Citations

AbstractBackgroundCutaneous melanoma (CM) is a significant health concern because of its high metastatic potential. Gene Expression Profile (GEP) testing, particularly the 31‐GEP test (DecisionDx‐Melanoma), has been increasingly used for risk stratification in CM patients. This study aimed to evaluate the clinical utility and performance of the 31‐GEP test in a real‐world setting.MethodsPatients with CM who underwent 31‐GEP testing from August 2014 to August 2022 at our institution were identified through searches of electronic health records. The study analyzed the influence of 31‐GEP testing on clinical decision‐making related to sentinel lymph node biopsy (SLNB), medical oncology referral, and postdiagnosis surveillance. Kaplan–Meier curves and Cox proportional hazard models were used to elucidate the test's performance, focusing on relapse‐free survival (RFS) and melanoma‐specific survival (MSS).ResultsThe study included 65 CM patients. Dermatologists ordered more than 80% of 31‐GEP tests. In 81.5% of cases, 31‐GEP results did not alter standard clinical management. SLNB decisions were unaffected in 92% of patients with pre‐SLNB 31‐GEP results. Among patients with stage I‐IIA melanoma, 25% of those with high‐risk 31‐GEP results were referred to medical oncology. Contrary to expectations, the rate of nodal metastasis was higher in low‐risk than in high‐risk 31‐GEP cases. Survival analysis showed overlapping RFS and MSS curves between different 31‐GEP classes, suggesting limited prognostic value.ConclusionsThe 31‐GEP test has a limited impact on clinical management decisions and shows limited prognostic value.

AbstractSelexipag is an oral selective agonist of the prostacyclin receptor approved to treat adults with pulmonary arterial hypertension (PAH). Selexipag is initiated at a dose of 200 μg twice daily (bid) and usually titrated up by 200 μg bid weekly (per label) or more slowly (e.g., every other week in real‐world clinical practice) to the highest tolerated individualized dose (ID) ranging from 200 to 1600 µg bid. In the Phase 3 GRIPHON trial, selexipag delayed disease progression and reduced risk of PAH‐related hospitalization compared with placebo; the effect was consistent across three prespecified ID groups: low (200–400 µg bid), medium (600–1000 µg bid), and high (1200–1600 µg bid). This study evaluated patient outcomes across selexipag dose ranges in real‐world practice. Data were analyzed from 1186 US adult patients with PAH on selexipag from the Komodo closed‐claims database (2015‒2022). Of these, 634 (53.5%) patients completed titration and reached their selexipag ID (43.8% high ID, 29.8% medium ID, 26.3% low ID). Subsequently, 72.4% of patients in the low ID group had dose adjustments compared with 61.9% (medium ID) and 34.5% (high ID; standardized mean difference 0.63). There were no significant differences in patient outcomes, i,e, persistence (time to discontinuation) and risk of all‐cause and PAH‐related hospitalization across ID groups. The findings in this diverse, real‐world population of patients with PAH reinforced an individualized approach to the dosing scheme to maximize benefit‐risk and achieve the highest tolerated dose with selexipag similar to findings from the GRIPHON trial and other studies.

AbstractBackgroundPhenomenological relative biological effectiveness (RBE) models for proton therapy, based on the dose‐averaged linear energy transfer (LET), have been developed to address the apparent RBE increase towards the end of the proton range. The results of these phenomenological models substantially differ due to varying empirical assumptions and fitting functions. In contrast, more theory‐based approaches are used in carbon ion radiotherapy, such as the microdosimetric kinetic model (MKM). However, implementing microdosimetry‐based models in LET‐based proton therapy treatment planning systems poses challenges.PurposeThis work presents a LET‐based version of the MKM that is practical for clinical use in proton radiotherapy.MethodsAt first, we derived an approximation of the Mayo Clinic Florida (MCF) MKM for relatively‐sparsely ionizing radiation such as protons. The mathematical formalism of the proposed model is equivalent to the original MKM, but it maintains some key features of the MCF MKM, such as the determination of model parameters from measurable cell characteristics. Subsequently, we carried out Monte Carlo calculations with PHITS in different simulated scenarios to establish a heuristic correlation between microdosimetric quantities and the dose averaged LET of protons.ResultsA simple allometric function was found able to describe the relationship between the dose‐averaged LET of protons and the dose‐mean lineal energy, which includes the contributions of secondary particles. The LET‐based MKM was used to model the in vitro clonogenic survival RBE of five human and rodent cell lines (A549, AG01522, CHO, T98G, and U87) exposed to pristine and spread‐out Bragg peak (SOBP) proton beams. The results of the LET‐based MKM agree well with the biological data in a comparable or better way with respect to the other models included in the study. A sensitivity analysis on the model results was also performed.ConclusionsThe LET‐based MKM integrates the predictive theoretical framework of the MCF MKM with a straightforward mathematical description of the RBE based on the dose‐averaged LET, a physical quantity readily available in modern treatment planning systems for proton therapy.

Introduction Women with previous pregnancy-related cardiovascular risk indicators, including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP), have an increased risk of future cardiovascular disease (CVD). Although CVD screening and preventive care beginning in the early postpartum period are recommended, certain barriers limit access to such services. We plan to conduct a scoping review of the literature to explore and summarise evidence on the barriers and facilitators of postpartum CVD preventive services in women with a history of GDM and HDP. Methods and analysis This scoping review will be conducted in line with the Arksey and O’Malley’s (2005) methodological framework and the Joanna Briggs Institute guidance for conducting a systematic scoping review and will follow the Evidence for Policy and Practice Information and the Coordinating Centre at the Institute of Education guidelines. The review results will be reported using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. We will search the following databases: Medline, Embase and CINAHL. We will conduct grey literature searches for registered dissertations and theses. Inclusion and exclusion criteria will be kept broad. Qualitative and quantitative studies published in English or French that investigated and reported percieved barriers or facilitators to postpartum CVD screening and preventive care among women with previous GDM and HDP will be included. Individual, interpersonal, organizational, and system level factors will be reported. Qualitative findings will be summarised narratively, and quantitative findings will be absorbed within the themes using the multisource synthesis method. Ethics and dissemination This review represents one objective of a larger project that was reviewed by the Ottawa Health Sciences Network Research Ethics Board (QI-184). We will disseminate knowledge emanating from this review through open-access publication, presentation/public forums on women’s cardiovascular health, women’s CVD prevention forums and social media. We will also present the findings of this review at the annual meeting of the Canadian Women’s Heart Health Alliance.

AbstractSynoptic operative notes for pediatric surgical oncology provide standardized and structured documentation of surgical procedures performed on pediatric patients with cancer. These reports capture essential details such as preoperative diagnosis, intraoperative findings, surgical technique, and tumor characteristics in a concise and uniform format. By promoting consistency, accuracy, and completeness in reporting, synoptic operative notes facilitate effective communication among multidisciplinary healthcare teams, enhance quality assurance efforts, and streamline data extraction for research purposes. The integration of synoptic reporting within electronic medical record systems further enhances accessibility and usability, ensuring efficient documentation practices and improved patient care outcomes in pediatric surgical oncology.

AbstractBackground and PurposeTo compare the performance of the photon‐counting detector (PCD)‐CT against a cutting‐edge energy‐integrated detector (EID)‐CT to visualize different segments of the chorda tympani nerve.Materials and MethodsAn IRB‐approved protocol prospectively enrolled patients for temporal bone CT on both EID‐CT and PCD‐CT scanners. Fellowship‐trained neuroradiologists compared visualization of chorda tympani segments on each scanner using a 5‐point Likert scale (1 indicating EID is far superior to PCD, 3 indicating they are equivalent, and 5 indicating PCD is far superior to EID). Scores were averaged across segments and tested using a one‐sample Wilcoxon signed‐rank test with a one‐sided alternative hypothesis.ResultsForty temporal bones were evaluated. Average Likert scores for visualization of chorda tympani segments‐chorda tympani canal/proximal segment, middle ear/posterior tympanic segment, and petrotympanic fissure/distal segment‐ on the PCD compared to EID scanner were 4.2 (SD = 0.4), 4.4 (0.5), and 4 (0.0), respectively. The anterior tympanic segment of the chorda tympani was not well visualized on either platform or therefore not scored. PCD compared to the EID scanner had better overall performance (Median = 4.2, 95% CI: [4.1, 5.0], p‐value < .001).ConclusionPCD‐CT improves visualization of the petrous and intratympanic chorda tympani nerve segments, chorda tympani canaliculus, and petrotympanic fissure compared to comparable EID‐CT examinations. The improved visualization of the chorda tympani is important for the characterization of middle ear pathology involving this structure and presurgical planning to determine the size of the facial recess for cochlear implantation and to estimate the risk of nerve injury.

OBJECTIVE Posterior lumbar interbody fusion (PLIF) and/or transforaminal lumbar interbody fusion (TLIF), referred to as "PLIF/TLIF," is a commonly performed operation for lumbar spondylolisthesis. Its long-term cost-effectiveness has not been well described. The aim of this study was to determine the 5-year cost-effectiveness of PLIF/TLIF for grade 1 degenerative lumbar spondylolisthesis using prospective data collected from the multicenter Quality Outcomes Database (QOD). METHODS Patients enrolled in the prospective, multicenter QOD grade 1 lumbar spondylolisthesis module were included if they underwent single-stage PLIF/TLIF. EQ-5D scores at baseline, 3 months, 12 months, 24 months, 36 months, and 60 months were used to calculate gains in quality-adjusted life years (QALYs) associated with surgery relative to preoperative baseline. Healthcare-related costs associated with the index surgery and related reoperations were calculated using Medicare reimbursement–based cost estimates and validated using price transparency diagnosis-related group (DRG) charges and Medicare charge-to-cost ratios (CCRs). Cost per QALY gained over 60 months postoperatively was assessed. RESULTS Across 12 surgical centers, 385 patients were identified. The mean patient age was 60.2 (95% CI 59.1–61.3) years, and 38% of patients were male. The reoperation rate was 5.7%. DRG 460 cost estimates were stable between our Medicare reimbursement–based models and the CCR-based model, validating the focus on Medicare reimbursement. Across the entire cohort, the mean QALY gain at 60 months postoperatively was 1.07 (95% CI 0.97–1.18), and the mean cost of PLIF/TLIF was $31,634. PLIF/TLIF was associated with a mean 60-month cost per QALY gained of $29,511. Among patients who did not undergo reoperation (n = 363), the mean 60-month QALY gain was 1.10 (95% CI 0.99–1.20), and cost per QALY gained was $27,591. Among those who underwent reoperation (n = 22), the mean 60-month QALY gain was 0.68 (95% CI 0.21–1.15), and the cost per QALY gained was $80,580. CONCLUSIONS PLIF/TLIF for degenerative grade 1 lumbar spondylolisthesis was associated with a mean 60-month cost per QALY gained of $29,511 with Medicare fees. This is far below the well-established societal willingness-to-pay threshold of $100,000, suggesting long-term cost-effectiveness. PLIF/TLIF remains cost-effective for patients who undergo reoperation.

OBJECTIVE Patients with cervical spondylotic myelopathy (CSM) experience progressive neurological impairment. Surgical intervention is often pursued to halt neurological symptom progression and allow for recovery of function. In this paper, the authors explore predictors of patient satisfaction following surgical intervention for CSM. METHODS This is a retrospective review of prospectively collected data from the multicenter Quality Outcomes Database. Patients who underwent surgical intervention for CSM with a minimum follow-up of 2 years were included. Patient-reported satisfaction was defined as a North American Spine Society (NASS) satisfaction score of 1 or 2. Patient demographics, surgical parameters, and outcomes were assessed as related to patient satisfaction. Patient quality of life scores were measured at baseline and 24-month time points. Univariate regression analyses were performed using the chi-square test or Student t-test to assess patient satisfaction measures. Multivariate logistic regression analysis was conducted to assess for factors predictive of postoperative satisfaction at 24 months. RESULTS A total of 1140 patients at 14 institutions with CSM who underwent surgical intervention were included, and 944 completed a patient satisfaction survey at 24 months postoperatively. The baseline modified Japanese Orthopaedic Association (mJOA) score was 12.0 ± 2.8. A total of 793 (84.0%) patients reported satisfaction (NASS score 1 or 2) after 2 years. Male and female patients reported similar satisfaction rates (female sex: 47.0% not satisfied vs 48.5% satisfied, p = 0.73). Black race was associated with less satisfaction (26.5% not satisfied vs 13.2% satisfied, p < 0.01). Baseline psychiatric comorbidities, obesity, and length of stay did not correlate with 24-month satisfaction. Crossing the cervicothoracic junction did not affect satisfactory scores (p = 0.19), and minimally invasive approaches were not associated with increased patient satisfaction (p = 0.14). Lower baseline numeric rating scale neck pain scores (5.03 vs 5.61, p = 0.04) and higher baseline mJOA scores (12.28 vs 11.66, p = 0.01) were associated with higher satisfaction rates. CONCLUSIONS Surgical treatment of CSM results in a high rate of patient satisfaction (84.0%) at the 2-year follow-up. Patients with milder myelopathy report higher satisfaction rates, suggesting that intervention earlier in the disease process may result in greater long-term satisfaction.