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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.

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.

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.

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.

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.

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.

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

Index finger metacarpophalangeal (MCP) joint arthrodesis is a potential reconstructive option for recalcitrant MCP arthritis. Due to lateral forces applied by the thumb, our institutional experience supports index finger MCP arthrodesis as a successful option in younger, higher demand patients and in the setting of significant joint instability. We present our technique of performing index finger MCP arthrodesis using a dorsal locking plate. The proposed benefits of this technique include the ability to position the MCP joint in the desired degree of flexion, generation of parallel fusion surfaces with even compression across the arthrodesis site, and stable fixation.

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.

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.

Functional magnetic resonance imaging (fMRI) adaptation (also known as fMRI repetition suppression) has been widely used to characterize stimulus selectivity in vivo, a fundamental feature of neuronal processing in the brain. We investigated whether SZ patients and BD patients show aberrant fMRI adaptation for object perception. About 52 SZ patients, 55 BD patients, and 53 community controls completed an object discrimination task with three conditions: the same object presented twice, two exemplars from the same category, and two exemplars from different categories. We also administered two functional localizer tasks. A region of interest analysis was employed to evaluate a priori hypotheses about the lateral occipital complex (LOC) and early visual cortex (EVC). An exploratory whole brain analysis was also conducted. In the LOC and EVC, controls showed the expected reduced fMRI responses to repeated presentation of the same objects compared with different objects (i.e., fMRI adaptation for objects, p

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).

Background Chronic elbow instability after trauma is a challenging problem. Clinical results of external elbow fixation in this setting are limited, with most studies focusing on hinged external fixation. A static fixator is an alternative for maintaining joint reduction. Advantages of a static frame include ease of application, decreased need for special instrumentation, and more secure maintenance of a concentrically reduced joint in the setting of bone or soft tissue instability. The primary limitation of static fixation is the potential for stiffness. Methods This retrospective review represents the largest reported cohort evaluating the use of static elbow external fixation for the treatment of chronic elbow instability. Twenty-seven cases treated by a single surgeon between 2004 and 2015 were identified. Results Twenty patients were available for a clinical evaluation, including radiographs and a physical examination at a mean follow-up of 5.8 years (range, 1.4-12.4 years). Of note, 19 of 20 were clinically obese or overweight. At final evaluation, range of motion averaged from 20° ± 13° of extension to 134° ± 9° of flexion. All patients had stable elbows, except 1 patient who had valgus and varus laxity on stress examination. Radiographs of this patient showed an incongruous joint. Eight patients required an additional operation after external fixator removal, 3 for infection and 5 for stiffness. Conclusions At almost 6 years of follow-up, static elbow external fixator resulted in a congruous joint with adequate functional and clinical outcomes in 95% of patients.

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.

Adrenocortical carcinoma is a rare and aggressive malignancy with poor survival. With limited treatment options and high risk of relapse, identifying improved targets and therapies for adrenocortical carcinoma is important. We hypothesized that analysis of the database of The Cancer Genome Atlas could identify important novel biomarkers for improved therapeutic targeting of adrenocortical carcinoma.We utilized the University of Alabama interactive web resource to identify novel biomarkers observed in 79 adrenocortical carcinoma patients. Identified biomarkers were then examined for prognostic correlations using the cBioPortal and analyzed for statistical significance using STATA 13.0.The Cancer Genome Atlas data mining in the University of Alabama interactive web resource for pathways associated with poor survival of patients with adrenocortical carcinoma revealed significant upregulation of genes involved in DNA damage and regulation of cell-cycle pathways, such as AURKA, AURKB, CDK1, CDK4, CDK6, PLK1, CHEK1, CHEK2, CDC7, BUB3, and MCM3 (P.001-.05). On outcome correlation, greater expression levels of all the genes except CDK4 were associated with worse survival compared with medium or low levels of gene expression (P.001 all) irrespective of age orsex. Consistent with our University of Alabama interactive web resource findings, data mining in the cBioPortal also revealed upregulation of genes regulating DNA-damage and cell cycle-related genes in 82% of patients (z score = 1.5).Large data mining from the The Cancer Genome Atlas and cBioPortal databases identified overexpression of genes involved in DNA damage and those regulating pathways of the cell cycle, which correlated with poorer overall survival in adrenocortical carcinoma patients.

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.

Background Withanolides are naturally derived heat shock protein 90 inhibitors that are potent in preclinical models of triple negative breast cancers. Conjugation to synthetic high-density lipoprotein nanoparticles improves solubility and targets delivery to the scavenger receptor B1. Triple negative breast cancers highly overexpress the scavenger receptor B1, and we hypothesize that encapsulation of the novel withalongolide A 4,19,27-triacetate by synthetic high-density lipoprotein will have enhanced efficacy against triple negative breast cancers in vivo. Methods Validated human triple negative breast cancer cell lines were evaluated for the scavenger receptor B1 expression by quantitative polymerase chain reaction and Western blot. Withalongolide A 4,19,27-triacetate inhibitory concentration50 values were obtained using CellTiter-Glo assays (Promega, Madison, WI, USA). The scavenger receptor B1–mediated drug uptake was evaluated in vitro under fluorescence microscopy and in vivo with IVIS imaging of mouse xenografts (MD-MBA-468LN). To evaluate drug efficacy, mice were treated with synthetic high-density lipoprotein alone, withalongolide A 4,19,27-triacetate alone, withalongolide A 4,19,27-triacetate synthetic high-density lipoprotein, and chemotherapy or Prussian blue stain (control). Results Triple negative breast cancer cell lines had greater scavenger receptor B1 expression by quantitative polymerase chain reaction and Western blot versus controls. Fluorescent-labeled synthetic high-density lipoprotein uptake was scavenger receptor B1–mediated in vitro, and in vivo tumor uptake using IVIS imaging demonstrated significantly increased tumor radiant efficiency versus control. Inhibitory concentration50 for withalongolide A 4,19,27-triacetate–treated cells with or without synthetic high-density lipoprotein encapsulation were 70-fold to 200-fold more potent than synthetic high-density lipoprotein alone. In triple negative breast cancer mouse xenografts, treatment with synthetic high-density lipoprotein withalongolide A 4,19,27-triacetate resulted in a 54% decrease in tumor volume compared with the control or with synthetic high-density lipoprotein alone. Conclusion The synthetic high-density lipoprotein withalongolide A 4,19,27-triacetate nanoconjugates are potent against triple negative breast cancers and show improved scavenger receptor B1–mediated targeting. Treatment with synthetic high-density lipoprotein–encapsulated withalongolide A 4,19,27-triacetate is able to significantly decrease the growth of tumor in mice compared with the control and has better efficacy than the current standard of care, warranting further evaluation as a novel therapeutic agent.

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

Determination of outcomes after adrenalectomy for primary aldosteronism (PA) is limited by the lack of standardized definitions of cure. The Primary Aldosteronism Surgical Outcomes (PASO) group recently established new consensus definitions for biochemical and clinical cure of PA. We hypothesize that utilization of PASO definitions will better stratify patient outcomes after surgery compared to original and current criteria utilized to document cure. Patients undergoing adrenalectomy for PA from 1996 to 2016 were studied. Clinical data were reviewed. Three different sets of criteria (original, current, and PASO) were evaluated for differences in documentation of cure. Demographic data were reported as median (range). Comparisons were made using the Mann–Whitney U test; p

SummaryObjective Low-cost evidence-based tools are needed to facilitate the early identification of patients with possible psychogenic nonepileptic seizures (PNES). Prior to accurate diagnosis, patients with PNES do not receive interventions that address the cause of their seizures and therefore incur high medical costs and disability due to an uncontrolled seizure disorder. Both seizures and comorbidities may contribute to this high cost. Methods Based on data from 1,365 adult patients with video-electroencephalography–confirmed diagnoses from a single center, we used logistic and Poisson regression to compare the total number of comorbidities, number of medications, and presence of specific comorbidities in five mutually exclusive groups of diagnoses: epileptic seizures (ES) only, PNES only, mixed PNES and ES, physiologic nonepileptic seizurelike events, and inconclusive monitoring. To determine the diagnostic utility of comorbid diagnoses and medication history to differentiate PNES only from ES only, we used multivariate logistic regression, controlling for sex and age, trained using a retrospective database and validated using a prospective database. Results Our model differentiated PNES only from ES only with a prospective accuracy of 78% (95% confidence interval =72–84%) and area under the curve of 79%. With a few exceptions, the number of comorbidities and medications was more predictive than a specific comorbidity. Comorbidities associated with PNES were asthma, chronic pain, and migraines (p < 0.01). Comorbidities associated with ES were diabetes mellitus and nonmetastatic neoplasm (p < 0.01). The population-level analysis suggested that patients with mixed PNES and ES may be a population distinct from patients with either condition alone. Significance An accurate patient-reported medical history and medication history can be useful when screening for possible PNES. Our prospectively validated and objective score may assist in the interpretation of the medication and medical history in the context of the seizure description and history.

Purpose The aim of this study was to assess the treatment and complications of a distinct type of partial intra-articular distal radius fracture. Methods Seven patients treated by the senior author between 2008 and 2013 for a partial intra-articular distal radius fracture with isolated involvement of the volar lunate facet were included. All fragments had the distinctive shape of a triangular-base pyramid (tetrahedron) extending from the metaphysis distally. All fractures were preoperatively assessed with computed tomography (CT) scans. Patients underwent surgical treatment using a standard flexor carpi radialis approach (2 patients) or a volar ulnar approach (5 patients) and were followed postoperatively for a minimum of 12 months. Results Patient age ranged from 33 to 66 years. On average, fragments measured 34 ± 6 mm in length (range, 27–43 mm) and were 48% as wide as the distal radius (range, 40% to 56%) and 58% as deep as the anterior-posterior dimension of the lesser sigmoid notch (range, 33% to 83%). Loss of reduction requiring revision surgery occurred at 4 weeks in 1 patient who underwent internal fixation through the flexor carpi radialis approach. The remaining cases healed uneventfully. At the final follow-up, all, except the patient requiring revision surgery, had a painless wrist. Average total wrist motion measured 87% of the opposite side. Radiographic healing with anatomic wrist alignment was observed in all except the patient requiring revision. This patient had persistent joint subluxation. The remaining patients all achieved good or excellent functional outcomes. Conclusions Isolated tetrahedron volar lunate facet fractures of the distal radius are rare. In our experience, the use of a volar ulnar approach leads to satisfactory fixation and outcomes, yielding excellent radiographic and clinical outcomes. Type of study/level of evidence Therapeutic V.

Background We report the long-term results of a cohort of patients after radial head replacement with a bipolar design and a smooth cementless stem at a mean follow-up of 10.4 years. Methods Of 17 possible patients from a previous minimum 2-year follow-up study, 16 were available for review. Patients were assessed using clinical and radiographic examination and with standardized outcome measures. Range of motion, stability, and radiographic evaluation of implant loosening and joint degeneration were assessed. Comparisons were performed using the Wilcoxon signed rank test for unequal groups. Results The average follow-up was 10.5 years (range, 8.5-12 years). The median visual analog scale was 1 (range, 0-5), Minnesota Elbow Performance Index was 93 (range, 70-100), and the Disabilities of the Arm, Shoulder and Hand was 7.5 (range, 0-53). Range of motion was decreased on the operative side compared with the nonoperative side for flexion/extension (P = .005) and pronation/supination (P = .015). Grip strength was decreased on the affected side (P = .045). No patients had elbow instability. Significant arthritic changes developed in 2 patients at the ulnohumeral joint. The median cantilever quotient was 0.4 (range, 0.30-0.50). Osteolysis in zones 1 to 7 was found in all but 2 patients. The median stem radiolucency was 0.5 mm (range, 0.2-0.9 mm). No reoperations occurred since our previous report. Implant survival in this cohort was 97%. Conclusion Bipolar radial head prosthesis with a smooth cementless stem effectively restores elbow stability and function after comminuted radial head fractures with or without concomitant elbow instability. Our study demonstrates excellent long-term implant survival.

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are potentially life-threatening conditions whose partially overlapping phenomenology-distorted perception of appearance, obsessions/compulsions, and limited insight-can make diagnostic distinction difficult in some cases. Accurate diagnosis is crucial, as the effective treatments for AN and BDD differ. To improve diagnostic accuracy and clarify the contributions of each of the multiple underlying factors, we developed a two-stage machine learning model that uses multimodal, neurobiology-based, and symptom-based quantitative data as features: task-based functional magnetic resonance imaging data using body visual stimuli, graph theory metrics of white matter connectivity from diffusor tensor imaging, and anxiety, depression, and insight psychometric scores. In a sample of unmedicated adults with BDD (n = 29), unmedicated adults with weight-restored AN (n = 24), and healthy controls (n = 31), the resulting model labeled individuals with an accuracy of 76%, significantly better than the chance accuracy of 35% ([Formula: see text]). In the multivariate model, reduced white matter global efficiency and better insight were associated more with AN than with BDD. These results improve our understanding of the relative contributions of the neurobiological characteristics and symptoms of these disorders. Moreover, this approach has the potential to aid clinicians in diagnosis, thereby leading to more tailored therapy.

Increasing utilization of genetic expression profiling (GEP) for thyroid nodules with indeterminate fine needle aspiration (FNA) results will potentially decrease the number of patients requiring diagnostic thyroidectomy. This study sought to determine the potential effects of GEP for indeterminate thyroid FNA results on thyroidectomy volume. A retrospective review of thyroidectomy procedures performed over 1 year at the University of Michigan in the endocrine surgery division evaluated the indications for thyroidectomy, FNA Bethesda classification, and final surgical pathology to determine how application of GEP on indeterminate FNA results would affect decision for surgery and subsequent thyroidectomy volume. During the study period, 358 thyroidectomies were performed. The indication for procedure included: FNA findings, n = 122; symptomatic multinodular goiter, n = 85; nodule >4 cm, n = 30; Graves’, n = 26; other, n = 95. FNA was performed in 231 patients. Bethesda classification included: benign, n = 69; malignant, n = 55; follicular lesion of undetermined significance, n = 59; follicular neoplasm, n = 20; suspicious for malignancy, n = 16; nondiagnostic, n = 12. If standard GEP was performed for all indeterminate FNA results, it would have influenced the decision for surgery in 68 (19 %) patients. Assuming 38 % of indeterminate FNA specimens will have benign results on genetic profiling, 27 patients would not have undergone thyroidectomy, translating into a 7.2 % decrease in overall thyroidectomy volume over a year. In an academic endocrine surgery program, the most common indication for thyroidectomy is an FNA result; however, standard application of GEP for all indeterminate thyroid FNAs would result in a minimal reduction in overall thyroidectomy volume.

Background Ongoing experience has documented equivalence of minimally invasive parathyroidectomy (MIP) and standard bilateral parathyroid exploration (BPE) for primary hyperparathyroidism in most patients; however, intraoperative conversion of MIP to BPE is required for multiple indications. This study analyzes the factors, predictors, and cure rates in converted MIP. Methods We retrospectively analyzed a database of 1,002 patients undergoing initial parathyroidectomy for primary hyperparathyroidism from 2008 to 2011 for rate of successful MIP, converted MIP, planned BPE, and factors leading to conversion from MIP to BPE. Results Of 989 included parathyroidectomies, 647 (65%) were successful MIP, 186 (19%) were converted MIP, and 156 (16%) were planned BPE. The most common indication for conversion included intraoperative parathyroid hormone (IOPTH) criteria not met (46%), localization incorrect (36%), and evidence of multigland disease (17%). Converted MIP had lower preoperative calcium and PTH and lower baseline IOPTH compared with successful MIP. Complication rates were similar; however, rates of persistent hyperparathyroidism were highest in converted MIPs (6%) versus planned BPEs (3%) and successful MIPs (2%; P Conclusion Patients requiring conversion of MIP to BPE have lower preoperative serum calcium and PTH levels, a less dramatic decrease in IOPTH, and a greater rate of persistent disease than successful MIP.

Proximal ulnar fractures have traditionally been fixed with either tension band wiring or plate and screw fixation. These traditional techniques often irritate the surrounding soft tissues, potentially leading to subsequent secondary hardware removal surgeries. Intramedullary proximal ulnar fixation provides similar rigid fixation, however, no review yet exists to support the clinical use of currently available implants.To investigate the clinical and radiographic short-term outcomes for multiplanar locked intramedullary nails used to treat proximal ulnar fractures.A retrospective multicenter review was conducted in 28 patients with unstable olecranon fractures treated with a new multiplanar locked intramedullary nailing system (OlecraNail, Mylad Orthopedic Solutions, McLean, VA). Radiographic union was estimated, and serial clinical outcome up to one year was assessed by strength, motion, pain (visual analog scale), and a subcutaneous ulna border palpation (SCUBP) test to assess hardware prominence.All fractures achieved union by 8 weeks. At 12 weeks postoperatively, all motion was within 10 degrees of the contralateral side in all directions. Of the 18 patients who underwent SCUBP testing, all 18 patients reported to have no pain at 12 weeks. At one-year follow-up, all patients had resumed normal activities, including work and athletics. All of the patients who underwent the SCUBP testing continued to have no pain.Multiplanar locked intramedullary nails offer effective management for proximal ulna fractures similar to those reported with plating techniques.Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Introduction Deficits in visual perception are well-established in schizophrenia and are linked to abnormal activity in the lateral occipital complex (LOC). Related deficits may exist in bipolar disorder. LOC contains neurons tuned to object features. It is unknown whether neural tuning in LOC or other visual areas is abnormal in patients, contributing to abnormal perception during visual tasks. This study used multivariate pattern analysis (MVPA) to investigate perceptual tuning for objects in schizophrenia and bipolar disorder. Methods Fifty schizophrenia participants, 51 bipolar disorder participants, and 47 matched healthy controls completed five functional magnetic resonance imaging (fMRI) runs of a perceptual task in which they viewed pictures of four different objects and an outdoor scene. We performed classification analyses designed to assess the distinctiveness of activity corresponding to perception of each stimulus in LOC (a functionally localized region of interest). We also performed similar classification analyses throughout the brain using a searchlight technique. We compared classification accuracy and patterns of classification errors across groups. Results Stimulus classification accuracy was significantly above chance in all groups in LOC and throughout visual cortex. Classification errors were mostly within-category confusions (e.g., misclassifying one chair as another chair). There were no group differences in classification accuracy or patterns of confusion. Conclusions The results show for the first time MVPA can be used successfully to classify individual perceptual stimuli in schizophrenia and bipolar disorder. However, the results do not provide evidence of abnormal neural tuning in schizophrenia and bipolar disorder., Highlights • Abnormal visual perception exists in schizophrenia and, likely, bipolar disorder • Neural processing abnormalities underlying those deficits are not well understood • We used multivariate analyses of fMRI data to assess patients' visual processing • We establish for the first time that such methods work well in these patient groups • The analyses did not show group differences in neural processing of visual stimuli

Background This study aimed to present the outcomes of patients undergoing surgical management of persistent, symptomatic olecranon physes. Methods Consecutive patients undergoing surgical management for symptomatic persistent olecranon physeal abnormalities were reviewed. Preoperative data, intraoperative findings, and postoperative clinical outcomes including physical examination findings, radiographs, complications, and reoperations were analyzed. Results A total of 13 elbows in 12 patients (100% male; average age, 18 ± 4 years) were identified. All patients were pitchers at the high-school or college level. Two unique radiographic patterns were identified: distal persistent olecranon physis (n = 9), identified by an irregular sclerotic lucency at the site of the olecranon physis; and proximal persistent olecranon physis (n = 4), identified by a radiolucency exiting proximal to the triceps insertion at the site of an accessory ossification center that failed to unite. Surgical management included debridement, autograft bone grafting, and internal fixation. There were 3 reoperations (1 for infection, 2 for painful hardware). All patients achieved successful radiographic union (average, 8 ± 2 weeks). At an average follow-up of 4.4 ± 1.2 years, the average postoperative Disabilities of the Arm, Shoulder, and Hand score was 1.1 ± 1.6; the Mayo Elbow Performance Score was 98.5 ± 2.4; the American Shoulder and Elbow Surgeons score was 99.3 ± 0.4; and average Likert score for satisfaction was 9.95 ± 0.2. At final follow-up, there were no significant differences in strength, motion, or stability in comparing the operative with the nonoperative elbow ( P > .05 for all). Conclusions Two unique patterns of olecranon physeal abnormalities in young, overhead throwing athletes have been identified. Open reduction with internal fixation is clinically and radiographically successful in obtaining union and symptom resolution in these patients.

ObjectiveEarly and accurate diagnosis of patients with psychogenic nonepileptic seizures (PNES) leads to appropriate treatment and improves long-term seizure prognosis. However, this is complicated by the need to record seizures to make a definitive diagnosis. Suspicion for PNES can be raised through knowledge that patients with PNES have increased somatic sensitivity and report more positive complaints on review-of-systems questionnaires (RoSQs) than patients with epileptic seizures. If the responses on the RoSQ can differentiate PNES from other seizure types, then these forms could be an early screening tool.MethodsOur dataset included all patients admitted from January 2006 to June 2016 for video-electroencephalography at UCLA. RoSQs prior to May 2015 were acquired through retrospective chart review (n=405), whereas RoSQs from subsequent patients were acquired prospectively (n=190). Controlling for sex and number of comorbidities, we used binomial regression to compare the total number of symptoms and the frequency of specific symptoms between 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 RoSQs to differentiate PNES only from ES only, we used multivariate logistic regression, controlling for sex and the number of medical comorbidities.ResultsOn average, patients with PNES or mixed PNES and ES reported more than twice as many symptoms than patients with isolated ES or PSLE (p0.1).DiscussionThis analysis of RoSQs confirms that patients with PNES with and without comorbid ES report more symptoms on a population level than patients with epilepsy or PSLE. While these differences help describe the population of patients with PNES, the consistency of RoSQ responses was neither accurate nor specific enough to be used solely as an early screening tool for PNES. Our results suggest that the RoSQ may help differentiate PNES from ES only when, based on other information, the pre-test probability of PNES is at least 50%.

Enthesopathy of the extensor carpi radialis brevis, often referred to as "tennis elbow," is common and responds to nonsurgical treatment in 80% to 90% of patients within 1 year. For those who proceed with surgery, much remains unclear regarding the ideal treatment. This paper discusses controversies in surgical management of extensor carpi radialis brevis enthesopathy including clinical outcomes of open versus arthroscopic techniques, the relevance of concomitant pathology addressed arthroscopically, and avenues for assessing comparative cost data.

Objective—To determine the effects of intratumoral injection of a hyaluronan-cisplatin nanoconjugate on local and systemic platinum concentrations and systemic toxicosis. Animals—5 dogs with spontaneous soft tissue sarcomas (STSs). Procedures—For each dog, approximately 1.5 mL of hyaluronan nanocarrier conjugated with 20 mg of cisplatin was injected into an external STS. Blood samples were collected immediately before (0 hours) and at 0.5, 1, 2, 3, 4, 24, and 96 hours after hyaluronan-cisplatin injection for pharmacokinetic analyses. Urine samples were obtained at 0 and at 96 hours after hyaluronan-cisplatin injection for urinalysis. Each treated STS and its sentinel lymph nodes were surgically removed 96 hours after the hyaluronan-cisplatin injection. Inductively coupled plasma mass spectrometry was used to measure platinum concentrations in blood samples, tumors, and lymph nodes. Results—No tissue reactions were detected 96 hours after hyaluronan-cisplatin injection. Mean ± SD area under the curve, peak concentration, and terminal half-life for unbound (plasma) and total (serum) platinum were 774.6 ± 221.1 ng•h/mL and 3,562.1 ± 2,031.1 ng•h/mL, 56.5 ± 20.9 ng/mL and 81.6 ± 40.4 ng/mL, and 33.6 ± 16.1 hours and 51.2 ± 29.1 hours, respectively. Platinum concentrations ranged from 3,325 to 8,229 ng/g in STSs and 130 to 6,066 ng/g in STS-associated lymph nodes. Conclusions and Clinical Relevance—Intratumoral injection of the hyaluronan-cisplatin nanoconjugate was well tolerated in treated dogs. Following intratumoral hyaluronan-cisplatin injection, platinum concentration was 1,000-fold and 100-fold greater within treated tumors and tumor-draining lymphatics, respectively, compared with that in plasma.

Purpose To evaluate the biomechanical alterations that occur after traditional scaphoid excision and midcarpal arthrodesis with and without excision of the triquetrum. The hypothesis of this study was that removal of the triquetrum increases the radiolunate contact pressure. Methods We cyclically moved 10 fresh cadaver wrists using a wrist joint motion simulator while measuring the contact pressures between the proximal carpal row and the distal radius and ulna using a dynamic pressure sensor. We acquired data in the intact wrist, after a midcarpal arthrodesis with the scaphoid excised, and then again with the triquetrum removed, which is also known as a capitolunate arthrodesis. Results The peak pressures in the radiolunate fossa significantly increased with either of the midcarpal arthrodeses compared with the intact wrist during each of the 3 dynamic wrist motions. In comparing the 2 midcarpal arthrodeses, the peak pressure in the ulnocarpal fossa significantly decreased after the triquetrum was removed during wrist radioulnar deviation and in the static ulnarly deviated position. After arthrodesis, we could identify no differences during any motion or static wrist position in the peak radiolunate pressures with or without the triquetrum. Conclusions We found that scaphoid excision and 4-corner arthrodesis shifts loads to the radiolunate joint. Isolated capitolunate arthrodesis with excision of the scaphoid and triquetrum further alters carpal kinematics and loading patterns. Clinical relevance These findings raise concern about routine excision of the triquetrum when performing a midcarpal arthrodesis.

Objective Withaferin A, a natural withanolide, has shown anti-cancer properties in various cancers including breast cancer, but its effects in ovarian cancer remain unexplored. Notch 1 and Notch3 are critically involved in ovarian cancer progression. We decided to examine the effects of Withaferin A in ovarian carcinoma cell lines and its molecular mechanism of action including its regulation of Notch. Methods The effects of Withaferin A were examined in CaOV3 and SKOV3 ovarian carcinoma cell lines using MTS assay, clonogenic assay, annexin V/propidium iodide flow cytometry, and cell cycle analysis. Western analysis was conducted to examine the molecular mechanisms of action. Results Withaferin A inhibited the growth and colony formation of CaOV3 and SKOV3 cells by inducing apoptosis and cell cycle arrest. These changes correlated with down-regulation of Notch1, Notch3, cdc25C, total and phosphorylated Akt, and bcl-2 proteins. Conclusions Withaferin A inhibits CaOV3 and SKOV3 ovarian carcinoma cell growth, at least in part by targeting Notch1 and Notch3.

This study evaluated the clinical outcomes and radiographic features of surgically treated traumatic ulnocarpal translocation in nine patients (ten cases). All ligament and fracture repairs were completed within 2 months of injury. Seven cases were examined at a mean of 6.5 years, and information in three cases was obtained from medical records at a mean of 13 months after injury. At final evaluation, the mean disabilities of the arm, shoulder, and hand score was 6 (range, 0–16), and the mean Mayo modified wrist score was 76 (range, 40–100). Ulnocarpal translocation was evident in nine of the injured wrists, six of which showed arthritis, and in four of the uninjured wrists. Ulnar variance measured negative in nine cases and neutral in one case. Pre-existing medial alignment of the carpus and ulnar minus variance may predispose to traumatic ulnocarpal translocation. Early injury repair does not assure restoration of radiocarpal alignment or prevent joint deterioration; however, these changes do not always portend a suboptimal result.

Development of the DNA gyrase inhibitor, novobiocin, into a selective Hsp90 inhibitor was accomplished through structural modifications to the amide side chain, coumarin ring, and sugar moiety. These species exhibit ~700-fold improved anti-proliferative activity versus the natural product as evaluated by cellular efficacies against breast, colon, prostate, lung, and other cancer cell lines. Utilization of structure–activity relationships established for three novobiocin synthons produced optimized scaffolds, which manifest mid-nanomolar activity against a panel of cancer cell lines and serve as lead compounds that manifest their activities through Hsp90 inhibition.

Machine learning methods have been applied to classifying fMRI scans by studying locations in the brain that exhibit temporal intensity variation between groups, frequently reporting classification accuracy of 90% or better. Although empirical results are quite favorable, one might doubt the ability of classification methods to withstand changes in task ordering and the reproducibility of activation patterns over runs, and question how much of the classification machines' power is due to artifactual noise versus genuine neurological signal. To examine the true strength and power of machine learning classifiers we create and then deconstruct a classifier to examine its sensitivity to physiological noise, task reordering, and across-scan classification ability. The models are trained and tested both within and across runs to assess stability and reproducibility across conditions. We demonstrate the use of independent components analysis for both feature extraction and artifact removal and show that removal of such artifacts can reduce predictive accuracy even when data has been cleaned in the preprocessing stages. We demonstrate how mistakes in the feature selection process can cause the cross-validation error seen in publication to be a biased estimate of the testing error seen in practice and measure this bias by purposefully making flawed models. We discuss other ways to introduce bias and the statistical assumptions lying behind the data and model themselves. Finally we discuss the complications in drawing inference from the smaller sample sizes typically seen in fMRI studies, the effects of small or unbalanced samples on the Type 1 and Type 2 error rates, and how publication bias can give a false confidence of the power of such methods. Collectively this work identifies challenges specific to fMRI classification and methods affecting the stability of models.

Purpose Arthritis of the thumb carpometacarpal (CMC) joint is a common condition, for which reconstruction using the flexor carpi radialis (FCR) is a standard treatment. We describe the technique and clinical results for thumb CMC arthroplasty using interference screw fixation of the FCR to the first metacarpal through a single incision. Methods Over 12 months, 29 consecutive CMC arthroplasties were performed in 29 patients using FCR transfer tenotomized at the level of the scaphoid with an absorbable biotenodesis screw for fixation. There were 24 women and 5 men, with a mean age of 58 years. Patients were evaluated at a minimum of one year with radiographs, standardized outcome instruments, and measurements of motion and strength. The scaphoid to first metacarpal distance was measured at 2 weeks, 3 months, and greater than 1 year to assess settling. Results A total of 28 patients were available at a mean of 19 months. No arthroplasties required revision. Postoperative scaphoid to first metacarpal distance was 5.9 mm, which had decreased by a mean of 1.4 mm at final follow-up. There were no side-to-side differences in range of motion or strength in the entire cohort except for lateral key pinch, which was lower on the reconstructed side. The mean postoperative Disabilities of the Arm, Shoulder, and Hand score was 15, and the mean visual analog scale score was 1. Correlations were found between age and lateral key pinch strength for the reconstructed and contralateral sides. There were no significant relationships among Disabilities of the Arm, Shoulder, and Hand score, visual analog scale, radiographic settling, side-to-side strength or range of motion versus gender, Eaton stage, or workers' compensation status. Conclusions Our series demonstrates excellent clinical outcomes with no revisions at an average of 19 months for this technique. Strength, range of motion, and radiographic settling compare favorably with published results of alternative techniques. Except for lateral key pinch, there was no statistically significant difference in strength compared with the contralateral side. Type of study/level of evidence Therapeutic IV.

Background Debate exists whether frozen-section analysis of sentinel lymph nodes (SLNs) for melanoma is an accurate method to detect disease that has metastasized to the lymph nodes. The purpose of this study was to evaluate the utility of intraoperative frozen section for SLNs in melanoma. Methods We reviewed 133 patients (271 nodes) who underwent SLN biopsy with frozen section for melanoma between April 2003 and September 2007. Frozen-section diagnosis was compared with final diagnosis to determine concordance between intraoperative and postsurgical diagnosis. Results A total of 11 nodes (8% of patients) were found to have metastatic disease. All patients underwent lymph node dissections at the time of SLN biopsy. No false-positive SLNs were found on frozen section. The false-negative rate for SLN biopsy frozen section was 8% (1 of 133 patients). Conclusions Intraoperative frozen section can be an accurate and reliable tool in the right setting for analysis of sentinel nodes in cutaneous melanoma and deserves further study.

Purpose The purpose of this study is to evaluate the coverage patterns of whole and split flexor carpi ulnaris (FCU) pedicle muscle flaps for posterior elbow soft-tissue defects. Methods Seventeen fresh-frozen cadaveric upper extremities were used. The whole FCU was raised to the dominant vascular pedicle and transposed proximally over the olecranon. The widths of coverage at 2-cm distances about the posterior elbow were measured. Widths were also measured after making 3 longitudinal cuts in the fascia and after suturing the muscle to adjacent soft tissue under tension. The FCU was also split into its ulnar and humeral heads along the central tendon. The larger ulnar head was transposed and the widths again measured. Mid-forearm circumference, elbow circumference, and ulnar length were assessed for ability to predict flap width. Results The whole muscle under no tension provided an average of 2.7 cm width coverage at the tip of the olecranon process. Cutting the fascia provided approximately 15% additional width and suturing the muscle to the surrounding soft tissue an additional 25%, to approximately 4 cm. The isolated FCU ulnar head provided approximately 75% of the width of the entire muscle. Mid-forearm circumference was the most predictive of flap width, and divisors were generated that improved the accuracy of predicting the width for outlier specimens. The dominant pedicle was a consistent distance relative to the end of the central tendon and the olecranon tip. Conclusions The whole and split FCU pedicle flaps provide predictable coverage for 2- to 4-cm posterior elbow soft-tissue defects. For especially large and small arms, the divisors improve accuracy in predicting flap width. Consistent locations of the olecranon tip and the end of the central tendon in relation to the dominant pedicle make them useful surgical landmarks.

Schizophrenia patients exhibit deficits in various stages of visual information processing. Despite recent informative efforts to examine visual processing in schizophrenia with functional magnetic resonance imaging (fMRI), much remains unknown about the basic function, structure, and organization of key early visual processing areas in schizophrenia. This study examined magnitude and topography of regional brain activity in three early visual processing areas: early retinotopically organized areas (V1-V4), motion-sensitive areas (human area MT, hMT+), and object-recognition areas (lateral occipital complex, LO). Using visual stimuli that are known to preferentially activate each respective region, we compared responses in these areas in 22 schizophrenia patients and 19 normal controls. Activity in all three regions was of similar amplitude in schizophrenia patients and normal controls. Activity in retinotopically organized areas and hMT+ showed good spatial overlap between groups. However, activation of LO was more widely distributed in patients compared with normal controls. The findings of abnormal spatial organization of LO in schizophrenia patients may converge with behavioral evidence of deficits in schizophrenia patients for object-recognition tasks that are believed to be mediated by LO activity.

Surgical repair is the most reliable method of restoring flexion and supination strength of the elbow and forearm after acute rupture of the distal biceps tendon. Although there may be small measurable deficits in power, endurance, and terminal forearm rotation when carefully evaluated, most of the patients regain near normal upper extremity motion and function and can return to preinjury activities. There are currently 2 basic surgical approaches for distal biceps tendon repair, using 1 anterior incision or using 1 anterior and 1 lateral incision. Anterior repair alone has the advantage of a minimal risk of heterotopic bone formation, but carries a greater chance of injury to the posterior interosseous nerve. In turn, the 2-incision technique markedly diminishes the risk of radial nerve palsy, but is associated with a greater likelihood of heterotopic bone formation limiting forearm rotation. Rerupture of the distal biceps tendon after repair is uncommon with either technique, and the risk of all complications seems to increase with a delay in surgical intervention after rupture. When motion limiting heterotopic ossification does occur, surgical resection can proceed when the process becomes mature as defined by plain radiographs. Fortunately, functional forearm motion can be commonly restored in these cases with careful attention to surgical details and postoperative rehabilitation.

Background Breast cancers typically spread to regional lymph nodes once they disseminate from the primary tumor, thus adequate evaluation and treatment of the axillary lymph nodes is paramount in early stage disease. One significant problem with current therapy is the side effects chemotherapy agents create systemically, either alone or in combination. The purpose of this study is to determine whether lymphatically targeted cisplatin carriers will increase the localized dose in lymphatic metastases without systemic toxicities. Methods Hyaluronan (HA) is a highly biocompatible polymer that follows lymphatic drainage from the interstitial spaces. We formed complexes of HA and cisplatin by non-covalent conjugation. Complexes were injected subcutaneously into the upper mammary fat pad of female rats, and the tissue distribution determined. Results Cisplatin–HA contained up to 0.25 w/w of Pt and released drug with a half-life of 10 h in saline. Cisplatin–HA conjugates had high anti-tumor activity in vitro similar to the free drug: cisplatin–HA IC 50 7 μg/mL in MCF7 and MDA-MB-231 human breast cancer cells (free cisplatin IC 50 7 μg/mL). Cisplatin–HA conjugates were well tolerated in rodents with no signs of injection site morbidity or major organ toxicity after 96 h. The area-under-the-curve of cisplatin in the axially lymph nodes after injection with cisplatin–HA increased 74% compared with normal cisplatin. Conclusions This study demonstrates a novel intralymphatic drug delivery method in breast cancer to preferentially treat at-risk regional lymph nodes and avoid systemic toxicities. Further in vivo testing related to efficacy of this approach with regard to survival, toxicity, and pharmacokinetics is warranted to support its use in human trials.