Fractional CO2 Laser for Burn Scars: A Comparison of Patient Reported Outcomes Between Those With and Without Laser Treatment.

Burn reconstruction outcomes are an area of growing investigation. Although there is evidence of measured physical improvements in scar characteristics after laser treatment, there is little information on patient reported outcomes. The purpose of this study is to compare patient reported outcomes between burn survivors with and without laser treatment. The study included participants in the Burn Model Systems National Database at a single center; participants that received outpatient laser treatment for burn scars were compared to a matched group of burn survivors that did not receive laser. The following outcomes were examined: Satisfaction With Life Scale, Mental and Physical Component Summary of the Veterans Rand Survey, and the PROMIS Pain Intensity Scale. Regression analyses examined the associations between laser treatment and each outcome at 12 and 24 months. The study population included 287 adult burn survivors (65 laser group, 222 control group). The significant differences found between the two groups included: burn size (laser: 14.9, 13.5 SD, control: 8.9, 11.1 SD; p<0.001), insurance type (p=0.036), inhalation injury (laser: 17.2%, control: 2.7%; p<0.001), and ventilator requirement (laser: 27.7%, control: 13.5%; p=0.013). Laser treatment was not associated with any of the outcomes at both follow-up time points. Further research is needed to develop patient reported outcome measures that are more sensitive to the clinical changes experienced by burn survivors receiving laser treatment.

Preliminary Exploration of Long-Term Patient Outcomes After Tracheostomy in Burns: A Burn Model System Study.

INTRODUCTION: Upper airway management is crucial to burn care. Endotracheal intubation is often performed in the setting of inhalation injury, burns of the face and neck, or large burns requiring significant resuscitation. Tracheostomy may be necessary in patients requiring prolonged ventilatory support. This study compares long-term, patient-reported outcomes in burn patients with and without tracheostomy. MATERIALS AND METHODS: Data from the Burn Model System Database, collected from 2013 to 2020, were analyzed. Demographic and clinical data were compared between those with and without tracheostomy. The following patient-reported outcomes, collected at 6-, 12-, and 24-mo follow-up, were analyzed: Veterans RAND 12-Item Health Survey (VR-12), Satisfaction with Life, Community Integration Questionnaire, Patient-Reported Outcomes Measurement Information System 29-Item Profile Measure, employment status, and days to return to work. Regression models and propensity-matched analyses were used to assess the associations between tracheostomy and each outcome. RESULTS: Of 714 patients included in this study, 5.5% received a tracheostomy. Mixed model regression analyses demonstrated that only VR-12 Physical Component Summary scores at 24-mo follow-up were significantly worse among those requiring tracheostomy. Tracheostomy was not associated with VR-12 Mental Component Summary, Satisfaction with Life, Community Integration Questionnaire, or Patient-Reported Outcomes Measurement Information System 29-Item Profile Measure scores. Likewise, tracheostomy was not found to be independently associated with employment status or days to return to work. CONCLUSIONS: This preliminary exploration suggests that physical and psychosocial recovery, as well as the ability to regain employment, are no worse in burn patients requiring tracheostomy. Future investigations of larger scale are still needed to assess center- and provider-level influences, as well as the influences of various hallmarks of injury severity. Nonetheless, this work should better inform goals of care discussions with patients and families regarding the use of tracheostomy in burn injury.

Augmenting Vaccine Efficacy against Delta Variant with 'Mycobacterium-w'-Mediated Modulation of NK-ADCC and TLR-MYD88 Pathways.

Mycobacterium-w (Mw) was shown to boost adaptive natural killer (ANK) cells and protect against COVID-19 during the first wave of the pandemic. As a follow-up of the trial, 50 healthcare workers (HCW) who had received Mw in September 2020 and subsequently received at least one dose of ChAdOx1 nCoV-19 vaccine (Mw + ChAdOx1 group) were monitored for symptomatic COVID-19 during a major outbreak with the delta variant of SARS-CoV-2 (April-June 2021), along with 201 HCW receiving both doses of the vaccine without Mw (ChAdOx1 group). Despite 48% having received just a single dose of the vaccine in the Mw + ChAdOx1 group, only two had mild COVID-19, compared to 36 infections in the ChAdOx1 group (HR-0.46, p = 0.009). Transcriptomic studies revealed an enhanced adaptive NK cell-dependent ADCC in the Mw + ChAdOx1 group, along with downregulation of the TLR2-MYD88 pathway and concomitant attenuation of downstream inflammatory pathways. This might have resulted in robust protection during the pandemic with the delta variant.

The Effect of Distance to Treatment Center on Long-Term Outcomes of Burn Patients.

Geospatial proximity to American Burn Association (ABA)-verified burn centers or self-designated burn care facilities varies across the country. This study evaluates the effect of distance to treatment center on long-term, patient-reported outcomes. Data from the Burn Model System (BMS) National Longitudinal Database were analyzed. Demographic and clinical data were compared between three cohorts stratified by distance to BMS center (<20, 20-49.9, ≥50 miles). Distance to BMS center was calculated as driving distance between discharge and BMS center ZIP code centroids. The following patient-reported outcomes, collected at 12-months follow-up, were examined: Veterans RAND 12-Item Health Survey (VR-12), Satisfaction with Life (SWL) scale, employment status, and days to return to work. Mixed model regression analyses were used to examine the associations between distance to BMS center and each outcome, controlling for demographic and clinical variables. Of 726 patients included in this study, 26.3% and 28.1% were <20 and between 20 and 49.9 miles to a BMS center, respectively; 46.6% were ≥50 miles to a BMS center. Greater distance was associated with white/non-Hispanic race/ethnicity, preinjury employment, flame injury, and larger burn size (P < .001). Regression analyses did not identify significant associations between distance to BMS center and any patient-reported outcomes. This study suggests that patients treated at BMS centers have similar long-term, patient-reported outcomes of physical and psychosocial function, as well as employment, despite centralization of burn care and rehabilitation services. Given a steady decline in the incidence of burn injury, continued concentration of key resources is logical and safe.

Impact of an Immune Modulator Mycobacterium-w on Adaptive Natural Killer Cells and Protection Against COVID-19.

The kinetics of NKG2C+ adaptive natural killer (ANK) cells and NKG2A+inhibitory NK (iNK) cells with respect to the incidence of SARS-CoV-2 infection were studied for 6 months in a cohort of healthcare workers following the administration of the heat-killed Mycobacterium w (Mw group) in comparison to a control group. In both groups, corona virus disease 2019 (COVID-19) correlated with lower NKG2C+ANK cells at baseline. There was a significant upregulation of NKG2C expression and IFN-γ release in the Mw group (p=0.0009), particularly in those with a lower baseline NKG2C expression, along with the downregulation of iNK cells (p<0.0001). This translated to a significant reduction in the incidence and severity of COVID-19 in the Mw group (incidence risk ratio-0.15, p=0.0004). RNA-seq analysis at 6 months showed an upregulation of the ANK pathway genes and an enhanced ANK-mediated antibody-dependent cellular cytotoxicity (ADCC) signature. Thus, Mw was observed to have a salutary impact on the ANK cell profile and a long-term upregulation of ANK-ADCC pathways, which could have provided protection against COVID-19 in a non-immune high-risk population.

Early and Sustained Expansion of Adaptive Natural Killer Cells Following Haploidentical Transplantation and CTLA4Ig-Primed Donor Lymphocyte Infusions Dissociate Graft-versus-Leukemia and Graft-versus-Host Effects.

BACKGROUND: Adaptive or memory natural killer (NK) cells with epigenetic imprints similar to memory T cells have been shown to develop in response to cytomegalovirus (CMV) infection with upregulation of activating receptor NKG2C. These cells have been shown to possess strong anti-tumour efficacy both in-vitro as well as in-vivo. OBJECTIVES: To determine if reconstitution of adaptive NK cells (CD56dimNKG2C+NKG2A-) in patients with advanced leukemia undergoing haploidentical HCT had any impact on disease progression (DP). STUDY DESIGN: The study cohort comprised of 60 patients with advanced acute leukemia, aged 2-65 years, receiving myeloablative PTCy based haploidentical transplantation from CMV seropositive donors, followed by CTLA4Ig-primed donor lymphocyte infusions (DLI). They were evaluated for the kinetics of reconstitution of adaptive NK cells, both phenotypic and functional, at days +30,+60, +90 and at regular intervals, to 3 years of follow-up, in relation to DP. Reconstitution of adaptive NK cells was compared with a retrospective cohort of patients in the same protocol receiving DLI without CTLA4Ig. RESULTS: Non-relapse mortality, acute and chronic GVHD were 5.1%, 10.3% and 14.5%. DP was 17.5% at a median follow-up of 28 months. Adaptive NK cells were significantly higher in patients without DP at days+30, +60 and +90 (p = 0.0001), irrespective of CMV reactivation and remained elevated until 36 months post-HCT. These cells maintained their functional competence as measured by robust interferon-gamma production with higher expressions of KIR, NKG2D and CD57, without any increase in PD1 expression. Grafts from donors with higher adaptive NK cells were associated with a lower risk of DP (p = 0.0001). In multivariate analysis, adaptive NK cell recovery at day +90 had the most favorable impact on DP (HR-0.7). Tregs reconstituted briskly along with the adaptive NK cells and were sustained as well, without compromising the GVL effect. Comparison with a retrospective cohort receiving the same protocol with DLI without CTLA4Ig, showed a superior reconstitution of adaptive NK cells in those receiving CTLA4Ig-DLI (p < 0.0001). CONCLUSION: Our study suggests that myeloablative transplantation from CMV seropositive haploidentical donors augmented with CTLA4Ig-primed DLI might favor early and sustained expansion of functionally competent adaptive NK cells irrespective of CMV reactivation, with a favorable outcome.

Splenic torsion after congenital diaphragmatic hernia repair: case report and review of the literature.

Wandering spleen with torsion, a rare clinical diagnosis, was found to be the cause of chronic abdominal pain in an 11-year-old female with a history of congenital diaphragmatic hernia repaired at three days of age. Doppler ultrasound revealed patent vessels with splenomegaly, and computed tomography (CT) showed an absence of the spleen in the left subphrenic space with torsion at the splenic hilum. Due to the chronicity of pain and risk of ischemia from torsion, open splenopexy with Vicryl mesh was performed. This case report/review of the literature discusses the rarity of this condition, and the importance of timely diagnosis and intervention.

Biplanar flap reconstruction for pressure ulcers: experience in patients with immobility from chronic spinal cord injuries.

BACKGROUND: Surgical therapy for advanced-stage pressure ulcers recalcitrant to healing is a widely accepted practice. The present study examined the incidence of wound recurrence after reconstruction with fasciocutaneous versus combined (biplanar) muscle and fasciocutaneous flaps. METHODS: A retrospective review identified 90 nonambulatory patients with spinal cord injury who underwent reconstruction for persistent decubitus ulcers from 2002 to 2008. Electronic medical records were surveyed for patient comorbidities and postoperative complications. Statistical methods included the Fisher exact test and the Mann-Whitney U test with a 2-sided P value of less than .05. RESULTS: Among 90 patients reviewed, 33% (n = 30) received fasciocutaneous flaps and 66% (n = 60) underwent biplanar reconstruction. Comorbidities were the same between cohorts with the exception of a greater prevalence of diabetes in the biplanar group (27% vs 50%; P < .05). The incidence of recurrence for biplanar flaps (25%) was significantly lower than for fasciocutaneous reconstruction (53%; P < .01). CONCLUSIONS: Biplanar flap reconstruction should be considered for chronically immobilized patients at high risk for recurrent decubitus ulceration.

Efficiency of mammalian selenocysteine incorporation.

Five components have thus far been identified that are necessary for the incorporation of selenocysteine (Sec) into approximately 25 mammalian proteins. Two of these are cis sequences, a SECIS element in the 3'-untranslated region and a Sec codon (UGA) in the coding region. The three known trans-acting factors are a Sec-specific translation elongation factor (eEFSec), the Sec-tRNA(Sec), and a SECIS-binding protein, SBP2. Here we describe a system in which the efficiency of Sec incorporation was determined quantitatively both in vitro and in transfected cells, and in which the contribution of each of the known factors is examined. The efficiency of Sec incorporation into a luciferase reporter system in vitro is maximally 5-8%, which is 6-10 times higher than that in transfected rat hepatoma cells, McArdle 7777. In contrast, the efficiency of Sec incorporation into selenoprotein P in vitro is approximately 40%, suggesting that as yet unidentified cis-elements may regulate differential selenoprotein expression. In addition, we have found that SBP2 is the only limiting factor in rabbit reticulocyte lysate but not in transfected rat hepatoma cells where SBP2 is found to be mostly if not entirely cytoplasmic despite having a strong putative nuclear localization signal. The significance of these findings with regard to the function of known Sec incorporation factors is discussed.