RESUMO
BACKGROUND: Hormone receptor (HR)-positive breast cancer is a disease for which no immune checkpoint inhibitors have shown promise as effective therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors synergistically increased the effectiveness of antiprogrammed cell death protein-1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) antibodies in preclinical studies. METHODS: This non-randomized, multicohort, phase II study evaluated the efficacy and safety of the anti-PD-1 antibody nivolumab 240 mg administered every 2 weeks in combination with the CDK4/6 inhibitor abemaciclib 150 mg twice daily and either fulvestrant (FUL) or letrozole (LET) as a first-line or second-line treatment for HR-positive HER2-negative metastatic breast cancer. The primary end point was the objective response rate (ORR), and secondary end points were toxicity, progression-free survival, and overall survival. Blood, tissue, and fecal samples were collected at multiple points for correlative studies to evaluate immunity biomarkers. RESULTS: From June 2019 to early study termination due to safety concerns on July 2020, 17 patients were enrolled (FUL: n=12, LET: n=5). One patient with a prior treatment history in the FUL cohort was excluded. ORRs were 54.5% (6/11) and 40.0% (2/5) in the FUL and LET cohorts, respectively. Treatment-emergent (TE) adverse events (AEs) of grade ≥3 occurred in 11 (92%) and 5 (100%) patients in the FUL and LET cohorts, respectively. The most common grade ≥3 TEAEs were neutropenia (7 (58.3%) and 3 (60.0%) in the FUL and LET cohorts, respectively), followed by alanine aminotransferase elevation (5 (41.6%) and 4 (80.0%)). One treatment-related death from interstitial lung disease occurred in the LET cohort. Ten patients developed liver-related grade ≥3 AEs. Liver biopsy specimens from 3 patients showed hepatitis characterized by focal necrosis with predominant CD8+ lymphocyte infiltration. Marked elevation of tumor necrosis factor-related cytokines and interleukin-11, and a decrease in peripheral regulatory T cells (Tregs), were observed in patients with hepatotoxicity. These findings suggest that treatment-related toxicities were immune-related AEs likely caused by proinflammatory cytokine production and suppression of Treg proliferation due to the addition of abemaciclib to nivolumab therapy. CONCLUSIONS: Although the combination of nivolumab and abemaciclib was active, it caused severe and prolonged immune-related AEs. TRIAL REGISTRATION NUMBER: JapicCTI-194782, jRCT2080224706, UMIN000036970.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Nivolumabe/uso terapêutico , Aminopiridinas/uso terapêutico , Benzimidazóis/uso terapêutico , Letrozol , AnticorposRESUMO
BACKGROUND: The simple risk index recorded in the emergency room (ER-SRI), which is calculated using the formula (heart rate × [age / 10]2) / systolic blood pressure, was shown to be able to stratify the prognosis in ST-elevation myocardial infarction (STEMI) patients. However, the prognostic impact of the prehospital simple risk index (Pre-SRI) remains unknown.MethodsâandâResults: This study enrolled 2,047 STEMI patients from the Mie Acute Coronary Syndrome (ACS) registry. Pre-SRI was calculated using prehospital data and ER-SRI was calculated using emergency room data. The primary endpoint was 30-day all-cause mortality. The cut-off values of Pre-SRI and ER-SRI for predicting 30-day mortality were 34.8 and 34.1, with accuracies of 0.816 and 0.826 based on receiver operating characteristic analyses (P<0.001 for both). There was no difference in the accuracy of the 2 indices. Multivariate Cox regression analysis demonstrated that a High Pre-SRI (≥34) was a significant independent predictor of 30-day mortality. With combined Pre-SRI and ER-SRI assessment, patients with High Pre-SRI/High ER-SRI showed significantly higher mortality than those with High Pre-SRI/Low ER-SRI, Low Pre-SRI/High ER-SRI, and Low Pre-SRI/Low ER-SRI (P<0.001). The addition of High Pre-SRI to High ER-SRI showed incremental prognostic value of the Pre-SRI. CONCLUSIONS: Pre-SRI can identify high-risk STEMI patients at an early stage and combined assessment with Pre-SRI and ER-SRI could be of incremental prognostic value for risk stratification in STEMI patients.
Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Criança , Prognóstico , Risco , Síndrome Coronariana Aguda/diagnóstico , Serviço Hospitalar de Emergência , Medição de RiscoRESUMO
BACKGROUND: Higher body mass index (BMI) is associated with worse prognosis in pre- and postmenopausal patients with breast cancer (BC). However, there is insufficient evidence regarding the optimal adjuvant endocrine therapy for obese premenopausal women with hormone receptor (HR)-positive BC. AIM: To evaluate the impact of obesity and adjuvant endocrine therapy on prognosis in premenopausal patients with BC. METHODS AND RESULTS: We retrospectively reviewed the medical record of premenopausal women who received curative surgery for clinical stage I-III HR-positive BC from 2007 to 2017. Patients were classified into five groups according to BMI: underweight (UW), normal weight (NW), obese 1 degree (OB1), obese 2 degree (OB2), and obese 3 degree (OB3) categories. The primary analysis was a comparison of BC-specific survival (BCSS) according to BMI (UW/NW vs. OB1-3) and adjuvant endocrine therapy (with or without ovarian function suppression [OFS]). Of 13 021 patients, the data of 3380 patients were analyzed. BCSS in OB1-3 patients was significantly worse than that in patients with UW/NW (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.40-4.02: p = .0009). In OB1-3 patients who received tamoxifen (TAM), BCSS was significantly worse than that in UW/NW patients (p = .0086); however, a significant difference was not shown in patients who received TAM and OFS (p = .0921). CONCLUSION: High BMI was associated with worse prognosis in premenopausal patients with HR-positive BC who received adjuvant TAM. The role of OFS as adjuvant endocrine therapy remains unclear, and further studies are required to explore the adequate management of obese premenopausal patients.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Estudos Retrospectivos , Antineoplásicos Hormonais/uso terapêutico , Tamoxifeno , Prognóstico , ObesidadeRESUMO
Background: Even though hospital admissions for acute myocardial infarction (AMI) decreased globally during the COVID-19 pandemic in early 2020, limited information is available on subsequent demographic trends in the number of cases and management of AMI through the first 12 months of the COVID-19 pandemic. MethodsâandâResults: We assessed demographic trends, patient characteristics, and AMI outcomes (n=730) during the first 12 months of the COVID-19 pandemic and compared them with corresponding months during the control period (February 2016-January 2020; n=2,742) using data from the Mie ACS Registry. Although a 25.8% reduction in hospitalizations for AMI was observed in the 3 months following the declaration of a state of emergency (47.7 vs. 64.3/month; P=0.002), the total number of AMI patients was similar between the 12-month COVID-19 and control periods (60.8 vs. 57.2/month; P=0.58). The number of patients requiring direct ambulance transport was lower in the first half of the COVID-19 than control period (44.4% vs. 51.5; P=0.028). In-hospital mortality was higher in the second half of the COVID-19 than control period (8.9% vs. 5.8%; P=0.032). Conclusions: Through the first 12 months of the COVID-19 pandemic, the number of AMI cases was similar to that in previous years. The COVID-19 pandemic changed the behavior of AMI patients and both pre- and in-hospital medical management, which significantly affected the severity and prognosis of AMI.
RESUMO
PURPOSE: This study investigated the clinical impact of pretreatment neutrophil-to-lymphocyte ratio (NLR) on survival in patients with oligometastatic breast cancer. PATIENTS AND METHODS: We collected data from 397 patients who underwent primary breast surgery from 2004 to 2015 and developed recurrence during the follow-up. We reviewed the images and clinical information and defined OMD according to the European Society for Medical Oncology advanced breast cancer guidelines. The NLR was calculated using pretreatment data of primary breast cancer. The cutoff value of the NLR was determined by receiver operating characteristic curve with Youden Index. RESULTS: Among 397 patients, 131 had OMD at recurrence. The low-NLR group included patients of significantly older age at primary cancer than those in the high-NLR group. A low NLR indicated a better overall survival (p = 0.023) after adjusting for relevant factors, including estrogen receptor status, surgical resection of metastatic disease, metastatic organ number, disease-free interval, and liver metastasis than did the high-NLR group. We developed prognostic models for OMD using six independent prognostic factors, including the NLR. The number of factors was associated with overall survival; patients with all six favorable factors showed a good overall survival of 90.9% at 8 years and those with four or more factors showed 70.4%. CONCLUSIONS: The NLR was an independent prognostic factor for overall survival in OMD. The number of favorable prognostic factors was associated with overall survival. A prognostic model, including the NLR, will help identify patients with a favorable prognosis.
Assuntos
Neoplasias da Mama , Neutrófilos , Humanos , Feminino , Neutrófilos/patologia , Neoplasias da Mama/patologia , Contagem de Linfócitos , Receptores de Estrogênio , Linfócitos/patologia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Aortic valve stenosis (AS) leads to increased cardiovascular mortality and morbidity, and recent studies reported that even mild-to-moderate AS was associated with poor prognosis in the general population. This study investigated the prognostic impact of mild or moderate AS, defined as 2.0 m/s ≤ peak aortic jet velocity (Vmax) ≤3.9 m/s using echocardiography in acute myocardial infarction (AMI) patients.MethodsâandâResults: This study enrolled 3,049 AMI patients using data from the Mie ACS registry. Patients were divided into 2 groups according to Vmax: Group 1: Vmax <2.0 m/s and/or visually intact aortic valve in which all 3 leaflets are fully and evenly open; Group 2: 2.0 m/s ≤ Vmax ≤ 3.9 m/s. There were 2,976 patients in Group 1and 73 patients in Group 2. The Group 2 patients were older, had a higher percentage of males and had lower body mass index and Killip ≥2 than the Group 1 patients. Angiographic data, door-to-balloon time, and mechanical support were not different between the 2 groups. The Group 2 patients demonstrated a significantly higher all-cause mortality rate (P<0.01) and composite of cardiovascular death and heart failure hospitalization (P<0.01), and Kaplan-Meier analysis showed the same tendency in propensity score-matched patients. CONCLUSIONS: The present study revealed that mild or moderate AS based on Vmax is associated with poor prognosis following AMI.
Assuntos
Estenose da Valva Aórtica , Infarto do Miocárdio , Humanos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Prognóstico , Índice de Gravidade de Doença , Volume SistólicoRESUMO
BACKGROUND: Although serum uric acid (UA) is considered as a risk factor for cardiovascular disease, few data exist regarding the relationship between hyperuricemia, coronary blood flow, and subsequent outcome in patients with acute myocardial infarction (AMI). The purpose of our study is to assess whether hyperuricemia is associated with suboptimal coronary flow and increased risk of mortality in patients with AMI after percutaneous coronary intervention (PCI). METHODS: Using the Rural AMI registry data, 989 consecutive patients with AMI who underwent emergent PCI and had UA measurement at admission were analyzed. We defined hyperuricemia as serum UA ≥7.0â¯mg/dL in men andâ¯≥â¯6.0â¯mg/dL in women. The primary endpoint was suboptimal coronary flow, defined as post PCI Thrombosis In Myocardial Infarction flow gradeâ¯≤â¯2. The secondary outcome was in-hospital mortality. RESULTS: Hyperuricemia was found in 249 (25.2%) patients. Patients with hyperuricemia were more often complicated with cardiogenic shock compared with those without (16.9% vs. 7.4%, pâ¯<â¯0.001). In addition, the median high-sensitivity C-reactive protein was significantly higher in patients with hyperuricemia (0.18â¯mg/dL; IQR, 0.09-0.71â¯mg/dL) than in those without (0.14â¯mg/dL; IQR, 0.07-0.41â¯mg/dL, pâ¯<â¯0.05). Under these conditions, the prevalence of suboptimal coronary flow after PCI (17.3% vs. 10.1%, pâ¯<â¯0.05) and in-hospital mortality (10.8% vs. 3.6%, pâ¯<â¯0.001) were significantly higher in patients with hyperuricemia compared with those without. Multivariable logistic regression analysis revealed that hyperuricemia was significantly associated with suboptimal coronary flow [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.02-2.49; pâ¯<â¯0.05] and in-hospital mortality (OR, 2.08; 95% CI, 1.05-4.12; pâ¯<â¯0.05). CONCLUSIONS: Assessment of serum UA upon admission provides useful information for predicting suboptimal coronary flow and in-hospital mortality in patients with AMI undergoing PCI.
Assuntos
Hiperuricemia , Infarto do Miocárdio , Intervenção Coronária Percutânea , Feminino , Mortalidade Hospitalar , Humanos , Hiperuricemia/complicações , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Ácido ÚricoRESUMO
BACKGROUND: The diagnostic criteria for disseminated intravascular coagulation (DIC) vary and are complicated and the cut-off values are different. Simple and quick diagnostic criteria for DIC are required in physicians for critical care. MATERIAL AND METHODS: Platelet counts, prothrombin time-international normalized ratio (PT-INR) and D-dimer levels were examined in 1293 critical ill patients. Adequate cut-off values of these parameters were determined and a quick DIC score using these biomarkers was proposed. The quick DIC score was evaluated using a receiver operating characteristic (ROC) analysis. RESULTS: Using the Japanese Ministry of Health, Labor and Welfare diagnostic criteria, 70 and 109 patients were diagnosed with DIC and pre-DIC, respectively. The ROC analysis of factors difference between DIC and non-DIC, revealed the following cut-off values: PT-INR, 1.20; platelet count, 12.0 × 1010/L and D-dimer, 10.0 µg/mL. Based on the above results, the quick DIC score system was proposed. All patients with DIC had a quick DIC score of 3, 4 or 5, and 85.3% of the patients with pre-DIC had a quick DIC score of ≥3 points. All patients with pre-DIC had a score of ≥2 points. In the ROC analysis, the area under the curve was 0.997 for DIC vs. non-DIC, and 0.984 for pre-DIC + DIC vs. non-DIC, and the cut-off value was 3 points for DIC and 2 points for DIC + pre-DIC. The quick DIC scores of non-survivors were significantly higher than those of survivors. CONCLUSIONS: The Quick DIC score system is a simple and useful tool that can be used for the diagnosis of DIC and pre-DIC. Further evaluation of the quick DIC score system in a large-scale study is required.
RESUMO
BACKGROUND: Trastuzumab and fulvestrant combination therapy is one of the treatment options for patients with hormone receptor- and human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer; however, there are limited studies evaluating the efficacy of this combination therapy. METHODS: We retrospectively reviewed the data of women with hormone receptor- and HER2-positive metastatic breast cancer who received trastuzumab and fulvestrant combination therapy between August 1997 and August 2020 at the Cancer Institute Hospital. The primary endpoint of this study was progression-free survival, and the secondary endpoints were response rate, overall survival and safety. RESULTS: We reviewed the data of 1612 patients with recurrent or metastatic breast cancer, of which 118 patients were diagnosed with hormone receptor- and HER2-positive breast cancer. Of these, 28 patients who received trastuzumab and fulvestrant combination therapy were eligible for this study. The median treatment line for advanced breast cancer was 6 (range, 1-14), the median progression-free survival was 6.4 months (95% confidence interval [CI], 3.46-8.17), and the median overall survival was 35.3 months (95% CI, 20.0-46.7). Of the 28 patients, partial response was observed in 1 (4%), stable disease in 17 (61%), and progressive disease in 10 (36%) patients. The disease control rate was 64%. Adverse events of grade ≥ 3 were not observed. CONCLUSIONS: Trastuzumab and fulvestrant combination therapy showed moderate clinical efficacy and no severe toxicity after standard anti-HER2 treatment, which is a reasonable treatment option for patients with hormone receptor- and HER2-positive metastatic breast cancer. These data contribute to understanding the efficacy of trastuzumab and fulvestrant combination therapy as control data for further development of anti-HER2 agents plus hormone therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Fulvestranto/administração & dosagem , Receptor ErbB-2/metabolismo , Trastuzumab/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Target activation-induced cytidine deaminase (Target-AID), a novel CRISPR/Cas9-based genome-editing tool, confers the base-editing capability on the Cas9 genome-editing system. It involves the fusion of cytidine deaminase (CDA), which catalyzes cytidine (C) to uridine (U) substitutions, to the mutated nickase-type nCas9 or deactivated-type dCas9. To confirm and extend the applicability of the Target-AID genome-editing system in tomatoes (Solanum lycopersicum L.), we transformed the model tomato cultivar "Micro-Tom" and commercial tomato cultivars using this system by targeting SlDELLA, which encodes a negative regulator of the plant phytohormone gibberellic acid (GA) signaling pathway. We confirmed that the nucleotide substitutions were induced by the Target-AID system, and we isolated mutants showing high GA sensitivity in both "Micro-Tom" and the commercial cultivars. Moreover, by successfully applying this system to ETHYLENE RECEPTOR 1 (SlETR1) with single sgRNA targeting, double sgRNA targeting, as well as dual-targeting of both SlETR1 and SlETR2 with a single sgRNA, we demonstrated that the Target-AID genome-editing system is a promising tool for molecular breeding in tomato crops. This study highlights an important aspect of the scientific and agricultural potential of the combinatorial use of the Target-AID and other base-editing systems.
RESUMO
Cardiovascular events and death are more prevalent in hemodialysis (HD) patients than in the general population. However, a detailed prognostic risk stratification of HD patients with acute myocardial infarction (AMI) has not yet been performed in the modern interventional era. We examined 4509 AMI patients (89 AMI/HD and 4420 AMI/non-HD) from the Mie ACS registry and detailed prognostic analyses based on the Killip classification were performed (Cohort A). In addition, prognosis of Killip class1 AMI/HD was compared with those of 313 non-AMI/HD patients from the MIE-CARE HD study using propensity score-matching method (Cohort B). Primary endpoint was all-cause mortality for up to 2 years. All-cause death occurred in 13.0% of AMI/non-HD and 35.8% of AMI/HD during follow-up, and patients with Killip class 1 had lower 30-day and 2-year mortality than those with Killip class ≥ 2 in both AMI/non-HD and AMI/HD. Cox regression analyses identified that Killip class ≥ 2 was the strongest independent prognostic factor of 30-day mortality with a hazard ratio of 7.44 (p < 0.001), whereas both presence of HD and Killip class ≥ 2 were the independent prognostic factors of mortality for up to 2 years. In Cohort B, a propensity score-matching analysis revealed similar all-cause mortality rates between Killip class 1 AMI/HD and non-AMI/HD. In HD patients with Killip class 1 AMI, 30-day mortality was around 6%, and long-term mortality among 30-day survivors after AMI was comparable with the natural course of HD patients in the modern interventional era. Clinical trial registration: URL: https://www.umin.ac.jp/ctr/index-j.htm . UMIN000036020 and UMIN000008128.
Assuntos
Infarto do Miocárdio , Estudos de Coortes , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Prognóstico , Modelos de Riscos Proporcionais , Diálise RenalRESUMO
OBJECTIVE: Helicopter emergency medical services (HEMS) are effective for time-sensitive conditions, such as stroke and trauma. However, prognostic data on helicopter transport for acute myocardial infarction (AMI) patients are insufficient. METHODS: We registered 2,681 AMI patients in the Mie Acute Coronary Syndrome Registry and enrolled 163 patients from rural areas to HEMS base hospitals with HEMS or ground emergency medical services (GEMS). They were categorized into 4 groups according to the transportation method for interhospital transfer (direct HEMS: nâ¯=â¯52, direct GEMS: nâ¯=â¯54, interhospital HEMS: nâ¯=â¯32, and interhospital GEMS: nâ¯=â¯25). The primary end point was the emergency medical services (EMS) call-to-balloon time. The secondary end point was 2-year major adverse cardiac and cerebrovascular events. RESULTS: The direct HEMS group was younger than the direct GEMS group (Pâ¯=â¯.029). The EMS call-to-balloon time was shorter in the direct HEMS and interhospital HEMS groups than in each GEMS group (Pâ¯=â¯.015 and Pâ¯=â¯.046). The incidence of 2-year major adverse cardiac and cerebrovascular events tended to be lower in both HEMS groups than in each GEMS group. CONCLUSION: Direct HEMS for AMI in rural areas shortens the time from the EMS call to reperfusion when the transport distance is expected to exceed 30 km, which may result in a better patient prognosis. In addition, prehospital diagnostic modalities, such as 12-lead electrocardiography and echocardiography, may shorten the duration from the EMS call to reperfusion.
Assuntos
Síndrome Coronariana Aguda , Resgate Aéreo , Infarto do Miocárdio , Síndrome Coronariana Aguda/terapia , Aeronaves , Humanos , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Sistema de Registros , Reperfusão , Estudos RetrospectivosRESUMO
OBJECT: Although many Japanese patients infected with coronavirus disease 2019 (COVID-19) only experience mild symptoms, in some cases a patient's condition deteriorates, resulting in a poor outcome. This study examines the behavior of biomarkers in patients with mild to severe COVID-19. METHODS: The disease severity of 152 COVID-19 patients was classified into mild, moderate I, moderate II, and severe, and the behavior of laboratory biomarkers was examined across these four disease stages. RESULTS: The median age and male/female ratio increased with severity. The mortality rate was 12.5% in both moderate II and severe stages. Underlying diseases, which were not observed in 45% of mild stage patients, increased with severity. An ROC analysis showed that C-reactive protein (CRP), ferritin, procalcitonin (PCT), hemoglobin (Hb) A1c, albumin, and lactate dehydrogenase (LDH) levels were significantly useful for the differential diagnosis of mild/moderate I stage and moderate II/severe stage. In the severe stage, Hb levels, coagulation time, total protein, and albumin were significantly different on the day of worsening from those observed on the day of admission. The frequency of hemostatic biomarker abnormalities was high in the severe disease stage. CONCLUSION: The evaluation of severity is valuable, as the mortality rate was high in the moderate II and severe stages. The levels of CRP, ferritin, PCT, albumin, and LDH were useful markers of severity, and hemostatic abnormalities were frequently observed in patients in the severe disease stage.
RESUMO
BACKGROUND: Acute cerebral infarction (ACI) includes cardiogenic ACI treated with anticoagulants and atherosclerotic ACI treated with antiplatelet agents. The differential diagnosis between cardiogenic and atherosclerotic ACI is still difficult. MATERIALS AND METHODS: The plasma sCLEC-2 and D-dimer levels were measured using the STACIA system. RESULTS: The plasma sCLEC-2 level was significantly high in patients with ACI, especially those in patients with atherosclerotic or lacunar ACI, and plasma D-dimer levels were significantly high in patients with cardioembolic ACI. The plasma levels of sCLEC-2 and the sCLEC-2/D-dimer ratios in patients with atherosclerotic or lacunar ACI were significantly higher than those in patients with cardioembolic ACI. The plasma D-dimer levels in patients with atherosclerotic or lacunar ACI were significantly lower than those in patients with cardioembolic ACI. The plasma levels of sCLEC-2 and the sCLEC-2/D-dimer ratios were significantly higher in patients with atherosclerotic or lacunar ACI or acute myocardial infarction in comparison to patients with cardioembolic ACI or those with deep vein thrombosis. CONCLUSION: Using both the plasma sCLEC-2 and D-dimer levels may be useful for the diagnosis of ACI, and differentiating between atherosclerotic and cardioembolic ACI.
RESUMO
Background: We hypothesized that symptom presentation in patients with acute myocardial infarction (AMI) may affect their management and subsequent outcome. MethodsâandâResults: Using Rural AMI Registry data, 1,337 consecutive patients with AMI who underwent percutaneous coronary intervention were analyzed. Typical symptoms were defined as any symptoms of chest pain or pressure due to myocardial ischemia. We considered the specific symptoms of dyspnea, nausea, or vomiting as atypical symptoms. The primary outcome was 30-day mortality. There were 150 (11.2%) and 1,187 (88.8%) patients who presented with atypical and typical symptoms, respectively. Those who presented with atypical symptoms were significantly older (mean [±SD] age 74±12 vs. 68±13 years; P<0.001) and had a higher Killip class (46.7% vs. 21.8%; P<0.001) than patients presenting with typical symptoms. The prevalence of door-to-balloon time of ≤90 min was significantly lower in patients with atypical than typical symptoms (40.0% vs. 66.3%; P<0.001). At 30 days, there were 55 incidents of all-cause death. Multivariate Cox proportional hazards regression analysis revealed that symptom presentation was associated with 30-day mortality (hazard ratio 2.33; 95% confidence interval 1.20-4.38; P<0.05). Conclusions: Atypical symptoms in patients with AMI are less likely to lead to timely reperfusion and are associated with increased risk of 30-day mortality.
RESUMO
BACKGROUND: Chronic total occlusion (CTO) in a non-infarct-related artery (IRA) in patients with acute coronary syndrome (ACS) is associated with a poor prognosis. However, whether the prognostic impact of non-IRA CTO differs according to left ventricular ejection fraction (LVEF) is unclear. METHODS AND RESULTS: A total of 2060 consecutive acute myocardial infarction (AMI) patients who underwent primary percutaneous coronary intervention (PCI) were classified into 2 groups according to their LVEF (reduced EF: LVEF < 50%, preserved EF: LVEF ≥ 50%) and further subdivided according to the presence of concomitant non-IRA CTO. In the reduced EF group, patients with CTO had a higher 1-year all-cause death rate (20.3% vs. 34.3%, P = 0.001) and major adverse cardiac event rate (MACE: 19.6% vs. 39.6%, P < 0.001) compared to those without CTO, but they were similar between patients with and without CTO in the preserved EF group. Non-IRA CTO was an independent predictor of all-cause death (HR 1.58, 95% CI 1.06-2.33, P = 0.02) and MACE (HR 1.67, 95% CI 1.14-2.46, P = 0.009) only in the reduced EF group. In addition, the outcomes of successful CTO-PCI seemed to be similar to those without CTO in the reduced EF group. CONCLUSIONS: CTO in a non-IRA may contribute to a poor prognosis only in AMI patients with reduced LVEF.
RESUMO
Residual metastasis is a major cause of cancer-associated death. Recent advances in understanding the molecular basis of the epithelial-mesenchymal transition (EMT) and the related cancer stem cells (CSCs) have revealed the landscapes of cancer metastasis and are promising contributions to clinical treatments. However, this rarely leads to practical advances in the management of cancer in clinical settings, and thus cancer metastasis is still a threat to patients. The reason for this may be the heterogeneity and complexity caused by the evolutional transformation of tumor cells through interactions with the host environment, which is composed of numerous components, including stromal cells, vascular cells, and immune cells. The reciprocal evolution further raises the possibility of successful tumor escape, resulting in a fatal prognosis for patients. To disrupt the vicious spiral of tumor-immunity aggravation, it is important to understand the entire metastatic process and the practical implementations. Here, we provide an overview of the molecular and cellular links between tumors' biological properties and host immunity, mainly focusing on EMT and CSCs, and we also highlight therapeutic agents targeting the oncoimmune determinants driving cancer metastasis toward better practical use in the treatment of cancer patients.
RESUMO
BACKGROUND: Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. METHODS: In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). RESULTS: The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1-28.0], DCR = 66.6% (95% CI 60.8-72.0), median PFS = 6.1 months (95% CI 5.3-6.7), median TTF = 5.1 months (95% CI 4.4-5.6), and median OS = 23.7 months (95% CI 20.7-27.4). CONCLUSION: The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.