Faculty Bibliography

The benefits of tissue expansion go unrealized if flap design and coverage concepts do not exist in pre-operative thinking. Without proper analysis, the surgeon will likely burden the patient with more expanders than necessary. Tissue coverage needs can be simplified in forms of triangles and rectangles to determine expanded tissue advancement. Single or double back cuts allow usage of all the expanded tissue. Furthermore, early subtotal excisions, especially in children less than four months old, can reduce the number of expanders required. With methods presented herein, the face can be resurfaced with better color and less distortion. Eyebrows should be maintained and positioned by keeping the lower frontalis muscles intact. Cheeks can be covered with a large "Schrudde" design and color can be improved by using upper neck skin preferentially over lower neck harvest. Laser hair removal allows larger swaths of forehead to be covered by hair-bearing scalp tissue. Prior incisional delay can expedite success with no tissue loss. The results speak for themselves when surfaces are covered with large, expanded flaps which are expeditiously harvested.

BACKGROUND:Malar augmentation is a key procedure sought out by transfeminine individuals seeking to feminize their facial appearance. Different surgical techniques have been described in the literature including fat transfer to the cheeks and malar implant placement. Because of the paucity of information in the literature, there is no consensus on best practices for this procedure. The objective of our study is to determine the effectiveness and safety of malar implants as compared with fat transfer to the cheeks in transfeminine individuals. METHODS:We examined all patients with the diagnosis of gender dysphoria that were referred to the senior author seeking consultation for feminizing facial procedures between June 2017 and August 2022. Patients who underwent fat transfer to the cheeks or malar implant placement were included in our study. We reviewed the electronic medical record of each patient, and we retrieved and analyzed data regarding demographics, medical and surgical history, operative dictations, clinic notes, and postoperative follow-up. Univariate analysis was used to assess for differences in postoperative complications between these 2 groups. RESULTS:We identified 231 patients underwent feminizing facial gender affirming surgery, with 152 patients receiving malar augmentation through malar implants or fat grafting. One hundred twenty-nine patients (84.9%) underwent malar implant placement and 23 (15.1%) underwent fat grafting to the cheeks. The mean follow-up time was 3.6 ± 2.7 months. Patient satisfaction was greater in the malar implant group (126/129, 97.7%) compared with the fat transfer group (20/23, 87%, P < 0.045). Two patients who received implants (1.8%) experienced postoperative complications. No patient undergoing fat transfer experiences similar adverse outcomes. Nevertheless, the difference was not statistically significant (P = 1.00). CONCLUSIONS:Our findings support the contention that malar implants are a safe alternative for malar augmentation among transfeminine individuals. While autologous fat transfer to the cheek is an indispensable option in patients requiring minor malar enhancement, malar implants offer a more permanent option with a better aesthetic outcome in patients requiring major malar enhancement. To minimize postoperative complications, surgeons should emphasize patient compliance with postoperative directions.

The present study aimed to evaluate the effect of dipyridamole, an indirect adenosine 2A receptors (A_2AR), on the osseointegration of titanium implants in a large, translational pre-clinical model. Sixty tapered, acid-etched titanium implants, treated with four different coatings ((i) Type I Bovine Collagen (control), (ii) 10 μM dipyridamole (DIPY), (iii) 100 μM DIPY, and (iv) 1000 μM DIPY), were inserted in the vertebral bodies of 15 female sheep (weight ~65 kg). Qualitative and quantitative analysis were performed after 3, 6, and 12 weeks in vivo to assess histological features, and percentages of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO). Data was analyzed using a general linear mixed model analysis with time in vivo and coating as fixed factors. Histomorphometric analysis after 3 weeks in vivo revealed higher BIC for DIPY coated implant groups (10 μM (30.42% ± 10.62), 100 μM (36.41% ± 10.62), and 1000 μM (32.46% ± 10.62)) in comparison to the control group (17.99% ± 5.82). Further, significantly higher BAFO was observed for implants augmented with 1000 μM of DIPY (43.84% ± 9.97) compared to the control group (31.89% ± 5.46). At 6 and 12 weeks, no significant differences were observed among groups. Histological analysis evidenced similar osseointegration features and an intramembranous-type healing pattern for all groups. Qualitative observation corroborated the increased presence of woven bone formation in intimate contact with the surface of the implant and within the threads at 3 weeks with increased concentrations of DIPY. Coating the implant surface with dipyridamole yielded a favorable effect with regard to BIC and BAFO at 3 weeks in vivo. These findings suggest a positive effect of DIPY on the early stages of osseointegration.

Chronic pain involves sensitization of nociceptors and synaptic transmission of painful signals in nociceptive circuits in the dorsal horn of the spinal cord. We investigated the contribution of clathrin-dependent endocytosis to sensitization of nociceptors by G protein-coupled receptors (GPCRs) and to synaptic transmission in spinal nociceptive circuits. We determined whether therapeutic targeting of endocytosis could ameliorate pain. mRNA encoding dynamin (Dnm) 1-3 and adaptor-associated protein kinase 1 (AAK1), which mediate clathrin-dependent endocytosis, were localized to primary sensory neurons of dorsal root ganglia of mouse and human and to spinal neurons in the dorsal horn of the mouse spinal cord by RNAScope®. When injected intrathecally to mice, Dnm and AAK1 siRNA or shRNA knocked-down Dnm and AAK1 mRNA in dorsal root ganglia neurons, reversed mechanical and thermal allodynia and hyperalgesia, and normalized non-evoked behavior in preclinical models of inflammatory and neuropathic pain. Intrathecally administered inhibiters of clathrin, Dnm and AAK1 also reversed allodynia and hyperalgesia. Disruption of clathrin, Dnm and AAK1 did not affect normal motor functions of behaviors. Patch clamp recordings of dorsal horn neurons revealed that Dnm1 and AAK1 disruption inhibited synaptic transmission between primary sensory neurons and neurons in lamina I/II of the spinal cord dorsal horn by suppressing release of synaptic vesicles from presynaptic primary afferent neurons. Patch clamp recordings from dorsal root ganglion nociceptors indicated that Dnm siRNA prevented sustained GPCR-mediated sensitization of nociceptors. By disrupting synaptic transmission in the spinal cord and blunting sensitization of nociceptors, endocytosis inhibitors offer a therapeutic approach for pain treatment.

UNLABELLED:Head and neck reconstruction poses unique challenges due to the complex structure of the region. Primary goals include soft-tissue coverage, adequate color and texture match, and minimal donor-site morbidity. Local and musculocutaneous regional flaps have largely been replaced with fasciocutaneous free flaps (FFF) over recent years. The supraclavicular artery island flap (SCAIF), a locoregional, fasciocutaneous, axially-based flap, has been shown to produce similar outcomes to FFF. We present our 15-year experience using the SCAIF for head and neck reconstruction, discuss its evolution, and provide case examples for its range of indications. METHODS/UNASSIGNED:Retrospective chart review identified 128 patients who underwent reconstruction of the head and neck with the SCAIF between the years 2006-2021 at Tulane University Medical Center. Patient demographics, lengths of stay, operative times, surgical indications, and complications were recorded. RESULTS/UNASSIGNED:The cohort mean age was 66.9 years. Mean lengths of stay and follow-up times were 6.9 days and 9.1 months, respectively. The most common indications for SCAIF reconstruction were recurrent radiated neck disease (n=27, 21.1%), pharyngeal wall defects (n=23, 18.0%), and parotidectomy defects (n=21, 16.4%). Overall complication rate was 17.2%. Partial thickness flap loss (5.5%), contained pharyngeal leak (3.2%), and distal tip necrosis (2.4%) were the most common complications. No functional donor site morbidity was encountered. CONCLUSIONS/UNASSIGNED:The SCAIF is a versatile, fasciocutaneous, axially-based flap able to produce similar outcomes to FFF in the reconstruction of the head and neck region while reducing costs, lengths of stay, operative times, and donor site morbidity.

UNLABELLED:Fat grafting is an effective treatment for craniofacial deformities. Stromal vascular fraction (SVF) is a concentrated form of adipose derived stem cells that can be isolated from fat. The aim of this clinical trial was to assess the impact of SVF enrichment on craniofacial fat grafting. METHODS/UNASSIGNED:Twelve subjects with at least two regions of craniofacial volume deficit were enrolled, and they underwent fat grafting with SVF-enriched or standard fat grafting to each area. All patients had bilateral malar regions injected with SVF-enriched graft on one side and control standard fat grafting to the contralateral side. Outcome assessments included demographic information, volume retention determined by CT scans, SVF cell populations assessed by flow cytometry, SVF cell viability, complications, and appearance ratings. Follow-up was 9 months. RESULTS/UNASSIGNED:0.027). CONCLUSIONS/UNASSIGNED:Autologous fat transfer for reconstruction of craniofacial defects is effective and safe, leading to reliable volume retention. However, SVF enrichment does not significantly impact volume retention.

BACKGROUND/UNASSIGNED:" osseodensification rotary drilling compacts the bone fragments into the osteotomy walls, creating nucleating sites for regeneration. METHODS/UNASSIGNED:This study aimed to compare both manual versus rotary Osseodensification (OD) instrumentation as well as two different pedicle screw thread designs in a controlled split animal model in posterior lumbar stabilization to determine the feasibility and potential advantages of each variable with respect to mechanical stability and histomorphology. A total of 164 single thread (82 per thread configuration), pedicle screws (4.5 × 35 mm) were used for the study. Each animal received eight pedicles (four per thread design) screws, which were placed in the lumbar spine of 21 adult sheep. One side of the lumbar spine underwent rotary osseodensification instrumentation, while the contralateral underwent conventional, hand, instrumentation. The animals were euthanized after 6- and 24-weeks of healing, and the vertebrae were removed for biomechanical and histomorphometric analyses. Pullout strength and histologic analysis were performed on all harvested samples. RESULTS/UNASSIGNED: = 0.026) greater pullout strength (1060.6 N ± 181) relative to hand instrumentation (769.3 N ± 181) at the 24-week healing time point. Histomorphometric analysis exhibited significantly higher degrees of bone to implant contact for the rotary instrumentation only at the early healing time point (6 weeks), whereas bone area fraction occupancy was statistically higher for rotary instrumentation at both healing times. The levels of soft tissue infiltration were lower for pedicle screws placed in osteotomies prepared using OD instrumentation relative to hand instrumentation, independent of healing time. CONCLUSION/UNASSIGNED:The rotary instrumentation yielded enhanced mechanical and histologic results relative to the conventional hand instrumentation in this lumbar spine stabilization model.

Sodium glucose cotransporter-2 inhibitors (SGLT2is) promote urinary glucose excretion and decrease plasma glucose levels independent of insulin. Canagliflozin (CANA) is an SGLT2i, which is widely prescribed, to reduce cardiovascular complications, and as a second-line therapy after metformin in the treatment of type 2 diabetes mellitus. Despite the robust metabolic benefits, reductions in bone mineral density (BMD) and cortical fractures were reported for CANA-treated subjects. In collaboration with the National Institute on Aging (NIA)-sponsored Interventions Testing Program (ITP), we tested skeletal integrity of UM-HET3 mice fed control (137 mice) or CANA-containing diet (180 ppm, 156 mice) from 7 to 22 months of age. Micro-computed tomography (micro-CT) revealed that CANA treatment caused significant thinning of the femur mid-diaphyseal cortex in both male and female mice, did not affect trabecular bone architecture in the distal femur or the lumbar vertebra-5 in male mice, but was associated with thinning of the trabeculae at the distal femur in CANA-treated female mice. In male mice, CANA treatment is associated with significant reductions in cortical bone volumetric BMD by micro-CT, and by quantitative backscattered scanning electron microscopy. Raman microspectroscopy, taken at the femur mid-diaphyseal posterior cortex, showed significant reductions in the mineral/matrix ratio and an increased carbonate/phosphate ratio in CANA-treated male mice. These data were supported by thermogravimetric assay (TGA) showing significantly decreased mineral and increased carbonate content in CANA-treated male mice. Finally, the sintered remains of TGA were subjected to X-ray diffraction and showed significantly higher fraction of whitlockite, a calcium orthophosphate mineral, which has higher resorbability than hydroxyapatite. Overall, long-term CANA treatment compromised bone morphology and mineral composition of bones, which likely contribute to increased fracture risk seen with this drug.

The hypothesis that sustained G protein-coupled receptor (GPCR) signaling from endosomes mediates pain is based on studies with endocytosis inhibitors and lipid-conjugated or nanoparticle-encapsulated antagonists targeted to endosomes. GPCR antagonists that reverse sustained endosomal signaling and nociception are needed. However, the criteria for rational design of such compounds are ill-defined. Moreover, the role of natural GPCR variants, which exhibit aberrant signaling and endosomal trafficking, in maintaining pain is unknown. Herein, substance P (SP) was found to evoke clathrin-mediated assembly of endosomal signaling complexes comprising neurokinin 1 receptor (NK₁R), Gα_q/i, and βarrestin-2. Whereas the FDA-approved NK₁R antagonist aprepitant induced a transient disruption of endosomal signals, analogs of netupitant designed to penetrate membranes and persist in acidic endosomes through altered lipophilicity and pKa caused sustained inhibition of endosomal signals. When injected intrathecally to target spinal NK₁R+ve neurons in knockin mice expressing human NK₁R, aprepitant transiently inhibited nociceptive responses to intraplantar injection of capsaicin. Conversely, netupitant analogs had more potent, efficacious, and sustained antinociceptive effects. Mice expressing C-terminally truncated human NK₁R, corresponding to a natural variant with aberrant signaling and trafficking, displayed attenuated SP-evoked excitation of spinal neurons and blunted nociceptive responses to SP. Thus, sustained antagonism of the NK₁R in endosomes correlates with long-lasting antinociception, and domains within the C-terminus of the NK₁R are necessary for the full pronociceptive actions of SP. The results support the hypothesis that endosomal signaling of GPCRs mediates nociception and provides insight into strategies for antagonizing GPCRs in intracellular locations for the treatment of diverse diseases.