Identification of the RANKL/OPG/RANK signaling pathway as the principal regulator of osteoclast (OC) formation and action began with the discoveries of new members of the tumor necrosis factor (TNF) superfamily (RANKL, OPG, and RANK). Subsequently, genetically altered mice revealed the importance of these molecules for bone biology and helped to show that binding of RANKL to RANK promotes osteoclastogenesis and increases skeletal remodeling, whereas coupling of RANKL to OPG inhibits these processes. The significance of this pathway for humans was then demonstrated by the discoveries that mutations in the genes that encode RANK ( TNFRSF11A ), OPG ( TNFRSF11B ), and RANKL ( TNFSF11 ) explain: (1) several rare mendelian disorders (familial expansile osteolysis, early-onset Paget’s disease of bone, expansile skeletal hyperphosphatasia, and juvenile Paget’s disease) that resemble classic late-onset Paget’s disease of bone featuring enhanced osteoclastogenesis; or (2) forms of osteopetrosis featuring impaired OC formation. This chapter reviews the disease features and genetic bases for these instructive disorders of skeletal biology.
Cell suspension autograft (CSA) is a non-cultured, autologous cellular suspension used in partial-thickness burns or as an adjunct to widely meshed split-thickness skin grafts (STSGs). While CSA has been shown to improve patient outcomes in burn care, literature is limited in highlighting its impact on mortality when used in combination with STSG. This retrospective, matched, case–control study investigates the clinical efficacy of CSA in adult patients with burn injuries admitted to a regional burn center from 2015 to 2023. Patients treated with CSA and STSG (n = 63, “CSA-treated”) were compared against patients treated with STSG alone (n = 126, “non-CSA-treated”). Non-CSA-treated patients were matched in a 2:1 fashion to CSA-treated patients based on third-degree burned TBSA and age. Outcomes included mortality, length of stay (LOS), intensive care unit LOS (ICU LOS), and number of procedures. Multivariate analyses revealed that CSA-treated patients had a significant reduction in mortality (P = .0445) and a 78.9% reduction in odds of death (OR: 0.211) compared to non-CSA-treated patients. Cell suspension autograft-treated patients displayed nonsignificant increases in LOS (P = .0670), ICU LOS (P = .0851), and number of procedures (P = .9084). Selection and chronology bias may partially account for the improved mortality in the CSA-treated group. The nonsignificant increases in LOS, ICU LOS, and number of procedures may be reflective of increased survivorship. These findings demonstrate that CSA enhances survival in patients with burn injuries when used with STSG, warranting further research to confirm these results.
The Department of Agriculture estimates that 1 in 7 Americans live in rural areas. When patients from these regions sustain burn injuries, previous research shows they tend to experience larger burns and higher mortality rates compared to their urban counterparts. This demographic is often older, and experiences more chronic health conditions, factors often associated with frailty. Despite these findings, there is limited research on how frailty impacts burn outcomes among rural populations. This study aims to fill that gap by analyzing the effect of frailty on burn patient outcomes across these different communities. Following IRB approval, a retrospective chart review was conducted for burn patients over 50 admitted to a burn center between January 2021 and December 2022. Data collected included burn injury details, substance use, and patients’ reported zip codes. Rural-Urban Commuting Area (RUCA) codes determined by zip code were used to determine if patients lived in rural or urban areas. Frailty scores were calculated using the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA CFS). Statistical analysis was conducted using SAS software (version 9.4) to perform Chi-square, Fisher Exact, and Wilcoxon 2-sample tests. Results are presented as median (interquartile range). The study analyzed 451 patients with a median age of 62 (IQR 14). Of these, 305 (67.6%) were male, and the median burn size was 5% (IQR 11). A total of 46 (10.2%) died from their injuries. Among the participants, 110 patients (24.4%) resided in rural areas, and the median frailty score was 4 (IQR 2). Rural patients were more likely to be White (20.9% vs. 15.5%, p=0.005). No statistically significant differences were found between rural and urban patients in terms of age (63.5 years [IQR 16] vs. 62 [IQR 13], p=0.18), burn size (6% [IQR 12] vs. 5% [IQR 11], p=0.17), frailty (4 [IQR 1] vs. 4 [IQR 2], p=0.15), or mortality (9.1% vs. 10.6%, p=0.66). There were also no significant differences in length of hospital stay (13 days [IQR 19] vs. 10 days [IQR 18], p=0.37). There were also no differences in positive toxicology screen results (25.5% vs. 24.3%, p=0.19), methamphetamine positivity (24.6% vs. 23.3%, p=0.79), or alcohol use (6.4% vs. 6.1%, p=0.39) between rural and urban patients. This study found no significant burn characteristics or outcomes differences between rural and urban patients. Moreover, rural patients had similar rates of substance use compared to their urban counterparts. Based on these findings, healthcare providers should avoid making assumptions about a patient’s substance use or outcomes based solely on whether they come from a rural or urban area. Burn injury outcomes for patients from rural areas may be comparable to those from urban areas. This challenges previous assumptions and highlights the need for further research to address the specific needs of burn survivors, regardless of community type. N/A
Older adults represent a significant portion of the burn patient population, presenting unique physiological challenges and requiring tailored treatment approaches. Yet, comprehensive data specific to this demographic are limited. The relatively small number of older burn patients at each center makes single-center studies insufficient to address key questions about their care. The development of a multicenter trial group focused on older adult burn patients could yield valuable insights into clinical outcomes, yet funding for such initiatives is often restricted. This study explores the feasibility of creating an unfunded multicenter trial group and conducting a retrospective pilot study to examine clinical trends and outcomes for older adult burn patients. Following IRB approval and the creation of data use agreements, a retrospective pilot study was conducted across twelve burn centers in North America. Each center was tasked with collecting standardized data on burn patients aged 60 and older from January 2017 to December 2019. Data included demographic information, burn characteristics (total body surface area burned, type of burn, etc.), treatment interventions, and outcomes such as mortality, length of hospital stay, and complications. Where possible, data were sourced from each center’s submission to the Burn Care Quality Platform (BCQP). BCQP and additional data were manually entered into a centralized REDCap database managed by one institution. Descriptive statistics of the pilot study are presented. The study included 1,632 older adult burn patients. Median age was 68 years (interquartile range [IQR] 13); 1,095 patients (67%) were male and 1,187 (73%) were White with a median BMI of 27.5 (IQR 7.87). The median burn size was 3.5% total body surface area (IQR 9, range 0-100%). Patients presented a median of 4.68 hours after injury (IQR 15.35), with a median modified Baux score of 76.21 (IQR 20.5). These patients underwent a median of 1 operation (IQR 1), typically 3 days after injury (IQR 6). The median length of hospital stay was 6 days (IQR 13), with an ICU stay of 1 day (IQR 5). In-hospital mortality was 10.4% and the median time to wound healing was 40 days (IQR 48). Creating an unfunded multicenter trial group for older adult burn patients is feasible. The group successfully conducted a retrospective study on care trends for burn-injured older adults. Key factors in the success of this initiative included standardized data collection protocols and strong collaboration between centers. Although challenges remain, this project illustrates the potential for establishing a larger, sustainable multicenter trial group aimed at improving clinical practices and outcomes for older burn patients. No financial compensation or technical support was provided to the participating institutions.
It is common for burn patients to require blood transfusions as part of their treatment. Various transfusion strategies have been studied to manage these needs. Previous studies, including the Transfusion Requirement in Burn Care Evaluation (TRIBE) study, have examined restrictive (transfusing to a hemoglobin ≥ 7g/dL) and liberal (transfusing to a hemoglobin ≥ 10 g/dL) transfusion strategies. They found that both strategies yield similar outcomes in the general population. Older adult burn patients present unique physiological challenges, but these transfusion strategies have not been specifically evaluated in this group. This study aims to assess the impact of age and transfusion strategies on outcomes, including mortality and transfusion requirements. A secondary analysis from the prospective, randomized, multicenter TRIBE study was conducted. Patients were randomized to either a liberal or restrictive treatment strategy. The relationship between age, transfusion strategy, and outcomes was examined. Statistical analyses, including Chi-square or Fisher’s Exact test for categorical variables, Wilcoxon two-sample, or Kruskal-Wallis test for continuous variables, were conducted. Spearman’s Correlation Coefficient was used for comparing two continuous variables, and multivariable regression analysis for mortality was performed. In total, 347 patients with a median age of 41 (Interquartile Range [IQR] = 26) years, 274 men, and 73 women, were analyzed. The median total body surface area burned (TBSA) was 32% (IQR = 22), 23% had inhalation injuries, and 12.4% died during the study period. Mortality was significantly associated with age (Odds Ratio [OR] 1.052, p < 0.0001), but not with liberal or restrictive transfusion strategies (p = 0.53). On multivariate logistic regression analysis, age was independently associated with mortality (OR 1.052, p < 0.0001), while transfusion strategy, controlling for age, was not associated with mortality (p = 0.34). There was no significant correlation between age and the number of total transfusions required or transfusions of each blood product type, regardless of the transfusion strategy. The TRIBE study data, when examined by age, showed no differences in the number or volume of transfusions required for each blood product. Additionally, transfusion strategy was not a predictor of mortality when controlling for age and burn size. Established transfusion triggers seem applicable to older adults, though further research is needed. Previously established transfusion triggers appear applicable to older adult burn patients. N/A
