Identifying Surrogates for Heart and Ipsilateral Lung Dose to Guide Field Placement and Treatment Modality Selection during Virtual Simulation of Breast Radiotherapy

AIMS: Virtual simulation (VSim) of tangential photon fields is a common method of field localisation for breast radiotherapy. Heart and ipsilateral lung dose is unknown until the dosimetric plan is produced. If heart and ipsilateral lung tolerance doses are exceeded, this can prolong the pre-treatment pathway, particularly if a change of technique is required. The aim of this study was to identify predictive surrogates for heart and ipsilateral lung dose during VSim to aid optimum field placement and treatment modality selection. MATERIALS AND METHODS: Computed tomography data from 50 patients referred for left breast/chest wall radiotherapy were retrospectively analysed (model-building cohort). The prescribed dose was 40.05 Gy in 15 fractions using a tangential photon technique. The heart and ipsilateral lung contours were duplicated, cropped to within the field borders and labelled heart-in-field (HIF) and ipsilateral lung-in-field (ILF). The percentage of HIF (%HIF) and ILF (%ILF) was calculated and correlated with mean heart dose (MHD) and volume of the ipsilateral lung receiving 18 Gy (V18Gy). Linear regression models were calculated. A validation cohort of 10 left- and 10 right-sided cases with an anterior supraclavicular fossa (SCF) field, and 10 left- and 10 right-sided cases including the internal mammary nodes using a wide tangential technique and anterior SCF field, tested the predictive model. Threshold values for %HIF and %ILF were calculated for clinically relevant MHD and ipsilateral lung V18Gy tolerance doses. RESULTS: For the model-building cohort, the median %HIF and MHD were 2.6 (0.4-16.7) and 2.3 (1.2-8) Gy. The median %ILF and ipsilateral lung V18Gy were 12.1 (2.8-33.6) and 12.6 (3.3-35) %. There was a statistically significant strong positive correlation of %HIF with MHD (r2 = 0.97, P < 0.0001) and of %ILF with ipsilateral lung V18Gy (r2 = 0.99, P < 0.0001). For the validation cohort, the median %HIF and MHD were 3.9 (0.6-8) and 2.5 (1.4-4.7) Gy. The median %ILF and ipsilateral lung V18Gy were 20.1 (12.4-32.0) and 20.9 (12.4-34.4) %. The validation cohort confirmed that %HIF and %ILF continue to be predictive surrogates for heart and ipsilateral lung dose during VSim of left- and right-sided cases when including the SCF ± internal mammary nodes with a three-field photon technique. DISCUSSION: The ability to VSim breast radiotherapy (±nodal targets) and accurately predict the heart and ipsilateral lung doses on the dosimetric plan will ensure that tolerance doses are not exceeded, and identify early in the pre-treatment pathway those cases where alternative techniques or modalities should be considered

Improved treatment completion for tuberculosis patients: The case for a dedicated social care team

OBJECTIVES: The increasing social needs of people with Tuberculosis (TB), and the poor adherence to anti-TB therapy (ATT) associated with homelessness, drug or alcohol abuse, and prison history, led us to introduce a social care team (SCT) to support patient engagement with care within this low TB incidence setting. METHODS: Using a risk assessment, patients with social risk factors (SRF) for non-adherence to ATT are identified and a referral made to the SCT, who then provide intensive casework support for areas including homelessness, housing, benefits, debt and immigration. Retrospective data analysis of the social care database from 2017 to 2019 was conducted. Patients who were (n = 170) and were not referred to the SCT (n = 734) were compared. RESULTS: Patients referred were significantly more likely to complete treatment for TB than those not (88.2% versus 77.7% respectively, p = 0.0025), irrespective of receipt of Directly/Video Observed Therapy and adjusting for confounders. CONCLUSIONS: This paper demonstrates important evidence for the positive impact of a dedicated SCT within a TB service, and these improved treatment outcomes provide a strong argument for development of similar SCTs within UK TB services and similar healthcare settings

The experience of brace treatment in children/adolescents with scoliosis

BACKGROUND: Idiopathic scoliosis is a chronic illness with several different braces used for its treatment. Brace treatment during childhood/adolescence can produce stress. There are studies supporting that it can decrease body-image perception while other studies support that it has no such effect. The purpose of this study was to explore the experience of brace treatment in children/adolescents with scoliosis. The aim was to investigate which feelings are created by the bracing experience in children/adolescents with scoliosis and what are the children/adolescents' with scoliosis opinions of the support provided to them by health-care professionals and by their families. METHODS: We conducted interviews with the help of a semi-structured interview guide in order to address the topic of the experience of brace treatment. A convenient sample of twelve children and adolescents with scoliosis was selected from patients attending follow-up appointments at the Outpatient Scoliosis Clinics of two Greek hospitals. The data was analysed using the method of content analysis. RESULTS: Patients in the sample were 10–16 years old and they were mainly females (71%). Almost all of the participants reported having to deal with stress, denial, fear, anger, and shame. They were satisfied with the information they received regarding their condition and therapy. However, the information was not accompanied by support from the health care professionals. They reported that they were receiving support mainly from their families, friends, and classmates. CONCLUSION: The present study is contributing to the development of a better understanding of significant issues related to the experience of bracing therapy. It is clear that scoliosis children/adolescents have to be provided with support during the long period of bracing. It is apparent that those children/adolescents have unmet needs for care and health professionals and policy makers should try to find a way to address those needs

Signal-Dependent Recruitment of BRD4 to Cardiomyocyte Super-Enhancers Is Suppressed by a MicroRNA

BRD4 governs pathological cardiac gene expression by binding acetylated chromatin, resulting in enhanced RNA polymerase II (Pol II) phosphorylation and transcription elongation. Here, we describe a signal-dependent mechanism for the regulation of BRD4 in cardiomyocytes. BRD4 expression is suppressed by microRNA-9 (miR-9), which targets the 3′ UTR of the Brd4 transcript. In response to stress stimuli, miR-9 is downregulated, leading to derepression of BRD4 and enrichment of BRD4 at long-range super-enhancers (SEs) associated with pathological cardiac genes. A miR-9 mimic represses stimulus-dependent targeting of BRD4 to SEs and blunts Pol II phosphorylation at proximal transcription start sites, without affecting BRD4 binding to SEs that control constitutively expressed cardiac genes. These findings suggest that dynamic enrichment of BRD4 at SEs genome-wide serves a crucial role in the control of stress-induced cardiac gene expression and define a miR-dependent signaling mechanism for the regulation of chromatin state and Pol II phosphorylation