Citations

Abstract Darier disease (DD) is a rare autosomal dominant genodermatosis. This comprehensive review, developed by the Darier Disease International Task Force (DDITF), consolidates current knowledge on the genetic basis, molecular pathophysiology, clinical presentation, diagnosis and management of DD, offering a global perspective that unites shared expertise. The disease arises from pathogenic variants in the ATP2A2 gene, which encodes sarco/endoplasmic reticulum Ca 2+ ‐ATPase isoform 2 (SERCA2), leading to disrupted calcium homeostasis and impaired desmosomal integrity. Clinically, DD is classified based on lesion type (classic vs. non‐classic) and is often accompanied by significant extracutaneous manifestations. Management remains challenging and requires a multifaceted approach, including topical therapies, systemic retinoids and lifestyle modifications. Emerging treatments that target the underlying molecular mechanisms offer promise for improved outcomes. This review aims to provide an updated reference and practical guidance for clinicians involved in the care and study of DD.

Abstract Aims To characterize global variation in cardiac rehabilitation (CR) staffing, indications, and prescribed dose by country income classification and compare findings with the International Council of Cardiovascular Prevention and Rehabilitation’s 2016 Global Audit. Methods and results Cross-sectional REDCap survey of Phase II/post-discharge CR programmes (May–September 2025). Outcomes were multidisciplinary team size/composition, accepted cardiac and non-cardiac indications, and centre-based CR dose. Comparisons were made across World Bank country income classifications and Audit decade (2016 vs. 2025). Of 7025 programmes identified globally, 1505 (median programme response rate = 62%/country) initiated a survey, from 90/113 (80%) countries with CR. CR was delivered by a multidisciplinary team of 7 (median; P25–P75 = 5–8; nurses, physiotherapists, cardiologists, and dietitians most common); teams were smaller in low-income countries (median = 4; P < 0.001), and physician specialty varied. Non-low-income programmes consistently accepted (≥90%) patients with acute coronary syndrome, with programmes in low-income countries less often accepting related interventions (e.g. surgery: low-income 0% vs. high-income 97%; P < 0.01), but non-cardiac indications were more frequently accepted (e.g. primary prevention, diabetes, and lung disease). Acceptance of heart failure increased compared with the previous Audit (70% vs. 87%; P < 0.001). Centre-based programmes prescribed a median of 20 h (P25–P75 = 12–30), typically two sessions/week over 8 weeks. Globally, 65 (72%) countries prescribed a median ≥12 sessions/programme. Programmes in upper-middle-income countries prescribed more sessions (median = 24, P25–P75 = 12–36; P < 0.001). Dose did not differ meaningfully between Audits (P = 0.07). Conclusion CR programmes globally are offered by small, but multidisciplinary teams. They accept guideline-indicated patients, with applicable variation by context. Insufficient dose in one-quarter of countries underscores investment need.

7028 Background: Axi-cel, autologous anti-CD19 CAR T-cell therapy, showed long-term survival and curative potential in R/R LBCL (ZUMA-1; Neelapu et al. Blood . 2023). Few studies have examined long-term outcomes beyond clinical trials. Here we report long-term real-world outcomes of axi-cel in R/R LBCL using large-sample CIBMTR data. Methods: A total of 1500 adults from 79 US centers receiving commercial axi-cel after ≥2 LOT for LBCL from Oct 2017-Aug 2020 were enrolled in a post-marketing requirement study. A protocol was developed prior to the study’s implementation, reviewed by Kite and CIBMTR. This is a secondary analysis of said study. Key outcomes were progression-free survival (PFS), overall survival (OS), time to next therapy (TTNT), disease-specific mortality (competing risks were non-relapse deaths), subsequent malignancies, and non-relapse mortality (NRM). Outcomes were analyzed descriptively. Cases with missing data were excluded separately for each endpoint. Results: As of Aug 2025, 1446 patients (pts) were included in the analysis. Median age at infusion was 62.2 y (range, 19.6-90.8: 38% of pts ≥65 y); 65% were male. Five percent of pts had ECOG PS ≥2 and 16% had high-grade lymphoma. Pts had a median of 3 (range, 2-4) prior LOT, 28% had prior autologous hematopoietic cell transplantation, and 50% received bridging therapy. At 59.7 mo median follow-up, median PFS (95% CI) was 7.9 mo (6.3-10.9) and 5-y PFS was 30% (27-32). The median OS was 25.7 mo (21.6-30.2); 5-y OS was 38% (35-41). The 5-y cumulative incidence of disease-specific mortality was 51%. Among pts who were progression-free at 2, 3, 4, or 5 y post-infusion, the OS at 6 y (95% CI) was 73% (68-78), 81% (76-86), 90% (84-94), and 94% (89-97), respectively. The median duration of response (DOR) was 25.3 mo (95% CI, 20.7-32.8) and 5-y DOR was 38% (35-41). The median TTNT was 12.2 mo and 30% did not need additional LOT at 5 y. Of pts who received subsequent salvage therapy, 12 (2%) received cell therapy, 39 (7%) received hematopoietic cell transplant, and 475 (90%) received other therapy. The 1, 2, 3, 4, and 5-y cumulative incidence of relapse (95% CI) was 49% (46-51), 52% (50-55), 54% (52-57), 55% (53-58), and 56% (53-59), respectively. No new safety signals were observed. The primary causes of death (n=864; 60%) were primary disease (540; 63%), infection (111; 13%), and organ failure (57; 7%). The 5-y cumulative incidence of NRM was 16% (95% CI, 14-18). At 5 y, 11% (95% CI, 10-13) had subsequent malignancies, mostly therapy-related myeloid neoplasms (6%) and non-melanoma skin cancer (3%); none were directly attributed to axi-cel. Conclusions: This real-world study showed sustained survival at 5 y among pts with R/R LBCL treated with axi-cel after ≥2 LOT, consistent with ZUMA-1. Infection and organ failure were common causes of NRM. These results continue to support the use of axi-cel with curative intent in R/R LBCL.

525 Background: Adjuvant endocrine therapy (ET) decreases breast cancer (BC) recurrence and improves overall survival (OS) for patients (pts) with estrogen receptor positive (ER+) BC. Omission of adjuvant ET and nonadherence are major issues contributing to worse clinical outcomes. Recent data suggest that the number of pts who omit adjuvant ET may be increasing in Europe [1]. These data have yet to be evaluated in the U.S. We previously reported data from the National Cancer Database (NCDB) that ET omission was more likely in pts with ER+/HER2+ disease who achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) [2]. Herein we report an updated analysis with a larger cohort designed to examine trends in ET omission over time and the impact on OS in a group of pts at high risk of recurrence. Methods: The NCDB was queried from 2010-2022 for pts with stage I-III ER+BC treated with NAC and surgery. pCR was defined as ypT0, ypN0. Use of adjuvant ET and the impact of adjuvant ET omission on OS in pts with and without pCR were assessed separately based on HER2 status. Adjuvant ET initiation by 1 year was summarized using the cumulative incidence estimate to account for the competing risk of death. OS was analyzed with ET as a time-dependent covariate using multivariable Cox proportional hazards regression. Results: We identified 130,438 pts with ER+BC (78,778 ER+/HER2-, 51,660 ER+/HER2+) who received NAC. Median follow-up was 5 years. Overall, pCR was achieved in 10.0% of ER+/HER2- and 35.9% of ER+/HER2+. On multivariable analysis, ET omission was significantly associated with worse OS in pts with residual disease (RD) [ER+/HER2- (HR 1.80 p<0.001) ER+/HER2+ (HR 1.66 p<0.001] and in those with a pCR [ER+/HER2- (HR 1.38 p=0.002) ER+/HER2+ (HR 1.42 p<0.001)]. Between 2010-2017, adjuvant ET omission was stable, with approximately 10.0% of pts not having initiated ET by 1 year after surgery. The proportion of pts omitting ET overall increased thereafter to 12.9% in 2018, rising to 24.4% in 2022. A sharp increase in ET omission was observed 2021-2022 in ER+/HER2- BC who achieved pCR, with 42.4% omitting ET compared to 25.1% for 2018-2020 and 18.8% for 2010-2017 (p<0.001). Adjuvant ET omission showed more modest but significant increases for other subgroups (p<0.001): ER+/HER2- with RD (8.5% 2010-2017, 12.3% 2018-2020, 18.7% 2021-2022), ER+/HER2+ with pCR (15.1% 2010-2017, 14.0% 2018-2020, 24.4% 2021-2022), and ER+/HER2+ with RD (9.5% 2010-2017, 12.5% 2018-2020, 22.2% 2021-2022). Conclusions: In ER+BC treated with NAC, omission of ET is increasing over time and associated with a higher risk of death, regardless of HER2, RD, or pCR status. These findings have substantial public health implications as they may result in a reversal of the 4-decade improvements in breast cancer mortality. Additional intervention is critical to improve adherence to guidelines. [1] Verreck et al. Breast 2025 [2] Choong et al. SABCS 2022.

Introduction The WHO/UNICEF Nurturing Care Framework (NCF) features five domains necessary for child development—physical/mental health, responsive caregiving, adequate nutrition, security and safety and opportunities for early learning. We explored caregiver perspectives on the NCF in two African settings. Methods Between November 2023 and July 2024, 14 focus group discussions (FGDs) were conducted with caregivers living with and without HIV; eight with mothers in Gaborone, Botswana, and six with mothers and fathers in Nairobi, Kenya. FGDs were stratified by country, sex, HIV status and partnership status. Semi-structured interviews with interactive activities elicited caregiver perspectives on the NCF to identify the most ‘important’, ‘easiest’ and ‘challenging’ domains to fulfil. Thematic analyses identified key themes and compared perspectives. Results Our qualitative study included 101 caregivers, 55 from Kenya (30 mothers, 25 fathers) and 46 mothers from Botswana. Overall, caregivers identified physical/mental health as the ‘most important’ domain to fulfil for children and caregivers, noting how closely tied they were (“ If you have pain, that pain affects your child” ). The ‘most challenging’ domain was adequate nutrition in Botswana and security and safety in Kenya. The ‘easiest’ domains were responsive caregiving in Botswana and opportunities for early learning in Kenya. Kenyan caregivers noted that spiritual nourishment was also critical for well-being but missing from the NCF. Caregivers emphasised the importance of receiving social support with childcare. Caregivers living with HIV expressed similar views compared with caregivers without HIV, but mentioned that social isolation, stigma and treatment disruption impact their ability to provide adequate nurturing care. Conclusions Caregivers face unique parenting challenges depending on cultural environment. HIV disrupts caregivers’ health, which has important implications for raising children within families affected by HIV. Interventions that support caregivers’ abilities to fulfil all NCF domains and address challenges are essential to ensure children reach their developmental potential.

Abstract Background The Global Bipolar Cohort (GBC) was established to identify existing bipolar disorder (BD) cohorts worldwide and foster collaborations focused on descriptive and analytic outcomes relevant to BD. A distributed analytic framework has been implemented to engage multiple sites without the need for central data pooling. This report describes the GBC endeavor and global functional impairment patterns. Cross-cohort comparisons of functional correlates are limited by heterogeneous measures and data-sharing constraints. Large, culturally diverse comparisons are needed to distinguish broadly reproducible correlates from cohort-specific effects. Participating sites completed a 28-item descriptive survey covering diagnostic methods, cognition, genetics, treatment, functioning, and follow-up strategies. We implemented a harmonized local logistic regression model of dichotomized functional outcome and shared summary statistics only. Results We identified 69 cohorts across five continents. Thirty-seven cohorts contributed functional outcome analyses from 17,130 participants. Outcome measures included clinician-rated disability scales and social indicators such as employment and marital status. The proportion classified with poor functioning ranged from 16% to 77% (mean 50%). In 32 of 37 cohorts, the overall regression model significantly explained variance in functioning. Current depressive symptoms were the most robust and reproducible correlate of poor functional outcome: they were assessed in 29 cohorts, significant in 22 (75.8%), ranked among the top three correlates in 22, and were the top-ranked correlates in 19. Associations between depressive burden and poor functioning were observed across clinician-rated disability scales and work or social indicators, and across geographically diverse cohorts. Comorbid substance use disorder and medication-related variables were associated with poorer functioning in subsets of cohorts, whereas sex, ancestry, bipolar subtype, psychosis history, and premorbid IQ showed weak or inconsistent associations. Cognitive measures, available in a minority of regression models, showed modest and non-uniform effects. Conclusions Across heterogeneous international cohorts, current depressive symptom burden emerged as the most consistent correlate of poor functioning in bipolar disorder. These findings replicate earlier multisite work at a larger scale, show that protocol-based distributed analyses can identify reproducible clinical signals without sharing individual-level data, and support prioritizing detection and treatment of depressive symptoms when aiming to improve real-world functioning. Future work should expand longitudinal harmonization and representation of under-studied populations.

OBJECTIVE Overuse of broad-spectrum empiric antimicrobials remains common in children hospitalized with respiratory tract infections (RTI). A negative methicillin-resistant Staphylococcus aureus (MRSA) nasal swab (MNS) polymerase chain reaction (PCR) result has been shown to have a high negative predictive value for MRSA in RTI. In this quality improvement (QI) initiative, we developed a pharmacist-driven approach to reduce the duration of empiric vancomycin for RTI in children. The primary aim was the time to de-escalation of vancomycin, and the secondary aim was the reduction in vancomycin monitoring in patients hospitalized with RTI. METHODS Baseline duration of vancomycin therapy was assessed by conducting a retrospective chart review. After root cause analysis and engaging key stakeholders, an electronic health record OurPractice Advisory (OPA) was implemented, prompting pharmacists to order an MNS PCR during order verification for vancomycin with an RTI indication. RESULTS Preimplementation (01/01/2021 to 08/31/2023) included 89 patients, and 25 postimplementation (09/21/2023 to 05/31/2024). We found a 36% decrease in mean vancomycin duration from 53 to 34 hours after implementation of the pharmacist-driven OPA. Postimplementation, 24% of patients had a vancomycin concentration obtained, compared with 37% preimplementation. No patients were readmitted within 30 days postimplementation, compared with 1 patient preimplementation. CONCLUSIONS This QI initiative provides preliminary data that empiric vancomycin duration in pediatric patients with RTI may be impacted by pharmacist-facing OPA implementation, prompting ordering of MNS PCR at the time of vancomycin verification. This initiative could be replicated at other institutions seeking to reduce empiric vancomycin usage.