Citations

Objective To provide a comprehensive analysis of initial suicide attempts, covering incidence, risk factors, outcomes, and healthcare use in the month before and the month after the attempts. Design Comprehensive analysis of the Swedish population that included three designs: a retrospective cohort study to investigate incidence and healthcare use, a nested case-control study to investigate risk factors, and a matched cohort study to examine subsequent suicide attempts and mortality. Setting Comprehensive Swedish national registers that include patient diagnoses from hospitals and specialist outpatient care, and cause of death information updated to the end of 2019. Participants 3.7 million people born in Sweden in 1963-98 and followed from age 10 to 57 years. Main outcome measure First lifetime suicide attempt identified in patient and death registers using ICD (international classification of diseases) codes for intentional self-harm, any self-harm with lethal methods or requiring hospital admission, or any self-harm resulting in death. Results The lifetime risk of an initial suicide attempt in the study population was 4.6%, with greater risk in females and highest risk between ages 18 and 24. One in 10 families in Sweden had at least one family member who attempted suicide. Overdose and poisoning were the most common methods. Previous psychiatric disorders, general medical diseases, and adverse life events were associated with increased risk of initial suicide attempt, while higher socioeconomic status was associated with decreased risk. People with an initial suicide attempt were at substantially increased risk of subsequent attempts (hazard ratio 23.4), death by suicide (16.4), and all cause mortality (7.3). At least 60% of those who made an initial suicide attempt had a healthcare contact in the month before the attempt. Conclusions This study provides comprehensive data on the incidence, risk factors, outcomes, and healthcare use of initial suicide attempts in the Swedish population, highlighting the need for systematic prevention efforts for people who have attempted suicide for the first time.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45–1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35–5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18–0.88]; P interaction =0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Abstract New technologies enabling access to high-sensitivity cardiac troponin (hs-cTn) assays at the point of care (POC) are available for routine use. POC technology can accelerate cardiac troponin testing within the hospital setting and support testing in other healthcare environments. Pre-analytical and analytical issues unique to POC testing are discussed. The opportunities and the evidence needed to support the routine use of hs-cTn POC assays in clinical care are outlined. Based on recent developments, the potential impact of hs-cTn at the POC in multiple clinical settings is described, and a roadmap of the steps required for successful implementation is provided.

ImportanceHip fractures present a substantial public health challenge, with projections of more than 500 000 per year by 2040. As such, frailty indices such as the Revised Risk Analysis Index (RAI) and the Modified Five-Item Frailty Index (mFI-5) have been recently investigated as metrics for preoperative risk stratification for these patients.ObjectiveTo understand the accuracy of frailty, as measured by the RAI and the mFI-5, for estimating 30-day mortality following surgically managed hip fractures.Design, Setting, and ParticipantsThis retrospective cross-sectional analysis used the American College of Surgeons’ National Surgical Quality Improvement database. Patients aged 65 years old with surgically managed traumatic hip fracture from 2015 to 2019 were included. Frailty was evaluated using the RAI, a 5-domain scale with 14 weighted variables graded from 0 to 81, and the mFI-5, a 2-domain scale with 5 unweighted variables graded from 0 to 5; for both, a higher score denotes worse frailty. Data collection occurred from May to June 2024.ExposureDiagnosis of hip fracture and undergoing surgical fixation, hemiarthroplasty, or total hip arthroplasty.Main Outcomes and MeasuresThe primary outcome was 30-day mortality. Multivariable regression was conducted to assess the estimating value of frailty scales. Discriminatory accuracy was assessed using a receiver operating characteristic curve and quantified using a C-statistic.ResultsThe cohort consisted of 114 359 patients (70 038 female [69.9%]; median [IQR] age, 84 [77-89] years) with 51 071 prefrail patients (44.7%) according to the mFI-5 and 31 883 very frail patients (27.9%) according to the RAI comprising the largest frailty groups. Increasing frailty status was associated with greater odds ratio (OR) for 30-day mortality for both the mFI-5 (prefrail OR, 1.35 [95% CI, 1.24-1.47]; frail OR, 2.11 [95% CI, 1.94-2.30]; severely frail OR, 3.53 [95% CI, 3.20-3.90]; P < .001 for all) and RAI (normal OR, 1.55 [95% CI, 1.35-1.79]; frail OR, 2.97 [95% CI, 2.59-3.42]; very frail OR, 6.17 [95% CI, 5.38-7.08]; P < .001 for all). The RAI demonstrated superior discriminatory accuracy for 30-day mortality compared with the mFI-5 (area under the receiver operating characteristic curve, 0.73 [95% CI, 0.72-0.73] vs 0.61 [95% CI, 0.60-0.62]; P < .001).Conclusions and RelevanceIn this cross-sectional study of 114 359 patients, the RAI demonstrated superior odds and discriminatory accuracy for estimating 30-day mortality following surgical management of hip fractures. The RAI may be considered as a risk stratification tool for orthopedic surgeons to adjunct surgical planning, thereby reducing postoperative mortality.

ABSTRACTBackground/ObjectivesImmune‐mediated skin disorders, such as immunobullous dermatoses and leukocytoclastic vasculitis, rarely affect children. While direct immunofluorescence (DIF) biopsy is a standard diagnostic tool, limited data exist on pediatric DIF patterns, rates of positivity, pretest diagnostic concordance, and the relevance of biopsy site. This study sought to address these gaps.MethodsDIF data from all skin and mucosal specimens interpreted at Mayo Clinic's reference immunodermatology laboratory for patients aged 0–18 years (August 22, 2017 to November 30, 2023) were reviewed. DIF results were classified as positive if a characteristic pattern was seen and negative if the findings were negative or nondiagnostic.ResultsOf 986 pediatric DIF studies, 153 (15.5%) were positive and comparable to adult positivity rates (20.9%) during the same period. The most frequent DIF patterns were IgA‐predominant vasculitis (N = 85/153; 55.5%) and lichenoid tissue reaction (N = 21/153;13.7%). Concordance between pretest diagnosis and positive DIF results was highest for linear IgA bullous dermatosis (N = 7/7; 100%) and dermatitis herpetiformis (N = 6/6; 100%). Excluding these entities, DIF changed the pretest diagnosis in 16.7% (N = 19/114) of cases. While lower extremity biopsies were initially more likely to yield positive DIF results, this association disappeared when IgA vasculitis cases were excluded.ConclusionThe most frequent DIF pattern in children was that of IgA‐predominant vasculitis. Pediatric DIF positivity rates closely mirrored those of adults, supporting similar biopsy thresholds. DIF results differed from the pretest impression in a substantial percentage, supporting the value of DIF in select situations in the pediatric population. After controlling for IgA vasculitis, biopsy site was not associated with DIF positivity.

e19521 Background: Blindedindependent central review (BICR) committees are often established for oncology trials to assessbestoverall response (BOR), while real-world (RW) studies typically rely on physician-assessed responses. To emulate clinical trial rigor, a BICR committee was implemented in the R5458-ONC-21101 RW data-derived external control arm study (NCT05673967) to evaluate BOR using International Myeloma Working Group (IMWG) criteria. A pre-specified concordance analysis compared BOR assessments between the BICR committee and treating site physicians. Methods: RW data were obtained from chart reviews at 15 participating International Myeloma Foundation IMWG sites. The BICR committee, comprised of three multiple myeloma experts, evaluated BOR through consensus voting. Per protocol, the committee reviewed case report forms consisting of data on serum and urine myeloma protein and free light chain levels; and, where available, bone marrow plasma cell percentage, presence of plasmacytomas, and bone lesion changes. Concordance between BICR- and physician-assessed BOR was evaluated for objective response rate defined as ≥partial response (PR), ≥very good partial response (VGPR), ≥complete response (CR), and stringent complete response (sCR), with non-evaluable responses excluded from the analysis. Cohen’s kappa (κ) was used to measure agreement, with values >0.6 indicating strong concordance. 1 Results: Of 279 evaluable lines of therapy from 203 patients (Table), the BOR of ≥PR was 45.2% by BICR assessment and 42.3% by treating physicians (κ=0.622). Concordance improved for BOR of ≥VGPR (22.2% by BICR vs 24.7% by treating physicians; κ=0.731) but was low for BOR of ≥CR (3.9% vs. 10.8%; κ=0.508) and sCR (1.1% vs. 4.7%; κ=0.364). Conclusions: BICR- and physician-assessed responses showed strong concordance for BOR of ≥PR and ≥VGPR. However, as expected, lower concordance for ≥CR and sCR was observed, as evaluation of CR per IMWG criteria requires a bone marrow biopsy, which is rarely performed in clinical practice. While the reliability of CR and sCR in RW data is less certain, these results suggest that BOR of ≥VGPR or ≥PR may be reliably ascertained in academic settings based on treating physician evaluations. 1. Landis JR, Koch GG. Biometrics 1977;33(1):159–74. Clinical trial information: NCT05673967 . Agreement of BICR- and physician-assessed responses. BICR assessed Physician assessed Observed agreement, % Cohen’s kappa* Number of evaluable lines of therapy 279 279 - - ≥PR, n (%) 126 (45.2) 118 (42.3) 81.4 0.622 ≥VGPR, n (%) 62 (22.2) 69 (24.7) 90.3 0.731 ≥CR, n (%) 11 (3.9) 30 (10.8) 93.2 0.508 sCR, n (%) 3 (1.1) 13 (4.7) 96.4 0.364 *A kappa value >0.6 indicates strong concordance. 1

e13828 Background: Disparities in cancer outcomes between rural and urban populations are often linked to limited healthcare resources in rural areas. However, the impact of socioeconomic factors, particularly income inequality, requires further investigation. Methods: We analyzed cancer mortality rates using the Surveillance, Epidemiology, and End Results (SEER) database, focusing on rural-urban continuum codes and median county income, the proportions of patients with de novo metastatic disease at diagnosis, those aged 80 and older, and those experiencing a treatment delay of three months or more. Results: Our findings indicate that non-metropolitan counties (56.7%, 95% CI: 56.6%, 56.8%) and those with lower median incomes (54.9%, 95% CI: 54.8%, 55.1%) have significantly lower cancer survival rates than metropolitan counties (62.6%, 95% CI: 62.5%, 62.6%) and higher-income rural counties (62.6%, 95% CI: 62.6%, 62.7%), a trend consistent over the observation period. Higher proportions of de novo metastatic disease and increased treatment delays were observed in counties with lower income and greater rurality, with these counties also demonstrating higher annual percentage rates of change for both de novo metastatic disease (P < 0.05) and treatment delays (P < 0.05). Conclusions: Lower county-level median household income is associated with higher cancer mortality rates, increased de novo metastatic disease, and longer treatment delays. These results underscore the need to appreciate the role of income disparities in cancer outcomes and to improve access to oncology care in underserved rural populations.

1510 Background: The National Comprehensive Cancer Network (NCCN) Harmonized Guidelines for Sub-Saharan Africa (SSA) have emerged as leading cancer treatment guidelines in SSA. The NCCN-SSA guidelines, derived by adapting NCCN guidelines for the SSA context, offer standardized recommendations to guide cancer care and shape policy in SSA. This study examines the evidence cited in support of the NCCN-SSA guidelines, with a focus on population characteristics and generalizability to SSA. Methods: Two reviewers independently examined the NCCN-SSA guidelines for the eight most common cancers in SSA to identify all studies cited in support of treatment/management recommendations. Study selection discrepancies were resolved by discussion. Full-text articles were reviewed and data on age, sex, race, and recruitment geography were abstracted. Descriptive analyses were performed using R statistical software. Results: Overall, 4,589 citations were reviewed, and 2,938 (64.0%) studies with individual-level data were included, representing >10.4 million study participants. Of the 2,061 studies reporting geographic information (70%), 50 (2.4%) recruited in SSA; of these, 39 (83.0%) recruited from South Africa. Three studies (0.2%) recruited exclusively in SSA. Most studies (95.3%) recruited exclusively from high or upper-middle income countries. Only 29.2% of studies with race data included >10% Black study participants. Conclusions: Most studies cited in the NCCN-SSA guidelines were conducted in high-income countries outside SSA. A small minority of all study participants were Black. Our findings underscore potential limitations in the generalizability of the NCCN-SSA guidelines to SSA and highlight a pressing need to generate and incorporate context-specific data to guide care and inform policy. WHO region of recruitment, race, and country-level income of studies included in NCCN-SSA guidelines. Cancer type # (%) studies reporting geography # (%) studies by recruitment region*: Americas # (%) studies by recruitment region*: Europe # (%) studies by recruitment region*: Sub-Sah. Africa % participants, White % participants, Black % participants, Other race # (%) studies representing only HMIC (per World Bank) Overall 2061(70%) 1177 (57%) 921 (45%) 50 (2%) 79% 9% 11% 1964(95%) B-cell 325(57%) 173 (53%) 178 (55%) 5(2%) 82% 7% 10% 307(94%) Breast 206(44%) 123 (60%) 124 (60%) 12 (6%) 80% 9% 11% 179(87%) Cervical 163(90%) 100 (61 %) 44(27%) 3(2%) 64% 14% 22% 158(97%) Colorectal 584(82%) 278 (48%) 292 (50%) 11 (2%) 80% 10% 10% 571 (98%) Hepato-cellular 183(74%) 80(44%) 68(37%) 0(0%) 69% 9% 22% 169(92 %) Kaposi sarcoma 51(80%) 25 (49%) 19(37%) 5(10%) 38% 51% 10% 44(86%) Ovarian 115(56%) 76 (66%) 35 (30%) 0(0%) 83% 4% 13% 115(100%) Prostate 434(88 %) 322 (74 %) 161 (37%) 14 (3%) 79% 9% 12% 421(97%) HMIC = high and upper-middle income countries. *Percent of studies includes as the denominator only the number of studies with reported geographies.

9578 Background: Anti-PD1 immunotherapy has shown improved clinical outcomes in patients (pts) with advanced cSCC, and recently, in the neoadjuvant setting for resectable disease. Pathological (path) response is predictive of recurrence in melanoma and recent NeoIT trials suggests the same in cSCC; however, an analysis of clinical outcomes in pts with resectable cSCC treated with intended anti-PD1-based NeoIT in larger datasets remains unknown. Methods: Pts with resectable cSCC treated with intended anti-PD1-based NeoIT from 17 cancer centres globally were included. Baseline patient and disease characteristics, treatment regimen, path response and recurrence-free survival (RFS) or progression-free survival (PFS) were collected and examined. Results: 134 pts with resectable cSCC were treated with intended anti-PD1-based NeoIT. Median age was 75 years old (range, 39-97), 72% (n=97) were male. One fifth (22%, n=29) were immunocompromised and 43% (n=58) had ECOG PS of ≥1. Of 125 (93%) pts with known primary cSCC, 82% (n=102) were from the head & neck. Most pts (79%, n=106) were stage III/IV. The majority had anti-PD1 monotherapy (91%, n=122) and 9% (n=12) had anti-PD1+/-investigational agent. Median follow-up from commencement of NeoIT was 10 months (95% CI, 9 - 12). Nearly half of the pts (49%, n=66) underwent surgery; 37 (56%) pts had major pathological response (MPR; ≤10% viable tumour cells at the surgical specimen; 31 [47%] had complete path response [0% of viable tumour cells] and 6 [9%] had near complete path response [1-10% of viable tumour cells]), 6 (9%) had partial path response (pPR; >10% and ≤50% of viable tumour cells), and 23 (35%) had path non-response (pNR; >50% of viable tumour cells). Of the 66 pts who underwent surgery, 11% (n=7) had recurrence (5 loco-regional and 2 distant recurrence), all non-MPR pts (1 pPR and 6 pNR). 12-months RFS was improved with MPR vs non-MPR (100% vs 79%, p=0.004). 52% (n=34) pts had adjuvant treatment (23 anti-PD1 alone, 7 anti-PD1+/-investigational agent, 2 platinum and 2 cetuximab). Within non-MPR pts, 12 had adjuvant treatment (3 recurred; 25%), while 17 did not have adjuvant treatment (4 recurred; 24%). Fifty-one percent (n=68) of pts did not have surgery; 9 (13%) due to progressive disease (PD) and 53 (78%) due to clinical response. Of the 53 pts with a clinical response, 5 (9%) subsequently progressed. Fourteen (10%) pts have died, 6 (4%) related to cSCC; 2 had surgery (non-MPR) and 4 did not have surgery (all due to PD). Conclusions: Anti-PD1-based NeoIT is an active regimen in resectable stage II-IV cSCC and is associated with high clinical response and MPR rates. No pts with MPR from NeoIT has recurred to date, however, 9% of pts who did not have surgery due to clinical response eventually progressed. These findings highlight the importance of further research to investigate the role of surgery in this subgroup of patients.

2085 Background: Primary Central Nervous System Lymphoma (PCNSL) is a rare and aggressive non-Hodgkin lymphoma with no approved treatments for relapsed/refractory (R/R) patients, representing a critical unmet need. MyD88 mutations in ~70% of PCNSL patients drive Interleukin-1 receptor associated kinase 4 (IRAK4) activation, promoting NF-κB signaling, inflammation, and tumor progression. Emavusertib, a potent oral IRAK4 inhibitor, crosses the blood-brain barrier and shows preclinical synergy with Bruton tyrosine kinase inhibitors (BTKi), re-sensitizing BTKi-resistant cell lines. This study evaluates the molecular and pharmacokinetic (PK) data associated with responses to emavusertib + ibrutinib combination therapy in R/R PCNSL patients. Methods: The safety, clinical activity, and potential biomarkers of emavusertib in R/R PCNSL are being investigated in the ongoing open-label, Phase 1/2 TakeAim Lymphoma trial (NCT03328078). Pre-dose and 1.5-hour post-dose plasma samples were collected on Cycle 3 Day 1, Cycle 5 Day 1 and Cycle 7 Day 1. Cerebrospinal fluid (CSF) samples were obtained via a lumbar puncture within 1.5 hrs of collection of the post-dose plasma PK sample on Cycle 3 Day 1. Mutation analysis was based on patients’ molecular pathology reports provided by trial sites. Sequencing of archival tissues, CSF and plasma are in progress. Results: As of 06 December 2024, CSF concentration data were available for 7 PCNSL patients. The mean emavusertib concentration in CSF was 81.3 ng/ml (54.7-104.0) in patients receiving 100 mg emavusertib BID (n = 4). In patients receiving 200 mg emavusertib BID (n = 3), the mean emavusertib concentration in CSF was higher at 175.7 ng/ml (114.8-209.4), which is 2.2X the mean value in patients who received 100 mg emavusertib BID (p-value = 0.02). All 7 patients received 560 mg ibrutinib QD, and the ibrutinib concentrations in the CSF were consistent with findings from previously published clinical studies. MyD88 mutation status was available for 7 patients of which all had prior exposure to BTKi regimens. Among these, 6 patients had MyD88 mutation of which 4 patients had responded (3 complete responses and 1 partial response) to emavusertib + ibrutinib combination with duration of response (DOR) up to 18.9 months with data collection ongoing. Conclusions: Preliminary CNS pharmacokinetic data demonstrates that emavusertib concentration in CSF increases with increasing emavusertib dose. Patients with MyD88 mutations showed expected promising preliminary efficacy to emavusertib + ibrutinib combination and may overcome BTKi resistance. Enrollment in this trial is ongoing. Clinical trial information: NCT03328078 .