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Anticuerpos Monoclonales , Linfocitos T CD4-Positivos , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/farmacología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Persona de Mediana Edad , Linfocitos Intraepiteliales/efectos de los fármacos , Linfocitos Intraepiteliales/inmunología , Linfocitos Intraepiteliales/metabolismoRESUMEN
OBJECTIVE: The article tackles various issues arising in the context of the process of digitalization in the health sector. The communication and availability of health data, health registers, the electronic health record, consent procedures for the transfer of data and access to health data for research are considered. METHODS: The study is based on a computer-assisted telephone survey (dual-frame) of a random sample of adult people living in Germany. Data was collected in the period between June 01 and June 27, 2022 (nâ¯=â¯1,308). RESULTS: The level of knowledge concerning the transmission of health data to health insurers is good, whereas the existence of central death-, vaccination- and health registers as well as the access to health data by treating physicians is overestimated. The general acceptance of medical registers is very high. Half the population is unfamiliar with the electronic health record, and the willingness to use it is rather low. An opt-in procedure is preferred when transferring data, and more than eighty percent would release data in their electronic health file for research purposes. Three quarters would consent that their health data be handed over to general research, especially if reserach facilities were situated at German universities, under the condition that their data be treated confidentiallly. The willingness to release data correlates with the level of trust in the press as well as in universities and colleges and decreases when a data leak is considered to be serious. DISCUSSION AND CONCLUSION: In Germany, as in other European countries, we observe a great willingness of people to release health data for research purposes. However, the propensity to use the electronic health file is comparatively low, as is the acceptance of an opt-out procedure, which in the literature is considered a prerequisite for the successful implementation of electronic health records in other countries. Unsurprisingly, a general trust in research and government agencies that process health data is a key factor.
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Actitud , Registros Electrónicos de Salud , Adulto , Humanos , Alemania , Comunicación , Proyectos de InvestigaciónRESUMEN
AIM OF THE STUDY: This study was conducted in a pre-post design with a survey of patients who had undergone deep brain stimulation (DBS) as treatment for a neurological movement disorder. The aim of the study was to compare patients' expectations and beliefs before a DBS intervention with patients' subjective experience of this intervention. METHODOLOGY: The longitudinal study of patients (n=132) with an indication for DBS therapy was based on a written survey at the time points of preoperative screening (pre-op) and one-year follow-up (post-op). RESULTS: Preoperatively, a clear majority of respondents believed DSB to be similar to a pacemaker intervention, but one year after the intervention less than one third did so, as they compared DBS to using a walking stick or glasses. CONCLUSION: The experience of DBS in the patient's own body seems to be comparable by means of individually different associations, whereby the comparison with non-invasive aids predominates postoperatively. The discussion of these descriptions in the educational interview can contribute to a realistic horizon of patients' expectations before DBS.
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The study is based on a German single-topic population survey on vaccination willingness against COVID-19 (VWC) by the authors (2020, n = 2014). The single-topic survey allowed us to test several competing explanations for VWC, as discussed in the literature. The VWC in the sample was 67.3%. Logistic regression was used to identify factors affecting VWC. Being at high risk from COVID-19 and having received flu vaccination have a positive impact on VWC. Perceived VWC of friends has a strong positive effect on respondents' VWC. Bivariate relationships of gender, age, and level of education with VWC were no longer significant in a multivariate analysis. Trust in alternative medicine and belief in conspiracy theories have a negative effect on VWC.
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PURPOSE: Caveolin-1 and -2 (CAV1/2) dysregulation are implicated in driving cancer progression and may predict response to nab-paclitaxel. We explored the prognostic and predictive potential of CAV1/2 expression for patients with early-stage HER2-negative breast cancer receiving neoadjuvant paclitaxel-based chemotherapy regimens, followed by epirubicin and cyclophosphamide. EXPERIMENTAL DESIGN: We correlated tumor CAV1/2 RNA expression with pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS) in the GeparSepto trial, which randomized patients to neoadjuvant paclitaxel- versus nab-paclitaxel-based chemotherapy. RESULTS: RNA sequencing data were available for 279 patients, of which 74 (26.5%) were hormone receptor (HR)-negative, thus triple-negative breast cancer (TNBC). Patients treated with nab-paclitaxel with high CAV1/2 had higher probability of obtaining a pCR [CAV1 OR, 4.92; 95% confidence interval (CI), 1.70-14.22; P = 0.003; CAV2 OR, 5.39; 95% CI, 1.76-16.47; P = 0.003] as compared with patients with high CAV1/2 treated with solvent-based paclitaxel (CAV1 OR, 0.33; 95% CI, 0.11-0.95; P = 0.040; CAV2 OR, 0.37; 95% CI, 0.12-1.13; P = 0.082). High CAV1 expression was significantly associated with worse DFS and OS in paclitaxel-treated patients (DFS HR, 2.29; 95% CI, 1.08-4.87; P = 0.030; OS HR, 4.97; 95% CI, 1.73-14.31; P = 0.003). High CAV2 was associated with worse DFS and OS in all patients (DFS HR, 2.12; 95% CI, 1.23-3.63; P = 0.006; OS HR, 2.51; 95% CI, 1.22-5.17; P = 0.013), in paclitaxel-treated patients (DFS HR, 2.47; 95% CI, 1.12-5.43; P = 0.025; OS HR, 4.24; 95% CI, 1.48-12.09; P = 0.007) and in patients with TNBC (DFS HR, 4.68; 95% CI, 1.48-14.85; P = 0.009; OS HR, 10.43; 95% CI, 1.22-89.28; P = 0.032). CONCLUSIONS: Our findings indicate high CAV1/2 expression is associated with worse DFS and OS in paclitaxel-treated patients. Conversely, in nab-paclitaxel-treated patients, high CAV1/2 expression is associated with increased pCR and no significant detriment to DFS or OS compared with low CAV1/2 expression.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Caveolina 1/genética , Caveolina 1/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Paclitaxel , Expresión Génica , Terapia Neoadyuvante , Receptor ErbB-2/metabolismoRESUMEN
PURPOSE: Tumor microenvironment (TME) immune markers have been correlated with both response to neoadjuvant therapy and prognosis in patients with breast cancer. Here, immune-cell activity of breast cancer tumors was inferred by expression-based analysis to determine if it is prognostic and/or predictive of response to neoadjuvant paclitaxel-based therapy in the GeparSepto (G7) trial (NCT01583426). EXPERIMENTAL DESIGN: Pre-study biopsies from 279 patients with HER2-negative breast cancer in the G7 trial underwent RNA-seq-based profiling of 104 immune-cell-specific genes to assess inferred Immune Cell Activity (iICA) of 23 immune-cell types. Hierarchical clustering was used to classify tumors as iICA "hot," "warm," or "cold" by comparison of iICA in the G7 cohort relative to that of 1,467 samples from a tumor database established by Nantomics LLC. Correlations between iICA cluster, pathology-assessed tumor-infiltrating lymphocytes (TIL), and hormone receptor (HR) status for pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS) were determined. RESULTS: iICA cluster correlated with TIL levels. The highest pCR rates were observed in hot cluster tumors, and those with relatively higher TILs. Greater inferred activity of several T-cell types was significantly associated with pCR and survival. DFS and OS were prolonged in patients with hot or warm cluster tumors, the latter particularly for HR negative tumors, even if TILs were relatively low. CONCLUSIONS: Overall, TIL level better predicted pCR, but iICA cluster better predicted survival. Differences in associations between TILs, cluster, pCR, and survival were observed for HR-positive tumors versus HR-negative tumors, suggesting expanded study of the implication of these findings is warranted.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Paclitaxel/uso terapéutico , Pronóstico , Linfocitos Infiltrantes de Tumor , Supervivencia sin Enfermedad , Terapia Neoadyuvante , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Microambiente Tumoral/genéticaRESUMEN
CD8+ tumor-infiltrating lymphocytes with a tissue-resident memory T (TRM) cell phenotype are associated with favorable prognosis in patients with triple-negative breast cancer (TNBC). However, the relative contribution of CD8+ TRM cells to anti-tumor immunity and immune checkpoint blockade efficacy in breast cancer remains unknown. Here, we show that intratumoral CD8+ T cells in murine mammary tumors transcriptionally resemble those from TNBC patients. Phenotypic and transcriptional studies established two intratumoral sub-populations: one more enriched in markers of terminal exhaustion (TEX-like) and the other with a bona fide resident phenotype (TRM-like). Treatment with anti-PD-1 and anti-CTLA-4 therapy resulted in expansion of these intratumoral populations, with the TRM-like subset displaying significantly enhanced cytotoxic capacity. TRM-like CD8+ T cells could also provide local immune protection against tumor rechallenge and a TRM gene signature extracted from tumor-free tissue was significantly associated with improved clinical outcomes in TNBC patients treated with checkpoint inhibitors.
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Linfocitos T CD8-positivos , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Memoria Inmunológica , Fenotipo , Pronóstico , Linfocitos Infiltrantes de TumorRESUMEN
BACKGROUND/OBJECTIVES: The capacity of patients to give consent (CTC) is an indispensable prerequisite for informed consent to medical measures. When there is doubt about a patient's CTC, careful assessment is therefore required. Despite a broad theoretical discussion about the conception of CTC and possible procedures for its assessment, there is often a lack of orientation towards binding standardized procedural guidelines in everyday clinical practice. As a consequence, the results of CTC assessments are inconsistent, revealing both interdisciplinary and interindividual variability. In order to improve the quality of CTC assessment, more detailed knowledge about the procedures as well as the problems of CTC testing is needed. Therefore, the aim of this explorative telephone survey was to get an impression of the actual procedures that clinicians apply when in doubt about a patient's CTC. In particular, participants in the survey were asked about the weighting of individual CTC criteria and the difficulties with their application. METHODS: Based on structured questionnaires, telephone interviews with 26 physicians working in German hospitals in the fields of neurology, anaesthesiology, surgery, internal medicine, gynaecology, and reconstructive/aesthetic surgery were conducted. The answers were documented using the paper-and-pencil method, and answers to open questions were summarized with the help of a qualitative data analysis software and a thematic coding scheme. RESULTS: The majority of respondents reported that "sometimes to very often" they had doubts about their patients' CTC, with the examination being mostly conducted in an individual approach without formalized, standardized specifications. Regarding the question about the weighting of the seven assessment criteria proposed in the questionnaire, their importance was predominantly evaluated as being in the range of "partially important" to "very important". Difficulties in the clinical assessment were indicated in relation to the patients themselves, the relationship between physicians and patients, and the assessment situation. The perception of difficulties in the examination of CTC is apparently independent of the relevance attributed to the specific criterion for CTC. DISCUSSION AND CONCLUSION: Overall, the results show a high level of agreement with the relevance of the seven CTC criteria included in the survey, but at the same time revealed various verification difficulties. Some of the respondents would like to have more support in determining their patients' CTC. The survey results suggest that precise training and adequate time resources are paramount to this sensitive medical context.
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Consentimiento Informado , Médicos , Alemania , Humanos , Medicina Interna , Encuestas y CuestionariosRESUMEN
BACKGROUND: Current clinical guidelines suggest that breast cancers with low hormone receptor expression (LowHR) in 1-10% of tumor cells should be regarded as hormone receptor positive. However, clinical data show that these patients have worse outcome compared to patients with hormone receptor expression above 10%. We performed DNA methylation profiling on 23 LowHR breast cancer specimens, including 13 samples with HER2 amplification and compared our results with a reference breast cancer cohort from The Cancer Genome Atlas to clarify the status for this infrequent but important patient subgroup. RESULTS: In unsupervised clustering and dimensionality reduction, breast cancers with low hormone receptor expression that lacked HER2 amplification usually clustered with triple negative breast cancer (TNBC) reference samples (8/10; "LowHR TNBC-like"). In contrast, most specimens with low hormone receptor expression and HER2 amplification grouped with hormone receptor positive cancers (11/13; "LowHR HRpos-like"). We observed highly similar DNA methylation patterns of LowHR TNBC-like samples and true TNBCs. Furthermore, the Ki67 proliferation index of LowHR TNBC-like samples and clinical outcome parameters were more similar to TNBCs and differed from LowHR HRpos-like cases. CONCLUSIONS: We here demonstrate that LowHR breast cancer comprises two epigenetically distinct groups. Our data strongly suggest that LowHR TNBC-like samples are molecularly, histologically and clinically closely related to TNBC, while LowHR HRpos-like specimens are closely related to hormone receptor positive tumors.
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Neoplasias de la Mama/genética , Receptor ErbB-2/metabolismo , Adulto , Neoplasias de la Mama/clasificación , Metilación de ADN/genética , Metilación de ADN/fisiología , Femenino , Expresión Génica/genética , Humanos , Persona de Mediana Edad , Receptor ErbB-2/análisisRESUMEN
BACKGROUND: Parents are faced with a vaccination decision in the context of their own vaccination and that of their children with a COVID-19 vaccine. At present, there is no (complete) vaccination recommendation. RESEARCH QUESTION: The study investigates the willingness to vaccinate of parents of minors and people without children who are minors, in which gender differences in particular are examined. METHODS: The study is based on a random sample (telephone survey, nâ¯= 2,014, collected between 12 November and 10 December 2020). The evaluation is primarily based on the sub-sample of people with minors in the household (nâ¯= 461). RESULTS: Parents of minors consistently show a lower willingness to be vaccinated with a COVID-19 vaccine than respondents without minors (54.1% vs 71.1%). Fathers show a stronger willingness to be vaccinated than mothers. Furthermore, men are more willing to get their own child vaccinated with a COVID-19 vaccine than are women. CONCLUSIONS: Among parents and especially mothers, a considerable misrepresentation of vaccination risks and frequent beliefs in vaccination conspiracy theories can be observed. Clear and easily understandable information on the effects and side effects of vaccination with a COVID-19 vaccine by relevant institutions and physicians is recommended.
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BACKGROUND: About 80% of all people in Germany die in inpatient care. Around every fifth person in inpatient care is relocated to another care area in the last phase of their life. That is more than 150,000 people being relocated, often without indication. 13 risk factors were identified for these non-indicated relocations. METHOD: With the support of the AWMF, two regionally effective guidelines were developed and implemented in a maximum care hospital and a care facility. A palliative consultation service has been established in the university hospital. Comprehensive personnel and organizational development was carried out in the care facility. Different collaborations with relevant regional partners of both model institutions were systematically expanded. RESULTS AND CONCLUSIONS: The relocations could be significantly reduced despite the short duration of the project. This was also possible through the establishment of decision-making aids and digital implementation support. The results of the accompanying ethical and social research justify the procedure: There is an increase in the satisfaction of relatives and employees.
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Administración Financiera , Cuidados Paliativos , Alemania , Hospitalización , Humanos , Derivación y ConsultaRESUMEN
OBJECTIVE: The study examines the willingness to be vaccinated with a COVID-19 vaccine using a random sample of the general population and its determinants (perceived risks of disease, perceived side effects and general attitudes towards vaccination, trust in institutions, socio-structural factors, influence of social reference groups). METHODS: The study was based on a telephone, one-topic population survey (n=2,014) on willingness to be vaccinated (before the approval of a COVID-19 vaccine in Germany in November/December 2020). RESULTS: The willingness to be vaccinated was about 67% and increased with the proportion of peers and acquaintances who were willing to be vaccinated and had trust in the Robert Koch Institute; willingness was higher in members of a risk group, and in cases where there was an expectation of dangerous consequences of an infection. Experience with infection among the respondents or in peer-groups increased the willingness to be vaccinated. Men had a higher willingness to be vaccinated. The willingness to be vaccinated increased consistently with the level of formal education (with the exception of people with a technical college entrance qualification). Overestimating the likelihood of severe side effects of influenza vaccinations reduced the willingness to be vaccinated against COVID-19. Findings of considerable overestimations of the frequency of serious vaccination side effects were striking. CONCLUSION: Implications for a target group-appropriate information campaign and risk communication are derived. Efforts to promote the willingness of the population to be vaccinated should focus in particular on disadvantaged population groups.
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Vacunas contra la COVID-19 , COVID-19 , Alemania/epidemiología , Humanos , Masculino , SARS-CoV-2 , Encuestas y Cuestionarios , VacunaciónRESUMEN
AIM: To evaluate HER2-negative breast cancer (BC) with a low hormone receptor (HR) expression, with regard to pathological complete response (pCR) and survival, in comparison to triple-negative BC (TNBC) and strong HR-positive BC. METHODS: We compared negative [oestrogen (ER) and progesterone receptor (PR) <1%], low-positive (ER and/or PR 1-9%) and strong-positive (ER or PR 10-100%) HR-expression in neoadjuvant clinical trial cohorts (n = 2765) of BC patients. End-points were disease-free survival (DFS), distant-disease free survival (DDFS) and overall survival (OS). We performed RNA sequencing on available tumour tissue samples from patients with low-HR expression (n = 38). RESULTS: Ninety-four (3.4%) patients had low HR-positive tumours, 1769 (64.0%) had strong HR-positive tumours, and 902 (32.6%) had TNBC. There were no significant differences in pCR rates between women with low HR-positive tumours (27.7%) and women with TNBC (35.5%). DFS and DDFS were also not different [for DFS, hazard ratio 1.26, 95%-CI (confidence interval) : 0.87-1.83, log-rank test p = 0.951; for DDFS, hazard ratio 1.17, 95%-CI: 0.78-1.76, log-rank test p = 0.774]. Patients with strong HR-positive tumours had a significantly lower pCR rate (pCR 9.4%; odds ratio 0.38, 95%-CI: 0.23-0.63), but better DFS (hazard ratio 0.48, 95%-CI: 0.33-0.70) and DDFS (hazard ratio 0.49, 95%-CI: 0.33-0.74) than patients with low HR-positive tumours. Molecular subtyping (RNA sequencing) of low HR-positive tumours classified these predominantly into a basal subtype (86.8%). CONCLUSION: Low HR-positive, HER2-negative tumours have a similar clinical behaviour to TNBC showing high pCR rates and poor survival and also a basal-like gene expression signature. Patients with low HR-positive tumours should be regarded as candidates for therapy strategies targeting TNBC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Quimioterapia Adyuvante/mortalidad , Terapia Neoadyuvante/mortalidad , Neoplasias de la Mama Triple Negativas/mortalidad , Adulto , Anciano , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Humanos , Persona de Mediana Edad , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Inducción de Remisión , Tasa de Supervivencia , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
PURPOSE: We evaluated mRNA signatures to predict response to neoadjuvant PD-L1 inhibition in combination with chemotherapy in early triple-negative breast cancer. EXPERIMENTAL DESIGN: Targeted mRNA sequencing of 2,559 transcripts was performed in formalin-fixed, paraffin-embedded samples from 162 patients of the GeparNuevo trial. We focused on validation of four predefined gene signatures and differential gene expression analyses for new predictive markers. RESULTS: Two signatures [GeparSixto signature (G6-Sig) and IFN signature (IFN-Sig)] were predictive for treatment response in a multivariate model including treatment arm [G6-Sig: OR, 1.558; 95% confidence interval (CI), 1.130-2.182; P = 0.008 and IFN-Sig: OR, 1.695; 95% CI, 1.234-2.376; P = 0.002), while the CYT metric predicted pathologic complete response (pCR) in the durvalumab arm, and the proliferation-associated gene signature in the placebo arm. Expression of PD-L1 mRNA was associated with better response in both arms, indicating that increased levels of PD-L1 are a general predictor of neoadjuvant therapy response. In an exploratory analysis, we identified seven genes that were higher expressed in responders in the durvalumab arm, but not the placebo arm: HLA-A, HLA-B, TAP1, GBP1, CXCL10, STAT1, and CD38. These genes were associated with cellular antigen processing and presentation and IFN signaling. CONCLUSIONS: Immune-associated signatures are associated with pCR after chemotherapy, but might be of limited use for the prediction of response to additional immune checkpoint blockade. Gene expressions related to antigen presentation and IFN signaling might be interesting candidates for further evaluation.
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Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inmunidad/genética , Neoplasias de la Mama Triple Negativas/etiología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayos Clínicos Fase II como Asunto , Biología Computacional/métodos , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Perfilación de la Expresión Génica , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Terapia Neoadyuvante , Estadificación de Neoplasias , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
PURPOSE: Expression-based classifiers to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) are not routinely used in the clinic. We aimed to build and validate a classifier for pCR after NACT. PATIENTS AND METHODS: We performed a prospective multicenter study (EXPRESSION) including 114 patients treated with anthracycline/taxane-based NACT. Pretreatment core needle biopsies from 91 patients were used for gene expression analysis and classifier construction, followed by validation in five external cohorts (n = 619). RESULTS: A 20-gene classifier established in the EXPRESSION cohort using a Youden index-based cut-off point predicted pCR in the validation cohorts with an accuracy, AUC, negative predictive value (NPV), positive predictive value, sensitivity, and specificity of 0.811, 0.768, 0.829, 0.587, 0.216, and 0.962, respectively. Alternatively, aiming for a high NPV by defining the cut-off point for classification based on the complete responder with the lowest predicted probability of pCR in the EXPRESSION cohort led to an NPV of 0.960 upon external validation. With this extreme-low cut-off point, a recommendation to not treat with anthracycline/taxane-based NACT would be possible for 121 of 619 unselected patients (19.5%) and 112 of 322 patients with luminal breast cancer (34.8%). The analysis of the molecular subtypes showed that the identification of patients who do not achieve a pCR by the 20-gene classifier was particularly relevant in luminal breast cancer. CONCLUSIONS: The novel 20-gene classifier reliably identifies patients who do not achieve a pCR in about one third of luminal breast cancers in both the EXPRESSION and combined validation cohorts.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/genética , Neoplasias de la Mama/terapia , Toma de Decisiones Clínicas/métodos , Terapia Neoadyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Quimioterapia Adyuvante/métodos , Conjuntos de Datos como Asunto , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Mastectomía , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de Secuencia por Matrices de Oligonucleótidos , Selección de Paciente , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Sensor-based monitoring allows continuous observations of patient mobilization after proximal femoral fractures. A wrist-worn motion tracker allows long-term observation that is low in interruption and constraints for subjects. OBJECTIVE: Description of steps development after hip fracture surgery on a specialized geriatric trauma ward and beyond. MATERIAL AND METHODS: In the explorative long-term field research study, an applicable motion tracker observed steps per day of 20 patients (80% female, mean age 85.2 years⯱ 7.86 years) for 10 weeks. Weekly mean values (days 1-7, 8-14 etc.) of steps per day formed the database for descriptive analysis (mean, SD, min, max, median). RESULTS: During observation weeks (ow) a positive development of steps took place. A mean increase factor of 1.285 (±0.351) occurred from ow 1 (Mâ¯= 353.57⯱ 310.15) to ow 10 (Mâ¯= 2482.07⯱ 1374.12). The highest increase by a factor of 1.8 could be reported from ow 2 (Mâ¯= 556.27⯱ 478.11) to ow 3 (Mâ¯= 1024.86⯱ 921.24) as well as from ow 6 (Mâ¯= 1268.21⯱ 880.47) to 7 (Mâ¯= 2367.14⯱ 1680.08). A slight decrease of steps occurred from ow 4 (Mâ¯= 1208.27⯱ 1210.45) to ow 5 (0.99-fold) and from ow 9 (Mâ¯= 2689.98⯱ 2339.71) to 10 (0.92-fold). High ranges and standard deviations in relation to the mean occurred constantly. The presence of several step development groups could be presumed. CONCLUSION: Motion tracker and the variable steps per day can represent the ability to walk within an everyday environment, with a possible underestimation of <â¯10%. Differences regarding observation lengths and disruptions occurred. Cluster analysis should detect group attributes of different courses of development in subsequent studies.
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Fracturas del Fémur , Fracturas de Cadera , Anciano , Anciano de 80 o más Años , Femenino , Fracturas de Cadera/cirugía , Humanos , Estudios Longitudinales , Masculino , Pacientes , CaminataRESUMEN
BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer (BC). Due to the absence of targets such as HER2 or hormone receptors, early TNBC is treated with surgery and chemotherapy. Since TNBC is also considered the most immunogenic type of BC with tumor infiltrating lymphocytes that are predictive for chemotherapy response and prognostic for patients' survival, many different immunotherapeutic strategies are currently explored in clinical trials for the treatment of this disease. In order to efficiently combine chemotherapy with immunotherapy, it is important to evaluate the effect of chemotherapy on immune cells in vivo. METHODS: Peripheral blood was taken from 56 patients with TNBC undergoing neoadjuvant chemotherapy with nanoparticle albumin-bound paclitaxel (Nab-Pac) followed by epirubicin and cyclophosphamide (EC) at three different time points. Multicolor flow cytometry was used to characterize the immune cell composition and functional properties along neoadjuvant chemotherapy. RESULTS: Whereas the first phase of the neoadjuvant chemotherapy did not significantly alter the patients' immune cell composition, after the second phase of chemotherapeutic administration most B cells (>90%) were lost and the frequency of natural killer (NK) cells and CD4+ T lymphocytes decreased approximately to 50%. In contrast, the frequency of CD8+ T cells were less affected. CONCLUSIONS: Despite late consequences of Nab-Pac cannot be ruled out, these data suggest that different chemotherapeutics might have distinct effects on the immune cell repertoire and that different immune cell populations exhibit a specific susceptibility to these chemotherapies with B and NK cells being more affected than T cells. This might also have an impact on the combination of chemotherapies with immunotherapies. TRIAL REGISTRATION NUMBER: NCT02685059.