Shriners Hospitals for Children - Northern California

Abstract Radiation-induced skin injury is a common sequela after chemoradiotherapy for squamous cell carcinoma. We provide a case report of treating a moist desquamating wound in the neck with PermeaDerm, consisting of a silicone/nylon bilayer with a bio-coating of gelatin and aloe vera to optimize wound adherence. An 86-year-old man with stage 3 oropharyngeal squamous cell carcinoma was treated with 35 radiation fractions with a total dose of 70 Gray (Gy) to the left tonsil and involved neck nodes and weekly carboplatin. PermeaDerm was applied to the desquamating left neck after the last radiation treatment. The dressing adhered to the moist wound, reducing pain and simplifying wound care. Since the dressing is transparent and can be left in place, it was easy to tell that the wound was healed 6 days later. PermeaDerm is another good option for treating desquamating radiation-induced skin injury. It is easy to apply, transparent, and easy to remove when the wound has re-epithelialized. A great benefit is the dressing is left in place for several days without a need for replacement; the lack of replacement leads to a reduction in pain.

Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into all three germ layers. However, the primary regulators of hPSC cell cycle dynamics remain unclear. To identify novel regulators of hPSC proliferation, transcriptomic profiling of undifferentiated hPSCs and somatic cells was performed via next-generation sequencing. Stomatin-like protein 2 (STOML2) and prohibitin (PHB) were among the upregulated genes in hPSCs and were closely associated with the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway. Temporal expression analysis indicated that STOML2 and PHB decreased during differentiation and increased during reprogramming. Short hairpin RNA (shRNA)-mediated knockdown of STOML2 in hPSCs caused phenotypic changes. Gene expression analyses demonstrated reduced OCT4, NANOG, PHB, and phosphorylated ERK, alongside increased differentiation markers across all three germ layers. The STOML2-PHB axis is essential for maintaining hPSC identity by sustaining ERK/MAPK activity and cell cycle structure. This study identified STOML2 as a key pluripotency regulator and provides new insight into intrinsic stem cell fate control.

Disease-causing genetic variants can be found in a subset of individuals with cerebral palsy (CP), with variants deemed causal of CP having been published for at least 515 genes. We develop a statistical approach that treats CP as a phenotypic feature for which some genetic disorders confer an increased risk. Based on comprehensive literature curation we show that the null hypothesis of no CP association can be rejected for only 89 of the 515 genes. We applied these findings to the analysis of a cohort of 460 children diagnosed with CP in the Shriner Children’s network. We identified pathogenic or likely pathogenic (P/LP) variants in 60 genes in 15.8% of the children. Only 16 of the 60 genes had significant evidence for CP association in our literature analysis. Our results suggest that a stratified approach to attributing causality to genetic variants in CP could support precision genomic medicine for affected individuals.

Children with intoeing gait are at increased risk of tripping and consequent injury, reduced mobility, and psychological issues. Quantification of tripping is needed outside the gait lab during daily life for improved clinical assessment and treatment evaluation and to enrich the database for artificial intelligence (AI) learning. This paper presents the development of a low-cost, wearable tripping monitor to log a child's Tripping Hazard Events (THEs) and steps taken during two weeks of everyday activity. A combination of sensors results in a high probability of THE detection, even during rapid gait, while guarding against false positives and minimizing power and therefore monitor size. A THE is logged when the feet come closer than a predefined threshold during the intoeing foot swing phase. Foot proximity is determined by a Radio Frequency Identification (RFID) reader in "sniffer" mode on the intoeing foot and a target of passive Near-Field Communication (NFC) tags on the contralateral foot. A Force Sensitive Resistor (FSR) in the intoeing shoe sets a time window for sniffing during gait and enables step counting. Data are stored in 15 min epochs. Laboratory testing and an IRB-approved human participant study validated system performance and identified the need for improved mechanical robustness, prompting a redesign of the monitor. A custom Python (version 3.10.13)-based Graphical User Interface (GUI) lets clinicians initiate recording sessions and view time records of THEs and steps. The monitor's flexible design supports broader applications to real-world activity detection.

Abstract Disclosure: D. Levy: None. M. Do: None. J. Zhang: None. C. Olson: None. Z. Ehlinger: None. R. Flojo: None. J. Ku: None. K. Asano: None. D. Diebold: None. H. Afzali: None. A. Wang: None. B. Lu: None. Exosomes, nanoscale extracellular vesicles (EVs), are emerging as versatile platforms for targeted drug delivery and precision medicine. Recent studies suggest that viral envelope glycoproteins (GPs) can integrate into exosomal membranes, enhancing tissue specificity and cellular uptake. However, the molecular mechanisms underlying this process remain poorly understood. To address this gap, we fused viral GPs with green fluorescent protein (GFP) and expressed them in cultured human cells. Using confocal microscopy, we tracked the incorporation of GPs into exosomes. Our findings demonstrate that all five tested viral envelope GPs, derived from both DNA and RNA viruses, successfully integrated into exosomal membranes in transient and stable cell models. Molecular imaging revealed that viral GPs trafficked through endocytic compartments and co-localized with exosomal markers CD63 and XPACK, indicating that they hijacked endogenous exosome biogenesis pathways for integration. Further analysis showed that deletion of the GP ectodomain did not disrupt their incorporation into exosomes, confirming that while the ectodomain governs cell tropism, it is dispensable for exosome integration. Functional assays demonstrated that exosomes modified with vesicular stomatitis virus glycoprotein (VSVG) exhibited significantly enhanced uptake by recipient cells compared to unmodified exosomes, validating their functionalization. Collectively, these findings elucidate the mechanisms by which viral envelope GPs exploit exosome biogenesis pathways for membrane integration. This discovery advances our understanding of the shared biogenesis mechanisms between exosomes and viral-like particles (VLPs) and provides a novel approach for engineering exosome-based drug delivery systems with enhanced targeting and uptake capabilities. Presentation: Monday, July 14, 2025

This Clinical Practice Guideline addresses blood product transfusion among hospitalized acutely burned adults. The Investigator Panel, consisting of the authors of this paper, developed clinically relevant questions in PICO format (Population, Intervention, Comparator, Outcome). These questions informed a systematic literature search which returned 1947 titles, of which 10 articles met the criteria for inclusion and critical review. We strongly recommend the use of a restrictive red blood cell (RBC) transfusion threshold (hemoglobin level ≥ 7g/dL), to reduce the number of blood transfusions administered to adults with burns ≥ 20% total burn surface area (TBSA). We also recommend a restrictive RBC transfusion threshold because the outcomes of infection, length of stay, and mortality are no worse than with liberal RBC transfusion thresholds (hemoglobin level ≥ 10g/dL), while transfusing less blood. We make a weak recommendation to not use recombinant human erythropoietin to reduce the number of RBC transfusions. We make a weak conditional recommendation to consider the use of intraoperative intravenous tranexamic acid during major burn wound excision, to reduce the number of perioperative blood transfusions, preferably in conjunction with performing dynamic viscoelastic testing in this setting. We recommend that in the perioperative period during major burn debridement, thromboelastography and rotation thromboelastometry be used to guide blood product transfusion, to reduce the overall amount of blood product transfusion. No recommendation could be made on the use of a 1:1:1 RBC to fresh frozen plasma to platelet transfusion strategy to decrease the number of RBC transfusions or mortality in adult burn patients undergoing surgical burn wound excision.

Abstract Introduction Point of care for burn survivors has traditionally been the inpatient burn unit. Advances in burn care have resulted in significantly reduced length of stay or allowed survivors to avoid admission. However, an outpatient shift within burn care only emphasizes a growing need for rehabilitation resources. This study surveyed burn centers within the United States (US) to determine current outpatient burn clinic structure and evaluate utilization of burn therapy. Methods A 20-question survey was electronically distributed to burn clinicians at burn centers within the US. Questions included the location of their burn clinic, operational hours, dedicated staff, and utilization of burn therapy services. Chi-square test was used to analyze frequency differences between American Burn Association (ABA) verified and non-verified centers with significance set at < 0.05. Results The survey was completed by representatives of 54 burn centers treating Adults (n=17), Pediatric (n=7), or both (n=30). Burn centers were ABA verified (61%, n=33) and non-verified (39%, n=21) centers. Outpatient clinics included permanently dedicated burn therapists at 65% (n=35) of responding burn centers (OT= 32, PT =28) (Table 1). Respondents reported that therapy services in the outpatient clinics saw “Almost all patients,” 15% (n=8) of the time, while the majority stated therapist saw “Most” (30%, n=16) or “Some” patients (24%, n=13). Only 7 centers report standing therapy orders, while the majority report pre-screening by APPs/physicians (n=43). Only 39% (n=21) reported that reconstructive patients were “Often” referred for therapy. The greatest barriers to outpatient follow up were “distance from burn center”(n=43) and “transportation”(n=30), with 50% of respondents offering transportation support for patients. Verified burn centers were statistically more likely to have either PT or OT dedicated to the burn clinic (79%, p=0.007) than non-verified centers. However, there was no difference in verification status for therapy treating “Most” or “All” patients (50%, p=0.112), and having a dedicated burn therapy treatment space (59%, p=0.067) Conclusions Outpatient Burn Rehabilitation is currently being underutilized, with many centers setting standards below those established for inpatient burn care. Transitioning care to the outpatient setting does not eliminate, or reduce patients’ need for specialized burn therapy. Hospital, physician, and outpatient leaders must consider the rehabilitative needs of burn patients as care is shifted to outpatient and ensure adequate therapy involvement in care. Applicability of Research to Practice Burn centers must prepare to treat an increasing number of burn survivors throughout the entire burn continuum of care. Therapy resources must be optimized within the outpatient setting to match the shift in care toward the ambulatory environment to adequately support burn survivors. Funding for the Study N/A