Faculty Bibliography

BACKGROUND:Initially performed only in prophylactic cases, indications for nipple-sparing mastectomy have expanded. Trends and surgical outcomes stratified by nipple-sparing mastectomy indication have not yet been fully examined. METHODS:Demographics and outcomes for all nipple-sparing mastectomies performed from 2006 to 2017 were compared by mastectomy indication. RESULTS:A total of 1212 nipple-sparing mastectomies were performed: 496 (40.9 percent) for therapeutic and 716 (59.1 percent) for prophylactic indications. Follow-up time was similar between both the therapeutic and prophylactic nipple-sparing mastectomy groups (47.35 versus 46.83 months, respectively; p = 0.7942). Therapeutic nipple-sparing mastectomies experienced significantly greater rates of major (p = 0.0165) and minor (p = 0.0421) infection, implant loss (p = 0.0098), reconstructive failure (p = 0.0058), and seroma (p = 0.0043). Rates of major (p = 0.4461) and minor (p = 0.2673) mastectomy flap necrosis and complete (p = 0.3445) and partial (p = 0.7120) nipple necrosis were equivalent. The overall rate of locoregional recurrence/occurrence per nipple-sparing mastectomy was 0.9 percent: 2.0 percent in therapeutic nipple-sparing mastectomies and 0.1 percent in prophylactic nipple-sparing mastectomies (p < 0.0001). CONCLUSIONS:Approximately 40 percent of nipple-sparing mastectomies are currently performed for therapeutic indications. Therapeutic nipple-sparing mastectomies had higher rates of infectious complications and reconstructive failure. Rates of locoregional cancer recurrence/occurrence are low, but occur significantly more often after therapeutic nipple-sparing mastectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, III.

OBJECTIVES/OBJECTIVE:To investigate how muscle and fasciocutaneous flaps influence the progression of bone healing in acute Gustilo IIIB tibia fractures. DESIGN/METHODS:Retrospective Chart Review. SETTING/METHODS:Urban Academic Level I Trauma Center. PATIENTS/PARTICIPANTS/METHODS:Between 2006 and 2016, 39 patients from a database of operatively treated long bone fractures met the inclusion criteria, which consisted of adults with acute Gustilo IIIB tibia shaft fracture requiring flap coverage and having at least 6 months of radiographic follow-up. INTERVENTION/METHODS:Soft tissue coverage for patients with Gustilo IIIB open tibia fractures was performed with either a muscle flap or fasciocutaneous flap. MAIN OUTCOME MEASUREMENTS/METHODS:A radiographic union score for tibia (RUST) fractures, used to evaluate fracture healing, was assigned to patients' radiographs postoperatively, at 3, 6, and 12 months from the initial fracture date. Mean RUST scores at these time points were compared between those of patients with muscle flaps and fasciocutaneous flaps. Union was defined as a RUST score of 10 or higher. RESULTS:There was a significant difference (P = 0.026) in the mean RUST score at 6 months between the muscle group (8.54 ± 1.81) and the fasciocutaneous group (6.92 ± 2.46). There was no significant difference in the mean RUST score at 3 months (P = 0.056) and at 12 months (P = 0.947) between the 2 groups. There was also significance in the number of fractures reaching union, favoring muscle flaps, at 6 months (P = 0.020). CONCLUSIONS:Patients with acute Gustilo IIIB tibia fractures who received muscle flaps have significantly faster radiographic progression of bone healing in the first 6 months than do patients who received fasciocutaneous flaps. Furthermore, according to radiographic evaluation, more Gustilo IIIB tibia fractures receiving muscle flaps reach union by 6 months than those flapped with fasciocutaneous tissue. LEVEL OF EVIDENCE/METHODS:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

BACKGROUND:Barbed sutures have become increasingly popular in the field of aesthetic plastic surgery, particularly in body contouring and breast surgeries, in which the use of barbed sutures may offer both time and cost savings. Scar aesthetics is an important outcome for both the surgeons and patients in these procedures; however, there is a paucity of studies assessing the aesthetic outcome of barbed sutures with regards to scarring. METHODS:A systematic review of PubMed, EMBASE, and Cochrane databases was performed from the date of their inception through July 2017 using the search terms barbed suture combined with scar or wound. Studies were included if they were prospective evaluator-blind randomized controlled trials, closed the dermal layer of incisions using barbed sutures, and included an evaluator-blind aesthetic assessment of scarring. RESULTS:Six prospective randomized controlled trials met inclusion criteria. The cosmetic result of scars in 926 patients was evaluated after an average of 8.1 months. Five of the 6 controlled trials found the aesthetic results of wounds closed with barbed sutures to be equivalent to those closed with traditional sutures, and 1 study showed significantly superior aesthetic results with barbed sutures. Use of barbed sutures resulted in shorter operating times in 4 of the 5 studies that timed incision closure. Similar complication rates were observed in all evaluated studies. CONCLUSION/CONCLUSIONS:Based on this systematic review, the majority of studies concluded that there were no differences in scarring aesthetics when dermal layers were closed using barbed sutures compared with traditional suturing techniques.

BACKGROUND:A primary goal in chest wall reconstruction ('top surgery') for trans men is achieving a symmetrical, aesthetically pleasing position of the reconstructed male NAC. In the context of existing surgical techniques for top surgery, the ability to achieve this goal is limited. METHODS:The senior author's technique for component NAC creation in chest wall reconstruction for trans men with a modified skate flap and free areolar graft, in conjunction with double-incision mastectomy, is described. A retrospective analysis of 50 consecutive patients who underwent primary, bilateral chest wall reconstruction with this technique was undertaken for the period of March 2015 to October 2016. RESULTS:Average patient age was 30.64 years, with an average BMI of 28.54 kg/m. Eighty two percent of the sample received pre-operative testosterone therapy, and average operative time was 2 hours and 59 minutes. Average overall mastectomy specimen weight was 627.80 grams. Average length of hospital stay was 0.96 days. Average follow-up duration was 19.02 months.Complications occurred in 10% (n = 5) of patients, including seroma (4%), cellulitis (2%), hematoma (2%), and suture granuloma (2%). Only 5 patients (10%) underwent postoperative revision to adjust NAC size, projection, or symmetry. Twenty-eight patients (56%) underwent secondary revisions, including scar revisions (56%), liposuction (12%), and fat grafting (2%). CONCLUSIONS:The use of a modified nipple flap and free areolar graft in transgender chest wall reconstruction for trans men allows for flexible, component construction of the male NAC, in a safe and effective manner.

PURPOSE/OBJECTIVE:The increasing prevalence of obesity and/or metabolic syndrome (O/MS) and diabetes mellitus (DM) remains a global health concern. Clinically relevant and practical translational models mimicking human characteristics of these conditions are lacking. This study aimed to demonstrate proof of concept of the induction of stable O/MS and type 2 DM in a Göttingen minipig model and validate both of these disease-adjusted Göttingen minipig models as impaired healing models for the testing of dental implants. MATERIALS AND METHODS/METHODS:Nine minipigs were split into 3 groups-control (normal diet), obese (cafeteria diet), and diabetic (cafeteria diet plus streptozotocin)-followed by placement of dental implants. Inflammatory markers including tumor necrosis factor α, C-reactive protein, and cortisol were recorded for each study group. Removal torque was measured, and histomorphometric analysis (bone-to-implant contact and bone area fraction occupancy) was performed. RESULTS:O/MS pigs showed, on average, a 2-fold increase in plasma C-reactive protein (P < .05) and cortisol (P < .09) concentrations compared with controls; DM pigs showed, on average, a 40-fold increase in plasma tumor necrosis factor α levels (P < .05) and a 2-fold increase in cortisol concentrations (P < .05) compared with controls. The impact of O/MS and DM on implants was determined. The torque to interface failure was highest in the control group (200 N-cm) and significantly lower in the O/MS (90 N-cm) and DM (60 N-cm) groups (P < .01). Bone formation around implants was significantly greater in the control group than in the O/MS and DM groups (P < .02). CONCLUSIONS:Both O/MS and DM minipigs express a human-like disease phenotype, and both presented bone-healing impairment around dental implants. Our finding of no significant difference between type 2 DM and O/MS in bone formation around implants provides evidence that further investigation of the impact of O/MS is warranted.

Adenosine receptor activation has been explored as a modulator of the inflammatory process that propagates osteoarthritis. It has been reported that cartilage has enhanced regenerative potential when influenced by adenosine receptor activation. As adenosine's role in maintaining chondrocyte homeostasis at the cellular and molecular levels is explored, successful in vivo applications of adenosine delivery for cartilage repair continue to be reported. This review summarizes the role adenosine receptor ligation plays in chondrocyte homeostasis and regeneration of articular cartilage damaged in osteoarthritis. It also reports on all the modalities reported for delivery of adenosine through in vivo applications.

: The first facial transplantation in 2005 ushered in a new era in reconstructive surgery, offering new possibilities for the repair of severe disfigurements previously limited by conventional techniques. Advances in allograft design, computerized preoperative planning, surgical technique, and postoperative revisions have helped push the boundaries in this new frontier of vascularized composite allotransplantation. Over the past 12 years, 40 of these procedures have been performed across the world, offering the field the opportunity to reflect on current outcomes. Successes achieved in the brief history of facial transplantation have resulted in a new set of obstacles the field must now overcome. In this review, we aim to highlight the achievements, major challenges, and future directions of this rapidly evolving field.

BACKGROUND:Concerns exist that immediate breast reconstruction may delay adjuvant chemotherapy initiation, impacting oncologic outcomes. Here, we determine how post-operative complications impact chemotherapy timing, and identify factors associated with greater risk for delays. METHODS:Retrospective chart review identified patients undergoing immediate breast reconstruction and adjuvant chemotherapy at a single institution from 2010 to 2015. Patients were analyzed based on occurrence of post-operative complications and time to chemotherapy. RESULTS:A total of 182 patients (244 breast reconstructions) were included in the study; 210 (86%) reconstructions did not experience post-operative complications, 34 (13.9%) did. Patients who experienced post-operative complications had a higher mean age (53.6 vs. 48.1 years, p=0.002), and higher rates of diabetes (23.5% vs. 3.8%, p<0.001).The complication group had delays in initiation of chemotherapy (56 vs. 45 days, p=0.017). Only the immediate autologous reconstruction subgroup demonstrated a statistically significant delay in initiation of chemotherapy.Patients who initiated chemotherapy >48.5 days were of higher mean age (55.9 vs. 50.7 years, p=0.074), had increased rates of diabetes (36.8% vs. 6.7%, p=0.053), and immediate autologous reconstruction (31.6% vs. 0%, p=0.027). A predictive model based on these findings determined that patients with at least 1 of these 3 risk factors have a 74% chance of experiencing prolonged times to chemotherapy initiation vs. 18% without risk factors (p=0.003). CONCLUSIONS:Risk factors for delayed chemotherapy in the context of post-operative complications are age >51.7 years, diabetes, and autologous reconstruction. Reconstructive candidates who fit this profile are at highest risk and merit extra consideration and counseling.

Once activated at the surface of cells, G protein-coupled receptors (GPCRs) redistribute to endosomes, where they can continue to signal. Whether GPCRs in endosomes generate signals that contribute to human disease is unknown. We evaluated endosomal signaling of protease-activated receptor-2 (PAR₂), which has been proposed to mediate pain in patients with irritable bowel syndrome (IBS). Trypsin, elastase, and cathepsin S, which are activated in the colonic mucosa of patients with IBS and in experimental animals with colitis, caused persistent PAR₂-dependent hyperexcitability of nociceptors, sensitization of colonic afferent neurons to mechanical stimuli, and somatic mechanical allodynia. Inhibitors of clathrin- and dynamin-dependent endocytosis and of mitogen-activated protein kinase kinase-1 prevented trypsin-induced hyperexcitability, sensitization, and allodynia. However, they did not affect elastase- or cathepsin S-induced hyperexcitability, sensitization, or allodynia. Trypsin stimulated endocytosis of PAR₂, which signaled from endosomes to activate extracellular signal-regulated kinase. Elastase and cathepsin S did not stimulate endocytosis of PAR₂, which signaled from the plasma membrane to activate adenylyl cyclase. Biopsies of colonic mucosa from IBS patients released proteases that induced persistent PAR₂-dependent hyperexcitability of nociceptors, and PAR₂ association with β-arrestins, which mediate endocytosis. Conjugation to cholestanol promoted delivery and retention of antagonists in endosomes containing PAR₂ A cholestanol-conjugated PAR₂ antagonist prevented persistent trypsin- and IBS protease-induced hyperexcitability of nociceptors. The results reveal that PAR₂ signaling from endosomes underlies the persistent hyperexcitability of nociceptors that mediates chronic pain of IBS. Endosomally targeted PAR₂ antagonists are potential therapies for IBS pain. GPCRs in endosomes transmit signals that contribute to human diseases.