A Novel ex vivo Method for Investigating Vascularization of Transplanted Islets.

Revascularization of transplanted pancreatic islets is critical for survival and treatment of type 1 diabetes. Questions concerning how islets influence local microvascular networks and how networks form connections with islets remain understudied and motivate the need for new models that mimic the complexity of real tissue. Recently, our laboratory established the rat mesentery culture model as a tool to investigate cell dynamics involved in microvascular growth. An advantage is the ability to observe blood vessels, lymphatics, and immune cells. The objective of this study was to establish the rat mesentery tissue culture model as a useful tool to investigate islet tissue integration. DiI-labeled islets were seeded onto adult rat mesentery tissues and cultured for up to 3 days. Live lectin labeling enabled time-lapse observation of vessel growth. During culture, DiI-positive islets remained intact. Radial lectin-positive capillary sprouts with DiI labeling were observed to form from islets and connect to host networks. Lectin-positive vessels from host networks were also seen growing toward islets. PECAM and NG2 labeling confirmed that vessels sprouting from islets contained endothelial cells and pericytes. Our results introduce the rat mesentery culture model as a platform for investigating dynamics associated with the initial revascularization of transplanted islets.

The Impact of MassPAT on Opioid Prescribing Patterns for Otolaryngology Surgeries.

OBJECTIVE: Determine whether opioid prescriber patterns have changed for tonsillectomy, parotidectomy, and thyroidectomy after implementation of the Massachusetts Prescription Awareness Tool (MassPAT). STUDY DESIGN: Retrospective cohort study. SETTING: Single-center tertiary care hospital. METHODS: Patients were included if they received tonsillectomy, parotidectomy, or thyroid surgery at Lahey Hospital and Medical Center (Burlington, Massachusetts) between October 1, 2015, and October 1, 2019. Prescribing patterns were compared prior to implementation of MassPAT, October 1, 2015, to October 14, 2016, to postimplementation of MassPAT, October 15, 2016, to October 1, 2019. Quantity of opioids prescribed was described using total morphine milligram equivalents (MME). Data were analyzed using univariate analysis, multivariate analysis, and trend line using line of best fit. RESULTS: A total of 737 subjects were included in the study. There was a downward trend in the quantity of opioids prescribed for all 3 surgeries during the study period. There was a significant difference in the quantity of opioids prescribed pre- and postimplementation of MassPAT for tonsillectomy (647.70 ± 218.50 MME vs 474.60 ± 185.90 MME, P < .001), parotidectomy (241.20 ± 57.66 MME vs 156.70 ± 72.99 MME, P < .001), and thyroidectomy (171.20 ± 93.77 MME vs 108.50 ± 63.84 MME, P < .001). There was also a decrease in the number of patients who did not receive opioids for thyroidectomy pre- and post-MassPAT (7.56% vs 24.14%). CONCLUSION: We have demonstrated that there is an association with state drug monitoring programs and decrease in the amount of opioids prescribed for acute postoperative pain control for common otolaryngology surgeries.

Development and Validation of a Novel Surgical Simulation for Parotidectomy and Facial Nerve Dissection.

We present the development and validation of a low-cost novel model for training of parotid surgery. The model consists of a 3-dimensionally printed skeleton, silicone-based soft tissue, and facial nerve replicated with copper wire, circuited to indicate contact with instruments. The face validity of the simulator was evaluated with a 21-item 5-point Likert survey. Content validity was evaluated through a survey completed by the trainees after their first live parotidectomy following the simulation. Twelve residents and 6 faculty completed the simulated procedure of superficial parotidectomy after watching a video demonstration. Completion of 16 surgical steps evaluated by this model was graded for each participant. The mean ± SD total assessment score for faculty was 15.83 ± 0.41, as compared with 13.33 ± 2.06 for residents (P = .0081). The simulator as a training tool was well received by both faculty and residents (5 vs 4, P = .0206). Participants strongly agreed that junior residents would benefits from use of the model.

Perioperative safety, feasibility, and oncologic utility of transoral robotic surgery with da Vinci Xi platform.

Transoral robotic surgery (TORS) is a common modality for treatment of oropharyngeal and laryngeal cancer. Current FDA approval extends to the da Vinci S and Si platforms. Many hospitals are adopting the da Vinci Xi platform. Reports of head and neck surgical outcomes with this platform are scant. This study reports outcomes of TORS procedures performed with the da Vinci Xi platform including perioperative adverse events, functional outcomes, and short-term local control. A retrospective review of TORS performed with the da Vinci Xi platform is undertaken. Twenty-two consecutive TORS cases with the Xi platform are reviewed. Procedures performed include radical tonsillectomy, base of tongue resection, and lingual tonsillectomy. Two bleeding events occurred (9% of cases), both of intermediate severity as per Mayo criteria. Three procedures resulted in positive margin status, early in the case series, and two were cleared with revision resection. One-year local control rate, where available, is 100%. There were no perioperative deaths, long-term gastrostomy dependence, or performance of tracheostomy. Advantages of this platform include ease of robot deployment and setup. Disadvantages include increased width of instrumentation compared with previous platforms with crowding of access. The availability of a specific robotic platform may be dictated by hospital-wide policy across service lines. This report suggests that the da Vinci Xi permits performance of TORS with safety and oncologic outcomes similar to previous platforms; however, long-term follow-up is needed.

Mechanism and effects of pulsatile GABA secretion from cytosolic pools in the human beta cell.

Pancreatic beta cells synthesize and secrete the neurotransmitter γ-aminobutyric acid (GABA) as a paracrine and autocrine signal to help regulate hormone secretion and islet homeostasis. Islet GABA release has classically been described as a secretory vesicle-mediated event. Yet, a limitation of the hypothesized vesicular GABA release from islets is the lack of expression of a vesicular GABA transporter in beta cells. Consequentially, GABA accumulates in the cytosol. Here we provide evidence that the human beta cell effluxes GABA from a cytosolic pool in a pulsatile manner, imposing a synchronizing rhythm on pulsatile insulin secretion. The volume regulatory anion channel (VRAC), functionally encoded by LRRC8A or Swell1, is critical for pulsatile GABA secretion. GABA content in beta cells is depleted and secretion is disrupted in islets from type 1 and type 2 diabetic patients, suggesting that loss of GABA as a synchronizing signal for hormone output may correlate with diabetes pathogenesis.

Preparation tips for academic interviews.

Landing an academic interview can be difficult because there are very few global opportunities for PhD's and postdocs. However, when you are selected you want to be as prepared as possible. This article will highlight some strategies for preparation along with a detailed listing of actual academic interview questions provided by postdocs who shared their interview experiences. The content of the one-on-one interview questions could be very broad. However, most will be about your research, collaborations, teaching experience, possible funding opportunities and the potential future impact of your work.

Effective presentation skills.

Most PhD's will have a presentation component during the interview process, as well as presenting their work at conferences. This article will provide guidance on how to develop relevant content and effectively deliver it to your audience.

Dietary Genistein Influences Number of Acetylcholine Receptors in Female Diabetic Jejunum.

BACKGROUND: Intestinal dysfunction in the ob/ob mouse model of diabetes mimics that seen clinically. METHODS: We determined the effects of a 4-week genistein diet (600 mg genistein/kg food) on intestinal function (contractility, morphology, AChR, and motility) in female ob/ob and lean mice. RESULTS: Contractility of the jejunum in response to incrementally increasing concentrations of KCl was comparable in ob/ob females and lean controls regardless of a genistein-diet. There were no changes in the wall thickness measured. We assessed the number of clusters of AChR in the jejunum wall; AChR were decreased by 48% in ob/ob mice versus leans, and the genistein diet reversed this. In utilizing a video-imaging system to evaluate gastrointestinal motility, we determined that the distance between consecutive contractile events was significantly increased by 1.87-fold in ob/ob mice versus leans, and the genistein diet was without effect. CONCLUSIONS: These data suggest that slowed intestinal transit in the diabetic ob/ob mouse may be due in part to decreased AChR and decreased contraction events occurring per unit time. A genistein diet rescues the number of AChR to levels of leans yet did not change the number of contractile events. Feeding ob/ob mice a genistein-rich diet has potential therapeutic benefits towards improving the debilitating diabetes-related gastrointestinal dysfunction.

Results, Knowledge, and Attitudes Regarding an Incentive Compensation Plan in a Hospital-Based, Academic, Employed Physician Multispecialty Group.

EXECUTIVE SUMMARY: Hospitals and healthcare systems are introducing incentive metrics into compensation plans that align with value-based payment methodologies. These incentive measures should be considered a practical application of the transition from volume to value and will likely replace traditional productivity-based compensation in the future. During the transition, there will be provider resistance and implementation challenges. This article examines a large multispecialty group's experience with a newly implemented incentive compensation plan including the structure of the plan, formulas for calculation of the payments, the mix of quality and productivity metrics, and metric threshold achievement. Three rounds of surveys with comments were collected to measure knowledge and attitudes regarding the plan. Lessons learned and specific recommendations for success are described. The participant's knowledge and attitudes regarding the plan are important considerations and affect morale and engagement. Significant provider dissatisfaction with the plan was found. Careful metric selection, design, and management are critical activities that will facilitate provider acceptance and support. Improvements in data collection and reporting will be needed to produce reliable metrics that can supplant traditional volume-based productivity measures.

Dietary Genistein Rescues Reduced Basal Chloride Secretion in Diabetic Jejunum via Sex-Dependent Mechanisms.

BACKGROUND/AIMS: The goal of this study was to determine the effect of dietary genistein (naturally occurring phytoestrogen) on jejunal secretory function in a clinically relevant model of diabetes and obesity, the leptin-defIcient ob/ob mouse. METHODS: We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from 12-week old male and female ob/ob and lean C57Bl/6J mice fed a genistein diet (600 mg genistein/kg diet) for 4-weeks. Separate segments of jejunum were frozen for western blot determination of key proteins involved in secretory transport. RESULTS: Basal Isc was signifIcantly decreased (by 33%, P<0.05) in ob/ob females versus leans, and genistein-diet reversed this. Similarly, in males, basal Isc was decreased (by 47%, P<0.05) in ob/ob mice versus leans, and genistein-diet reversed this. Inhibition with either clotrimazole (100 µM, bilateral) or ouabain (100 µM, basolateral) was signifIcantly reduced in ob/ob mice compared to leans (P<0.05), and genistein-diet reversed clotrimazole-sensitive inhibition in ob/ob females, and reversed the ouabain-sensitive inhibition in males (indicating sex-dependent mechanisms). Our data suggested that PDE3 levels were dysregulated in ob/ob females and genistein reversed this. Expression of total CFTR (normalized to actin) was signifIcantly decreased ∼80% (P<0.05) in all ob/ob mice compared to leans, and genistein-diet was without effect. Expression of total NKCC1 (normalized to actin) was signifIcantly decreased ∼80% (P<0.05) in ob/ob male mice versus leans, and genistein-diet reversed this. CONCLUSIONS: Our data suggests that the reduced basal jejunal Isc in ob/ob female mice is a consequence of reduced CFTR expression, decreased activities of the basolateral KCa channel and Na+/K+-ATPase, and in male mice reduced basal jejunal Isc is a consequence of reduced CFTR and NKCC1 expression, along with decreased activities of the basolateral KCa channel and Na+/K+-ATPase. Genistein-diet has beneficial effects on basal Isc mediated by sex-dependent mechanisms in diabetic mice: in females via increased KCa-sensitive Isc and in males via increased Na+/K+-ATPase activity and increased NKCC1 expression. Improved understanding of intestinal dysfunctions in the ob/ob jejunum, may allow for the development of novel drug targets to treat obesity and diabetes, and may also be of benefit in CF-related diabetes.

Treatment Options for Distal Femur Fractures.

Despite advances in implant design, the management of distal femur fractures remains challenging. Fracture comminution and intra-articular extension can make it difficult to obtain an adequate reduction while preserving the soft tissue attachments to bone fragments to allow for bone healing. Many implant manufacturers have developed optimal anatomically contoured, distal femoral locking plates with percutaneous guides. This environment allows for the application of lateral locked plates in a biologically friendly manner. Although initial reports had high success rates, more recently a high rate of nonunion has been found, particularly in elderly patients. Limited literature is available for the treatment of patients with osteoporotic bone and associated ipsilateral total knee replacement and hip replacement. We present a patient with a distal femur fracture with significant comminution in the setting of an ipsilateral total hip replacement.

Practical applications of in-office fiberoptic transnasal esophagoscopy in the initial evaluation of patients with squamous cell cancer of the head and neck.

We conducted a study to analyze the effectiveness of transnasal esophagoscopy (TNE) as an alternative to operative endoscopy (OE) for the evaluation of primary head and neck cancers and for the surveillance of synchronous esophageal cancers. Our study population was made up of 96 consecutively presenting patients-75 men and 21 women, aged 45 to 88 years (mean: 64)-who were treated at our institution for squamous cell cancer of the head and neck. Of this group, 42 patients had been evaluated with TNE and 54 with OE. More OEs were performed in patients with an unknown primary (26 vs. 3). Incidental findings on TNE included 3 cases of gastritis, 2 cases each of hiatal hernia and esophagitis, 1 case of Barrett esophagus, and 1 inlet patch. No incidental findings were reported during OE. Primary cancers were biopsied by TNE through a port on the endoscope in 4 patients; 2 of these cancers were in the tongue base, 1 in the hypopharynx, and 1 in the aryepiglottic fold. After the initial visit, patients in the TNE group waited significantly fewer days for their endoscopy than did those in the OE group (median: 6.5 vs. 16; p < 0.05). Conversely, patients in the OE group waited significantly fewer days for treatment following endoscopy (median: 12 vs. 20; p < 0.05). However, there was no significant difference between the TNE patients and the OE patients in the total number of days comprising their entire course of management, from the initial visit to definite treatment (median: 27.5 and 33 days, respectively; p = 0.7). We conclude that TNE is a reasonable alternative to OE for the initial screening for synchronous esophageal cancers in patients with squamous cancers of the head and neck. OE is preferred for the initial workup of unknown primary cancers and for large tongue base cancers. The rate of detection of clinically relevant incidental findings is higher with TNE. Biopsy is possible during TNE for all subsites within the upper aerodigestive tract.

A survey of current practices, attitudes, and knowledge regarding human papillomavirus-related cancers and vaccines among head and neck surgeons.

IMPORTANCE: Understanding head and neck surgeons' current knowledge, practices, and opinions regarding human papillomavirus (HPV) education and prevention will enable efforts to assist surgeons in this important endeavor. OBJECTIVE: To assess knowledge, attitudes, and beliefs of head and neck surgeons regarding HPV education and vaccination. DESIGN, SETTING, AND PARTICIPANTS: Online survey of members of the American Head and Neck Society (AHNS) in late 2011 and early 2012. MAIN OUTCOMES AND MEASURES: Knowledge, attitudes, and current practices regarding HPV education and vaccination. RESULTS: All 1081 members of the AHNS were approached via e-mail, and 297 members completed the survey, for an overall response rate of 27.5%. Most respondents were male (86.2%) fellowship-trained head and neck surgeons (80.4%), and most practice in an academic setting (77.1%) in the United States (78.1%). More than 90% of respondents discuss risk factors for head and neck cancer and HPV as a specific risk factor with their patients. However, only 49.1% discuss the importance of vaccinating preadolescents for HPV, most commonly citing that they do not do so because their patients are adults (38.7%). Of those respondents with daughters, 68.9% reported that their daughters had received or they intend their daughters to receive the HPV vaccine. Of those respondents with sons, only 55.8% reported that their sons had been vaccinated or they intend for them to be. Respondents reported divergent attitudes toward HPV vaccination safety and efficacy. However, respondents were overwhelmingly supportive of possible future ANHS activities to educate clinicians, increase public awareness, educate patients, and advocate for health policy related to HPV. CONCLUSIONS AND RELEVANCE: Head and neck surgeons are knowledgeable about HPV and show generally positive attitudes and beliefs about HPV education and vaccination. They endorse AHNS actions to improve public and patient education, as well as health policy on HPV. These findings support AHNS developing a strategic plan and actions to improve knowledge and reduce HPV infection among the American public.

Novel neoadjuvant immunotherapy regimen safety and survival in head and neck squamous cell cancer.

BACKGROUND: Cellular immune suppression is observed in head and neck squamous cell cancer (HNSCC) and contributes to poor prognosis. Restoration of immune homeostasis may require primary cell-derived cytokines at physiologic doses. An immunotherapy regimen containing a biologic, with multiple-active cytokine components, and administered with cytoxan, zinc, and indomethacin was developed to modulate cellular immunity. METHODS: Study methods were designed to determine the safety and efficacy of a 21-day neoadjuvant immunotherapy regimen in a phase 2 trial that enrolled 27 therapy-naïve patients with stage II to IVa HNSCC. Methods included safety, clinical and radiologic tumor response, disease-free survival (DFS), overall survival (OS), and tumor lymphocytic infiltrate (LI) data collection. RESULTS: Acute toxicity was minimal. Patients completed neoadjuvant treatment without surgical delay. By independent radiographic review, 83% had stable disease during treatment. OS was 92%, 73%, and 69% at 12, 24, and 36 months, respectively. Histologic analysis suggested correlation between survival and tumor LI. CONCLUSION: Immunotherapy regimen was tolerated. Survival results are encouraging.