Large Animal Translational Validation of 3 Mitral Valve Repair Operations for Mitral Regurgitation Using a Mitral Valve Prolapse Model: A Comprehensive In Vivo Biomechanical Engineering Analysis.

BACKGROUND: Various mitral repair techniques have been described. Though these repair techniques can be highly effective when performed correctly in suitable patients, limited quantitative biomechanical data are available. Validation and thorough biomechanical evaluation of these repair techniques from translational large animal in vivo studies in a standardized, translatable fashion are lacking. We sought to evaluate and validate biomechanical differences among different mitral repair techniques and further optimize repair operations using a large animal mitral valve prolapse model. METHODS: Male Dorset sheep (n=20) had P2 chordae severed to create the mitral valve prolapse model. Fiber Bragg grating force sensors were implanted to measure chordal forces. Ten sheep underwent 3 randomized, paired mitral valve repair operations: neochord repair, nonresectional leaflet remodeling, and triangular resection. The other 10 sheep underwent neochord repair with 2, 4, and 6 neochordae. Data were collected at baseline, mitral valve prolapse, and after each repair. RESULTS: All mitral repair techniques successfully eliminated regurgitation. Compared with mitral valve prolapse (0.54±0.18 N), repair using neochord (0.37±0.20 N; P=0.02) and remodeling techniques (0.30±0.15 N; P=0.001) reduced secondary chordae peak force. Neochord repair further decreased primary chordae peak force (0.21±0.14 N) to baseline levels (0.20±0.17 N; P=0.83), and was associated with lower primary chordae peak force compared with the remodeling (0.34±0.18 N; P=0.02) and triangular resectional techniques (0.36±0.27 N; P=0.03). Specifically, repair using 2 neochordae resulted in higher peak primary chordal forces (0.28±0.21 N) compared with those using 4 (0.22±0.16 N; P=0.02) or 6 neochordae (0.19±0.16 N; P=0.002). No difference in peak primary chordal forces was observed between 4 and 6 neochordae (P=0.05). Peak forces on the neochordae were the lowest using 6 neochordae (0.09±0.11 N) compared with those of 4 neochordae (0.15±0.14 N; P=0.01) and 2 neochordae (0.29±0.18 N; P=0.001). CONCLUSIONS: Significant biomechanical differences were observed underlying different mitral repair techniques in a translational large animal model. Neochord repair was associated with the lowest primary chordae peak force compared to the remodeling and triangular resectional techniques. Additionally, neochord repair using at least 4 neochordae was associated with lower chordal forces on the primary chordae and the neochordae. This study provided key insights about mitral valve repair optimization and may further improve repair durability.

Biomechanical engineering analysis of neochordae length's impact on chordal forces in mitral repair.

OBJECTIVES: Artificial neochordae implantation is commonly used for mitral valve (MV) repair. However, neochordae length estimation can be difficult to perform. The objective was to assess the impact of neochordae length changes on MV haemodynamics and neochordal forces. METHODS: Porcine MVs (n = 6) were implanted in an ex vivo left heart simulator. MV prolapse (MVP) was generated by excising at least 2 native primary chordae supporting the P2 segments from each papillary muscle. Two neochordae anchored on each papillary muscle were placed with 1 tied to the native chord length (exact length) and the other tied with variable lengths from 2× to 0.5× of the native length (variable length). Haemodynamics, neochordal forces and echocardiography data were collected. RESULTS: Neochord implantation repair successfully eliminated mitral regurgitation with repaired regurgitant fractions of approximately 4% regardless of neochord length (P < 0.01). Leaflet coaptation height also significantly improved to a minimum height of 1.3 cm compared with that of MVP (0.9 ± 0.4 cm, P < 0.05). Peak and average forces on exact length neochordae increased as variable length neochordae lengths increased. Peak and average forces on the variable length neochordae increased with shortened lengths. Overall, chordal forces appeared to vary more drastically in variable length neochordae compared with exact length neochordae. CONCLUSIONS: MV regurgitation was eliminated with neochordal repair, regardless of the neochord length. However, chordal forces varied significantly with different neochord lengths, with a preferentially greater impact on the variable length neochord. Further validation studies may be performed before translating to clinical practices.

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.

Biomechanics and clinical outcomes of various conduit configurations in valve sparing aortic root replacement.

Background: Several conduit configurations, such as straight graft (SG), Valsalva graft (VG), anticommissural plication (ACP), and the Stanford modification (SMOD) technique, have been described for the valve-sparing aortic root replacement (VSARR) procedure. Prior ex vivo studies have evaluated the impact of conduit configurations on root biomechanics, but the mock coronary artery circuits used could not replicate the physical properties of native coronary arteries. Moreover, the individual leaflet's biomechanics, including the fluttering phenomenon, were unclear. Methods: Porcine aortic roots with coronary arteries were explanted (n=5) and underwent VSARR using SG, VG, ACP, and SMOD for evaluation in an ex vivo left heart flow loop simulator. Additionally, 762 patients who underwent VSARR from 1993 through 2022 at our center were retrospectively reviewed. Analysis of variance was performed to evaluate differences between different conduit configurations, with post hoc Tukey's correction for pairwise testing. Results: SG demonstrated lower rapid leaflet opening velocity compared with VG (P=0.001) and SMOD (P=0.045) in the left coronary cusp (LCC), lower rapid leaflet closing velocity compared with VG (P=0.04) in the right coronary cusp (RCC), and lower relative opening force compared with ACP (P=0.04) in the RCC. The flutter frequency was lower in baseline compared with VG (P=0.02) and in VG compared with ACP (P=0.03) in the LCC. Left coronary artery mean flow was higher in SG compared with SMOD (P=0.02) and ACP (P=0.05). Clinically, operations using SG compared with sinus-containing graft was associated with shorter aortic cross-clamp and cardiopulmonary bypass time (P<0.001, <0.001). Conclusions: SG demonstrated hemodynamics and biomechanics most closely recapitulating those from the native root with significantly shorter intraoperative times compared with repair using sinus-containing graft. Future in vivo validation studies as well as correlation with comprehensive, comparative clinical study outcomes may provide additional invaluable insights regarding strategies to further enhance repair durability.

Advances in 3D Bioprinting: Techniques, Applications, and Future Directions for Cardiac Tissue Engineering.

Cardiovascular diseases are the leading cause of morbidity and mortality in the United States. Cardiac tissue engineering is a direction in regenerative medicine that aims to repair various heart defects with the long-term goal of artificially rebuilding a full-scale organ that matches its native structure and function. Three-dimensional (3D) bioprinting offers promising applications through its layer-by-layer biomaterial deposition using different techniques and bio-inks. In this review, we will introduce cardiac tissue engineering, 3D bioprinting processes, bioprinting techniques, bio-ink materials, areas of limitation, and the latest applications of this technology, alongside its future directions for further innovation.

Comparing scrotoplasty complication rates in transgender and cisgender men: An ACS NSQIP study.

While masculinizing gender-affirming genital surgeries may include scrotoplasty, there has been limited research on the safety and outcomes of scrotoplasty among transgender men. We compared scrotoplasty complication rates between cisgender and transgender patients using data from the American College of Surgeon's National Surgical Quality Improvement Program (NSQIP) database. Data was queried between 2013 and 2019 for all patients with procedure codes for scrotoplasty. Transgender patients were identified through a gender dysphoria diagnosis code. T-tests and Fisher's exact test were used to identify any differences in demographics, operative characteristics, and outcomes. The primary outcomes of interest were demographic factors, operative details, and surgical outcomes. A total of 234 patients were identified between 2013 and 2019. Fifty were transgender and 184 were cisgender. Age and BMI were significantly different between the two cohorts, such that the cisgender cohort was older (M trans = 38 years (SD:14), M cis = 53 years (SD: 15)) and had higher BMI than the transgender cohort (M trans = 26.9 (SD: 5.5), M cis = 35.2 (SD: 11.2)). Cisgender patients also had poorer overall health (p = 0.001), and were more likely to have hypertension (p = 0.001) and diabetes (p = 0.001). Race and ethnicity did not vary significantly between the cohorts. Operative details differed significantly between cohorts, such that transgender patients had a longer operating time (M trans = 303 min (SD: 155), M cis = 147 min (SD: 107)) and fewer transgender patients had a simple scrotoplasty (p = 0.02). The majority of gender-affirming scrotoplasties were performed by plastic surgeons (62%) whereas the majority of cisgender scrotoplasties were performed by urologists (76%). Despite these demographic and pre-operative differences, the number of patients who underwent complex scrotoplasty experiencing any of the tested complications did not differ by gender. Our results support scrotoplasty as a safe procedure for transgender patients, with no significant differences in outcomes between transgender and cisgender patients.

Disparities in Telemedicine Literacy and Access in the United States.

BACKGROUND: Because of the expansion of telehealth services through the 2020 Coronavirus Aid, Relief, and Economic Security (CARES) Act, the potential of telemedicine in plastic surgery has gained visibility. This study aims to identify populations who may have limited access to telemedicine. METHODS: The authors created a telemedicine literacy index (TLI) using a multivariate regression model and data from the US Census and Pew Research Institute survey. A multivariate regression model was created using backwards elimination, with TLI as the dependent variable and demographics as independent variables. The resulting regression coefficients were applied to data from the 2018 US Census at the county level to create a county-specific technological literacy index (cTLI). Significance was set at P < 0.05. RESULTS: On multivariable analysis, the following factors were found to be significantly associated with telemedicine literacy: age, sex, race, employment status, income level, marital status, educational attainment, and urban or rural classification. Counties in the lowest tertile had significantly lower median annual income levels ($43,613 versus $60,418; P < 0.001) and lower proportion of the population with at least a bachelor's degree (16.7% versus 26%; P < 0.001). Rural areas were approximately three times more likely to be in the lowest cTLI compared with urban areas ( P < 0.001). Additional associations with low cTLI were Black race ( P = 0.045), widowed marital status ( P < 0.001), less than high school education ( P = 0.005), and presence of a disability ( P = 0.01). CONCLUSIONS: These results highlight disadvantaged groups at risk of being underserved with telehealth. Using these findings, key stakeholders may be able to target these communities for interventions to increase telemedicine literacy and access.

Financial Toxicity Among Patients With Breast Cancer Worldwide: A Systematic Review and Meta-analysis.

Importance: Financial toxicity (FT) is the negative impact of cost of care on financial well-being. Patients with breast cancer are at risk for incurring high out-of-pocket costs given the long-term need for multidisciplinary care and expensive treatments. Objective: To quantify the FT rate of patients with breast cancer and identify particularly vulnerable patient populations nationally and internationally. Data Sources: A systematic review and meta-analysis were conducted. Four databases-Embase, PubMed, Global Index Medicus, and Global Health (EBSCO)-were queried from inception to February 2021. Data analysis was performed from March to December 2022. Study Selection: A comprehensive database search was performed for full-text, English-language articles reporting FT among patients with breast cancer. Two independent reviewers conducted study screening and selection; 462 articles underwent full-text review. Data Extraction and Synthesis: A standardized data extraction tool was developed and validated by 2 independent authors; study quality was also assessed. Variables assessed included race, income, insurance status, education status, employment, urban or rural status, and cancer stage and treatment. Pooled estimates of FT rates and their 95% CIs were obtained using the random-effects model. Main Outcomes and Measures: FT was the primary outcome and was evaluated using quantitative FT measures, including rate of patients experiencing FT, and qualitative FT measures, including patient-reported outcome measures or patient-reported severity and interviews. The rates of patients in high-income, middle-income, and low-income countries who incurred FT according to out-of-pocket cost, income, or patient-reported impact of expenditures during breast cancer diagnosis and treatment were reported as a meta-analysis. Results: Of the 11 086 articles retrieved, 34 were included in the study. Most studies were from high-income countries (24 studies), and the rest were from low- and middle-income countries (10 studies). The sample size of included studies ranged from 5 to 2445 people. There was significant heterogeneity in the definition of FT. FT rate was pooled from 18 articles. The pooled FT rate was 35.3% (95% CI, 27.3%-44.4%) in high-income countries and 78.8% (95% CI, 60.4%-90.0%) in low- and middle-income countries. Conclusions and Relevance: Substantial FT is associated with breast cancer treatment worldwide. Although the FT rate was higher in low- and middle-income countries, more than 30% of patients in high-income countries also incurred FT. Policies designed to offset the burden of direct medical and nonmedical costs are required to improve the financial health of vulnerable patients with breast cancer.

Optimization of Freeform Reversible Embedding of Suspended Hydrogel Microspheres for Substantially Improved Three-Dimensional Bioprinting Capabilities.

Three-dimensional (3D) bioprinting demonstrates technology that is capable of producing structures comparable to native tissues in the human body. The freeform reversible embedding of suspended hydrogels (FRESH) technique involves hydrogel-based bio-inks printed within a thermo-reversible support bath to provide mechanical strength to the printed construct. Smaller and more uniform microsphere sizes of FRESH were reported to aid in enhancing printing resolution and construct accuracy. Therefore, we sought to optimize the FRESH generation protocol, particularly by varying stir speed and stir duration, in hopes to further improve microsphere size and uniformity. We observed optimal conditions at a stir speed of 600 rpm and stir duration for 20 h that generated the smallest microspheres with the best uniformity. Comparison of using the optimized FRESH to the commercial FRESH LifeSupport to bioprint single filament and geometrical constructs revealed reduced single filament diameters and higher angular precision in the optimized FRESH bio-printed constructs compared with those printed in the commercial FRESH. Overall, our refinement of the FRESH manufacturing protocol represents an important step toward enhancing 3D bioprinting resolution and construct fidelity. Improving such technologies allows for the fabrication of highly accurate constructs with anatomical properties similar to native counterparts. Such work has significant implications in the field of tissue engineering for producing accurate human organ model systems. Impact statement Freeform reversible embedding of suspended hydrogels (FRESH) is a method of sacrificial three-dimensional (3D) bioprinting that offers support to reinforce bio-ink extrusion during printing. During FRESH generation, the stir speed and stir duration of the mixture can significantly impact FRESH microsphere characteristics. In this study, we optimized FRESH microspheres to significantly improve resolution and accuracy in bioprinting. This advancement in FRESH-based 3D bioprinting technologies allows for the fabrication of highly accurate constructs with anatomical properties similar to native counterparts and has significant implications in the field of tissue engineering and translational medicine.

The Critical Biomechanics of Aortomitral Angle and Systolic Anterior Motion: Engineering Native Ex Vivo Simulation.

Systolic anterior motion (SAM) of the mitral valve (MV) is a complex pathological phenomenon often occurring as an iatrogenic effect of surgical and transcatheter intervention. While the aortomitral angle has long been linked to SAM, the mechanistic relationship is not well understood. We developed the first ex vivo heart simulator capable of recreating native aortomitral biomechanics, and to generate models of SAM, we performed anterior leaflet augmentation and sequential undersized annuloplasty procedures on porcine aortomitral junctions (n = 6). Hemodynamics and echocardiograms were recorded, and echocardiographic analysis revealed significantly reduced coaptation-septal distances confirming SAM (p = 0.003) and effective manipulation of the aortomitral angle (p < 0.001). Upon increasing the angle in our pathological models, we recorded significant increases (p < 0.05) in both coaptation-septal distance and multiple hemodynamic metrics, such as aortic peak flow and effective orifice area. These results indicate that an increased aortomitral angle is correlated with more efficient hemodynamic performance of the valvular system, presenting a potential, clinically translatable treatment opportunity for reducing the risk and adverse effects of SAM. As the standard of care shifts towards surgical and transcatheter interventions, it is increasingly important to better understand SAM biomechanics, and our advances represent a significant step towards that goal.

Biomechanical Engineering Analysis of Pulmonary Valve Leaflet Hemodynamics and Kinematics in the Ross Procedure.

The Ross procedure using the inclusion technique with anticommissural plication (ACP) is associated with excellent valve hemodynamics and favorable leaflet kinematics. The objective was to evaluate individual pulmonary cusp's biomechanics and fluttering by including coronary flow in the Ross procedure using an ex vivo three-dimensional-printed heart simulator. Ten porcine and five human pulmonary autografts were harvested from a meat abattoir and heart transplant patients. Five porcine autografts without reinforcement served as controls. The other autografts were prepared using the inclusion technique with and without ACP (ACP and NACP). Hemodynamic and high-speed videography data were measured using the ex vivo heart simulator. Although porcine autografts showed similar leaflet rapid opening and closing mean velocities, human ACP compared to NACP autografts demonstrated lower leaflet rapid opening mean velocity in the right (p = 0.02) and left coronary cusps (p = 0.003). The porcine and human autograft leaflet rapid opening and closing mean velocities were similar in all three cusps. Porcine autografts showed similar leaflet flutter frequencies in the left (p = 0.3) and noncoronary cusps (p = 0.4), but porcine NACP autografts versus controls demonstrated higher leaflet flutter frequency in the right coronary cusp (p = 0.05). The human NACP versus ACP autografts showed higher flutter frequency in the noncoronary cusp (p = 0.02). The leaflet flutter amplitudes were similar in all three cusps in both porcine and human autografts. The ACP compared to NACP autografts in the Ross procedure was associated with more favorable leaflet kinematics. These results may translate to the improved long-term durability of the pulmonary autografts.

Moving Beyond Psychiatric Gatekeeping for Gender-Affirming Surgery.

This Viewpoint describes gatekeeping in gender-affirming care and provides recommendations to improve access to gender-affirming surgery for transgender people.

Three-Dimensional Bioprinting with Alginate by Freeform Reversible Embedding of Suspended Hydrogels with Tunable Physical Properties and Cell Proliferation.

Extrusion-based three-dimensional (3D) bioprinting is an emerging technology that allows for rapid bio-fabrication of scaffolds with live cells. Alginate is a soft biomaterial that has been studied extensively as a bio-ink to support cell growth in 3D constructs. However, native alginate is a bio-inert material that requires modifications to allow for cell adhesion and cell growth. Cells grown in modified alginates with the RGD (arginine-glycine-aspartate) motif, a naturally existing tripeptide sequence that is crucial to cell adhesion and proliferation, demonstrate enhanced cell adhesion, spreading, and differentiation. Recently, the bioprinting technique using freeform reversible embedding of suspended hydrogels (FRESH) has revolutionized 3D bioprinting, enabling the use of soft bio-inks that would otherwise collapse in air. However, the printability of RGD-modified alginates using the FRESH technique has not been evaluated. The associated physical properties and bioactivity of 3D bio-printed alginates after RGD modification remains unclear. In this study, we characterized the physical properties, printability, and cellular proliferation of native and RGD-modified alginate after extrusion-based 3D bioprinting in FRESH. We demonstrated tunable physical properties of native and RGD-modified alginates after FRESH 3D bioprinting. Sodium alginate with RGD modification, especially at a high concentration, was associated with greatly improved cell viability and integrin clustering, which further enhanced cell proliferation.

Can gender-affirming surgeries be safely combined? An NSQIP analysis of 30-day outcomes and case planning factors.

As gender-affirming surgeries are being performed, new techniques have been developed to meet patient desires, including recent reports of several gender-affirming procedures being combined into a single operative encounter. Such a development may provide several advantages to both patients and providers. However, it is less clear whether combining these procedures affects patient safety and surgical case planning factors. To address this, we compared the complication rates and the length of hospital stay and operative time for standalone and combined gender-affirming procedures (e.g., hysterectomy and bilateral mastectomy, breast augmentation, and vaginoplasty) performed between 2005 and 2019 in the National Surgical Quality Improvement Program database. There were 1857 standalone mastectomies, 826 standalone hysterectomies, and 30 cases where they were combined. There were 379 vaginoplasties, 648 breast augmentations, and 31 cases where they were combined. There was no evidence of differences in overall health status between those undergoing combined and standalone procedures. Two-sample proportion testing did not find significant differences in any of the complications experienced between standalone and combined procedures. Similarly, two-sample t-tests did not find significant differences in the length of the hospital stays nor in the length of the operative encounter between standalone and combined masculinizing surgeries. Combining breast augmentation and vaginoplasty, however, saved an average of 97.86 min (p = .000) of operating time. These results suggest that combining gender-affirming procedures may be a safe and viable option for individuals who desire multiple gender-affirming procedures and may even be an advantageous option for patients and practitioners alike.

The need for craniofacial trauma and oncologic reconstruction in global surgery.

The global burden of surgical disease is concentrated in low- and middle-income countries and primarily consists of injuries and malignancies. While global reconstructive surgery has a long and well-established history, efforts thus far have been focused on addressing congenital anomalies. Craniofacial trauma and oncologic reconstruction are comparatively neglected despite their higher prevalence. This review explores the burden, management, and treatment gaps of craniofacial trauma and head and neck cancer reconstruction in low-resource settings. We also highlight successful alternative treatments used in low-resource settings and pearls that can be learned from these areas.

Is Clitoral Release Another Term for Metoidioplasty? A Systematic Review and Meta-Analysis of Metoidioplasty Surgical Technique and Outcomes.

INTRODUCTION: There has been an exponential increase in referrals for transmasculine patients seeking genital affirmation surgery. Despite transgender men's equal interest in metoidioplasty and phalloplasty, research has primarily focused on phalloplasty. AIM: To summarize and investigate the relationship between surgical technique, complications, and patient-satisfaction. METHODS: We performed a systematic review and meta-analysis of surgical techniques and physician- and patient-reported outcomes of gender-affirming clitoral release and metoidioplasty (PROSPERO# 158722) with literature from PubMed, Google Scholar, and ScienceDirect. Data were extracted using PRISMA guidelines. All searches, extractions, and grading were independently completed by 2 authors. MAIN OUTCOME MEASURES: Main measures were surgical technique, patient satisfaction, voiding, urethral stricture, and urethral fistula. RESULTS AND CONCLUSION: A total of 7 non-overlapping articles on metoidioplasty were identified, with a total of 403 patients. We identified 4 metoidioplasty techniques: Hage, Belgrade, labial ring flap, and extensive metoidioplasty. All techniques included urethral lengthening. The reported neophallus length ranged from 2 cm to 12 cm, with the smallest neophallus occurring with the labial ring flap technique and extensive metoidioplasty the largest. Across techniques, voiding while standing was reported in most patients, with the lowest rate reported with the labial ring flap (67%). Complications were impacted by surgical technique, with the lowest rates of fistula and stricture occurring with the Belgrade technique. Fistula rates ranged from 5% to 37%, while stricture ranged from 2% to 35% of patients. The Belgrade technique reported significantly lower rates of fistula and stricture (P = .000). The patient-reported outcomes were described for the Belgrade technique and extensive metoidioplasty. Both techniques showed high aesthetic and sexual satisfaction. Transgender individuals can achieve an aesthetically and sexually satisfactory neophallus using a variety of metoidioplasty techniques; however, urethral outcomes vary significantly by technique. The Belgrade technique reported the best outcomes, although data remains limited. Patient priorities should be used to determine surgical technique. Jolly D, Wu CA, Boskey ER, et al. Is Clitoral Release Another Term for Metoidioplasty? A Systematic Review and Meta-Analysis of Metoidioplasty Surgical Technique and Outcomes. Sex Med 2021;9:100294.