What information can we gain from performing adaptive radiotherapy of head and neck cancer patients from the past 10 years?

The aim of the review was to present the current literature status about replanning regarding anatomical and dosimetric changes in the target and OARs in the head and neck region during radiotherapy, to discuss and to analyze factors influencing the decision for adaptive radiotherapy of head and neck cancer patients. Significant progress has been made in head and neck patients’ evaluation and qualification for adapted radiotherapy over the past ten years. Many factors leading to anatomical and dosimetric changes during treatment have been identified. Based on the literature, the most common factors triggering re-plan are weight loss, tumor and nodal changes, and parotid glands shrinkage. The fluctuations in dose distribution in the clinical area are significant predictive factors for patients’ quality of life and the possibility of recovery. It has been shown that re-planning influence clinical outcomes: local control, disease free survival and overall survival. Regarding literature studies, it seems that adaptive radiotherapy would be the most beneficial for tumors of immense volume or those in the nearest proximity of the OARs. All researchers agree that the timing of re-planning is a crucial challenge, and there are still no clear consensus guidelines for time or criteria of re-planning. Nowadays, thanks to significant technological progress, the decision is mostly made based on observation and supported with IGRT verification. Although further research is still needed, adaptive strategies are evolving and now became the state of the art of modern radiotherapy.     

Impact of a web-based personally tailored physical activity intervention on depression,anxiety, stress and quality of life: Secondary outcomes from a randomized controlled trial

BackgroundFew studies have investigated the impact of web-based physical activity interventions on mental health outcomes. Therefore, this study examined the impact of a web-based personally tailored physical activity intervention on depression, anxiety, stress and quality of life.Methods501 participants were randomised into either a control group or a pooled intervention condition who received a 3-month web-based personally tailored physical activity intervention. Previously, this intervention has demonstrated to improve self-reported physical activity, but not device-measured physical activity. At baseline, 3- and 9-months, depression, anxiety and stress were assessed using the DASS21, and quality of life was assessed using the SF-12V2. General linear mixed models examined differences between groups over time.ResultsMost participants (>80%) reported normal levels of depression, anxiety or stress. Relative to baseline levels, significant reductions of depression, anxiety, stress and the SF12 mental health component were observed in the pooled intervention group at 3 and 9 months. Relative to the control group, significant reductions were observed in the pooled intervention group for depression and stress (3-months only) and anxiety (3- and 9-months), but not quality of life.ConclusionA web-based physical activity intervention can result in positive mental health outcomes, even in the absence of device-measured physical activity improvements. However, these findings need to be confirmed in future studies.Trial registration numberACTRN12615000057583.     

Pharmacokinetics and Early Tumor Response to Conventional Transarterial Chemoembolization with Sorafenib and Doxorubicin in a VX2 Rabbit Tumor Model

PurposeTo investigate the pharmacokinetics (PK) and early effects of conventional transarterial chemoembolization (TACE) using sorafenib and doxorubicin on tumor necrosis, hypoxia markers, and angiogenesis in a rabbit VX2 liver tumor model.Materials and MethodsVX2 tumor-laden New Zealand White rabbits (N = 16) were divided into 2 groups: 1 group was treated with hepatic arterial administration of ethiodized oil and doxorubicin emulsion (DOX-TACE), and the other group was treated with ethiodized oil, sorafenib, and doxorubicin emulsion (SORA-DOX-TACE). Animals were killed within 3 days of the procedure. Levels of sorafenib and doxorubicin were measured in blood, tumor, and adjacent liver using mass spectrometry. Tumor necrosis was determined by histopathological examination. Intratumoral hypoxia-inducible factor (HIF) 1α, vascular endothelial growth factor (VEGF), and microvessel density (MVD) were determined by immunohistochemistry.ResultsThe median intratumoral concentration of sorafenib in the SORA-DOX-TACE group was 17.7 μg/mL (interquartile range [IQR], 7.42–33.5 μg/mL), and its maximal plasma concentration (C_max) was 0.164 μg/mL (IQR, 0.0798–0.528 μg/mL). The intratumoral concentration and C_max of doxorubicin were similar between the groups: 4.08 μg/mL (IQR, 3.18–4.79 μg/mL) and 0.677 μg/mL (IQR, 0.315–1.23 μg/mL), respectively, in the DOX-TACE group and 1.68 μg/mL (IQR, 0.795–4.08 μg/mL) and 0.298 μg/mL (IQR, 0.241–0.64 μg/mL), respectively, in the SORA-DOX-TACE group. HIF-1α expression was increased in the SORA-DOX-TACE group than in the DOX-TACE group. Tumor volume, tumor necrosis, VEGF expression, and MVD were similar between the 2 groups.ConclusionsThe addition of sorafenib to DOX-TACE delivered to VX2 liver tumors resulted in high intratumoral and low systemic concentrations of sorafenib without altering the PK of doxorubicin.     

脑出血继发损伤中沉默信息调节因子2的表达和炎症反应*

目的：探讨脑出血对酵母沉默信息调节因子2（Sirt2）和炎症的影响。方法：将胶原酶Ⅳ注入SD大鼠右侧 纹状体中建立脑出血模型，通过免疫印迹和ELISA 等方法测定大鼠脑出血后48 h 的Sirt2 的表达及炎症变化。利 用Hemin 诱导PC12 细胞损伤模拟体外脑出血模型，并检测Sirt2 及炎症变化；采用短发夹RNA（shRNA）-Sirt2 沉 默Sirt2 在PC12 细胞中的表达及对炎症的影响。结果：手术后48 h 脑出血行为学评分最低。脑出血组Sirt2 的表达 显著高于假手术组。脑出血组IL-6、IL-1β 表达显著升高。结论：脑出血可以促进Sirt2 的表达和炎症反应，降低 Sirt2 的表达可减缓炎症反应。 关键词 脑出血；沉默信息调节     

Effects of state reinsurance programs on health insurance exchange premiums and insurer participation

Objective

The aim of the study was to estimate the effect of the state-based reinsurance programs through the section 1332 State Innovation Waivers on health insurance marketplace premiums and insurer participation.

Data Source

2015 to 2022 Robert Wood Johnson Foundation Health Insurance Exchange Compare Datasets.

Study Design

An event study difference-in-differences (DD) model separately for each year of implementation and a synthetic control method (SCM) are used to estimate year-by-year effects following program implementation.

Data Collection/Extraction Methods

Not applicable.

Principal Findings

Reinsurance programs were associated with a decline in premiums in the first year of implementation by 10%–13%, 5%–19%, and 11%–17% for bronze, silver, and gold plans (p < 0.05). There is a trend of sustained declines especially for states that implemented their programs in 2019 and 2020. The SCM analyses suggest some effect heterogeneity across states but also premium declines across most states. There is no evidence that reinsurance programs affected insurer participation.

Conclusion

State-based reinsurance programs have the potential to improve the affordability of health insurance coverage. However, reinsurance programs do not appear to have had an effect on insurer participation, highlighting the need for policy makers to consider complementary strategies to encourage insurer participation.     

Overview of CF lung pathophysiology

Defects of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein affect the homeostasis of chloride, bicarbonate, sodium, and water in the airway surface liquid, influencing the mucus composition and viscosity, which induces a severe condition of infection and inflammation along the whole life of CF patients. The introduction of CFTR modulators, novel drugs directly intervening to rescue the function of CFTR protein, opens a new era of experimental research. The review summarizes the most recent advancements to understand the characteristics of the infective and inflammatory pathology of CF lungs.