Multidose transient transfection of human embryonic kidney 293 cells modulates recombinant adeno-associated virus2/5 Rep protein expression and influences the enrichment fraction of filled capsids.

Recombinant adeno-associated virus (rAAV) is a commonly used in vivo gene therapy vector because of its nonpathogenicity, long-term transgene expression, broad tropism, and ability to transduce both dividing and nondividing cells. However, rAAV vector production via transient transfection of mammalian cells typically yields a low fraction of filled-to-total capsids (~1%-30% of total capsids produced). Analysis of our previously developed mechanistic model for rAAV2/5 production attributed these low fill fractions to a poorly coordinated timeline between capsid synthesis and viral DNA replication and the repression of later phase capsid formation by Rep proteins. Here, we extend the model by quantifying the expression dynamics of total Rep proteins and their influence on the key steps of rAAV2/5 production using a multiple dosing transfection of human embryonic kidney 293 (HEK293) cells. We report that the availability of preformed empty capsids and viral DNA copies per cell are not limiting to the capsid-filling reaction. However, optimal expression of Rep proteins (<240 ± 13 ag per cell) enables enrichment of the filled capsid population (>12% of total capsids/cell) upstream. Our analysis suggests increased enrichment of filled capsids via regulating the expression of Rep proteins is possible but at the expense of per cell capsid titer in a triple plasmid transfection. Our study reveals an intrinsic limitation of scaling rAAV2/5 vector genome (vg) production and underscores the need for approaches that allow for regulating the expression of Rep proteins to maximize vg titer per cell upstream.

A Randomized Controlled Trial of Home-Based Virtual Rehabilitation to Improve Adherence to Prescribed Home Therapy after Burn Injury: A Northwest Regional Burn Model System Trial.

Daily rehabilitation after burn injury is vital for prevention of function-limiting contractures. However, adherence to prescribed therapy following acute burn hospitalization has historically been low and not well-studied. Studies involving virtual reality technology have demonstrated an association with improved functional outcomes in burn therapy. We conducted a five-year randomized controlled trial comparing 12 weeks of a home-based virtual rehabilitation (HBVR) system with standard burn therapy. Our primary outcome was adherence to prescribed home therapy, measured by e-diary self-report. Secondary outcomes included steps walked daily and patient-reported outcomes regarding stiffness, upper extremity function, and mobility. We enrolled 50 subjects, of which 48 provided data for analysis (23 HBVR, 25 control). Overall adherence to prescribed home therapy was low, 37.2% in the HBVR group and 60.0% in the control group. Reasons for non-adherence in the HBVR group included lack of time, engagement, and replacement of therapy with other physical activity. However, some subjects enjoyed HBVR and believed it aided their recovery. There was no difference in daily steps walked between the two groups. Daily walking gradually improved from 3,500 steps per day in the first week after baseline and plateaued at 6,000 steps per day at week five. There were no differences in stiffness, upper extremity function, and mobility between the two groups at baseline and 3-, 6-, and 12-month follow-up. Subjects demonstrated improved upper extremity function and mobility in the first year after discharge that coincided with increasing stiffness.

Precursors to oliguria during major burn resuscitation: An analysis of a prospective observational trial at 5 major US burn centers.

Currently, urine output is the leading variable used to tailor fluid resuscitation in patients with large TBSA burns. However, this metric often lags with respect to resuscitation. Our group sought to identify derangements in variables that precede development of oliguria (<30 cc/hr) that we hypothesize will aid in more efficient resuscitation. We performed a retrospective analysis of 146 adult patients admitted within 4 h of a large TBSA (>20%) burn. We then divided them into two cohorts: those who developed oliguria within 6 h of admission and those who did not. Patients who experienced early oliguria had a higher incidence of invasive SBP < 90 (p = 0.02) or DBP < 40 (p = 0.009), lower minimum bicarbonate level (p = 0.04), more full thickness burns (p = 0.004), and higher TBSA (p = 0.01). More female patients were found in the oliguric group (p = 0.003). Multivariate analysis was used to develop a model to predict development of oliguria. When evaluated together, minimum DBP, sex, TBSA (or percent full thickness burn), and maximum base deficit constituted the most parsimonious model that significantly predicted oliguria (AUC = 0.92). Interestingly, the model lost significance when DBP was omitted, highlighting the importance of diastolic pressure in the development of oliguria.

Implementation of a geriatric care bundle for older adults with acute burns.

BACKGROUND: Frailty and comorbidities are important outcome determinants in older patients (age ≥65) with burns. A Geriatric Burn Bundle (Geri-B) was implemented in 2019 at a regional burn center to standardize care for older adults. Components included frailty screening and protocolized geriatric co-management, malnutrition screening with nutritional support, and geriatric-centered pain regimens. METHODS: This study aimed to qualitatively evaluate the implementation of Geri-B using the Proctor Framework. From June-August 2022, older burn-injured patients, burn nurses, and medical staff providers (attending physicians and advanced practice providers) were surveyed and interviewed. Transcribed interviews were coded and thematically analyzed. From May 2022 to August 2023, the number of inpatient visits aged 65 + with a documented frailty screening was monitored. RESULTS: The study included 23 participants (10 providers, 13 patients). Participants highly rated Geri-B in all implementation domains. Most providers rated geriatric care effectiveness as 'good' or 'excellent' after Geri-B implementation. Providers viewed it as a reminder to tailor geriatric care and a safeguard against substandard geriatric care. Staffing shortages, insufficient protocol training, and learning resources were reported as implementation barriers. Many providers advocated for better bundle integration into the hospital electronic health record (EHR) (e.g., frailty screening tool, automatic admission order sets). Most patients felt comfortable being asked about their functional status with strong patient support for therapy services. The average frailty screening completion rate from May 2022 to August 2023 was 86%. CONCLUSIONS: Geri-B was perceived as valuable for the care of older burn patients and may serve as a framework for other burn centers.

Amphetamine Positivity Prior to Burn Surgery Does not Adversely Affect Intraoperative Outcomes.

The treatment of burn patients using amphetamines is challenging due hemodynamic liabilty and altered physiology. Wide variation exists in the operative timing for this patient population. We hypothesize that burn excision in patients admitted with amphetamine positivity is safe regardless of timing. Data from two verified burn centers between 2017 and 2022 with differing practice patterns in operative timing for amphetamine-positive patients. Center A obtains toxicology only on admission and proceeds with surgery based on hemodynamic status and operative urgency, whereas Center B sends daily toxicology until a negative test results. The primary outcome was the use of vasoactive agents during the index operation, modeled using logistic regression adjusting for burn severity and hospital days to index operation. Secondary outcomes included death and inpatient complications. A total of 270 patients were included, and there were no significant differences in demographics or burn characteristics between centers. Center A screened once and Center B obtained a median of four screens prior to the surgery. The adjusted OR of requiring vasoactive support intraoperatively was not associated with negative toxicology result (P = .821). Having a body surface area burned >20% conferred a significantly higher risk of vasoactive support (adj. OR 13.42 [3.90-46.23], P < .001). Mortality, number of operations, stroke, and hospital length of stay were similar between cohorts. Comparison between two verified burn centers indicates that waiting until a negative amphetamine toxicology result does not impact intraoperative management or subsequent burn outcomes. Serial toxicology tests are unnecessary to guide operative timing of burn patients with amphetamine use.

Can the positive buffer the negative? Testing the impact of protective childhood experiences on adjustment in adults following trauma exposure.

BACKGROUND: It is unclear if protective childhood experiences (PCEs), like emotional support and economic stability, exert influence on adulthood adjustment. Prior research suggests PCEs can promote childhood resilience through increased social connection. In contrast, research has demonstrated potential life-long negative impacts of adverse childhood experiences (ACEs) on psychological health. This study examined the role of PCEs and ACEs in psychological symptoms following potentially traumatic events (PTE) in adults. METHODS: Participants (N = 128) were adults admitted to two Level 1 Trauma Centers following violence, motor-vehicle crashes, or other accidents. Participants reported childhood experiences and completed assessments of depression, PTSD, and social support at one, four, and nine months post-PTE. RESULTS: Structural Equation Modeling was used to simultaneously model PCEs and ACEs as predictors of psychological symptoms over time, with potential mediation through social support. PCEs overall did not directly affect psychological symptoms nor indirectly through social support. However, the emotional support component of PCEs had an indirect effect on psychological symptoms at baseline through social support. ACEs predicted greater psychological symptoms at baseline and over time. CONCLUSION: PCEs consisting of childhood emotional support indirectly promote adjustment in adults after PTEs through initial social support, while ACEs exert direct effects on psychological symptoms.

Implementation evaluation of tiered tele-triage pathways for burn center consultations and transfers.

BACKGROUND: Early transfer to specialized centers improves trauma and burn outcomes; however, overtriage can result in unnecessary burdens to patients, providers, and health systems. Our institution developed novel burn triage pathways in 2016 to improve resource allocation. We evaluated the implementation of these pathways, analyzing trends in adoption, resource optimization, and pathway reliability after implementation. METHODS: Triage pathways consist of transfer nurses (RNs) triaging calls based on review of burn images and clinical history: green pathway for direct outpatient referral, blue pathway for discussion with the on-call provider, red pathway for confirmation of transfer as requested by referring provider, and black pathway for the rapid transfer of severe burns. We used the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework to evaluate implementation. These pathways affected all acute burn referrals to our center from January 2017 to December 2019 (reach). Outcomes of interest were pathway assignment over time (adoption), changes to burn provider call volume (effectiveness), and the concordance of pathway assignment with final disposition (implementation reliability). RESULTS: Transfer RNs triaged 5,272 burn referrals between 2017 and 2019. By January 2018, >98% of referrals were assigned a pathway. In 2018-2019, green pathway calls triaged by RNs reduced calls to burn providers by a mean of 40 (SD, 11) per month. Patients in green/blue pathways were less likely to be transferred, with >85% receiving only outpatient follow-up ( p < 0.001). Use of the lower acuity pathways increased over time, with a concordant decrease in use of the higher acuity pathways. Younger adults, patients referred from Level III to Level V trauma centers and nontrauma hospitals, and patients referred by APPs were less likely to be triaged to higher acuity pathways. CONCLUSION: Implementation of highly adopted, reliable triage pathways can optimize existing clinical resources by task-shifting triage of lower acuity burns to nursing teams. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

American Burn Association Clinical Practice Guidelines on Burn Shock Resuscitation.

This Clinical Practice Guideline (CPG) addresses the topic of acute fluid resuscitation during the first 48 hours following a burn injury for adults with burns ≥20% of the total body surface area (%TBSA). The listed authors formed an investigation panel and developed clinically relevant PICO (Population, Intervention, Comparator, Outcome) questions. A systematic literature search returned 5978 titles related to this topic and after 3 levels of screening, 24 studies met criteria to address the PICO questions and were critically reviewed. We recommend that clinicians consider the use of human albumin solution, especially in patients with larger burns, to lower resuscitation volumes and improve urine output. We recommend initiating resuscitation based on providing 2 mL/kg/% TBSA burn in order to reduce resuscitation fluid volumes. We recommend selective monitoring of intra-abdominal and intraocular pressure during burn shock resuscitation. We make a weak recommendation for clinicians to consider the use of computer decision support software to guide fluid titration and lower resuscitation fluid volumes. We do not recommend the use of transpulmonary thermodilution-derived variables to guide burn shock resuscitation. We are unable to make any recommendations on the use of high-dose vitamin C (ascorbic acid), fresh frozen plasma (FFP), early continuous renal replacement therapy, or vasopressors as adjuncts during acute burn shock resuscitation. Mortality is an important outcome in burn shock resuscitation, but it was not formally included as a PICO outcome because the available scientific literature is missing studies of sufficient population size and quality to allow us to confidently make recommendations related to the outcome of survival at this time.

Impact of Tele-Triage Pathways on Short-Stay Admission after Transfer to a Regional Burn Center for Acute Burn Injury.

BACKGROUND: Regionalized care for burn-injured patients requires accurate triage. In 2016, we implemented a tele-triage system for acute burn consultations. We evaluated resource utilization following implementation, hypothesizing that this system would reduce short-stay admissions and prioritize inpatient care for those with higher burn severity. STUDY DESIGN: We conducted a retrospective study of all transferred patients with acute burn injuries from January 1, 2010 to December 31, 2015, and January 1, 2017 to December 31, 2019. We evaluated the proportions of short-stay admissions (discharges less than 24 hours without operative intervention, ICU admission, or concern for nonaccidental trauma) among patients transferred before (2010 to 2015) and after (2017 to 2019) triage system implementation. Multivariable Poisson regression was used to evaluate factors associated with short-stay admissions. Interrupted time series analysis was used to evaluate the effect of the triage system. RESULTS: There were 4,688 burn transfers (3,244 preimplementation and 1,444 postimplementation) in the study periods. Mean age was higher postimplementation (32 vs 29 years, p < 0.001). Median hospital length of stay (LOS) and ICU LOS were both 1 day higher, more patients underwent operative intervention (19% vs 16%), and median time to first operation was 1 day lower postimplementation. Short-stay admissions decreased from 50% (n = 1,624) to 39% (n = 561), and patients were 17% less likely to have a short-stay admission after implementation (adjusted relative risk [aRR], 0.83; 95% CI, 0.8 to 0.9). Pediatric patients younger than 15 years old composed 43% of all short-stay admissions and were much more likely than adult patients to have a short-stay admission independent of transfer timing (aRR, 2.36; 95% CI, 1.84 to 3.03). CONCLUSIONS: Tele-triage burn transfer center protocols reduced short-stay admissions and prioritized inpatient care for patients with more severe injuries. Pediatric patients remain more likely to have short-stay admission after transfer.

Higher Initial Formula for Resuscitation After Severe Burn Injury Means Higher 24-Hour Volumes.

Initial fluid infusion rates for resuscitation of burn injuries typically use formulas based on patient weight and total body surface area (TBSA) burned. However, the impact of this rate on overall resuscitation volumes and outcomes have not been extensively studied. The purpose of this study was to determine the impact of initial fluid rates on 24-hour volumes and outcomes using the Burn Navigator (BN). The BN database is composed of 300 patients with ≥20% TBSA, >40 kg that were resuscitated utilizing the BN. Four study arms were analyzed based on the initial formula-2 ml/kg/TBSA, 3 ml/kg/TBSA, 4 ml/kg/TBSA or the Rule of Ten. Total fluids infused at 24 hours after admission were compared as well as resuscitation-related outcomes. A total of 296 patients were eligible for analysis. Higher starting rates (4 ml/kg/TBSA) resulted in significantly higher volumes at 24 hours (5.2 ± 2.2 ml/kg/TBSA) than lower rates (2 ml/kg/TBSA resulted in 3.9 ± 1.4 ml/kg/TBSA). No shock was observed in the high resuscitation cohort, whereas the lowest starting rate exhibited a 12% incidence, lower than both the Rule of Ten and 3 ml/kg/TBSA arms. There was no difference in 7-day mortality across groups. Higher initial fluid rates resulted in higher 24-hour fluid volumes. The choice of 2ml/kg/TBSA as initial rate did not result in increased mortality or more complications. An initial rate of 2ml/kg/TBSA is a safe strategy.

Impact of Alcohol and Methamphetamine Use on Burn Resuscitation.

Mortality associated with burn injuries is declining with improved critical care. However, patients admitted with concurrent substance use have increased risk of complications and poor outcomes. The impact of alcohol and methamphetamine use on acute burn resuscitation has been described in single-center studies; however, has not been studied since implementation of computerized decision support for resuscitation. Patients were evaluated based presence of alcohol, with a minimum blood alcohol level of 0.10, or positive methamphetamines on urine drug screen. Fluid volumes and urine output were examined over 48 hours. A total of 296 patients were analyzed. 37 (12.5%) were positive for methamphetamine use, 50 (16.9%) were positive for alcohol use, and 209 (70.1%) with negative for both. Patients positive for methamphetamine received a mean of 5.30 ± 2.63 cc/kg/TBSA, patients positive for alcohol received a mean of 5.41 ± 2.49 cc/kg/TBSA, and patients with neither received a mean of 4.33 ± 1.79 cc/kg/TBSA. Patients with methamphetamine or alcohol use had significantly higher fluid requirements. In the first 6 hours patients with alcohol use had significantly higher urinary output (UO) in comparison to patients with methamphetamine use which had similar output to patients negative for both substances. This study demonstrated that patients with alcohol and methamphetamine use had statistically significantly greater fluid resuscitation requirements compared to patients without. The effects of alcohol as a diuretic align with previous literature. However, patients with methamphetamine lack the increased UO as a cause for their increased fluid requirements.

Temperature Derangement on Admission is Associated With Mortality in Burn Patients-A Nationwide Analysis and Opportunity for Improvement.

Although single-institution studies have described the relationship between hypothermia, burn severity, and complications, there are no national estimates on how temperature on admission impacts hospital mortality. This study aims to evaluate the relationship between admission temperature and complications on a national scale to expose opportunities for improved outcomes. The US National Trauma Data Bank (NTDB) was analyzed between 2007 and 2018. Mortality was modeled using multivariable logistic regression including burn severity variables (% total burn surface area (TBSA), inhalation injury, emergency department (ED) temperature), demographics, and facility variables. Temperature was parsed into three categories: hypothermia (<36.0°C), euthermia (36.0-37.9°C), and hyperthermia (≥38.0°C). A total of 116,796 burn encounters were included of which 77.9% were euthermic, 20.6% were hypothermic and 1.45% were hyperthermic on admission. For every 1.0C drop in body temperature from 36.0°C, mortality increased by 5%. Both hypothermia and hyperthermia were independently associated with increased odds of mortality when controlling for age, gender, inhalation injury, number of comorbidities, and %TBSA burned (p < .001). All temperatures below 36.0°C were significantly associated with increased odds of mortality. Patients with ED temperatures between 32.5 and 33.5°C had the highest odds of mortality (22.0, 95% CI 15.6-31.0, p < .001). ED hypothermia and hyperthermia are independently associated with mortality even when controlling for known covariates associated with inpatient death. These findings underscore the importance of early warming interventions both at the prehospital stage and upon ED arrival. ED temperature could become a quality metric in benchmarking burn centers to improve mortality.

Use of Dermal Regenerative Templates for Burns.

Autologous skin grafting has permitted survival and restoration of function in burn injuries of ever larger total body surface area (TBSA) sizes. However, the goal of replacing "like with like" skin structures is often impossible because full-thickness donor harvesting requires primary closure at the donor site for it to heal. Split-thickness skin grafting (STSG), on the other hand, only harvests part of the dermis at the donor site, allowing it to re-epithelialize on its own. The development of the first dermal regenerative template (DRT) in the late 1970s represented a major advance in tissue engineering that addresses the issue of insufficient dermal replacement when STSGs are applied to the full-thickness defect. This review aims to provide an overview of currently available DRTs in burn management from a clinician's perspective. It focuses on the main strengths and pitfalls of each product and provides clinical pearls based on clinical experience and evidence.

The Battle of the Titans-Comparing Resuscitation Between Five Major Burn Centers Using the Burn Navigator.

The goal of burn resuscitation is to provide the optimal amount of fluid necessary to maintain end-organ perfusion and prevent burn shock. The objective of this analysis was to examine how the Burn Navigator (BN), a clinical decision support tool in burn resuscitation, was utilized across five major burn centers in the United States, using an observational trial of 300 adult patients. Subject demographics, burn characteristics, fluid volumes, urine output, and resuscitation-related complications were examined. Two hundred eighty-five patients were eligible for analysis. There was no difference among the centers on mean age (45.5 ± 16.8 years), body mass index (29.2 ± 6.9), median injury severity score (18 [interquartile range: 9-25]), or total body surface area (TBSA) (34 [25.8-47]). Primary crystalloid infusion volumes at 24 h differed significantly in ml/kg/TBSA (range: 3.1 ± 1.2 to 4.5 ± 1.7). Total fluids, including colloid, drip medications, and enteral fluids, differed among centers in both ml/kg (range: 132.5 ± 61.4 to 201.9 ± 109.9) and ml/kg/TBSA (3.5 ± 1.0 to 5.3 ± 2.0) at 24 h. Post-hoc adjustment using pairwise comparisons resulted in a loss of significance between most of the sites. There was a total of 156 resuscitation-related complications in 92 patients. Experienced burn centers using the BN successfully titrated resuscitation to adhere to 24 h goals. With fluid volumes near the Parkland formula prediction and a low prevalence of complications, the device can be utilized effectively in experienced centers. Further study should examine device utility in other facilities and on the battlefield.

A National Analysis of Discharge Disposition in Older Adults with Burns-Estimating the Likelihood of Independence at Discharge.

Whereas older age predicts higher burn mortality, the impact of age on discharge disposition is less well defined in older adults with burns. This investigation assesses the relationship between older age and discharge disposition after burns in a nationally representative sample. We queried the 2007 to 2015 National Trauma Data Bank for non-fatal burn hospitalizations in older adults. Pre-defined age categories were 55 to 64 years (working-age comparison group), 65 to 74 years (young-old), 75 to 84 years (middle-old), and 85+ years (old-old). Covariables included inhalation injury, comorbidities, burn total body surface area, injury mechanism, and race/ethnicity. Discharge to non-independent living (nursing home, rehabilitation, and other facilities) was the primary outcome. Logistic regression assessed the association between older age and discharge to non-independent living. There were 25,840 non-fatal burn hospitalizations in older adults during the study period. Working-age encounters comprised 53% of admissions, young-old accounted for 28%, middle-old comprised 15% and old-old comprised 4%. Discharge to non-independent living increased with burn TBSA and older age in survivors. Starting in young-old, the majority (65 %) of patients with burns ≥20% TBSA were discharged to non-independent living. Adjusted odd ratios for discharge to non-independent living were 2.0 for young-old, 3.3 for middle-old, and 5.6 for old-old patients, when compared with working-age patients (all P < .001). Older age strongly predicts non-independent discharge after acute burn hospitalization. Matrix analysis of discharge disposition indicates a stepwise rise in discharge to non-independent living with higher age and TBSA, providing a realistic discharge framework for treatment decisions and expectations about achieving independent living after burn hospitalization.

Manufacturing specialized wax esters in plants.

Biologically produced wax esters can fulfil different industrial purposes. These functionalities almost drove the sperm whale to extinction from hunting. After the ban on hunting, there is a niche in the global market for biolubricants with properties similar to spermaceti. Wax esters can also serve as a mechanism for producing insect sex pheromone fatty alcohols. Pheromone-based mating disruption strategies are in high demand to replace the toxic pesticides in agriculture and manage insect plagues threatening our food and fiber reserves. In this study we set out to investigate the possibilities of in planta assembly of wax esters, for specific applications, through transient expression of various mix-and-match combinations of genes in Nicotiana benthamiana leaves. Our synthetic biology designs were outlined in order to pivot plant lipid metabolism into producing wax esters with targeted fatty acyl and fatty alcohols moieties. Through this approach we managed to obtain industrially important spermaceti-like wax esters enriched in medium-chain fatty acyl and/or fatty alcohol moieties of wax esters. Via employment of plant codon-optimized moth acyl-CoA desaturases we also managed to capture unusual, unsaturated fatty alcohol and fatty acyl moieties, structurally similar to moth pheromone compounds, in plant-accumulated wax esters. Comparison between outcomes of different experimental designs identified targets for stable transformation to accumulate specialized wax esters and helped us to recognize possible bottlenecks of such accumulation.

The prognostic significance of HIST1H3B/C and H3F3A K27M mutations in diffuse midline gliomas is influenced by patient age.

INTRODUCTION: Diffuse midline gliomas (DMGs) are infiltrative midline gliomas harboring H3K27M mutations and are generally associated with poor outcomes. H3K27M mutations include mutations in HIST1H3B/C (H3.1), HIST2H3B/D (H3.2), or H3F3A (H3.3) genes. It is still unclear whether these mutations each portend a universally poor prognosis, or if there are any factors which modulate outcome. The main objective of this study was to study overall survival (OS) of H3.1 versus H3.3 K27M-mutant DMGs in pediatric and adult patients. METHODS: PubMed and Web of Science were searched, and we included studies if they have individual patient data of DMGs with available H3K27M genotype. Kaplan-Meier analysis and Cox regression models were used to analyze the survival of H3.1 and H3.3 mutations in each subgroup. RESULTS: We included 26 studies with 102 and 529 H3.1 and H3.3-mutant DMGs, respectively. The H3.1 mutation was more commonly seen in younger age. In pediatric population, H3.3 mutation conferred a shorter survival (median OS of 10.1 vs 14.2 months; p < 0.001) in comparison to H3.1-positive patients, which was further confirmed in the multivariate Cox analysis. Conversely, H3.3 was associated with a prolonged survival in adult patients as compared with H3.1 mutation (median OS of 14.4 vs 1.7 months; p = 0.019). CONCLUSION: We demonstrated that the prognosis of H3.1 and H3.3 K27M mutation in DMG patients is modulated by patient age. Routine H3K27M mutation genotyping in newly diagnosed DMGs may further stratify patients with these difficult tumors.

Appendicular Lean Mass and Frailty among Geriatric Outpatients.

The objective of this observational study was to examine the association between appendicular lean mass and frailty in adults aged 60 years and older. This study was conducted in the Outpatient Department of the National Geriatric Hospital in Hanoi, Vietnam. Appendicular lean mass (kg) was assessed by using Dual energy X-ray absorptiometry scans. Frailty was defined according to Fried's frailty criteria. A total of 560 outpatients were included in the study, with a mean age of 70 years. The prevalence of frailty was 12.0%. Frail patients had significantly lower appendicular lean mass compared with non-frail outpatients (9.6 ± 2.0 kg vs. 11.7 ± 3.1 kg, p<0.001). On multivariable logistic regression models, higher appendicular lean mass was associated with significantly reduced odds for frailty (adjusted OR = 0.74, 95%CI 0.59 - 0.93). These findings suggest that the assessment of appendicular lean mass should be considered in older patients attending outpatient geriatric clinics.