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BACKGROUND: The Neoadjuvant Breast Symphony Trial (NBRST) demonstrated the 70-gene risk of distant recurrence signature, MammaPrint, and the 80-gene molecular subtyping signature, BluePrint, precisely determined preoperative pathological complete response (pCR) in breast cancer patients. We report 5-year follow-up results in addition to an exploratory analysis by age and menopausal status. METHODS: The observational, prospective NBRST (NCT01479101) included 954 early-stage breast cancer patients aged 18-90 years who received neoadjuvant chemotherapy and had clinical and genomic data available. Chemosensitivity and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed. In a post hoc subanalysis, results were stratified by age (≤ 50 vs. > 50 years) and menopausal status in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) tumors. RESULTS: MammaPrint and BluePrint further classified 23% of tumors to a different subtype compared with immunohistochemistry, with more precise correspondence to pCR rates. Five-year DMFS and OS were highest in MammaPrint Low Risk, Luminal A-type and HER2-type tumors, and lowest in MammaPrint High Risk, Luminal B-type and Basal-type tumors. There was no significant difference in chemosensitivity between younger and older patients with Low-Risk (2.2% vs. 3.8%; p = 0.64) or High-Risk tumors (14.5% vs. 11.5%; p = 0.42), or within each BluePrint subtype; this was similar when stratifying by menopausal status. The 5-year outcomes were comparable by age or menopausal status for each molecular subtype. CONCLUSION: Intrinsic preoperative chemosensitivity and long-term outcomes were precisely determined by BluePrint and MammaPrint regardless of patient age, supporting the utility of these assays to inform treatment and surgical decisions in early-stage breast cancer.
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BACKGROUND: Cancer prevention and treatment systems are significantly impacted by interpersonal, organizational, and structural and systemic racism. A wide body of research has found that racial disparities in access to guideline-adherent cancer care are pervasive throughout the United States and contributing factors include social determinants of health, insurance status, and bias and discrimination in care delivery. Although the existence of racial disparities in cancer care and outcomes is well established, there has been limited research exploring the patient and caregiver experience with bias and discrimination in cancer care. METHODS: Two national surveys were conducted, one of patients and caregivers and one of oncologists. The surveys examined patient and caregiver experiences with and oncologist perceptions of racial disparities in cancer care. RESULTS: The surveys found that when patients and caregivers were asked about negative care experiences, differences across race were observed. Patients and caregivers identifying as African American/Black (AA/B) or Hispanic/Latino (H/L) were more likely to report at least one negative care experience than patients and caregivers identifying as White (W). Patients who were AA/B or H/L were also more likely than W patients to report that the healthcare system treats people unfairly based on their racial or ethnic background and that racial bias occurs often or very often when a patient and doctor are of different racial/ethnic background. A slight majority of oncologists reported that the healthcare system treats people unfairly based on their racial or ethnic background. CONCLUSIONS: The survey results highlight a need for improved racial representation in the oncology professional workforce, improved implicit bias training, and improved clinical trial recruitment efforts.
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Neoplasias , Oncologistas , Racismo , Negro ou Afro-Americano , Cuidadores , Atenção à Saúde , Disparidades em Assistência à Saúde , Humanos , Neoplasias/terapia , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: De-escalation of breast cancer treatment aims to reduce patient and financial toxicity without compromising outcomes. Level I evidence and National Comprehensive Cancer Network guidelines support omission of adjuvant radiation in patients aged >70 y with hormone-sensitive, pT1N0M0 invasive breast cancer treated with endocrine therapy. We evaluated radiation use in patients eligible for guideline concordant omission of radiation. METHODS: Subgroup analysis of patients eligible for radiation omission from two pooled randomized controlled trials, which included stage 0-III breast cancer patients undergoing breast conserving surgery, was performed to evaluate factors associated with radiation use. RESULTS: Of 631 patients, 47 (7.4%) met radiation omission criteria and were treated by 14 surgeons at eight institutions. The mean age was 75.3 (standard deviation + 4.4) y. Majority of patients identified as White (n = 46; 97.9%) and non-Hispanic (n = 44; 93.6%). The mean tumor size was 1.0 cm; 37 patients (88.1%) had ductal, 4 patients (9.5%) had lobular, and 17 patients (40.5%) had low-grade disease. Among patients eligible for radiation omission, 34 (72.3%) patients received adjuvant radiation. Those who received radiation were significantly younger than those who did not (74 y, interquartile range = 4 y, versus 78 y, interquartile range = 11 y, P = 0.03). There was no difference in radiation use based on size (P = 0.4), histology (P = 0.5), grade (P = 0.7), race (P = 1), ethnicity (P = 0.6), institution (P = 0.1), gender of the surgeon (P = 0.7), or surgeon (P = 0.1). CONCLUSIONS: Fewer than 10% of patients undergoing breast conservation met criteria for radiation omission. Nearly three-quarters received radiation therapy with younger age being a driver of radiation use, suggesting ample opportunity for de-escalation, particularly among younger eligible patients.
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Neoplasias da Mama , Carcinoma in Situ , Idoso , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma in Situ/cirurgia , Tratamento Conservador , Feminino , Hormônios , Humanos , Mastectomia Segmentar , Radioterapia AdjuvanteRESUMO
OBJECTIVE: To examine whether yearly fluctuations in acceptance from and disclosure to parents were associated with fluctuations in perceptions of patient-centered communication (PCC) with the healthcare provider and whether fluctuations in PCC were associated with self-efficacy, type 1 diabetes self-care, and HbA1c across four annual assessments during early emerging adulthood (EA). METHODS: A total of 228 high school seniors (M age = 17.76 years at time 1) reported on mothers' and fathers' acceptance and diabetes-related disclosure to parents, diabetes self-care, and PCC once per year for 4 years. HbA1c was collected from assay kits. RESULTS: Multilevel models revealed within-person associations such that in years when individuals reported greater maternal acceptance than their average, they reported higher PCC. In addition, between-person differences indicated that individuals who reported more maternal acceptance on average relative to others also perceived greater PCC. Similar associations were found for EAs' reports of fathers. No significant effects were found for disclosure to either mother or father. Yearly fluctuations in PCC were associated with self-efficacy such that in years when perceived PCC was higher, self-efficacy was higher. Between person-effects were found for self-efficacy, self-care, and HbA1c such that individuals who reported more PCC on average relative to others reported higher self-efficacy, better self-care, and lower HbA1c. CONCLUSIONS: Aspects of EA's relationships with parents fluctuate with perceptions of PCC with healthcare providers. Perceived PCC with the healthcare provider may be important in higher self-efficacy, diabetes self-care, and lower HbA1c across the early EA years.
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Diabetes Mellitus , Pais , Adolescente , Adulto , Comunicação , Diabetes Mellitus/terapia , Feminino , Hemoglobinas Glicadas , Pessoal de Saúde , Humanos , Assistência Centrada no PacienteRESUMO
The Growth Arrest and DNA Damage-inducible 45 (GADD45) family of proteins are critical stress sensors that mediate various cellular responses, including DNA repair, cell cycle arrest, and apoptosis. Here, we review current literature investigating GADD45 family members as they relate to normal development and carcinogenesis. We first describe how modulation of GADD45 in model organisms has facilitated our understanding of roles for GADD45 family members in development and homeostasis. We then review current literature exploring roles for GADD45 in human cancer, describing cancer-associated alterations in expression of GADD45 family members; tumor suppressive and tumor promoting functions attributed to GADD5; and roles for GADD45 in cancer therapy. In exploring roles for GADD45 in development, homeostasis, and carcinogenesis, we aim to provide an informational resource that both highlighst current knowledge on this topic while also noting key gaps in our understanding of the biology of GADD45 that may be filled in order to best guide the development of novel approaches to improve diagnosis, monitoring, and therapy of human malignancies.
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Proteínas de Ciclo Celular , Neoplasias , Carcinogênese , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Reparo do DNA , Humanos , Neoplasias/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismoRESUMO
OBJECTIVE: Single-center studies have demonstrated that resection of cavity shave margins (CSM) halves the rate of positive margins and re-excision in breast cancer patients undergoing partial mastectomy (PM). We sought to determine if these findings were externally generalizable across practice settings. METHODS: In this multicenter randomized controlled trial occurring in 9 centers across the United States, stage 0-III breast cancer patients undergoing PM were randomly assigned to either have resection of CSM ("shave" group) or not ("no shave" group). Randomization occurred intraoperatively, after the surgeon had completed their standard PM. Primary outcome measures were positive margin and re-excision rates. RESULTS: Between July 28, 2016 and April 13, 2018, 400 patients were enrolled in this trial. Four patients (2 in each arm) did not meet inclusion criteria after randomization, leaving 396 patients for analysis: 196 in the "shave" group and 200 to the "no shave" group. Median patient age was 65 years (range; 29-94). Groups were well matched at baseline for demographic and clinicopathologic factors. Prior to randomization, positive margin rates were similar in the "shave" and "no shave" groups (76/196 (38.8%) vs. 72/200 (36.0%), respectively, P = 0.604). After randomization, those in the "shave" group were significantly less likely than those in the "no shave" group to have positive margins (19/196 (9.7%) vs. 72/200 (36.0%), P < 0.001), and to require re-excision or mastectomy for margin clearance (17/196 (8.7%) vs. 47/200 (23.5%), P < 0.001). CONCLUSION: Resection of CSM significantly reduces positive margin and re-excision rates in patients undergoing PM.
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Neoplasias da Mama/cirurgia , Margens de Excisão , Mastectomia Segmentar/métodos , Estadiamento de Neoplasias , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Photoprotection of human skin is determined as the capacity of sunscreens to prevent ultraviolet (UV) B radiation-induced erythema and UVA radiation-induced pigmentation. It is unequivocal that, in addition to sunscreens, oral supplementation with carotenoids can protect human skin against UVB radiation-induced erythema. It is not known if this is also the case for UVA radiation-induced pigmentation. OBJECTIVE: To clinically evaluate the photoprotective effects of daily supplementation with carotenoids against UVA radiation-induced pigmentation. METHODS: In this double-blind, placebo-controlled trial, 60 subjects (Fitzpatrick types II-IV) were randomized to receive Nutrilite™ Multi Carotene supplement or placebo for 12 weeks. UVB-induced minimal erythemal dose (MED), UVA-induced minimal persistent pigmentation dose (MPPD) and skin carotenoid levels were measured at baseline, 4, 8, and 12 weeks of intervention. Skin color was evaluated by expert clinical graders and by colorimetry. Carotenoid levels in the skin were measured by the Biozoom® device. RESULTS: In the intervention group, a significant increase in comparison with the placebo group was observed in (a) skin carotenoid levels, (b) UVB-induced MED, and (c) UVA-induced MPPD values obtained by colorimetry. CONCLUSION: Daily supplementation with carotenoids protects human skin against both UVB-induced erythema and UVA-induced pigmentation.
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Carotenoides/uso terapêutico , Pigmentação da Pele/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Administração Oral , Adulto , Carotenoides/administração & dosagem , Carotenoides/análise , Método Duplo-Cego , Eritema/etiologia , Eritema/prevenção & controle , Humanos , Pele/química , Pigmentação da Pele/efeitos da radiação , Adulto JovemRESUMO
OBJECTIVE: To examine (a) changes in parental involvement across early emerging adulthood, (b) whether yearly fluctuations in parental involvement were associated with adherence and glycated hemoglobin (HbA1c) over time, and (c) whether higher involvement was more beneficial for those with poorer executive function (EF). METHODS: A total of 228 high school seniors (M age = 17.76) with type 1 diabetes reported on mothers' and fathers' acceptance, knowledge of diabetes activities, disclosure to mothers and fathers regarding diabetes, and adherence at four yearly time points. At baseline, participants completed performance-based measures of EF. HbA1c was collected from assay kits. RESULTS: Growth curve models revealed significant declines in disclosure to fathers and mothers' and fathers' knowledge of diabetes activities; no changes were found in mothers' or fathers' acceptance nor disclosure to mothers. Multilevel models indicated significant between-person effects for nearly all aspects of parental involvement with more acceptance, knowledge, and disclosure associated with better HbA1c and adherence. Within-person effects for disclosure to fathers, and mothers' and fathers' knowledge indicated that in years when emerging adults perceived higher amounts of these types of involvement (compared with their own average), HbA1c was lower. Within-person effects were found for acceptance to mothers, disclosure to mothers and fathers, and mothers' diabetes knowledge for adherence. Disclosure to fathers and mothers' knowledge of diabetes activities were especially beneficial for HbA1c for those with poorer EF performance. CONCLUSIONS: Parental involvement in diabetes management remains important during the high-risk time of emerging adulthood, especially for those with poorer EF.
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Disfunção Cognitiva/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/terapia , Função Executiva , Poder Familiar , Pais , Cooperação do Paciente , Adolescente , Adulto , Função Executiva/fisiologia , Feminino , Seguimentos , Humanos , Masculino , Adulto JovemRESUMO
Early emerging adulthood (ages 18-25) is a time of risk for type 1 diabetes (T1D) when relationships with parents and providers are changing. We examined whether individuals' high-quality relationships with mothers are associated with greater perceptions of patient-centered communication (PCC) with their doctor and whether PCC is associated with better adherence and glycemic control through diabetes-related self-efficacy. Additionally, we tested whether associations of PCC with self-efficacy and diabetes outcomes are stronger among those who had transferred to adult care. One-year post-high school, 217 individuals with T1D (60% women, 53% in adult care) reported perceptions of maternal relationship quality, PCC, self-efficacy, and adherence. Glycemic control was measured via HbA1c assay kits. Structural equation modeling indicated good model fit and revealed indirect paths linking higher maternal relationship quality to better adherence through higher PCC, and higher PCC to better HbA1c through adherence. Transfer status moderated the link between PCC and self-efficacy, suggesting PCC may be especially important when emerging adults transfer to adult care.
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Diabetes Mellitus Tipo 1/psicologia , Gerenciamento Clínico , Relações Mãe-Filho/psicologia , Assistência Centrada no Paciente/métodos , Autocuidado , Autoeficácia , Transição para Assistência do Adulto , Adolescente , Adulto , Comunicação , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Modelos Estruturais , Cooperação e Adesão ao Tratamento/psicologia , Adulto JovemRESUMO
The practice of operating room (OR) clinicians - nurses, surgeons, and anesthetists - is fundamentally about preserving life. Some patients, however, die in the OR. Clinicians are therefore vulnerable to moral and emotional trauma. In this paper, we discuss three forces that shape clinicians' moral and emotional experiences in OR care: biomedical values, normative death discourse, and socially (un)sanctioned grief. We suggest how each of these forces increases clinicians' vulnerability to feel traumatized when their patients die. We hope this discussion will stimulate clinicians and researchers to engage with social and cultural determinants of clinicians' experiences when patients die.
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Anestesistas , Emoções , Pesar , Enfermeiras e Enfermeiros , Salas Cirúrgicas , Relações Profissional-Paciente , Cirurgiões , Fadiga de Compaixão , HumanosRESUMO
Newborn screening for primary congenital hypothyroidism is part of the U.S. Recommended Uniform Screening Panel (1,2). Untreated congenital hypothyroidism can result in cognitive impairment and growth complications (decreased height/length). Initial newborn screening for congenital hypothyroidism is typically performed 24-48 hours after birth. Fourteen states, including Utah, perform a routine second screen at approximately 2 weeks of age.* During 2010-2016, a total of 359,432 infants in Utah were screened for congenital hypothyroidism, and 130 cases were diagnosed; among these, 98 had an abnormal first screen, and 25 had an abnormal second screen (seven infants were excluded because of missing data). A retrospective examination of Utah's screening data indicated that 20% of congenital hypothyroidism cases could not have been efficiently identified by a single screen alone. This study highlights the utility of a two-screen process and demonstrates that differential cutoff values for the first and second screens could optimize both screening sensitivity and specificity.
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Hipotireoidismo Congênito/diagnóstico , Triagem Neonatal/métodos , Hipotireoidismo Congênito/epidemiologia , Humanos , Recém-Nascido , Estudos Retrospectivos , Sensibilidade e Especificidade , Utah/epidemiologiaRESUMO
PURPOSE: Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT). OBJECTIVE: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity. METHODS: NBRST IHC/FISH HR+/HER2- breast cancer patients (n = 474) were classified into four molecular subgroups by MammaPrint/BluePrint subtyping: Luminal A, Luminal B, HER2, and Basal type. Pathological complete response (pCR) rates were compared with conventional IHC/FISH subtype. RESULTS: The overall pCR rate for 'clinical luminal' patients to NCT was 11 %; however, 87 of these 474 patients were reclassified as Basal type by BluePrint, with a high pCR rate of 32 %. The MammaPrint index was highly associated with the likelihood of pCR (p < 0.001). Fifty-three patients with BluePrint Luminal tumors received NET with an aromatase inhibitor and 36 (68 %) had a clinical response. CONCLUSIONS: With BluePrint subtyping, 18 % of clinical 'luminal' patients are classified in a different subgroup, compared with conventional assessment, and these patients have a significantly higher response rate to NCT compared with BluePrint Luminal patients. MammaPrint/BluePrint subtyping can help allocate effective treatment to appropriate patients. In addition, accurate identification of subtype biology is important in the interpretation of neoadjuvant treatment response since lack of pCR in luminal patients does not portend the worse prognosis associated with residual disease in Basal and HER2 subtypes.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/classificação , Neoplasias da Mama/tratamento farmacológico , Perfilação da Expressão Gênica , Tipagem Molecular/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Quimioterapia Adjuvante , Tomada de Decisão Clínica , Ciclofosfamida/administração & dosagem , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Letrozol , Mastectomia Segmentar , Pessoa de Meia-Idade , Terapia Neoadjuvante , Nitrilas/administração & dosagem , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Sistema de Registros , Tamoxifeno/administração & dosagem , Taxoides/administração & dosagem , Resultado do Tratamento , Triazóis/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: Pertuzumab became a standard part of neoadjuvant therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancers approximately halfway through Neoadjuvant Breast Registry Symphony Trial (NBRST) enrollment, providing a unique opportunity to determine biologically which clinical HER2+ patients benefit most from dual targeting. As a neoadjuvant phase 4 study, NBRST classifies patients by both conventional and molecular subtyping. METHODS: Of 308 clinical HER2+ patients enrolled in NBRST between 2011 and 2014 from 62 U.S. institutions, 297 received neoadjuvant chemotherapy (NCT) with HER2-targeted therapy and underwent surgery. This study compared the pathologic complete response (pCR) rate of BluePrint versus clinical subtypes with treatment, specifically differences between trastuzumab (T) treatment and trastuzumab and pertuzumab (T/P) treatment. RESULTS: In this study, 60% of the patients received NCT-T, and 40% received NCT-T/P. The overall pCR rate (ypT0/isN0) was 47%. BluePrint classified 161 tumors (54%) as HER2 type, with a pCR rate of 65%. This was significantly higher than the pCR rate for the 91 HER2+ tumors (31%) classified as luminal (18%) (p = 0.00001) and the 45 tumors (15%) classified as basal (44%) (p = 0.0166). The patients treated with T/P had higher pCR rates than those treated with trastuzumab alone. The difference was most pronounced in the BluePrint luminal patients (8 vs. 31%). The highest pCR was reached by the BluePrint HER2-type patients treated with T/P (76%). CONCLUSIONS: The addition of pertuzumab leads to increased pCR rates for all HER2+ patient groups except for the BluePrint basal-type patients. This better response was most pronounced for the BluePrint luminal-type patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Testes Genéticos , Genômica , Humanos , Terapia Neoadjuvante , Estudos Prospectivos , Trastuzumab/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVES: Good glycemic control is an important goal of diabetes management. Late adolescents with type 1 diabetes (T1D) are at risk for poor glycemic control as they move into young adulthood. For a subset of these patients, this dysregulation is extreme, placing them at risk for life-threatening health complications and permanent cognitive declines. The present study examined whether deficiency in emotional decision making (as measured by the Iowa Gambling Task; IGT) among teens with T1D may represent a neurocognitive risk factor for subsequent glycemic dysregulation. METHODS: As part of a larger longitudinal study, a total of 241 high-school seniors (147 females, 94 males) diagnosed with T1D underwent baseline assessment that included the IGT. Glycated hemoglobin (HbA1c), which reflects glycemic control over the course of the past 2 to 3 months, was also assessed at baseline. Of the 241,189 (127 females, 62 males, mean age=17.76, mean HbA1c=8.11) completed HbA1c measurement 1 year later. RESULTS: Baseline IGT performance in the impaired range (per norms) was associated with greater dysregulation in glycemic control 1 year later, as evidenced by an average increase in HbA1c of 2%. Those with normal IGT scores (per norms) exhibited a more moderate increase in glycemic control, with an HbA1c increase of 0.7%. Several IGT scoring approaches were compared, showing that the total scores collapsed across all trials was most sensitive to change in glycemic control. CONCLUSIONS: IGT assessment offers promise as a tool for identifying late adolescents at increased risk for glycemic dysregulation. (JINS, 2017, 23, 204-213).
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Glicemia/fisiologia , Tomada de Decisões/fisiologia , Diabetes Mellitus Tipo 1 , Jogos Experimentais , Adolescente , Afeto/fisiologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/psicologia , Feminino , Seguimentos , Hemoglobinas Glicadas/metabolismo , Humanos , Modelos Lineares , Masculino , Análise de Componente Principal , Adulto JovemRESUMO
BACKGROUND: Haemodialysis patients receive very little involvement in their end-of-life care decisions. Issues relating to death and dying are commonly avoided until late in their illness. This study aimed to explore the experiences and perceptions of doctors and nurses in nephrology for involving haemodialysis patients in end-of-life care decisions. METHODS: A semi-structured qualitative interview study with 15 doctors and five nurses and thematic analysis of their accounts was conducted. The setting was a large teaching hospital in Wales, UK. RESULTS: Prognosis is not routinely discussed with patients, in part due to a difficulty in estimation and the belief that patients do not want or need this information. Advance care planning is rarely carried out, and end-of-life care discussions are seldom initiated prior to patient deterioration. There is variability in end-of-life practices amongst nephrologists; some patients are felt to be withdrawn from dialysis too late. Furthermore, the possibility and implications of withdrawal are not commonly discussed with well patients. Critical barriers hindering better end-of-life care involvement for these patients are outlined. CONCLUSIONS: The study provides insights into the complexity of end-of-life conversations and the barriers to achieving better end-of-life communication practices. The results identify opportunities for improving the lives and deaths of haemodialysis patients.
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Comunicação , Tomada de Decisões , Diálise Renal , Assistência Terminal , Adulto , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros/psicologia , Médicos/psicologia , Relações Profissional-Paciente , Pesquisa Qualitativa , País de GalesRESUMO
Using skin autofluorescence (SAF) as a marker of advanced glycation end-products (AGEs) has been extensively studied in the last decade since the introduction of the noninvasive in vivo measurement technique. Data have shown the level of skin AGEs increases with chronological age in healthy human beings, and this increase is substantially higher in age-matched diabetic patients. In skin research, glycation with the accompanying accumulation of skin AGEs has been regarded as one of the primary skin aging mechanisms that contribute to skin wrinkling and the loss of skin elasticity. To date, the totality of SAF data reported in literature has been obtained from measurements on the arm, and noninvasive measurement of facial skin AGE accumulation would add great value to skin aging research. In this study, we report the levels of facial and forearm skin AGEs in 239 men and women of 21-65 year of age. Significantly lower levels of AGEs were detected in the facial skin than in the forearm skin from the young Caucasian groups, and the difference was much larger for men than for women. The rate of change in skin AGE level over age was found to be about 50% higher in men than in women, which further highlights the gender difference. A statistically significant correlation between the levels of skin AGE and facial wrinkling was also observed. The facial skin AGE data may provide new insight into skin aging research.
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Face/fisiologia , Produtos Finais de Glicação Avançada/química , Envelhecimento da Pele/fisiologia , Pele/química , Adulto , Idoso , Braço , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Airway epithelial CD55 down-regulation occurs in several hypoxia-associated pulmonary diseases, but the mechanism is unknown. Using in vivo and in vitro assays of pharmacologic inhibition and gene silencing, the current study investigated the role of hypoxia-inducible factor (HIF)-1α in regulating airway epithelial CD55 expression. Hypoxia down-regulated CD55 expression on small-airway epithelial cells in vitro, and in murine lungs in vivo; the latter was associated with local complement activation. Treatment with pharmacologic inhibition or silencing of HIF-1α during hypoxia-recovered CD55 expression in small-airway epithelial cells. HIF-1α overexpression or blockade, in vitro or in vivo, down-regulated CD55 expression. Collectively, these data show a key role for HIF-1α in regulating the expression of CD55 on airway epithelium.
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Antígenos CD55/metabolismo , Epitélio/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Pulmão/metabolismo , Aminoácidos Dicarboxílicos/farmacologia , Animais , Hipóxia Celular/efeitos dos fármacos , Ativação do Complemento/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Epitélio/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: The prospective Neoadjuvant Breast Symphony Trial (NBRST) study found that MammaPrint/BluePrint functional molecular subtype is superior to conventional immunohistochemistry/fluorescence in situ hybridization subtyping for predicting pathologic complete response (pCR) to neoadjuvant chemotherapy. The purpose of this substudy was to determine if the rate of pCR is affected by tumor size. METHODS: The NBRST study includes breast cancer patients who received neoadjuvant chemotherapy. MammaPrint/BluePrint subtyping classified patients into four molecular subgroups: Luminal A, Luminal B, HER2 (human epidermal growth factor receptor 2), and Basal type. Probability of pCR (ypT0/isN0) as a function of tumor size and molecular subgroup was evaluated. RESULTS: A total of 608 patients were evaluable with overall pCR rates of 28.5 %. Luminal A and B patients had significantly lower rates of pCR (6.1 and 8.7 %, respectively) than either basal (37.1 %) or HER2 (55.0 %) patients (p < 0.001). The probability of pCR significantly decreased with tumor size >5 cm [p = 0.022, odds ratio (OR) 0.58, 95 % confidence interval (CI) 0.36, 0.93]. This relationship was statistically significant in the Basal (p = 0.026, OR 0.46, 95 % CI 0.23, 0.91) and HER2 (p = 0.039, OR 0.36, 95 % CI 0.14, 0.95) subgroups. In multivariate logistic regression analyses, the dichotomized tumor size variable was not significant in any of the molecular subgroups. DISCUSSION: Even though tumor size would intuitively be a clinical determinant of pCR, the current analysis showed that the adjusted OR for tumor size was not statistically significant in any of the molecular subgroups. Factors significantly associated with pCR were PR status, grade, lymph node status, and BluePrint molecular subtyping, which had the strongest correlation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Terapia Neoadjuvante , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Indução de Remissão , Taxa de Sobrevida , Carga Tumoral , Adulto JovemRESUMO
A major decision for patients with stage 5 chronic kidney disease (CKD) relates to vascular access (VA) for treatment. Patients who receive pre-dialysis care often defer making a decision, which results in initiation of hemodialysis (HD) with a central venous catheter (CVC) in an urgent or emergent situation. Little is known about how individuals make decisions around VA. In this context, a mixed-methods study was undertaken to explore uncertainty related to changing their VA from an existing CVC to a graft or fistula. Quantitative assessment was measured using the SURE tool and interviews with patients and nurses were conducted. Results revealed that none of the 16 patient participants reported uncertainty. Qualitative findings revealed that patient decisions about access were impacted by observations, experiences, and dialogue in the hemodialysis unit. Study findings have important implications including the challenge of reconciling epidemiologic population-based risk measurement to the individual patient's situation. Moreover, the SURE tool was viewed as a mechanism to open a dialogue to confirm patients' decisions and provide further education and/or support following HD initiation.