Variability in Medicaid Coverage for Gender-affirming Surgeries Across U.S. States.

OBJECTIVE: To describe the current Medicaid coverage landscape for gender-affirming surgery across the United States at the procedure level and identify factors associated with coverage. BACKGROUND: Medicaid coverage for gender-affirming surgery differs by state, despite a federal ban on gender identity-based discrimination in health insurance. States that cover gender-affirming surgery also differ in which procedures are included in Medicaid coverage, leading to confusion among patients and clinicians. METHODS: State Medicaid policies in 2021 for gender-affirming surgery were queried for each of the 50 states and the District of Columbia (D.C.). State partisanship, state-level Medicaid protections, and coverage of gender-affirming procedures in 2021 were recorded. The linear correlation between electorate partisanship and total procedures covered was assessed. Pairwise t tests were used to compare coverage based on state partisanship and the presence or absence of state-level Medicaid protections. RESULTS: Medicaid coverage for gender-affirming surgery was covered in 30 states and Washington, D.C. The most commonly covered procedures were genital surgeries and mastectomy (n = 31), followed by breast augmentation (n = 21), facial feminization (n = 12), and voice modification surgery (n = 4). More procedures were covered in Democrat-controlled or leaning states, as well as in states with explicit protections for gender-affirming care in Medicaid coverage. CONCLUSIONS: Medicaid coverage for gender-affirming surgery is patchwork across the United States and is especially poor for facial and voice surgeries. Our study provides a convenient reference for patients and surgeons detailing which gender-affirming surgical procedures are covered by Medicaid within each state.

Epidemiological Predictors of Financial Toxicity in Surgical Burn Injuries: A Multicenter, Longitudinal, Cohort Study.

BACKGROUND: Burns constitute a major global health challenge, causing over 11 million injuries and 300,000 deaths annually and surpassing the economic burden of cervical cancer and HIV combined. Despite this, patient-level financial consequences of burn injuries remain poorly quantified, with a significant gap in data from low- and middle-income countries. In this study, we evaluate financial toxicity in burn patients. METHODS: A prospective, multicenter cohort study was conducted across two tertiary care hospitals in India, assessing 123 adult surgical in-patients undergoing operative interventions for burn injuries. Patient sociodemographic, clinical, and financial data were collected through surveys and electronic records during hospitalization and at 1, 3, and 6 months postoperatively. Out-of-pocket costs (OOPCs) for surgical burn treatment were evaluated during hospitalization. Longitudinal changes in income, employment status, and affordability of basic subsistence needs were assessed at the 1-, 3-, and 6-month postoperative time point. Degree of financial toxicity was calculated using a combination of the metrics catastrophic health expenditure and financial hardship. Development of financial toxicity was compared by sociodemographic and clinical characteristics using logistic regression models. RESULTS: Of the cohort, 60% experienced financial toxicity. Median OOPCs was US$555.32 with the majority of OOPCs stemming from direct nonmedical costs (US$318.45). Cost of initial hospitalization exceeded monthly annual income by 80%. Following surgical burn care, income decreased by US$318.18 within 6 months, accompanied by a 53% increase in unemployment rates. At least 40% of the cohort consistently reported inability to afford basic subsistence needs within the 6-month perioperative period. Significant predictors of developing financial toxicity included male gender (odds ratio, 4.17; 95% confidence interval, 1.25-14.29; P = 0.02) and hospital stays exceeding 20 days (odds ratio, 11.17; 95% confidence interval, 2.11-59.22; P ≤ 0.01). CONCLUSIONS: Surgical treatment for burn injuries is associated with substantial financial toxicity. National and local policies must expand their scope beyond direct medical costs to address direct nonmedical and indirect costs. These include burn care insurance, teleconsultation follow-ups, hospital-affiliated subsidized lodging, and resources for occupational support and rehabilitation. These measures are crucial to alleviate the financial burden of burn care, particularly during the perioperative period.

Outcomes of Dermal Regeneration Templates in Irradiated and Nonirradiated Scalp Defects.

OBJECTIVES: Dermal regeneration templates (DRTs) are frequently used to treat scalp defects. The aim was to compare the time course of healing for DRTs in scalp defects with and without preoperative radiation. METHODS: The authors conducted a retrospective cohort study of DRT-based scalp reconstruction at 2 academic medical centers between 2013 and 2022. Information was collected on demographic variables, comorbidities, medication use, history of radiation, and DRT outcomes. The primary outcome was DRT loss, defined as exposed calvarium or DRT detachment based on postoperative follow-up documentation. Kaplan-Meier survival analysis and multivariable Cox proportional-hazard regressions were used to compare DRT loss in irradiated and nonirradiated defects. Multivariable logistic regressions were used to compare 30-day postoperative complications (infection, hematoma, or seroma) in irradiated and nonirradiated defects. RESULTS: In total, 158 cases were included. Twenty-eight (18%) patients had a preoperative history of radiation to the scalp. The mean follow-up time after DRT placement was 2.6 months (SD: 4.5 mo). The estimated probability of DRT survival at 2 months was 91% (95% CI: 83%-100%) in nonirradiated patients and 65% (95% CI: 48%-88%) in irradiated patients. In the 55 patients with a bony wound base, preoperative head radiation was associated with a higher likelihood of DRT loss (hazard ratio: 11). Half the irradiated defects experienced uncomplicated total wound closure using Integra Wound Matrix Dressing with or without second-stage reconstruction. CONCLUSIONS: Dermal regeneration template can offer durable coverage in nonirradiated scalp defects. Although DRT loss is more likely in irradiated scalp defects, successful DRT-based reconstruction is possible in select cases.

Unmet Social Health Needs as a Driver of Inequitable Outcomes After Surgery: A Cross-sectional Analysis of the National Health Interview Survey.

OBJECTIVE: This study aims to identify opportunities to improve surgical equity by evaluating unmet social health needs by race, ethnicity, and insurance type. BACKGROUND: Although inequities in surgical care and outcomes based on race, ethnicity, and insurance have been well documented for decades, underlying drivers remain poorly understood. METHODS: We used the 2008-2018 National Health Interview Survey to identify adults age 18 years and older who reported surgery in the past year. Outcomes included poor health status (self-reported), socioeconomic status (income, education, employment), and unmet social health needs (food, housing, transportation). We used logistic regression models to progressively adjust for the impact of patient demographics, socioeconomic status, and unmet social health needs on health status. RESULTS: Among a weighted sample of 14,471,501 surgical patients, 30% reported at least 1 unmet social health need. Compared with non-Hispanic White patients, non-Hispanic Black, and Hispanic patients reported higher rates of unmet social health needs. Compared with private insurance, those with Medicaid or no insurance reported higher rates of unmet social health needs. In fully adjusted models, poor health status was independently associated with unmet social health needs: food insecurity [adjusted odds ratio (aOR)=2.14; 95% confidence interval (CI): 1.89-2.41], housing instability (aOR=1.69; 95% CI: 1.51-1.89), delayed care due to lack of transportation (aOR=2.58; 95% CI: 2.02-3.31). CONCLUSIONS: Unmet social health needs vary significantly by race, ethnicity, and insurance, and are independently associated with poor health among surgical populations. As providers and policymakers prioritize improving surgical equity, unmet social health needs are potential modifiable targets.

A Prospective Evaluation of the Quality of Life and Mental Health Implications of Mastectomy Alone on Women in sub-Saharan Africa.

OBJECTIVE: Assess quality of life and mental health implications of mastectomy for breast cancer on sub-Saharan African women. BACKGROUND: Mortality rates amongst women diagnosed with breast cancer in sub-Saharan Africa (SSA) are high, with disparities in survival relative to women in high income countries partly attributed to advanced disease at presentation. Fears of the sequelae of mastectomy are a prominent reason for presentation delays. There is a critical need to better understand the effects of mastectomy on women in SSA to inform preoperative counseling and education for women with breast cancer. METHODS: Women with breast cancer in Ghana and Ethiopia undergoing mastectomy were followed prospectively. Breast related quality-of-life and mental health measures were evaluated preoperatively, 3 and 6 months postoperatively, using BREAST-Q, PHQ-9, and GAD-7. Bivariate and logistic regression analyses evaluated changes in these measures for the total cohort and between sites. RESULTS: A total of 133 women from Ghana and Ethiopia were recruited. The majority of women presented with unilateral disease (99%) and underwent unilateral mastectomy (98%) with axillary lymph node dissection. Radiation was more common in Ghana ( P <0.001). Across most BREAST-Q subscales, women from both countries reported significantly decreased scores at 3 months postoperative. At 6 months, the combined cohort reported decreased scores for breast satisfaction (mean difference, -3.4). Women in both countries reported similar improvements in anxiety and depression scores postoperatively. CONCLUSIONS: Women from Ghana and Ethiopia who underwent mastectomy experienced a decline in breast-related body image while also experiencing decreased levels of depression and anxiety.

Therapeutic Efficacy of Adipose-Derived Stem Cells Versus Bone Marrow Stromal Cells for Irradiated Mandibular Fracture Repair.

BACKGROUND: Mesenchymal stem cells have immense potential in applications of bone healing and regeneration. However, few studies have evaluated the therapeutic efficacy of adipose-derived stem cells (ASCs) and bone marrow stromal cells (BMSCs) in irradiated bone. The purpose of this study is to compare the ability of ASCs versus BMSCs to enhance healing outcomes in a murine model of irradiated mandibular fracture repair. METHODS: Forty-eight isogenic male Lewis rats underwent radiation therapy followed by mandibular osteotomy with intraoperative placement of either ASCs or BMSCs. Animals were killed on postoperative day 40. Mandibles were analyzed for union rate, biomechanical strength, vascularity, and mineralization. Groups were compared at P < 0.05 significance. RESULTS: The ASC and BMSC groups demonstrated 92% and 75% union rates. Compared with the BMSC group, the ASC group demonstrated a trending increase in maximum load ( P = 0.095) on biomechanical strength analysis and a significant increase in vessel number ( P = 0.001), vessel thickness ( P = 0.035), and vessel volume fraction ( P = 0.007) on micro-computed tomography angiography analysis. No significant differences in bone mineralization were identified on micro-computed tomography analysis. CONCLUSION: This study demonstrates the superior therapeutic efficacy of ASCs over BMSCs in irradiated fracture healing as evidenced by union rate, vascular morphometry, and a trend in biomechanical strength. We posit that the robust vascular response induced by ASCs better recapitulates the sequence and synchronicity of physiologic bone healing compared with BMSCs, thereby improving the reliability of irradiated fracture repair.

The Global Macroeconomic Burden of Breast Cancer: Implications for Oncologic Surgery.

OBJECTIVE: In this study, we quantified the global macroeconomic burden of breast cancer to underscore the critical importance of improving access to oncologic surgical care internationally. SUMMARY BACKGROUND DATA: Breast cancer mortality in many low and middle-income countries (LMICs) is dramatically higher than in high-income countries. Prior to identifying solutions, however, it is important to first define the burden of disease. METHODS: Data from the Institute of Health Metrics and Evaluation (2005-2015) were used to assess epidemiologic trends for 194, middle, and low-income countries. Economic burden defined by Welfare Loss (WL) was calculated by measuring disability-adjusted-life-years lost to breast cancer alongside the dollar equivalent of a value of statistical life year and as a function of each country's gross domestic product (GDP). RESULTS: Annual mortality rates among breast cancer patients were significantly greater in LMICs in South Asia (3.06 per 100 women) and Sub-Saharan Africa (2.76 per 100 women), compared with high-income countries like the United States (1.69 per 100 women). From 2005-2015, mortality in South Asia increased by 8.20% and decreased by 6.45% in Sub-Saharan Africa; mortality rates in 2015 were observed as 27.9 per 100,000 in South Asia and 18.61 per 100,000 in Sub-Saharan Africa. Countries in South Asia demonstrated the greatest rise in WL due to breast cancer, from 0.05% to 0.08% of GDP. CONCLUSIONS: The burden of disease and economic impact of breast cancer is intensifying in LMICs. Global efforts to improve access to surgical care for women with breast cancer could reduce mortality and mitigate the social and financial impact of this disease in LMICs.

Coordinating Tissue Regeneration Through Transforming Growth Factor-ß Activated Kinase 1 Inactivation and Reactivation.

Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of transforming growth factor-ß activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by reactivation to elicit differentiation and extracellular matrix production. Although the current regenerative medicine paradigm is centered on the effects of drug treatment ("drug on"), the impact of drug withdrawal ("drug off") implicit in these regimens is unknown. Because current TAK1 inhibitors are unable to phenocopy genetic Tak1 loss, we introduce the dual-inducible COmbinational Sequential Inversion ENgineering (COSIEN) mouse model. The COSIEN mouse model, which allows us to study the response to targeted drug treatment ("drug on") and subsequent withdrawal ("drug off") through genetic modification, was used here to inactivate and reactivate Tak1 with the purpose of augmenting tissue regeneration in a calvarial defect model. Our study reveals the importance of both the "drug on" (Cre-mediated inactivation) and "drug off" (Flp-mediated reactivation) states during regenerative therapy using a mouse model with broad utility to study targeted therapies for disease. Stem Cells 2019;37:766-778.

Short-wave infrared light imaging measures tissue moisture and distinguishes superficial from deep burns.

Existing clinical approaches and tools to measure burn tissue destruction are limited resulting in misdiagnosis of injury depth in over 40% of cases. Thus, our objective in this study was to characterize the ability of short-wave infrared (SWIR) imaging to detect moisture levels as a surrogate for tissue viability with resolution to differentiate between burns of various depths. To accomplish our aim, we constructed an imaging system consisting of a broad-band Tungsten light source; 1,200-, 1,650-, 1,940-, and 2,250-nm wavelength filters; and a specialized SWIR camera. We initially used agar slabs to provide a baseline spectrum for SWIR light imaging and demonstrated the differential absorbance at the multiple wavelengths, with 1,940 nm being the highest absorbed wavelength. These spectral bands were then demonstrated to detect levels of moisture in inorganic and in vivo mice models. The multiwavelength SWIR imaging approach was used to diagnose depth of burns using an in vivo porcine burn model. Healthy and injured skin regions were imaged 72 hours after short (20 seconds) and long (60 seconds) burn application, and biopsies were extracted from those regions for histologic analysis. Burn depth analysis based on collagen coagulation histology confirmed the formation of superficial and deep burns. SWIR multispectral reflectance imaging showed enhanced intensity levels in long burned regions, which correlated with histology and distinguished between superficial and deep burns. This SWIR imaging method represents a novel, real-time method to objectively distinguishing superficial from deep burns.

Epidemiology of facial fractures: incidence, prevalence and years lived with disability estimates from the Global Burden of Disease 2017 study.

BACKGROUND: The Global Burden of Disease Study (GBD) has historically produced estimates of causes of injury such as falls but not the resulting types of injuries that occur. The objective of this study was to estimate the global incidence, prevalence and years lived with disability (YLDs) due to facial fractures and to estimate the leading injurious causes of facial fracture. METHODS: We obtained results from GBD 2017. First, the study estimated the incidence from each injury cause (eg, falls), and then the proportion of each cause that would result in facial fracture being the most disabling injury. Incidence, prevalence and YLDs of facial fractures are then calculated across causes. RESULTS: Globally, in 2017, there were 7 538 663 (95% uncertainty interval 6 116 489 to 9 493 113) new cases, 1 819 732 (1 609 419 to 2 091 618) prevalent cases, and 117 402 (73 266 to 169 689) YLDs due to facial fractures. In terms of age-standardised incidence, prevalence and YLDs, the global rates were 98 (80 to 123) per 100 000, 23 (20 to 27) per 100 000, and 2 (1 to 2) per 100 000, respectively. Facial fractures were most concentrated in Central Europe. Falls were the predominant cause in most regions. CONCLUSIONS: Facial fractures are predominantly caused by falls and occur worldwide. Healthcare systems and public health agencies should investigate methods of all injury prevention. It is important for healthcare systems in every part of the world to ensure access to treatment resources.

Noncultured Minimally Processed Adipose-Derived Stem Cells Improve Radiated Fracture Healing.

Adipose-derived stem cells mitigate deleterious effects of radiation on bone and enhance radiated fracture healing by replacing damaged cells and stimulating angiogenesis. However, adipose-derived stem cell harvest and delivery techniques must be refined to comply with the US Food and Drug Administration restrictions on implantation of cultured cells into human subjects prior to clinical translation. The purpose of this study is to demonstrate the preservation of efficacy of adipose-derived stem cells to remediate the injurious effects of radiation on fracture healing utilizing a novel harvest and delivery technique that avoids the need for cell culture. Forty-four Lewis rats were divided into 4 groups: fracture control (Fx), radiated fracture control (XFx), radiated fracture treated with cultured adipose-derived stem cells (ASC), and radiated fracture treated with noncultured minimally processed adipose-derived stem cells (MP-ASC). Excluding the Fx group, all rats received a fractionated human-equivalent dose of radiation. All groups underwent mandibular osteotomy with external fixation. Following sacrifice on postoperative day 40, union rate, mineralization, and biomechanical strength were compared between groups at P < 0.05 significance. Compared with Fx controls, the XFx group demonstrated decreased union rate (100% vs 20%), bone volume fraction (P = 0.003), and ultimate load (P < 0.001). Compared with XFx controls, the MP-ASC group tripled the union rate (20% vs 60%) and demonstrated statistically significant increases in both bone volume fraction (P = 0.005) and ultimate load (P = 0.025). Compared with the MP-ASC group, the ASC group showed increased union rate (60% vs 100%) and no significant difference in bone volume fraction (P = 0.936) and ultimate load (P = 0.202). Noncultured minimally processed adipose-derived stem cells demonstrate the capacity to improve irradiated fracture healing without the need for cell proliferation in culture. Further refinement of the cell harvest and delivery techniques demonstrated in this report will enhance the ability of noncultured minimally processed adipose-derived stem cells to improve union rate and bone quality, thereby optimizing clinical translation.

Decision Making in Pediatric Plastic Surgery: Autonomy and Shared Approaches.

BACKGROUND: Although shared decision-making is essential to patient-centered healthcare, its role in pediatric plastic surgery remains unclear. The objective of this study was to define the preferred level of involvement in surgical decision-making among children, caregivers, and surgeons. METHODS: The authors surveyed pediatric plastic surgery patients (n = 100) and their caregivers regarding their preferences on child involvement during surgical decision-making. Fleiss' kappa was used to assess agreement between groups. Bivariate Chi-square tests and multinomial logistic regression were used to assess the relationship between decision-making preferences and select demographic factors. RESULTS: Only 34% of children and their caregivers agreed upon their decision-making preferences (k = 0.04). The majority of children (40%) and caregivers (67%) favored shared decision-making between the patient, caregiver, and surgeon. Only 16% of children preferred physician-driven decisions, while 20% of children desired complete autonomy. Children's preferences were significantly associated with their age; the relative risk of children deferring to caregivers or surgeons over a shared approach was lower for adolescents and teens compared to children under 10 years old (relative risk = 0.20; 95% confidence interval: 0.054-0.751; P = 0.02). Caregiver's preferences did not change based on the child's age, but rather were related to the child's gender. Caregivers were more likely to choose the option that gave the child more autonomy when the child was male. CONCLUSIONS: While most caregivers preferred a shared approach to decision-making, children desired greater autonomy, particularly with increasing age. Since there was limited agreement between caregivers and children, surgeons must be cognizant of differing preferences when discussing treatment plans to optimize both patient and parent satisfaction.

Sociodemographic Predictors of Patient Age at Time of Cleft Lip and Palate Repair.

OBJECTIVE: To identify the impact of sociodemographic and health variables on the age at which patients undergo cleft lip repair, cleft palate repair, and primary speech evaluation. DESIGN: A retrospective, noninterventional quality assessment, and quality improvement study was designed. SETTING: This institutional study was performed at Michigan Medicine in Ann Arbor, MI. PATIENTS: All patients born between 2011 and 2014 who received surgical cleft repair, excluded those who were adopted (n = 165). MAIN OUTCOME MEASURE: The age at which patients undergo cleft lip repair, cleft palate repair, and primary speech evaluation. RESULTS: Cleft lip repair was performed significantly later for patients identifying as Asian (18 weeks, P = .01), patients with Child Protective Services contact (19 weeks, P = .01), patients with a significant comorbidity (14 weeks, P = .02), and patients who underwent preliminary lip adhesion surgery (19 weeks, P < .01). Cleft palate repair was performed significantly later for patients identifying racially as Asian (19 weeks, P = .03) and other (22 weeks, P = .03). Preliminary speech and language evaluation were performed significantly later for patients identifying as black (55 weeks, P = .03) and patients diagnosed with an isolated cleft lip (71 weeks, P < .01). CONCLUSIONS: Timing of cleft lip, cleft palate repair, and primary speech and language evaluation are subject to variation which may be predicted by clinically accessible factors. By identifying race, Child Protective Services contact, and care variables as significant predictors of increased patient age at time of intervention, multidisciplinary cleft care teams can proactively allocate patient support resources.

Decision-Making in Cleft-Related Surgery: A Qualitative Analysis of Patients and Caregivers.

OBJECTIVE: Preference-sensitive surgical decisions merit shared decision-making, as decision engagement can reduce decisional conflict and regret. Elective cleft-related procedures are often preference sensitive, and therefore, we sought to better understand decision-making in this population. DESIGN: Semistructured interviews were conducted to elicit qualitative data. A hierarchical codebook was developed through an iterative process in preparation for thematic analysis. Thematic analysis was performed to examine differences between patients and caregivers. SETTING: Multidisciplinary cleft clinic at a tertiary care center. PARTICIPANTS: Patients with cleft lip aged 8 and older (n = 31) and their caregivers (n = 31) were purposively sampled. Inability to converse in English, intellectual disability, or syndromic diagnoses resulted in exclusion. MAIN OUTCOME MEASURES: Preferences surrounding surgical decision-making identified during thematic analysis. RESULTS: Mean patient age was 12.7 (standard deviation: 3.1). Most had unilateral cleft lip and palate (43.8%). Three themes emerged: Insufficient Understanding of Facial Difference and Treatment, Diversity of Surgical Indications, and Barriers to Patient Autonomy. Almost half of caregivers believed their children understood their clefts, but most of these children failed to provide information about their cleft. Although many patients and caregivers acknowledged that surgery addressed function and/or appearance, patients and caregivers exhibited differences regarding the necessity of surgery. Furthermore, a large proportion of patients believed their opinions mattered in decisions, but less than half of caregivers agreed. CONCLUSIONS: Patients with clefts desire to participate in surgical decisions but have limited understanding of their facial difference and surgical indications. Cleft surgeons must educate patients and facilitate shared decision-making.

Characterizing the Circulating Cell Populations in Traumatic Heterotopic Ossification.

Heterotopic ossification (HO) occurs secondary to trauma, causing pain and functional limitations. Identification of the cells that contribute to HO is critical to the development of therapies. Given that innate immune cells and mesenchymal stem cells are known contributors to HO, we sought to define the contribution of these populations to HO and to identify what, if any, contribution circulating populations have to HO. A shared circulation was obtained using a parabiosis model, established between an enhanced green fluorescent protein-positive/luciferase+ donor and a same-strain nonreporter recipient mouse. The nonreporter mouse received Achilles tendon transection and dorsal burn injury to induce HO formation. Bioluminescence imaging and immunostaining were performed to define the circulatory contribution of immune and mesenchymal cell populations. Histologic analysis showed circulating cells present throughout each stage of the developing HO anlagen. Circulating cells were present at the injury site during the inflammatory phase and proliferative period, with diminished contribution in mature HO. Immunostaining demonstrated that most early circulatory cells were from the innate immune system; only a small population of mesenchymal cells were present in the HO. We demonstrate the time course of the participation of circulatory cells in trauma-induced HO and identify populations of circulating cells present in different stages of HO. These findings further elucidate the relative contribution of local and systemic cell populations to HO.

Computed Tomography Evidence of Psoas Muscle Atrophy Without Concomitant Tendon Wasting in Early Sepsis.

BACKGROUND: Morphomic studies have demonstrated a correlation between sarcopenia and clinical outcomes in septic patients. However, tendon morphomics has not yet been studied in this context. The purpose of the present study was to evaluate tendon morphology in septic patients through analytic morphomics. We hypothesized that morphomic analyses would reveal concomitant muscle and tendon wasting in sepsis patients. The results of this study may help to implement different rehabilitation modalities for critically ill patients. MATERIALS AND METHODS: The volume and fat content of bilateral psoas muscles and tendons were measured on abdominal computed tomography scans of 25 ICU septic and 25 control trauma patients admitted to the University of Michigan between 2011 and 2012. Univariate and multivariate analyses were performed to determine the relationship between psoas muscle and tendon morphometric data, and the association with clinical variables such as smoking and comorbidities. RESULTS: Average psoas muscle volume was 12.21 ± 5.6 cm3 for control patients and 9.318 ± 3.3 cm3 in septic patients (P = 0.0023). The average psoas muscle/fat ratio for septic patients was 0.0288 ± 0.071 cm3, compared with 0.0107 ± 0.008 cm3 in the control group (P = 0.075). Average tendon volume in the septic population (0.508 ± 0.191 cm3) was not different than the control cohort (0.493 ± 0.182 cm3) (P = 0.692). CONCLUSIONS: Our results demonstrate significantly smaller psoas muscle volume in septic patients than in age-, gender-, and BMI-matched trauma patients but no demonstrable change in tendon morphology between patient groups. These findings begin to define the boundaries of clinical application within the field of morphomics.

Inhibition of Hif1α prevents both trauma-induced and genetic heterotopic ossification.

Pathologic extraskeletal bone formation, or heterotopic ossification (HO), occurs following mechanical trauma, burns, orthopedic operations, and in patients with hyperactivating mutations of the type I bone morphogenetic protein receptor ACVR1 (Activin type 1 receptor). Extraskeletal bone forms through an endochondral process with a cartilage intermediary prompting the hypothesis that hypoxic signaling present during cartilage formation drives HO development and that HO precursor cells derive from a mesenchymal lineage as defined by Paired related homeobox 1 (Prx). Here we demonstrate that Hypoxia inducible factor-1α (Hif1α), a key mediator of cellular adaptation to hypoxia, is highly expressed and active in three separate mouse models: trauma-induced, genetic, and a hybrid model of genetic and trauma-induced HO. In each of these models, Hif1α expression coincides with the expression of master transcription factor of cartilage, Sox9 [(sex determining region Y)-box 9]. Pharmacologic inhibition of Hif1α using PX-478 or rapamycin significantly decreased or inhibited extraskeletal bone formation. Importantly, de novo soft-tissue HO was eliminated or significantly diminished in treated mice. Lineage-tracing mice demonstrate that cells forming HO belong to the Prx lineage. Burn/tenotomy performed in lineage-specific Hif1α knockout mice (Prx-Cre/Hif1α(fl:fl)) resulted in substantially decreased HO, and again lack of de novo soft-tissue HO. Genetic loss of Hif1α in mesenchymal cells marked by Prx-cre prevents the formation of the mesenchymal condensations as shown by routine histology and immunostaining for Sox9 and PDGFRα. Pharmacologic inhibition of Hif1α had a similar effect on mesenchymal condensation development. Our findings indicate that Hif1α represents a promising target to prevent and treat pathologic extraskeletal bone.

Stem Cells for Bone Regeneration: Current State and Future Directions.

Mesenchymal stem cells (MSCs) are capable of differentiating into osteoblasts, chondrocytes, and adipocytes, each of which is important for musculoskeletal tissue regeneration and repair. Reconstruction and healing of bony defects remains a major clinical challenge. Even as surgical practices advance, some severe cases of bone loss do not yield optimal recovery results. New techniques involving implantation of stem cells and tissue-engineered scaffolds are being developed to help improve bone and cartilage repair. The invasiveness and low yield of harvesting MSCs from the bone marrow (BMSCs) has led to the investigation of alternatives, including adipose-derived mesenchymal stem cells (ASCs). A review of the literature yielded several studies concerning the use of BMSCs and ASCs for the treatment of bone defects in both in vitro and in vivo models. Although both ASCs and BMSCs have demonstrated bone regenerative capabilities, BMSCs have outperformed ASCs in vitro. Despite these in vitro study findings, in vivo study results remain variable. Analysis of the literature seems to conclude there is no significant difference between bone regeneration using ASCs or BMSCs in vivo. Improved study design and standardization may enhance the application of these studies to patient care in the clinical setting.