Background: Environmental exposures are common, may impact health, and may cause concerns. There have been calls to improve clinical care for exposure concerns through an “informed care” approach, which designs care in consideration of the patient’s experiences with the concern. Understanding Veterans’ experiences and concerns about military environmental exposures through an “informed care” approach may help with care; however, there is a need to better define the core components of this model of care. Objectives: The current project aimed to define the core components of “exposure-informed care” using a modified Delphi quality improvement study. Research Design: Delphi methodology utilizes expert opinion in a series of rounds and is appropriate to use when there is incomplete knowledge, uncertainty, or lack of evidence on a specific topic. Results: Experts in military environmental exposures (n=35) provided their feedback on the definition of “exposure-informed care.” After 4 rounds of rating, 20 statements were agreed upon as core components of exposure-informed care. Accepted statements about the core components of exposure-informed care were coded into a 6-part framework: (1) use concordant communication, (2) build trust, (3) provide resources and support, (4) assess and document, (5) take professional responsibility, and (6) integrate into care. Conclusions: The 6-part exposure-informed care framework represents experts’ definition of the core components of “exposure-informed care.” Future implementation of exposure-informed care and the impact of each theme are discussed.
Nucleophosmin-1 ( NPM1 ) mutations define a major molecular subtype of acute myeloid leukemia (AML) and is generally associated with favorable prognosis. However, the impact of myelodysplasia-associated mutations (MDSm+) on patient outcomes within this subgroup remains uncertain. We retrospectively analyzed 271 NPM1 -mutated AML patients from three independent cohorts (SWOG, Fred Hutch, and Beat AML) to assess the prognostic significance of MDSm+ and its interaction with age. MDSm+ occurred in 17% of cases, most commonly involving SRSF2 and SF3B1 . Although MDSm+ was associated with inferior overall survival compared to MDSm-in ELN2022 favorable-risk patients (HR 2.0, p =0.008), this effect was largely driven by worse outcomes in older patients ( ≥ 65 years) as older ELN22 favorable-risk patients had poor OS regardless of presence of MDSm+ compared to younger patients. After stratification of patients by age, there was not a significant difference between MDSm+ and MDSm-in either younger patients (HR 0.99, p=0.98) or older patients (HR 1.42, p =0.33). These findings indicate that MDSm+ in NPM1 + AML is not independently associated with adverse risk after adjusting for age and highlight the need for age-adjusted AML risk models.
Central serous chorioretinopathy is an eye disease characterized by fluid buildup under the central retina whose etiology is not well understood. Abnormal choroidal veins in central serous chorioretinopathy patients have been shown to have similarities with varicose veins. To identify potential mechanisms, we analyzed genotype data from 1,477 patients and 455,449 controls in FinnGen. We identified an association for a low-frequency (allele frequency = 0.5%) missense variant (rs113791087) in PTPRB, the gene encoding vascular endothelial protein tyrosine phosphatase (odds ratio=2.85, P = 4.5 × 10-9). This was confirmed in a meta-analysis of 2,452 patients and 865,767 controls from 4 studies (odds ratio=3.06, P = 7.4 × 10-15). Rs113791087 was associated with a 56% higher prevalence of retinal abnormalities (35.3% vs 22.6%, P = 8.0 × 10-4) in 708 UK Biobank participants and, surprisingly, with increased risk of varicose veins (odds ratio=1.31, P = 2.3 × 10-11) and reduced risk of glaucoma (odds ratio=0.82, P = 6.9 × 10-9). Predicted loss-of-function variants in PTPRB, though rare in number, were associated with central serous chorioretinopathy in All of Us (odds ratio=17.09, P = 0.018). These findings highlight the significance of vascular endothelial protein tyrosine phosphatase in diverse ocular and systemic veno-vascular diseases.
Refugees, migrants, asylum seekers, and internally displaced persons face significant barriers to healthcare access, particularly dermatologic services. Infectious skin diseases are especially prevalent in these populations due to multiple intersecting risk factors. This systematic review aimed to identify common infectious dermatologic conditions among these populations, their associated risk factors, and implications for clinical and public health management. A comprehensive literature search was conducted across multiple databases through September 2024, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were eligible if they reported on infectious skin diseases in refugee and migrant populations. Two independent reviewers screened articles, with discrepancies resolved by a third reviewer. Across 63 studies including 5210 individuals, 3647 (70.0%) were diagnosed with infectious skin conditions. Among the 2772 cases specifying disease type, the most common were fungal infections (1084; 39.1%), leprosy (719; 25.9%), and leishmaniasis (397; 14.3%). Other diagnoses included viral skin infections (171; 6.2%), scabies (165; 6.0%), parasitic infections (126; 4.5%), bacterial infections (106; 3.8%), and tuberculid eruptions (4; 0.1%). The study populations represented migrants from 73 countries who relocated to 23 different host nations. Key risk factors included migration from endemic regions, overcrowded living conditions, and poor hygiene. These findings underscore the disproportionate burden of infectious skin disease in displaced populations and the need for targeted screening, culturally appropriate education, and improved access to dermatologic care. Addressing modifiable risk factors is essential to improving outcomes in these vulnerable groups.
4508 Background: Treatment options are limited for ccRCC after disease progression on immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor (VEGF) inhibitors. CD70 is highly expressed on ccRCC. ALLO-316 is an investigational, healthy donor–derived allogeneic CD70 CAR T-cell product designed to recognize and kill both CD70 positive tumor cells and CD70 positive host T cells that drive allorejection. Initial data from the multicenter, phase 1a/b TRAVERSE study (NCT04696731) showed that ALLO-316 had manageable safety and promising antitumor activity. Updated results are presented. Methods: Patients were aged ≥18 years, had advanced ccRCC, ECOG PS of 0 or 1, and disease progression after ICI and VEGF-targeted therapy. After lymphodepletion (LD) with fludarabine and cyclophosphamide ± ALLO-647 (anti-CD52), patients received a single infusion of ALLO-316 following a 3+3 design (40-240 × 10 6 allogeneic CAR+ T cells). Primary end points were incidence of dose-limiting toxicities and adverse events. Objective response rate (ORR) was a secondary end point. Results: Of 44 patients who underwent LD, 39 received ALLO-316, and 38 were evaluable for disease outcome. Median age was 60 years, median of 3 prior therapies (range, 1-8), and 36 (82%) had CD70 positive ccRCC. As of January 2, 2025, median follow-up was 6.8 months (range, 0.8-39.5). Dose-limiting toxicities occurred in 2 patients (autoimmune hepatitis and cardiogenic shock in the setting of multiorgan failure). Treatment-emergent adverse events occurred in 42 patients (96%; grade ≥3, 37 patients [84%]). Grade ≥3 CRS occurred in 1 patient (2%; any grade, 25 patients [57%]), grade ≥3 ICANS in 0 patients (any grade, 4 patients [9%]), and grade ≥3 IEC-HS in 1 patient (2%; any grade, 8 patients [18%]). No GvHD occurred. As previously reported, 3 grade 5 adverse events were related to ALLO-316 (cardiogenic shock, failure to thrive, and sepsis). ORR for all LD regimens was 20% (6/30) overall for patients with CD70 positive tumors (Table). Confirmed ORR was 33% (3/9) for patients with CD70 ≥50% treated with the phase 1b regimen; all confirmed responses were ongoing (2.1, 6.7, and 8.4 months at the data cut-off). Conclusions: After a median follow-up of 6.8 months, a single infusion of ALLO-316 had manageable safety and encouraging antitumor activity in heavily pretreated patients. Further evaluation of ALLO-316 in CD70 positive ccRCC is warranted. Clinical trial information: NCT04696731 . All CD70 positiven = 30 CD70 positive receiving phase 1b regimen a n = 12 CD70 negative or unknownn = 8 Best overall response (CR or PR at any visit), n/N (%) 8/30 (27) 4/12 (33) 0/8 (0) CD70 ≥50 b 8/24 (33) 4/9 (44) – CD70 <50 b 0/6 (0) 0/3 (0) – ORR (confirmed CR or PR), n/N (%) 6/30 (20) 3/12 (25) 0/8 (0) CD70 ≥50 b 6/24 (25) 3/9 (33) – CD70 <50 b 0/6 (0) 0/3 (0) – a ALLO-316 80 × 10 6 CAR+ T cells and LD with fludarabine 30 mg/m 2 + cyclophosphamide 500 mg/m 2 . b IHC-based tumor proportion score.
