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BACKGROUND: Biomarkers for predicting response to the immunotherapy and chemotherapy combination in breast cancer patients are not established. In this study, we report exploratory genomic and transcriptomic analyses of pretreatment tumor tissues from patients enrolled in phase II clinical trial of a combination of eribulin and nivolumab for HER-2-negative metastatic breast cancer (MBC) (KORNELIA trial, NCT04061863). METHODS: We analyzed associations between tumor molecular profiles based on genomic (n = 76) and transcriptomic data (n = 58) and therapeutic efficacy. Patients who achieved progression-free survival (PFS) ≥ 6 months were defined as PFS6-responders and PFS6-nonresponders otherwise. FINDINGS: Analyses on tumor mutation burden (TMB) showed a tendency toward a favorable effect on efficacy, while several analyses related to homologous recombination deficiency (HRD) indicated a potentially negative impact on efficacy. Patients harboring TP53 mutations showed significantly poor PFS6 rate and PFS, which correlated with the enrichment of cell cycle-related signatures in PFS6-nonresponders. High antigen presentation gene set enrichment scores (≥ median) were significantly associated with longer PFS. Naïve B-cell and plasma cell proportions were considerably higher in long responders (≥ 18 months). INTERPRETATION: Genomic features including TMB, HRD, and TP53 mutations and transcriptomic features related to immune cell profiles and cell cycle may distinguish responders. Our findings provide insights for further exploring the combination regimen and its biomarkers in these tumors.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Furanos , Cetonas , Nivolumabe , Receptor ErbB-2 , Transcriptoma , Humanos , Feminino , Cetonas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Furanos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Nivolumabe/uso terapêutico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Pessoa de Meia-Idade , Genômica/métodos , Idoso , Biomarcadores Tumorais/genética , Adulto , Mutação , Metástase Neoplásica , Perfilação da Expressão Gênica , Policetídeos de PoliéterRESUMO
PURPOSE: To identify symptom clusters among breast cancer survivors and investigate differences in health-related quality of life (HRQoL) and distress based on these discerned symptom clusters using latent profile analysis. METHODS: We enrolled 655 adult breast cancer survivors aged 19 years and older, registered with the Cancer Survivor Integrated Supportive Center from May 2020 to July 2022. The study measured five symptoms-pain, fatigue, insomnia, anxiety, and depression-using a Visual Analogue Scale ranging from 0 to 10 points. Distress was measured using the National Comprehensive Cancer Network Distress Thermometer, with scores ranging from 0 to 10 points. HRQoL was determined using the EuroQol-5 Dimension questionnaire. Data analysis was conducted using the Jamovi and Mplus 8.8 software programs. RESULTS: The Cluster with Few Symptoms (46.8%) was the most common, whereas the Psychological Cluster with a very high degree of depression and anxiety accounted for 20.0%, and the Moderate symptom cluster with symptoms of 3 or more points accounted for 14.4%. Distress scores were relatively high in the Psychological Cluster and the Pain-Fatigue-Insomnia Cluster, and were lowest in the Cluster with Few Symptoms (F = 103.92, p < 0.001). HRQoL scores were highest in the Cluster with Few Symptoms and lowest in the Pain-Fatigue-Insomnia Cluster (F = 177.62, p < 0.001). CONCLUSIONS: Approximately half of breast cancer survivors who had completed the major treatment experienced persistent high symptoms such as depression and anxiety or pain, fatigue, and insomnia. IMPLICATIONS FOR CANCER SURVIVORS: These findings provide foundational data for developing tailored intervention strategies and programs based on symptom experiences.
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Breast cancer is the most commonly diagnosed cancer among women worldwide. Breast cancer patients experience significant distress relating to their diagnosis and treatment. Managing this distress is critical for improving the lifespan and quality of life of breast cancer survivors. This study aimed to assess the level of distress in breast cancer survivors and analyze the variables that significantly affect distress using machine learning techniques. A survey was conducted with 641 adult breast cancer patients using the National Comprehensive Cancer Network Distress Thermometer tool. Participants identified various factors that caused distress. Five machine learning models were used to predict the classification of patients into mild and severe distress groups. The survey results indicated that 57.7% of the participants experienced severe distress. The top-three best-performing models indicated that depression, dealing with a partner, housing, work/school, and fatigue are the primary indicators. Among the emotional problems, depression, fear, worry, loss of interest in regular activities, and nervousness were determined as significant predictive factors. Therefore, machine learning models can be effectively applied to determine various factors influencing distress in breast cancer patients who have completed primary treatment, thereby identifying breast cancer patients who are vulnerable to distress in clinical settings.
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Neoplasias da Mama , Sobreviventes de Câncer , Aprendizado de Máquina , Angústia Psicológica , Humanos , Neoplasias da Mama/psicologia , Feminino , Sobreviventes de Câncer/psicologia , Pessoa de Meia-Idade , Adulto , Qualidade de Vida , Estresse Psicológico/psicologia , Idoso , Depressão/psicologia , Inquéritos e QuestionáriosRESUMO
In the shipbuilding industry, welding automation using welding robots often relies on arc-sensing techniques due to spatial limitations. However, the reliability of the feedback current value, core sensing data, is reduced when welding target workpieces have significant curvature or gaps between curved workpieces due to the control of short-circuit transition, leading to seam tracking failure and subsequent damage to the workpieces. To address these problems, this study proposes a new algorithm, MBSC (median-based spatial clustering), based on the DBSCAN (density-based spatial clustering of applications with noise) clustering algorithm. By performing clustering based on the median value of data in each weaving area and considering the characteristics of the feedback current data, the proposed technique utilizes detected outliers to enhance seam tracking accuracy and responsiveness in unstructured and challenging welding environments. The effectiveness of the proposed technique was verified through actual welding experiments in a yard environment.
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Cardio-oncology is a critical field due to the escalating significance of cardiovascular toxicity as a side effect of anticancer treatments. Cancer therapy-related cardiac dysfunction (CTRCD) is a prevalent condition associated with cardiovascular toxicity, necessitating effective strategies for prediction, monitoring, management, and tracking. This comprehensive review examines the definition and risk stratification of CTRCD, explores monitoring approaches during anticancer therapy, and highlights specific cardiovascular toxicities linked to various cancer treatments. These include anthracyclines, HER2-targeted agents, vascular endothelial growth factor inhibitors, immune checkpoint inhibitors, chimeric antigen receptor T-cell therapies, and tumor-infiltrating lymphocytes therapies. Incorporating the Korean data, this review offers insights into the regional nuances in managing CTRCD. Using systematic follow-up incorporating cardiovascular imaging and biomarkers, a better understanding and management of CTRCD can be achieved, optimizing the cardiovascular health of both cancer patients and survivors.
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Various contaminants of emerging concern (CECs) including pharmaceuticals and personal care products (PPCPs) have been known to threaten the aquatic ecosystem and human health even at low levels in surface water. Among them, the wide variety use of parabens as preservatives may pose potential threat to human because parabens may present estrogenic activity. Various advanced oxidation processes have been attempted to reduce parabens, but challenges using cold plasma (CP) are very rare. CP is worth paying attention to in reducing parabens because it has the advantage of generating radical ions, including reactive oxygen/nitrogen species and various ions. Accordingly, this study demonstrates how CP can be utilized and how CP competes with other advanced oxidation processes in energy requirements. Quantified ethyl-, propyl-, and butyl-paraben indicate that CP can effectively degrade them up to 99.1% within 3 h. Regression reveals that the kinetic coefficients of degradation can be increased to as high as 0.0328 min-1, comparable to other advanced oxidation processes. Many by-products generated from the oxidation of parabens provide evidence of the potential degradation pathway through CP treatment. In addition, we found that the electrical energy consumption per order of CP (39-95 kWh/m3/order) is superior to other advanced oxidation processes (69â¼31,716 kWh/m3/order). Overall, these results suggest that CP may be a viable option to prevent adverse health-related consequences associated with parabens in receiving water.
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Oxirredução , Parabenos , Poluentes Químicos da Água , Parabenos/química , Poluentes Químicos da Água/química , Gases em Plasma/química , Cinética , Conservantes Farmacêuticos/químicaRESUMO
Tetramethylammonium hydroxide (TMAH), which is a chemical used in the electronic industry, is classified as a hazardous material (HAZMAT class 8) that threatens aquatic ecosystems and human health. Consequently, numerous studies have attempted to remove TMAH using various treatment methods, including advanced oxidation processes such as ozone, UV, or Fenton oxidation. However, prior research has indicated a low kinetic rate of TMAH removal. In this context, we proposed an alternative to TMAH degradation by combining a cold plasma (CP) process with periodate oxidation. As for the kinetics of TMAH removal, the kinetic constant was improved by 5 times (0.1661 and 0.0301 for 40.56 and 2.2 W, respectively) as the electric power of a CP system increased from 2.2 to 40.56 W. The kinetic constant of a 40.56 W CP system further increased by 54 times (1.6250) than a 2 W CP system when 4 mM periodate was used simultaneously. As a result, the integrated CP/periodate system represented 2 times higher TMAH removal efficiency (29.5%) than a 2 W CP system (14.4%). This excellent TMAH degradation capability of the integrated CP/periodate system became pronounced at pH 10 and 25 °C. Overall, the integrated CP/periodate system is expected to be a viable management option for effectively controlling hazardous TMAH chemicals.
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Oxirredução , Compostos de Amônio Quaternário , Poluentes Químicos da Água , Cinética , Compostos de Amônio Quaternário/química , Ácido Periódico/química , Gases em Plasma , AnimaisRESUMO
INTRODUCTION: Well-designed simulation-based learning (SBL) experiences enhance students' self-confidence, self-efficacy, clinical judgment, and psychomotor skill development. An emerging concept in SBL research is psychological safety. There is currently no research on factors influencing psychological safety specifically related to the SBL environment, nor is there any literature found to determine whether intrinsic student characteristic, such as self-compassion and resilience, contributes to SBL learning outcomes. The aim of this study is to determine whether there is a relationship between nursing students' intrinsic characteristics (self-compassion, resilience, and anxiety sensitivity) and their psychological safety. METHODS: Bivariate correlation was used to examine associations among sociodemographic variables and outcome variables. Multiple regression was used to determine the predictive nature of the sociodemographic variables. Assumptions for variables in multiple regression models were tested (normal distribution, heteroscedasticity, multicollinearity). All data were analyzed in SPSS, Version 28. The P value of significance was set at 0.05 for all analyses. RESULTS: Most of the 118 participants were non-Hispanic (89%), White (65%), and females (95%). Results of the demographic bivariate analysis revealed no significant differences among this diverse group or semester in the curriculum for psychological safety. The multiple regression found self-compassion (ß = 29, P = 0.004), anxiety sensitivity (ß = -0.16, P = 0.049), and resilience (ß = 0.26, P = 0.004) predict psychological safety. CONCLUSIONS: The importance of creating a psychologically safe learning environment has been recognized as essential to best practices. Our findings suggest that an understanding of student characteristics that impact their perception of psychological safety will allow educators to develop strategies to better support learners in the simulation environment.
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Introduction: Previous studies have demonstrated associations between sex and racialized group on pain sensitivity and tolerance. We analyzed the association of sex and racialized group on heat pain sensitivity, sensibility to painful suprathreshold mechanical pain (STMP), and pain sensitivity questionnaire (PSQ). We hypothesized that anxiety and pain catastrophizing reported by racialized minority groups and women would mediate enhanced pain sensitivity. Our secondary aim was to evaluate validity of the PSQ in a diverse population. Methods: Using quantitative sensory testing for painful heat, STMP (forces: 64, 128, 256, and 512 mN), and PSQ, we evaluated pain sensitivity in 134 healthy participants [34 (18 women) Asian, 25 (13 women) Black, and 75 (41 women) White]. We used general linear and linear mixed models to analyze outcomes. We assessed mediation of state and trait anxiety and pain catastrophizing on pain sensitivity. Results: Racialized minority status was associated with greater heat pain sensitivity (F = 7.63; P = 0.00074) and PSQ scores (F = 15.45; P = 9.84 × 10-7) but not associated with STMP (F = 1.50; P = 0.23). Female sex was associated with greater heat pain sensitivity (F = 4.9; P = 0.029) and lower PSQ (F = 9.50; P = 0.0025) but not associated with STMP (F = 0.0018; P = 0.97). Neither anxiety nor pain catastrophizing mediated associations between sex or racialized group with heat pain threshold or PSQ. Differential experience of individual items (F = 19.87; P = 3.28 × 10-8) limited PSQ face validity in racialized minorities. Conclusion: Consistent with previous research, sensitivity to painful heat was associated with racialized minority status and female sex. By contrast, there was no significant effect of racialized minority status or female sex on STMP. Some PSQ items are inapplicable to participants from racialized minority groups.
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INTRODUCTION: Metastatic breast cancer refractory to anthracycline and taxanes often shows rapid progression. The development of effective and tolerable combination regimens for these patients is needed. This phase II trial investigated the efficacy of pemetrexed plus vinorelbine in patients with metastatic breast cancer. METHODS: This randomized, open-label, phase II trial was conducted in 17 centers in Korea. Patients with advanced breast cancer who had previously been treated with anthracyclines and taxanes were randomly assigned in a 1:1 ratio to receive either vinorelbine or pemetrexed plus vinorelbine. Randomization was stratified by prior capecitabine treatment and hormone receptor status. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included the objective response rate, overall survival, safety, and quality of life. RESULTS: Between March 2017 and August 2019, a total of 125 patients were enrolled. After a median follow-up duration of 14.1 months, 118 progression events and 88 death events had occurred. Sixty-two patients were assigned to the pemetrexed plus vinorelbine arm, and 63 were assigned to the vinorelbine arm. Pemetrexed plus vinorelbine significantly prolonged PFS compared to vinorelbine (5.7 vs. 1.5 months, p < 0.001). The combination arm had higher disease control rate (76.8% vs. 45.9%, p = 0.001) and a tendency toward longer overall survival (16.8 vs. 10.5 months, p = 0.102). Anemia was more frequent in the pemetrexed plus vinorelbine arm per cycle compared with vinorelbine (7.9% vs. 1.9%, p < 0.001), but there was no difference in the incidence of grade 3-4 neutropenia per cycle between the pemetrexed plus vinorelbine arm and the vinorelbine single arm (14.7% vs. 19.5%, p = 0.066). CONCLUSIONS: This phase II study showed that pemetrexed plus vinorelbine led to a longer PFS than vinorelbine. Adverse events of pemetrexed plus vinorelbine were generally manageable.
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Neoplasias da Mama , Pemetrexede , Vinorelbina , Feminino , Humanos , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Pemetrexede/uso terapêutico , Qualidade de Vida , Taxoides/uso terapêutico , Vinorelbina/uso terapêuticoRESUMO
AIM: We evaluated the efficacy and safety of nivolumab and eribulin combination therapy for metastatic breast cancer (BC) in Asian populations. METHODS: In this parallel phase II study, adult patients with histologically confirmed recurrent/metastatic hormone receptor-positive/HER2-negative (HR+HER2-) or triple-negative BC (TNBC) were prospectively enroled from 10 academic hospitals in Korea (ClinicalTrials.gov Identifier: NCT04061863). They received nivolumab (360 mg) on day 1 plus eribulin (1.4 mg/m2) on days 1 and 8 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was the investigator-assessed 6-month progression-free survival (PFS) rate in each subtype. Secondary endpoints included investigator-assessed objective response rate (ORR) as per Response Evaluation Criteria in Advanced Solid Tumors version 1.1, disease control rate, overall survival, and treatment toxicity. The association between PD-L1 expression and efficacy was investigated. RESULTS: Forty-five patients with HR+HER2- BC and 45 with TNBC were enroled. Their median age was 51 (range, 31-71) years, and 74 (82.2%) received one or two prior treatments before enrolment. Six-month PFS was 47.2% and 25.1% in the HR+HER2- and TNBC cohorts, respectively. Median PFS was 5.6 (95% confidence interval [CI]: 5.3-7.4) and 3.0 (95% CI: 2.1-5.2) months in the HR+HER2- and TNBC groups, respectively. ORRs were 53.3% (complete response [CR]: 0, partial response [PR]: 24) and 28.9% (CR: 1, PR: 12). Patients with PD-L1+ tumours (PD-L1 expression ≥1%) and PD-L1- tumours (ORR 50% versus 53.8% in HR+HER2-, 30.8% versus 29.0% in TNBC) had similar ORRs. Neutropenia was the most common grade 3/4 adverse event; the most common immune-related adverse events (AEs) were grades 1/2 hypothyroidism and pruritus. Five patients discontinued therapy because of immune-related AEs. CONCLUSION: Nivolumab plus eribulin showed promising efficacy and tolerable safety in previously treated HER2- metastatic BC. TRIAL REGISTRATION: NCT04061863.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1 , Neoplasias da Mama/patologia , Nivolumabe/uso terapêutico , Receptor ErbB-2/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , IdosoRESUMO
OBJECTIVES: Menopause presents various physical and psychological disturbances for women and comes at a high financial cost. Therefore, this study aimed to identify factors influencing menopause symptoms. STUDY DESIGN: Data of Korean perimenopausal women aged 40-60 (n = 1060; mean age, 46.03 ± 4.08) were collected by a research company. Participants were classified into a "functional" group (n = 716) or a "dysfunctional" group (n = 344) according to the severity of their perimenopausal psychosomatic symptoms. To investigate the association of obstetric and psychiatric history with membership of the "dysfunctional" group, a hierarchical logistic regression analysis was conducted. RESULTS: The outcomes of all three hierarchical logistic regression models presented significant overall model fit. Among the independent variables, family history of menopausal symptoms, menarcheal age, number of pregnancies, history of postpartum depression, postpartum psychosis, and other psychiatric disorders were positively associated with being in the "dysfunctional" group, whereas age and number of deliveries were negatively associated with being in the "dysfunctional" group. CONCLUSION: A short reproductive period and short exposure to estrogen due to late menarche and early menopausal transition may be related to severe perimenopausal symptoms. The relationship between the history of postpartum mental illness and severe perimenopausal symptoms may be associated with heightened sensitivity to hormonal triggers when a woman is exposed to fluctuating ovarian sex steroid levels. The relationship between parity or gravidity and the severity of menopausal symptoms in Korean women differed from that in studies conducted in other countries, possibly due to the low birth rate in Korea.
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Transtornos Mentais , Perimenopausa , Gravidez , Feminino , Humanos , Perimenopausa/psicologia , Menopausa/psicologia , Transtornos Mentais/epidemiologia , Estrogênios , República da Coreia/epidemiologiaRESUMO
OBJECTIVE: Women experience many physical and psychological changes with the reduction of progesterone and estrogen as ovarian function gradually weakens. This study applied a music psychotherapy program as a nonpharmacological treatment method in addition to treatment using drugs such as hormone therapy for perimenopausal women. METHOD: This study's pre-post, control-experimental research compared 20 women in the music psychotherapy experimental group and 20 in the cognitive behavioral therapy (CBT) control group. The perimenopausal women aged between 40 and 60 years experienced no menstrual period for 1 year. We provided eight sessions of music psychotherapy, including CBT, each lasting 60 minutes. The study period was 4 months from the time of recruitment. RESULTS: The music therapy group showed a more significant decrease in the Menopause Rating Scale total (change over time, 9.2 points and 3.5 points, respectively; P = 0.008) and psychology subcategory (change over time, 6.5 points and 0.9 points, respectively; P = 0.004) of Menopause Rating Scale scores, compared with the CBT group. In addition, the music therapy group increased their quality of life psychological score, but the CBT group did not. CONCLUSIONS: These results suggest that music therapy can help the psychological and emotional symptoms of perimenopausal women and is effective for treatment. The study result provides a therapeutic basis for developing treatments for nonpharmacological mediation.
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Terapia Cognitivo-Comportamental , Musicoterapia , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Perimenopausa , Qualidade de Vida , Menopausa , SíndromeRESUMO
BACKGROUND: Music is regarded as a beneficial tool for assessing the clinical symptoms and communication skills in individuals with autism spectrum disorder (ASD) or autism. The present study developed a music-based attention test (MAT) for individuals with autism using music parameters and the algorithm of the comprehensive attention test (CAT). METHODS: We recruited 51 autistic individuals and 50 neurotypical individuals to participate in the CAT, MAT, and social intelligence tests. The reliability and validity of the MAT were assessed using exploratory factor analysis, concurrent validity, and criterion-related validity. RESULTS: The MAT had sound internal consistency (high Cronbach's α = 0.948). In addition, the MAT had suitable concurrent validity in the correlation between CAT and MAT, as well as good criterion validity when attention was measured using the MAT and was compared between autistic individuals and neurotypical individuals. Attention evaluated using the MAT was associated with the social quotient in individuals with autism. CONCLUSIONS: The MAT could be a relevant tool for gauging attention in individuals with ASD. Furthermore, attention determined using the MAT may be correlated with social quotient in autistic individuals. Future studies should consider that using music in the field of attention could improve the social quotient of individuals with autism.
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Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Reprodutibilidade dos Testes , Algoritmos , Análise FatorialRESUMO
We explored accumulated genomic alterations in patients with heavily treated HER2 + metastatic breast cancer enrolled in the KCSG BR18-14/KM10B trial. Targeted sequencing was performed with circulating tumor DNAs (ctDNAs) collected before the treatment of 92 patients. ctDNAs collected at the time of disease progression from seven patients who had a durable response for > 12 months were also analyzed. Sixty-five genes were identified as pathogenic alterations in 99 samples. The most frequently altered genes were TP53 (n = 48), PIKCA (n = 21) and ERBB3 (n = 19). TP53 and PIK3CA mutations were significantly related with shorter progression free survival (PFS), and patients with a higher ctDNA fraction showed a worse PFS. The frequency of homologous recombination deficiency (HRD)-related gene mutations was higher than that in matched tumor tissues, and these mutations tended to be associated with shorter PFS. New pathogenic variants were found at the end of treatment in all seven patients, including BRCA2, VHL, RAD50, RB1, BRIP1, ATM, FANCA, and PIK3CA mutations. In conclusion, TP53 and PIK3CA mutations, as well as a higher ctDNA fraction, were associated with worse PFS with trastuzumab and cytotoxic chemotherapy. The enrichment of HRD-related gene mutations and newly detected variants in ctDNA may be related to resistance to treatment.
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Neoplasias da Mama , DNA Tumoral Circulante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , DNA Tumoral Circulante/genética , Trastuzumab/uso terapêutico , Genômica , Mutação , Classe I de Fosfatidilinositol 3-Quinases/genética , Biomarcadores Tumorais/genéticaRESUMO
PURPOSE: We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1-4 brain metastases (BMs) and those with 5-10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients. METHODS: Between 2008 and 2014, 471 patients were diagnosed with 1-10 BMs. They were divided into two groups based on the number of BM: 1-4 BMs (n = 337) and 5-10 BMs (n = 134). Median follow-up duration was 14.0 months. RESULTS: Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1-4 BMs group. In contrast, 80% (n = 107) of patients with 5-10 BMs were treated with WBRT. The median OS of the entire cohort, 1-4 BMs, and 5-10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months. CONCLUSION: The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.
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Neoplasias Encefálicas , Neoplasias da Mama , Radiocirurgia , Humanos , Feminino , Neoplasias da Mama/patologia , Irradiação Craniana , Neoplasias Encefálicas/secundário , Encéfalo/patologia , Terapia de Salvação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Purpose: This study aimed to investigate the relationship between DNA damage response (DDR)-related protein expression and the clinical outcomes of patients with gastric cancer stage IV and recurrent advanced gastric cancer patients after gastrectomy treated with palliative first-line chemotherapy. Materials and Methods: A total of 611 gastric cancer patients underwent D2 radical gastrectomy at Chung-Ang University Hospital between January 2005 and December 2017, of which 72 patients who received gastrectomy treatment with palliative chemotherapy were enrolled in this study. We performed the immunohistochemical assessment of MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), at-rich interaction domain 1 (ARID1A), poly adenosine diphosphate-ribose polymerase 1 (PARP-1), breast cancer susceptibility gene 1 (BRCA1), and ataxia-telangiectasia mutated (ATM) using formalin-fixed paraffin-embedded samples. In addition, Kaplan-Meier survival analysis and Cox regression models were used to evaluate independent predictors of overall survival (OS) and progression-free survival (PFS). Results: Among the 72 patients studied, immunohistochemical staining analysis indicated deficient DNA mismatch repair (dMMR) in 19.4% of patients (n = 14). The most common DDR gene with suppressed expression was PARP-1 (n = 41, 56.9%), followed by ATM (n = 26, 36.1%), ARID1A (n = 10, 13.9%), MLH1 (n = 12, 16.7%), BRCA1 (n = 11, 15.3%), and MSH2 (n = 3, 4.2%). HER2 (n = 6, 8.3%) and PD-L1 (n = 3, 4.2%) were expressed in 72 patients. The dMMR group exhibited a significantly longer median OS than the MMR proficient (pMMR) group (19.9 months vs. 11.0 months; hazard ratio [HR] 0.474, 95% confidence interval [CI] = 0.239-0.937, P = 0.032). The dMMR group exhibited a significantly longer median PFS than the pMMR group (7.0 months vs. 5.1 months; HR= 0.498, 95% CI = 0.267-0.928, P = 0.028). Conclusions: Of stage IV gastric cancer and recurrent gastric cancer patients who underwent gastrectomy, the dMMR group had a better survival rate than the pMMR group. Although dMMR is a predictive factor for immunotherapy in advanced gastric cancer, further studies are needed to determine whether it is a prognostic factor for gastric cancer patients treated with palliative cytotoxic chemotherapy.
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Introduction: Pain is a prominent contributor to negative personal and social outcomes, including increased disability and mortality, in many rheumatic diseases. In the Biopsychosocial model of chronic pain, psychological and social factors share roles with the biology of the injury in determining each patient's pain and suffering. The current study explored factors associated with clinical pain intensity and interference among patients with chronic secondary musculoskeletal pain in rheumatic diseases. Methods: In total, 220 patients experiencing chronic secondary musculoskeletal pain participated. Biological factors (age, biological sex, pain condition, pain duration, pain sensitivity, and comorbidity), socio-economic factors, psychological factors (pain catastrophizing and depressive symptoms), and pain intensity and interference were measured. Descriptive, multivariable linear regression and partial correlation analyses were conducted. Subgroup analysis by sex was conducted to examine differences in how different factors affect the pain experience. Results: The mean age of the participants was 52.3 years (SD = 12.07) and ranged from 22 to 78. Average pain intensity was 3.01 (0-10 scale) and average total pain interference score was 21.07 (0-70 scale). Partial correlation found positive correlations between pain intensity and interference with depression (intensity: R = 0.224; p = 0.0011; interference: R = 0.351; p < 0.001) and pain catastrophizing (intensity: R = 0.520; p < 0.001; interference: R = 0.464; p < 0.001). In males, pain condition (ß = -0.249, p = 0.032) and pain catastrophizing (R = 0.480, p < 0.001) were associated with pain intensity. In males, the simple correlation between pain intensity and depression (R = 0.519; p < 0.001) was driven by pain catastrophizing. In females, pain catastrophizing (R = 0.536, p < 0.001) and depressive symptoms (R = 0.228, p = 0.0077) were independently associated with pain intensity. Age (ß = -0.251, p = 0.042) and pain catastrophizing (R = 0.609, p < 0.001) were associated with pain interference in males, while depressive symptoms (R = 0.439, p < 0.001) and pain catastrophizing (R = 0.403, p < 0.001) were associated with pain interference in females. Again, in males, the simple correlation between pain interference and depression (R = 0.455; p < 0.001) was driven by pain catastrophizing. Discussion: In this study, females were more directly affected by depressive symptoms than males, regarding pain intensity and interference. Pain catastrophizing was a significant factor influencing chronic pain for both males and females. Based on these findings, a sex-specific approach to the Biopsychosocial model should be considered in understanding and managing pain among Asians with chronic secondary musculoskeletal pain.
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Background: Black thyroid is a rare incidental finding during surgery. We report the case of a patient with papillary thyroid cancer who was incidentally found to have minocycline-induced black thyroid. Case Description: A 29-year-old woman presented with a left thyroid nodule and metastatic papillary thyroid cancer involving the left neck level IV lymph nodes. She had a medical history of anxiety disorder with depression, severe acne, and rosacea, and had been taking benzodiazepines, selective serotonin reuptake inhibitors, isotretinoin, and minocycline for a few years. The patient underwent a total thyroidectomy with left central compartment neck dissection and ipsilateral modified radical neck dissection. A black thyroid gland was identified during thyroidectomy. During level IV dissection, we noticed a similar black discoloration in the adipose tissue of the lower neck. Pathological examination revealed brown pigmentation with few macrophages on several foci of the thyroid parenchyma. Brown pigmentation was not identified in the thyroid tumor, metastatic and normal lymph nodes, or background adipose tissue. Conclusions: We report a case of papillary thyroid microcarcinoma with cervical lymph node metastases in a black thyroid. The clinical findings were consistent with those of previous reports. Based on the literature, it remains unclear if this minocycline triggered finding is associated with an increased frequency and/or aggressiveness of thyroid carcinomas. In the absence of adequate evidence, prolonged minocycline users should ideally undergo routine thyroid assessment to identify possible malignancy.