Socioeconomic disparities in risk of financial toxicity following elective cardiac operations in the United States.

BACKGROUND: While insurance reimbursements allay a portion of costs associated with cardiac operations, uncovered and additional fees are absorbed by patients. An examination of financial toxicity (FT), defined as the burden of patient medical expenses on quality of life, is warranted. Therefore, the present study used a nationally representative database to demonstrate the association between insurance status and risk of financial toxicity (FT) among patients undergoing major cardiac operations. METHODS: Adults admitted for elective coronary artery bypass grafting (CABG) and isolated or concomitant valve operations were assessed using the 2016-2019 National Inpatient Sample. FT risk was defined as out-of-pocket expenditure >40% of post-subsistence income. Regression models were developed to determine factors associated with FT risk in insured and uninsured populations. To demonstrate the association between insurance status and risk of FT among patients undergoing major cardiac operations. RESULTS: Of an estimated 567,865 patients, 15.6% were at risk of FT. A greater proportion of uninsured patients were at risk of FT (81.3 vs. 14.8%, p<0.001), compared to insured. After adjustment, FT risk among insured patients was not affected by non-income factors. However, Hispanic race (Adjusted Odds Ratio [AOR] 1.60), length of stay (AOR 1.17/day), and combined CABG-valve operations (AOR 2.31, all p<0.05) were associated with increased risk of FT in the uninsured. CONCLUSION: Uninsured patients demonstrated higher FT risk after undergoing major cardiac operation. Hispanic race, longer lengths of stay, and combined CABG-valve operations were independently associated with increased risk of FT amongst the uninsured. Conversely, non-income factors did not impact FT risk in the insured cohort. Culturally-informed reimbursement strategies are necessary to reduce disparities in already financially disadvantaged populations.

Long-term outcomes of sphincter pharyngoplasty in patients with cleft palate.

OBJECTIVE: The purpose of this study was to evaluate long-term outcomes of sphincter pharyngoplasties, including speech outcomes, revision surgeries, and postoperative incidence of obstructive sleep apnea (OSA). DESIGN: Retrospective matched-cohort study SETTING: Two craniofacial centers in Los Angeles, CA PATIENTS: Patients (n = 166) with cleft lip and palate (CLP) or isolated cleft palate (iCP) who underwent sphincter pharyngoplasty from 1992 to 2022 were identified. An age- and diagnosis-matched control group of 67 patients with CLP/iCP without velopharyngeal insufficiency (VPI) was also identified. INTERVENTIONS: The pharyngoplasty group underwent sphincter pharyngoplasty, whereas the non-VPI group had no history of VPI surgery or sphincter pharyngoplasty. MAIN OUTCOME MEASURES: Postoperative speech outcomes, revision surgeries, and incidence of OSA were evaluated. Multivariable regression was used to evaluate independent predictors of OSA. RESULTS: Among the patients in the pharyngoplasty cohort, 63.9% demonstrated improved and sustained speech outcomes after a single pharyngoplasty, with a median postoperative follow-up of 8.8 years (interquartile range [IQR], 3.6-12.0 years). One-third of the patients who underwent pharyngoplasty required a revision surgery, with a median time to primary revision of 3.9 years (IQR, 1.9-7.0 years). OSA rates increased significantly among the pharyngoplasty cohort, from 3% before surgery to 14.5% after surgery (p < 0.001). The average time from sphincter pharyngoplasty to OSA diagnosis was 4.4 ± 2.4 years. Multivariable analysis results indicated that sphincter pharyngoplasty surgery was independently associated with a fourfold increase in OSA (p = 0.03). CONCLUSIONS: Although sphincter pharyngoplasty remains successful in improving long-term speech outcomes, persistent OSA is a sequela that should be monitored beyond the immediate postoperative period.

Duration of Feminizing Hormone Therapy on Facial Fat Volumes.

BACKGROUND: Gender-affirming feminizing hormone therapy induces body fat redistribution. However, the amount and timing of facial fat changes in response to feminizing hormone therapy are unknown, albeit relevant to counseling and surgical planning for facial gender-affirming surgery. In this work, we assessed the influence of feminizing hormone therapy duration on malar and temporal fat volume. METHODS: Malar and temporal fat volumes were compared using computed tomography in transfeminine patients (age 20-29 years, body mass index [BMI] 18.5-24.9) treated with feminizing hormone therapy for <2 years versus ≥2 years. Patients with prior surgical or non-surgical facial soft-tissue interventions were excluded. Multivariable linear regressions evaluated the contribution of hormone therapy duration to malar and temporal fat volumes. RESULTS: 45 patients were included with 30 patients (66.7%) treated with feminizing hormone therapy for ≥2 years and 15 patients (33.3%) treated for <2 years (median[interquartile range, IQR]: 44.5[33.5-65.6] vs. 15.0[11.0-18.0] months, p<0.001). Patients treated with hormone therapy for ≥2 years demonstrated a 1.6-fold greater malar fat volume (5.5[4.2-6.3] vs. 3.4[2.3-4.2] cm 3,p<0.001) and 1.4-fold greater temporal fat volume (2.8[2.4-3.6] cm 3 vs. 2.0[1.7-2.4] cm 3, p=0.01) compared to those treated for <2 years. When accounting for other contributory variables such as BMI, skull size, and total soft-tissue depth in multivariable linear regression models, hormone therapy duration ≥2 years independently predicted higher malar (ß=0.51, p<0.001) and temporal (ß=0.32, p=0.02) fat volumes. CONCLUSIONS: Feminizing hormone therapy increases malar and temporal fat volumes by approximately 2 cm 3 and 0.8 cm 3 for each area, respectively, after 2 years of treatment.

A scoping review of graphene-based biomaterials for in vivo bone tissue engineering.

The growing demand for more efficient materials for medical applications brought together two previously distinct fields: medicine and engineering. Regenerative medicine has evolved with the engineering contributions to improve materials and devices for medical use. In this regard, graphene is one of the most promising materials for bone tissue engineering and its potential for bone repair has been studied by several research groups. The aim of this study is to conduct a scoping review including articles published in the last 12 years (from 2010 to 2022) that have used graphene and its derivatives (graphene oxide and reduced graphene) in preclinical studies for bone tissue regeneration, searching in PubMed/MEDLINE, Embase, Web of Science, Cochrane Central, and clinicaltrials.gov (to confirm no study has started with clinical trial). Boolean searches were performed using the defined key words "bone" and "graphene", and manuscript abstracts were uploaded to Rayyan, a web-tool for systematic and scoping reviews. This scoping review was conducted based on Joanna Briggs Institute Manual for Scoping Reviews and the report follows the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Extension for Scoping Reviews (PRISMA-ScR) statement. After the search protocol and application of the inclusion criteria, 77 studies were selected and evaluated by five blinded researchers. Most of the selected studies used composite materials associated with graphene and its derivatives to natural and synthetic polymers, bioglass, and others. Although a variety of graphene materials were analyzed in these studies, they all concluded that graphene, its derivatives, and its composites improve bone repair processes by increasing osteoconductivity, osteoinductivity, new bone formation, and angiogenesis. Thus, this systematic review opens up new opportunities for the development of novel strategies for bone tissue engineering with graphene.

Therapeutic downregulation of neuronal PAS domain 2 (Npas2) promotes surgical skin wound healing.

Attempts to minimize scarring remain among the most difficult challenges facing surgeons, despite the use of optimal wound closure techniques. Previously, we reported improved healing of dermal excisional wounds in circadian clock neuronal PAS domain 2 (Npas2)-null mice. In this study, we performed high-throughput drug screening to identify a compound that downregulates Npas2 activity. The hit compound (Dwn1) suppressed circadian Npas2 expression, increased murine dermal fibroblast cell migration, and decreased collagen synthesis in vitro. Based on the in vitro results, Dwn1 was topically applied to iatrogenic full-thickness dorsal cutaneous wounds in a murine model. The Dwn1-treated dermal wounds healed faster with favorable mechanical strength and developed less granulation tissue than the controls. The expression of type I collagen, Tgfß1, and α-smooth muscle actin was significantly decreased in Dwn1-treated wounds, suggesting that hypertrophic scarring and myofibroblast differentiation are attenuated by Dwn1 treatment. NPAS2 may represent an important target for therapeutic approaches to optimal surgical wound management.

In vitro assessment of Neuronal PAS domain 2 mitigating compounds for scarless wound healing.

Background: The core circadian gene Neuronal PAS domain 2 (NPAS2) is expressed in dermal fibroblasts and has been shown to play a critical role in regulating collagen synthesis during wound healing. We have performed high throughput drug screening to identify genes responsible for downregulation of Npas2 while maintaining cell viability. From this, five FDA-approved hit compounds were shown to suppress Npas2 expression in fibroblasts. In this study, we hypothesize that the therapeutic suppression of Npas2 by hit compounds will have two effects: (1) attenuated excessive collagen deposition and (2) accelerated dermal wound healing without hypertrophic scarring. Materials and methods: To test the effects of each hit compound (named Dwn1, 2, 3, 4, and 5), primary adult human dermal fibroblasts (HDFa) were treated with either 0, 0.1, 1, or 10 µM of a single hit compound. HDFa behaviors were assessed by picrosirius red staining and quantitative RT-PCR for in vitro collagen synthesis, cell viability assay, in vitro fibroblast-to-myofibroblast differentiation test, and cell migration assays. Results: Dwn1 and Dwn2 were found to significantly affect collagen synthesis and cell migration without any cytotoxicity. Dwn3, Dwn4, and Dwn5 did not affect collagen synthesis and were thereby eliminated from further consideration for their role in mitigation of gene expression or myofibroblast differentiation. Dwn1 also attenuated myofibroblast differentiation on HDFa. Conclusion: Dwn1 and Dwn2 may serve as possible therapeutic agents for future studies related to skin wound healing.