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Deep brain stimulation (DBS) is a neurosurgical procedure that depends on high-accuracy targeting of structures to implant electrodes within the brain. The positioning of these electrodes in the brain determines the long-term efficacy of treating diseases such as Parkinson's disease, essential tremor, or dystonia. Misplaced electrodes in DBS can lead to poor efficacy and stimulation-induced side effects. Widespread targeting errors and variability have been published throughout the literature. As such, improvement in targeting accuracy is needed to enhance the quality of the procedures. A stereotactic phantom was utilized to test and adjust targeting before the surgical placement in the brain for 91 sequential electrodes. The tip of the microelectrode, the first rigid point in time, was measured and compared to the planned target. The technique utilized a to-target cannula with an XY stage that allowed x-axis and y-axis adjustments and correction for inaccuracies relative to the phantom. A calculation was developed to convert anatomical angles (sagittal and coronal) provided by commercial planning stations to spherical angles to calculate points along a trajectory. Error calculations included each dimensional axis, Euclidean error, and radial error. Bends in the cannula and microelectrode were observed and corrected by referencing the phantom. All 91 first-pass tracks traversed the intended target, and three electrodes required a second mapping track beyond the first penetration due to neurophysiological and intraoperative testing. The results showed overall ultra-high (0-0.5 mm) to high (>0.5-1 mm) accuracy, an average Euclidean error of 0.66±0.30 mm, and a radial error of 0.45±0.28 mm with dimensional errors of less than 0.5 mm per axis. The utilization of a stereotactic phantom is an important tool to enhance the stereotactic targeting before insertion into the brain. This phantom technique yielded ultra-high to high accuracy in error calculations. Future methods and studies should focus on error minimization to enhance these DBS mechanical accuracy and correlations with clinical outcomes., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sedrak et al.)

Background: Hyperglycemia is recognized as a common adverse event for patients receiving alpelisib but has been little studied outside of clinical trials. We report the frequency of alpelisib-associated hyperglycemia in a real-world setting and evaluate proposed risk factors., Patients and Methods: We retrospectively identified patients with PIK3CA-mutated, hormone receptor-positive, metastatic breast cancer who initiated treatment with alpelisib plus fulvestrant between August 2019 and December 2021. Ordinal logistic regression evaluated 5 characteristics (diabetes, prediabetes, body mass index [BMI], age, and Asian ancestry) as independent risk factors for ALP-associated hyperglycemia grades 2-4. Risk of error from multiple hypothesis testing was controlled using the false discovery rate method., Results: The study included n = 92 subjects, all but 1 female, mean age 59.9 (+11.9) years with 50% non-Hispanic White, 15% Hispanic/Latino, 13% Asian, 9% African/Black, and 13% other/unknown. In total 34% of patients had diabetes, 10% had pre-diabetes, and 56% had normoglycemia. Thirty-six percent were obese, 32% were overweight, 25% were normal weight, and 7% were lean. Frequency of grades 1-4 hyperglycemia in current subjects (64.1%) was similar to hyperglycemia reported in the SOLAR-1 trial (63.7%). Our subjects' risk of grades 2-4 hyperglycemia was independently increased by pre-existing diabetes (Odds ratio 3.75, 95% CI, 1.40-10.01), pre-diabetes (6.22, 1.12-34.47), Asian ancestry (7.10, 1.75-28.84), and each unit of BMI above 20 (1.17, 1.07-1.28)., Conclusion: While receiving alpelisib, patients of Asian ancestry, as well as patients with pre-existing hyperglycemia and/or BMI above 20, should be closely monitored for hyperglycemia. The mechanism underlying the current association of alpelisib-associated hyperglycemia with Asian ancestry is independent of BMI and merits further study. The high incidence of hyperglycemia resulted in a change in practice to include consultation with a diabetes nurse educator or endocrinologist at the start of alpelisib., (© The Author(s) 2023. Published by Oxford University Press.)

Introduction: Aging-related concerns can increase the risk of treatment toxicities among older adults considering adjuvant chemotherapy. We previously demonstrated that older adults with cancer who reported feeling older than their chronological age (i.e., self-perceived age) were more likely to have aging-related concerns identified during a geriatric assessment. We explored how decisions about adjuvant chemotherapy vary with or are related to older adults' self-perceived age., Materials and Methods: We conducted a secondary analysis of a multi-phased feasibility pilot using semi-structured interviews that were conducted to explore the patient decision-making process for adjuvant chemotherapy. Interviews incorporated questions about chronological and perceived age as factors for decision-making. Patient eligibility for the study included (1) age ≥ 70 years and older, (2) a diagnosis of breast, colon, or lung cancer and considering adjuvant chemotherapy, and (3) able to read size 18 font in English. Interview data were analyzed using constant comparative method., Results: Twenty-one patients were enrolled. The mean chronological age was 78 years (range 71-91). The average perceived age of patients was 57 years (range 21-80). Eleven patients chose to receive treatment while ten patients did not. Aging-related themes illustrated that self-perceived age plays an important role when patients make decisions about adjuvant chemotherapy. More specifically, patients who reported their self-perceived age as younger than their chronological age also reported better perceived health status and chose to receive adjuvant chemotherapy., Discussion: Patients' experiences of aging and self-perceived age may have different implications for decision-making., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Glucocorticoids, which are administered with chemotherapy, cause hyperglycemia. Glycemic variability among breast cancer patients without diabetes is not well known. A retrospective cohort study was conducted involving early-stage breast cancer patients without diabetes who received dexamethasone prior to neoadjuvant or adjuvant taxane chemotherapy between August 2017-December 2019. Random blood glucose levels were analyzed, and steroid-induced hyperglycemia (SIH) was defined as a random glucose level of >140 mg/dL. A multivariate proportional hazards model was used to identify the risk factors of SIH. Out of 100 patients, the median age was 53 years (IQR: 45-63.5). A total of 45% of patients were non-Hispanic White, 28% Hispanic, 19% Asian, and 5% African American. The incidence of SIH was 67%, and glycemic fluctuations were highest in those with glucose levels of >200 mg/dL. Non-Hispanic White patients represented a significant predictor for time to SIH, with a hazard ratio of 2.5 (95% CI: 1.04, 5.95, p = 0.039). SIH was transient in over 90% of the patients, and only seven patients remained hyperglycemic after glucocorticoid and chemotherapy completion. Pretaxane dexamethasone-induced hyperglycemia was observed in 67% of the patients, with the greatest glycemic lability in those patients with blood glucose levels of >200 mg/dL. The non-Hispanic White patients had a higher risk of developing SIH.

Frame-based stereotactic localization is an important step for targeting during a surgical procedure. The motion may cause artifacts in this step reducing the accuracy of surgical targeting. While modeling of motion in real-life scenarios may be difficult, herein we analyzed the case where motion was suspected to impact the localization step. In this case, a scan with and without motion was performed with a 3N localizer, allowing for a thorough analysis. Pseudo-bending of straight rods was seen when analyzing the data. This pseudo-bending appears to occur because head-frame motion during imaging acquisition decreases the accuracy of the subsequent reconstruction, which depends on Digital Imaging and Communications in Medicine (DICOM) metadata to specify the slice-to-slice location that assumes embedded object stability. Comparison of single-slice and multi-slice stereotactic localization allowed for comparative errors for each slice in a volume. This comparative error demonstrated low error when the patient was under general anesthesia and presumed not to have moved, whereas a higher error was present during the scan with motion. Pseudo-bending can be corrected by using only localizer fiducial-based information to reorient the pixels in the volume, thus creating a reoriented localizer scan. Finally, targeting demonstrated a low error of 0.1 mm (+/- 0.1 mm) using this reoriented localizer scan, signifying that this method could be used to improve or recover from motion problems. Finally, it is concluded that stability and elimination of motion for all images utilized for stereotactic surgery are critical to ensure the best possible accuracy for the procedure., Competing Interests: Armando Bouza is 50% owner of MNPS, stereotactic software, (Copyright © 2022, Sedrak et al.)

Objectives: There is a lack of effective patient education regarding diagnosis/treatment of neuroendocrine tumors (NETs), possibly related to their rare incidence., Methods: In this cross-sectional survey study, NET patients attending the 2019 Annual Los Angeles NET Education Conference were approached to complete NET VITALS, a self-assessment tool gauging patients' perception/awareness of their NET diagnosis/treatment, and a satisfaction survey. Feasibility of NET VITALS, patient satisfaction with NET VITALS, and patients' perception/awareness of their NET diagnosis/treatment were evaluated., Results: This analysis included 68 patients (median age, 63 years; 47.1% gastrointestinal NETs; 88.2% metastatic disease). Participation was 88.3% (68/77), with a median of 85.7% of items completed (range, 61.9%-100.0%). More than 30% of the patients answered "Don't know/Not familiar"/left blank questions related to tumor characteristics, years of symptoms, and liver-directed therapies. In addition, 69.5% of the patients did not feel sufficient information about NETs was provided at diagnosis. Overall, 67.8% of the patients felt that NET VITALS provides topics to discuss with providers and 76.3% would recommend NET VITALS to others., Conclusions: NET VITALS is a feasible and acceptable self-assessment tool to potentially help patients improve communication about their NET diagnosis/treatment with their physician. Further studies will examine NET VITALS' generalizability and discuss its incorporation into clinical care., Competing Interests: D.L. reports research funding to his institution from AstraZeneca and Brooklyn ImmunoTherapeutics. He serves as a consultant and has received honoraria from Adagene, Advanced Accelerator Applications, Bayer, Coherus, Eisai, Exelixis, Genentech, Ipsen Biopharmaceuticals, Lexicon, Merck, MiNA Therapeutics, QED, Servier, Sun Pharma, Taiho, and TerSera Therapeutics, all outside the submitted work. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Frame-based stereotactic localization generally assumes that all required fiducials are present in a single-slice image which can then be used to form targeting coordinates. Previously, we have published the use of novel localizers and mathematics that can improve stereotactic localization. As stereotactic procedures include numerous imaging slices, we sought to investigate, develop, and test techniques that utilize multiple slices for stereotactic localization and provide a solution for a parallel bipanel N-localizer.  Several multi-slice equations were tested. Specifically, multi-slice stereotactic matrices (ms-SM) and multi-slice normal to parallel planes (ms-nPP) were of particular interest. Bipanel (2N) and tripanel (3N) localizer images were explored to test approaches for stereotactic localization. In addition, combination approaches using single-slice stereotactic matrices (ss-SM) and multi-slice methods were tested. Modification of ss-SM to form ms-SM was feasible. Likewise, a method to determine ms-nPP was developed. For the special case of the parallel bipanel N-localizer, single-slice and multi-slice methods fail, but a novel non-linear solution is a robust solution for ms-nPP. Several methods for single-slice and multi-slice stereotactic localization are described and can be adapted for nearly any stereotactic system. It is feasible to determine ms-SM and ms-nPP. In particular, these methods provide an overdetermined means to calculate the vertical z, which is determined for a tripanel system using single-slice methods. In addition, the multi-slice methods can be used for extrapolation outside of the localizer space. Importantly, a novel non-linear solution can be used for parallel bipanel N-localizer systems, where other methods fail. Finally, multi-slice stereotactic localization assumes strict patient and imaging system stability, which should be carefully assessed for each case., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Sedrak et al.)

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Background: CDK4/6 inhibitors modulate immune response in breast cancer. This phase I/II trial was designed to test the safety and efficacy of palbociclib, pembrolizumab and letrozole in women with hormone receptor positive (HR + ) human epidermal growth factor receptor 2 negative (HER2 - ) metastatic breast cancer (MBC)., Patients and Methods: Women with stage IV HR + HER2 - MBC were enrolled and treated with palbociclib, pembrolizumab and letrozole. Primary end-points were safety, tolerability and efficacy., Results: Between November 2016 and July 2020, 23 patients were enrolled with 20 evaluable for response, including 4 patients in cohort 1 and 16 patients in cohort 2. Cohort 1 median age was 48 years (33-70) and cohort 2 median age was 55 (37-75). Cohort 1 closed early due to limited accrual. Grade III-IV adverse events were neutropenia (83%), leucopaenia (65%), thrombocytopenia (17%) and elevated liver enzymes (17%). In cohort 1, 50% achieved a partial response (PR) and 50% had stable disease (SD). In cohort 2, 31% achieved complete response (CR), 25% had PR and 31% had SD by Response Evaluation Criteria in Solid Tumours version 1.1. Median progression-free survival was 25.2 months (95% confidence interval [CI] 5.3, not reached) and median overall survival was 36.9 months (95% CI 36.9, not reached) in cohort 2 with a median follow-up of 24.8 months (95% CI 17.1, not reached). A correlative immune biomarker analysis was published separately., Conclusion: The combination of palbociclib, pembrolizumab and letrozole is well tolerated, and a complete response rate of 31% was identified in HR + MBC patients who received this combination as front-line therapy. Confirmatory trials are required to better understand the immune-priming effects of CDK4/6 inhibitors., Competing Interests: Conflict of interest statement Dr. Yuan has contracted research sponsored by Merck, Eisai, Novartis, Puma, Genentech, Celgene, and Pfizer; is a consultant for Puma, Pfizer, and Immunomedics; and is on the Speakers Bureau for Eisai, Genentech, AstraZeneca, Daiichi Sankyo, Pfizer, Merck, and Immunomedics. The other authors declare they have no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Image-guidance for frame-based stereotaxis is facilitated by incorporating three to four N-localizers or Sturm-Pastyr localizers into a stereotactic frame. An extant frame that incorporates only two N-localizers violates the fundamental principle of the N-localizer, which requires three non-colinear points to define a plane in three-dimensional space. Hence, this two N-localizer configuration is susceptible to error. The present article proposes the V-localizer that comprises multiple diagonal bars to provide four or more non-colinear points to minimize error., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Brown et al.)

Introduction: The N-localizer is generally utilized in a 3-panel or, more rarely, a 4-panel system for computing stereotactic positions. However, a stereotactic frame that incorporates a 2-panel (bipanel) N-localizer system with panels affixed to only the left and right sides of the frame offers several advantages: improved ergonomics to attach the panels, reduced claustrophobia for the patient, mitigation of posterior panel contact with imaging systems, and reduced complexity. A bipanel system that comprises two standard N-localizer panels yields only two three-dimensional (3D) coordinates, which are insufficient to solve for the stereotactic matrix without further information. While additional information to determine the stereotactic positions could include scalar distances from Digital Imaging and Communications in Medicine (DICOM) metadata or 3D regression across the imaging volume, both have risks related to noise and error propagation. Therefore, we sought to develop new stereotactic localizers that comprise only lateral fiducials (bipanel) that leave the front and back regions of the patient accessible but that contain enough information to solve for the stereotactic matrix using each image independently.  Methods: To solve the stereotactic matrix, we assumed the need to compute three or more 3D points from a single image. Several localizer options were studied using Monte Carlo simulations to understand the effect of errors on the computed target location. The simulations included millions of possible combinations for computing the stereotactic matrix in the presence of random errors of 1mm magnitude. The matrix then transformed coordinates for a target that was placed 50mm anterior, 50mm posterior, 50mm lateral, or 50mm anterior and 50mm lateral to the centre of the image. Simulated cross-sectional axial images of the novel localizer systems were created and converted into DICOM images representing computed tomography (CT) images.  Results: Three novel models include the M-localizer, F-localizer, and Z-localizer. For each of these localizer systems, optimized results were obtained using an overdetermined system of equations made possible by more than three diagonal bars. In each case, the diagonal bar position was computed using standard N-localizer mathematics. Additionally, the M-localizer allowed adding a computation using the Sturm-Pastyr method. Monte Carlo simulation demonstrated that the Z-localizer provided optimal results., Conclusion: The three proposed novel models meet our design objectives. Of the three, the Z-localizer produced the least propagation of error. The M-localizer was simpler and had slightly more error than the Z-localizer. The F-localizer produced more error than either the Z-localizer or M-localizer. Further study is needed to determine optimizations using these novel models., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2021, Sedrak et al.)

Obsessive-compulsive disorder (OCD), a leading cause of disability, affects ~1-2% of the population, and can be distressing and disabling. About 1/3 of individuals demonstrate poor responsiveness to conventional treatments. A small proportion of these individuals may be deep brain stimulation (DBS) candidates. Candidacy is assessed through a multidisciplinary process including assessment of illness severity, chronicity, and functional impact. Optimization failure, despite multiple treatments, is critical during screening. Few patients nationwide are eligible for OCD DBS and thus a multi-center approach was necessary to obtain adequate sample size. The study was conducted over a six-year period and was a NIH-funded, eight-center sham-controlled trial of DBS targeting the ventral capsule/ventral striatum (VC/VS) region. There were 269 individuals who initially contacted the sites, in order to achieve 27 participants enrolled. Study enrollment required extensive review for eligibility, which was overseen by an independent advisory board. Disabling OCD had to be persistent for ≥5 years despite exhaustive medication and behavioral treatment. The final cohort was derived from a detailed consent process that included consent monitoring. Mean illness duration was 27.2 years. OCD symptom subtypes and psychiatric comorbidities varied, but all had severe disability with impaired quality of life and functioning. Participants were randomized to receive sham or active DBS for three months. Following this period, all participants received active DBS. Treatment assignment was masked to participants and raters and assessments were blinded. The final sample was consistent in demographic characteristics and clinical features when compared to other contemporary published prospective studies of OCD DBS. We report the clinical trial design, methods, and general demographics of this OCD DBS sample., (© 2021 The Authors.)

Introduction:  Frame-based stereotaxis has been widely utilized for precise neurosurgical procedures throughout the world for nearly 40 years. The N-localizer is an integral component of most of the extant systems. Analysis of targeting errors related to the N-localizer has not been carried out in sufficient detail. We highlight these potential errors and develop methods to reduce them.  Methods: N-localizer systems comprising three and four N-localizers of various geometries were analyzed using Monte Carlo (MC) simulations. The simulations included native and altered geometric dimensions (Width [W] x Height [H]). Errors were computed using the MC simulations that included the x- and y-axes of vertically oriented rods, that altered the W/H ratio, and that added a fourth N-localizer to a three N-localizer system.  Results: The inclusion of an overdetermined system of equations and the geometries of the N-localizer systems had significant effects on target errors. Root Mean Square Errors (RMS-e) computed via millions of MC iterations for each study demonstrated that errors were reduced by (1) inclusion of the x- and y-coordinates of the vertically oriented rods, (2) a greater triangular area enclosed by the diagonal fiducials of the N-localizer system (stereotactic triangle), (3) a larger W/H ratio, and (4) an N-localizer system that comprised four N-localizers., Conclusion: Monte Carlo simulations of Root Mean Square error (RMS-e) is a useful technique to understand targeting while using N-localizer systems in stereotactic neurosurgery. The application of vertical rod positions enhances computational accuracy and can be performed on any N-localizer system. Keeping the target point within the stereotactic triangle enclosed by the diagonal rods can also reduce errors. Additional optimizations of N-localizer geometry may also reduce potential targeting errors. Further analysis is needed to confirm these findings which may have clinical importance., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2021, Sedrak et al.)

Lessons Learned: The combination of enobosarm and pembrolizumab was well tolerated and showed a modest clinical benefit rate of 25% at 16 weeks. Future trials investigating androgen receptor-targeted therapy in combination with immune checkpoint inhibitors are warranted., Background: Luminal androgen receptor is a distinct molecular subtype of triple-negative breast cancer (TNBC) defined by overexpression of androgen receptor (AR). AR-targeted therapy has shown modest activity in AR-positive (AR+) TNBC. Enobosarm (GTx-024) is a nonsteroidal selective androgen receptor modulator (SARM) that demonstrates preclinical and clinical activity in AR+ breast cancer. The current study was designed to explore the safety and efficacy of the combination of enobosarm and pembrolizumab in patients with AR+ metastatic TNBC (mTNBC)., Methods: This study was an open-label phase II study for AR+ (≥10%, 1+ by immunohistochemistry [IHC]) mTNBC. Eligible patients received pembrolizumab 200 mg intravenous (IV) every 3 weeks and enobosarm 18 mg oral daily. The primary objective was to evaluate the safety of enobosarm plus pembrolizumab and determine the response rate. Peripheral blood, tumor biopsies, and stool samples were collected for correlative analysis., Results: The trial was stopped early because of the withdrawal of GTx-024 drug supply. Eighteen patients were enrolled, and 16 were evaluable for responses. Median age was 64 (range 36-81) years. The combination was well tolerated, with only a few grade 3 adverse events: one dry skin, one diarrhea, and one musculoskeletal ache. The responses were 1 of 16 (6%) complete response (CR), 1 of 16 (6%) partial response (PR), 2 of 16 (13%) stable disease (SD), and 12 of 16 (75%) progressive disease (PD). Response rate (RR) was 2 of 16 (13%). Clinical benefit rate (CBR) at 16 weeks was 4 of 16 (25%). Median follow-up was 24.9 months (95% confidence interval [CI], 17.5-30.9). Progression-free survival (PFS) was 2.6 months (95% CI, 1.9-3.1) and overall survival (OS) was 25.5 months (95% CI, 10.4-not reached [NR])., Conclusion: The combination of enobosarm and pembrolizumab was well tolerated, with a modest clinical benefit rate of 25% at 16 weeks in heavily pretreated AR+ TNBC without preselected programmed death ligand-1 (PD-L1). Future clinical trials combining AR-targeted therapy with immune checkpoint inhibitor (ICI) for AR+ TNBC warrant investigation., (© AlphaMed Press; the data published online to support this summary are the property of the authors.)

Background: The purpose of this study was to determine the effects of time from diagnosis to treatment (TTI) on survival in patients with nonmetastatic non-small-cell lung cancer (NSCLC)., Materials and Methods: The National Cancer Database was queried for patients with stages 1 to 3 NSCLC between 2004 and 2013. Patients with missing survival status/time, unknown TTI, or receipt of palliative therapy were excluded. Multivariable Cox proportional hazards modeling, logistic regression, and recursive partitioning analysis were performed to determine associated variables and survival outcomes., Results: Altogether, 1,393,232 patients met inclusion criteria. The median follow-up was 36 months. The median TTI increased between 2004 and 2013 from 35 to 39 days (P < .001). On multivariable Cox proportional hazards modeling, TTI groups 31 to 60 days, 61 to 90 days, and > 90 days were independently related to poorer overall survival (OS) compared with TTI 1 to 30 days (hazard ratio, 1.04, 1.10, and 1.14; 95% confidence interval [CI], 1.02-1.06, 1.07-1.12, and 1.11-1.17, respectively; P < .001 for all). Recursive partitioning analysis revealed that TTI of ≤ 45 days was the most optimal threshold for survival (P < .001); patients with TTI ≤ 45 days had a median OS of 70.2 months (95% CI, 69.3-71.1 months) versus 61.5 months (95% CI, 60.5-62.4) (P < .001). There were significant disparities by age, race, ethnicity, and income for delayed (> 45 days) TTI (P < .001 for all). Subgroup analysis revealed that stage 1 and 2 patients with TTI > 45 days had a higher risk of mortality compared with TTI ≤ 45 days (hazard ratio, 1.15 and 1.05; 95% CI, 1.12-1.17 and 1.01-1.09, respectively) (P < .001)., Conclusions: Increased TTI is independently associated with poorer survival in non-metastatic NSCLC. TTI ≤ 45 days is a clinically targetable time frame associated with improved outcomes and ought to be considered for patients with lung cancer undergoing definitive therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Efficacy in deep brain stimulation (DBS) is dependent on precise positioning of electrodes within the brain. Intraoperative fluoroscopy, computed tomography (CT), or magnetic resonance imaging are used for stereotactic intraoperative localization (StIL), but the utility of biplanar X-ray has not been evaluated in detail., Objective: To determine if analysis of orthogonal biplanar X-rays using graphical analysis (GA), ray tracing (RT), and/or perspective projection (PP) can be utilized for StIL., Methods: A review of electrode tip positions comparing postoperative CT to X-ray methods was performed for DBS operations containing orthogonal biplanar X-ray with referential spheres and pins., Results: Euclidean (Re) errors for final DBS electrode position on intraoperative X-rays vs postoperative CT using GA, RT, and PP methods averaged 1.58 mm (±0.75), 0.74 mm (±0.45), and 1.07 mm (±0.64), respectively (n = 56). GA was more accurate with a ventriculogram. RT and PP predicted positions that correlated with third ventricular structures on ventriculogram cases. RT was the most stable but required knowledge of the geometric setup. PP was more flexible than RT but required well-distributed reference points. A single case using the O-arm demonstrated Re errors of 0.43 mm and 0.28 mm for RT and PP, respectively. In addition, these techniques could also be used to calculate directional electrode rotation., Conclusion: GA, RT, and PP can be employed for precise StIL during DBS using orthogonal biplanar X-ray. These methods may be generalized to other stereotactic procedures or instances of biplanar imaging such as angiograms, radiosurgery, or injection therapeutics., (Copyright © 2019 by theCongress of Neurological Surgeons.)

The development of new HER2-directed therapies has resulted in a significant prolongation of survival for women with metastatic HER2-positive breast cancer. Discoveries in the laboratory inform clinical trials which are the basis for improving the standard of care and are also the backbone for quality improvement. Clinical trials can be completed more rapidly by expanding trial enrollment to community sites. In this article we review some of the challenges in treating metastatic breast cancer with HER2-directed therapies and our strategies for incorporating our community partners into the research network.

All stereotactic neurosurgical procedures utilize coordinate systems to allow navigation through the brain to a target. During the surgical planning, indirect and direct targeting determines the planned target point and trajectory. This targeting allows a surgeon to precisely reach points along the trajectory while minimizing risks to critical structures. Oftentimes, once a target point and a trajectory are determined, a frame-based coordinate system is used for the actual procedure. Considerations include the use of various coordinate spaces such as the anatomical ([Formula: see text]), the frame ([Formula: see text]), the head-stage ([Formula: see text]), and an atlas. Therefore, the relationships between these coordinate systems are integral to the planning and implementation of the neurosurgical procedure. Although coordinate transformations are handled in planning via stereotactic software, critical understanding of the mathematics is required as it has implications during surgery. Further, intraoperative applications of these coordinate conversions, such as for surgical navigation from the head-stage, are not readily available in real-time. Herein, we discuss how to navigate these coordinate systems and provide implementations of the techniques with samples., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2020, Sedrak et al.)

Background: Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease., Methods: This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396., Findings: Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p<0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation., Interpretation: This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes., Funding: Boston Scientific., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Older adults are underrepresented in landmark trials that determine treatment guidelines for pancreatic cancer. We used the National Cancer Database (NCDB) to compare treatment patterns and outcomes in stage I-III pancreatic cancer between older adult patients, defined as age 80 or older, to patients younger than 80., Material and Methods: We identified 140,678 patients in the NCDB diagnosed with pancreatic cancer from 2004 to 2015. Patients with metastatic disease or non-adenocarcinoma histologies were excluded. Descriptive statistics comparing patients age 80+ and age <80 were generated. Logistic regression was used to evaluate predictors of cancer-directed therapy receipt (defined as receipt of chemotherapy, radiation, or surgery) in older patients, and Cox proportional hazards modeling was performed to evaluate survival in the older cohort., Results: We identified 140,678 patients with non-metastatic pancreatic cancer, of which 23,395 patients (16.6%) were 80 or older. Among older patients, 44.5% of patients received cancer-directed therapy compared to 78.7% among other patients (p < .001). Older patients had worse 2-year survival at 11.3% versus 27.5% for younger (p < .001). 2-year survivorship decreased further in older patients who received no cancer-directed treatment, at 4.7% compared with 19.5% for older patients receiving treatment (p < .001). After propensity score matching, cancer-directed treatment remained associated with improved survival for older patients (hazard ratio 0.42; 95% confidence interval 0.41-0.43; p < .001)., Discussion: Rates of cancer-directed therapy were low in patients age 80+, with 55.5% receiving no therapy. Cancer-directed treatment was associated with an overall survival benefit. Future trials are needed to define optimal treatment paradigms in this population., Competing Interests: Declaration of Competing Interest We have no conflicts of interest to declare., (Copyright © 2019. Published by Elsevier Ltd.)

Ray tracing (RT) and perspective projection (PP) using fiducial-based registration can be used to determine points of interest in biplanar X-ray imaging. We sought to investigate the implementation of these techniques as they pertain to X-ray imaging geometry. The mathematical solutions are presented and then implemented in a phantom and actual case with numerical tables and imaging. The X-ray imaging is treated like a Cartesian system in millimeters (mm) with a standard frame-based stereotactic system. In this space, the point source is the X-ray emitter (focal spot), the plane is the X-ray detector, and fiducials are in between the source and plane. In a phantom case, RT was able to predict locations of fiducials after moving the point source. Also, a scaled PP matrix could be used to determine imaging geometry, which could then be used in RT. Automated identification of spherical fiducials in 3D was possible using a center of mass computation with average Euclidean error relative to manual measurement of 0.23 mm. For PP, RT projection or a combinatorial approach could be used to facilitate matching 3D to 2D points. Despite being used herein for deep brain stimulation (DBS), utilization of this kind of imaging analysis has wide medical and non-medical applications., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2020, Sedrak et al.)

Objective: The WHISPER randomized controlled trial (RCT) evaluates safety and clinical effectiveness of subperception spinal cord stimulation (SCS) at ≤1.2 kHz in subjects previously implanted with an SCS system for treatment of chronic, neuropathic pain., Methods: WHISPER is a prospective, multicenter RCT with a crossover design sponsored by Boston Scientific, Marlborough, MA (ClinicalTrials.gov: NCT02314000). Eligible subjects were randomized (N = 140) to receive subperception or supraperception for three months and then crossed over to receive the alternative. Upon completion of crossover period, subjects who preferred subperception were followed up to one year. Overall pain, quality-of-life, and other outcomes were collected in the study. The primary endpoint was the overall pain responder rate (≥50% improvement from baseline) with no increase in medications. Secondary endpoints consisted of pain scores, physical disability, quality of life, and treatment preference., Results: The study met its primary endpoint and demonstrated noninferiority between supraperception and subperception in a prespecified cohort of 70 randomized subjects (Interim Analysis). Thirty-nine percent of subjects with subperception settings and 29% with supraperception settings had a greater than or equal to 50% reduction in their overall pain scores with no increase in average daily medication at three-months post-activation as compared with baseline. Further assessment of all participating study subjects (N = 140) revealed similar results. Subjects were previously implanted 3.8 ± 2 years and had a disability score (Oswestry Disability Index) of 70.2 ± 11.4 at study start. Of the randomized subjects that completed the End of Period 2 Visit, 93 (66%) preferred subperception SCS and their mean overall pain reduced from 7.3 ± 1.1 (N = 89) at baseline to 4.0 ± 2.1 (N = 80) at 12-months post-activation. Post hoc analysis also demonstrated that multiple options provide superior outcomes, as supported by a 74% increase in the responder rate when subjects could choose their most effective option (47%) compared with supraperception alone (27%)., Discussion: Subperception SCS at ≤1.2 kHz is safe and effective in subjects with extreme physical disability and previously implanted for chronic pain. Further, by providing study participants with different waveform options, increased pain relief was achieved., (© 2019 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.)

Extraskeletal osteosarcoma (ESOS) is a rare variant of osteosarcoma that arises without attachment to the underlying skeleton. These cancers are typically found embedded in deeper tissues, most commonly the muscle or fascia, and are rarely found within the skin or subcutis. Most tumors are large in size upon initial presentation, and carry a poor prognosis. We discuss the case of a 48-year-old Caucasian woman who presented to a dermatology clinic with an asymptomatic, small, mobile, subcutaneous mass that appeared clinically benign. After elective removal and histopathologic examination, the patient was diagnosed with ESOS. ESOS presenting in this manner is exceedingly rare, and this case highlights the importance of sending all excised specimens, even those with a benign presentation, for pathologic examination., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The rapid expansion of physician assistant (PA) programs over the past decade has led to a shortage of experienced PA faculty. This has prompted many faculty development initiatives to help provide the skills needed by new faculty making the jump from clinical practice to academia. Faculty development is a key necessity in health professions education because many of the professionals attracted to the educator role are primarily trained as clinicians. Although this issue has been extensively evaluated by our colleagues in medical, nursing, and health education and various faculty development interventions have been implemented, this has not been done in the PA profession. In an effort to correct this, the Physician Assistant Education Association assembled a task force of experienced PA educators and charged them to evaluate the literature on faculty competencies in health professions education and to develop a set of PA educator competencies to help codify the essential knowledge, skills, attitudes, and behaviors that faculty need to be successful in their academic roles.The task force met its charge by engaging in an extensive review of the literature, developing a competency framework and proposed competencies, and soliciting the input of a diverse panel of experts in PA education to vet the proposed competencies. Using the insights and recommendations from the expert panel, the task force refined the competencies-resulting in the framework of PA educator competencies presented in this document.

Introduction: Facial pain is often debilitating and can be characterized by a sharp, stabbing, burning, aching, and dysesthetic sensation. Specifically, trigeminal neuropathic pain (TNP), anesthesia dolorosa, and persistent idiopathic facial pain (PIFP) are difficult diseases to treat, can be quite debilitating and an effective, enduring treatment remains elusive., Methods: We retrospectively reviewed our early experience with stimulation involving the trigeminal and sphenopalatine ganglion stimulation for TNP, anesthesia dolorosa, and PIFP between 2010-2014 to assess the feasibility of implanting at these ganglionic sites. Seven patients received either trigeminal and/or sphenopalatine ganglion stimulation with or without peripheral nerve stimulation, having failed multiple alternative modalities of treatment. The treatments were tailored on the physical location of pain to ensure regional coverage with the stimulation., Results: Fluoroscopy or frameless stereotaxy was utilized to place the sphenopalatine and/or trigeminal ganglion stimulator. All patients were initially trialed before implantation. Trial leads implanted in the pterygopalatine fossa near the sphenopalatine ganglion were implanted via transpterygoid (lateral-medial, infrazygomatic) approach. Trial leads were implanted in the trigeminal ganglion via percutaneous Hartel approach, all of which resulted in masseter contraction. Patients who developed clinically significant pain improvement underwent implantation. The trigeminal ganglion stimulation permanent implants involved placing a grid electrode over Meckel's cave via subtemporal craniotomy, which offered a greater ability to stimulate subdivisions of the trigeminal nerve, without muscular (V3) side effects. Two of the seven overall patients did not respond well to the trial and were not implanted. Five patients reported pain relief with up to 24-month follow-up. Several of the sphenopalatine ganglion stimulation patients had pain relief without any paresthesias. There were no electrode migrations or post-surgical complications., Conclusions: Refractory facial pain may respond positively to ganglionic forms of stimulation. It appears safe and durable to implant electrodes in the pterygopalatine fossa via a lateral transpterygoid approach. Also, implantation of an electrode grid overlying Meckel's cave appears to be a feasible alternative to the Hartel approach. Further investigation is needed to evaluate the usefulness of these approaches for various facial pain conditions.

Atypical marginal zone hyperplasia (AMZH) is a recently described disease entity seen mainly in children. AMZH most commonly affects tonsils and appendices. Cutaneous AMZH is rare. The authors report here a recurrent AMZH in the lip of a 9-year-old child who presented originally with a lip swelling for approximately 3 months. The lip lesion recurred after each incomplete excision for 4 times. Pathologically, the lesion demonstrated marginal zone B-cell hyperplasia with kappa monoclonality by flow cytometry and immunohistochemistry studies. Lymphoepithelial lesions were noted with involvement of minor salivary glands. Polymerase chain reaction for immunoglobulin heavy-chain gene rearrangement has been repeatedly negative. Polymerase chain reaction for Borrelia species DNA was negative on both paraffin-embedded tissue and plasma. Serum antibodies IgG and IgM for Helicobacter Pylori were positive. A diagnosis of AMZH was made. Two courses of anti H. Pylori therapy did not improve the lip lesion, which completely regressed after a course of prednisone therapy. With differential diagnosis of cutaneous marginal zone lymphoma, the case illustrated diagnostic challenges, especially with recurrent lesions. This is the first case of recurrent cutaneous AMZH that has uncharacteristic kappa light-chain restriction. AMZH should be considered in children with mucocutaneous lesions with features of marginal zone lymphoma.

Aim: To determine if esophageal capsule endoscopy (ECE) is an adequate diagnostic alternative to esophagogastroduodenoscopy (EGD) in pre-bariatric surgery patients., Methods: We conducted a prospective pilot study to assess the diagnostic accuracy of ECE (PillCam ESO2, Given Imaging) vs conventional EGD in pre-bariatric surgery patients. Patients who were scheduled for bariatric surgery and referred for pre-operative EGD were prospectively enrolled. All patients underwent ECE followed by standard EGD. Two experienced gastroenterologists blinded to the patient's history and the findings of the EGD reviewed the ECE and documented their findings. The gold standard was the findings on EGD., Results: Ten patients with an average body mass index of 50 kg/m(2) were enrolled and completed the study. ECE identified 11 of 14 (79%) positive esophageal/gastroesophageal junction (GEJ) findings and 14 of 17 (82%) combined esophageal and gastric findings identified on EGD. Fisher's exact test was used to compare the findings and no significant difference was found between ECE and EGD (P = 0.64 for esophageal/GEJ and P = 0.66 for combined esophageal and gastric findings respectively). Of the positive esophageal/GEJ findings, ECE failed to identify the following: hiatal hernia in two patients, mild esophagitis in two patients, and mild Schatzki ring in two patients. ECE was able to identify the entire esophagus in 100%, gastric cardia in 0%, gastric body in 100%, gastric antrum in 70%, pylorus in 60%, and duodenum in 0%., Conclusion: There were no significant differences in the likelihood of identifying a positive finding using ECE compared with EGD in preoperative evaluation of bariatric patients.

Deep brain stimulation is a rapidly expanding therapy initially designed for the treatment of movement disorders and pain syndromes. The therapy includes implantation of electrodes in specific targets of the brain, delivering programmable small and safe electric impulses, like a pacemaker, that modulates both local and broad neurologic networks. The effects are thought to primarily involve a focus in the brain, probably inhibitory, which then restores a network of neural circuitry. Psychiatric diseases can be refractory and severe, leading to high medical costs, significant morbidity, and even death. Whereas surgery for psychiatric disease used to include destructive procedures, deep brain stimulation allows safe, reversible, and adjustable treatment that can be tailored for each patient. Deep brain stimulation offers new hope for these unfortunate patients, and the preliminary results are promising.

Background: Natural orifice transluminal endoscopic surgery (NOTES) has been the focus of several studies as a less invasive alternative to conventional laparoscopy to access and treat intracavitary organs. For the last 5 years, much has been accomplished with animal studies, yet the clinical utilization of this novel technique is still modest. After 2 years of experience in the laboratory, we started our clinical experience. We report our experience with clinical utilization of NOTES procedures from 2007 to 2010., Methods: Under UCSD institutional review board-approved trials, 104 patients were enrolled under seven different NOTES protocols from 2007 to 2010, where a NOTES procedure was offered as an alternative to conventional treatments. The treated pathologies were cholelithiasis, biliary dyskinesia, acute and chronic appendicitis, ventral hernias, morbid obesity, and achalasia. The access routes included transgastric (TG), transvaginal (TV), transesophageal (TE), and perirectal (PR)., Results: Among the 104 patients enrolled, 103 underwent a surgical procedure starting with diagnostic laparoscopy, and 94 cases were deemed appropriate to proceed via a NOTES approach. There were 9 aborted NOTES procedures at the time of the initial peritoneoscopy before creating a NOTES access route. The reasons to not proceed with a NOTES procedure in the TV cholecystectomy group (n = 5) were a large amount of pelvic adhesions in 4 patients and a severe inflammation of the gallbladder in 1 patient. In the TG cholecystectomy group (n = 1), it was severe inflammation of the gallbladder. In the TG appendectomy group (n = 1), it was the presence of localized peritonitis. In the TE endoscopic myotomy group (n = 2), it was the presence of megaesophagus with an inability to clean the esophagus of food debris. The NOTES procedures performed were 48 TV cholecystectomies, 4 TV appendectomies, 8 TG cholecystectomies, 2 PR peritoneoscopies, 3 TG appendectomies, 3 TV ventral hernia repairs, 5 TE endoscopic myotomies, 3 TV sleeve gastrectomies, and 18 TG sleeve gastrectomies. The average body mass indexes for those in the sleeve gastrectomy group was 42.1 kg/m(2) (TG route) and 40.6 kg/m(2) (TV route). There were no intraoperative complication and no conversions to standard laparoscopy during these procedures. The average hospital stay was 1-2 days. One patient who underwent TV cholecystectomy required an emergency department visit for nausea and vomiting. To date, 3 patients who underwent TV cholecystectomy have become pregnant and delivered normally., Conclusions: NOTES is safe, feasible, and reproducible with previous training in the laboratory and a consistent team at a high-volume center. Prospective randomized studies of a large patient population are necessary to assess long-term results.

Background: From our early experience with NOTES, our group has acquired familiarity with transesophageal submucosal dissection and myotomy in swine model, which allowed us to perfect a model to perform purely endoscopic transesophageal myotomy (TEEM) for the treatment of achalasia and apply it into clinical practice. This study was designed to assess the safety, feasibility, and efficacy of TEEM in a series of patients with achalasia., Methods: Under institutional review board approval, patients were enrolled on our study, where TEEM was offered as an alternative to laparoscopic or robotic Heller myotomy. The inclusion criteria were patients with achalasia confirmed by esophageal manometry, between age 18 and 50 years, and ASA class 2 or lower. The exclusion criteria were pregnancy, prior esophageal surgery, immunosuppression, coagulopathies, and severe medical comorbidities. The procedures were performed under general anesthesia, with the patient in supine position on positive pressure ventilation. With a GIF-180 (Olympus, Tokyo, Japan) positioned at 10 cm above the GEJ, a mucosotomy was performed at the 2 o'clock position, and a submucosal space was developed caudally creating a controlled submucosal tunnel extending 2 cm distal to the GEJ. Upon completion of this tunnel the gastroesophageal lumen was inspected for mucosal integrity. The scope was then reinserted into the submucosal tunnel and using a triangle-tip knife, myotomy was performed starting at 5 cm above the GEJ and ending at 2 cm below the GEJ. During this process the circular muscle layer of the esophagus was carefully divided with preservation of the longitudinal layer. At the end of the procedure, the mucosal incision was closed longitudinally with endoscopic clips and surgical glue., Results: Five patients underwent TEEM, with no perioperative complication. All patients reported significant improvement of their dysphagia immediately after the procedure. On the first postoperative day, all barium swallows showed disappearance of the classical bird beak taper, rapid emptying of contrast into the stomach, and absence of leaks. All patients were discharged on the second postoperative day on liquid diet. Two patients reported transient heartburn, which were well controlled with medications. The average preoperative GERD-HRQL was 20, which improved to 11.3 at 7 days postoperative and 2 at 30 days postoperative. To date, three patients have already returned for their 6-month follow-up, reporting adequate swallowing and low LES pressures on esophageal manometry (their mean preoperative LES resting pressure was 36.46 mmHg and residual pressure was 43.16 mmHg, whereas the 6-month follow-up mean LES resting pressure was 10.06 mmHg and residual pressure was 0.43 mmHg)., Conclusions: TEEM seems to be safe, feasible, and effective for the treatment of patients with achalasia. Long-term data are still necessary for wide-spread utilization of this novel technique.

Over the past several years, leaders in healthcare have noticed an increase in generational tension among employees, most often focused on the attitudes and behaviors of the arriving millennials (generation Y). While these employee relations issues were a nuisance, they rarely rose to the level of a priority demanding leadership intervention. Some leaders, in fact, hoped that the issues would resolve themselves as these young employees settled in and learned that they had to demonstrate new behaviors to be successful in the workplace. Most organizations adopted this wait-and-see attitude. Not so today. As the boomer generation has begun its exodus from the workplace, organizations are increasingly looking at the millennials as not a problem but a solution to the workplace manpower transition that is under way. Our problem is that we don't yet know how best to lead such a diverse, multigenerational workforce. This article examines the generational topic and provides advice concerning a variety of changes that leaders may implement to advance their organization's ability to attract and to retain the millennials.

A case report is presented detailing the successful use of awake intraoperative memory testing while using white matter stimulation in order to isolate the fornix tracks involved in memory function. The identification of the white matter tracks of the fornix that were involved in memory function was used to tailor the neurosurgical resection of a third ventricle tumor that was impinging on the fornix in order to successfully preserve memory functioning in the patient.

Purpose: The study examined participation in the Basic Skills Faculty Development Workshops (BSW) offered by the Physician Assistant Education Association (PAEA). The aim was to determine the effects of participation on perceived mastery of teaching skills and job satisfaction., Methods: The 1,290 faculty and program director members of PAEA were invited to complete an electronic survey regarding their past participation in a BSW, levels of satisfaction with various aspects of their work, and their perception of their level of mastery of various teaching skills. Additionally, those who had participated in these workshops completed a section on colleague relationships that were developed or strengthened through workshop participation., Results: Approximately half (n = 248) of the 493 respondents had participated in a BSW. Mean scores for satisfaction with salary, rank, position, and overall satisfaction did not differ significantly according to BSW participation. Perceived mastery of various teaching skills was significantly higher for nonattendees of BSW. However, controlling for "years in physician assistant education" nullified that association. Attendees reported a mean of 1.02 (SD = 1.47) new mentoring relationships and 2.45 (SD = 2.97) new peer relationships. Satisfaction with current position was significantly positively correlated with the number of colleague relationships. The number of new and strengthened mentor relationships correlated significantly with perceived mastery of advising students., Conclusions: Basic Skills Workshop attendees experience acceleration in their perceived mastery of teaching skills, closing the proficiency gap between them and their more-experienced colleagues who did not attend a Basic Skills Workshop. Also, participation is associated with an increased number of colleague relationships, which has a positive effect on satisfaction.

Background: The ventralis intermedius (VIM) nucleus of the thalamus is the primary surgical target for treatment of tremor. Most centers rely on indirect targeting based on atlas-defined coordinates rather than patient-specific anatomy, making intraoperative physiological mapping critical. Detailed identification of this target based on patient-specific anatomic features can help optimize the surgical treatment of tremor., Objective: To study colored fractional anisotropic images and diffusion tensor imaging (DTI) tractography to identify characteristic magnetic resonance appearances of the VIM nucleus., Methods: Four patients undergoing stereotactic surgery for essential tremor (ET) were retrospectively studied with analysis of magnetic resonance imaging-based colored fractional anisotropy (FA) images and fiber tractography. All were scanned with a 1.5-T magnetic resonance imaging unit, and all sequences were obtained before frame placement. Because the goal of this study was to identify the DTI characteristics of physiologically defined VIM nucleus, we selected and studied patients who had undergone DTI and had efficacious tremor control with intraoperative microlesioning effect and tremor reduction with less than 2.0-V stimulation., Results: Analysis of color FA maps, which graphically illustrate fiber directionality, revealed consistent anatomic patterns. The region of the VIM nucleus can be seen as an intermediate region where there is a characteristic transition of color. Presumptive VIM nucleus interconnectivity with sensorimotor cortex and cerebellum was identified via the internal capsule and the superior cerebellar peduncle, respectively. FA maps could also be used to distinguish segments of gray matter, white matter, and gray-white matter boundaries., Conclusion: Analysis of DTI and FA maps on widely available 1.5-T magnetic resonance imaging yields clear identification of various structures key to neurosurgical targeting. Prospective evaluation of integrating DTI into neurosurgical planning may be warranted.

Aim: This study evaluates the use of cell-free fetal DNA in the plasma of RhD-negative women for noninvasive early detection of fetal RhD status and gender., Method: Ninety RhD-negative pregnant women were enrolled in the study. Amplification by real-time polymerase chain reaction (PCR) of RhD gene sequences and SRY gene sequence for the diagnosis of fetal RhD and sex was performed., Results: Among 90 RhD-negative women, according to phenotypic diagnosis, there were 61 RhD-positive and 29 RhD-negative fetuses. Also, 37 were males and 53 were females. In the first trimester, the sensitivity and the diagnostic accuracy of real-time PCR for Rh genotyping were 93.5% and 91.1%, increasing to 100% and 97.78%, respectively, in the second trimester. With regard to fetal sex determination, in the first trimester, PCR results had a sensitivity of 95.2% and a diagnostic accuracy of 97.8%, both increasing to 100% in the second trimester., Conclusion: The use of cell-free fetal DNA in prenatal noninvasive early detection of fetal RhD status and gender by real-time PCR is highly sensitive and accurate as early as the 11th week of gestation for RhD status and the 7th week of gestation for fetal sex.