The separate use of the terms 'radiosensitivity' and 'radiosusceptibility' has been suggested to describe variability in the risk of, respectively, adverse tissue reactions (deterministic effect) ...following radiotherapy and radiation-induced cancer (stochastic effect). The aim of this note is to present arguments against such distinction. We feel that it is premature to make a concrete final judgement on these definitions because of the limited understanding of the mechanisms underlying individual sensitivity to both radiation-related cancers and radiation-related tissue injury. Moreover, the exclusive application of 'radiosensitivity' in relation to deterministic effects and the term 'radiosusceptibility' in relation to cancer carries the risk of being wrongly interpreted as evidence for a high, genetically driven sensitivity to radiation in all patients who develop adverse tissue reactions and a high genetic susceptibility to cancer in those who develop radiation-induced malignancies. There is a need for further research to better define these phenomena and their interrelationships.
Abstract
Background
Demographic changes are leading to growing care needs of older people and creating a challenge for healthcare systems worldwide. Nursing homes (NHs) need to provide care for ...growing numbers of residents while ensuring a high-quality care. We aimed to examine an innovative NH in Germany and apply a theory of change (ToC) approach to develop a best practice model (BPM) for therapeutic care in NHs.
Methods
A multimethod qualitative study conducted from February to July 2021 in Germany involved interviews with 14 staff members of an innovative NH and 10 directors and care managers of other NHs. The interview guidelines included questions on nursing practices, infrastructure, resources, interprofessional collaboration, and working culture. Additional material on the participating NH (website, promotion videos, newsletters, care documentation) were collected. Contextual literature on NH culture and therapeutic care in Germany, ToC methodology, and NH culture change were reviewed. Following a question-focused analysis of all material, we generated a ToC model towards a BPM of therapeutic care and meaningful living in NHs. Results were verified in interdisciplinary team meetings, with study participants and other stakeholders to establish consensus.
Results
The participating NH’s care concept aims to improve residents’ functional abilities and wellbeing as well as staff members’ job satisfaction. Central components of their approach include therapeutic elements such as music and movement in all nursing activities, multidisciplinary collaboration, a broad therapy and social activity offer, the continuation of therapy in everyday activities, a focus on individual life history, values, needs, and skills, social integration into the regional community, and the creation of a meaningful living environment for residents and staff.
Conclusion
The BPM we developed shows how a meaningful living environment can be created through therapeutic care and integrative activities. The ToC sheds light onto the contextual factors and cultural values which should be considered in the development of NH interventions. Research on not only biomedical aspects, but also psychosocial dynamics and narrative co-constructions in nursing practice should inform NH innovations. The ToC also highlights the importance of developing adequate political frameworks and infrastructures for implementing such innovative practices on a larger scale.
Multigene assays have been developed and validated to determine the prognosis of breast cancer. In this study, we assessed the additional predictive value of the 70-gene MammaPrint signature for ...chemotherapy (CT) benefit in addition to endocrine therapy (ET) from pooled study series. For 541 patients who received either ET (n = 315) or ET + CT (n = 226), breast cancer-specific survival (BCSS) and distant disease-free survival (DDFS) at 5 years were assessed separately for the 70-gene high and low risk groups. The 70-gene signature classified 252 patients (47%) as low risk and 289 (53%) as high risk. Within the 70-gene low risk group, BCSS was 97% for the ET group and 99% for the ET + CT group at 5 years with a non-significant univariate hazard ratio (HR) of 0.58 (95% CI 0.07-4.98; P = 0.62). In the 70-gene high risk group, BCSS was 81% (ET group) and 94% (ET + CT group) at 5 years with a significant HR of 0.21 (95% CI 0.07-0.59; P < 0.01). DDFS was 93% (ET) versus 99% (ET + CT), respectively, in the 70-gene low risk group, HR 0.26 (95% CI 0.03-2.02; P = 0.20). In the high risk group DDFS was 76 versus 88%, HR of 0.35 (95% CI 0.17-0.71; P < 0.01). Results were similar in multivariate analysis, showing significant survival benefit by adding CT in the 70-gene high risk group. A significant and clinically meaningful benefit was observed by adding chemotherapy to endocrine treatment in 70-gene high risk patients. This benefit was not significant in low risk patients, who were at such low risk for recurrence and cancer-related death, that adding CT does not appear to be clinically meaningful.
Abstract
Whether low-dose ionizing radiation can cause cancer is a critical and long-debated question in radiation protection. Since the Biological Effects of Ionizing Radiation report by the ...National Academies in 2006, new publications from large, well-powered epidemiological studies of low doses have reported positive dose-response relationships. It has been suggested, however, that biases could explain these findings. We conducted a systematic review of epidemiological studies with mean doses less than 100 mGy published 2006–2017. We required individualized doses and dose-response estimates with confidence intervals. We identified 26 eligible studies (eight environmental, four medical, and 14 occupational), including 91 000 solid cancers and 13 000 leukemias. Mean doses ranged from 0.1 to 82 mGy. The excess relative risk at 100 mGy was positive for 16 of 22 solid cancer studies and 17 of 20 leukemia studies. The aim of this monograph was to systematically review the potential biases in these studies (including dose uncertainty, confounding, and outcome misclassification) and to assess whether the subset of minimally biased studies provides evidence for cancer risks from low-dose radiation. Here, we describe the framework for the systematic bias review and provide an overview of the eligible studies.
Abstract
Background
Our aim was to determine the best operative procedure in human participants with a displaced or non-displaced femoral neck fracture comparing cannulated screw (CS) fixation, ...dynamic hip screw (DHS) fixation, hemiarthroplasty (HA), and total hip arthroplasty (THA) in terms of surgical and functional outcomes, reoperation and postoperative complications.
Methods
We searched PubMed, The Cochrane Library, Clinical trials, CINAHL, and Embase for randomized controlled trials (RCTs) or quasi-RCTs up to 31 July 2022. A frequentist network meta-analysis was performed to assess the comparative effects of the four operative procedures, using fixed-effects and random-effects models. Mean differences (MDs) with 95% confidence intervals (CIs) were estimated for continuous variables and odds ratios (ORs) with 95% CIs were estimated for binary variables.
Results
A total of 33 RCTs with 5703 patients were included in our network meta-analysis. CS fixation was best in terms of operation time (CS: MD = − 57.70, 95% CI − 72.78; − 42.62; DHS: MD = − 53.56, 95% CI − 76.17; − 30.95; HA: MD = − 20.90, 95% CI − 30.65; − 11.15; THA: MD = 1.00 reference) and intraoperative blood loss (CS: MD = − 3.67, 95% CI − 4.44; − 2.90; DHS: MD = − 3.20, 95% CI − 4.97; − 1.43; HA: MD = − 1.20, 95% CI − 1.73; − 0.67; THA: MD = 1.00 reference). In life quality and functional outcome, measured at different time points with EQ-5D and the Harris Hip Score (HHS), THA ranked first and HA second (e.g. EQ-5D 2 years postoperatively: CS: MD = − 0.20, 95% CI − 0.29; − 0.11; HA: MD = − 0.09, 95% CI − 0.17; − 0.02; THA: MD = 1.00 reference; HHS 2 years postoperatively: CS: MD = − 5.50, 95% CI − 9.98; − 1.03; DHS: MD = − 8.93, 95% CI − 15.08; − 2.78; HA: MD = − 3.65, 95% CI − 6.74; − 0.57; THA: MD = 1.00 reference). CS fixation had the highest reoperation risk, followed by DHS fixation, HA, and THA (CS: OR = 9.98, 95% CI 4.60; 21.63; DHS: OR = 5.07, 95% CI 2.15; 11.96; HA: OR = 1.60, 95% CI 0.89; 2.89; THA: OR = 1.00 reference).
Conclusion
In our cohort of patients with displaced and non-displaced femoral neck fractures, HHS, EQ-5D, and reoperation risk showed an advantage of THA and HA compared with CS and DHS fixation. Based on these findings, we recommend that hip arthroplasty should be preferred and internal fixation of femoral neck fractures should only be considered in individual cases. Level of evidence I: a systematic review of randomized controlled trials.
Trial registration
: PROSPERO on 10 August 2022 (CRD42022350293).
•Patients received a new MRI during fractionated SRS for brain metastases.•The observed target volume changes deteriorated the target dose coverage.•Tumor volume changes before treatment may predict ...changes during treatment.
To study the impact of target volume changes in brain metastases during fractionated stereotactic radiosurgery (fSRS) and identify patients that benefit from MRI guidance.
For 15 patients (18 lesions) receiving fSRS only (fSRSonly) and 19 patients (20 lesions) receiving fSRS postoperatively (fSRSpostop), a treatment planning MRI (MR0) and repeated MRI during treatment (MR1) were acquired. The impact of target volume changes on the target coverage was analyzed by evaluating the planned dose distribution (based on MR0) on the planning target volume (PTV) during treatment as defined on MR1. The predictive value of target volume changes before treatment (using the diagnostic MRI (MRD)) was studied to identify patients that experienced the largest changes during treatment.
Target volume changes during fSRS did result in large declines of the PTV dose coverage up to −34.8% (median = 3.2%) for fSRSonly patients. For fSRSpostop the variation and declines were smaller (median PTV dose coverage change = −0.5% (−4.5% to 1.9%)). Target volumes changes did also impact the minimum dose in the PTV (fSRSonly; −2.7 Gy (−16.5 to 2.3 Gy), fSRSpostop; −0.4 Gy (−4.2 to 2.5 Gy)). Changes in target volume before treatment (i.e. seen between the MRD and MR0) predicted which patients experienced the largest dose coverage declines during treatment.
Target volume changes in brain metastases during fSRS can result in worsening of the target dose coverage. Patients benefiting the most from a repeated MRI during treatment could be identified before treatment.
BRCA-mutated breast cancer cells lack the DNA-repair mechanism homologous recombination that is required for error-free DNA double-strand break (DSB) repair. Homologous recombination deficiency (HRD) ...may cause hypersensitivity to DNA DSB-inducing agents, such as bifunctional alkylating agents and platinum salts. HRD can be caused by BRCA mutations, and by other mechanisms. To identify HRD, studies have focused on triple-negative (TN) breast cancers as these resemble BRCA1-mutated breast cancer closely and might also share this hypersensitivity. However, ways to identify HRD in non-BRCA-mutated, estrogen receptor (ER)-positive breast cancers have remained elusive. The current study provides evidence that genomic patterns resembling BRCA1- or BRCA2-mutated breast cancers can identify breast cancer patients with TN as well as ER-positive, HER2-negative tumors that are sensitive to intensified, DSB-inducing chemotherapy.
Array comparative genomic hybridization (aCGH) was used to classify breast cancers. Patients with tumors with similar aCGH patterns as BRCA1- and/or BRCA2-mutated breast cancers were defined as having a BRCA-likeCGH status, others as non-BCRA-likeCGH. Stage-III patients (n = 249) had participated in a randomized controlled trial of adjuvant high-dose (HD) cyclophosphamide-thiotepa-carboplatin (CTC) versus 5-fluorouracil-epirubicin-cyclophosphamide (FE90C) chemotherapy.
Among patients with BRCA-likeCGH tumors (81/249, 32%), a significant benefit of HD-CTC compared to FE90C was observed regarding overall survival (adjusted hazard ratio 0.19, 95% CI: 0.08 to 0.48) that was not seen for patients with non-BRCA-likeCGH tumors (adjusted hazard ratio 0.90, 95% CI: 0.53 to 1.54) (P = 0.004). Half of all BRCA-likeCGH tumors were ER-positive.
Distinct aCGH patterns differentiated between HER2-negative patients with a markedly improved outcome after adjuvant treatment with an intensified DNA-DSB-inducing regimen (BRCA-likeCGH patients) and those without benefit (non-BRCA-likeCGH patients).
Female Hodgkin lymphoma (HL) patients treated with chest radiotherapy (RT) have a very high risk of breast cancer. The contribution of genetic factors to this risk is unclear. We therefore examined ...211 155 germline single-nucleotide polymorphisms (SNPs) for gene-radiation interaction on breast cancer risk in a case-only analysis including 327 breast cancer patients after chest RT for HL and 4671 first primary breast cancer patients. Nine SNPs showed statistically significant interaction with RT on breast cancer risk (false discovery rate, <20%), of which 1 SNP in the PVT1 oncogene attained the Bonferroni threshold for statistical significance. A polygenic risk score (PRS) composed of these SNPs (RT-interaction-PRS) and a previously published breast cancer PRS (BC-PRS) derived in the general population were evaluated in a case-control analysis comprising the 327 chest-irradiated HL patients with breast cancer and 491 chest-irradiated HL patients without breast cancer. Patients in the highest tertile of the RT-interaction-PRS had a 1.6-fold higher breast cancer risk than those in the lowest tertile. Remarkably, we observed a fourfold increased RT-induced breast cancer risk in the highest compared with the lowest decile of the BC-PRS. On a continuous scale, breast cancer risk increased 1.4-fold per standard deviation of the BC-PRS, similar to the effect size found in the general population. This study demonstrates that genetic factors influence breast cancer risk after chest RT for HL. Given the high absolute breast cancer risk in radiation-exposed women, these results can have important implications for the management of current HL survivors and future patients.
•The risk of RT-induced breast cancer after HL is strongly associated with a PRS for breast cancer in the general population.•A PRS, based on 9 SNPs interacting with RT in the occurrence of breast cancer after HL, also increased RT-induced breast cancer risk.
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To evaluate the linear quadratic (LQ) model for hypofractionated radiotherapy within the context of predicting radiation pneumonitis (RP) and to investigate the effect if a linear (L) model in the ...high region (LQL model) is used.
The radiation doses used for 128 patients treated with hypofractionated radiotherapy were converted to the equivalent doses given in fractions of 2 Gy for a range of alpha/beta ratios (1 Gy to infinity) according to the LQ(L) model. For the LQL model, different cut-off values between the LQ model and the linear component were used. The Lyman model parameters were fitted to the events of RP grade 2 or higher to derive the normal tissue complication probability (NTCP). The lung dose was calculated as the mean lung dose and the percentage of lung volume (V) receiving doses higher than a threshold dose of xGy (V(x)).
The best NTCP fit was found if the mean lung dose, or V(x), was calculated with an alpha/beta ratio of 3 Gy. The NTCP fit of other alpha/beta ratios and the LQL model were worse but within the 95% confidence interval of the NTCP fit of the LQ model with an alpha/beta ratio of 3 Gy. The V(50) NTCP fit was better than the NTCP fit of lower threshold doses.
For high fraction doses, the LQ model with an alpha/beta ratio of 3 Gy was the best method for converting the physical lung dose to predict RP.
Introduction: Evidence on the association of socioeconomic deprivation with occurrence of acute myocardial infarction (AMI) is available from international studies and urban settings in western ...Germany. This study aimed to assess this association based on small geographical areas in a rural setting in eastern Germany. Methods: This study used routine data of all patients with AMI who were treated in the Hospital Brandenburg in the city of Brandenburg, Germany, between May 2019 and May 2020. Hospitalisation rates of AMI were calculated for postal code regions that were located within the catchment area of the Hospital Brandenburg. Poisson regression was used to compare hospitalisation rates in areas with medium socioeconomic deprivation to areas with high deprivation, controlling for age group, sex and period (before or during COVID-19 pandemic). Publicly available social, infrastructure and healthcare-related features were mapped to characterise the study region. Results: In total, 265 cases of AMI were registered in the study area, which comprised 116,126 inhabitants. The city of Brandenburg was characterised by the highest level of socioeconomic deprivation, while neighbouring areas showed a rural settlement structure and medium levels of deprivation. The number of general practitioners per 10 000 inhabitants did not differ between both areas. The adjusted rate ratio comparing hospitalisations due to AMI in areas with medium socioeconomic deprivation to areas with high socioeconomic deprivation was 0.71 (95%CI 0.56-0.91, p=0.01). Conclusion: This study adds evidence about the association of socioeconomic deprivation and AMI occurrence from a rural area in eastern Germany. Further research about the relationship of socioeconomic deprivation and cardiovascular health is needed from heterogeneous contexts.
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