RESUMO
Importance: Biomarkers to guide the use of pertuzumab in the treatment of early-stage ERBB2 (formerly HER2)-positive breast cancer beyond simple ERBB2 status are needed. Objective: To determine if use of the HER2DX genomic assay (Reveal Genomics) in pretreatment baseline tissue samples of patients with ERBB2-positive breast cancer is associated with response to neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab. Design, Setting, and Participants: This is a retrospective diagnostic/prognostic analysis of a multicenter academic observational study in Spain performed during 2018 to 2022 (GOM-HGUGM-2018-05). In addition, a combined analysis with 2 previously reported trials of neoadjuvant cohorts with results from the assay (DAPHNe and I-SPY2) was performed. All patients had stage I to III ERBB2-positive breast cancer, signed informed consent, and had available formalin-fixed paraffin-embedded tumor specimens obtained prior to starting therapy. Exposures: Patients received intravenous trastuzumab, 8 mg/kg, loading dose, followed by 6 mg/kg every 3 weeks in combination with intravenous docetaxel, 75 mg/m2, every 3 weeks and intravenous carboplatin area under the curve of 6 every 3 weeks for 6 cycles, or this regimen plus intravenous pertuzumab, 840 mg, loading dose, followed by an intravenous 420-mg dose every 3 weeks for 6 cycles. Main Outcome and Measures: Association of baseline assay-reported pathologic complete response (pCR) score with pCR in the breast and axilla, as well as association of baseline assay-reported pCR score with response to pertuzumab. Results: The assay was evaluated in 155 patients with ERBB2-positive breast cancer (mean [range] age, 50.3 [26-78] years). Clinical T1 to T2 and node-positive disease was present in 113 (72.9%) and 99 (63.9%) patients, respectively, and 105 (67.7%) tumors were hormone receptor positive. The overall pCR rate was 57.4% (95% CI, 49.2%-65.2%). The proportion of patients in the assay-reported pCR-low, pCR-medium, and pCR-high groups was 53 (34.2%), 54 (34.8%), and 48 (31.0%), respectively. In the multivariable analysis, the assay-reported pCR score (as a continuous variable from 0-100) showed a statistically significant association with pCR (odds ratio [OR] per 10-unit increase, 1.43; 95% CI, 1.22-1.70; P < .001). The pCR rates in the assay-reported pCR-high and pCR-low groups were 75.0% and 28.3%, respectively (OR, 7.85; 95% CI, 2.67-24.91; P < .001). In the combined analysis (n = 282), an increase in pCR rate due to pertuzumab was found in the assay-reported pCR-high tumors (OR, 5.36; 95% CI, 1.89-15.20; P < .001) but not in the assay-reported pCR-low tumors (OR, 0.86; 95% CI, 0.30-2.46; P = .77). A statistically significant interaction between the assay-reported pCR score and the effect of pertuzumab in pCR was observed. Conclusions and Relevance: This diagnostic/prognostic study demonstrated that the genomic assay predicted pCR following neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab. This assay could guide therapeutic decisions regarding the use of neoadjuvant pertuzumab.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Genômica , Terapia Neoadjuvante/métodos , Receptor ErbB-2/genética , Receptor ErbB-2/análise , Estudos Retrospectivos , Trastuzumab/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION AND OBJECTIVES: To analyze the profile of left atrial wall velocities by pulsed wave tissue Doppler imaging, and to compare the relationship between these observations and the transmitral and pulmonary vein flow velocities obtained by conventional pulsed Doppler echocardiography. PATIENTS AND METHOD: We studied 90 patients (50 women and 40 men, mean age 48 [22] years). Pulsed tissue Doppler images of the left atrial wall were obtained and analyzed in all subjects. The study population was then divided in two groups: group I (age < 45 years) and group II (age > 45 years). Transmitral and pulmonary vein flow velocity tracings were obtained simultaneously by pulsed Doppler echocardiography. RESULTS: With pulsed tissue Doppler interrogation of the left atrial wall, a triphasic signal was recorded in all patients, consisting of a positive wave (A1) followed by two negative waves (A2 and A3). Younger subjects (group I) showed a pattern with a prominent A2 wave and an A2/A3 ratio > 1. In older patients (group II) peak velocity of the A2 wave diminished and peak velocity of the A3 wave increased, so that the A2/A3 ratio was < 1. We found no differences in peak velocity of the A1 wave between the two age groups (13.5 (3.9) cm/s in group I vs 13.1 (5.4) cm/s in group II; P = .59). Significant concordance was observed between the transmitral flow pattern and the left atrial pulsed tissue Doppler tracing (kappa = 0.584; P < .0001). CONCLUSIONS: Evaluation of the left atrial wall using pulsed tissue Doppler imaging is feasible and reproducible. Tissue Doppler imaging provides new quantitative insights of potential use in the assessment of left atrial function.
Assuntos
Função do Átrio Esquerdo/fisiologia , Átrios do Coração/diagnóstico por imagem , Adolescente , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Criança , Ecocardiografia Doppler de Pulso , Feminino , Átrios do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/fisiologiaRESUMO
INTRODUCTION AND OBJECTIVES: Myocardial contractile reserve studies with low-dose dobutamine echocardiography have been shown to be useful to assess functional myocardial status. However, the variables associated with contractile reserve after inotropic stimulation are not well known. PATIENTS AND METHOD: We studied 50 patients (35 men, mean age 56.4 +/- 9.5 years) with nonischemic dilated cardiomyopathy (NIDC), LVEF 28.7% +/- 8.5% and wall motion score index (WMSI) 2.42 +/- 0.34 with low-dose dobutamine echocardiography. Left ventricular contractile reserve was assessed by a differential parameter defined as the difference between rest and stress WMSI (DeltaWMSI). RESULTS: After dobutamine infusion the WMSI was 1.95 +/- 0.58; from this value we calculated a DeltaWMSI of 0.45 +/- 0.39. None of the clinical variables showed a relationship with the presence of contractile reserve. In contrast, the following echocardiographic parameters correlated with DeltaWMSI: end-diastolic (p=0.05) and end-systolic (p=0.02) diameters, end-systolic volume index (p=0.01) and LVEF (p=0.002). In the multivariate analysis, only end-diastolic diameter was an independent predictor of contractile reserve (hazard ratio=0.852; 95% CI, 0.735-0.987; p=0.03). CONCLUSIONS: Ventricular diameters, end-systolic volume index and LVEF are related with improvements in myocardial contractility after dobutamine infusion, although only end-diastolic diameter was an independent predictor of contractile reserve. Thus, this parameter should receive particular attention in evaluations of the functional status of the myocardium in patients with NIDC.
Assuntos
Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/fisiopatologia , Ecocardiografia sob Estresse , Contração Miocárdica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
INTRODUCTION AND OBJECTIVES: C-reactive protein (CRP), whose synthesis in the liver is regulated by interleukin 6 (IL-6), is related with the prognosis for ischemic heart disease. The aim of this study was to evaluate the effect of early administration of pravastatin on plasma levels of CRP and IL-6 in patients with acute myocardial infarction and ST segment elevation. PATIENTS AND METHOD: 71 patients were randomized during the first 10 hours from the onset of symptoms to receive 40 mg of pravastatin once a day or not. CRP and IL-6 were measured on admission, 48 hours and 7 days later. CRP was also measured 2 months later. RESULTS: On admission, levels of CRP and IL-6 were similar in both groups. After 7 days of treatment the administration of pravastatin was associated with a lower level of CRP (P=.002). Mean and median CRP levels decreased from 48 hours to day 7 by 48.4% and 51.9% respectively in the pravastatin group, and by 32.5% and 15.9% respectively in the control group. In contrast, no significant differences in IL-6 levels were observed between the two groups. After 2 months of follow-up, 50% of the treated patients and 25% of the control patients had CRP levels lower than 6.6 mg/L (P=.039). CONCLUSIONS: Early administration of pravastatin in the acute phase of myocardial infarction with ST segment elevation was associated with a lower level of CRP after 7 days of treatment, with no concomitant changes in IL-6 levels.
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Anticolesterolemiantes/administração & dosagem , Proteína C-Reativa/análise , Interleucina-6/sangue , Infarto do Miocárdio/tratamento farmacológico , Pravastatina/administração & dosagem , Idoso , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Fatores de TempoAssuntos
Anafilaxia/diagnóstico , Anticorpos Monoclonais Humanizados/efeitos adversos , Teste de Degranulação de Basófilos , Basófilos/imunologia , Neoplasias da Mama/diagnóstico , Dessensibilização Imunológica , Hipersensibilidade a Drogas/diagnóstico , Adulto , Anafilaxia/etiologia , Anafilaxia/prevenção & controle , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/terapia , Feminino , Humanos , Metástase Neoplásica , Receptor ErbB-2/metabolismo , Resultado do TratamentoRESUMO
Fracture-dislocation of the humeral head into the thoracic cavity is a rare injury. We present one such case in a 70-year-old woman. She presented with a 4-part fracture-dislocation of the proximal humerus, with displacement of the humeral head into the thoracic cavity. She had no signs of acute distress or hemodynamic instability. She underwent hemiarthroplasty of the right shoulder, but the humeral head fragment could not be removed. At 27-month follow-up, the patient had limited mobility of her right shoulder due to axillary nerve palsy but no pain or intrathoracic complications. In the absence of intrathoracic complications, the removal of the humeral head may not be necessary.
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Fraturas do Úmero/complicações , Procedimentos Ortopédicos/métodos , Luxação do Ombro/complicações , Traumatismos Torácicos/etiologia , Idoso , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Luxação do Ombro/diagnóstico por imagem , Luxação do Ombro/cirurgia , Traumatismos Torácicos/diagnóstico por imagem , Traumatismos Torácicos/cirurgia , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION AND OBJECTIVES: Tumor necrosis factor-alpha (TNFalpha in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to determine the prognostic value of TNFalpha in this clinical setting at six-month follow-up. METHODS: The levels of TNFalpha, C-reactive protein (CRP), interleukin 6 and type 1 soluble intercellular adhesion molecules measured within the first 10 h of symptom onset and at 48 h in 74 consecutive patients admitted with STEMI. The relationships between these levels and the incidence of ischemic events (i.e., angina, reinfarction, and death), heart failure (HF), or both (i.e., all cardiovascular events) were studied. RESULTS: Overall, TNFalpha levels were significantly higher in patients who had an ischemic event or HF than in those who did not (P<.02 for both). At 48 h, the adjusted odds ratios of those in the highest TNFalpha quartile (2.92 pg/mL) for the development of ischemic events, HF, and all cardiovascular events combined were 13.1, 9.59 and 9.75, respectively. A TNFalpha level of 2.04 pg/mL at 48 h had a sensitivity of 78% and a specificity of 72.5% in predicting a cardiovascular event of any form. The CRP level, but not the TNFalpha level, at admission was found to be an independent predictor of the development of a cardiovascular events. CONCLUSIONS: In patients with STEMI, the plasma TNFalpha level 48 h after symptom onset and the CRP level at admission were independent predictors of cardiovascular events.
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Angina Pectoris/sangue , Insuficiência Cardíaca/sangue , Infarto do Miocárdio/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/etiologia , Angina Pectoris/mortalidade , Biomarcadores/sangue , Proteína C-Reativa/análise , Métodos Epidemiológicos , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Prognóstico , Recidiva , Fatores de Tempo , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
In this work an excitation emission molecular fluorescence technique with PARAFAC calibration is proposed for enrofloxacine determination in feeding water from poultry farms. In accordance with the working criteria of the 2002/657/EC European Decision, the proposed method has a capability of detection, CCbeta, of 6.8 microg l(-1), for both probabilities of false positive and false negative of 5%. The accuracy of the method is demonstrated and its precision is 1.7 microg l(-1), expressed as standard deviation. This method allows one to identify and determine the quantity of enrofloxacine present in water samples from poultry farms without it being necessary to determine the possible interferents, nor separate them in a step previous to calibration.