Aim: To test inter-fraction reproducibility, intrafraction stability, technician aspects, and patient/physician’s comfort of a dedicated immobilization solution for Brain Linac-based radiation therapy (RT). Methods: A pitch-enabled head positioner with an open-face mask were used and, to evaluate inter- and intrafraction variations, 1–3 Cone-Beam Computed Tomography (CBCT) were performed. Surface Guided Radiation Therapy (SGRT) was used to evaluate intrafraction variations at 3 time points: initial (i), final (f), and monitoring (m) (before, end, and during RT). Data regarding technician mask aspect were collected. Results: Between October 2019 and April 2020, 69 patients with brain disease were treated: 45 received stereotactic RT and 24 conventional RT; 556 treatment sessions and 863 CBCT’s were performed. Inter-fraction CBCT mean values were longitudinally 0.9 mm, laterally 0.8 mm, vertically 1.1 mm, roll 0.58°, pitch 0.59°, yaw 0.67°. Intrafraction CBCT mean values were longitudinally 0.3 mm, laterally 0.3 mm, vertically 0.4 mm, roll 0.22°, pitch 0.33°, yaw 0.24°. SGRT intrafraction mean values were: i_, m_, f_ longitudinally 0.09 mm, 0.45 mm, 0.31 mm; i_, m_, f_ laterally 0.07 mm, 0.36 mm, 0.20 mm; i_, m_, f_ vertically 0.06 mm, 0.31 mm, 0.22 mm; i_, m_, f_ roll 0.025°, 0.208°, 0.118°; i_, m_, f_ pitch 0.036°, 0.307°, 0.194°; i_, m_, f_ yaw 0.039°, 0.274°, 0.189°. Conclusions: This immobilization solution is reproducible and stable. Combining CBCT and SGRT data confirm that 1 mm CTV-PTV margin for Linac-based SRT was adequate. Using open-face mask and SGRT, for conventional RT, radiological imaging could be omitted.

Purpose: Errors and incidents may occur at any point within radiotherapy (RT). The aim of the present retrospective analysis is to evaluate the impact of a customized ARIA Visual Care Path (VCP) on quality assurance (QA) for the RT process. Materials and Methods: The ARIA VCP was implemented in June 2019. The following tasks were customized and independently verified (by independent checks from radiation oncologists, medical physics, and radiation therapists): simulation, treatment planning, treatment start verification, and treatment completion. A retrospective analysis of 105 random and unselected patients was performed, and 945 tasks were reviewed. Patients’ reports were categorized based on treatment years period: 2019–2020 (A); 2021 (B); and 2022–2023 (C). The QA metrics included data for timeliness of task completion and data for minor and major incidents. The major incidents were defined as incorrect prescriptions of RT dose, the use of different immobilization systems during RT compared to the simulation, the absence of surface-guided RT data for patients’ positioning, incorrect dosimetric QA for treatment plans, and failure to complete RT as originally planned. A sample size of approximately 100 was able to obtain an upper limit of 95% confidence interval below 5–10% in the case of zero or one major incident. Results: From June 2019 to December 2023, 5300 patients were treated in our RT department, an average of 1300 patients per year. For the purpose of this analysis, one hundred and five patients were chosen for the study and were subsequently evaluated. All RT staff achieved a 100% compliance rate in the ARIA VCP timely completion. A total of 36 patients were treated in Period A, 34 in Period B, and 35 in Period C. No major incidents were identified, demonstrating a major incident rate of 0.0% (95% CI 0.0–3.5%). A total of 26 out of 945 analyzed tasks (3.8%) were reported as minor incidents: absence of positioning photo in 32 cases, lack of patients’ photo, and absence of plan documents in 4 cases. When comparing periods, incidents were statistically less frequent in Period C. Conclusions: Although the present analysis has some limitations, its outcomes demonstrated that software for the RT workflow, which is fully integrated with both the record-and-verify and treatment planning systems, can effectively manage the patient’s care path. Implementing the ARIA VCP improved the efficiency of the RT care path workflow, reducing the risk of major and minor incidents.

Noonan syndrome (NS) is a genetic disorder characterized by distinctive craniofacial and skeletal features, short stature, mild to moderate developmental impairment, and multisystem involvement, notably affecting the cardiovascular, musculoskeletal, and endocrine systems. Although abnormalities of the bone matrix, as well as osteopenia and osteoporosis, are well recognized in individuals with NS and other RASopathies, the specific impact of RAS/MAPK pathway dysregulation on bone health remains poorly understood. Objectives: The aim of this study was to evaluate bone turnover and bone remodeling markers in a cohort of children with NS, to gain further insights into the bone status of these patients. Methods: In this cross-sectional, case-control study, we analyzed 28 children (20 males) with a molecular diagnosis of NS and 35 healthy subjects (21 males), matched by age and sex. We assessed markers of bone metabolism and bone turnover (calcium, phosphate, PTH, 25(OH)-vitamin D, osteocalcin, procollagen I N-propeptide-P1NP, bone alkaline phosphatase-BALP, C-telopeptides of type I collagen-CTX) and bone remodeling (RANKL, OPG, and sclerostin). Bone mineralization was measured at the lumbar spine (L2–L4) using dual-energy X-ray absorptiometry (DEXA). Results: Serum CTX levels were significantly higher in NS patients compared to controls (1.8 ± 0.7 vs. 1.3 ± 0.5 ng/mL, p = 0.0004). RANKL levels were higher in NS patients, although the difference did not reach statistical significance. No significant differences were found for OPG, sclerostin, or other markers of bone metabolism between patients and controls. Conclusions: Children with NS exhibit increased bone resorption, as indicated by elevated CTX levels, suggesting a potential imbalance in bone remodeling processes. Further studies are warranted to better define the impact of RAS/MAPK pathway dysregulation on bone health in this population.

Background/Objectives: People affected by COVID-19 are exposed to abnormal clotting and endothelial dysfunction, which may trigger thromboembolic events. This study aimed at retrospectively investigating whether oral anticoagulant therapy (OAT), encompassing either direct oral anticoagulants (DOACs), mainly apixaban, or the vitamin K antagonist (VKA) warfarin, could have impacted medium-term mortality in a cohort of SARS-CoV-2 patients. Methods: Among 1238 COVID-19 patients, hospitalized from 17 March 2020 to 15 June 2021, 247 survivors and 247 deceased within 90 days from hospitalization were matched 1:1 based on age, sex, and intensive care unit (ICU) admission within three days. Conditional logistic regression was used to estimate associations by means of odds ratio (OR) with a 95% confidence interval (CI). Results: A univariate regression analysis suggested that OAT, no differently from subcutaneous low-molecular-weight heparins (LMWHs) during hospitalization, has no significant impact (p value > 0.05) on medium-term mortality. A multivariate analysis, limited to baseline variables (i.e., comorbidities and pharmacotherapies at hospital admission) showing significant association (p < 0.05) to mortality in a univariate analysis, revealed that, compared to patients living at 90 days from hospitalization, deceased patients had cancer histories (OR 1.75, CI 1.06–2.90, p = 0.029) or suffered from asthma (OR 2.25, CI 1.13–4.47, p = 0.021). In contrast, heart failure (HF), atrial fibrillation (AF), arteriopathy, chronic obstructive pulmonary disease (COPD), and kidney failure (KF), which, in a univariate analysis, were found to be associated with the endpoint (p < 0.05), lost significance in a multivariate analysis. Therapy at admission with aldosterone antagonists also appeared to be associated with medium-term mortality (OR 2.49, CI 1.52–4.08, p < 0.001); whereas, vitamin D supplementation during hospitalization appeared to be beneficial. Although not conclusive, a search into the Eudravigilance database, combined with consulting a digital predictive platform (PLATO, polypharmacology platform prediction), suggested potential off-target activities, which might contribute to increasing the severity of SARS-CoV-2 infection. Conclusions: This retrospective clinical study furnished evidences of the impact of OAT, comorbidities and other pharmacological treatments on COVID-19 clinical course.