Association of inflammatory biomarkers with overall survival in burn patients: a systematic review and meta-analysis.

INTRODUCTION: The inflammatory response to burn injuries can lead to organ dysfunction that ultimately results in increased mortality and morbidity. This meta-analysis was conducted to determine the efficacy of inflammatory biomarkers, including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), procalcitonin (PCT), and C-reactive protein (CRP) as predictive tools of mortality among burn patients. MATERIAL AND METHODS: The biomarker levels of survivors and non-survivors were consolidated according to guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Three main databases were searched electronically: PubMed, Web of Science, and Scopus, on December 8, 2022. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to evaluate and score the methodological quality of the included studies. The standard mean difference (SMD) with a 95% confidence interval (CI) was utilized. RESULTS: Twenty-four studies were included in our systematic review and meta-analysis, (3636 total burn patients), of whom 2878 survived. We found that deceased burn patients had elevated levels of NLR (SMD = 0.60, 95% CI; 0.19-1.00, P < 0.001), CRP (SMD = 0.80, 95% CI; 0.02-1.58, P = 0.04), and PCT (SMD = 0.85, 95% CI; 0.45-1.24, P < 0.001), compared to survivors. However, we found no association between PLR and mortality among burn patients (SMD = 0.00, 95% CI; -0.14-0.15, P < 0.001). In addition, CRP was significantly higher in non-survivors (SMD = 0.80, 95% CI; 0.02-1.58, P =0.04). Similar results were also found about PCT (SMD = 0.85, 95% CI; 0.45-1.24, P < 0.001). When we analyzed the PCT data, collected in the first 24-48 hours, we found similar results; the PCT level was significantly higher in non-survivors in the immediate postinjury-period (SMD = 0.67, 95% CI; 0.31-1.02, P < 0.001). There was no publication bias among studies on the role of NLR in burn (Egger's test P = 0.91). The based cut-off values for NLR (13), CRP (71), and PCT (1.77) yielded sensitivities of 69.2%, 100%, and 93.33%, and specificities of 76%, 72.22%, and 72.22% respectively. DISCUSSION/CONCLUSIONS: PCT is a marker of sepsis, therefore its elevated level is presumably associated with a higher incidence and severity of sepsis among non-survivors. In addition, NLR and CRP are promising biomarkers for predicting and guiding prevention against burn deaths in clinical settings.

Durable transgene expression and efficient re-administration after rAAV2.5T-mediated fCFTRΔR gene delivery to adult ferret lungs.

The dosing interval for effective recombinant adeno-associated virus (rAAV)-mediated gene therapy of cystic fibrosis lung disease remains unknown. Here, we assessed the durability of rAAV2.5T-fCFTRΔR-mediated transgene expression and neutralizing antibody (NAb) responses in lungs of adult wild-type ferrets. Within the first 3 months following rAAV2.5T-fCFTRΔR delivery to the lung, CFTRΔR transgene expression declined ∼5.6-fold and then remained stable to 5 months at ∼26% the level of endogenous CFTR. rAAV NAbs in the plasma and bronchoalveolar lavage fluid (BALF) peaked at 21 days, coinciding with peak ELISpot T cell responses to AAV capsid peptides, after which both responses declined and remained stable at 4-5 months post dosing. Administration of reporter vector rAAV2.5T-gLuc (gaussia luciferase) at 5 months following rAAV2.5T-fCFTRΔR dosing gave rise to similar levels of gLuc expression in the BALF as observed in age-matched reporter-only controls, demonstrating that residual BALF NAbs were functionally insignificant. Notably, the second vector administration led to a 2.6-fold greater ELISpot T cell response and ∼2.3-fold decline in fCFTRΔR mRNA and vector genomes derived from the initial rAAV2.5T-fCFTRΔR administration, suggesting selective destruction of transduced cells from the first vector dose. These findings provide insights into humoral and cellular immune response to rAAV that may be useful for optimizing gene therapy to the cystic fibrosis lung.

Association of neutrophil to lymphocyte ratio with bone mineral density in post-menopausal women: a systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to compare the neutrophil lymphocyte ratio (NLR) levels between women with post-menopausal osteopenia or osteoporosis to those with normal bone mineral density (BMD). METHODS: We used Web of Science, PubMed, and Scopus to conduct a systematic search for relevant publications published before June 19, 2022, only in English language. We reported standardized mean difference (SMD) with a 95% confidence interval (CI). Because a significant level of heterogeneity was found, we used the random-effects model to calculate pooled effects. We used the Newcastle-Ottawa scale for quality assessment. RESULTS: Overall, eight articles were included in the analysis. Post-menopausal women with osteoporosis had elevated levels of NLR compared to those without osteoporosis (SMD = 1.03, 95% CI = 0.18 to 1.88, p = 0.017, I2 = 98%). In addition, there was no difference between post-menopausal women with osteopenia and those without osteopenia in neutrophil lymphocyte ratio (NLR) levels (SMD = 0.58, 95% CI=-0.08 to 1.25, p = 0.085, I2 = 96.8%). However, there was no difference between post-menopausal women with osteoporosis and those with osteopenia in NLR levels (SMD = 0.75, 95% CI=-0.01 to 1.51, p = 0.05, I2 = 97.5%, random-effect model). CONCLUSION: The results of this study point to NLR as a potential biomarker that may be easily introduced into clinical settings to help predict and prevent post-menopausal osteoporosis.