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1.
Int J Cancer ; 155(1): 128-138, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38447007

RESUMO

BRAWO, a real-world study, assessed the efficacy, quality of life (QoL) and safety of EVE + EXE in postmenopausal women with HR+/HER2- advanced breast cancer (ABC) in routine clinical practice. Postmenopausal women with HR+/HER2-ABC with recurrence or progression after a NSAI were included. Primary Observation parameters included the evaluation of the effectiveness of EVE + EXE. A multivariate-analysis using Cox proportional hazard model was built to identify predictors of progression. Overall, 2100 patients were enrolled (August 2012-December 2017); 2074 were evaluable for efficacy and safety analyses. Majority of patients (60.6%) received EVE + EXE as first (28.7%) or second-line (31.9%) therapy. Visceral metastases were present in 54.1% patients. Median progression-free survival (mPFS) reported as 6.6 months (95%CI: 6.3-7.0). Multivariate-analysis in a subset of patients (n = 1837) found higher body mass index (BMI) and non-visceral metastases to be independent predictors of favorable PFS. Patients with a BMI of 20 to <25 had a mPFS of 6.0 (95%CI: 5.4-6.4) and those with a BMI ≥30 had mPFS of 8.5 (95%CI: 6.9-9.9). 41.2% patients achieved stable disease and 7.3% partial response. No major changes were observed QoL; 86.4% patients received stomatitis prophylaxis and 41.4% experienced EVE related AEs of stomatitis, mainly low grade. AEs occurred in 91.2% of patients, of which stomatitis (42.6%) and fatigue (19.8%) were most frequent. The BRAWO study provides real-world evidence of efficacy and safety of EVE + EXE in patients with HR+, HER2- ABC. A high BMI and the absence of visceral metastases were independent predictors of PFS in this cohort of patients.


Assuntos
Androstadienos , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Everolimo , Qualidade de Vida , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Receptor ErbB-2/metabolismo , Idoso , Pessoa de Meia-Idade , Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Androstadienos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptores de Progesterona/metabolismo , Receptores de Estrogênio/metabolismo , Idoso de 80 Anos ou mais , Adulto , Pós-Menopausa , Intervalo Livre de Progressão
2.
BMC Med ; 22(1): 442, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39379960

RESUMO

BACKGROUND: Increased levels of physical activity are associated with a reduction of breast cancer mortality, especially in postmenopausal women with positive hormone receptor status. So far, previous observational case-control and cohort studies have focused on associations between overall leisure time physical activity and survival of women with breast cancer in general. METHODS: In this multicenter prospective cohort study, conducted in Germany between 30th August 2012 to 29th December 2017, we investigated general physical activity in a homogenous sample of n = 1440 postmenopausal women with advanced (inoperable locally advanced or metastatic), hormone receptor-positive breast cancer receiving the same therapy (everolimus and exemestane). Self-reported physical activity was assessed using the Godin Leisure Time Exercise Questionnaire (GLTEQ) before and every 3 months during treatment. Participants were then classified into "active" and "insufficiently active" to screen their activity behavior the week prior to medical treatment. In addition, changes in physical activity patterns were assessed. Adjusted Cox regression analyses were performed for the activity categories to determine hazard ratios (HR). Besides progression-free survival (PFS), adverse events (AEs), QoL, and fatigue were assessed every 3 months until study termination. RESULTS: Compared to "insufficiently active" patients, "active" individuals indicated a significantly longer PFS (HR: 0.84 [0.74; 0.984], p = .0295). No significant differences were observed for changes of physical activity behavior. Patients who reported to be "active" at baseline revealed significantly fewer AEs compared to "insufficiently" active patients. In detail, both severe and non-severe AEs occurred less frequently in the "active" patients group. In line with that, QoL and fatigue were better in physical "active" patients compared to their insufficient active counterparts at the last post-baseline assessment. Participants who remained or become active indicated less AEs, a higher QoL, and reduced fatigue levels. CONCLUSIONS: Physical activity behavior prior to medical treatment might have prognostic value in patients with advanced breast cancer in terms of extending the PFS. Moreover, physical activity before and during treatment may reduce treatment-related side effects and improve patients' QoL and fatigue. TRIAL REGISTRATION: EUPAS9462. Registered 30th October 2012 "retrospectively registered."


Assuntos
Neoplasias da Mama , Exercício Físico , Humanos , Feminino , Exercício Físico/fisiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Alemanha , Intervalo Livre de Progressão , Androstadienos/uso terapêutico , Everolimo/uso terapêutico , Qualidade de Vida , Receptores de Estrogênio/metabolismo , Pós-Menopausa , Fadiga
3.
Int J Mol Sci ; 25(20)2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39456897

RESUMO

Interleukins play dual roles in breast cancer, acting as both promoters and inhibitors of tumorigenesis within the tumor microenvironment, shaped by their inflammatory functions. This study analyzed the subtype-specific prognostic significance of an acute inflammatory versus a chronic inflammatory interleukin signature using microarray-based gene expression analysis. Correlations between these interleukin signatures and immune cell markers (CD8, IgKC, and CD20) and immune checkpoints (PD-1) were also evaluated. This study investigated the prognostic significance of an acute inflammatory IL signature (IL-12, IL-21, and IFN-γ) and a chronic inflammatory IL signature (IL-4, IL-5, IL-10, IL-13, IL-17, and CXCL1) for metastasis-free survival (MFS) using Kaplan-Meier curves and Cox regression analyses in a cohort of 461 patients with early breast cancer. Correlations were analyzed using the Spearman-Rho correlation coefficient. Kaplan-Meier curves revealed that the prognostic significance of the acute inflammatory IL signature was specifically pronounced in the basal-like subtype (p = 0.004, Log Rank). This signature retained independent prognostic significance in multivariate Cox regression analysis (HR 0.463, 95% CI 0.290-0.741; p = 0.001). A higher expression of the acute inflammatory IL signature was associated with longer MFS. The chronic inflammatory IL signature showed a significant prognostic effect in the whole cohort, with higher expression associated with shorter MFS (p = 0.034). Strong correlations were found between the acute inflammatory IL signature and CD8 expression (ρ = 0.391; p < 0.001) and between the chronic inflammatory IL signature and PD-1 expression (ρ = 0.627; p < 0.001). This study highlights the complex interaction between acute and chronic inflammatory interleukins in breast cancer progression and prognosis. These findings provide insight into the prognostic relevance of interleukin expression patterns in breast cancer and may inform future therapeutic strategies targeting the immune-inflammatory axis.


Assuntos
Neoplasias da Mama , Interleucinas , Microambiente Tumoral , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/imunologia , Neoplasias da Mama/genética , Microambiente Tumoral/imunologia , Prognóstico , Interleucinas/metabolismo , Interleucinas/genética , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Adulto , Inflamação/metabolismo , Inflamação/patologia , Estimativa de Kaplan-Meier , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica
4.
Environ Monit Assess ; 196(5): 470, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658409

RESUMO

Recent studies suggest that arthropod diversity in German forests is declining. Currently, different national programs are being developed to monitor arthropod trends and to unravel the effects of forest management on biodiversity in forests. To establish effective long-term monitoring programs, a set of drivers of arthropod diversity and composition as well as suitable species groups have to be identified. To aid in answering these questions, we investigated arthropod data collected in four Hessian forest reserves (FR) in the 1990s. To fully utilize this data set, we combined it with results from a retrospective structural sampling design applied at the original trap locations in central European beech (Fagus sylvatica) forests. As expected, the importance of the different forest structural, vegetation, and site attributes differed largely between the investigated arthropod groups: beetles, spiders, Aculeata, and true bugs. Measures related to light availability and temperature such as canopy cover or potential radiation were important to all groups affecting either richness, composition, or both. Spiders and true bugs were affected by the broadest range of explanatory variables, which makes them a good choice for monitoring general trends. For targeted monitoring focused on forestry-related effects on biodiversity, rove and ground beetles seem more suitable. Both groups were driven by a narrower, more management-related set of variables. Most importantly, our study approach shows that it is possible to utilize older biodiversity survey data. Although, in our case, there are strong restrictions due to the long time between species and structural attribute sampling.


Assuntos
Artrópodes , Biodiversidade , Monitoramento Ambiental , Fagus , Florestas , Animais , Monitoramento Ambiental/métodos , Conservação dos Recursos Naturais/métodos , Agricultura Florestal/métodos
5.
Breast Cancer Res ; 25(1): 60, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37254150

RESUMO

Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman's lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.


Assuntos
Neoplasias da Mama , Progesterona , Feminino , Humanos , Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Ciclo Menstrual/fisiologia , Estrogênios , Estradiol , Preparações Farmacêuticas
6.
Oncologist ; 28(12): e1152-e1159, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37555463

RESUMO

BACKGROUND: Eribulin, a halichondrin-class microtubule dynamics inhibitor, is a preferred treatment option for patients with advanced breast cancer who have been pretreated with an anthracycline and a taxane. Peripheral neuropathy (PN) is a common side effect of chemotherapies for breast cancer and other tumors. The Incidence and Resolution of Eribulin-Induced Peripheral Neuropathy (IRENE) noninterventional postauthorization safety study assessed the incidence and severity of PN in patients with breast cancer treated with eribulin. PATIENTS AND METHODS: IRENE is an ongoing observational, single-arm, prospective, multicenter, cohort study. Adult patients (≥18 years of age) with locally advanced or metastatic breast cancer and disease progression after 1-2 prior chemotherapeutic regimen(s) for advanced disease were treated with eribulin. Patients with eribulin-induced PN (new-onset PN or worsening of preexisting PN) were monitored until death or resolution of PN. Primary endpoints included the incidence, severity, and time to resolution of eribulin-induced PN. Secondary endpoints included time to disease progression and safety. RESULTS: In this interim analysis (data cutoff date: July 1, 2019), 67 (32.4%) patients experienced any grade eribulin-induced PN, and 12 (5.8%) patients experienced grade ≥3 eribulin-induced PN. Median time to resolution of eribulin-induced PN was not reached. Median time to disease progression was 4.6 months (95% CI, 4.0-6.5). Treatment-emergent adverse events (TEAEs) occurred in 195 (93.8%) patients and serious TEAEs occurred in 107 (51.4%) patients. CONCLUSION: The rates of any grade and grade ≥3 eribulin-induced PN observed in this real-world study were consistent with those observed in phase III randomized clinical trials. No new safety findings were observed.


Assuntos
Neoplasias da Mama , Doenças do Sistema Nervoso Periférico , Adulto , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Estudos de Coortes , Progressão da Doença , Furanos/efeitos adversos , Incidência , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologia , Estudos Prospectivos , Resultado do Tratamento , Moduladores de Tubulina/efeitos adversos
7.
Chemistry ; 29(72): e202302301, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-37740670

RESUMO

During the investigation of the binary system Be-Ru two new phases - Be7 Ru4 and Be12 Ru7 - with similar compositions (63.6 at. % Be and 63.2 at. % Be, respectively), are discovered. They both represent new structural prototypes. The phases are located between Be2 Ru (Fe2 P-type structure) and Be3 Ru2 (U3 Si2 -type structure) in the phase diagram. This explains why their crystal structures, solved and refined from single crystal X-ray diffraction data, are described as 2D intergrowth of Fe2 P and U3 Si2 motives. The calculated electronic density of stats (DOS) reveals pronounced minima in the vicinity of the Fermi level for both compounds. Position-space analysis of chemical bonding exhibits the formation of three- and four-atomic polar bonds, involving both, Ru and Be, atoms, and a strong charge transfer from Be to the more electronegative Ru.

8.
Chemistry ; 29(33): e202300578, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-36916324

RESUMO

The structural features of the hexagonal layered crystal structure of Be2 Ru (a=5.7508(3) Å, c=3.0044(2) Å, space group P 6 ‾ ${\bar{6}}$ 2m) were investigated by single crystal X-ray diffraction and transmission electron microscopy (TEM). The residual electron density and high-resolution TEM images show that the real structure can be described as an intergrowth of the main hexagonal matrix of the Fe2 P type with minor orthorhombic inclusions of its stacking variants. Such atomic arrangement is stabilized by the charge transfer from Be to Ru and by a system of polar three- and four-atomic bonds involving both components. The calculated electronic density of states (DOS) of Be2 Ru revealed, contrarily to typical intermetallic compounds, a pseudo gap (dip) in the vicinity of the Fermi level. The temperature dependence of the electrical resistivity of Be2 Ru shows metal behaviour in agreement with the non-zero DOS at the Fermi level.


Assuntos
Eletricidade , Cristalografia por Raios X , Microscopia Eletrônica de Transmissão , Temperatura
9.
Crit Rev Food Sci Nutr ; : 1-18, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37000015

RESUMO

Fermentable oligo-, di- and monosaccharides and polyols (FODMAP) comprise several previously unrelated carbohydrates, such as fructans, fructo-oligosaccharides, galacto-oligosaccharides, fructose (in excess of glucose), mannitol and sorbitol, and among others. For many patients with gastro-intestinal disorders, such as irritable bowel syndrome, the ingestion of FODMAP triggers symptoms and causes discomfort. Among the main contributors to the dietary FODMAP intake are baking products, in particular bread as a major global staple food. This is primarily due to the fructan content of the cereal flours, but also process induced accumulation of FODMAP is possible. To provide low-FODMAP baking products, researchers have investigated various approaches, such as bio-process reduction by yeast, lactic acid bacteria, germination of the raw material or the use of exogenous enzymes. In addition, the selection of appropriate ingredients, which are either naturally or after pretreatment suitable for low-FODMAP products, is discussed. The sensory and nutritional quality of low-FODMAP baking products is another issue, that is addressed, with particular focus on providing sufficient dietary fiber intake. Based on this information, the current state of low-FODMAP baking and future research necessities, to establish practical strategies for low-FODMAP products, are evaluated in this article.

10.
Inorg Chem ; 62(23): 9054-9062, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37227413

RESUMO

Na2Ga7 crystallizes with the orthorhombic space group Pnma (no. 62; a = 14.8580(6) Å, b = 8.6766(6) Å, and c = 11.6105(5) Å; Z = 8) and constitutes a filled variant of the Li2B12Si2 structure type. The crystal structure consists of a network of icosahedral Ga12 units with 12 exohedral bonds and four-bonded Ga atoms in which the Na atoms occupy the channels and cavities. The atomic arrangement is consistent with the Zintl [(4b)Ga]- and Wade [(12b)Ga12]2- electron counting approach. The compound forms peritectically from Na7Ga13 and the melt at 501 °C and does not show a homogeneity range. The band structure calculations predict semiconducting behavior consistent with the electron balance [Na+]4[(Ga12)2-][Ga-]2. Magnetic susceptibility measurements show that Na2Ga7 is diamagnetic.

11.
Nature ; 547(7663): 324-327, 2017 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-28726829

RESUMO

The conservation laws, such as those of charge, energy and momentum, have a central role in physics. In some special cases, classical conservation laws are broken at the quantum level by quantum fluctuations, in which case the theory is said to have quantum anomalies. One of the most prominent examples is the chiral anomaly, which involves massless chiral fermions. These particles have their spin, or internal angular momentum, aligned either parallel or antiparallel with their linear momentum, labelled as left and right chirality, respectively. In three spatial dimensions, the chiral anomaly is the breakdown (as a result of externally applied parallel electric and magnetic fields) of the classical conservation law that dictates that the number of massless fermions of each chirality are separately conserved. The current that measures the difference between left- and right-handed particles is called the axial current and is not conserved at the quantum level. In addition, an underlying curved space-time provides a distinct contribution to a chiral imbalance, an effect known as the mixed axial-gravitational anomaly, but this anomaly has yet to be confirmed experimentally. However, the presence of a mixed gauge-gravitational anomaly has recently been tied to thermoelectrical transport in a magnetic field, even in flat space-time, suggesting that such types of mixed anomaly could be experimentally probed in condensed matter systems known as Weyl semimetals. Here, using a temperature gradient, we observe experimentally a positive magneto-thermoelectric conductance in the Weyl semimetal niobium phosphide (NbP) for collinear temperature gradients and magnetic fields that vanishes in the ultra-quantum limit, when only a single Landau level is occupied. This observation is consistent with the presence of a mixed axial-gravitational anomaly, providing clear evidence for a theoretical concept that has so far eluded experimental detection.

12.
Scand J Med Sci Sports ; 33(6): 1021-1033, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36703247

RESUMO

PURPOSE: To (1) identify neuromuscular and biomechanical injury risk factors in elite youth soccer players and (2) assess the predictive ability of a machine learning approach. MATERIAL AND METHODS: Fifty-six elite male youth soccer players (age: 17.2 ± 1.1 years; height: 179 ± 8 cm; mass: 70.4 ± 9.2 kg) performed a 3D motion analysis, postural control testing, and strength testing. Non-contact lower extremities injuries were documented throughout 10 months. A least absolute shrinkage and selection operator (LASSO) regression model was used to identify the most important injury predictors. Predictive performance of the LASSO model was determined in a leave-one-out (LOO) prediction competition. RESULTS: Twenty-three non-contact injuries were registered. The LASSO model identified concentric knee extensor peak torque, hip transversal plane moment in the single-leg drop landing task and center of pressure sway in the single-leg stance test as the three most important predictors for injury in that order. The LASSO model was able to predict injury outcomes with a likelihood of 58% and an area under the ROC curve of 0.63 (sensitivity = 35%; specificity = 79%). CONCLUSION: The three most important variables for predicting the injury outcome suggest the importance of neuromuscular and biomechanical performance measures in elite youth soccer. These preliminary results may have practical implications for future directions in injury risk screening and planning, as well as for the development of customized training programs to counteract intrinsic injury risk factors. However, the poor predictive performance of the final model confirms the challenge of predicting sports injuries, and the model must therefore be evaluated in larger samples.


Assuntos
Traumatismos em Atletas , Traumatismos do Joelho , Futebol , Humanos , Masculino , Adolescente , Futebol/lesões , Extremidade Inferior/lesões , Traumatismos do Joelho/prevenção & controle , Fatores de Risco , Traumatismos em Atletas/epidemiologia , Traumatismos em Atletas/diagnóstico
13.
Arch Gynecol Obstet ; 308(2): 527-534, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36707423

RESUMO

PURPOSE: Despite the growing understanding of the carcinogenesis of pelvic high-grade serous carcinoma (HGSC) of the ovary and peritoneum and its precursor lesion serous tubal intraepithelial carcinoma (STIC), evidence-based proven recommendations on the clinical management of patients with STIC are lacking so far. METHODS: A questionnaire containing 21 questions was developed to explore the clinical experience with patients with the diagnosis of STICs and the diagnostic, surgical and histopathological approaches in Germany. Overall, 540 clinical heads of department in all German gynaecological centres were asked to participate. RESULTS: 131 questionnaires (response rate 24.3%) were included in this survey. 45.8% of the respondents had treated one to three STIC patients during their career. 75.6% of the respondents performed opportunistic bilateral salpingectomies during other gynaecological surgeries. Most of the participants (31.3%) started with the SEE-FIM (Sectioning and Extensively Examining the FIMbria) protocol in 2014. It was requested by 39.7% centres for prophylactic salpingectomies, by 13.7% for both prophylactic and opportunistic salpingectomies and by 22.1% for neither of both. 38.2%, 1.5% and 24.4% of the participants would use the laparoscopic, transverse and midline laparotomic approach for a surgical staging procedure, respectively. 25.6% (54.7%) of the respondents recommended a hysterectomy in premenopausal (versus postmenopausal) patients with a STIC, 24.4% (88.4%) a bilateral oophorectomy and 50.0% (4.7%) an affected side oophorectomy (all p values < 0.001). Omentectomy, pelvic and para-aortic lymphadenectomy would be performed by 60.5% (64.0%), 9.3% (11.6%) and 9.3% (11.6%) of respondents in premenopausal (versus postmenopausal) patients (all p values > 0.05). CONCLUSION: Our survey highlights significant inconsistency in the management of patients with STIC. Prospective data are urgently needed to elucidate the clinical impact of a STIC lesion and its clinical management.


Assuntos
Carcinoma in Situ , Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Feminino , Humanos , Estudos Prospectivos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias das Tubas Uterinas/patologia , Cistadenocarcinoma Seroso/patologia , Inquéritos e Questionários , Carcinoma in Situ/patologia
14.
Arch Gynecol Obstet ; 307(6): 1929-1940, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36434440

RESUMO

PURPOSE: Frailty is a frequent and underdiagnosed multidimensional age-related syndrome, involving decreased physiological performance reserves and marked vulnerability against major stressors. To standardize the preoperative frailty assessment and identify patients at risk of adverse surgical outcomes, commonly used global health assessment tools were evaluated. We aimed to assess three interdisciplinary preoperative screening assessments to investigate the influence of frailty status with in-hospital complications irrespective of surgical complexity and radicality in older women with ovarian cancer (OC). METHODS: Preoperative frailty status was examined by the G8 geriatric screening tool (G8 Score-geriatric screening), Eastern Cooperative Oncology Group performance status (ECOG PS-oncological screening), and American Society of Anesthesiologists Physical Status System (ASA PS-anesthesiologic screening). The main outcome measures were the relationship between perioperative laboratory results, intraoperative surgical parameters and the incidence of immediate postoperative in-hospital complications with the preoperative frailty status. RESULTS: 116 consecutive women 60 years and older (BMI 24.8 ± 5.2 kg/m2) with OC, who underwent elective oncological surgery in University Medical Center Mainz between 2008 and 2019 were preoperatively classified with the selected global health assessment tools as frail or non-frail. The rate of preoperative anemia (hemoglobin ≤ 12 g/dl) and perioperative transfusions were significantly higher in the G8-frail group (65.9% vs. 34.1%; p = 0.006 and 62.7% vs. 41.8%, p = 0.031; respectively). In addition, patients preoperatively classified as G8-frail exhibited significantly more postoperative clinical in-hospital complications (27.8% vs. 12.5%, p = 0.045) independent of chronological age and BMI. In contrast, ECOG PS and ASA PS did not predict the rates of postoperative complications (all p values > 0.05). After propensity score matching, the complication rate in the G8-frail cohort was approximately 1.7 times more common than in the G8-non-frail cohort. CONCLUSION: Preoperative frailty assessment with the G8 Score identified elderly women with OC recording a significantly higher rate of postoperative in-hospital complications. In G8-frail patients, preoperative anemia and perioperative transfusions were significantly more recorded, regardless of chronological age, abnormal BMI and surgical complexity. Standardized preoperative frailty assessment should be added to clinical routine care to enhance risk stratification in older cancer individuals for surgical patient-centered decision-making.


Assuntos
Fragilidade , Neoplasias Ovarianas , Humanos , Feminino , Idoso , Fragilidade/complicações , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Idoso Fragilizado , Detecção Precoce de Câncer , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Fatores de Risco
15.
Int J Mol Sci ; 24(20)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37894900

RESUMO

Due to a higher mutational load, triple-negative breast cancer (TNBC) is characterized by a higher immunogenicity compared to other subtypes. In this context, we analyzed the prognostic significance of tumor-infiltrating plasma cells in a cohort of 107 triple-negative breast cancer patients. Tumor-infiltrating plasma cells were analyzed via immunohistochemistry using the plasma cell markers CD38 and IgκC. The prognostic impact of the CD38 and IgκC expression was evaluated using the Kaplan-Meier plots and Cox regression analyses. A Spearman-Rho correlation coefficient was used to evaluate a possible association between plasma cell infiltration and the BRCA mutation status. The study cohort consisted of 107 patients with early-stage TNBC, who were treated between 2009 and 2016 at the Department of Gynecology and Obstetrics, University Medical Center Mainz, Germany. The median follow-up was five years. The Kaplan-Meier survival analysis showed that higher tumor infiltration with CD38-positive plasma cells was associated with significantly longer metastasis-free survival (MFS) (p = 0.039 Log Rank). In the multivariate Cox regression analysis for metastasis-free survival, in which additional clinicopathological factors (age, tumor size, nodal status, and grading) were considered, CD38 was identified as an independent prognostic factor within the analyzed cohort (HR 0.438, 95% CI 0.195-0.983; p = 0.045). In addition to the CD38 expression, the nodal status was also identified as an independent prognostic factor in multivariate Cox regression. Regarding the IgκC expression, a higher IgκC expression was shown to be associated with a better outcome, although this effect was not statistically significant. Furthermore, we were able to show a significant correlation between plasma cell infiltration and the BRCA mutation status. A favorable prognostic significance of tumor-infiltrating plasma cells could be demonstrated in triple-negative breast cancer immunohistochemically analyzed for the CD38 and IgκC expression. CD38 was identified as an independent prognostic factor via multivariate Cox regression.


Assuntos
Plasmócitos , Neoplasias de Mama Triplo Negativas , Humanos , Biomarcadores Tumorais/metabolismo , Intervalo Livre de Doença , Linfócitos do Interstício Tumoral/metabolismo , Plasmócitos/metabolismo , Prognóstico , Neoplasias de Mama Triplo Negativas/patologia
16.
Breast Cancer Res Treat ; 191(1): 147-157, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34626275

RESUMO

PURPOSE: Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany. METHODS: A total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account. RESULTS: After a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85-1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88-1.25). CONCLUSIONS: Even though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy.


Assuntos
Neoplasias da Mama , Radioterapia Conformacional , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/radioterapia , Feminino , Alemanha/epidemiologia , Coração , Humanos , Radioterapia Adjuvante , Estudos Retrospectivos
17.
Crit Rev Food Sci Nutr ; 62(12): 3281-3300, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33356495

RESUMO

Cereal ß-glucan describes a group of soluble dietary fiber primarily found in barley and oats. It is characterized by the mixed occurrence of ß-(1,3) and ß-(1,4) bonds between the glucose monomers, forming long polysaccharide chains with unique properties. Alongside their technological benefits, they exhibit a number of health-beneficial properties. Nevertheless, ß-glucan applications as nutraceutical food ingredient, are rarely utilized. The changes in physicochemical (molar mass, solubility and viscosity) and health-beneficial (glycemic control, lowering of blood glucose) properties during food processing and storage are a major drawback. The understanding of the complex mechanisms behind the health benefits of ß-glucan is still incomplete. In contrast to original believes, it becomes evident from recent literature, that physiological properties are not only based on the dose administered. A more thorough view on the molecule and its structure-size-function relationship is required to understand the impact of molar mass, molar ratio, solubility and viscosity. Therefore, this review evaluates the recent scientific data to identify ß-glucan key properties responsible for the nutraceutical function in the final product. This provides a guideline for future research which characteristics need careful monitoring and preservation throughout processing and help to fully utilize cereal ß-glucan as nutraceutical ingredient.


Assuntos
Ingredientes de Alimentos , Hordeum , beta-Glucanas , Avena , Glicemia , Fibras na Dieta/análise , Grão Comestível/química , Ingredientes de Alimentos/análise , Hordeum/química , beta-Glucanas/química
18.
Psychooncology ; 31(7): 1120-1126, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35124858

RESUMO

OBJECTIVE: Many preference-sensitive decisions have to be made in breast cancer care and little is known about the decision-making processes between breast cancer patients and the different health care professionals engaged in their treatment. METHODS: All female breast cancer patients who underwent surgery in four German breast centers between 07/2016 and 12/2018 were invited to fill in a survey. The decision-making process was evaluated using the 9-item Shared Decision Making Questionnaire (SDM-Q-9) and a German measure to assess satisfaction with care (ZAPA). The higher the total score (0-100), the higher the experienced degree of participation and satisfaction, respectively. Participants were asked to separately rate consultations with their inpatient hospital doctors, outpatient gynecologists, outpatient oncologists and primary care providers. An overall mean score for the degree of participation and the satisfaction with care was calculated for each patient across all consultations assessed. Differences between the 4 treating physician groups were analyzed as well. RESULTS: Of 1068 approached patients, 563 with a mean age of 62 and a standard deviation (SD) of 12.2 years filled in the survey (response rate: 53%). The overall SDM-Q-9 score was 73.8 (SD: 20.8). Older patients stated a higher level of participation than younger, different physician groups were rated quite similarly. Overall satisfaction with care was 87.4 (SD: 15.5). CONCLUSIONS: Overall, patients reported to have experienced a high level of shared decision-making (SDM) and were quite satisfied with their treatment. However, we do not know whether non-responders might have had different experiences.


Assuntos
Neoplasias da Mama , Tomada de Decisão Compartilhada , Neoplasias da Mama/terapia , Estudos Transversais , Tomada de Decisões , Feminino , Alemanha , Humanos , Pessoa de Meia-Idade , Participação do Paciente , Relações Médico-Paciente
19.
Inorg Chem ; 61(40): 16148-16155, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36166747

RESUMO

Mg29-xPt4+y represents the family of complex intermetallic compounds (complex metallic alloys, CMAs). It crystallizes in the cubic non-centrosymmetric space group F4̅3m with a = 20.1068(2) Šand around 400 atoms in a predominantly ordered arrangement. The local disorder around the unit cell origin is experimentally resolved by single-crystal X-ray diffraction in combination with atomic-resolution transmission electron microscopy (TEM, high-angle dark-field scanning TEM) studies. The quantum theory of atoms in molecules-based analysis of atomic charges shows that the unusual mixed Mg/Pt site occupation around the origin results from local charge equilibration in this region of the crystal structure. Chemical bonding analysis reveals for Mg29-xPt4+y─rather unexpected for a crystal structure of this size─space-separated regions of hetero- and homoatomic bonds involving three to six partners (bonding inhomogeneity). Pt-containing 11- and 13-atomic units formed by heteroatomic 3a-, 4a-, and 5a-bonds are condensed via edges and faces to large super-tetrahedrons, which are interlinked by Mg-only 6a-bonds. Spatial separation of the regions with different bonding features is the key difference between the title compound and other CMAs, which are characterized by a predominantly homogeneous distribution of heteroatomic bonds.

20.
Gerontology ; 68(10): 1101-1110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34875663

RESUMO

BACKGROUND: We evaluated the prognostic impact of various global health assessment tools in patients older than 60 years with ovarian cancer (OC). METHODS: G-8 geriatric screening tool (G-8 score), Lee Schonberg prognostic index, Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson Comorbidity Index (CCI) were determined retrospectively in a consecutive cohort of elderly patients with OC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze the impact of the preoperative global health status on survival. RESULTS: 116 patients entered the study. In multivariate analysis adjusted for clinical-pathological factors, only the G-8 score retained significance as a prognostic parameter of progression-free survival (PFS) (hazard ratio [HR]: 1.970; 95% confidence interval [CI] [1.056-3.677]; p = 0.033). Fifty-six patients were classified as G-8-nonfrail with an increased PFS compared to 50 G-8-frail patients (53.4% vs. 16.7%; p = 0.010). A higher CCI was associated with decreased PFS (45.1% vs. 22.2%; p = 0.012), but it did not influence the risk of recurrences or death (p = 0.360; p = 0.111). The Lee Schonberg prognostic index, the ECOG, and age were not associated with survival. CONCLUSIONS: The G-8 score independently predicted PFS in elderly OC patients regardless of maximal surgical effort. Thus, it could be useful to assess surgical treatment based on frailty rather than age alone.


Assuntos
Detecção Precoce de Câncer , Neoplasias Ovarianas , Idoso , Estudos de Coortes , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Intervalo Livre de Progressão , Estudos Retrospectivos
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