Citations

Introduction Primary spinal osteosarcomas are rare and aggressive neoplasms with poor outcomes. Enneking appropriate, en bloc resection is recommended for appendicular osteosarcomas. Obtaining even marginal margins is technically demanding in the spine, resulting in significant morbidity and possible functional sacrifice. The aim of this study was to identify prognostic variables on local recurrence and mortality, in surgically treated patients diagnosed with a primary osteosarcoma of the spine. Methods A multicenter ambispective database of surgically treated patients with primary spine osteosarcomas was developed by the AOSpine knowledge forum tumor. Patient demographic, diagnosis, treatment, perioperative morbidity, local recurrence, and cross-sectional survival data were collected. Tumors were classified according to Enneking principles and analyzed in the following two cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI). EA was defined by the final pathology margin matching the Enneking recommended surgical margin and EI by not matching. Prognostic variables including age, previous spine tumor operation, biopsy type, spine level, tumor size, and chemotherapy timing were analyzed in reference to local recurrence and survival. Results Between 1987 and 2012, 57 patients (31 females and 26 males) underwent surgical treatment for a primary spinal osteosarcoma at a mean age of 36 ± 16 years. Patients were followed for a mean period of 3.4 ± 3.5 years (range, 0.5 days–14.3 years). Median survival for the entire cohort was 6.7 years postoperative. Overall, 24 (42%) patients died and 17 (30%) patients suffered a local recurrence, 10 (59%) of which died. Overall, 28 (52%) patients underwent EA resection while 26 (48%) patients were treated by EI resection. Median survival for patients with EA was 6.8 years postoperative, whereas median survival for EI patients was 3.7 years postoperatively ( p = 0.062). EI patients were at a higher risk of local recurrence than EA patients ( p = 0.002). Patient age, previous spine tumor operation, tumor size, spine level, and chemotherapy timing did not significantly influence recurrence and survival. Conclusion Osteosarcoma of the spine presents a significant challenge and most patients die from their disease in spite of aggressive surgery. There is a significant decrease in recurrence with en bloc resection when compared with intralesional resection.

Abstract Metastatic epidural spinal cord compression (MESCC) is an oncologic emergency and if left untreated, permanent paralysis will ensue. The treatment of MESCC is governed by disease, patient, and treatment factors. Patient's preferences and goals of care are to be weighed into the treatment plan. Ideally, a patient with MESCC is evaluated by an interdisciplinary team promptly to determine the urgency of the clinical scenario. Treatment recommendations must take into consideration the risk-benefit profiles of surgical intervention and radiotherapy for the particular individual's circumstance, including neurologic status, performance status, extent of epidural disease, stability of the spine, extra-spinal disease status, and life expectancy. In patients with high spinal instability neoplastic score (SINS) or retropulsion of bone fragments in the spinal canal, surgical intervention should be strongly considered. The rate of development of motor deficits from spinal cord compression may be a prognostic factor for ultimate functional outcome, and should be taken into account when a treatment recommendation is made. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Context Self‐regulated learning ( SRL ) requires an active learner who has developed a set of processes for managing the achievement of learning goals. Simulation‐based training is one context in which trainees can safely practise learning how to learn. Objectives The purpose of the present study was to evaluate, in the simulation‐based training context, the effectiveness of interventions designed to support trainees in SRL activities. We used the social‐cognitive model of SRL to guide a systematic review and meta‐analysis exploring the links between instructor supervision, supports or scaffolds for SRL , and educational outcomes. Methods We searched databases including MEDLINE and Scopus, and previous reviews, for material published until December 2011. Studies comparing simulation‐based SRL interventions with another intervention for teaching health professionals were included. Reviewers worked independently and in duplicate to extract information on learners, study quality and educational outcomes. We used random‐effects meta‐analysis to compare the effects of supervision (instructor present or absent) and SRL educational supports (e.g. goal‐setting study guides present or absent). Results From 11 064 articles, we included 32 studies enrolling 2482 trainees. Only eight of the 32 studies included educational supports for SRL . Compared with instructor‐supervised interventions, unsupervised interventions were associated with poorer immediate post‐test outcomes (pooled effect size: −0.34, p = 0.09; n = 19 studies) and negligible effects on delayed (i.e. > 1 week) retention tests (pooled effect size: 0.11, p = 0.63; n = 8 studies). Interventions including SRL supports were associated with small benefits compared with interventions without supports on both immediate post‐tests (pooled effect size: 0.23, p = 0.22; n = 5 studies) and delayed retention tests (pooled effect size: 0.44, p = 0.067; n = 3 studies). Conclusions Few studies in the simulation literature have designed SRL training to explicitly support trainees’ capacity to self‐regulate their learning. We recommend that educators and researchers shift from thinking about SRL as learning alone to thinking of SRL as comprising a shared responsibility between the trainee and the instructional designer (i.e. learning using designed supports that help prepare individuals for future learning).

Context The relative advantages and disadvantages of checklists and global rating scales ( GRS s) have long been debated. To compare the merits of these scale types, we conducted a systematic review of the validity evidence for checklists and GRS s in the context of simulation‐based assessment of health professionals. Methods We conducted a systematic review of multiple databases including MEDLINE , EMBASE and S copus to F ebruary 2013. We selected studies that used both a GRS and checklist in the simulation‐based assessment of health professionals. Reviewers working in duplicate evaluated five domains of validity evidence, including correlation between scales and reliability. We collected information about raters, instrument characteristics, assessment context, and task. We pooled reliability and correlation coefficients using random‐effects meta‐analysis. Results We found 45 studies that used a checklist and GRS in simulation‐based assessment. All studies included physicians or physicians in training; one study also included nurse anaesthetists. Topics of assessment included open and laparoscopic surgery ( n = 22), endoscopy ( n = 8), resuscitation ( n = 7) and anaesthesiology ( n = 4). The pooled GRS –checklist correlation was 0.76 (95% confidence interval [ CI ] 0.69–0.81, n = 16 studies). Inter‐rater reliability was similar between scales ( GRS 0.78, 95% CI 0.71–0.83, n = 23; checklist 0.81, 95% CI 0.75–0.85, n = 21), whereas GRS inter‐item reliabilities (0.92, 95% CI 0.84–0.95, n = 6) and inter‐station reliabilities (0.80, 95% CI 0.73–0.85, n = 10) were higher than those for checklists (0.66, 95% CI 0–0.84, n = 4 and 0.69, 95% CI 0.56–0.77, n = 10, respectively). Content evidence for GRS s usually referenced previously reported instruments ( n = 33), whereas content evidence for checklists usually described expert consensus ( n = 26). Checklists and GRS s usually had similar evidence for relations to other variables. Conclusions Checklist inter‐rater reliability and trainee discrimination were more favourable than suggested in earlier work, but each task requires a separate checklist. Compared with the checklist, the GRS has higher average inter‐item and inter‐station reliability, can be used across multiple tasks, and may better capture nuanced elements of expertise.

We have previously demonstrated that estrogen (E2) downregulates phosphate transporter NaPi-IIa and causes phosphaturia and hypophosphatemia in ovariectomized rats. In the present study, we examined whether E2directly targets NaPi-IIa in the proximal tubule (PT) and studied the respective roles of estrogen receptor isoforms (ERα and ERβ) in the downregulation of NaPi-IIa using both in vivo and an in vitro expression systems. We found that estrogen specifically downregulates NaPi-IIa but not NaPi-IIc or Pit2 in the kidney cortex. Proximal tubules incubated in a “shake” suspension with E2for 24 h exhibited a dose-dependent decrease in NaPi-IIa protein abundance. Results from OVX rats treated with specific agonists for either ERα [4,4′,4″;-(4-propyl-[1 H]-pyrazole-1,3,5-triyl) trisphenol, PPT] or ERβ [4,4′,4″-(4-propyl-[1 H]-pyrazole-1,3,5-triyl) trisphenol, DPN] or both (PPT + DPN), indicated that only the latter caused a sharp downregulation of NaPi-IIa, along with significant phosphaturia and hypophosphatemia. Lastly, heterologous expression studies demonstrated that estrogen downregulated NaPi-IIa only in U20S cells expressing both ERα and ERβ, but not in cells expressing either receptor alone. In conclusion, these studies demonstrate that rat PT cells express both ERα and ERβ and that E2induces phosphaturia by directly and specifically targeting NaPi-IIa in the PT cells. This effect is mediated via a mechanism involving coactivation of both ERα and ERβ, which likely form a functional heterodimer complex in the rat kidney proximal tubule.

We used whole‐exome sequencing to identify variants other than APOE associated with the rate of hippocampal atrophy in amnestic mild cognitive impairment. An in‐silico predicted missense variant in REST (rs3796529) was found exclusively in subjects with slow hippocampal volume loss and validated using unbiased whole‐brain analysis and meta‐analysis across 5 independent cohorts. REST is a master regulator of neurogenesis and neuronal differentiation that has not been previously implicated in Alzheimer's disease. These findings nominate REST and its functional pathways as protective and illustrate the potential of combining next‐generation sequencing with neuroimaging to discover novel disease mechanisms and potential therapeutic targets. Ann Neurol 2015;77:547–552

AbstractObjectivesCentral line–associated bloodstream infection (CLABSI) is a preventable nosocomial infection. Simulation‐based training in sterile technique during central venous catheter (CVC) placement for emergency medicine (EM) residents, and its effect on changing the medical intensive care unit (MICU) practice of routine replacement of CVCs placed under sterile technique in the emergency department (ED), has not been evaluated.MethodsEmergency medicine residents received simulation‐based sterile technique training during CVC placement between May 2008 and September 2010. Between June 2008 and January 2011, the authors reviewed records of patients who had CVCs placed in the ED under sterile technique by EM residents and were admitted to the MICU (group 1) and CVCs placed in the MICU under sterile technique by internal medicine (IM) residents (group 2). IM residents completed similar simulation‐based training before May 2008. Changes in EM residents' sterile technique performance scores were compared, as well as CLABSI rates in both groups. EM residents' CVC procedural skills were not assessed.ResultsSeventy‐six EM residents completed simulation‐based training with significant improvement in performance (median scores 13 out of 24 before training, 24 out of 24 after training; p < 0.001). CLABSI rates per 1,000 catheter‐days were 1.02 in group 1 and 1.02 in group 2 (p = 0.99). Both groups had similar demographics, acuity, and mortality (p > 0.5).ConclusionsRoutine replacement of CVCs placed in the ED under sterile technique after simulation‐based training would appear to be unnecessary. These findings demonstrate patient‐centered outcomes that are comparable for CVCs in ED‐admitted MICU patients, regardless of whether the CVC was placed in the ED or MICU.

Background. Radiotherapy has been utilized for metastatic and recurrent osteosarcoma and Ewing sarcoma (ES), in order to provide palliation and possibly prolong overall or progression-free survival. Stereotactic body radiotherapy (SBRT) is convenient for patients and offers the possibility of increased efficacy. We report our early institutional experience using SBRT for recurrent and metastatic osteosarcoma and Ewing sarcoma.Methods. We reviewed all cases of osteosarcoma or ES treated with SBRT between 2008 and 2012.Results. We identified 14 patients with a total of 27 lesions from osteosarcoma(n=19)or ES(n=8). The median total curative/definitive SBRT dose delivered was 40 Gy in 5 fractions (range, 30–60 Gy in 3–10 fractions). The median total palliative SBRT dose delivered was 40 Gy in 5 fractions (range, 16–50 Gy in 1–10 fractions). Two grade 2 and 1 grade 3 late toxicities occurred, consisting of myonecrosis, avascular necrosis with pathologic fracture, and sacral plexopathy. Toxicity was seen in the settings of concurrent chemotherapy and reirradiation.Conclusions. This descriptive report suggests that SBRT may be a feasible local treatment option for patients with osteosarcoma and ES. However, significant toxicity can result, and thus systematic study is warranted to clarify efficacy and characterize long-term toxicity.

The resection of large pelvic tumors is challenging due to their infiltrative nature into multiple structures and organ systems. In this report, we describe the use of multiple vascularized and nonvascularized spare parts to reconstruct a pelvic defect in a patient with a uniquely large pelvic sarcoma invading the spinal canal. A 39‐year‐old Caucasian female who presented with a large retroperitoneal sarcoma where the tumor encased the left ureter, kidney, colon, and external iliac vessels and invaded the L3‐S1 vertebral bodies. An extensive hemipelvectomy and reconstruction was performed over two days. A free thigh and leg fillet flap together with ipsilateral fibula flap, based on the superficial femoral artery and venae comitantes, was used for spinal reinforcement as well as abdominal and pelvic wall reconstruction. The postoperative course was uneventful without complications, no flap compromise or wound healing problems. After a follow‐up period of 4 months, the patient had no complications and returned to activities of daily living with mild limitations. The success of this flap procedure shows the practicality and usefulness of using the full spectrum of tissue transfer for the purposes of a large pelvic reconstruction. © 2014 Wiley Periodicals, Inc. Microsurgery 35:320–323, 2015.