Citations

ABSTRACT Importance Risk stratification of cutaneous squamous cell carcinoma (CSCC) is central to effective management. Despite advancements in the 8th edition of the American Joint Committee on Cancer (AJCC8) staging system, the distinctiveness of T‐stages remains limited. Objective To evaluate the effectiveness of the Brigham and Women's Hospital (BWH) and the AJCC8 staging systems in predicting poor outcomes in head and neck (HN) CSCC. Design A retrospective, multinational cohort study of CSCCs diagnosed between January 10, 1991, and December 31, 2023. Setting Twelve centers across the United States (10), Spain (1), and Brazil (1). Participants Patients with invasive CSCC who underwent curative‐intent surgical treatment. Exclusions included cases of lip CSCC, cases with prior HN cancer with associated regional disease, patients with a history of chemotherapy/radiotherapy for other HN neoplasms, and recurrent primary tumors. Exposure Tumors were staged according to both the AJCC8 TNM staging system and the BWH tumor classification. Main Outcomes and Measures Local recurrence (LR), nodal recurrence (NR), distant recurrence (DR), and disease‐specific death (DSD). Results A total of 9852 excised tumors from 3168 patients were included. The 2 systems had comparable monotonicity and homogeneity. Significant differences could be observed in 5‐year cumulative incidence for DSD in both BWH and AJCC8, and also for LR in BWH. Higher T‐stages exhibited similar curves regarding NR and DR for both AJCC8 and BWH staging systems. Overall, we observed high specificity and NPV, low sensitivity and PPV, and moderately high c‐indices for both the BWH and AJCC8 staging systems in predicting the main outcomes for HNCSCC. Conclusion and Relevance Current AJCC8 and BWH staging systems can accurately predict survival in HNCSCC, although there are still important characteristics to be addressed in future staging systems for better stratification according to the other main outcomes.

Importance Women diagnosed with breast cancer at a young age are felt to have a higher risk for locoregional recurrence (LRR) regardless of type of local therapy. Objective To assess the long-term incidence of isolated LRR by molecular subtype in a modern multicenter cohort of young women. Design, Setting, and Participants This cohort study, a multicenter prospective study named the Young Women’s Breast Cancer Study, enrolled 1302 women diagnosed with breast cancer at 40 years or younger from 2006 to 2016. Treatment information and incident LRR (ipsilateral breast/chest or lymph node recurrence) were self-reported on study surveys and confirmed with medical record review; molecular subtype was determined by record review. Analysis was reported from February 2023 to May 2025. Main Outcomes and Measures Cumulative incidence of isolated LRR was calculated using the Kaplan-Meier method; hazard ratios were estimated by Cox proportional hazards regression. Results The cohort included 1135 women with stage I through III breast cancer who had a median follow-up of 10.1 years (range, 0.4-16.3 years). The age at diagnosis was younger than 30 years for 145 patients (12.8%), 31 to 35 years for 318 patients (28.0%), and 36 to 40 years for 672 patients (59.2%). There were 59 isolated local recurrences (5.2%) and 4 isolated regional recurrences (0.4%). Among patients with local therapy and subtype data available (n = 1128), 366 (32%) had luminal A–like tumors; 240 (21%), luminal B–like tumors; 231 (20%) luminal ERBB2 positive (+)–like (formerly HER2 positive); 90 (8%) ERBB2 +-like; and 201 (18%) triple negative. A total of 346 women (30%) had breast-conserving therapy (BCT) (98% of whom had radiation), 296 (26%) unilateral mastectomy, and 487 (43%) bilateral mastectomy. Of women who had mastectomy, 425 (54%) had radiation. The cumulative incidence of LRR at 10.1 years by subtype was as follows: luminal A, 4.4% (range, 1.0%-6.9%); luminal B, 4.7% (range 1.8%-7.7%); luminal ERBB2 +, 6.1% (range, 3.1%-8.3%); ERBB2 +, 2.2% (range, 0%-6.3%); and triple negative, 6.5% (range, 4.2%-10.1%). The cumulative incidence of LRR by locoregional treatment type at 10.1 years was 6.7% after BCT (range, 4.3%-10.1%), 6.5% after mastectomy without radiation (range, 0%-7.7%), and 2.4% after mastectomy with radiation (range, 1%-4.2%). Although mastectomy with radiation was associated with the lowest risk of LRR on multivariable analysis, when examined within molecular subtype, there were no differences seen. Conclusions and Relevance In this contemporary cohort of women diagnosed with breast cancer at age 40 years or younger, risk of isolated LRR was relatively low (5.6%) at a median follow-up of 10.1 years, and significant differences were not seen by tumor subtype. Concerns for long-term risk of LRR should not influence surgical decision-making with young women, irrespective of molecular subtype.

ImportanceCancer imposes a substantial economic burden on patients that may be worse in patients with higher-stage disease due to the need for more therapy.ObjectiveTo investigate the out-of-pocket costs (OOPCs) attributable to the initial treatment of common cancers among privately insured individuals diagnosed at different stages.Design, Setting, and ParticipantsThis retrospective cohort study used administrative claims data of a large national insurer in the US linked to the Surveillance, Epidemiology, and End Results (SEER) cancer registry to compare OOPCs of individuals diagnosed with breast, colorectal, and lung cancer at different stages with OOPCs of similar individuals without cancer using difference-in-differences methods. Individuals living in the US between 2008 and 2022, aged younger than 65 years, insured through a large national private health insurer, and with 6 or more months of continuous enrollment were included. Data were analyzed from June 2024 through February 2025.ExposureThe presence or absence of an incident cancer diagnosis and disease stage from the SEER registry diagnosed from 2008 to 2019.Main Outcomes and MeasuresThe primary outcome was OOPCs among individuals with breast, colorectal, and lung cancer diagnosed at different disease stages compared with those with no cancer diagnosis.ResultsThe cohort consisted of 46 158 patients (mean [SD] age at diagnosis, 46 [12] years; 30 733 female [66.6%]; 2543 Asian [5.5%], 4114 Black [8.9%], 3590 Hispanic [7.8%], and 31 099 White [67.4%]), including 19 656 patients with cancer and 26 502 patients without cancer in the control group. Among patients with cancer, 14 581 patients had breast cancer, 2842 patients had colorectal cancer, and 2233 patients had lung cancer. An incident cancer diagnosis was associated with a mean increase in OOPCs of $592.53 per month (95% CI, $528.01-$627.04 per month) for the 6 months after the diagnosis. Cost monotonically increased with stage at diagnosis (mean OOPC increase range, $462.01 per month [95% CI, $417.92-$506.11 per month] for stage 0 to $719.97 per month [95% CI, $626.11-$813.83 per month] for stage 4).Conclusions and RelevanceIn this study of individuals with private insurance, patients faced high OOPCs after an incident diagnosis of cancer, with patients with more advanced cancer having the highest OOPCs. Further research is needed to determine the clinical and financial effects of increased OOPCs for patients with cancer.

Abstract Background and Aims Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv. Methods An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM. Results A total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80–30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06–5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27–3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (<30 years) disease (OR, 4.75; 95% CI, 2.35–9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08–.23). Conclusions Disease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.

ImportanceThe Ophthalmic Knowledge Assessment Program (OKAP) has been widely used to determine readiness to take the high-stakes Written Qualifying Examination (WQE). However, it is unclear how well OKAP performance can predict WQE outcomes.ObjectiveTo examine the association between the OKAP and WQE nationally.Design, Setting, and ParticipantsThis was a retrospective cohort study conducted from 2017 to 2022. This national data analysis included residents from ophthalmology residency programs in the US. Study data were analyzed June 2023 to December 2024.ExposuresOKAP and WQE data.Main Outcomes and MeasuresThe national OKAP examination data and the WQE data were matched. Candidates who had complete data for the OKAP during postgraduate year (PGY) 2, 3, and 4 and completed the WQE were included in the study. Two-sample t tests, logistic regression analysis, receiver operating characteristic curves, and confusion matrix were used to examine the association of various test scores (PGY-2 OKAP, PGY-3 OKAP, PGY-4 OKAP, minimum OKAP, maximum OKAP, average OKAP) as predictors for WQE outcomes (pass or fail). Multiple logistic regression analyses were also used to assess the association of gender, time since graduation, program size, and WQE pass/fail outcomes.ResultsA total of 1597 residents (907 male [56.8%]) from 117 residency programs were included in this study. First-time pass rate of the WQE was 89% (1418 of 1597 residents). OKAP scores, particularly average OKAP, maximum OKAP, and PGY-4 OKAP scores (all had area under the curve = 0.88), were the most useful predictor of WQE outcomes. PGY-4 OKAP scores were used for the rest of the analysis for simplicity. A PGY-4 OKAP scaled score of 550 corresponded to 94% of candidates passing the WQE. Using PGY-4 OKAP scores to predict passing/failing, the WQE had 90.7% accuracy. Gender (odds ratio [OR], 1.50; 95% CI, 1.01-2.26; P = .048), program size (OR, 1.55; 95% CI, 0.98-2.41; P = .06), and time since residency graduation (OR, 1.00; 95% CI, 1.00-1.00; P = .14) were not included in the logistic regression model investigating the association of PGY-4 OKAP scores with the likelihood of passing the WQE.Conclusions and RelevanceResults suggest that OKAP examination scores were associated with passing the WQE after adjusting for program size, gender, and time since residency graduation. Further analyses may be warranted to predict failing the WQE so that potential interventions can be attempted.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain provide recommendations for the comprehensive management of pain in patients with cancer. This article will focus on methods for screening for pain, safe and appropriate prescription of opioid and miscellaneous analgesics, and the optimization of nonpharmacologic interventions including integrative and interventional strategies for treatment of cancer-related pain. Additionally, the NCCN Guidelines discuss methods for the safe reduction of opioids when appropriate, as well as techniques for encouraging the judicious use of opioids. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional issues that are not covered here, including management of pain during a pain crisis, management of procedure-related pain and anxiety, pain management for cancer survivors, and the use of nonopioid and adjuvant analgesics for cancer-related pain.

Context.— After-death care can be complicated and time-consuming for clinical staff, and frustrating for bereaved families. Delays and errors can have damaging legal and reputational consequences for hospitals. Offices of Decedent Affairs (ODAs) have been proposed as a solution, and their potential benefits have been described in several single institution reports. The literature lacks a contemporary and comprehensive review of existing ODAs and their approaches. Objective.— To describe the process of establishing a new ODA and to provide a snapshot of the spectrum of structure, function, and impact of existing ODAs in the United States. Design.— A survey was administered to 11 established ODAs spread across the continental United States. Programs were identified through the College of American Pathologists Autopsy Committee and a Medical Autopsy Listserv. Results.— Eleven ODAs returned the survey, representing more than 190 cumulative years of experience in decedent care in the hospital setting (median, 10 years). There was a wide range in staffing (both staff size and background) as well as scope of services offered. The median ratio of hospital deaths to full-time equivalent (FTE) staffing was 360 deaths per FTE. Respondents reported that ODAs unburden clinical providers and facilitate decedent management. Some respondents reported a quicker turnover of hospital beds and shorter intervals between pronouncement of death and autopsy. ODAs increased autopsy rates when the autopsy services were part of the ODA. Conclusions.— This survey provides practical information for hospitals considering establishing a new ODA and useful benchmarks for existing ODA programs.

Context.— Decedent Affairs Offices and Programs can serve as an avenue to assist medical centers in facilitating efficient and comprehensive decedent management, despite a paucity of literature on their roles, establishment, and efficacy. Objective.— To characterize the motivations and rationales for establishing Decedent Affairs Offices. Design.— A survey was administered to 11 established Decedent Affairs Offices/Programs, identified through the College of American Pathologists Autopsy Committee and a Medical Autopsy Listserv. The questions comprehensively cover establishment, operations, and outcomes data available by institution. Results.— Survey respondents reported the rationale for starting their programs and the benefits such offices can have. Conclusions.— Decedent Affairs Offices and Programs provide a useful option to medical centers to navigate the increasingly complex task of comprehensive decedent management. The present survey helps to delineate the similarities and differences between these programs at 11 institutions, to aid nascent programs in their establishment and growth over time.

Background: Autonomic dysfunction is common after spinal cord injury (SCI). There are currently limited tools to comprehensively characterize its deficits. While individual established autonomic tests have a long history and sound scientific background, translating these autonomic testing results to inform clinical understanding is a major barrier. Objectives: To assess a strategic battery of autonomic tests to characterize and act as a biomarker of autonomic regulation for individuals with SCI and to develop a novel graphical representation of these data to facilitate understanding of autonomic dysfunction after SCI. Methods: We outline a battery of six laboratory autonomic tests that were curated to collectively describe the ability of individuals with SCI to inhibit and recruit sympathetic activity through the injured spinal cord. Heart rate/blood pressure variability, bolus phenylephrine, hand and foot cold pressor, Valsalva maneuver, and bladder pressor are herein described. Incorporating normative control data for 30 uninjured individuals completing this testing battery, we further demonstrate the utility of a composite biomarker, comparing these control results to 11 individuals with SCI. Results: Results demonstrate strong normality of data with testing psychometrics, suggesting stable reproducibility with repeat testing. Even in this preliminary sample of individuals with SCI, clear differences begin to emerge compared to uninjured norms. This illustrates the ability of this collective testing battery to characterize autonomic regulation after SCI. To aid in clinical translation, we further present a graphical representation, an autonomic phenotype , which serves as a snapshot of how normal or abnormal sympathetic inhibition and recruitment of activation may be after SCI. Conclusion: Utilizing these autonomic phenotypes, three example cases of individuals with SCI highlight evidence of varied degrees of autonomically complete SCI. Together, this represents a key advancement in our understanding of autonomic function after SCI.

Background Statin Choice is a shared decision-making encounter tool embedded in the electronic health record. Objective To describe the association between the use of Statin Choice, statin prescriptions by clinicians, prescription fills (primary adherence), and statin adherence at 12 mo (secondary adherence). Design Observational cohort study at the Cleveland Clinic Health System. Subjects Statin-naïve adults aged 40 to 75 y with a 10-y atherosclerotic cardiovascular disease (ASCVD) risk of ≥5% and a primary care appointment between January 2020 and July 2021. Main Measures The primary exposure was the use of Statin Choice during a clinical encounter. We measured whether the use of Statin Choice was associated with statin prescriptions. We measured statin adherence based on pharmacy fill data at 60 d (primary adherence) and 12 mo (secondary adherence). We used mixed-effects logistic regression to estimate the adjusted odds of statin prescriptions and adherence at the 3 time points by the use of Statin Choice. Key Results Among 17,001 statin-naïve patients, 13% viewed Statin Choice and 7% were prescribed a statin. The median ASCVD risk was 10%. Patients who were shown Statin Choice had 9.04 higher odds of being prescribed a statin compared with patients not shown Statin Choice (95% confidence interval [CI]: 7.86–10.4). Among patients prescribed a statin, the use of Statin Choice was associated with 5.75 higher odds of primary adherence compared with usual care (95% CI: 4.22–7.83). At 12 mo, Statin Choice use was significantly associated with adherence in the unadjusted analysis (OR: 1.58; 95% CI: 1.05–2.08) but was not significant after adjustment for patient factors. Patients shown Statin Choice had an average of 12 mg/dL reduction in low-density lipoprotein cholesterol at 12 mo (95% CI: −16 mg/dL, −10) compared with those not shown Statin Choice. Conclusion In this observational study, Statin Choice use was strongly associated with statin prescription and fills and weakly associated with adherence to statins for up to 1 y. A randomized trial is needed to confirm causality. Highlights Statin Choice is an electronic health record–embedded shared decision-making encounter tool available for free in many health care systems. Small randomized controlled trials have found modest associations between the use of Statin Choice and statin adherence using patient-reported data. In our large study using pharmacy fill data, clinician use of Statin Choice during a medical encounter was associated with significantly greater patient adherence with statins up to 1 y later. Exposure to Statin Choice was associated with a significant reduction in low-density lipoprotein cholesterol over 1 y.