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.

An enhanced recovery after surgery protocol for facial feminization surgery reduces perioperative opioid usage, pain, and hospital stay.

BACKGROUND: Prescription drug misuse in transgender individuals is estimated to be three times higher than that of the general population in the United States, suggesting that opioid-reduction strategies deserve significant consideration in gender-affirming surgeries. In this work, we describe the implementation of an enhanced recovery after surgery (ERAS) protocol to reduce opioid use after facial feminization surgery. METHODS: A total of 79 patients who underwent single-stage facial feminization surgery before (n = 38) or after (n = 41) ERAS protocol implementation were included. Primary outcomes assessed were perioperative opioid consumption (morphine equivalent dose/kilogram, MED/kg), average patient-reported pain scores, and length of hospital stay. Comparisons between groups and multivariable linear regression analyses were conducted to define the contribution of the ERAS protocol to each of the three primary outcomes. RESULTS: Age, body mass index, mental health diagnoses, and length of surgery did not differ between pre-ERAS and ERAS groups. Compared to pre-ERAS patients, patients treated under the ERAS protocol consumed less opioids (median [interquartile range, IQR], 0.8 [0.5-1.1] versus 1.5 [1.0-2.1] MED/kg, p < 0.001), reported lower pain scores (2.5 ± 1.8 versus 3.7 ± 1.6, p = 0.002), and required a shorter hospital stay (median [IQR], 27.3 [26.3-49.8] versus 32.4 [24.8-39.1] h, p < 0.001). When controlling for other contributing variables such as previous gender-affirming surgeries, mental health diagnoses, and length of surgery using multivariable linear regression analyses, ERAS protocol implementation independently predicted reduced opioid use, lower pain scores, and shorter hospital stay after facial feminization surgery. CONCLUSIONS: The current work details an ERAS protocol for facial feminization surgery that reduces perioperative opioid consumption, patient-reported pain scores, and hospital stays.

Association of Patient-Reported Anxiety and Pain After Alveolar Bone Grafting.

OBJECTIVE: To evaluate the role of psychosocial well-being on perioperative pain and opioid use among patients with cleft lip and palate (CLP) undergoing alveolar bone grafting (ABG). DESIGN: Retrospective review. SETTING: Tertiary level craniofacial clinic. PARTICIPANTS: 34 patients with CLP (median age: 11.7 years), including 25 (73.5%) unilateral CLP and 9 (26.5%) bilateral CLP, who underwent ABG from 2015 to 2022. INTERVENTIONS: ABG using iliac crest bone graft. Patients were prospectively administered four patient-reported psychosocial instruments from the Patient-Reported Outcomes Measurement Information System. MAIN OUTCOME MEASURES: Perioperative opioid use in morphine equivalent dosage/kilogram, patient-reported pain scores, and length of hospital stay after ABG. RESULTS: Patient-reported anxiety (r = 0.41, p = 0.02) and depressive symptoms (r = 0.35, p = 0.04) correlated to higher perioperative opioid usage. Multivariable regression models including psychosocial scores, total acetaminophen usage, length of surgery, and other simultaneous surgeries were developed for total opioid usage, patient-reported pain, and length of hospital stay. Patient-reported anxiety was independently predictive of higher perioperative opioid use (ß=0.36, p = 0.01) and higher pain scores (ß=0.39, p = 0.02), but not length of hospital stay. CONCLUSIONS: We identified an association for patient-reported anxiety and perioperative opioid use and pain in a CLP cohort undergoing ABG. Future considerations in preoperative patient and family consultation may be indicated in patients self-reporting higher anxiety in an effort to minimize perioperative opioid usage.

Effect of Gender-affirming Facial Feminization Surgery on Psychosocial Outcomes.

OBJECTIVE: This study investigates the effect of gender-affirming facial feminization surgery (FFS) on psychosocial outcomes in patients with gender dysphoria. BACKGROUND: Comprehensive analyses of psychosocial outcomes after gender-affirming FFS are absent in the literature resulting in a paucity of information on the impact of FFS on quality of life as well as ramifications in health insurance coverage of FFS. METHODS: Scores from 11 validated, quantitative instruments from the Patient-Reported Outcomes Measurement Information System (PROMIS) assessing anxiety, anger, depression, global mental health, global physical health, satisfaction with sex life, positive affect, emotional support, social isolation, companionship, and meaning and purpose. Patients within the preoperative group (pre-FFS) were evaluated >30 days before surgery and patients within the postoperative group (post-FFS) were evaluated ≥10 weeks after surgery. RESULTS: A total of 169 patients [mean (SD) age, 33.5 (10.8) years] were included. Compared with the pre-FFS group (n=107), the post-FFS group (n=62) reported improved scores anxiety (56.8±8.8 vs 60.1±7.9, P =0.01), anger (47.4±7.6 vs 51.2±9.6, P =0.01), depression (52.2±9.2 vs 57.0±8.9, P =0.001), positive affect (46.6±8.9 vs 42.9±8.7, P =0.01), meaning and purpose (49.9±10.7 vs 46.2±10.5, P =0.03), global mental health (46.7±7.6 vs 43.1±9.2, P =0.01), and social isolation (52.2±7.5 vs 55.4±7.4, P =0.01). Multivariable analysis to account for the effects of other gender-affirming surgeries, hormone therapy duration, preexisting mental health diagnoses, socioeconomic disparities, and patient-reported quality of social relationships on psychosocial functioning demonstrated that completion of FFS was independently predictive of improved scores. CONCLUSIONS: Gender-affirming FFS improves the quality of life by multiple psychosocial domains in transfeminine patients.

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.

ß-Catenin Limits Osteogenesis on Regenerative Materials in a Stiffness-Dependent Manner.

Targeted refinement of regenerative materials requires mechanistic understanding of cell-material interactions. The nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) scaffold is shown to promote skull regeneration in vivo without additive exogenous growth factors or progenitor cells, suggesting potential for clinical translation. This work evaluates modulation of MC-GAG stiffness on canonical Wnt (cWnt) signaling. Primary human bone marrow-derived mesenchymal stem cells (hMSCs) are differentiated on two MC-GAG scaffolds (noncrosslinked, NX-MC, 0.3 kPa vs conventionally crosslinked, MC, 3.9 kPa). hMSCs increase expression of activated ß-catenin, the major cWnt intracellular mediator, and the mechanosensitive YAP protein with near complete subcellular colocalization on stiffer MC scaffolds. Overall Wnt pathway inhibition reduces activated ß-catenin and osteogenic differentiation, while elevating BMP4 and phosphorylated Smad1/5 (p-Smad1/5) expression on MC, but not NX-MC. Unlike Wnt pathway downregulation, isolated canonical Wnt inhibition with ß-catenin knockdown increases osteogenic differentiation and mineralization specifically on the stiffer MC. ß-catenin knockdown also increases p-Smad1/5, Runx2, and BMP4 expression only on the stiffer MC material. Thus, while stiffness-induced activation of the Wnt and mechanotransduction pathways promotes osteogenesis on MC-GAG, activated ß-catenin is a limiting agent and may serve as a useful target or readout for optimal modulation of stiffness in skeletal regenerative materials.