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1.
Bone Joint J ; 101-B(10): 1199-1208, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31564148

RESUMO

AIMS: We compared implant and patient survival following intraoperative periprosthetic femoral fractures (IOPFFs) during primary total hip arthroplasty (THA) with matched controls. PATIENTS AND METHODS: This retrospective cohort study compared 4831 hips with IOPFF and 48 154 propensity score matched primary THAs without IOPFF implanted between 2004 and 2016, which had been recorded on a national joint registry. Implant and patient survival rates were compared between groups using Cox regression. RESULTS: Ten-year stem survival was worse in the IOPFF group (p < 0.001). Risk of revision for aseptic loosening increased 7.2-fold following shaft fracture and almost 2.8-fold after trochanteric fracture (p < 0.001). Risk of periprosthetic fracture of the femur revision increased 4.3-fold following calcar-crack and 3.6-fold after trochanteric fracture (p < 0.01). Risk of instability revision was 3.6-fold after trochanteric fracture and 2.4-fold after calcar crack (p < 0.001). Risk of 90-day mortality following IOPFF without revision was 1.7-fold and 4.0-fold after IOPFF with early revision surgery versus uncomplicated THA (p < 0.001). CONCLUSION: IOPFF increases risk of stem revision and mortality up to ten years following surgery. The risk of revision depends on IOPFF subtype and mortality risk increases with subsequent revision surgery. Surgeons should carefully diagnose and treat IOPFF to minimize fracture progression and implant failure. Cite this article: Bone Joint J 2019;101-B:1199-1208.


Assuntos
Artroplastia de Quadril/efeitos adversos , Osteoartrite do Quadril/cirurgia , Fraturas Periprotéticas/cirurgia , Sistema de Registros , Reoperação/métodos , Fatores Etários , Idoso , Artroplastia de Quadril/métodos , Estudos de Casos e Controles , Inglaterra , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/cirurgia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Irlanda do Norte , Osteoartrite do Quadril/diagnóstico por imagem , Fraturas Periprotéticas/diagnóstico por imagem , Fraturas Periprotéticas/epidemiologia , Modelos de Riscos Proporcionais , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Reino Unido , País de Gales
2.
Bone Joint J ; 101-B(10): 1313-1320, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31564158

RESUMO

AIMS: The aim of this study was to report the outcomes of patients who underwent definitive surgery for secondary chondrosarcomas arising from osteochondromas. PATIENTS AND METHODS: A total of 51 patients with secondary chondrosarcomas occurring from osteochondromas were reviewed. Median age was 36 years (interquartile range (IQR) 15 to 82). Median follow-up was 6.9 years (IQR 2.8 to 10.6). The pelvis was the most commonly affected site (59%). Histological grades were grade I in 35 (69%), grade II in 13 (25%), and grade III in three patients (6%). RESULTS: Preoperative biopsy histology correctly predicted the final histological grade in 27% of patients. The ten-year disease-specific survival (DSS) for all patients was 89.4%. Local recurrence occurred in 15 patients (29%), more commonly in pelvic tumours (37%) compared with limb tumours (19%). Four patients with pelvic tumours died from progression of local recurrence. No patient with limb tumours died of disease. Wide/radical margin was associated with improved local recurrence-free survival (p = 0.032) and local recurrence was associated with worse DSS (p = 0.005). CONCLUSION: We recommend that a secondary chondrosarcoma arising from osteochondroma of the pelvis is resected with wide/radical resection margins. The balance between the morbidity of surgery and risk of local recurrence needs to be considered in patients with limb secondary chondrosarcomas. Cite this article: Bone Joint J 2019;101-B:1313-1320.


Assuntos
Neoplasias Ósseas/patologia , Condrossarcoma/secundário , Recidiva Local de Neoplasia/mortalidade , Osteocondroma/patologia , Adulto , Biópsia por Agulha , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Condrossarcoma/diagnóstico por imagem , Condrossarcoma/mortalidade , Condrossarcoma/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Extremidades/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Osteocondroma/diagnóstico por imagem , Osteocondroma/mortalidade , Osteocondroma/cirurgia , Ossos Pélvicos/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
3.
Anticancer Res ; 39(10): 5353-5359, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570429

RESUMO

BACKGROUND: Identification of genetic prognostic biomarkers, such as germline variants, are urgently needed to choose optimal treatment for metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: The prognostic value of anoctamin 7 (ANO7) rs77559646 on docetaxel response was tested in a prospective PROSTY randomized trial and a retrospective Auria Biobank set. The variant rs77559646 was genotyped and its association with progression-free survival (PFS) and overall survival (OS) was tested. RESULTS: In comparison with the non-carriers, the variant carriers had longer PFS (p=0.005) and OS (p=0.003) in the PROSTY cohort. In the retrospective cohort, there was a borderline association with PFS (p=0.09), but not in OS (p=0.9). In both cohorts, Cox regression multivariate models revealed that rs77559646 was an independent prognostic factor for favourable PFS. CONCLUSION: The rs77559646 was shown to be a prognostic germline biomarker for better response to docetaxel treatments. To our knowledge, this is the first time that a non-coding germline variant has been associated with chemotherapy of mCRPC.


Assuntos
Anoctaminas/genética , Antineoplásicos/uso terapêutico , Docetaxel/uso terapêutico , Variação Genética/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Idoso , Biomarcadores Tumorais/genética , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos
4.
Anticancer Res ; 39(10): 5669-5674, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570465

RESUMO

BACKGROUND/AIM: We evaluated factors associated with mortality among men with breast cancer. MATERIALS AND METHODS: We used the National Cancer Database to identify men with breast cancer and evaluated factors associated with mortality, using a Cox regression model. RESULTS: Black patients experienced an increased risk of death from any cause compared to white patients [hazard ratio (HR)=1.19, 95%CI=1.05-1.37]. Patients with government insurance had a greater risk of death compared to privately insured patients (HR=1.57, 95%CI=1.41-1.75). When compared to patients with an income of >$46,000, those with an income <$30,000 presented an increased risk of death (HR=1.35, 95%CI=1.14-1.60). Finally, patients treated at a comprehensive community cancer program (HR=1.129, 95%CI=1.021-1.248), community cancer program (HR=1.164, 95%CI=1.010-1.343), or integrated network cancer program (HR=1.216; 95%CI=1.056-1.401) experienced elevated risk of death compared to those treated at academic/research-programs. CONCLUSION: Race, insurance, income, education, and facility type are associated with the risk of mortality in male patients with breast cancer.


Assuntos
Neoplasias da Mama Masculina/mortalidade , Adolescente , Adulto , Afro-Americanos , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Europeu , Disparidades em Assistência à Saúde , Humanos , Cobertura do Seguro , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores Socioeconômicos , Adulto Jovem
5.
Medicine (Baltimore) ; 98(38): e17069, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567942

RESUMO

Although serum magnesium (Mg) levels are closely associated with the prognosis of heart failure (HF) patients, the clinical significance of sMg levels on the cardiovascular outcomes of HF with preserved ejection fraction (HFpEF) patients is not fully understood. This study was a retrospective, single-center, observational study. We enrolled 452 consecutive HFpEF patients admitted to Kumamoto University Hospital. We defined lower sMg as <2.0 mg/dl (=0.8 mmol/L) based on recent clinical evidence and compared their clinical characteristics and prognosis. There were no significant differences between groups in the use of all medications (loop diuretics, mineralocorticoid receptor antagonists, renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, beta blockers, statins, and Mg preparations). The lower sMg group showed a significantly higher prevalence of diabetes mellitus (DM), uric acid levels, and BNP levels compared with the higher sMg group. Kaplan-Meier curve revealed a significantly higher probability of HF-related events in the lower sMg group compared with the higher sMg group (log-rank test, P = .012). Multivariate Cox-proportional-hazard analysis revealed that the lower sMg group had significantly and independently higher probabilities of HF-related events compared with the higher sMg group (hazard ratio = 2.37, 95% confidence intervals = 1.27-4.41, P = .007). We reclassified the risk of HF-related events after adding the lower sMg to the other prognostic factors (age, previous hospitalization for HF, DM, Ln-BNP); the continuous net reclassification improvement was 29.0% (P = .041). sMg levels might provide important prognostic information in regard to HFpEF.


Assuntos
Insuficiência Cardíaca/mortalidade , Magnésio/sangue , Volume Sistólico , Idoso , Ecocardiografia , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Japão , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
6.
Anticancer Res ; 39(10): 5551-5557, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570449

RESUMO

BACKGROUND/AIM: Digestive system cancers are the leading cause of cancer mortality and have poor survival particularly in men. The study aimed to assess the association between pre-diagnosis cardiorespiratory fitness (CRF) and cancer mortality in a pilot sample of men who developed digestive system cancers. PATIENTS AND METHODS: Pre-diagnosis CRF (treadmill exercise test) was assessed in 342 men (68.9±21.8 years) who developed digestive system cancers during 6.7±5 years from baseline evaluation. Cox multivariable hazard models were analyzed for total cancer mortality. RESULTS: During 7.2±5 years follow-up from baseline, 120 participants died from cancer. Compared to low CRF, moderate and high CRF levels were associated with 57% [0.43, 95%CI=0.24-0.74] and 73% [0.27, 95%CI=0.12-0.59] reduced risks for cancer mortality, respectively (p trend=0.002). Survival time from baseline was longer among those with moderate [13.5 (range=12.1-14.9) years] and high [16.1 (range=14.0-18.2) years] compared to low CRF [7.9 (range=5.7-10.1) years]. CONCLUSION: Higher pre-diagnosis CRF is independently associated with lower risk of cancer mortality and longer survival in men who later developed digestive system cancers.


Assuntos
Aptidão Cardiorrespiratória/fisiologia , Neoplasias do Sistema Digestório/mortalidade , Neoplasias do Sistema Digestório/fisiopatologia , Idoso , Índice de Massa Corporal , Teste de Esforço/métodos , Humanos , Masculino , Projetos Piloto , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
7.
J Cancer Res Clin Oncol ; 145(10): 2529-2539, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485768

RESUMO

PURPOSE: This study aimed to determine the potential of positron emission tomography/computed tomography (PET/CT) in replacing routine bone-marrow biopsies (BMB) in newly diagnosed extranodal natural killer/T-cell lymphoma (ENKTCL). METHODS: Newly diagnosed patients underwent PET/CT imaging and routine BMB to assess bone/bone marrow involvement (BMI). Clinical stage and treatment plan were determined, and survival was compared. RESULTS: In a total of 101 patients, 78 were diagnosed as stage I/II and 23 as stage III/IV without using the BMB results. No BMB-positive patients were identified in stages I/II, and therefore, the BMB results did not alter the stage and treatment choice in any patients. The sensitivity and specificity of focal skeletal PET/CT lesion(s) in assessing BMI was 100% and 92.8%, respectively, taking routine BMB as the reference standard. The overall survival (OS) and progression-free survival (PFS) of BMB-positive patients was significantly inferior (P = 0.0011 and 0.0465, respectively, in advanced-stage patients; both P < 0.0001 in all patients), and this was corroborated by the PET/CT findings (P = 0.0006 and 0.0116, respectively, in advanced-stage patients; both P < 0.0001 in all patients). CONCLUSIONS: Based on the results, PET/CT demonstrated satisfactory predictive performance in terms of staging and prognosis in ENKTCL. BMB did not influence staging and treatment in newly diagnosed ENKTCL, and routine non-targeted BMB is not obligatory for early stage patients undergoing PET/CT. Targeted BMB is recommended to confirm BMI in advanced-stage patients.


Assuntos
Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Linfoma Extranodal de Células T-NK/diagnóstico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Idoso , Biomarcadores , Biópsia , Feminino , Humanos , Linfoma Extranodal de Células T-NK/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Modelos de Riscos Proporcionais , Sensibilidade e Especificidade , Análise de Sobrevida , Adulto Jovem
8.
Pan Afr Med J ; 33: 89, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489067

RESUMO

Introduction: Mortality of adult patients who are on antiretroviral therapy (ART) is higher in low-income than in high-income countries. After the failure of standard first-line treatment, patients switch to second-line regimens. However, there are limited data about the outcome of patients after switching to a second-line regimen in the study area. This study aimed to measure the rate of mortality and its determinants among HIV patients on second-line ART regimens. Methods: Multicenter institution based retrospective follow up study was conducted among 1192 adult patients who started second-line ART between 2008 and 2016 in eight selected hospitals of Amhara region. Patients who started second-line treatment after the failure of first-line treatment were included. Patient medical records, registration books, and computer database were used to collect the data. Time to death after a switch to second-line ART was the primary outcome of interest. Cox proportional hazard model was fitted to identify determinant factors of mortality. Results: Among 1192 patients who were on second-line ART, 136 (11.4%) died with 3,157 person-years of follow up. Over the study period, the mortality rate was 4.33 per 100 person-years. Not taking isoniazid preventive therapy (IPT) (Adjusted Hazard Ratio (AHR): 6.6; 95% CI: 2.9, 15.0), did not make modification on second-line regimen (AHR: 4.4; 95% CI: 2.8, 6.8), poor clinical adherence (AHR: 2.5; 95% CI: 1.4, 4.5), functional status of bedridden (AHR: 2.7; 95% CI: 1.5, 4.8), and having attained a tertiary level of education (AHR: 0.4; 95% CI: 0.2, 0.8) were independent determinants of mortality. Conclusion: The incidence rate of mortality was high and most of the deaths occurred within 12 months after switching to second-line ART. Higher mortality among adult HIV-infected patients was associated with poor adherence, no formal education, not taking IPT, being bedridden at the time of the switch, and not modifying second-line treatment. Improving treatment adherence of patients by providing consistent adherence counseling, providing INH prophylaxis and monitoring patient's regimen more closely during the first twelve months after switch could decrease mortality of HIV patients on a second-line regimen.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Isoniazida/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Adolescente , Adulto , Pessoas Acamadas/estatística & dados numéricos , Escolaridade , Etiópia/epidemiologia , Feminino , Seguimentos , Infecções por HIV/mortalidade , Hospitais , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto Jovem
9.
Zhonghua Yi Xue Za Zhi ; 99(35): 2750-2755, 2019 Sep 17.
Artigo em Chinês | MEDLINE | ID: mdl-31550797

RESUMO

Objective: To assess whether acute-phase plasma PCSK9 levels predict recurrent cardiovascular (CV) events in acute myocardial infarction (AMI) patients without receiving reperfusion therapy. Methods: Plasma PCSK9 levels were measured during the acute phase (≤24 hours) in 882 patients who did not undergo reperfusion therapy from the China PEACE-Prospective AMI Study (2012-2014). Associations of acute-phase PCSK9 tertiles with patient characteristics and recurrent CV events at 1 year were assessed using multivariable logistic and Cox proportional hazards regression models. Results: Female gender (odds ratio [OR] 2.86, 95% confidence interval [CI] 1.36-5.98), premature coronary heart disease (CHD) (OR 2.82, 95%CI 1.43-5.53), higher high-sensitivity C-reactive protein (OR 1.69, 95%CI 1.35-2.13), and higher triglycerides (OR 1.93, 95%CI 1.10-3.38) were associated with higher baseline PCSK9 levels. Patients with PCSK9 levels in the highest tertile (versus lowest) did not have an increased risk of 1-year recurrent CV events (HR 0.77, 95%CI 0.44-1.34). Conclusion: Acute-phase plasma PCSK9 levels are associated with levels of inflammation and triglycerides, premature CHD, and gender in AMI patients without reperfusion therapy, however it do not predict recurrent CV events at 1 year.


Assuntos
Infarto do Miocárdio/sangue , Pró-Proteína Convertase 9/sangue , China , Doença das Coronárias/epidemiologia , Feminino , Humanos , Inflamação , Masculino , Infarto do Miocárdio/diagnóstico , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Fatores Sexuais , Triglicerídeos/sangue
10.
Zhonghua Yi Xue Za Zhi ; 99(35): 2781-2784, 2019 Sep 17.
Artigo em Chinês | MEDLINE | ID: mdl-31550803

RESUMO

Objective: To explore the risk factors in HBV-associated hepatocellular carcinoma (HCC) patients with early recurrence after ablation and to establish predictive model. Methods: A total of 81 patients with HBV-related HCC who underwent ablation from January 2016 to December 2016 were included in Beijing Youan Hospital, including 66 males and 15 females. Standard medical records were collected, which were summarized as follows: demographic data, liver function, the number and size of tumors and the modality of ablation. Univariate and multivariate analysis were performed to identify the independent risk factors.The ROC curve was used to determine prognostic value. Cox proportional hazards model was used to establish predictive model, and the scores of risk factors were assigned according to HR value. Patients were divided into high-risk group and low-risk group in accordance with scores.The analysis of early recurrence rate was performed by the Kaplan-Meier method. Results: Tumor number, fibrinogen (Fib) and platelet-lymphocyte rate (PLR) were independently correlated with recurrence-free survival (RFS). The AUCs of Fib, PLR and Fib-PLR were 72.9%, 71.5% and 81.8%. The recurrence rates of the low-risk group were 4.9%,7.3% and 29.3% at 6 months,12 months and 24 months while 14.6%,43.9% and 78.1% in high-risk group. Two groups revealed statistically significant differences (all P<0.05). Conclusion: Tumor number, Fib, and PLR may be used as a set of predictive indicator of early recurrence in HBV-associated HCC patients after ablation.


Assuntos
Carcinoma Hepatocelular/sangue , Fibrinogênio/análise , Hepatite B/sangue , Neoplasias Hepáticas/sangue , Contagem de Linfócitos , Contagem de Plaquetas , Carcinoma Hepatocelular/virologia , Feminino , Humanos , Neoplasias Hepáticas/virologia , Masculino , Recidiva Local de Neoplasia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(9): 845-850, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31506140

RESUMO

OBJECTIVE: To investigate the factors in first-time adrenocorticotropic hormone (ACTH) therapy and their influence on spasm control time in infants with infantile spasms. METHODS: A total of 72 infants with infantile spasms who were admitted from January 2008 to October 2013 were enrolled. Their clinical data were collected, and the exposure factors for infantile spasms were selected. A Cox proportional-hazards regression model analysis was performed for these factors to analyze their influence on spasm control time. RESULTS: Clarification of the etiology (known or unexplained etiology), frequency of spasms before treatment, and presence or absence of combination therapy (ACTH used alone or in combination with magnesium sulfate) had a significant influence on spasm control time in infants with infantile spasms. The infants with a known etiology had a significantly shorter spasm control time than those with unexplained etiology, and the infants with a low frequency of spasms before treatment and receiving ACTH combined with magnesium sulfate early had a significantly longer spasm control time than their counterparts (P<0.05). CONCLUSIONS: For infants with infantile spasms at initial diagnosis, etiology should be clarified, which may helpful for evaluating prognosis. A combination of ACTH and magnesium sulfate should be given as soon as possible, which may improve their prognosis.


Assuntos
Hormônio Adrenocorticotrópico/uso terapêutico , Espasmos Infantis , Anticonvulsivantes , Humanos , Lactente , Modelos de Riscos Proporcionais , Espasmo , Espasmos Infantis/tratamento farmacológico
12.
N Engl J Med ; 381(12): 1103-1113, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31475793

RESUMO

BACKGROUND: There are limited data from randomized trials evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease. METHODS: In a multicenter, open-label trial conducted in Japan, we randomly assigned 2236 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) more than 1 year earlier or who had angiographically confirmed coronary artery disease not requiring revascularization to receive monotherapy with rivaroxaban (a non-vitamin K antagonist oral anticoagulant) or combination therapy with rivaroxaban plus a single antiplatelet agent. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause; this end point was analyzed for noninferiority with a noninferiority margin of 1.46. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority. RESULTS: The trial was stopped early because of increased mortality in the combination-therapy group. Rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point, with event rates of 4.14% and 5.75% per patient-year, respectively (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P<0.001 for noninferiority). Rivaroxaban monotherapy was superior to combination therapy for the primary safety end point, with event rates of 1.62% and 2.76% per patient-year, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01 for superiority). CONCLUSIONS: As antithrombotic therapy, rivaroxaban monotherapy was noninferior to combination therapy for efficacy and superior for safety in patients with atrial fibrillation and stable coronary artery disease. (Funded by the Japan Cardiovascular Research Foundation; AFIRE UMIN Clinical Trials Registry number, UMIN000016612; and ClinicalTrials.gov number, NCT02642419.).


Assuntos
Fibrilação Atrial/tratamento farmacológico , Doença das Coronárias/terapia , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Ponte de Artéria Coronária , Doença das Coronárias/complicações , Quimioterapia Combinada/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Modelos de Riscos Proporcionais , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Rivaroxabana/efeitos adversos
13.
JAMA ; 322(9): 834-842, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479138

RESUMO

Importance: The optimal international normalized ratio (INR) to prevent venous thromboembolism (VTE) in warfarin-treated patients with recent arthroplasty is unknown. Objective: To determine the safety and efficacy of a target INR of 1.8 vs 2.5 for VTE prophylaxis after orthopedic surgery. Design, Setting, and Participants: The randomized Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis enrolled 1650 patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions: In a 2 × 2 factorial design, participants were randomized to a target INR of 1.8 (n = 823) or 2.5 (n = 827) and to either genotype-guided or clinically guided warfarin dosing. For the first 11 days of therapy, open-label warfarin dosing was guided by a web application. Main Outcomes and Measures: The primary outcome was the composite of VTE (within 60 days) or death (within 30 days). Participants underwent screening duplex ultrasound postoperatively. The hypothesis was that an INR target of 1.8 would be noninferior to an INR target of 2.5, using a noninferiority margin of 3% for the absolute risk of VTE. Secondary end points were bleeding and INR values of 4 or more. Results: Among 1650 patients who were randomized (mean age, 72.1 years; 1049 women [63.6%]; 1502 white [91.0%]), 1597 (96.8%) received at least 1 dose of warfarin and were included in the primary analysis. The rate of the primary composite outcome of VTE or death was 5.1% (41 of 804) in the low-intensity-warfarin group (INR target, 1.8) vs 3.8% (30 of 793) in the standard-treatment-warfarin group (INR target, 2.5), for a difference of 1.3% (1-sided 95% CI, -∞ to 3.05%, P = .06 for noninferiority). Major bleeding occurred in 0.4% of patients in the low-intensity group and 0.9% of patients in the standard-intensity group, for a difference of -0.5% (95% CI, -1.6% to 0.4%). The INR values of 4 or more occurred in 4.5% of patients in the low-intensity group and 12.2% of the standard-intensity group, for a difference of -7.8% (95% CI, -10.5% to -5.1%). Conclusions and Relevance: Among older patients undergoing hip or knee arthroplasty and receiving warfarin prophylaxis, an international normalized ratio goal of 1.8 compared with 2.5 did not meet the criterion for noninferiority for risk of the composite outcome of VTE or death. However, the trial may have been underpowered to meet this criterion and further research may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01006733.


Assuntos
Anticoagulantes/administração & dosagem , Artroplastia de Quadril , Artroplastia do Joelho , Coeficiente Internacional Normatizado , Tromboembolia Venosa/prevenção & controle , Varfarina/administração & dosagem , Idoso , Anticoagulantes/efeitos adversos , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Tromboembolia Venosa/mortalidade , Varfarina/efeitos adversos
14.
Pan Afr Med J ; 33: 111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489089

RESUMO

Introduction: High mortality among individuals receiving retreatment for tuberculosis (RT-TB) persists, although reasons for these poor outcomes remain unclear. Methods: We retrospectively reviewed 394 RT-TB patients diagnosed between January 2010 and June 2016 in Accra, Ghana. Results: Of RT-TB patients, 161 (40.9%) were treated empirically (negative/absent smear, culture or Xpert), of whom 30.4% (49/161) had only extrapulmonary TB signs or symptoms. Mortality during treatment was 19.4%; 15-day mortality was 10.8%. In multivariable proportional hazards regression, living with HIV (aHR=2.69 [95 CI: 1.51, 4.80], p<0.01) and previous loss-to-follow up (aHR=8.27 (95 CI: 1.10, 62.25), p=0.04) were associated with mortality, while drug susceptibility testing (DST, aHR=0.36 (95 CI: 0.13, 1.01), p=0.052) was protective. Isoniazid resistance was observed in 40% (23/58 tested) and rifampin resistance in 19.1% (12/63 tested). Conclusion: High rates of extrapulmonary TB and smear/culture negative disease highlight the barriers to achieving DST-driven RT-TB regimens and the need for improved diagnostics. Our finding of poly-drug resistance in rifampin-susceptible cases supports access to comprehensive first line DST. Additionally, interventions to reduce mortality, especially in HIV co-infected RT-TB patients, are urgently needed.


Assuntos
Antituberculosos/administração & dosagem , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose/tratamento farmacológico , Adulto , Antituberculosos/farmacologia , Estudos de Coortes , Farmacorresistência Bacteriana Múltipla , Feminino , Gana , Infecções por HIV/epidemiologia , Humanos , Isoniazida/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Retratamento , Estudos Retrospectivos , Rifampina/farmacologia , Tuberculose/microbiologia , Tuberculose/mortalidade , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade
15.
Anticancer Res ; 39(9): 4603-4612, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519557

RESUMO

BACKGROUND/AIM: Sarcopenia describes the loss of skeletal muscle mass. While this condition is associated with a high mortality in cancer patients, its influence on survival is still underestimated. PATIENTS AND METHODS: A systematic review for articles was performed using the PubMed database, Cochrane Library, Biomed Central, Science Direct and by manual search. We used data of overall survival in sarcopenic patients for assessing the death risk. We extracted hazard ratio estimates from univariate and multivariate Cox proportional hazards models for meta-analysis. RESULTS: A total of 15 studies were eligible for meta-analysis including a total of 2,521 lung cancer patients. Univariate meta-analysis revealed a two-fold increased death risk in sarcopenic patients; multivariate meta-analysis yielded a significant, three-fold elevated risk of death. This higher mortality is independent of tumour stage. CONCLUSION: Muscle loss is an independent risk factor for increased death risk in lung cancer patients independent of cancer stage. This argues for implementing screening for sarcopenia into cancer care.


Assuntos
Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Sarcopenia/etiologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Músculo Esquelético/patologia , Estadiamento de Neoplasias , Tamanho do Órgão , Prognóstico , Modelos de Riscos Proporcionais , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia
16.
Anticancer Res ; 39(9): 4699-4709, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519569

RESUMO

BACKGROUND/AIM: Metformin, a drug for type 2 diabetes, also exerts anticancer effects. This study addressed the immunological effects of metformin on peritoneal dissemination. MATERIALS AND METHODS: We developed a mouse model of peritoneal dissemination via intraperitoneal injection of RLmale1, an X-ray-induced leukemia cell line, into BALB/c mice. Cell-surface markers, cytokine production, and myeloid-derived suppressor cells (MDSCs) were examined in cells from spleen and peritoneal lavage fluid. RESULTS: Metformin-treated mice exhibited suppressed intraperitoneal tumor growth and extended survival, and these effects were lost in mice with severe combined immunodeficiency. MDSCs induction was inhibited in metformin-treated mice. Although MDSC mobilization into the peritoneal cavity was correlated with suppression of interferon-γ production by tumor-infiltrating lymphocytes, the T-helper 1 ability of these lymphocytes was preserved in metformin-treated mice. CONCLUSION: Our findings demonstrate the action of metformin on both intraperitoneal tumors and immune-suppressive cells and might contribute to the development of immunotherapy against peritoneal dissemination.


Assuntos
Imunomodulação/efeitos dos fármacos , Metformina/farmacologia , Neoplasias Peritoneais/imunologia , Neoplasias Peritoneais/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Animais , Biomarcadores , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Imunofenotipagem , Masculino , Camundongos , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Metástase Neoplásica , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/mortalidade , Modelos de Riscos Proporcionais , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Anticancer Res ; 39(9): 4987-4993, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519605

RESUMO

BACKGROUND/AIM: For immune checkpoint inhibitor (ICI)-pretreated patients, docetaxel and ramucirumab (DOC+RAM) combination therapy may be more effective compared to patients not receiving ICI treatment. PATIENTS AND METHODS: From June 2013 to July 2018, 39 patients with advanced/recurrent non-small cell lung cancer underwent DOC+RAM therapy. We analyzed the efficacy and safety of DOC+RAM therapy based on the presence (pre-ICI+) or absence (pre-ICI-) of ICI pretreatment history. RESULTS: Of the 39 patients treated with DOC+RAM, we identified 18 (46%) pre-ICI+ patients. Overall response rates for DOC+RAM concerning pre-ICI+ and pre-ICI- patients were 38.9% vs. 19.0%, respectively. Median progression-free survival (PFS) was 5.7 vs. 2.3 months [hazard ratio(HR)=0.36; 95% confidence interval (CI)=0.16-0.80]. Adverse events such as fever, myalgia, arthritis, pleural effusion, and pneumonitis tended to be increased in pre-ICI+ patients. CONCLUSION: Despite increased toxicity concerns, DOC+RAM therapy in pre-ICI+ patients showed a trend for tumor regression improvement and statistically significant prolongation of PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Docetaxel/administração & dosagem , Sinergismo Farmacológico , Feminino , Humanos , Imunomodulação/efeitos dos fármacos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
18.
Anticancer Res ; 39(9): 5009-5018, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519608

RESUMO

BACKGROUND/AIM: Interleukin (IL)-18, which belongs to the IL-1 superfamily of cytokines, is a known interferon-gamma (IFN-γ)-inducing factor. Since IFN-γ plays an essential role in anticancer immunity mediated through cytotoxic T cells, IL-18 may also contribute to the function of immunosurveillance. The aim of the study was to examine the association of IL-18 with the outcomes of patients with breast cancer. PATIENTS AND METHODS: Serum IL-18 levels were determined at baseline in 270 patients operated for breast cancer, and the relapse-free survival (RFS) was compared between IL-18-high and -low groups. The relationships between IL-18 and tumor-infiltrating lymphocytes (TILs) or the neutrophil-to-lymphocyte ratio (NLR) were also investigated. RESULTS: The RFS of patients was significantly better in the IL-18-low group than in the IL-18-high group (p=0.032). According to the multivariate analysis, IL-18 was a significant and independent predictive factor for RFS (hazard ratio(HR)=0.336; 95% confidence interval(CI)=0.147-0.727; p=0.0053). No association was observed between the IL-18 levels and TILs or NLRs. CONCLUSION: IL-18 levels may be useful for predicting the prognosis of patients who have received surgical treatment for breast cancer.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Interleucina-18/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Citocinas/sangue , Citocinas/metabolismo , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neutrófilos/imunologia , Neutrófilos/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Valores de Referência , Estudos Retrospectivos , Carga Tumoral
19.
Anticancer Res ; 39(9): 5027-5031, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519610

RESUMO

AIM: The purpose of this study was to identify patient-, facility-, disease-, and treatment-specific characteristics that increase mortality in patients with upper limb osteosarcoma. PATIENTS AND METHODS: The National Cancer Data Base (NCDB) was queried for bone cancer. With Cox regression, the demographic, facility, tumor-specific and treatment characteristics were analyzed to identify factors that increased mortality. RESULTS: Cox regression model showed that patients older than 40 years had a significantly higher likelihood of dying from upper limb osteosarcoma than those aged 0-14 years [hazard ratio (HR)=4.12, 95% confidence interval (CI)=2.261-7.508]. Patients with an income of $38,000-47,999 (HR=3.335, 95%CI=1.694-657) or less than $38,000 (HR=2.41, 95%CI=1.098-5.288) were also at greater risk of dying from their tumor. Patients who received radiation therapy (HR=2.457, 95%CI=1.056-5.717) had a higher likelihood of dying than patients who did not undergo this therapy. CONCLUSION: Age, gender, income, education, stage at diagnosis, radiation therapy and type of surgery seem to increase mortality from upper limb osteosarcoma.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Extremidade Superior/patologia , Adolescente , Adulto , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estadiamento de Neoplasias , Osteossarcoma/epidemiologia , Osteossarcoma/terapia , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Socioeconômicos , Carga Tumoral , Estados Unidos/epidemiologia , Adulto Jovem
20.
Anticancer Res ; 39(9): 5135-5142, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519625

RESUMO

AIM: To compare the overall survival (OS) of patients with locoregional and metastatic breast cancer (BC) considering baseline demographic, clinical and contextual characteristics. MATERIALS AND METHODS: A retrospective analysis of a cancer registry was conducted, using the Kaplan-Meier and Mantel-Cox analyses for the calculation of median OS and cumulative survival. RESULTS: The median OS was 112 months, being longer in patients with locoregional versus those with metastatic BC at diagnosis (115 vs. 31 months, p<0.001). The cumulative survival at 1, 3 and 5 years were 94.9%, 85.6% and 76.5%, respectively. More recent year of diagnosis [hazard ratio (HR)=1.09] and age at diagnosis (≥65 vs. 40 years, HR=2.79) and presence of metastatic disease (HR=5.69) were associated with a shorter OS. The region of residence, morphology and topography of the tumor were also associated with survival in patients with BC. Rurality was only associated with lower survival in patients with metastatic BC. CONCLUSION: This study identified significant differences in the median OS of patients with locoregional and those with metastatic BC considering their baseline characteristics.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Adulto Jovem
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