Faculty Bibliography

PURPOSE/OBJECTIVE:The aim of the present study was to systematically analyze how a multifactorial surgical instrumentation approach affects osseointegration on both narrow-diameter and wide-diameter short implants. MATERIALS AND METHODS/METHODS:Twelve skeletally mature female sheep were used in the study along with 144 plateau-root-form healing chamber titanium (Ti-6Al-4V) implants (Bicon LLC, Boston, MA), evenly distributed between narrow (3.5 mm) and wide (6.0 mm) diameters. The presence or the absence of irrigation, different drilling speeds, and 2 time points quantifying bone-implant contact (BIC) and bone area fraction occupancy (BAFO) to evaluate the osteogenic parameters around the implants. RESULTS:There were no signs of inflammation, infection, or failure of the implants observed at either healing period. The narrow 3.5-mm implant, at 6 weeks, yielded significant differences in terms of BIC at a drilling speed of 50 rotations per minute (RPM), with higher values of the samples using irrigation (30.6 ± 6.1%) compared with those without (19.7 ± 6.1%). No statistical differences were detected for 500 and 1,000 RPM with or without irrigation. The wide 6-mm diameter implant showed differences with respect to drilling speed, 500 and 1,000 RPM, with higher values associated with samples subjected to irrigation. BAFO results, for both diameters, only detected statistical differences between the 2 times (3 vs 6 weeks); no statistical differences were detected when evaluating as a function of time, drilling speed, and irrigation. CONCLUSIONS:Surgical instrumentation variables (ie, drilling speed [RPM] and irrigation) yielded to be more of an effect for BIC at longer healing time (6 weeks) for the wider implants. Furthermore, deploying narrow or wide plateau-root-form implants, where conditions allow, has shown to be a safe alternative, considering the high BIC and BAFO values observed, independent of irrigation.

BACKGROUND:Cutaneous wounds in patients with diabetes exhibit impaired healing due to physiological impediments and conventional care options are severely limited. Multipotent stromal cells (MSCs) have been touted as a powerful new therapy for diabetic tissue repair owing to their trophic activity and low immunogenicity. However, variations in sources and access are limiting factors for broader adaptation and study of MSC-based therapies. Amniotic fluid presents a relatively unexplored source of MSCs and one with wide availability. Here, we investigate the potential of amniotic fluid-derived multipotent stromal cells (AFMSCs) to restore molecular integrity to diabetic wounds, amend pathology and promote wound healing. METHOD/METHODS:diabetic mouse skin, and splinted them open to allow for humanized wound modeling. Immediately after wounding, we applied AFMSCs topically to the sites of injuries on diabetic mice, while media application only, defined as vehicle, served as controls. Post-treatment, we compared healing time and molecular and cellular events of AFMSC-treated, vehicle-treated, untreated diabetic, and non-diabetic wounds. A priori statistical analyses measures determined significance of the data. RESULT/RESULTS:Average time to wound closure was approximately 19 days in AFMSC-treated diabetic wounds. This was significantly lower than the vehicle-treated diabetic wounds, which required on average 27.5 days to heal (p < 0.01), and most similar to time of closure in wild type untreated wounds (an average of around 18 days). In addition, AFMSC treatment induced changes in the profiles of macrophage polarizing cytokines, resulting in a change in macrophage composition in the diabetic wound bed. We found no evidence of AFMSC engraftment or biotherapy induced immune response. CONCLUSION/CONCLUSIONS:Treatment of diabetic wounds using amniotic fluid-derived MSCs encourages cutaneous tissue repair through affecting inflammatory cell behavior in the wound site. Since vehicle-treated diabetic wounds did not demonstrate accelerated healing, we determined that AFMSCs were therapeutic through their paracrine activities. Future studies should be aimed towards validating our observations through further examination of the paracrine potential of AFMSCs. In addition, investigations concerning safety and efficacy of this therapy in clinical trials should be pursued.

ABSTRACT/UNASSIGNED:Orbital floor fractures are common sequalae of trauma to the orbit. These fractures present as an isolated orbital floor (I-OF) fracture or with other midface fractures, typically the zygomaticomaxillary complex. The authors sought to better understand the differences in patient presentation, surgical decision-making, and outcomes in I-OF fractures compared with those associated with zygomaticomaxillary complex fractures (Z-OF). A retrospective review of patients with orbital floor fractures was conducted to generate an I-OF fracture group and a Z-OF fracture group. Demographics, preoperative symptoms, surgical choices, and postoperative complications were assessed. Complications were assessed individually and as 2 composite groups consisting of orbital complications and eyelid complications. There were 156 patients that met inclusion criteria with 75 I-OF fractures and 81 Z-OF fractures. The most common mechanism of injury for I-OF fractures was assault (34.7%) and motor vehicle accidents (39.5%) for Z-OF fractures. The I-OF group presented more often with diplopia (P = 0.01) whereas the Z-OF group had more trauma symptoms (P = 0.01), which included subconjunctival hemorrhages, retrobulbar hemorrhages, and relative afferent pupillary defects. I-OF fractures had longer preoperative observational periods (P < 0.001). Postoperatively, I-OF fractures had more motility restrictions (P = 0.002) but Z-OF fractures had higher risk for eyelid complications (P = 0.03). There was no significant difference in reoperation rates (P = 0.93). Multivariate analysis showed Z-OF fractures had reduced a rate of postoperative motility defects by 72% (P = 0.03) but had 2.6 times higher risk of eyelid complications (P = 0.04). Z-OF fractures present differently, vary in surgical management, and have complications that differ from an I-OF fracture.

OBJECTIVE:To describe a technique for perineal urethrostomy (PU) revision using a posterior thigh propeller flap for a complex repair at high risk for stenosis. METHODS:Our technique utilizes the consistent posterior thigh perforators for a local flap with ideal length and thickness for repair. The stenotic PU is incised. Potential flaps are marked around a perforator blood supply closest to the defect. The flap is then elevated and rotated on its pedicle with its apex placed directly in the defect. Absorbable sutures partially tubularize the flap apex at the level of the urethrotomy which is calibrated to 30 Fr. We subsequently monitored the patient's clinical progress. RESULTS:With 17 months of follow-up the patient is voiding well without complaint, reports improved quality of life with a patent PU. Post void residuals have been less than 100cc. The patient, who has had a long history of urinary tract infections requiring hospitalization, has only reported one infection during follow up which was treated as an out-patient. CONCLUSION/CONCLUSIONS:For challenging PU revisions a distant local propeller flap of healthy tissue outside the zone of injury is the ideal choice for length, thickness, and minimal morbidity resulting in excellent clinical results for our patient.

BACKGROUND:The operating microscope is used in many centers for microvascular hepatic arterial reconstruction in living as well as deceased donor liver transplantation in adult and pediatric recipients. To date, a systematic review of the literature examining this topic is lacking. METHODS:This systematic review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Three different electronic databases (PubMed, Embase OVID, and Cochrane CENTRAL) were queried. RESULTS:A total of 34 studies were included. The rate of hepatic artery thrombosis (HAT) in noncomparative studies (28) ranged from 0% to 10%, with 8 studies reporting patient deaths resulting from HAT. Within comparative studies, the rate of HAT in patients who underwent arterial reconstruction using the operating microscope ranged from 0% to 5.3%, whereas the rate of HAT in patients who underwent arterial reconstruction using loupe magnification ranged from 0% up to 28.6%, and 2 studies reported patient deaths resulting from HAT. Two comparative studies did not find statistically significant differences between the 2 groups. CONCLUSIONS:Our comprehensive systematic review of the literature seems to suggest that overall, rates of HAT may be lower when the operating microscope is used for hepatic arterial reconstruction in liver transplantation. However, matched comparisons are lacking and surgical teams need to be mindful of the learning curve associated with the use of the operating microscope as compared with loupe magnification, as well as the logistical and time constraints associated with setup of the operating microscope.

INTRODUCTION/BACKGROUND:Clinical significance of internal mammary (IM) lymph node biopsy during microvascular free flap breast reconstruction remains controversial. Some microsurgeons may choose to biopsy an IM lymph node during routine IM vessel dissection. The authors reviewed the results of IM lymph node biopsy during autologous breast reconstruction. METHODS:A retrospective chart review of patients who underwent autologous breast reconstruction during a seven-year period (January 2010 to January 2017) was performed. Patient demographic data, disease staging, flap details, pathology reports, and adjuvant treatment were evaluated. RESULTS:A total of 230 patients with a mean age of 52.1 (SD 9.3) underwent IM lymph node biopsy (n = 297). Single IM lymph node was removed in 169 patients, 2 nodes were removed in 56 patients, 3 nodes in 4 patients, and 4 nodes in a single patient. Histopathologic analysis demonstrated presence of IM lymph node metastasis in 16 patients (7.0%). Thirteen patients were found to have metastatic IM lymph nodes in the setting of immediate reconstruction. Three patients were found to have metastatic IM lymph nodes in the setting of delayed. Five out of 16 patients (31.3%) had negative axillary sentinel lymph node biopsy and IM lymph nodes were the only site of nodal metastases. All five of these patients were upstaged accordingly and received adjuvant therapy based on the discussion at the multidisciplinary breast tumor conference. CONCLUSIONS:Opportunistic internal mammary lymph node sampling during autologous breast reconstruction can be performed with minimal morbidity and has significant impact on the disease staging and adjuvant treatment.

Chronic pain is a hallmark of functional disorders, inflammatory diseases and cancer of the digestive system. The mechanisms that initiate and sustain chronic pain are incompletely understood, and available therapies are inadequate. This review highlights recent advances in the structure and function of pronociceptive and antinociceptive G protein-coupled receptors (GPCRs) that provide insights into the mechanisms and treatment of chronic pain. This knowledge, derived from studies of somatic pain, can guide research into visceral pain. Mediators from injured tissues transiently activate GPCRs at the plasma membrane of neurons, leading to sensitisation of ion channels and acute hyperexcitability and nociception. Sustained agonist release evokes GPCR redistribution to endosomes, where persistent signalling regulates activity of channels and genes that control chronic hyperexcitability and nociception. Endosomally targeted GPCR antagonists provide superior pain relief in preclinical models. Biased agonists stabilise GPCR conformations that favour signalling of beneficial actions at the expense of detrimental side effects. Biased agonists of µ-opioid receptors (MOPrs) can provide analgesia without addiction, respiratory depression and constipation. Opioids that preferentially bind to MOPrs in the acidic microenvironment of diseased tissues produce analgesia without side effects. Allosteric modulators of GPCRs fine-tune actions of endogenous ligands, offering the prospect of refined pain control. GPCR dimers might function as distinct therapeutic targets for nociception. The discovery that GPCRs that control itch also mediate irritant sensation in the colon has revealed new targets. A deeper understanding of GPCR structure and function in different microenvironments offers the potential of developing superior treatments for GI pain.

BACKGROUND:Given the current national conundrum of decreasing microsurgery case volume performed by hand surgery fellows despite interest, program directors were surveyed to evaluate opinions of exposure gaps in training and to determine the current state of microsurgery training in 2020. METHODS:Anonymous national surveys were distributed to hand surgery fellowship program directors by the American Society for Surgery of the Hand. Subgroups were compared by training location and size of the fellowship program. Accreditation Council for Graduate Medical Education public national data on graduate case log procedures by hand surgery fellows were reviewed. RESULTS:Eighty-eight surveys were distributed by the American Society for Surgery of the Hand to hand surgery fellowship program directors with a 44% (n = 39) response rate. Hand surgery fellowship programs from 19 US states participated. Most program's fellows had previous orthopedic surgery residency training with 41.03% of programs surveyed having 100% orthopedic surgery-trained fellows. The average number of weekly vascular microsurgical cases ranged from 25% of fellowships having no microsurgery cases per week, 46.2% having 1 per week, and only 7.7% having 5 or more cases per week. However, 60.5% of program directors prioritized a microvascular surgery case as the most valuable educational opportunity for fellows. Most program directors agreed (79.5%) that a 1-year hand surgery fellowship is sufficient to train a competent hand surgeon, who is proficient in microsurgery. In contrast, the majority disagreed (53.8%) that hand surgery microsurgery skills after a 1-year hand surgery fellowship are equivalent among graduates, regardless of a prior plastic surgery or orthopedic surgery residency training. There was a statistically significant difference in program directors' responses by geographic location regarding prior residency background impacting microsurgical skills (Kendall Ï„, -0.439; P = 0.001). Graduate case log data revealed an increasing trend in the number of microsurgery procedures performed by orthopedic hand surgery fellows until 2014, with a decline in cases per year and stagnating trend at 7% thereafter. CONCLUSIONS:In 2020, most hand surgery fellowship program directors highly value and prioritize microsurgery exposure for their hand surgery fellows' education despite the decrease in case volume for hand surgery fellows.

Oral squamous cell carcinoma (OSCC) is one of the most painful cancers, which interferes with orofacial function including talking and eating. We report that legumain (Lgmn) cleaves protease-activated receptor-2 (PAR₂) in the acidic OSCC microenvironment to cause pain. Lgmn is a cysteine protease of late endosomes and lysosomes that can be secreted; it exhibits maximal activity in acidic environments. The role of Lgmn in PAR₂-dependent cancer pain is unknown. We studied Lgmn activation in human oral cancers and oral cancer mouse models. Lgmn was activated in OSCC patient tumors, compared to matched normal oral tissue. After intraplantar, facial or lingual injection, Lgmn evoked nociception in wild-type (WT) female mice but not in female mice lacking PAR₂ in Na_V1.8-positive neurons (Par₂Na_v1.8), nor in female mice treated with a Lgmn inhibitor, LI-1. Inoculation of an OSCC cell line caused mechanical and thermal hyperalgesia that was reversed by LI-1. Par₂Na_v1.8 and Lgmn deletion attenuated mechanical allodynia in female mice with carcinogen-induced OSCC. Lgmn caused PAR₂-dependent hyperexcitability of trigeminal neurons from WT female mice. Par₂ deletion, LI-1 and inhibitors of adenylyl cyclase or protein kinase A prevented the effects of Lgmn. Under acidified conditions, Lgmn cleaved within the extracellular N-terminus of PAR₂ at Asn³⁰↓Arg³¹, proximal to the canonical trypsin activation site. Lgmn activated PAR₂ by biased mechanisms in HEK293 cells to induce Ca²⁺ mobilization, cAMP formation and protein kinase A/D activation, but not β-arrestin recruitment or PAR₂ endocytosis. Thus, in the acidified OSCC microenvironment Lgmn activates PAR₂ by biased mechanisms that evoke cancer pain.SIGNIFICANCE STATEMENTOral squamous cell carcinoma (OSCC) is one of the most painful cancers. We report that legumain (Lgmn), which exhibits maximal activity in acidic environments, cleaves protease-activated receptor-2 (PAR₂) on neurons to produce OSCC pain. Active Lgmn was elevated in OSCC patient tumors, compared to matched normal oral tissue. Lgmn evokes pain-like behavior through PAR₂ Exposure of pain-sensing neurons to Lgmn decreased the current required to generate an action potential through PAR₂ Inhibitors of adenylyl cyclase and protein kinase A prevented the effects of Lgmn. Lgmn activated PAR₂ to induce calcium mobilization, cAMP formation and activation of protein kinase D and A, but not β-arrestin recruitment or PAR₂ endocytosis. Thus, Lgmn is a biased agonist of PAR₂ that evokes cancer pain.

BACKGROUND: Collaboration has been shown to be beneficial when we have complex problems and highly specialized groups, such as in head and neck reconstruction. Otolaryngology, plastic surgery, and oral maxillofacial surgeons perform head and neck reconstruction research. While the specialties represent unique backgrounds, the degree of interdisciplinary collaboration and subtopic focus is unknown. We sought to describe the frequency of interinstitutional interdisciplinary collaboration and examine the association of specialty with research subtopics. METHODS: Oral presentations from 2014 to 2018 focused on head and neck reconstruction or associated principles at the main reconstructive academic meetings in otolaryngology (American Head and Neck Society), plastic surgery (American Society for Reconstructive Microsurgery), and oral maxillofacial surgery (American Association of Oral and Maxillofacial Surgeons) were reviewed. Author specialty and institution data were recorded. All abstracts were assigned a research subtopic, chosen based on identified themes. Subtopic frequencies among the specialties were compared. RESULTS: Thirteen of 88 (15%) US institutions participate in interdisciplinary collaboration in head and neck reconstruction research. Of the remaining institutions, 23 (31%) have researchers performing parallel work and not collaborating. Certain research subtopics were more often presented by each specialty, representing differing interests. CONCLUSION/CONCLUSIONS: Collaboration among head and neck reconstruction research at the US institutions is low compared with the potential. Specialties focus on different research subtopics, and therefore can benefit from working together.