos de Dados como Assunto , Armazenamento e Recuperação da Informação , Registro Médico Coordenado , Algoritmos , Estudos de Coortes , Humanos , Sistemas Computadorizados de Registros MédicosRESUMO
How T cells integrate environmental cues into signals that limit the magnitude and length of immune responses is poorly understood. Here, we provide data that demonstrate that B55ß, a regulatory subunit of protein phosphatase 2A, represents a molecular link between cytokine concentration and apoptosis in activated CD8+ T cells. Through the modulation of AKT, B55ß induced the expression of the proapoptotic molecule Hrk in response to cytokine withdrawal. Accordingly, B55ß and Hrk were both required for in vivo and in vitro contraction of activated CD8+ lymphocytes. We show that this process plays a role during clonal contraction, establishment of immune memory, and preservation of peripheral tolerance. This regulatory pathway may represent an unexplored opportunity to end unwanted immune responses or to promote immune memory.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Memória Imunológica , Proteína Fosfatase 2/imunologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/imunologia , Camundongos , Camundongos Transgênicos , Neuropeptídeos/genética , Neuropeptídeos/imunologia , Proteína Fosfatase 2/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/imunologiaRESUMO
BACKGROUND: Research using linked routine population-based data collected for non-research purposes has increased in recent years because they are a rich and detailed source of information. The objective of this study is to present an approach to prepare and link data from administrative sources in a middle-income country, to estimate its quality and to identify potential sources of bias by comparing linked and non-linked individuals. METHODS: We linked two administrative datasets with data covering the period 2001 to 2015, using maternal attributes (name, age, date of birth, and municipally of residence) from Brazil: live birth information system and the 100 Million Brazilian Cohort (created using administrative records from over 114 million individuals whose families applied for social assistance via the Unified Register for Social Programmes) implementing an in house developed linkage tool CIDACS-RL. We then estimated the proportion of highly probably link and examined the characteristics of missed-matches to identify any potential source of bias. RESULTS: A total of 27,699,891 live births were submited to linkage with maternal information recorded in the baseline of the 100 Million Brazilian Cohort dataset of those, 16,447,414 (59.4%) children were found registered in the 100 Million Brazilian Cohort dataset. The proportion of highly probably link ranged from 39.3% in 2001 to 82.1% in 2014. A substantial improvement in the linkage after the introduction of maternal date of birth attribute, in 2011, was observed. Our analyses indicated a slightly higher proportion of missing data among missed matches and a higher proportion of people living in an urban area and self-declared as Caucasian among linked pairs when compared with non-linked sets. DISCUSSION: We demonstrated that CIDACS-RL is capable of performing high quality linkage even with a limited number of common attributes, using indexation as a blocking strategy in larg e routine databases from a middle-income country. However, residual records occurred more among people under worse living conditions. The results presented in this study reinforce the need of evaluating linkage quality and when necessary to take linkage error into account for the analyses of any generated dataset.
Assuntos
Bases de Dados Factuais , Parto , Brasil , Estudos de Coortes , Feminino , Humanos , Masculino , Registro Médico Coordenado , GravidezRESUMO
Clinical success attained in patients with cancer treated with checkpoint inhibitors has renewed the interest in the immune system and in particular in T cells as a therapeutic tool to eliminate tumors. Here, we discuss recent studies that evaluate the anti-tumor role of CD8 T cells and the mechanisms that interfere with this function. In particular, we review recent literature that has reported on the phenotype and transcriptome of tumor-infiltrating CD8 T cells and deciphered the mechanisms associated with failed tumor rejection.
Assuntos
Neoplasias , Linfócitos T CD8-Positivos/imunologia , Humanos , Linfócitos do Interstício Tumoral/imunologia , Monitorização Imunológica , Receptor de Morte Celular Programada 1RESUMO
BACKGROUND: Brazil, Russia, India, China, and South Africa (BRICS) are emerging economies making up almost half the global population. We analyzed trends in cardiovascular disease (CVD) mortality across the BRICS and associations with age, period, and birth cohort. METHODS: Mortality estimates were derived from the Global Burden of Disease Study 2017. We used age-period-cohort modeling to estimate cohort and period effects in CVD between 1992 and 2016. Period was defined as survey year, and period effects reflect population-wide exposure at a circumscribed point in time. Cohort effects are defined as differences in risks across birth cohort. Net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks were calculated. RESULTS: In 2016, there were 8.4 million CVD deaths across the BRICS. Between 1992 and 2016, the reduction in CVD age-standardized mortality rate in BRICS (-17%) was less than in North America (-39%). Eighty-eight percent of the increased number of all-cause deaths resulted from the increase in CVD deaths. The age-standardized mortality rate from stroke and hypertensive heart disease declined by approximately one-third across the BRICS, whereas ischemic heart disease increased slightly (2%). Brazil had the largest age-standardized mortality rate reductions across all CVD categories, with improvement both over time and in recent birth cohorts. South Africa was the only country where the CVD age-standardized mortality rate increased. Different age-related CVD mortality was seen in those ≥50 years of age in China, ≤40 years of age in Russia, 35 to 60 years of age in India, and ≥55 years of age in South Africa. Improving period and cohort risks for CVD mortality were generally found across countries, except for worsening period effects in India and greater risks for ischemic heart disease in Chinese cohorts born in the 1950s and 1960s. CONCLUSIONS: Except for Brazil, reductions of CVD mortality across the BRICS have been less than that in North America, such that China, India, and South Africa contribute an increasing proportion of global CVD deaths. Brazil's example suggests that prevention policies can both reduce the risks for younger birth cohorts and shift the risks for all age groups over time.
Assuntos
Fatores Etários , Doenças Cardiovasculares/epidemiologia , Carga Global da Doença/estatística & dados numéricos , Adulto , Brasil/epidemiologia , Doenças Cardiovasculares/mortalidade , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Risco , Federação Russa/epidemiologia , África do Sul/epidemiologia , Análise de SobrevidaAssuntos
Dissecação/métodos , Biópsia Guiada por Imagem/métodos , Linfonodos/diagnóstico por imagem , Idoso , Dissecação/tendências , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Biópsia Guiada por Imagem/estatística & dados numéricos , Linfonodos/patologia , Linfoma não Hodgkin/complicações , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Radiologia Intervencionista/métodos , SegurançaRESUMO
Health technology assessment (HTA) is the systematic evaluation of the properties and impacts of health technologies and interventions. In this article, we presented a discussion of HTA and its evolution in Brazil, as well as a description of secondary data sources available in Brazil with potential applications to generate evidence for HTA and policy decisions. Furthermore, we highlighted record linkage, ongoing record linkage initiatives in Brazil, and the main linkage tools developed and/or used in Brazilian data. Finally, we discussed the challenges and opportunities of using secondary data for research in the Brazilian context. In conclusion, we emphasized the availability of high quality data and an open, modern attitude toward the use of data for research and policy. This is supported by a rigorous but enabling legal framework that will allow the conduct of large-scale observational studies to evaluate clinical, economical, and social impacts of health technologies and social policies.
RESUMO
ABSTRACT Introduction: To determine the impact of time from biopsy to surgery on outcomes following radical prostatectomy (RP) as the optimal interval between prostate biopsy and RP is unknown. Material and methods: We identified 7, 350 men who underwent RP at our institution between 1994 and 2012 and had a prostate biopsy within one year of surgery. Patients were grouped into five time intervals for analysis: ≤ 3 weeks, 4-6 weeks, 7-12 weeks, 12-26 weeks, and > 26 weeks. Oncologic outcomes were stratified by NCCN disease risk for comparison. The associations of time interval with clinicopathologic features and survival were evaluated using multivariate logistic and Cox regression analyses. Results: Median time from biopsy to surgery was 61 days (IQR 37, 84). Median follow-up after RP was 7.1 years (IQR 4.2, 11.7) while the overall perioperative complication rate was 19.7% (1,448/7,350). Adjusting for pre-operative variables, men waiting 12-26 weeks until RP had the highest likelihood of nerve sparing (OR: 1.45, p = 0.02) while those in the 4-6 week group had higher overall complications (OR: 1.33, p = 0.01). High risk men waiting more than 6 months had higher rates of biochemical recurrence (HR: 3.38, p = 0.05). Limitations include the retrospective design. Conclusions: Surgery in the 4-6 week time period after biopsy is associated with higher complications. There appears to be increased biochemical recurrence rates in delaying RP after biopsy, for men with both low and high risk disease.
Assuntos
Humanos , Masculino , Idoso , Complicações Pós-Operatórias/etiologia , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Tempo para o Tratamento , Complicações Intraoperatórias/etiologia , Prostatectomia/métodos , Fatores de Tempo , Biópsia , Modelos Logísticos , Estudos Retrospectivos , Fatores de Risco , Análise de Variância , Resultado do Tratamento , Antígeno Prostático Específico/sangue , Medição de Risco , Progressão da Doença , Gradação de Tumores , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de NeoplasiasRESUMO
INTRODUCTION: To determine the impact of time from biopsy to surgery on outcomes following radical prostatectomy (RP) as the optimal interval between prostate biopsy and RP is unknown. MATERIAL AND METHODS: We identified 7, 350 men who underwent RP at our institution between 1994 and 2012 and had a prostate biopsy within one year of surgery. Patients were grouped into five time intervals for analysis: ≤ 3 weeks, 4-6 weeks, 7-12 weeks, 12-26 weeks, and > 26 weeks. Oncologic outcomes were stratified by NCCN disease risk for comparison. The associations of time interval with clinicopathologic features and survival were evaluated using multivariate logistic and Cox regression analyses. RESULTS: Median time from biopsy to surgery was 61 days (IQR 37, 84). Median followup after RP was 7.1 years (IQR 4.2, 11.7) while the overall perioperative complication rate was 19.7% (1,448/7,350). Adjusting for pre-operative variables, men waiting 12-26 weeks until RP had the highest likelihood of nerve sparing (OR: 1.45, p = 0.02) while those in the 4-6 week group had higher overall complications (OR: 1.33, p = 0.01). High risk men waiting more than 6 months had higher rates of biochemical recurrence (HR: 3.38, p = 0.05). Limitations include the retrospective design. CONCLUSIONS: Surgery in the 4-6 week time period after biopsy is associated with higher complications. There appears to be increased biochemical recurrence rates in delaying RP after biopsy, for men with both low and high risk disease.
Assuntos
Complicações Intraoperatórias/etiologia , Complicações Pós-Operatórias/etiologia , Prostatectomia/efeitos adversos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Tempo para o Tratamento , Idoso , Análise de Variância , Biópsia , Progressão da Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Prostatectomia/métodos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: The association between coronary artery disease (CAD) and thyroid function remains controversial. We evaluated the thyroid function and graduated well-defined CAD as confirmed by quantitative coronary angiography (CA). SUBJECTS AND METHODS: We evaluated the serum TSH, free thyroxine, free triiodothyronine and thyroid antibody levels in 300 consecutive patients (age 61.6 ± 9.9 years and 54% were male) undergoing CAD diagnosis as confirmed by CA. Plaques with ≥ 50% stenosis being indicative of obstructive CAD, and patients were divided into groups according to main epicardial coronary arteries with plaques (0, 1, 2, 3). Lipid profiles and a homeostasis model assessment (HOMA-IR) were determined. RESULTS: Serum median (25% and 75% percentile) TSH levels in patients with group 2 and 3 (2.25; 1.66-3.12 mU/L and 4.99; 4.38-23.60 mU/L, respectively) had significantly higher TSH concentrations (p < 0.0001) than the group 0 (1.82; 1.35-2.51 mU/L). Furthermore, patients of group 3 had higher TSH concentration (p < 0.0001) than those of group 1 (1.60; 0.89-2.68 mU/L). Group 3 were older (64 ± 8.5 vs. 59 ± 9.5, p = 0.001), had more patients with dyslipidemia (84% versus 58%, p < 0.001), male (54% versus 44%, p = 0.01), hypertension (100% versus 86%, p < 0.001), and smoking (61% versus 33%, p < 0.001) than group 0. Multivariate stepwise logistic analysis showed TSH, age, HbA1c, and HOMA-IR were the CAD associated variables. CONCLUSIONS: In this cohort, elevated TSH levels in the high normal range or above are associated with the presence and severity of CAD besides may represent a weak CAD risk factor.