Anesthesia for gender-affirming surgery: a practical review.

PURPOSE OF REVIEW: Gender-affirming surgery (GAS) is an effective, well studied, and often necessary component of gender-affirming care and mitigation of gender dysphoria for transgender and gender-diverse (TGD) individuals. GAS is categorized as chest surgeries, genitourinary surgeries, facial feminization/masculinization, and vocal phonosurgery. Despite increased incidence of GAS during recent years, there is a gap in knowledge and training on perioperative care for TGD patients. RECENT FINDINGS: Our review discusses the relevant anesthetic considerations for the most common GAS, which often involve highly specialized surgical techniques that have unique implications for the anesthesia professional. SUMMARY: Anesthesiology professionals must attend to the surgical and anesthetic nuances of various GAS procedures. However, as many considerations are based on common practice, research is warranted on anesthetic implications and outcomes of GAS.

Development of male and female models of long urethral strictures in swine.

Background: Preclinical animal models which mimic the dimensions of long urethral strictures (>2 cm in length) encountered in the clinic are necessary to evaluate prospective graft designs for urethroplasty. The purpose of this study was to develop both male and female porcine models of long urethral strictures (∼4 cm in length) and characterize histological and functional outcomes of iatrogenic stricture formation between genders. Methods: Focal, partial thickness urethral injuries were created over 5-6 cm long segments in male and female swine (N = 4 per gender) via electrocoagulation and the degree of stricture formation was monitored for up to 6 weeks by urethroscopy and retrograde urethrography. Animals were sacrificed following stricture confirmation and histological, immunohistochemical, and histomorphometric analyses were performed on strictured and uninjured control urethral segments to profile wound healing responses. Results: Urethral stricture formation was detected in all female swine by 2 weeks and 100 % of male swine at 3.2 ± 1.8 weeks, post-operatively. The mean length of urethral strictures in both male and female swine was ∼4 cm. Substantial variations in the degree of stricture severity between sexes were observed with males exhibiting significant urethral stenosis and loss of α-smooth muscle actin+ smooth muscle bundles in comparison to controls, while females primarily displayed defects in pan-cytokeratin+ epithelia as well as functional urethral obstruction. Conclusions: Electrocoagulation injury is sufficient to produce long urethral strictures in male and female swine and the degree of stricture severity and nature of urethral obstruction was observed to be dependent on gender. Animal Protocol: AUP-19-150. Key message: Novel male and female models of long urethral strictures in swine were created to characterize histological and functional outcomes of iatrogenic stricture formation between genders.

Evaluation of silk fibroin-based urinary conduits in a porcine model of urinary diversion.

Background: The primary strategy for urinary diversion in radical cystectomy patients involves incorporation of autologous gastrointestinal conduits into the urinary tract which leads to deleterious consequences including chronic infections and metabolic abnormalities. This report investigates the efficacy of an acellular, tubular bi-layer silk fibroin (BLSF) graft to function as an alternative urinary conduit in a porcine model of urinary diversion. Materials and methods: Unilateral urinary diversion with stented BLSF conduits was executed in five adult female, Yucatan mini-swine over a 3 month period. Longitudinal imaging analyses including ultrasonography, retrograde ureteropyelography and video-endoscopy were carried out monthly. Histological, immunohistochemical (IHC), and histomorphometric assessments were performed on neoconduits at harvest. Results: All animals survived until scheduled euthanasia and displayed moderate hydronephrosis (Grades 1-3) in reconstructed collecting systems over the course of the study period. Stented BLSF constructs supported formation of vascularized, retroperitoneal tubes capable of facilitating external urinary drainage. By 3 months post-operative, neoconduits contained α-smooth muscle actin+ and SM22α+ smooth muscle as well as uroplakin 3A+ and pan-cytokeratin + urothelium. However, the degree of tissue regeneration in neotissues was significantly lower in comparison to ureteral controls as determined by histomorphometry. In addition, neoconduit stenting was necessary to prevent stomal occlusion. Conclusion: BLSF biomaterials represent emerging platforms for urinary conduit construction and may offer a functional replacement for conventional urinary diversion techniques following further optimization of mechanical properties and regenerative responses.

DNA Methylation Dynamics During Esophageal Epithelial Regeneration Following Repair with Acellular Silk Fibroin Grafts in Rat.

Esophageal pathologies such as atresia and benign strictures often require surgical reconstruction with autologous tissues to restore organ continuity. Complications such as donor site morbidity and limited tissue availability have spurred the development of acellular grafts for esophageal tissue replacement. Acellular biomaterials for esophageal repair rely on the activation of intrinsic regenerative mechanisms to mediate de novo tissue formation at implantation sites. Previous research has identified signaling cascades involved in neoepithelial formation in a rat model of onlay esophagoplasty with acellular silk fibroin grafts, including phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) signaling. However, it is currently unknown how these mechanisms are governed by DNA methylation (DNAme) during esophageal wound healing processes. Reduced-representation bisulfite sequencing is performed to characterize temporal DNAme dynamics in host and regenerated tissues up to 1 week postimplantation. Overall, global hypermethylation is observed at postreconstruction timepoints and an inverse correlation between promoter DNAme and the expression levels of differentially expressed proteins during regeneration. Site-specific hypomethylation targets genes associated with immune activation, while hypermethylation occurs within gene bodies encoding PI3K-Akt signaling components during the tissue remodeling period. The data provide insight into the epigenetic mechanisms during esophageal regeneration following surgical repair with acellular grafts.

Iron-containing metal-organic framework thin film as a drug delivery system.

Selective bulk metal-organic frameworks (MOFs) have exhibited great potential in biomedical applications. However, topical treatments and drug elution coatings will require uniform films as drug delivery systems. This work studies the use of surface supportive MOF thin films for drug loading and releasing. More specifically, we focus on an iron-containing MOF, MIL-88B(Fe), on a COOH-terminated self-assembled monolayer (SAM) modified Au surface for encapsulating ibuprofen as a model drug. A combined experimental and computational approach was employed to study the fabrication of MIL-88B(Fe) film on functionalized Au surfaces. We used several surface characterization techniques, including infrared spectroscopy and scanning electron microscopy, to confirm the chemical composition and morphological changes of the surface after each modification step. The resulting MIL-88B(Fe) thin film was found capable of loading 8.7 wt% of ibuprofen using quartz crystal microbalance analysis. Moreover, we applied cluster simulations to study the binding mechanisms of MIL-88B(Fe) and its interactions with ibuprofen based on the density functional theory (DFT). The unsaturated Fe site was confirmed kinetically more favorable to bind to the COOH-end group on the SAM. Hydrogen bonding and π-CH interactions between ibuprofen and MIL-88B(Fe) promote ibuprofen being retained inside of the cages of MIL-88B(Fe).

Tuning Crystal Structures of Iron-Based Metal-Organic Frameworks for Drug Delivery Applications.

Iron-based metal-organic frameworks (Fe-MOFs) have emerged as promising candidates for drug delivery applications due to their low toxicity, structural flexibility, and safe biodegradation in a physiological environment. Here, we studied two types of Fe-MOFs: MIL-53 and MIL-88B, for in vitro drug loading and releasing of ibuprofen as a model drug. Both Fe-MOFs are based on the same iron clusters and organic ligands but form different crystal structures as a result of two different nucleation pathways. The MIL-53 structure demonstrates one-dimensional channels, while MIL-88B exhibits a three-dimensional cage structure. Our studies show that MIL-53 adsorbs more ibuprofen (37.0 wt %) compared to MIL-88B (19.5 wt %). A controlled drug release was observed in both materials with a slower elution pattern in the case of the ibuprofen-encapsulated MIL-88B. This indicates that a complex cage structure of MIL-88 is beneficial to control the rate of drug release. A linear correlation was found between cumulative drug release and the degree of material degradation, suggesting the biodegradation of Fe-MILs as the main drug elution mechanism. The cytotoxicity of MIL-88B was evaluated in vitro with NIH-3T3 Swiss mouse fibroblasts, and it shows that MIL-88B has no adverse effects on cell viability up to 0.1 mg/mL. This low toxicity was attributed to the morphology of MIL-88B nanocrystals. The very low toxicity and controlled drug release behavior of Fe-MIL-88B suggest that better materials for drug-delivery applications can be created by controlling not only the composition but also the crystal structure and nanoparticle morphology of the material.