Citations

BackgroundCertification by the American Board of Physical Medicine and Rehabilitation (ABPMR) requires passing both a written multiple choice examination (Part I) and an oral examination (Part II), but it has been unclear whether the two examinations measure the same or different dimensions of knowledge.ObjectiveTo evaluate the concordance between the Part I and Part II examinations for ABPMR initial certification with regard to candidate performance on the examinations and their subsets. Our question is whether the Part II examination provides additional assessment of a candidate beyond what Part I provides.DesignRetrospective psychometric evaluation of deidentified board examination scores.SettingABPMR database of Part I and Part II examination scores.ParticipantsCandidates for the ABPMR Part I and Part II examinations after 2005, with a more detailed analysis of candidates for the Part I examination from 2014 to 2016. Examination scores of candidates who took the Part II examination both before and after the examination was standardized in 2005 were also used for an additional analysis.MethodsCorrelations, simple linear regressions, and principal components analysis.Main Outcome MeasurementsCorrelation coefficients, variance analysis, and unexplained variance in the principal components analysis.ResultsThere is a weak to moderate correlation between performance on the Part I and Part II examinations: r = 0.33, P < .001. There is an additional dimension of assessment that is demonstrated on the Part II examination, with this being primarily in the domains of systems‐based practice and interpersonal communication skills.ConclusionThe Part I and Part II examinations, although with some overlap, contribute different and meaningful components to the overall evaluation of candidates for board certification in PM&R.Level of EvidenceIII.

Abstract We have previously shown that a vesicular stomatitis virus-based cDNA library expressing xenogeneic altered self-epitopes led to T-cell mediated rejection of prostate cancer, glioma and melanoma. The use of a library of altered self-peptides which reflects the transcriptome of the tumor circumvents the necessity for a priori knowledge of which antigens may be immunogenic in a patient, and primes a polyclonal T-cell response that provides strong cumulative antitumor selective pressure. We have expanded this concept of altered-self library vaccination using tumor vaccines modified by the overexpression of APOBEC3B, a cytosine deaminase that generates C to T transition mutations. A freeze-thawed whole tumor cell vaccine prepared from B16 melanoma cells stably overexpressing human APOBEC3B treated established subcutaneous parental B16 tumors and, when combined with PD-1 checkpoint blockade, cured between 75%-100% of mice. T-cells from mice treated with the vaccine and anti-PD1 produced high levels of IFN-γ when restimulated with parental unmodified B16 melanoma cells in vitro. Whole-genome sequencing of B16APOBEC3B overexpressing cells identified 301 C to T or G to A missense mutations unique to the APOBEC3B line. Using an in silico MHC binding affinity algorithm, we identified and experimentally validated a short list of 10 APOBEC3B- induced heteroclitic peptides. We have also shown that this approach can be extended to an orthotopic brainstem model of high grade glioma. GL261 tumors stereotactically implanted into the brainstem were significantly responsive to treatment with an APOBEC3B- modified GL261 vaccine in combination with anti-PD-1 checkpoint blockade. In summary, when overexpressed in tumor cells, APOBEC3B generates a library of heteroclitic sequences that primes both CD4 and CD8 T-cells that have escaped central tolerance and that recognize both newly mutated antigens from the vaccine, and the corresponding unaltered self epitopes expressed on the tumor cells. Citation Format: Richard Vile, Laura Evgin, Timothy Kottke, Matthew Schuelke, Christopher B. Driscoll, Amanda L. Huff, Jill Thompson, Amy Molan, Reuben S. Harris, Jose S. Pulido, Phonphimon Wongthida. Cancer immunotherapy with APOBEC3B-induced heteroclitic library tumor cell vaccines and immune checkpoint blockade [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B138.

Abstract Tumor cells are able to evade cytotoxic therapies through the accumulation of genomic mutations and rapid evolution. In the case of oncolytic virotherapy, understanding the mechanisms by which cancer cells develop resistance to infection and lysis is critical to the development of more effective viral-based platforms. Here, we identify APOBEC3 as an important factor involved in the restriction of vesicular stomatitis virus (VSV). We show that VSV infection of B16 murine melanoma cells upregulated APOBEC3 in an IFNβ-dependent manner, which was responsible for the evolution of virus-resistanT-cell populations and suggested that APOBEC3 expression promoted the acquisition of a virus-resistant phenotype. ShRNA knockdown of APOBEC3 in B16 cells diminished their capacity to develop resistance to VSV infection in vitro, and enhanced the therapeutic effect of VSV in vivo. Similarly, overexpression of human APOBEC3B promoted the acquisition of resistance to oncolytic VSV in murine melanoma and glioblastoma lines, as well as in a human melanoma cell line in vitro and in vivo. Finally, we demonstrate that progeny virus obtained after passage through APOBEC3B overexpressing cells contained more defective interfering particles, thereby indicating that APOBEC3B directly affected the fitness of VSV, an RNA virus that has not previously been identified to be restricted by APOBEC3B. This research identifies APOBEC3 enzymes as key players to target in order to improve the efficacy of oncolytic viruses as well as broader nucleic acid-based therapeutic platforms. Citation Format: Amanda L. Huff, Phonphimon Wongthida, Timothy Kottke, Jill Thompson, Christopher B. Driscoll, Matthew Schuelke, Kevin G. Shim, Reuben S. Harris, Amy Molan, Jose S. Pulido, Peter J. Selby, Kevin J. Harrington, Alan Melcher, Laura Evgin, Richard Vile. APOBEC3 confers resistance to oncolytic VSV therapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A133.

Background: Safe and effective portal placement is crucial for successful elbow arthroscopy. Various techniques for anterolateral portal placement in elbow arthroscopy have been described, yet radial nerve injuries are commonly reported. Purpose: To report on the technique and safety of anterolateral portal placement by the needle-and-knife method and its clinical applications. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review was completed of patients who underwent an arthroscopic procedure in the anterior compartment of the elbow and anterolateral portal placement. Patients were evaluated immediately postoperatively and at subsequent visits and were monitored for signs of radial nerve injury. Results: A total of 460 patients met the inclusion criteria, of which 309 (67%) underwent the needle-and-knife technique. There was 1 case (0.3%) of temporary radial nerve palsy. For the remaining 151 patients who underwent anterolateral portal placement by other techniques, there were 2 cases of temporary radial nerve palsy (1.3%). There were no cases of the needle-and-knife technique being unsuccessful or abandoned in lieu of a different technique. Use of the needle-and-knife technique increased over time with experience and practice. Initially, contraindications to this technique included impaired view of the lateral side of the anterior compartment of the elbow caused by severe intra-articular scar (65%), extensive synovitis (10%), or large osteophytes or loose bodies (10%). For the remaining patients (15%) who did not have portals placed via the needle-and-knife technique, alternate techniques were used for teaching purposes. Conclusion: The needle-and-knife technique is reproducible and easy to perform by a clinician instructed in its use and trained in elbow arthroscopy. Its main advantage is that it permits the surgeon to safely slide the knife along the lateral supracondylar ridge, releasing the scarred capsule and thereby increasing the available space in which to work. Enlarging the working space inside scarred and contracted elbows cannot be accomplished by distending the capsule.

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell‐released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV‐associated functional activities. Finally, a checklist is provided with summaries of key points.

OBJECTIVEMiddle fossa surgery is challenging, and reliable surgical landmarks are essential to perform accurate and safe surgery. Although many descriptions of the middle fossa components have been published, a clinically practical description of this very complex anatomical region is lacking. Small structure arrangements in this area are often not well visualized or accurately demarcated with neuronavigation systems. The objective is to describe a “roadmap” of key surgical reference points and landmarks during middle fossa surgery to help the surgeon predict where critical structures will be located.METHODSThe authors studied 40 dry skulls (80 sides) obtained from the anatomical board at their institution. Measurements of anatomical structures in the middle fossa were made with a digital caliper and a protractor, taking as reference the middle point of the external auditory canal (MEAC). The results were statistically analyzed.RESULTSThe petrous part of the temporal bone was found at a mean of 16 mm anterior and 24 mm posterior to the MEAC. In 87% and 99% of the sides, the foramen ovale and foramen spinosum, respectively, were encountered deep to the zygomatic root. The posterior aspect of the greater superficial petrosal nerve (GSPN) groove was a mean of 6 mm anterior and 25 mm medial to the MEAC, nearly parallel to the petrous ridge. The main axis of the IAC projected to the root of the zygoma in all cases. The internal auditory canal (IAC) porus was found 5.5 mm lateral and 4.5 mm deep to the lateral aspect of the trigeminal impression along the petrous ridge (mean measurement values). A projection from this point to the middle aspect of the root of the zygoma, being posterior to the GSPN groove, could estimate the orientation of the IAC.CONCLUSIONSIn middle fossa approaches, the external acoustic canal is a reliable reference before skin incision, whereas the zygomatic root becomes important after the skin incision. Deep structures can be related to these 2 anatomical structures. An easy method to predict the location of the IAC in surgery is described. Careful study of the preoperative imaging is essential to adapt this knowledge to the individual anatomy of the patient.

BackgroundPosterior lumbar vertebral endplate fracture occurs with avulsion of the ring apophysis from the posterior vertebral body. Although this has been described in adolescents and young adults, proper diagnosis is often delayed or missed entirely. Surgery may be curative.ObjectiveTo determine the common clinical features and treatment outcomes in youth and young adults with posterior lumbar vertebral endplate fractures.DesignRetrospective case series.SettingAcademic medical institution.PatientsPatients 10 to 25 years old from 2000 through 2012 with posterior vertebral endplate fracture diagnosis.Main Outcome MeasurementsDemographic characteristics, diagnostic studies, interventions, and change in symptoms postoperatively.ResultsA total of 16 patients had posterior vertebral endplate fractures (8 male patients; mean age, 15.2 years)—8.3% of 192 patients with inclusion age range undergoing spinal surgery for causes unrelated to trauma, scoliosis, or malignancy. The most common signs and symptoms were low back and radiating leg pain, positive straight leg raise, hamstring contracture, and abnormal gait. Cause was sports related for 12 patients (75%). Mean (range) time to diagnosis was 13.0 (3.0‐63.0) months. Diagnosis was most commonly made with lumbar magnetic resonance imaging (n = 6). Most fractures occurred at L5 (n = 8, 50%) and L4 (n = 5, 31.3%). Conservative measures were trialed before surgery. Nine patients had “complete relief” following surgery and seven “improved.”ConclusionsPosterior vertebral endplate fracture should be considered in differential diagnosis of a youth or young adult with back pain, radiating leg pain, and limited knee extension, regardless of symptom onset. For patients in whom conservative management fails, consultation with an experienced physician whose practice specializes in spine medicine is recommended.Level of EvidenceIV

Introduction Although numerous anatomical and operative atlases have been published, those that have focused on the skull base either have provided views that are quite difficult to achieve in the operating room to better depict surgical anatomy or are written at the level of an audience with considerable knowledge and experience. Methods Five sides of three formalin-fixed latex-injected specimens were dissected under microscopic magnification. A posterior petrosectomy approach was performed by three neurosurgical residents at different training levels with limited previous experience in anatomical dissection mentored by the senior authors (C. L. W. D. and M. J. L.) and a clinical skull base fellow with additional anatomical dissection experience (M. P. C.). Anatomical dissections were performed until the expected level of dissection quality was achieved to demonstrate each important step of the surgical approach that would be understandable to all trainees of all levels. Following dissection education, representative case applications were reviewed. Results The posterior petrosectomy (also known as presigmoid retrolabyrinthine approach) affords excellent access to cranial nerves III to XI and a diverse array of pathologies. Key steps include positioning and skin incision, scalp and muscle flaps, burr holes, craniotomy flap elevation, superficial mastoidectomy, otic capsule exposure and presigmoid dura decompression, primary presigmoid durotomy, inferior temporal durotomy, superior petrosal sinus ligation, tentorium sectioning, and final exposure. Conclusion The posterior petrosectomy is a challenging approach; thorough operative-style laboratory dissection is essential to provide trainees with a suitable guide. We describe a comprehensive approach to learning this technique, intended to be understandable and usable by a resident audience.

Aims The aim of this study was to evaluate two hypotheses. First, that disruption of posterior bundle of the medial collateral ligament (PMCL) has to occur for the elbow to subluxate in cases of posteromedial rotatory instability (PMRI) and second, that ulnohumeral contact pressures increase after disruption of the PMCL. Materials and Methods Six human cadaveric elbows were prepared on a custom-designed apparatus which allowed muscle loading and passive elbow motion under gravitational varus. Joint contact pressures were measured sequentially in the intact elbow (INTACT), followed by an anteromedial subtype two coronoid fracture (COR), a lateral collateral ligament (LCL) tear (COR + LCL), and a PMCL tear (COR + LCL + PMCL). Results There was no subluxation or joint incongruity in the INTACT, COR, and COR + LCL specimens. All specimens in the COR + LCL + PMCL group subluxated under gravity-varus loads. The mean articular contact pressure of the COR + LCL group was significantly higher than those in the INTACT and the COR groups. The mean articular contact pressure of the COR + LCL + PMCL group was significantly higher than that of the INTACT group, but not higher than that of the COR + LCL group. Conclusion In the presence of an anteromedial fracture and disruption of the LCL, the posterior bundle of the MCL has to be disrupted for gross subluxation of the elbow to occur. However, elevated joint contact pressures are seen after an anteromedial fracture and LCL disruption even in the absence of such subluxation. Cite this article: Bone Joint J 2018;100-B:1060–5.