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Adrenocortical carcinoma is a rare endocrine cancer with poor overall survival. Linking survival outcomes to a common target across multiple genomic datasets incorporating microRNA-long non-coding RNA dysregulation have not been well described. We hypothesized that a multi-database analysis of microRNA-long noncoding RNA-messenger RNA regulatory networks associated with survival will identify novel biomarkers.Significantly dysregulated genes or microRNA in adrenocortical carcinoma compared to normal adrenal was identified from sequencing data for 260 human adrenocortical carcinomas using GEO2R. The miRnet identified hub microRNA and genes and long noncoding RNA and microRNA associated with survival genes. The R2 generated Kaplan-Meier curves. The database miRTarBase linked genes associated with poor survival and dysregulated microRNA.Analysis of genes and microRNAs differentially regulated in50% of datasets revealed 75 genes and 12 microRNAs were upregulated, and 167 genes and 12 microRNAs were downregulated (bonf. P.05). Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed cell cycle, P53 signaling, arachidonic acid and innate immune response, and PI3/Akt are altered in adrenocortical carcinoma. A microRNA-target interaction network of differentially regulated microRNAs identified upregulated miRNA107, 103a-3p and 27a-3p, 16-5p, and downregulated 335-5p to have the highest degree of interaction with upregulated (ie, TPX2, CDK1, BIRC5, PRC1, CCNB1, GINS1) and downregulated (ie, RSPO3, NR2F1, TLR4, HOXA5, USP53, SLC16A9) hub genes as well as hub long noncoding RNAs XIST, NEAT1, KCNQ1OT1, and PAX8-AS1. Survival analysis revealed that the hub genes are associated with poor overall survival (P.05) of adrenocortical carcinoma in the Cancer Genome Atlas data.A messenger RNA-microRNA-long noncoding RNA network analysis identified the BIRC5-miR335-5p-PAX8-AS1 network as one that was associated with poor overall survival in adrenocortical carcinoma, warranting further validation as a potential therapeutic target.

Osteocapsular débridement is a surgical treatment for functionally limiting primary elbow osteoarthritis (PEOA). We hypothesized that postoperative improvement in range of motion (ROM) following elbow osteocapsular débridement could be grouped into predictable patterns. We also hypothesized that significant improvements in ROM frequently take place for up to 6 months after surgery.A retrospective chart review of patients who underwent open elbow débridement for PEOA was performed. Demographic information and surgical approach were recorded. ROM data were also collected at preoperative, intraoperative, and postoperative intervals of 2 weeks, 6 weeks, 3 months, and 6 months. Growth mixture modeling and latent class growth analysis were performed to identify groups of motion recovery trajectories, while Student's t-tests were performed to compare ROM data between intervals.Our study included 76 patients who underwent open elbow débridement (9 with a lateral approach, 55 medial, and 12 both) for PEOA. The mean preoperative arc of motion was 95° ± 22°. This improved to a mean final motion arc of 127° ± 11 at final follow-up, which was 92% of the mean intraoperative arc. The mean time to achieve final motion was 3 months, with 79% of patients achieving their final ROM arc by this point. Patients achieved an average of 85% of their final arc of motion by the 2-week postoperative visit (92% of final flexion and 61% of final extension). Growth mixture modeling and latent class growth analysis did not identify any statistically significant groupings for postoperative ROM progression trajectories. Arc of motion preoperatively, intraoperatively, and at 2 weeks postoperatively did not correlate with the final arc of motion. There were no characteristics or thresholds of motion which conferred a higher likelihood of achieving a better result postoperatively.ROM recovery after osteocapsular débridement for PEOA is not dependent on preoperative, intraoperative, or 2-week postoperative arcs of motion. Most of the ROM recovery occurs in the early postoperative period, with flexion restored preferentially faster than extension. The final arc of motion can be expected by 3 months postoperatively. This knowledge has potential benefit in affecting patients' personal time commitment to rehabilitation and the overall cost for therapy and splinting beyond the 3-month time point.

Four-corner fusion (4CF) is a surgical option for refractory scapholunate advanced collapse and scaphoid nonunion advanced collapse wrist arthritis. Preoperative range of motion (ROM) predicts outcomes in many orthopedic procedures. This study investigates ROM in a cohort of 4CF patients to examine the relationship between preoperative and postoperative motion and identifies different clinical patterns.We performed a retrospective review of 4CF patients. Patients with a history of inflammatory arthritis and radiographic characteristics of inflammation were excluded. Demographics, prior wrist surgery history, and ROM data were collected at preoperative and postoperative intervals after cast removal at 8 weeks, 3 months, and 8 months. Regression analysis compared the motion before and after 4CF. Subsequent cluster analysis to reduce confounding compared postoperative motion differences in the top 20% to the bottom 20% of patients by preoperative motion.We included 148 patients; 27 had prior surgery on the ipsilateral wrist. Preoperative arc averaged 86° ± 28° (flexion 46° ± 17°, extension 40° ± 15°); 8-week arc 43° ± 19° (flexion 19° ± 12°, extension 24° ± 12°); 3-month arc 62° ± 17° (flexion 30° ± 12°, extension 32° ± 11°); and 8-month arc 74° ± 17° (flexion 36° ± 11°, extension 37° ± 12°). Preoperative and final arcs were (r = 0.39). Clustering by the preoperative arc, the top 20% (mean 124° ± 15°) achieved a mean final arc of 81° ± 16°, while the bottom 20% (mean 47° ± 16°) achieved a mean final arc of 65° ± 19°. Intercluster differences were statistically significant. The bottom 20% gained motion postoperatively. Most patients in the middle 60% did not differ significantly in postoperative motion.Although wrist motion following 4CF correlates positively with preoperative motion, most patients do not differ significantly in postoperative motion. Patients with substantial preoperative motion deficits gain motion after 4CF. This information is important when counseling patients, determining the timing of surgical intervention, and managing expectations related to motion outcomes.Prognostic II.

Coronavirus disease 2019 created unintended but significant experiential barriers for surgical learners to interact at the bedside for teaching/case presentations. We hypothesized that an international grand rounds using the Microsoft HoloLens 2 extended reality (XR) headset would create an improved bedside-learning experience compared to traditional grand rounds formats.From December 2020 to March 2021, the world's first 2 international mixed reality grand rounds events using the HoloLens 2 headset were held, broadcasting transatlantically (between the University of Michigan and the Imperial College of London) bedside rounding experiences on 5 complex surgical patients to an international audience of 325 faculty, residents, and medical trainees. Participants completed pre- and post-event surveys to assess their experience.Of the 325 participants, 267 (80%) completed pre-surveys, and 95 (29%) completed both the pre- and post-surveys. Respondents (average age, 38 y; 44% women, 56% men; 211 US, 56 UK) included 92 (34%) medical students and residents and 175 faculty and staff. In the pre-event survey, 76% had little or no earlier experience with XR devices, and 94% thought implementation of XR into medical curricula was valuable. In the post-survey, 96% thought telerounding using XR technology was important for the current era, and 99% thought the ability to visualize the examination, imaging, and laboratory results at bedside via XR rounding was highly valuable and that this format was superior to traditional grand rounds.Almost all of the participants in the mixed reality international grand rounds felt the immersive XR experiences-allowing visualization of clinical findings, imaging, and laboratory results at the patient's bedside-were superior to a traditional grand rounds format, and that it could be a valuable tool for surgical teaching and telerounding.

A study of the seasonality and overall quantity and quality of Chinese patenting, including international comparisons, suggests that government planning and annual targets encouraged gaming of the system, which increased patent counts but negatively affected patent quality.

Traction tenolysis is an alternative, less invasive way of performing flexor tendon tenolysis by winding affected tendons around a surgical instrument. This study assessed outcomes and complications in a cohort of patients who underwent traction tenolysis to determine its effectiveness.We retrospectively reviewed 97 patients who underwent traction tenolysis performed by 4 fellowship-trained hand surgeons from 2010 to 2019. We collected data on preoperative and postoperative ranges of motion, the number and type of prior ipsilateral hand surgeries, and the duration of therapy and follow-up. Cases of traditional open tenosynovectomy tenolysis were excluded.Approximately two-thirds of the patients achieved more than 75% of the normal total active motion, and 80% achieved at least 50% of the normal total active motion. The mean total active flexion increased significantly by 42° and passive flexion by 25°. The differences in active and passive flexion significantly decreased from 28° before the surgery to 9° after the surgery. The active and passive flexion of the distal interphalangeal and proximal interphalangeal joints improved similarly, at approximately 20° and 10°, respectively. The average duration of follow-up was 11 ± 8 weeks. The complication rate was 5%: 1 case of intraoperative flexor digitorum superficialis tendon rupture, 1 case of postoperative infection, and 3 reoperations because of failure to progress.Traction tenolysis is an alternative to traditional open tenolysis surgery in selected patients.Therapeutic IV.

Major histocompatibility complex-I (MHC-I) presents tumour antigens to CD8+ T cells and triggers anti-tumour immunity. Humans may have 30,000–60,000 long noncoding RNAs (lncRNAs). However, it remains poorly understood whether lncRNAs affect tumour immunity. Here, we identify a lncRNA, lncRNA inducing MHC-I and immunogenicity of tumour (LIMIT), in humans and mice. We found that IFNγ stimulated LIMIT, LIMIT cis-activated the guanylate-binding protein (GBP) gene cluster and GBPs disrupted the association between HSP90 and heat shock factor-1 (HSF1), thereby resulting in HSF1 activation and transcription of MHC-I machinery, but not PD-L1. RNA-guided CRISPR activation of LIMIT boosted GBPs and MHC-I, and potentiated tumour immunogenicity and checkpoint therapy. Silencing LIMIT, GBPs and/or HSF1 diminished MHC-I, impaired antitumour immunity and blunted immunotherapy efficacy. Clinically, LIMIT, GBP- and HSF1-signalling transcripts and proteins correlated with MHC-I, tumour-infiltrating T cells and checkpoint blockade response in patients with cancer. Together, we demonstrate that LIMIT is a cancer immunogenic lncRNA and the LIMIT–GBP–HSF1 axis may be targetable for cancer immunotherapy. Li et al. identify LIMIT as a lncRNA that modulates MHC-I expression through HSP90 and HSF1, thereby regulating antitumour immune response and the efficacy of immunotherapy.

Background Patients with advanced differentiated thyroid cancer develop resistance to lenvatinib treatment from metabolic dysregulation. Heat shock protein 90 is a molecular chaperone that plays an important role in glycolysis and metabolic pathway regulation. We hypothesize that lenvatinib-resistant differentiated thyroid cancer cells will have an increased dependency on glycolysis and that a novel C-terminal heat shock protein 90 inhibitor (KU757) can effectively treat lenvatinib-resistant cells by targeting glycolysis. Methods Inhibitory concentration 50 values of thyroid cancer cells were determined by CellTiter-Glo assay (Promega Corp, Madison, WI). Glycolysis was measured through Seahorse experiments. Reverse transcription-polymerase chain reaction and Western blot evaluated glycolytic pathway genes/proteins. Exosomes were isolated/validated by nanoparticle tracking analysis and Western blot. Differentially expressed long non-coding ribonucleic acids in exosomes and cells were evaluated using quantitative polymerase chain reaction. Results Extracellular acidification rate demonstrated >2-fold upregulation of glycolysis in lenvatinib-resistant cells versus parent cells and was downregulated after KU757 treatment. Lenvatinib-resistant cells showed increased expression of the glycolytic genes lactic acid dehydrogenase, pyruvate kinase M1/2, and hexokinase 2. KU757 treatment resulted in downregulation of these genes and proteins. Several long non-coding ribonucleic acids associated with glycolysis were significantly upregulated in WRO-lenvatinib–resistant cells and exosomes and downregulated after KU757 treatment. Conclusion Lenvatinib resistance leads to increased glycolysis, and KU757 effectively treats lenvatinib-resistant cells and overcomes this increased glycolysis by targeting key glycolytic genes, proteins, and long non-coding ribonucleic acids.

While bedside training has always presented its own unique challenges, the COVID-19 pandemic era has intensified barriers to suitable provider and trainee experiences for both patient care and medical education.This project introduced an innovative solution with the Extended Reality International Grand Rounds, a collaboration between the University of Michigan Center for Medical and Surgical Extended Reality and Imperial College London. Three complex cases were presented to trainees through a wireless, extended reality (XR) headset and augmented by holographic visual aids and expert commentary. This pilot rounding experience was performed through the first-person view of one clinician at the bedside.In 2020, 140 attendees participated in XR International Grand Rounds, and 82 (59%) and 61 (44%) completed pre- and postsurveys, respectively. Survey analysis showed that the majority of respondents (65, 79.3%) had very little to no baseline experience with XR technologies and nearly all (75, 91.5%) agreed that the development and implementation of XR curricula are important in medical training, indicating an unmet need. Nearly all respondents (59, 96.7%) found value in the ability to visualize patients' clinical findings in the XR rounding experience and 60 (98.4%) found value in the ability to visualize patient-specific imaging and test findings in an XR format. Limiting exposure to high-risk patients and care team members with this innovative format was believed to be important to 79 (96.3%) respondents at baseline and that perception was unchanged following the event.This solution to a long-standing dilemma, newly stressed by a unique era in medicine, was a successful collaboration using state-of-the-art XR technology. Next steps will include introducing more advanced physical exam visualization and detection and comprehensive evaluation of the patient experience, as well as expanding the international experience in a format that is scalable to other interested institutions.

Post-traumatic stiffness of the elbow may be treated surgically with open osteocapsular release. This study investigated postoperative range of motion (ROM) improvements after this procedure. We hypothesized that there would be predictable recovery patterns and significant progress up to 6 months after surgery.A retrospective chart review of patients who underwent open elbow release for post-traumatic stiffness (PTS) was performed. Demographic information and surgical approach were recorded. Patients with ipsilateral primary elbow osteoarthritis were excluded. Range of motion (ROM) data were collected at preoperative, intraoperative, and postoperative intervals of 2 weeks, 6 weeks, 3 months, and 6 months. Growth mixture modeling (GMM) and latent class growth analysis (LCGA) were performed to identify motion recovery trajectory groups, and Student's t-tests were performed to compare ROM data between intervals.One hundred and eighty-seven patients who underwent open elbow release for PTS were included (112 with a medial approach, 50 lateral, and 25 both). The mean preoperative arc was 84° ± 31, and the arc of motion at final follow-up was 119° ± 19 (ROM recovery after surgical release for post-traumatic elbow stiffness did not depend on the preoperative, intraoperative, or 2-week postoperative arcs of motion. Most ROM recovery occurs early after surgery, and maximal arc of motion can be expected by approximately 16 weeks postoperatively. This knowledge may inform patients about their expected rehabilitation and splinting time and reduce the total costs of therapy.

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.

In patients with triple‐negative breast cancer (TNBC), evidence suggests that tumor‐initiating cells (TIC) have stem cell‐like properties, leading to invasion and metastasis. HSP90 plays a critical role in the conformational maintenance of many client proteins in TIC development. Therefore, we hypothesize that the novel C‐terminal HSP90 inhibitors KU711 and KU758 can target TIC and represent a promising strategy for overcoming metastasis. Human breast cancer cells (MDA‐MB‐468LN, MDA‐MB‐231) treated with the HSP90 inhibitors KU711, KU758, and 17‐AAG showed a 50–80% decrease in TIC markers CD44 and aldehyde dehydrogenase (P, C‐terminal HSP90 inhibitors KU711 and KU758 reduce tumor growth of triple‐negative breast cancer xenografts by targeting Akt/mTOR and MAPK/ERK pathways, cancer stem cells, migration, and EMT transition.

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.

Treatment of distal biceps tendon ruptures with surgical repair has been shown to restore peak elbow flexion and supination strength, as well as minimize fatigue with repetitive activity. The anatomic footprint of the biceps is slightly posterior to the apical prominence of the bicipital tuberosity. Single-incision and double-incision methods for repairing distal biceps tendon ruptures have been described. However, previously described single-incision techniques have been unable to accurately re-establish the anatomic position of the tendinous insertion. We describe our technique of performing an anatomic distal biceps repair using a single anterior incision. The proposed benefits of this technique include the restoration of the anatomic footprint area, insertion site, and consequently the native cam effect of the bicipital tuberosity all through a single incision. From a patient's perspective, the proposed benefit of this technique includes the restoration of supination strength using a single incision.

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.

Introduction Adrenocortical carcinoma is an aggressive cancer with a poor prognosis. Long noncoding RNAs are differentially expressed in cancer patients and contribute to cellular homeostasis, survival, and metastasis. We hypothesize that our novel C-terminal Hsp90 inhibitor KU758 can effectively target adrenocortical carcinoma cells and favorably alter long noncoding RNA expression. Methods Cell viability after KU758 treatment was measured in the adrenocortical carcinoma cell lines SW13, RL251, and NCI-H295R by MTS assay. Cellular mobility and metastatic potential after Hsp90 inhibition was measured through migration, invasion, and aggregate formation assays. β-catenin activity in NCI-H295R cells was determined by immunofluorescence and polymerase chain reaction. Long noncoding RNA expression was determined by polymerase chain reaction array after Hsp90 inhibition. Results KU758 is selective for adrenocortical carcinoma cells with IC50 values of 0.6 to 2.4 μM. KU758 treatment can effectively reduce migration, invasion, and aggregate formation in NCI-H295R and SW13 cells. β-catenin activity is decreased after treatment with KU758. Treatment with KU758 is associated with overall statistically significant upregulation of long noncoding RNA expression, including the tumor suppressor GAS5, which is implicated in the β-catenin and mammalian target of rapamycin pathways in adrenocortical carcinoma. Conclusion The novel C-terminal Hsp90 inhibitor KU758 is effective in the treatment of adrenocortical carcinoma cells and can significantly alter long noncoding RNA expression for tumor suppression.

Treatment regimens for head and neck squamous cell carcinoma (HNSCC) typically include cisplatin and radiotherapy and are limited by toxicities. We have identified naturally derived withalongolide A triacetate (WGA-TA) from Physalis longifolia as a lead compound for targeting HNSCC. We hypothesized that combining WGA-TA with cisplatin may allow for lower, less toxic cisplatin doses. HNSCC cell lines were treated with WGA-TA and cisplatin. After treatment with the drugs, the cell viability was determined by MTS assay. The combination index was calculated using CompuSyn. The expression of proteins involved in the targeting of translational initiation complex, epithelial to mesenchymal transition (EMT), and apoptosis were measured by western blot. Invasion and migration were measured using the Boyden-chamber assay. Treatment of MDA-1986 and UMSCC-22B cell lines with either WGA-TA or cisplatin alone for 72 h resulted in a dose dependent decrease in cell viability. Cisplatin in combination with WGA-TA resulted in significant synergistic cell death starting from 1.25 μM cisplatin. Combination treatment with WGA-TA resulted in lower cisplatin dosing while maintaining the downregulation of translational initiation complex proteins, the induction of apoptosis, and the blockade of migration, invasion, and EMT transition. These results suggest that combining a low concentration of cisplatin with WGA-TA may provide a safer, more effective therapeutic option for HNSCC that warrants translational validation.

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.

Introduction: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, with very poor prognosis as a majority of the patients have advanced disease at the time of diagnosis. Currently, adjuvant therapy for most patients consists of either mitotane (M) alone or in combination with multi-drug chemotherapeutics such as etoposide (E), doxorubicin (D), and cisplatin (P), known as the Italian protocol (IP, EDPM). This multi-drug treatment regimen, however, carries significant toxicity potential for patients. One way to improve toxicity profiles with these drugs in combination is to understand where their synergy occurs and over what dosing range so that lower dose regimens could be applied in combination with equal or improved efficacy. We hypothesize that a better understanding of the synergistic effects as well as the regulation of steroidogenic enzymes during combination therapy may provide more optimized combinational options with good potency and lower toxicity profiles. Methods: Two human ACC cell lines, NCI-H295R (hormonally active) and SW13 (hormonally inactive), were grown in 2D culture in appropriate growth medium. The viability of the cells after treatment with varying concentrations of the drugs (E, D, and P) either alone or in combinations with M was determined using the CellTiter Glow assay after 72 h, and the combination index for each was calculated using Compusyn by the Chou–Talalay method. The expression levels of enzymes associated with steroidogenesis were evaluated by RT-PCR in NCI-H295R. Results: When both cell lines were treated with M (ranging 25–50 μM), +E (ranging 18.75–75 μM), and +D (ranging 0.625–2.5 μM) we observed a synergistic effect (CI &lt, 1) with potency equivalent to the full Italian protocol (IP), whereas combining M + P + D had an antagonistic effect (CI &gt, 1) indicating the negative effect of adding cisplatin in the combination. Comparing the hormonally active and inactive cell lines, M + P + E was antagonistic in NCI-H295R and synergistic in SW13. Treatment of NCI-H295R cells with antagonistic combinations (M + P + D, M + P + E) resulted in a significant decrease in the levels of steroidogenic enzymes STAR, CYP11A1, and CYP21A2 compared to IP (p &lt, 0.05) while M + E + D resulted in increased expression or no significant effect compared to IP across all genes tested. Conclusions: The synergistic effect for M + E + D was significant and equivalent in potency to the full IP in both cell lines and resulted in a steroidogenic gene expression profile similar to or better than that of full IP, warranting further evaluation. Future in vivo evaluation of the combination of M + E + D (with removal of P from the IP regimen) may lower toxicity while maintaining anticancer efficacy in ACC.

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 Historically, treatment of partial articular radial head fractures has hinged on radiographic assessment and application of the Mason classification. The inter- and intra-rater reliability of radiographic assessment and classification of radial head fractures may be lower than previously reported. We hypothesized that radiographic assessment leads to an underestimation of the number of fragments, percentage of articular surface involved, and displacement in millimeters. Methods We performed a retrospective review of all Mason II radial head fractures treated at our institution. Four independent observers performed radiographic assessment of the cohort. An independent observer performed these measurements on high-resolution computed tomography (CT) imaging, the reference standard. Radiographic assessments were then correlated with the CT findings using Pearson's correlation coefficient and Kappa statistic, where indicated. Results Fifty-nine Mason II radial head fractures were reviewed. These results were not impressive, with all comparisons showing a Kappa statistic less than 0.5 (ie, weak agreement). Intra-rater reliability was similar: displacement (measured by Pearson's correlation coefficient) was 0.58, percent articular involvement was 0.74, and the number of fragments (measured by the Kappa statistic) was 0.28. Fracture displacement was generally underestimated on radiographic measurements when compared to CT scan. Nearly half (45%) of all cases demonstrated inaccurate fragment number assessment when compared to the reference standard. Conclusion Radiographs show poor inter- and intra-observer reliability for determining radial head fracture morphology. Assessment of the number of fragments was particularly inaccurate. High-resolution CT should be considered for patients with Mason II radial head fractures, especially in cases of poorly visualized fracture characteristics or borderline amounts of displacement, in an effort to appropriately indicate patients for the variety of treatment options available today.

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.

The study investigated the effects of focused ultrasound on human brain tissue to assess intensities at which focused ultrasound might cause irreversible structural cell damage. FUS does not appear to cause significant heating or cavitation to brain tissue when Ispta remains below 25 W/cm2. However, as the tissue was fixed immediately post-sonication, there was not sufficient time for apoptosis to develop, leaving open the possibility that a lower intensity over a longer period of time may cause stress and damage to the cell, leading to its eventual death. While additional studies should continue to further ensure the safety of this novel and important technology, this furthers the notion that, at the current FDA-approved levels, and potentially beyond, tFUS is likely a safe clinical technology.

Melanoma remains the most aggressive and fatal form of skin cancer, despite several FDA-approved targeted chemotherapies and immunotherapies for use in advanced disease. Of the 100 350 new patients diagnosed with melanoma in 2020 in the US, more than half will develop metastatic disease leading to a 5-year survival rate

Adrenocortical carcinoma while rare, often presents with advanced metastatic disease carrying a 5-year survival of15%. Despite adrenocortical carcinoma tumors having high avidity for cholesterol, the role of lipids in adrenocortical carcinoma has not been well described. Therefore, we performed an integrated bioinformatic analysis to identify novel lipid biomarkers correlating with poor survival that may help identify adrenocortical carcinoma tumor progression or therapy resistance.A meta-analysis of collated adrenocortical carcinoma studies from the correlation engine identified lipid metabolism genes differentially expressed between adrenocortical carcinoma and the normal adrenal, which were then selected for enrichment analysis by the Database for Annotation, Visualization and Integrated Discovery database. A protein-protein interaction network of genes was constructed using Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. Top hub genes identified were validated using the Xena database. Survival analysis of hub genes was performed in the R2 genomic analysis platform using The Cancer Genome Atlas program data set.Examination of pathways by correlation engine identified a unique subset of lipid metabolism-related genes that are differentially regulated in adrenocortical carcinoma tumors versus normal tissues (P.01). Enrichment pathway analysis in Database for Annotation, Visualization and Integrated Discovery indicated that genes involved in sphingolipid, steroid, and peroxisome proliferator-activated receptor-α metabolism is upregulated in adrenocortical carcinoma, whereas glycerol phospholipid, fatty acid, and phosphatidylinositol metabolism are downregulated. Survival analysis of differentially regulated genes indicated that upregulation of SGPL1, FDFT1, SQLE and downregulation of PIK3C2B, PIK3CD, SYNJ2, DGAT1, PLA2G16, PLD1, GPD1 are all significantly associated with poor overall survival (P.05) in adrenocortical carcinoma patients.Upregulation of sphingolipid and steroid synthesis genes and downregulation of phosphatidylinositol and glycerol phospholipid metabolism are associated with worse survival in patients with adrenocortical carcinoma.

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.

The purpose of this investigation was to examine the timeline of return-to-sport following distal triceps repair; evaluate the degree of participation and function upon returning to sport; and identify risk factors for failure to return to sport.Patients who underwent distal triceps repair with a minimum of 1 year of follow-up were retrospectively reviewed. Patients completed a subjective sports questionnaire and were scored on a visual analog scale for pain; the Mayo Elbow Performance Index; the Quick Disabilities of the Arm, Shoulder, and Hand; and the Single Assessment Numerical Evaluation.Out of 113 eligible patients who had a distal triceps repair, 81 patients (71.7%) were contacted. Sixty-eight patients (84.0%) who participated in sports prior to surgery were included at 6.0 ± 4.0 years after surgery, and the average age was 46.6 ± 11.5 years. Sixty-one patients (89.7%) resumed playing at least 1 sport by 5.9 ± 4.4 months following distal triceps repair. However, 18 patients (29.5%) returned to a lower level of activity intensity. The average postoperative Quick Disabilities of the Arm, Shoulder, and Hand; Mayo Elbow Performance; visual analog scale for pain; and Single Assessment Numerical Evaluation scores were 8.2 ± 14.0, 89.5 ± 13.4, 2.0 ± 1.7, and 82.2 ± 24.3, respectively. No patients underwent revision surgery at the time of final follow-up.Distal triceps repair enables 89.7% of patients to return to sport by 5.9 ± 4.4 months following surgery. However, 29.5% of patients were unable to return to their preinjury level of activity. It is imperative that patients are appropriately educated to manage postoperative expectations regarding sport participation following distal triceps repair.Therapeutic IV.

Early identification of and response to barriers in telehealth settings will help patients receive optimal care. Here, the authors, based on institutional experience, provide advice on such strategies. This guidance focuses on standardizing expectations, assessing technological knowledge and resource access, evaluating understanding and comfort with telehealth, and assessing social support.

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.

INTRODUCTION: Binimetinib is an uncompetitive, small molecule inhibitor of selective mitogen-activated protein kinase (MEK1/2) and was recently approved in 2018 in combination with encorafenib for the treatment of metastatic melanomas. Preclinical and clinical trial data on the drug demonstrate its potent efficacy in cancers, especially melanomas with BRAF and NRAS mutations. AREAS COVERED: The authors review the preclinical as well as clinical Phase 1, 2 and 3 trial data leading to its FDA approval in 2018 for metastatic melanoma. Phase 3 data in combination with encorafenib demonstrated double the PFS (14.9 months) compared to vemurafenib alone (7.3 months) in patients with BRAF-mutated metastatic melanoma. EXPERT OPINION: No longer-term data is available yet to demonstrate any durable complete responses to therapy with binimetinib or improvements in overall survival compared to other FDA approved therapies including immunotherapy or vemurafenib. Treatment approaches to patients with BRAF mutated metastatic melanoma should be individualized and binimetinib in combination with encorafenib is a reasonable oral strategy with a reasonably tolerated toxicity profile. Cost of treatment and durability of response should be incorporated into the discussion as part of the overall medical decision making.