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Background Tranexamic acid (TXA) has been effective in reducing perioperative blood loss in hip, knee, and shoulder arthroplasty. Our purpose was to assess the effect of TXA on perioperative blood loss for open elbow release. Methods Consecutive open elbow releases performed between October 2016 and March 2020 were identified. Patients were included if both anterior and posterior joint releases with a single medial approach was performed. From November 2018 onward, intravenous TXA and topical TXA infused through a deep hemovac drain were administered as part of the perioperative protocol. Drain output, intraoperative blood loss, postoperative aspiration rate, and postoperative transfusion frequency were assessed. Results Fifty patients (25 TXA, 25 non-TXA) were included. Drain output was significantly lower in the TXA-treated group compared to the non-treated group (121 mL vs. 221 mL; p = 0.003). There was no significant difference in intraoperative blood loss and the incidence of postoperative aspiration between groups. None of the patients received a blood transfusion or had a documented thromboembolic event. Discussion The use of tranexamic acid with open elbow release surgeries resulted in decreased drain output, with no thromboembolic events. Perioperative tranexamic acid can be a safe and effective modality in reducing perioperative blood loss for open elbow release surgery.

Background Although ulnar neuritis can occur secondary to ulnar collateral ligament pathology, stress fractures, and traction apophysitis, isolated ulnar nerve dysfunction can lead to medial elbow pain. The purpose of this study was to evaluate the short-term outcomes of overhead athletes undergoing anterior ulnar nerve transposition for ulnar neuropathy. Methods All overhead athletes who underwent isolated ulnar nerve transposition between 2009 and 2016 for refractory ulnar neuritis were identified. The primary outcome was return to sport, and secondary outcome measures included the Kerlan-Jobe Orthopaedic Clinic score; Mayo Elbow Performance Score; Quick Disabilities of the Arm, Shoulder and Hand score; Single Assessment Numeric Evaluation score; and visual analog scale score for pain. Complication and reoperation rates were recorded. Results A total of 26 overhead athletes (21 male and 5 female athletes) underwent ulnar nerve transposition at an average age of 18.4 years (range, 11-25 years). Of the patients, 24 (92%) returned to their sporting activity at an average of 2.7 months postoperatively, including 16 (62%) at the previous level of play. The average visual analog scale pain score improved from 4.7 (±2.5) to 0.4 (±1.5) (P = .015). The average postoperative patient-reported outcome scores were as follows: Kerlan-Jobe Orthopaedic Clinic score, 80 (95% confidence interval [CI], 72.7-87.0); Single Assessment Numeric Evaluation score, 85 (95% CI, 75.4-94.7); Quick Disabilities of the Arm, Shoulder and Hand score, 5 (95% CI, 2.1-7.7); and Mayo Elbow Performance Score, 91 (95% CI, 86.8-96.0). Conclusion Cubital tunnel syndrome can cause medial elbow pain in overhead athletes in the presence of a normal ulnar collateral ligament. At mid-term follow-up, 92% of overhead athletes returned to sport after ulnar nerve transposition, with 62% resuming their previous level of performance.

Background Distal biceps reconstruction for chronic rupture often requires a graft to recover length and allow for distal tendon reattachment to bone. Our purpose was to assess peak strength and endurance recovery following biceps reconstruction with tendon grafts. Hypothesis We hypothesized that allograft reconstruction would result in decreased flexion and supination peak strength and endurance. Methods Consecutive distal biceps reconstructions with allograft, performed for chronic ruptures between January 2008 and March 2018 at a single institution, were reviewed. Isokinetic dynamometry for peak strength and endurance testing was performed on the operative and contralateral arms in flexion and supination. Functional outcomes and overall satisfaction with the operation were determined. Results Eleven patients were available for a complete evaluation, including dynamometry, at a mean of 46 months postoperatively. Reconstructions demonstrated a nonsignificant trend toward decreased peak flexion strength (P = .06), and significantly decreased peak supination strength (P = .01) compared with the unaffected arm. There were no differences in flexion and supination endurance between the affected and unaffected arms. Using standardized outcome scales, patients reported excellent function. Conclusion Chronic biceps ruptures undergoing reconstruction are highly functional and patients are satisfied. Somewhat surprisingly, supination and flexion endurance were equal to the contralateral, uninvolved arm. However, this procedure does not restore peak supination strength.

Background Patients received care over telemedicine during the COVID-19 pandemic, and their perspective is useful for hand surgeons. Methods Online surveys were sent October-November 2020 to 497 patients who received telemedicine care. Questions were free-response and multi-item Likert scales asking about telehealth in general, limitations, benefits, comparisons to in-person visits, and opinions on future use. Results The response rate was 26% (n = 130). Prior to the pandemic, 55% had not used telemedicine for hand surgery consultation. Patients liked their telemedicine visit and felt their provider spent enough time with them (means = 9/10). In all, 48% would have preferred in-person visits despite the pandemic, and 69% would prefer in-person visits once the pandemic concludes. While 43% had no concerns with telemedicine, 36% had difficulties explaining their symptoms. Telemedicine was easy to access and navigate (M = 9/10). However, 23% saw telemedicine of limited value due to the need for an in-person visit soon afterward. Of these patients, 46% needed an in-person visit due to inadequate physical examination. Factors that make telemedicine more favorable to patients included convenience, lack of travel, scheduling ease, and time saved. Factors making telemedicine less favorable included need for in-person examination or procedure, pain assessment, and poor connectivity. There was no specific appointment time the cohort preferred. Patient recommendations to improve telemedicine included decreasing wait times and showing patient queue, wait time, or physician status online. Conclusions Telemedicine was strongly liked by patients during the COVID-19 pandemic. However, nearly 70% of patients still preferred in-person visits for the future.

Objective The aim of the study is to survey hand surgeons' perspectives on telemedicine during the coronavirus disease 2019 (COVID-19) pandemic and intended applications after the pandemic. Methods Online surveys were sent to 285 Canadian and American surgeons in late April and early May 2020. Results Response rate was 63% (180)—84% (152) American and 16% (28) Canadian. Forty-three percent (76) of respondents were in private practice, 36% (64) academics, 13% (24) privademics, and 6% (12) hospital employed. The most common telemedicine platform was Zoom. During the pandemic, 42% of patient visits were conducted via telemedicine; however, 37% required a subsequent in-person office visit. The most common complaint by surgeons was the inability to provide routine in-office procedures. The most beneficial feature was ease of use, and the most frustrating feature was connectivity difficulty. Time spent was similar to in-person visits, and surgeons were likely to recommend their platforms. Surgeons were neutral about using telehealth in the future and were most likely to use it for follow-up visits. New patient visits for traumatic injuries or fractures were of limited value. Canadians used telemedicine for a greater proportion than Americans (50 vs. 40%, p Conclusion Telemedicine comprised nearly half of patient encounters during the COVID-19 pandemic, but limitations remain.

BACKGROUND: Indications for adjuvant radiation therapy (XRT) in breast cancer have expanded. Although highly effective, XRT damages surrounding tissues and vasculature, often resulting in delayed or compromised breast reconstruction. Thus, effective, yet safe methods of radiation injury prophylaxis would be desirable. Amifostine is a FDA-approved radio-protectant, however, concerns about its potential to also protect cancer remain. The purpose of this study was to evaluate the oncologic safety of Amifostine in vitro and determine its effect on human breast cancer cells in the setting of XRT. METHODS: One ER+/PR+/Her2- (MCF-7) and two ER-/PR-/Her2- (MDA-MB-231,MDA-MB-468) breast cancer cell lines were investigated. Female Fibroblasts (FF) were utilized as controls. Cells were treated with WR-1065, the active metabolite of Amifostine, 20 minutes before 0Gy, 10Gy, or 20Gy XRT. Live and dead cells were quantified; percent cell death was calculated. RESULTS: WR-1065 treatment significantly preserved viability and reduced healthy FF death after XRT compared to untreated controls. All three breast cancer cells lines exhibited radio-sensitivity with substantial cell death. Cancer cells retained their radio-sensitivity despite WR-1065 pretreatment, achieving the same degree of cell death as untreated controls. CONCLUSIONS: This study demonstrated the proficiency of Amifostine to selectively protect healthy cells from XRT, while breast cancer cells continued to remain radiosensitive. These results support the oncologic safety of Amifostine in breast cancer in vitro. Further investigation is now warranted in vivo to ascertain the translational potential of using Amifostine as a radio-protectant for breast reconstruction after radiation treatment.

Background In-transit metastatic melanoma of the extremity is a clinically aggressive disease. For patients with disease confined to the limb, regional chemotherapy remains an effective option. However, no studies thus far have included cytoreduction or perfusion/infusion without using a limb tourniquet as part of the operative procedure. We hypothesize that combining cytoreduction with no-tourniquet HILP/HILI is safe in patients of all ages and results in durable responses. Methods A retrospective analysis was performed of a prospectively collected database of patients with in-transit malignant melanoma who underwent cytoreduction and HILP/HILI between 2013 and 2017. The primary endpoint was RECIST response at 3–12 months. Secondary endpoints included length of hospital stay, adverse effects, overall survival, and time to recurrence. A subgroup analysis was performed in patients ≥80 years old. Results HILP patients had significantly higher disease burdens than HILI patients. Complete response rates for HILP and HILI were 95% and 75%, respectively at 3 months and 47% and 50%, respectively at 1 year (50% for patients >80) with 100% 1-year survival rates for both HILP and HILI patients. Three-year survival rates were 57% (HILP), 52% (HILI) and 68% (patients >80 years old). The average length of stay for all patients was 3.6 ± 1.4 days. Conclusion Combining cytoreduction with no-tourniquet HILP/HILI for in-transit metastatic melanoma of the extremity resulted in 100% survival regardless of age at 1 year and 68% 3-year survival in patients over 80 without any increase in adverse events.

Intraoperative parathyroid hormone (IOPTH) monitoring is used to predict biochemical cure during parathyroidectomy for primary hyperparathyroidism; however, there is variability in the intraoperative parathyroid hormone criteria used by surgeons to predict normocalcemia after parathyroidectomy. This study sought to determine the intraoperative parathyroid hormone criteria correlated with the lowest rates of persistent hyperparathyroidism after parathyroidectomy for primary hyperparathyroidism.This is a retrospective cohort study of 2,654 patients with primary hyperparathyroidism who underwent parathyroidectomy with intraoperative parathyroid hormone monitoring at a single institution from 1999 to 2014. Multivariate logistic regression analysis was used to measure the association between the lowest intraoperative parathyroid hormone level and the persistence of primary hyperparathyroidism after parathyroidectomy.A total of 66 patients (2.5%) had persistent hyperparathyroidism after parathyroidectomy. Using the traditional intraoperative parathyroid hormone criteria of a ≥50% decrease from the baseline level, the rate of persistent primary hyperparathyroidism was greater when intraoperative parathyroid hormone did not decrease to ≥50% from the baseline level (17 of 180 patients [9.4%] vs 49 of 2,474 [2.0%], [OR 5.9, 95% CI 3.2-10.5, P.001]). Regardless of whether intraoperative parathyroid hormone decreased ≥50%, patients with a lowest intraoperative parathyroid hormone above the normal range (10-65 pg/mL) had greater persistence rates compared with patients with an intraoperative parathyroid hormone65 pg/mL (30 of 350 [8.6%] vs 36 of 2,304 [1.6%], [OR 6.6, 95% CI 3.4-12.7, P .001]). Furthermore, patients with a lowest intraoperative parathyroid hormone 40 to 65 pg/mL had increased rates of adjusted persistence compared with patients with lowest intraoperative parathyroid hormone ≤40 pg/mL (13 of 385 [3.4%] vs 23 of 1,919 [1.2%], [OR 4.2, 95% CI 2.0-8.7, P.001]). Patients with lowest intraoperative parathyroid hormone5 to 20 pg/mL did not have decreased rates of persistence compared with patients with lowest intraoperative parathyroid hormone 20 to 40 pg/mL (9 of 996 [0.9%] vs 14 of 923 [1.5%], [OR 0.5, 95% CI 0.2-1.2, P = .14]).Patients with a lowest intraoperative parathyroid hormone ≤40 pg/mL compared with the traditional criteria of a ≥50% decrease from baseline and a final parathyroid hormone in the normal range (65 pg/mL) had the lowest rates of persistent primary hyperparathyroidism after parathyroidectomy for primary hyperparathyroidism. The single criteria of a lowest intraoperative parathyroid hormone level ≤40 pg/mL may best predict the lowest persistent disease rates after parathyroidectomy for primary hyperparathyroidism.

Background Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine has immense potential to up-regulate angiogenesis and improve reconstructive outcomes. The purpose of this study was to determine the impact of deferoxamine on breast cancer cell proliferation in vitro, to delineate oncologic safety concerns regarding the use of deferoxamine as a regenerative therapeutic. Methods The dose-dependent effect of radiation and deferoxamine on two triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) was determined by means of MTS (percentage cell viability) and tumorsphere (sphere number) analysis. Radiation therapy and deferoxamine were delivered both individually and in combination, and all experiments were completed in triplicate. Intracellular iron, nuclear factor-κB localization, and apoptosis/necrosis assays were performed to delineate mechanism. Analysis of variance statistical analysis was performed using SPSS (p Results For both cell lines, percentage viability and sphere number significantly decreased following exposure to 10 Gy of radiation. Surprisingly, the administration of 25 µM deferoxamine also significantly decreased each metric. The administration of deferoxamine (100 µM) in combination with radiation (10 Gy) resulted in significantly reduced percentage viability and sphere number compared with the administration of radiation alone. Deferoxamine treatment decreased intracellular iron, suppressed nuclear factor-κB activation, and induced apoptosis. Conclusion Radiation and deferoxamine significantly decrease breast cancer proliferation when delivered independently and in combination, suggesting deferoxamine may be safely used to facilitate improved reconstructive outcomes among triple-negative breast cancer survivors. Clinical question/level of evidence Therapeutic, V.

Approximately 6.3 million fractures occur in the U.S. annually, with 5–10% resulting in debilitating nonunions. A major limitation to achieving successful bony union is impaired neovascularization. To augment fracture healing, we designed an implantable drug delivery technology containing the angiogenic stimulant, deferoxamine (DFO). DFO activates new blood vessel formation through iron chelation and upregulation of the HIF-1α pathway. However, due to its short half-life and rapid clearance, maintaining DFO at the callus site during peak fracture angiogenesis has remained challenging. To overcome these limitations, we composed an implantable formulation of DFO conjugated to hyaluronic acid (HA). This compound immobilizes DFO within the fracture callus throughout the angiogenic window, making it a high-capacity iron sponge that amplifies blood vessel formation and prevents nonunions. We investigated implanted HA-DFO’s capacity to facilitate fracture healing in the irradiated rat mandible, a model whereby nonunions routinely develop secondary to obliteration of vascularity. HA-DFO implantation significantly improved radiomorphometrics and metrics of biomechanical strength. In addition, HA-DFO treated mandibles exhibited a remarkable 91% bone union rate, representing a 3.5-fold improvement over non-treated/irradiated controls (20% bone union rate). Collectively, our work proposes a unique methodology for the targeted delivery of DFO to fracture sites in order to facilitate neovascularization. If these findings are successfully translated into clinical practice, millions of patients will benefit from the prevention of nonunions.

Background Open injuries communicating with the wrist joint are essential to detect to facilitate timely, appropriate treatment. While the saline load test to detect traumatic arthrotomy has been well studied in the knee and ankle, it has not been studied in the wrist, and therefore the appropriate volume of saline infusion to detect traumatic arthrotomy is not known. Purpose The purpose of this study was to utilize wrist arthroscopy to determine the saline infusion volume necessary to achieve 99% sensitivity in detecting traumatic arthrotomy. Methods Twenty consecutive patients undergoing elective wrist arthroscopy were prospectively enrolled. A 5-mm arthrotomy was established between the third and fourth dorsal extensor compartments. An 18-gauge needle was inserted into the 6R portal on the radial side of the extensor carpi ulnaris. Sterile normal saline was injected into the wrist joint through the needle at a rate of 0.1 mL per second until extravasation from the 3–4 portal was visualized. Saline volumes required for extravasation were analyzed. Results The mean saline volume required for extravasation was 0.8 mL. The volume of saline needed to achieve sensitivities of 50, 90, 95, and 99% were 0.4, 2.2, 2.3, and 2.5 mL respectively. Conclusions The saline infusion volume required to detect a dorsal radiocarpal arthrotomy with 99% sensitivity was 2.5 mL. We recommend using at least 2.5 mL when performing the saline load test to rule out a potential arthrotomy to the wrist in the traumatic setting. Level of Evidence: This is a Level II, diagnostic study.

Background Patterns and prognostic implications of recurrent adrenocortical carcinoma are poorly understood. In this study, we aim to describe temporal and spatial patterns of adrenocortical carcinoma recurrence. Methods This is a retrospective review of 576 patients with adrenocortical carcinoma evaluated at a single institution. Clinicopathologic and follow-up data were collected longitudinally. Results A total of 354 patients underwent resection of stage I-III adrenocortical carcinoma. We found that 249 (70%) patients developed disease recurrence. The median recurrence-free interval after primary resection was 11 months. The most common sites of initial recurrence were lung and tumor bed. The shortest time to recurrence was associated with lung or multiple site metastases. We found that 142 of 249 patients developed one or more additional sites of recurrence (median 5 months), most commonly involving the lungs. A total of 20 patients developed a third site of recurrence. We found that 100 patients underwent one or more reoperations or metastasectomies and 79 recurred again after reoperation. Same organ or site recurrence was common after reoperation (67%). Although lung metastases occurred early, recurrences to the peritoneal cavity or to multiple sites were associated with worse survival. Metastasectomy beyond three total operations did not improve overall survival. Conclusion Survival varies according to site of recurrence and other clinicopathologic factors. Knowledge of patterns of recurrence may assist in anticipating disease course and lead to better informed selection of treatment.

Introduction Therapeutic strategies for melanoma have evolved significantly over the last decade shifting from cytotoxic chemotherapies like dacarbazine to targeted therapies and immunotherapies including immune checkpoint inhibitors. These new drug therapies have improved overall as well as progression-free survival, lowering the mortality of this cancer for melanoma patients with advanced disease. Newer strategies incorporate combination therapies that harness synergies between mechanisms of anticancer efficacy as well as help overcome resistance issues of monotherapies, which remain a challenge. Areas covered This review looks at each class of drug therapy for melanoma and provides an overview of the preclinical mechanism of action, the clinical efficacy data, and their applications in combination therapy regimens. NCCN treatment guidelines, safety, toxicity, and immune related adverse events are also described as well as a note on cost. Expert opinion Numerous ongoing trials continue to evaluate the role of novel therapies and combinations for this challenging disease and understanding their mechanism of action, risks, benefits, and treatment guidelines can help care providers and patients have a more comprehensive and tailored discussion of treatment options and expectations.

Objective Functional seizures often are managed incorrectly as a diagnosis of exclusion. However, a significant minority of patients with functional seizures may have abnormalities on neuroimaging that typically are associated with epilepsy, leading to diagnostic confusion. We evaluated the rate of epilepsy-associated findings on MRI, FDG-PET, and CT in patients with functional seizures. Methods We studied radiologists' reports from neuroimages at our comprehensive epilepsy center from a consecutive series of patients diagnosed with functional seizures without comorbid epilepsy from 2006 to 2019. We summarized the MRI, FDG-PET, and CT results as follows: within normal limits, incidental findings, unrelated findings, non-specific abnormalities, post-operative study, epilepsy risk factors (ERF), borderline epilepsy-associated findings (EAF), and definitive EAF. Results Of the 256 MRIs, 23% demonstrated ERF (5%), borderline EAF (8%), or definitive EAF (10%). The most common EAF was hippocampal sclerosis, with the majority of borderline EAF comprising hippocampal atrophy without T2 hyperintensity or vice versa. Of the 87 FDG-PETs, 26% demonstrated borderline EAF (17%) or definitive EAF (8%). Epilepsy-associated findings primarily included focal hypometabolism, especially of the temporal lobes, with borderline findings including subtle or questionable hypometabolism. Of the 51 CTs, only 2% had definitive EAF. Significance This large case series provides further evidence that, while uncommon, EAF are seen in patients with functional seizures. A significant portion of these abnormal findings are borderline. The moderately high rate of these abnormalities may represent framing bias from the indication of the study being “seizures,” the relative subtlety of EAF, or effects of antiseizure medications.

Objective Transcranial Focused Ultrasound (tFUS) is a promising new potential neuromodulation tool. However, the safety of tFUS neuromodulation has not yet been assessed adequately. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of tFUS neuromodulation. Histological changes in tissue after tFUS can be examined after surgical resection, while further potential safety concerns can be assessed using neuropsychological testing. Methods Neuropsychological functions were assessed in eight patients before and after focused ultrasound sonication of the temporal lobe at intensities up to 5760 mW/cm2. Using the BrainSonix Pulsar 1002, tFUS was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed using various batteries. Histological changes were assessed using hematoxylin and eosin staining, among others. Results With respect to safety, the histological analysis did not reveal any detectable damage to the tissue, except for one subject for whom the histology findings were inconclusive. In addition, neuropsychological testing did not show any statistically significant changes in any test, except for a slight decrease in performance on one of the tests after tFUS. Significance This study supports the hypothesis that low-intensity Transcranial Focused Ultrasound (tFUS) used for neuromodulation of brain circuits at intensities up to 5760 mW/cm2 may be safe for use in human research. However, due to methodological limitations in this study and inconclusive findings, more work is warranted to establish the safety. Future directions include greater number of sonications as well as longer exposure at higher intensity levels to further assess the safety of tFUS for modulation of neuronal circuits.

Background Rupture of the distal biceps tendon is an increasingly frequent injury sustained predominantly by middle-aged men. Despite the prevalence of sport in this age group, little is known regarding return to sport outcomes following surgery. Methods Patients undergoing distal biceps tendon repair (DBR) between January 2015 and January 2017 were contacted electronically via e-mail and via telephone to administer a previously validated and standard return to sport survey. Patients self-reported preinjury and current level of sport and activity as well as preinjury and current level of select weightlifts. Results A total of 77 of 124 patients were available for follow-up (62.1%). Of these patients, 61 endorsed preoperative sport and were included for analysis. Average follow-up was 38.7 ± 6.7 months. The mean age at surgery was 47.5 ± 8.8 years, and the mean body mass index was 30.3 ± 5.1. The dominant side was affected in 25 of 61 cases. Of the 61 included patients, 57 (93.4%) were able to return to sport at any level (lower, same, or higher intensity than preinjury activity level). Forty of the patients (65.6%) were able to return to sport at same or higher intensity. Mean time to return to sport was 6.0 ± 2.8 months. Days from injury to surgery (odds ratio [OR] 0.999, 95% confidence interval [CI] 0.998-0.999), suture anchor fixation in comparison to suture button (OR 0.602, 95% CI 0.427-0.850), and dominant-side surgery (OR 0.749, 95% CI 0.582-0.963) were associated with a decreased likelihood to return to sport at same or higher level of duty. Single-sided incision in comparison to double (OR 5.209, 95% CI 1.239-20.903) and dominant-side surgery (OR 6.370, 95% CI 1.639-24.762) were associated with increased duration to return to sport. Conclusion Distal biceps tendon rupture is a significant injury; however, patients can expect high levels of return to sport following DBR with some residual impairment compared with baseline. It is important to counsel patients on their expectations while taking into account the results of this study: that there will be a small but appreciable decrease in strength compared with preinjury levels.

Background: Little is known about the clinical indications of performing a revision distal biceps tendon repair/reconstruction, and there is even less data available on the clinical outcomes of patients after revision surgery. Purpose: To determine the clinical outcomes of patients undergoing revision distal biceps tendon repair/reconstruction and evaluate the causes of primary repair failure. Study Design: Case series; Level of evidence, 4. Methods: We performed a retrospective review of patients undergoing ipsilateral primary and revision distal biceps tendon repair/reconstruction at a single institution. Between 2011 and 2016, a total of 277 patients underwent distal biceps tendon repair, with 8 patients requiring revision surgery. Patient characteristics, surgical technique, and patient-reported outcome scores (shortened version of Disabilities of Arm, Shoulder and Hand [QuickDASH], 12-Item Short Form Health Survey [SF-12], visual analog scale [VAS] for pain, and Mayo Elbow Performance Score [MEPS]), were assessed. Complications as well as indications for reoperation after primary and revision surgery were examined. Results: The overall revision rate was 2.9%. The number of single- and double-incision techniques utilized were similar among the primary repairs (50% single-incision, 50% double-incision) and revision repairs/reconstructions (62.5% single-incision, 37.5% double-incision). Reasons for reoperation included continued pain and weakness (n = 7), limited range of motion (n = 2), and acute traumatic re-rupture (n = 1). The median duration between primary and revision surgery was 9.5 months (interquartile range [IQR], 5.8-12.8 months). Intraoperatively, the most common finding during revision was a partially ruptured, fibrotic distal tendon with extensive adhesions. At a median of 33.7 months after revision surgery (IQR, 21.7-40.7 months), the median QuickDASH was 12.5 (IQR, 1.7-23.3), MEPS was 92.5 (IQR, 80.0-100), SF-12 mental component measure was 53.4 (IQR, 47.6-58.2), SF-12 physical component measure was 52.1 (IQR, 36.9-55.4), and VAS for elbow pain was 1.0 (IQR, 0-2.0). Revision surgery had a complication rate of 37.5% (3 of 8 patients), consisting of persistent pain and weakness (2 patients; 25%) and numbness over the dorsal radial sensory nerve (1 patient; 12.5%). Two patients required reoperation (25% reoperation rate). Conclusion: The overall revision distal biceps repair/reconstruction rate was approximately 3%. While patients undergoing revision distal biceps repair demonstrated improved outcomes after revision surgery, these outcomes remained inferior to previously reported outcomes of patients undergoing only primary distal biceps repair.

The purpose of this study was to evaluate the rate and duration of return to work in patients undergoing distal triceps repair (DTR).Consecutive patients undergoing DTR from 2009 to 2017 at our institution were retrospectively reviewed at a minimum of 1 year postoperatively. Patients completed a standardized and validated work questionnaire; a visual analog scale for pain; the Mayo Elbow Performance Score; the short version of the Disabilities of the Arm, Shoulder and Hand questionnaire; and a satisfaction survey.Of 113 eligible patients who underwent DTR, 81 (71.7%) were contacted. Of these patients, 74 (91.4%) were employed within 3 years prior to surgery (mean age, 46.0 ± 10.7 years; mean follow-up, 5.9 ± 3.9 years). Sixty-nine patients (93.2%) returned to work by 2.2 ± 3.2 months postoperatively. Sixty-six patients (89.2%) were able to return to the same level of occupational intensity. Patients who held sedentary-, light-, medium-, and high-intensity occupations were able to return to work at a rate of 100.0%, 100.0%, 80.0%, and 76.9%, respectively, by 0.3 ± 0.5 months, 1.8 ± 1.5 months, 2.5 ± 3.6 months, and 4.8 ± 3.9 months, respectively, postoperatively. Of the workers' compensation patients, 15 (75%) returned to work by 6.5 ± 4.3 months postoperatively, whereas 100% of non-workers' compensation patients returned to work by 1.1 ± 1.6 months (P.001). Seventy-one patients (95.9%) were at least somewhat satisfied, with 50 patients (67.6%) reporting excellent satisfaction. Seventy-two patients (97.3%) would undergo the operation again if presented the opportunity. A single patient (1.4%) required revision DTR.Approximately 93% of patients who underwent DTR returned to work by 2.2 ± 3.2 months postoperatively. Patients with higher-intensity occupations had an equivalent rate of return to work but took longer to return to their preoperative level of occupational intensity. Information regarding return to work is imperative in preoperative patient consultation to manage expectations.

A form of telehealth, a surgical electronic clinic (E-clinic, video or telephone visit) is a safe and efficient way for delivering care; however, factors leading to poor clinic utilization are not well-described. This study was performed to gather electronic clinic utilization data and to better define barriers to visit completion.A retrospective review of 199 patients cared for by a general surgery service with subsequent referral to the electronic clinic (January 2019 to June 2019) was performed. Data regarding demographics, medical characteristics, travel distance, and postoperative complications were collected. Patients were categorized based upon visit completion. The χMore than 1/5 of all patients (21.6%) failed to complete the visit. No differences were observed in completion rates according to the type of operation, American Society of Anesthesiologists classification, and age. The failed-completion group had a significantly (P.05) higher proportion of non-Caucasian patients and those with a marital status of single. Travel distance had no impact. Complication rates were low. Pre-clinic readmission within 30 days contributed to failed completion. Reasons for cancellation included medical issues, technical difficulties, and patient preference to have no follow-up in the electronic clinic.Several factors contribute to a patient's failure to complete an electronic clinic visit including marital status, medical complications, technical issues, and patient preference. Electronic clinic utilization patterns also demonstrate racial disparities. Successful electronic clinic program implementation requires understanding the factors that contribute to failed visits to address them and improve access.

ObjectiveLow-Intensity Focused Ultrasound Pulsations (LIFUP) is a promising new potential neuromodulation tool. However, the safety of LIFUP neuromodulation has not yet been adequately assessed. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of LIFUP neuromodulation. Because the brain tissue in these patients will be removed, histological changes in tissue after LIFUP can be examined. Evidence of effective neuromodulation was assessed using functional MRI and EEG, while further potential safety concerns were assessed using neuropsychological testing.MethodsEEG, functional MRI, and neuropsychology were assessed in six patients before and after focused ultrasound sonication of the temporal lobe at intensities up to 5760 mW/cm2. Using the BrainSonix Pulsar 1002, LIFUP was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed using various batteries. EEG was recorded using the Electrical Geodesics EGI 256 channel system. Histological changes were assessed using hematoxylin and eosin staining, among others.ResultsLIFUP was not able to modulate the BOLD signal on fMRI in a reliable and consistent manner. The EEG data that was available did not demonstrate a change in activity after LIFUP in all but one subject. Likewise, the neuropsychology testing did not show any statistically significant changes in any test, except for a slight decrease in performance on the one test after LIFUP. Lastly, the histology did not reveal any detectable damage to the tissue, except for one subject for whom the histology findings were inconclusive.SignificanceThe safety in the histology was the primary endpoint, and as such, longer exposure at the highest intensity levels will be administered moving forward.Key PointsLIFUP is a novel brain stimulation technique with not yet fully established safety guidelines.LIFUP was administered to patients electing to undergo resective brain surgery.LIFUP does not appear to cause damage to tissue.Longer exposure times are needed to further show safety at these intensity levels.

Existing theories suggest that moderate arousal improves selective attention, as would be expected in the context of competitive sports or sensation-seeking activities. Here we investigated how riding a motorcycle, an attention-demanding physical activity, affects sensory processing. To do so, we implemented the passive auditory oddball paradigm and measured the EEG response of participants as they rode a motorcycle, drove a car, and sat at rest. Specifically, we measured the N1 and mismatch negativity to auditory tones, as well as alpha power during periods of no tones. We investigated whether riding and driving modulated non-CNS metrics including heart rate and concentrations of the hormones epinephrine, cortisol, DHEA-S, and testosterone. While participants were riding, we found a decrease in N1 amplitude, increase in mismatch negativity, and decrease in relative alpha power, together suggesting enhancement of sensory processing and visual attention. Riding increased epinephrine levels, increased heart rate, and decreased the ratio of cortisol to DHEA-S. Together, these results suggest that riding increases focus, heightens the brain's passive monitoring of changes in the sensory environment, and alters HPA axis response. More generally, our findings suggest that selective attention and sensory monitoring seem to be separable neural processes.

Background: Physician extenders, such as physician assistants (PAs) and nurse practitioners (NPs), have been incorporated into health systems in response to the rising demand for care. There is a paucity of literature regarding patient perspectives toward physician extenders in hand surgery. Methods: We anonymously surveyed 939 consecutive new patients before their clinic visit. Our questionnaire assessed patient perspectives toward physician extenders, including optimal scope of practice, the effect of the extender when choosing a hand surgeon, and pay equity for the same clinical services. Results: Of 939 patients, 784 (84%) responded: 54% were male and 46% were female with a mean age of 44.1 years. Most (65%) patients consider the extender’s training background when choosing a hand surgeon, with 31% of all patients considering PAs to have higher training than NPs and 17% the reverse. Patients responded that certain services should be physician-provided, including determining the need for advanced imaging (eg, magnetic resonance imaging), follow-up for abnormal diagnostics, and new patient visits. Patients were amenable to services being extender-provided, including minor in-office procedures, preoperative teaching, and postoperative clinic visits. Patients lacked a consensus toward reimbursement equity for hand surgeons and physician extenders providing the same clinical services. Conclusions: Our data suggest that patients presenting to a hand surgeon are comfortable receiving direct care from a physician extender in many, but not all, circumstances. Hand surgeons can use these data when deciding how to use extenders to optimize patient satisfaction and practice efficiency as health care systems become increasingly consumer-focused and value-based.

The influence of chronic kidney disease on intraoperative parathyroid hormone monitoring during parathyroidectomy for primary hyperparathyroidism has not been well-established. We hypothesize that chronic kidney disease influences intraoperative parathyroid hormone degradation kinetics during parathyroidectomy.This is a single institution retrospective cohort study of consecutive patients with primary hyperparathyroidism underdoing parathyroidectomy. Patients were stratified according to normal kidney function (glomerular filtration rates ≥60 mL/min/1.73 mOf the 964 study patients, 235 had chronic kidney disease (24.4%), while 729 (75.6%) had normal kidney function. The chronic kidney disease population had a greater median preoperative serum parathyroid hormone (PTH) (125 vs 114 pg/mL; P .001), but similar median intraoperative parathyroid hormone levels (chronic kidney disease versus normal): baseline (190 vs 189; P=.232), 5 minutes (51 vs 47; P = .667), 10 minutes (37 vs 35; P=.626), and at 15 minutes postexcision (28 vs 27; P=.539). There was no significant difference in the kinetics of the intraoperative parathyroid hormone degradation slope from the baseline to the 15-minute postexcision levels comparing chronic kidney disease with normal kidney function (-21.02 vs -20.83; P=.957). Patients with chronic kidney disease had 15-minute postexcision intraoperative parathyroid hormone levels within the normal range (12 - 65 pg/mL) as frequently as patients with normal kidney function (81% vs 82%; P=.906) and had similar rates of persistent disease (3.4% vs 3.4%; P=.985).Patients with chronic kidney disease undergoing parathyroidectomy for primary hyperparathyroidism have similar intraoperative parathyroid hormone degradation kinetics, and the intraoperative parathyroid hormone criteria used to predict cure should be similar to those with normal kidney function.

Posterolateral rotatory instability is caused by insufficiency of the lateral stabilizers of the elbow. Acute instability occurs as a consequence of trauma and is best treated by primary repair. Chronic instability may be a consequence of trauma, but has also been described in the setting of corticosteroid injections for lateral epicondylitis and repetitive varus load. In this setting, ligament reconstruction is typically required.

Advanced head and neck squamous cell carcinoma (HNSCC) remains a therapeutic challenge due to the development of therapy resistance. Several studies have implicated the development of cancer stem cells as a possible mechanism for therapy resistance in HNSCC. Heat shock protein 90’s (Hsp90’s) molecular chaperone function is implicated in pathways of resistance in HNSCC. Therefore, in the present study, we investigated the efficacy of novel C-terminal Hsp90 inhibitors (KU711 and KU757) in targeting HNSCC cancer stem cells (CSCs). Treatment of HNSCC human cell lines MDA1986, UMSCC 22B, and UMSCC 22B cisplatin-resistant cells with the KU compounds indicated complete blockage of self-renewal for the resistant and parent cell lines starting from 20 μM KU711 and 1 μM KU757. Dose-dependent decrease in the cancer stem cell markers CD44, ALDH, and CD44/ALDH double-positive cells was observed for all cell lines after treatment with KU711 and KU757. When cells were treated with either drug, migration and invasion were downregulated greater than 90% even at the lowest concentrations of 20 μM KU711 and 1 μM KU757. Western blot showed >90% reduction in client protein “stemness” marker BMI-1 and mesenchymal marker vimentin, as well as increase in epithelial marker E-cadherin for both cell lines, indicating epithelial to mesenchymal transition quiescence. Several CSC-mediated miRNAs that play a critical role in HNSCC therapy resistance were also downregulated with KU treatment. In vivo, KU compounds were effective in decreasing tumor growth with no observed toxicity. Taken together, these results indicate that KU compounds are effective therapeutics for targeting HNSCC CSCs.

The purpose of this study was to measure the radiographic parameters of proximal pole scaphoid fractures, and calculate the ideal starting points and trajectories for antegrade screw insertion. Computed tomography scans of 19 consecutive patients with proximal pole fractures were studied using open source digital imaging and communications in medicine (DICOM) imaging measurement software. For scaphoid sagittal measurements, fracture inclination was measured with respect to the scaphoid axis. The ideal starting point for a screw in the proximal pole fragment was then identified on the scaphoid sagittal image that demonstrated the largest dimensions of the proximal pole, and hence the greatest screw thread purchase. Measurements were then taken for a standard screw trajectory in the axis of the scaphoid, and a trajectory that was perpendicular to the fracture line. The fracture inclination in the scaphoid sagittal plane was 25 (SD10) °, lying from proximal palmar to dorsal distal. The fracture inclination in the coronal plane was 9 (SD16) °, angling distal radial to proximal ulnar with reference to the coronal axis of the scaphoid. Using an ideal starting point that maximized the thread purchase in the proximal pole, we measured a maximum screw length of 20 (SD 2) mm when using a screw trajectory that was perpendicular to the fracture line. This was quite different from the same measurements taken in a trajectory in the axis of the scaphoid. We also identified a mean distance of approximately 10 mm from the dorsal fracture line to the ideal starting point. A precise understanding of this anatomy is critical when treating proximal pole scaphoid fractures surgically.

Rui Kuai,1,2,* Chitra Subramanian,3,* Peter T White,3,* Barbara N Timmermann,4 James J Moon,1,2,5 Mark S Cohen,3,6 Anna Schwendeman1,2 1Department of Pharmaceutical Sciences, College of Pharmacy, 2Biointerfaces Institute, University of Michigan, 3Department of Surgery, University of Michigan, Ann Arbor, MI, 4Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, 5Department of Biomedical Engineering, 6Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA *These authors contributed equally to this work Abstract: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy and has a 5-year survival rate of

Background and Objectives Current literature may overestimate the risk of nodal metastasis from thin melanoma due to reporting of data only from lesions treated with SLNB. Our objective was to define the natural history of thin melanoma, assessing the likelihood of nodal disease, in order to guide selection for SLNB. Methods Retrospective review. The primary outcome was the rate of nodal disease. Clinicopathologic factors were evaluated to find associations with nodal disease. Results Five hundred and twelve lesions, follow up available for 488 (median: 48 months). Lesions treated with WLE/SLNB compared to WLE alone were more likely to have high-risk features. The rate of nodal disease was higher in the WLE/SLNB group (24 positive SLNB, five false-negative SLNB with nodal recurrence: 10.2%) compared to WLE alone (four nodal recurrences: 2.0%). Univariate analysis showed age ≤45, Breslow depth ≥0.85 mm, mitotic rate >1 mm2, and ulceration were associated with nodal disease. Multivariate analysis confirmed the association of age ≤45 and ulceration. Conclusions SLNB for melanoma 0.75-0.99 mm should be considered in patients age ≤45, Breslow depth ≥0.85 mm, mitotic rate >1 mm2, and/or with ulceration. Thin melanoma

Until recently, patients with advanced thyroid cancers had limited options for systemic treatment. With the introduction of tyrosine kinase inhibitors (TKIs) as a promising new class of targeted therapies for thyroid cancer, suddenly patients with advanced disease were given new options to extend survival. Guidelines worldwide have been updated to include general indications for these newer agents, but questions remain regarding which agent(s) to select, when to begin treatment, and how long therapy should continue. Additionally, the true impact of TKIs on overall survival and quality-of-life in thyroid cancer patients needs further clarification. As familiarity with approved agents and longer-term data become available, better strategies for implementation of these targeted drugs will evolve to optimize benefit for patients living with metastatic disease.

Background:Few large-scale series have described functional outcomes after distal triceps tendon repair. Predictors for operative success and a comparative analysis of surgical techniques are limited in the reported literature.Purpose:To evaluate short-term to midterm functional outcomes after distal triceps tendon repair in a broad patient population and to comparatively evaluate patient-reported outcomes in patients with and without pre-existing olecranon enthesopathy while also assessing for modifiable risk factors associated with adverse patient outcomes and/or revision surgery.Study Design:Case series; Level of evidence, 4.Methods:This study was a retrospective analysis of 69 consecutive patients who underwent surgical repair of distal triceps tendon injuries at a single institution. Demographic information, time from injury to surgery, mechanism of injury, extent of the tear, pre-existing enthesopathy, perioperative complications, and validated patient-reported outcome scores were included in the analysis. Patients with a minimum of 1-year follow-up were included.Results:The most common mechanisms of injury were direct elbow trauma (44.9%), extension/lifting exercises (20.3%), overuse (17.4%), and hyperflexion or hyperextension (17.4%). Eighteen patients were identified with pre-existing symptomatic enthesopathy, and 51 tears were caused by an acute injury. A total of 36 complete and 33 partial tendon tears were identified. Bone tunnels were most commonly used (n = 30; 43.5%), while direct sutures (n = 23; 33.3%) and suture anchors (n = 13; 18.8%) were also used. Perioperative complications occurred in 21.7% of patients, but no patients experienced a rerupture at the time of final follow-up. No statistically significant relationship was found between patient age ( P = .750), degree of the tear ( P = .613), or surgical technique employed ( P = .608) and the presence of perioperative complications.Conclusion:Despite the heightened risk of perioperative complications after primary repair of distal triceps tendon injuries, the current series found favorable functional outcomes and no cases of reruptures at short-term to midterm follow-up. Furthermore, age, surgical technique, extent of the tear, and mechanism of injury were not associated with adverse patient outcomes in this investigation. Pre-existing triceps enthesopathy was shown to be associated with increased complication rates.

Periprosthetic joint infection (PJI) is a potentially devastating complication after total elbow arthroplasty (TEA) that can lead to significant morbidity for the patient as well as increased health care-related costs. Despite the potential morbidity associated with TEA PJI, evidence is limited regarding an optimal treatment algorithm. Initial management typically consists of either irrigation and debridement or 2-stage revision. A stable implant, a functioning triceps, and an intact soft tissue envelope are necessary to perform irrigation and debridement. Irrigation and debridement is associated with a relatively high risk of infection recurrence especially in chronic infections. Two-stage revision offers a lower recurrence risk, although there is a 25% chance of not completing the second stage. Resection arthroplasty, arthrodesis, and amputation are salvage options, whereas medical treatment, in the form of antibiotics alone, is reserved for poor surgical candidates. Further multicenter prospective study and retrospective review of registry data focusing on different treatment algorithms, prevention strategies, and functional outcomes would be helpful to elucidate the ideal management of elbow PJI.

Purpose Differentiating psychogenic non-epileptic seizures (PNES) from epileptic seizures (ES) can be difficult, even when expert clinicians have video recordings of seizures. Moreover, witnesses who are not trained observers may provide descriptions that differ from the expert clinicians’, which often raises concern about whether the patient has both ES and PNES. As such, quantitative, evidence-based tools to help differentiate ES from PNES based on patients’ and witnesses’ descriptions of seizures may assist in the early, accurate diagnosis of patients. Methods Based on patient- and observer-reported data from 1372 patients with diagnoses documented by video-elect roencephalography (vEEG), we used logistic regression (LR) to compare specific peri-ictal behaviors and seizure triggers in five mutually exclusive groups: ES, PNES, physiologic non-epileptic seizure-like events, mixed PNES plus ES, and inconclusive monitoring. To differentiate PNES-only from ES-only, we retrospectively trained multivariate LR and a forest of decision trees (DF) to predict the documented diagnoses of 246 prospective patients. Results The areas under the receiver operating characteristic curve (AUCs) of the DF and LR were 75% and 74%, respectively (empiric 95% CI of chance 37–62%). The overall accuracy was not significantly higher than the naive assumption that all patients have ES (accuracy DF 71%, LR 70%, naive 68%, p > 0.05). Conclusions Quantitative analysis of patient- and observer-reported peri-ictal behaviors objectively changed the likelihood that a patient’s seizures were psychogenic, but these reports were not reliable enough to be diagnostic in isolation. Instead, our scores may identify patients with “probable” PNES that, in the right clinical context, may warrant further diagnostic assessment.

Ganglion cysts are benign soft tissue tumors that often occur adjacent to joints or tendons. We report a case of an elbow joint ganglion cyst in a patient who presented with a painful, progressive elbow contracture. The patient was successfully treated with resection of the subbrachialis ganglion cyst combined with an anterior capsular release and an ulnar nerve decompression to recover elbow motion. This case highlights the value of advanced imaging in patients presenting with an atraumatic, painful, and progressive elbow contracture.

Purpose Descriptions of seizure manifestations (SM), or semiology, can help localize the symptomatogenic zone and subsequently included brain regions involved in epileptic seizures, as well as identify patients with dissociative seizures (DS). Patients and witnesses are not trained observers, so these descriptions may vary from expert review of seizure video recordings of seizures. To better understand how reported factors can help identify patients with DS or epileptic seizures (ES), we evaluated the associations between more than 30 SMs and diagnosis using standardized interviews. Methods Based on patient- and observer-reported data from 490 patients with diagnoses documented by video-electoencephalography, we compared the rate of each SM in five mutually exclusive groups: epileptic seizures (ES), DS, physiologic seizure-like events (PSLE), mixed DS and ES, and inconclusive testing. Results In addition to SMs that we described in a prior manuscript, the following were associated with DS: light triggers, emotional stress trigger, pre-ictal and post-ictal headache, post-ictal muscle soreness, and ictal sensory symptoms. The following were associated with ES: triggered by missing medication, aura of deja vu, and leftward eye deviation. There were numerous manifestations separately associated with mixed ES and DS. Conclusions Reported SM can help identify patients with DS, but no manifestation is pathognomonic for either ES or DS. Patients with mixed ES and DS reported factors divergent from both ES-alone and DS-alone.

Background The utility of frozen section (FS) for indeterminate thyroid nodules is controversial. In 2009, the Bethesda System for Reporting Thyroid Cytopathology was established to further subcategorize indeterminate fine-needle aspiration results (follicular lesions, FL) into Bethesda category 3 (BC3) and Bethesda category 4 (BC4). We hypothesize that FS will have less utility in the evaluation of BC3 lesions when compared to BC4. Materials and methods A total of 479 patients who underwent thyroid lobectomy from January 2008 to July 2014 were retrospectively reviewed. Patients without appropriate Bethesda categorization were excluded. A total of 135 patients (65 FL, 45 BC3, 25 BC4) comprised the study groups. The sensitivity and specificity of FS within these three categories were determined. Results In the FL group, 6 of 65 patients were found to have thyroid cancer. Three were identified on frozen section (FS) resulting in a sensitivity and specificity of 50% and 100%, respectively. Thus, FS changed the operation in 3 of 65 cases (4.6%). In the BC3 group, 5 of 45 patients were found to have cancer. One was identified on FS resulting in a sensitivity and specificity of 20% and 100%, respectively. Thus, FS changed the operation in 1 of 45 patients (2.2%). In the BC4 group, 4 of 25 patients were found to have cancer. Two were identified on FS resulting in a sensitivity and specificity of 50% and 100% respectively. Thus, FS changed the operation in 2 of 25 patients (8%). Conclusions There is improved utility of FS in BC 4 patients as 8% avoided reoperation. However, this benefit hinges on surgeon practice regarding the management of differentiated thyroid cancer >1 cm and

Background Fractures of the capitellum are rare and are commonly classified into 4 types. Type II variants involve a shear injury with a mostly articular cartilage component and little subchondral bone. Symptoms upon presentation after these injuries are variable, and the diagnosis can be difficult to make in the immature skeleton. Methods We retrospectively reviewed 3 cases of type II capitellar fractures in adolescent athletes who presented for evaluation with the senior author. Results All patients were initially treated conservatively, without identification or treatment of the capitellar shear component of their injury. Unfortunately, radiocapitellar arthrosis rapidly developed in all 3 and required surgical intervention at our institution. At an average postoperative follow-up of 49 months from the index procedure, patients ultimately had positive outcomes despite advanced degenerative changes on imaging. One patient required 2 subsequent operations for mechanical symptoms and pain. Discussion The 3 reported cases represent adolescent, athletic patients with missed shear injuries to the capitellum. These patients exhibited low Disabilities of Arm, Shoulder and Hand scores and high Mayo Elbow Performance Scores at final follow-up, but each patient demonstrated advanced degenerative changes on imaging, and 1 patient required 2 subsequent operations for mechanical symptoms and pain. A high index of suspicion is necessary to identify this injury pattern, and proper plain radiographic imaging with a low threshold for advanced imaging is necessary. Although the overall long-term prognosis is unknown for these patients, early recognition likely would have changed the initial conservative management decision in each and, theoretically, might have altered the outcome for these patients.

Purpose The average delay from first seizure to diagnosis of psychogenic non-epileptic seizures (PNES) is over 7 years. The reason for this delay is not well understood. We hypothesized that a perceived decrease in seizure frequency after starting an anti-seizure medication (ASM) may contribute to longer delays, but the frequency of such a response has not been well established. Methods Time from onset to diagnosis, medication history and associated seizure frequency was acquired from the medical records of 297 consecutive patients with PNES diagnosed using video-electroencephalographic monitoring. Exponential regression was used to model the effect of medication trials and response on diagnostic delay. Results Mean diagnostic delay was 8.4 years (min 1 day, max 52 years). The robust average diagnostic delay was 2.8 years (95% CI: 2.2–3.5 years) based on an exponential model as 10 to the mean of log 10 delay. Each ASM trial increased the robust average delay exponentially by at least one third of a year (Wald t =3.6, p =0.004). Response to ASM trials did not significantly change diagnostic delay (Wald t =−0.9, p =0.38). Conclusion Although a response to ASMs was observed commonly in these patients with PNES, the presence of a response was not associated with longer time until definitive diagnosis. Instead, the number of ASMs tried was associated with a longer delay until diagnosis, suggesting that ASM trials were continued despite lack of response. These data support the guideline that patients with seizures should be referred to epilepsy care centers after failure of two medication trials.

Thyroid cancer stem cells (CSCs) with ALDH and CD44 markers contribute to tumor growth and aggressiveness. We hypothesized that novel HSP90 inhibitors (KU711, WGA-TA) and 17-AAG can effectively target the function of thyroid CSCs in vitro and prevent migration and invasion.Validated papillary (TPC1), follicular (FTC238,WRO), and anaplastic (ACT1) human thyroid cancer cell lines were treated with 3 HSP90 inhibitors. CSCs were quantified for aldehyde dehydrogenase by flow cytometry, CD44 expression by Western blot, and thyrosphere formation assay. Cellular pathway proteins were analyzed by Western blot and migration/invasion by Boyden-chambers.WGA-TA and 17-AAG induced HSP70 compensation (not observed with KU711) on Western blot in all cell lines (1,000 fold vs controls). Only WGA-TA degraded HSP90-Cdc37 complexing by 60-70% versus controls. Expression of HSP90 clients β-catenin, BRAF, Akt, and phospho-Akt were significantly inhibited by WGA-TA treatment (50-80%, 50-90%,80%, and90%) compared with controls, KU711, and 17-AAG treatment. KU711 and WGA-TA decreased CD44 expression in all cell lines (25-60% vs controls/17-AAG), decreased ALDEFLOR activity by 69-98% (P.005), and decreased sphere formation by 64-99% (P.05 each). Finally, cell migration was decreased by 31-98%, 100%, and 30-38%, and invasion by 75-100%, 100%, and 47% by KU711,WGA-TA, and 17-AAG treatment (P.05) each, respectively.KU711 and WGA-TA are novel HSP90 inhibitors targeting CSC function and inhibiting cell migration/invasion in differentiated and anaplastic thyroid cancers, warranting further translational evaluation in vivo.

Introduction With increasing interest in humanitarian surgical efforts, numerous opportunities for specialized mission trips have developed. Extreme short-term surgical “blitzes” of specialist teams have offered much-needed surgical care but lack efforts for patient continuity and local sustainability. We sought to define characteristics that aid in the long-term success of short-term international surgical missions to better apply this insight toward future dedicated humanitarian endocrine surgical efforts. Materials and methods A broad search engine review identified 1,954 reports of medical and surgical missions. One hundred and sixty-six of these abstracts involved surgical missions from 2009 to 2014 with 24 articles including details of specific mission trips. We identified factors deemed essential for improving patient care and affecting local infrastructure for longterm sustainability and included our prospective experience with an endocrine surgery-specific mission trip for comparison. Results Of the 24 articles reviewed, missions went to Africa (9), North America (8), South America (5), and Asia (5). Factors for mission sustainability and success included the following: (a) ability to educate local physicians and trainees, (b) multiple return trips to the same location, and (c) formal pre-mission planning and site visits. Emerging interest is on optimizing patient outcomes and cost-effectiveness. Conclusion Short-term surgical missions require a local infrastructure for optimal patient outcomes. Sustainability hinges on education and involvement of local physicians and surgical trainees, pre-mission planning, and return trips to the same location. For endocrine surgical missions, preoperative evaluation and postoperative follow-up by the operating surgeon is important for optimizing performance and outcomes. How to cite this article Long KL, Cohen M, Perrier N. Pay It forward: Strategies for Successful Implementation of Short-term Endocrine Surgical Mission. World J Endoc Surg 2016;8(2):137-140.

Objective To develop a Dissociative Seizures Likelihood Score (DSLS), which is a comprehensive, evidence-based tool using information available during the first outpatient visit to identify patients with “probable” dissociative seizures (DS) to allow early triage to more extensive diagnostic assessment. Methods Based on data from 1616 patients with video-electroencephalography (vEEG) confirmed diagnoses, we compared the clinical history from a single neurology interview of patients in five mutually exclusive groups: epileptic seizures (ES), DS, physiologic nonepileptic seizure-like events (PSLE), mixed DS plus ES, and inconclusive monitoring. We used data-driven methods to determine the diagnostic utility of 76 features from retrospective chart review and applied this model to prospective interviews. Results The DSLS using recursive feature elimination (RFE) correctly identified 77% (95% confidence interval (CI), 74–80%) of prospective patients with either ES or DS, with a sensitivity of 74% and specificity of 84%. This accuracy was not significantly inferior than neurologists’ impression (84%, 95% CI: 80–88%) and the kappa between neurologists’ and the DSLS was 21% (95% CI: 1–41%). Only 3% of patients with DS were missed by both the fellows and our score (95% CI 0–11%). Significance The evidence-based DSLS establishes one method to reliably identify some patients with probable DS using clinical history. The DSLS supports and does not replace clinical decision making. While not all patients with DS can be identified by clinical history alone, these methods combined with clinical judgement could be used to identify patients who warrant further diagnostic assessment at a comprehensive epilepsy center.

The aim of this study was to determine clinical outcomes in patients with differentiated thyroid cancer after surgery and activity-adjusted I therapy informed by diagnostic I scans with SPECT/CT (Dx scan).Single-institution retrospective cohort study analysis of clinical outcomes after 1 to 5 years (mean, 39.6 ± 23.4 months) of follow-up in 350 patients with differentiated thyroid cancer associated with histopathologic risk factors, nodal metastases, and/or distant metastases. Postoperatively, all patients underwent Dx scans for completion of staging and risk stratification, and I therapy was based on integration of information from histopathology, stimulated thyroglobulin and scintigraphy.Twenty-three patients (6.6%) underwent reoperative neck dissection for removal of unsuspected residual nodal metastases identified on Dx scans. Clinical outcomes were as follows: 84.3% complete response, 1.4% biochemical incomplete response, 2.3% indeterminate response, and 12% structural incomplete response. Of the entire cohort, only 8 patients (2.3%) had persistent iodine-avid metastatic disease, which required repeated I therapy. Of 31 patients with iodine-avid distant metastases identified on Dx scans, 13 patients (42%) achieved complete response with a single I treatment.Detection of regional and distant metastases on postoperative Dx scans permits adjustment of prescribed I activity for targeted treatment, as compared with fixed-activity ablation. This approach resulted in complete response after a single I treatment in 88% patients with histopathologic risk factors and regional metastases and 42% patients with distant metastases. Most patients with structural incomplete response (81%) had elevated thyroglobulin levels with negative follow-up I scans and positive PET/CT and/or CT scans consistent with altered tumor biology (non-iodine-avid disease).

Objective Psychogenic nonepileptic seizure (PNES) is a common diagnosis after evaluation of medication resistant or atypical seizures with video-electroencephalographic monitoring (VEM), but usually follows a long delay after the development of seizures, during which patients are treated for epilepsy. Therefore, more readily available diagnostic tools are needed for earlier identification of patients at risk for PNES. A tool based on patient-reported psychosocial history would be especially beneficial because it could be implemented in the outpatient clinic. Methods Based on the data from 1375 patients with VEM-confirmed diagnoses, we used logistic regression to compare the frequency of specific patient-reported historical events, demographic information, age of onset, and delay from first seizure until VEM in five mutually exclusive groups of patients: epileptic seizures (ES), PNES, physiologic nonepileptic seizure-like events (PSLE), mixed PNES plus ES, and inconclusive monitoring. To determine the diagnostic utility of this information to differentiate PNES only from ES only, we used multivariate piecewise-linear logistic regression trained using retrospective data from chart review and validated based on data from 246 prospective standardized interviews. Results The prospective area under the curve of our weighted multivariate piecewise-linear by-sex score was 73%, with the threshold that maximized overall retrospective accuracy resulting in a prospective sensitivity of 74% (95% CI: 70–79%) and prospective specificity of 71% (95% CI: 64–82%). The linear model and piecewise linear without an interaction term for sex had very similar performance statistics. In the multivariate piecewise-linear sex-split predictive model, the significant factors positively associated with ES were history of febrile seizures, current employment or active student status, history of traumatic brain injury (TBI), and longer delay from first seizure until VEM. The significant factors associated with PNES were female sex, older age of onset, mild TBI, and significant stressful events with sexual abuse, in particular, increasing the likelihood of PNES. Delays longer than 20 years, age of onset after 31 years for men, and age of onset after 40 years for women had no additional effect on the likelihood of PNES. Discussion Our promising results suggest that an objective score has the potential to serve as an early outpatient screening tool to identify patients with greater likelihood of PNES when considered in combination with other factors. In addition, our analysis suggests that sexual abuse, more than other psychological stressors including physical abuse, is more associated with PNES. There was a trend of increasing frequency of PNES for women during childbearing years and plateauing outside those years that was not observed in men.

Background: The Internet is a widely used resource by patients however, objective data on details such as frequency of usage and specific sites visited is lacking. We surveyed patients from hand surgery practices to describe patient preferences and utilization patterns for online resources. Methods: From October 2015 to June 2016, we enrolled patients presenting to 4 orthopedic hand surgeons at 2 academic institutions. Patients completed a survey, with questions related to their preference for learning about their diagnosis and Internet utilization both before and after the visit. Results: A total of 226 patients were enrolled in the study. Forty-five percent of the patients had done online research prior to the office visit, and 81% preferred to learn about their diagnosis through verbal communication, as opposed to only 8% who listed Web site information. Fifty percent indicated that there was a greater than 50% chance or they would definitely seek additional information on the Internet after the office visit. When asked to choose from a list of Web sites to visit, the most popular Web site was WebMD. Specialty society Web sites (American Society for Surgery of the Hand and American Academy of Orthopaedic Surgeons) were less popular. Conclusions: This survey-based study found that a majority of patients utilize the Internet both before and after the office visit; however, they often utilize unregulated sites for information. This information can help physicians guide patients to high-quality Web sites for information on their clinical diagnosis and treatment.

Malignant pheochromocytomas and paragangliomas are rare. Resection of the primary tumor and metastatic lesions, when feasible, is recommended. Goals of resection include improvement of clinical symptoms, reduction of catecholamine excess, local disease control, improved efficacy of subsequent non-operative therapies, and the possibility of improved survival. A R0 or R1 resection clearly provides more robust biochemical improvement when compared to a R2 resection or ‘surgical debulking.’ Additional non-surgical therapies can be used in conjunction with surgery or as the primary treatment modality in some cases. Non-surgical local therapies include external beam radiation, percutaneous tumor ablation, and directed transarterial chemoembolization. In addition, systemic therapies include radioactive iodine meta-iodobenzylguanidine (131I-MIBG), cytotoxic chemotherapy, and molecular targeted therapy. Care should be taken to provide patients with the appropriate pharmacologic adrenergic blockade prior to the initiation of most therapies. Patients benefit from a multidisciplinary approach at a center familiar with managing malignant pheochromocytoma patients.

Objectives/Hypothesis To evaluate the efficacy of peritumoral hyaluronic acid (HA)-cisplatin therapy in a murine model of laryngeal squamous cell carcinoma and to evaluate its effect on cancer stem cells (CSCs). Study Design An orthotopic murine study utilizing University of Michigan squamous cell carcinoma-12 (UMSCC-12) laryngeal cancer cells was conducted in randomized controlled fashion with three treatment arms: saline, systemic cisplatin, and peritumoral HA-cisplatin. Methods UMSCC-12 laryngeal cancer cells were inoculated into the buccal mucosa of athymic nude mice followed by weekly treatment with saline, systemic cisplatin, or peritumoral HA-cisplatin for 3 weeks. Tumor response and animal weight was monitored and change in CD44 proportion was analyzed ex vivo. Results HA-cisplatin demonstrated superior antitumor efficacy and greater reduction in CD44 positivity on ex vivo analysis. Conclusions Peritumoral nanoconjugated HA-cisplatin provides superior antitumor efficacy compared to standard cisplatin therapy in an in vivo laryngeal cancer model. There was also selective targeting of CD44+ cancer cells with HA-cisplatin. This therapeutic strategy could represent the first selective laryngeal CSC-targeted therapy. Further preclinical investigation is warranted to evaluate its role for locally advanced head and neck cancer treatment. Level of Evidence NA Laryngoscope, 2015

We present 20 patients with established proximal pole scaphoid nonunions treated with curettage and cancellous autograft from the distal radius and screw fixation. Fractures with significant proximal pole fragmentation were excluded. Patients were treated at a mean of 26 weeks after injury (range 12–72). Union occurred in 18 of 20 patients (90%) based on computed tomographic imaging. The two nonunions that did not heal were treated with repeat curettage and debridement and iliac crest bone grafting without revision of fixation. Union was achieved in both at a mean of 11 weeks after the revision procedures. Our findings suggest that non-vascularized cancellous autograft and antegrade fixation is a useful option for the treatment of proximal pole scaphoid nonunions.Level of evidence: IV