Meta-Analysis and Meta-Regression of Complications and Failures of Autologous Heterotopic Cranial Bone versus Alloplastic Cranioplasties.

BACKGROUND: Fresh autologous cranial bone graft has been traditionally regarded as the ideal cranioplasty material, however long-term comparisons of outcomes with modern alloplastic materials are absent in the literature. In this work, we evaluated complications and failures among cranioplasties performed with fresh, heterotopic, cranial bone graft versus three common alloplastic materials. METHODS: Random-effects meta-analyses of logit-transformed proportions were performed on studies published between 1971-2021 to evaluate complications and failures of cranioplasties performed with fresh, autologous, heterotopic cranial bone, polyetheretherketone (PEEK), polymethylmethacrylate (PMMA), or titanium with a mean follow-up ≥12 months. Generalized mixed model meta-regressions were performed to account for heterogeneity and to evaluate the contributions of moderators to outcomes variables. RESULTS: 1490 patients (mean age 33.9±10.8 years) were included. Pooled, all-cause complications were 6.2% for fresh, heterotopic, autologous cranial bone (95% confidence interval [CI]:2.1-17.0%; I2=55.0%, p=0.02), 18.5% for PEEK (95%CI:14.0-24.0%; I2=0.0%, p=0.58), 26.1% for titanium (95%CI:18.7-35.1%; I2=60.6%, p<0.01), and 28.4% for PMMA (95%CI:12.9-51.5%; I2=88.5%, p<0.01). Pooled all-cause failures were 2.2% for fresh, autologous cranial bone (95%CI:0.4-10.6%; I2=0.0%, p=0.45), 6.3% for PEEK (95%CI:3.2-12.3%; I2=15.5%, p=0.31), 11.4% for titanium (95%CI:6.7-18.8%; I2=60.8%, p<0.01), and 12.7% for PMMA (95%CI:6.9-22.0%; I2=64.8%, p<0.01). Meta-regression models indicated that each alloplastic subtype significantly and independently predicted higher complications, while titanium and PMMA were significant predictors for all-cause failures compared to autologous bone. All three subtypes were predictive of higher cranioplasty failures secondary to infection compared to autologous bone. CONCLUSIONS: Cranioplasties performed with fresh, autologous heterotopic cranial bone grafts resulted in lower complications and failures compared to alloplastic materials.

COVID-19 Pandemic Associated With Increased Self-reported Depressive Symptoms in Patients With Congenital Craniofacial Diagnoses.

OBJECTIVE: The current study investigated the influence of the coronavirus (COVID-19) pandemic on patients with congenital craniofacial diagnoses. METHODS: Patients (n = 66) with craniofacial diagnoses aged between 8 and 17 were prospectively evaluated with longitudinal psychosocial assessments using the anger, anxiety, depressive symptoms, and peer relationships instruments within the pediatric Patient-Reported Outcomes Measurement Information System (PROMIS). The COVID-19 cohort (n = 33) included patients with assessments within 2 years prior to the pandemic (t0) and during the pandemic (t1; March 2020 to March 2021). An age-matched comparison cohort (n = 33) with similar demographics and diagnoses included patients assessed twice over 3 years prior to the pandemic. RESULTS: All PROMIS measures were in the average range clinically for both groups across time points. However, the COVID-19 group reported a significant increase in depressive symptoms during the pandemic (t1) compared to pre-pandemic (t0) scores (48.2 ± 10.1 vs 44.3 ± 9.4, P = .04, d = -0.37), while the comparison group did not demonstrate any differences in psychosocial functioning between t0 and t1. For the COVID-19 cohort, only the pandemic timeframe (r = 0.21, P = .03) was significantly associated with increased depressive symptom scores, and no other sociodemographic or medical variables were associated with depressive symptoms. CONCLUSIONS: Self-reported depressive symptoms increased during the COVID-19 pandemic in patients with congenital craniofacial diagnoses. Longitudinal studies are needed to elucidate whether such changes will be persistent or compound known variables associated with psychosocial functioning.

Current Trends in Breast Reconstruction following Bilateral Prophylactic Mastectomy.

Background: Individuals with genetic susceptibility to breast cancer may pursue bilateral prophylactic mastectomy (BPM) and subsequent breast reconstruction. This study aimed to characterize immediate reconstructive trends following BPM. Methods: The ACS-NSQIP database (2010 -2019) was used to examine differences in demographics and operative outcomes based on breast reconstruction technique following BPM and factors predicting reconstruction type. Results: Of 1945 patients (mean age, 43.8 ± 11.3 years), implant-based reconstruction (IBR) was most frequently (71.8%) performed following BPM. Patients who underwent IBR (n = 1396) were younger (42.6 years, P < 0.001), more likely to be White (P < 0.05), and more likely to have a BMI less than 25 (P < 0.001). Patients who underwent autologous reconstruction (AR) (n = 186, 45.8 years) were more likely to be Black or African American and have a BMI of 25-30. Patients who underwent mastectomy only (MO) without immediate reconstruction (n = 363) were older (47.6 years), more likely to be Asian, and more likely to have a BMI greater than 35. The MO cohort had the highest frequency of diabetes or smoking history. AR was associated with longer operations, longer lengths of stay, and increased complications. Increasing age and BMI were predictive of AR or MO compared to IBR. Smoking was predictive of MO. Conclusion: This is the first large-scale study of genetically susceptible patients who underwent BPM demonstrating a significant relationship between patient demographics, operative outcomes, and immediate reconstruction technique. These results provide valuable insight for surgeons and patients during the shared decision-making process.

Lateral to medial fibro-adipogenic degeneration are greater in infraspinatus than supraspinatus following nerve and tendon injury of murine rotator cuff.

Small animal models of massive tears of the rotator cuff (RC) were introduced a decade ago and have been extensively used to study the pathophysiology of chronically injured RC. Transection of rodent suprascapular nerve and RC tendon results in progressive muscle atrophy, fibrosis and fat accumulation and affect the infraspinatus and supraspinatus muscles similarly to that seen in the setting of massive RC tears in humans. The purpose of this study was to perform a comprehensive and detailed analysis of the kinetics of fibrotic scar and adipose tissue development comparing phenotypic differences between chronically injured infraspinatus and supraspinatus. Automatic mosaic imaging was used to create large image of whole infraspinatus or supraspinatus sectioned area for quantification of spatial heterogeneity of muscle damage. Pathologic changes advanced from the lateral site of transection to the medial region far from the transection site. A prominent, accelerated muscle fibrosis and fat accumulation was measured in injured infraspinatus compared to supraspinatus. Furthermore, adipose tissue occupied significantly larger area than that of fibrotic tissue in both muscles but was greater in infraspinatus within 6 weeks post induction of injury. Our findings confirm that infraspinatus is more susceptible to accelerated chronic degeneration and can be used to identify the physiological functions that distinguish between the response of infraspinatus and supraspinatus in the setting of massive tears. Whether these pathologic differences observed in mice are reflected in humans is one key aspect that awaits clarification.

Aged Mice Demonstrate Greater Muscle Degeneration of Chronically Injured Rotator Cuff.

Massive tears of the rotator cuff (RC) are often associated with progressive and irreversible muscle degeneration due to fibrosis, fatty infiltration, and muscle atrophy. RC tears are common in individuals older than 60 years and the repair of these tears is amongst the most prevalent of orthopedic procedures. However, most current models of this injury are established in young animals, which may not accurately recapitulate the clinical condition. In this study, we used a murine model of massive RC tears to evaluate age-related muscle degeneration following chronic injury. The expression of the fibro-adipogenic genes encoding collagen type III and leptin was higher in aged RC compared with matched injured young tissue at 2 weeks post-injury, and development of fibrosis was accelerated in aged mice within 5 days post-injury. Furthermore, the synthesis of collagens type I and III and fat tissue accumulation were significantly higher in injured RCs of aged mice. Similar frequency of fibro-adipogenic PDGFRß+ PDGFRα+ progenitor cells was measured in non-injured RC of aged and young mice, but PDGFRß+ PDGFRα+ cells contributed to significantly larger fibrotic lesions in aged RCs within 2 weeks post-injury, implying a more robust fibrotic environment in the aged injured muscle. Altogether, these findings demonstrate age-dependent differences in RC response to chronic injury with a more profound fibro-adipogenic change in aged muscles. Clinically, cell therapies for muscular pathologies should not only consider the cell type being transplanted but also the recipient milieu into which these cells are seeded. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:320-328, 2020.

Non-fibro-adipogenic pericytes from human embryonic stem cells attenuate degeneration of the chronically injured mouse muscle.

Massive tears of the rotator cuff (RC) are associated with chronic muscle degeneration due to fibrosis, fatty infiltration, and muscle atrophy. The microenvironment of diseased muscle often impairs efficient engraftment and regenerative activity of transplanted myogenic precursors. Accumulating myofibroblasts and fat cells disrupt the muscle stem cell niche and myogenic cell signaling and deposit excess disorganized connective tissue. Therefore, restoration of the damaged stromal niche with non-fibro-adipogenic cells is a prerequisite to successful repair of an injured RC. We generated from human embryonic stem cells (hES) a potentially novel subset of PDGFR-ß+CD146+CD34-CD56- pericytes that lack expression of the fibro-adipogenic cell marker PDGFR-α. Accordingly, the PDGFR-ß+PDGFR-α- phenotype typified non-fibro-adipogenic, non-myogenic, pericyte-like derivatives that maintained non-fibro-adipogenic properties when transplanted into chronically injured murine RCs. Although administered hES pericytes inhibited developing fibrosis at early and late stages of progressive muscle degeneration, transplanted PDGFR-ß+PDGFR-α+ human muscle-derived fibro-adipogenic progenitors contributed to adipogenesis and greater fibrosis. Additionally, transplanted hES pericytes substantially attenuated muscle atrophy at all tested injection time points after injury. Coinciding with this observation, conditioned medium from cultured hES pericytes rescued atrophic myotubes in vitro. These findings imply that non-fibro-adipogenic hES pericytes recapitulate the myogenic stromal niche and may be used to improve cell-based treatments for chronic muscle disorders.