Citations

Abstract Background The rapid growth of FDA‐licensed and clinical trial cell and gene therapy products is causing significant growing pains for laboratories onboarding and processing these products for clinical use. While clinical programs have traditional and supplemental reimbursement models, many services provided by the laboratories are not directly reimbursed. Compounding this issue is the increasing diversity and complexity of products with unique processing requirements leading to resource‐intensive workflows. Study Design and Methods Our institution developed a three‐tiered cost structure for services provided by the cellular therapy laboratory billed to industry‐sponsored, externally manufactured clinical trials based on the level of start‐up and per product handling complexity. A list of tasks and time required to complete the tasks was recorded to account for the complexity of the specific trial. This data was used to determine the total cost billed to onboard and carry out cell processing and handling tasks by the cellular therapy laboratory to the principal investigator of the clinical trial. Results Our tiered fee structure enabled a more accurate accounting of laboratory personnel time based on the complexity of the clinical trial products, enabling our laboratory to recoup necessary costs. Conclusion A tiered fee structure corresponding to higher levels of onboarding and administrative complexities can more accurately estimate costs to enable cell processing laboratories to remain financially sustainable and continue to deliver cell and gene therapy products to patients.

Objective This study aimed to compare longitudinal cephalometric growth, speech outcomes, and secondary surgeries after 1-stage versus 2-stage palatoplasty in patients with non-syndromic unilateral cleft lip and palate (UCLP). Design Retrospective single-institution cohort study. Setting Tertiary academic craniofacial center. Patients/Participants Sixty-eight patients with non-syndromic UCLP treated between 1992 and 2015 who underwent primary palatal repair and had long-term clinical and radiographic follow-up. Forty-eight underwent 1-stage palatoplasty, and 20 underwent 2-stage palatoplasty. Interventions One-stage palatoplasty versus staged palatoplasty with initial soft palate repair followed by delayed hard palate closure. Main Outcome Measures Longitudinal cephalometric measurements at approximately 10 and 16 years, speech outcomes at 5, 10, 13, and 16 years, oronasal fistula, velopharyngeal insufficiency surgery, and need for continued speech follow-up after age 10. Results Mean follow-up was 15.2 ± 4.4 years. Linear fixed-effects modeling showed significant age-related worsening in sagittal skeletal relationships in both groups, including decreases in sella-nasion-A point angle (SNA), A point-nasion-B point angle (ANB), and Wits appraisal, without significant effects of palatoplasty strategy or age-by-strategy interaction for key sagittal outcomes. Speech outcomes were comparable between groups across all timepoints, including hypernasality, nasal emission, compensatory articulation, intelligibility, and Cleft Audit Protocol for Speech-Augmented (CAPS-A) scores. Rates of secondary velopharyngeal surgery and continued speech follow-up after age 10 did not differ significantly. Oronasal fistula occurred more frequently after 2-stage palatoplasty than 1-stage palatoplasty (30% vs 9%, P = .02). Conclusion One-stage and 2-stage palatoplasty demonstrated similar long-term growth and speech outcomes through adolescence. Two-stage repair was associated with a higher oronasal fistula rate but not greater secondary velopharyngeal or speech burden.

Background: Measles is a highly transmissible virus. A single case can result in significant exposures within a healthcare facility and prompt action is needed to prevent secondary cases. In October 2025, Infection Prevention and Control (IPAC) was notified of a patient being admitted to our facility with recent international travel and symptoms consistent with measles. The patient was unvaccinated and had five healthcare facility visits prior to measles being suspected and subsequently confirmed. Objective: To describe our facility’s effective identification, prioritization, and prophylaxis of individuals exposed to measles. Methods: IPAC leveraged the electronic medical record to identify potentially exposed patients. Patients were quickly assessed for age and immune status, then prioritized and assigned to primary care teams. These teams promptly contacted patients and coordinated PEP administration. Results: Across five encounters, the index patient exposed 539 other patients. Due to delayed notification, our teams had less than four days to administer PEP for those exposed and still within PEP window. PEP administration began within hours of the index case’s positive test and patients received PEP within three days (Table 1). No secondary measles cases occurred within our facility. Conclusion: Timely and coordinated multidisciplinary effort enabled us to rapidly respond to our first measles case and control secondary transmission. Although the index case resulted in a large exposure, patients that were exposed and eligible for PEP were quickly prioritized to prevent secondary transmission.

Background: Advanced planning and adaptable response strategies are essential for preventing measles transmission in healthcare facilities. Objective: To describe a measles management plan and subsequent modifications in response to a cluster of measles cases. Methods: Drawing on previously published work (doi:10.1017/ice.2025.49), the Infection Prevention and Control (IPAC) team initiated a multi-disciplinary team and developed a measles preparedness plan with the following domains: Guidance and education; early detection and testing; isolation and patient movement; contact tracing and exposure management (Table 1). In October 2025, a patient was admitted during their fifth healthcare encounter and was diagnosed with measles. Two family members were later hospitalized with measles. Delayed recognition of the first case prompted enhancements to our preparedness framework (Table 1). Results: The first case resulted in 539 exposed patients. The second resulted in 87 exposures, and the third resulted in no exposure. Despite the extensive exposure, zero secondary measles were reported. Conclusion: Proactive planning enabled rapid response to our first case and controlled secondary transmission. Despite extensive planning, delayed identification of the first case caused significant exposures. As the cluster unfolded, we refined our plan, resulting in zero exposures from the last patient and zero secondary cases, despite over 850 exposures. These efforts may guide other healthcare facilities in improving their measles preparedness and response.

Objective: This post hoc analysis of the CHAMPION-NMOSD trial evaluated the safety and efficacy of ravulizumab in patients with aquaporin-4 antibody-positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) previously exposed or naïve to rituximab (RTX). Methods: Patients received weight-based intravenous ravulizumab with a loading dose followed by maintenance dosing every 8 weeks. Patients were stratified by prior RTX exposure: no RTX exposure (RTX-naïve) vs RTX exposure > 3 months before initiating ravulizumab (RTX-exposed). Key outcomes included treatment-emergent adverse events (TEAEs), serious TEAEs (TESAEs), relapse rates, and vaccination timing from the last RTX dose. Results: Of the 58 patients enrolled, 89.7% were female, with a mean age of 47.4 years, and 21/58 (36.2%) were RTX-exposed. Relapses occurred in 12/21 (57.1%) RTX-exposed patients between their first RTX dose and study entry. The safety profile of ravulizumab was generally similar between RTX-exposed and RTX-naïve groups. Common TEAEs included COVID-19, headache, urinary tract infection, and upper respiratory tract infection. UTIs were more frequent in RTX-exposed individuals. One patient in each group experienced a meningococcal infection. No adjudicated on-trial relapses were reported while on ravulizumab. Conclusions: Following initiation of ravulizumab, RTX-exposed and RTX-naïve patients with AQP4-Ab+ NMOSD achieved sustained disease control and demonstrated a manageable safety profile. Clinical Trial Information: The CHAMPION-NMOSD Trial; ClinicalTrials.gov identifier: NCT04201262 (registered October 06, 2020).

ABSTRACT Patients with neuromyelitis optica spectrum disorder (NMOSD) may experience increased signs and symptoms of their underlying disease when vaccinated against meningococcal disease before receiving complement component 5 inhibitor therapies. This retrospective analysis indicated an overall low relapse incidence (mean [range], 3.3% [0.7%–10.6%]) of physician‐reported relapses occurring within 4 weeks of meningococcal vaccination in those screened in CHAMPION‐NMOSD (NCT04201262), randomized to eculizumab or placebo in PREVENT (NCT01892345), and from the Japanese postmarketing surveillance of eculizumab in patients with anti‐aquaporin‐4 antibody‐positive NMOSD. Further studies are needed to determine if postvaccination relapses are attributable to vaccination or inherent relapse risk among these patients.

498 Background: Radiotherapy-based metastasis-directed therapy (MDT) has emerged as a viable treatment paradigm for oligometastatic clear cell renal cell carcinoma (ccRCC). However, the optimal integration of MDT with frontline immune checkpoint inhibition (ICI) is unclear, especially in light of the M1 NED subgroup analysis of KEYNOTE-564 suggestive of a larger benefit from adjuvant pembrolizumab. Here, we sought to compare the effects of MDT with or without pembrolizumab on clinical and translational outcomes among patients with oligometastatic ccRCC enrolled on two prospective phase II trials. Methods: We undertook an exploratory cohort study of two prospective, single-arm, investigator-initiated phase II trials. The RAPPORT trial (NCT02855203) assigned 30 patients to radiotherapy-based MDT followed by pembrolizumab 200 mg Q3W for eight cycles (MDT+ICI cohort). The MD Anderson trial (NCT03575611) assigned 121 patients to serial MDT (which was almost exclusively radiotherapy-based) without systemic therapy (MDT cohort). For both trials, eligibility criteria consisted of 1 to 5 ccRCC metastatic lesions amenable to MDT. For the present analysis, the primary endpoint was progression-free survival (PFS), prospectively defined by RECIST v1.1 and analyzed using Cox regression. Peripheral blood flow cytometry obtained at baseline, end of MDT in both cohorts (after 1 cycle of ICI in the MDT+ICI cohort), and after completion of all treatment in both cohorts (3 months in the MDT alone cohort and 12 months in the MDT+ICI cohort) was compared using adjusted linear mixed effect models. Results: A total of 150 patients were included for analysis (MDT+ICI: 30; MDT: 120). Median follow-up time was 34 months (MDT+ICI: 28; MDT: 36). At enrollment, the MDT+ICI cohort had a larger number of metastases (median 3 vs 1). Adjusted for prognostic factors, median PFS was 28 months after MDT+ICI and 17 months after MDT (HR, 0.57; 95% CI: 0.31 to 0.998; P = 0.049). Induction of activated systemic CD8 + T cells (ICOS + ) was observed in both cohorts following MDT; however, this increase was greater in the MDT+ICI cohort. Moreover, there was evidence of decreased systemic CD8 + T cell immunosuppression (CD73 + ) following treatment cessation in the MDT+ICI group. Conclusions: To our knowledge, this is the largest prospective analysis of MDT for ccRCC in the ICI era. The addition of maintenance ICI to MDT may improve clinical outcomes in patients with oligometastatic ccRCC. Greater immunomodulatory signals were observed with MDT+ICI, providing a mechanistic link to the clinical benefits. The ASTROs trial (NCT06004336) randomizing patients with oligometastatic ccRCC to MDT with or without pembrolizumab has been initiated to test the hypotheses generated by the present study. Clinical trial information: NCT02855203 and NCT03575611 .