Citations

AbstractBackgroundConventional approaches for emergent or expedited palliative radiotherapy (RT) involve the application of cumbersome vendor‐provided solutions and/or multiple patient appointments to complete the RT workflow within a compressed timeframe.PurposeThis report delineates the clinical development of an in‐house, semi‐automated Cone‐beam computed tomography (CBCT)‐based simulation‐free platform for expedited palliative RT on conventional linacs, intended to supplant existing techniques employed at this institution.MethodsThe internal software, termed SimFree Wizard (SFW), was engineered utilizing a C#‐based application programming interface integrated within the treatment planning system (TPS). Generated scripts were compiled as stand‐alone executables, with a graphical user interface (GUI) customized via an integrated development environment. The platform was conceived as a framework for accelerated CBCT‐based RT, bypassing the requirement for standard simulation imaging. SFW employs full automation where feasible to minimize user intervention, supplemented by graphical instructions for tasks requiring manual execution. During development, relevant temporal metrics from 10 end‐to‐end tests for palliative spine RT were quantified. User feedback was solicited via a simple questionnaire assessing the overall platform usability. Automated in‐house secondary verification software was developed for validation of the TPS‐calculated monitor units (MUs).ResultsThe mean duration for workflow execution was 41:42 ± 3:18 [mm:ss] (range ∼37–46 min). SFW satisfactorily generated simple, multi‐field CBCT‐based 3D treatment plans within seconds following delineation of the desired treatment area. User feedback indicated enhanced usability compared to previously employed solutions. Validation of the secondary verification software demonstrated accurate results for palliative spine RT and other simple cases wherein the dose calculation point resides in a predominantly homogenous medium.ConclusionA novel in‐house solution for expedited CBCT‐based RT was successfully developed, facilitating completion of the entire workflow within approximately 1‐hour or less for simple palliative/emergent scenarios. Overall, this application is expected to improve the quality and safety of palliative RT while greatly reducing workflow duration, thereby improving access to palliative care.

ImportanceFenestrated and branched endovascular aortic repairs (F/BEVAR) have been adopted by many centers. However, national trends of F/BEVAR use remain unclear, particularly at sites who perform them without an US Food and Drug Adminstration (FDA)–approved investigational device exemption (IDE).ObjectiveTo quantify the use of F/BEVAR in the US and to determine if mortality was different at IDE vs non-IDE sites.Design, Setting, and ParticipantsThis retrospective cohort study examined 100% fee-for-service Medicare claims data from 2016 to 2023. Participants were patients who underwent endovascular treatment of the visceral aorta incorporating 2 or more visceral artery endoprostheses. Hospitals with vs without an IDE were identified using hospitals’ Employer Identification Number as a time varying exposure.ExposureF/BEVAR.Main Outcomes and MeasuresTrends in the center-level F/BEVAR case volume stratified by IDE status were assessed using cumulative incidence curves. Mortality outcomes at 30 days and 3 years were compared using Kaplan-Meier methods and Cox proportional hazards models with adjustment for baseline patient characteristics.ResultsFrom 2016 to 2023, 8017 patients were treated with F/BEVAR at 549 hospitals. The median (IQR) age was 75.8 (71.3-80.8) years; 5795 patients (72.3%) were male and 2222 (27.7%) female. A total of 2226 F/BEVAR (27.8%) were performed at 22 hospitals with an IDE. The number of patients treated with F/BEVAR increased from 771 in 2016 to 1251 in 2023. The median (IQR) annual case volume per hospital was significantly higher at IDE sites (22.3 [11.0-30.4] vs 1.2 [1.0-2.0] cases/y; P < .001); 18 IDE sites (90.0%) and 20 non-IDE sites (3.7%) completed 9 or more cases per year. The 30-day mortality (3.0% vs 4.9%) but not 3-year mortality (26.0% vs 27.1%) was lower for patients treated at hospitals with vs without an IDE. After risk adjustment, both 30-day (odds ratio, 0.47; 95% CI, 0.32-0.69) and midterm mortality (hazard ratio, 0.81; 95% CI, 0.69-0.95) were lower for patients treated at IDE sites.Conclusions and RelevanceThe use of F/BEVAR is increasing across the United States, with the majority of cases being performed outside of IDE studies and at low-volume centers. F/BEVAR performed at non-IDE centers are associated with higher adjusted 30-day and midterm mortality. Transparent outcome reporting and identification of process measures from IDE sites may help achieve more equity in patient outcomes.

ABSTRACT Introduction Lack of social support negatively impacts medical trainees' wellness. Programmes to educate medical trainees and their support persons (SPs) have been developed to improve resident wellness, but implementation of these programmes at other institutions remains unclear. We aimed to demonstrate the feasibility of implementing the Family Anesthesia Experience (FAX) programme across multiple institutions and to assess the programme's utility. Methods FAX includes didactics on wellness, burnout, substance use disorder and institutional resources; a panel of senior residents and their SPs; and small‐group simulations of airway management, common procedures and a high‐fidelity intraoperative code. We assessed the programme qualitatively using semistructured interviews of 20 first year anaesthesiology residents and 20 SPs. Data analysis was performed via a content analysis approach. Results Twelve anaesthesiology programmes of varying size and geographic locations implemented FAX with minor adaptations. Minimal direct costs were incurred for the virtual programme. Participants enjoyed the event overall. Content analysis showed that FAX improved SPs' understanding of residency and communication between SPs and residents, had minimal impact on SPs' stress, reduced residents' interpersonal stress with SPs and modified perceptions on wellness and burnout. We developed a conceptual model in which we propose SPs' understanding and empathy for their residents would improve through FAX, which may improve communication with and support for residents. Conclusion We demonstrated that FAX can be implemented at varying anaesthesiology residency programmes. Family‐oriented educational events like FAX may be an effective approach to improve SPs' understanding of a resident's role, thereby increasing social support for residents.

Case: A 67-year-old woman sustained a periprosthetic tibial tubercle avulsion fracture with extensor mechanism disruption. She underwent open reduction internal fixation (ORIF) with orthogonal mini-fragment plates applied in a tension band fashion with patellar tendon suture augmentation. Radiographs, range of motion, and patient-reported outcomes were completed over 1 year. Conclusion: Isolated periprosthetic tibial tubercle fractures with disruption of the extensor mechanism can be treated with ORIF using orthogonal tension band plating. At 1-year follow-up, the surgical technique described in this report yielded radiographic union, clinical restoration of preinjury motion, and excellent patient-reported outcomes.

Abstract Background The majority of patients with prostate cancer (PCa) exhibit intrinsic resistance to immune checkpoint blockade (ICB) following radiotherapy (RT). This resistance is generally attributed to the limited antigen presentation of heterogeneous cells within tumors. Here, we aimed to isolate and characterize these diverse subgroups of tumor post‐RT to understand the molecular mechanisms of their resistance to ICB. Methods Single‐cell RNA‐sequencing (scRNA‐seq) was used to profile senescent cancer cell clusters induced by RT in LNCaP cells. The expression and phosphorylation levels of ataxia telangiectasia and Rad3‐related protein (ATR) were assessed by immunohistochemistry in clinical samples from patients with or without RT. Co‐immunoprecipitation, mutagenesis, and Western blotting were used to measure the interactions between proteins. Xenograft experiments were performed to assess the tumor immune response in the mice. Results We identified a subset of PCa cells that exhibited resistance to RT, characterized by a reduced antigen presentation capability, which enhanced their ability to evade immune detection and resist cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) blockade. scRNA‐seq revealed that the senescent state was a transient phase of PCa cells post‐RT, particularly in CTLA‐4 blockade treatment‐resistant cells. This state was marked by increased cytosolic ATR level. Cytosolic ATR phosphorylated CD86 in its cytosolic domain and enhanced the interaction between CD86 and its E3 ligase MARCH1 through electrostatic attraction. Depletion or inhibition of Atr increased the sensitivity to immune attack and improved responses to anti‐Ctla‐4 antibody treatment in a mouse model. Conclusions Our findings indicate that the activation of cytosolic ATR, which is associated with cellular senescence, impedes the effectiveness of combined RT and ICB treatments. This discovery may provide valuable insights for improving the efficacy of combined RT and ICB therapies in PCa.

Abstract The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell‐mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated. In March of 2023, the Alzheimer's Association convened the Alzheimer's Association International Conference (AAIC), Advancements: Immunity, to discuss the roles of the immune system in ADRD. A wide range of topics were discussed, such as animal models that replicate human pathology, immune‐related biomarkers and clinical trials, and lessons from other fields describing immune responses in neurodegeneration. This manuscript presents highlights from the conference and outlines avenues for future research on the roles of immunity in neurodegenerative disorders. Highlights The immune system plays a central role in the pathogenesis of Alzheimer's disease. The immune system exerts numerous effects throughout the brain on amyloid‐beta, tau, and other pathways. The 2023 AAIC, Advancements: Immunity, encouraged discussions and collaborations on understanding the role of the immune system.

Abstract Network-based methods utilize protein–protein interaction information to identify significantly perturbed subnetworks in cancer and to propose key molecular pathways. Numerous methods have been developed, but to date, a rigorous benchmark analysis to compare the performance of existing approaches is lacking. In this paper, we proposed a novel benchmarking framework using synthetic data and conducted a comprehensive analysis to investigate the ability of existing methods to detect target genes and subnetworks and to control false positives, and how they perform in the presence of topological biases at both gene and subnetwork levels. Our analysis revealed insights into algorithmic performance that were previously unattainable. Based on the results of the benchmark study, we presented a practical guide for users on how to select appropriate detection methods and protein–protein interaction networks for cancer pathway identification, and provided suggestions for future algorithm development.