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PURPOSE: Semiannually, U.S. pediatrics residency programs report resident milestone levels to the Accreditation Council for Graduate Medical Education (ACGME). The Pediatrics Milestones Assessment Collaborative (PMAC, consisting of the National Board of Medical Examiners, American Board of Pediatrics, and Association of Pediatric Program Directors) developed workplace-based assessments of 2 inferences: readiness to serve as an intern with a supervisor present (D1) and readiness to care for patients with a supervisor nearby in the pediatric inpatient setting (D2). The authors compared learner and program variance in PMAC scores with ACGME milestones. METHOD: The authors examined sources of variance in PMAC scores and milestones between November 2015 and May 2017 of 181 interns at 8 U.S. pediatrics residency programs using random effects models with program, competency, learner, and program × competency components. RESULTS: Program-related milestone variance was substantial (54% D1, 68% D2), both in comparison to learner milestone variance (22% D1, 14% D2) and program variance in the PMAC scores (12% D1, 10% D2). In contrast, learner variance represented 44% (D1) or 26% (D2) of variance in PMAC scores. Within programs, PMAC scores were positively correlated with milestones for all but one competency. CONCLUSIONS: PMAC assessments provided scores with little program-specific variance and were more sensitive to differences in learners within programs compared with milestones. Milestones reflected greater differences by program than by learner. This may represent program-based differences in intern performance or in use of milestones as a reporting scale. Comparing individual learner milestones without adjusting for programs is problematic.

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Mycobacterium fortuitum is a rare, opportunistic pathogen most frequently contracted through contact with a contaminated source. An immunocompetent 26-year-old female patient presented to our institution with an infected lumboperitoneal (LP) shunt presenting as continued nonhealing wounds. After multiple debridements, shunt revisions, and wound closure failures, infectious disease specialists were consulted. The wound cultures returned positive for M. fortuitum and the shunt was removed. Cerebrospinal fluid studies revealed significant pleocytosis with normal opening pressure, and the patient was diagnosed as having secondary meningitis. After shunt removal, the patient was treated with intravenous and oral antibiotics, resulting in infection resolution. Five months later, a new LP shunt was placed without infection recurrence. Although M. fortuitum was previously reported in neurosurgical patients with ventriculoperitoneal shunts, which are summarized here, to date this is the first case in the literature of M. fortuitum meningitis from an LP shunt. This case demonstrates the importance of clinicians considering uncommon and slow-growing pathogens, as well as consulting infectious disease specialists for patients with persistent, unexplained infections.

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BACKGROUND: This is a retrospective analysis of prospectively collected data. Our objective was to determine the incidence and assess the risk factors associated with surgical site wound complications in long segment (7+ vertebrae) instrumented thoracolumbar fusions. Surgical site complications lead to patient morbidity, increased financial burden, and further medical intervention. Risk factors for wound complications in spinal surgery include patient factors such as obesity and diabetes, and surgical factors such as operative time and procedure type. Fusion with instrumentation is one of the strongest associated risk factors in the literature. METHODS: A comprehensive search of the National Surgical Quality Improvement Program (NSQIP) from 2005 to 2014 was performed, selecting cases based on Current Procedural Terminology (CPT) codes. Cases were then stratified based on the presence of one of the following wound complications: superficial surgical site infection, deep surgical site infection, organ space infection, and wound dehiscence. Univariate and bivariate analyses were performed to determine risk factors. RESULTS: A total of 2,548 cases were identified, and the most common diagnoses were scoliosis (29%), spondylosis (17%) and spinal stenosis (14%). Overall, 4.24% of cases had at least one wound complication. Identified risk factors include obesity, preoperative transfusion, preoperative wound infection, and operative time. Associated outcomes include stroke with neurological deficit, perioperative transfusion, deep vein thrombosis (DVT), sepsis, septic shock, readmission, reoperation, and longer length of hospital stay. Many of these variables are independently associated with a wound complication. CONCLUSIONS: Our analysis of the NSQIP demonstrated risk factors and complications associated with wound infections in the setting of long segment fusions (7+ levels). These findings may aid surgeons in determining a patient's risk of developing a wound complication, with the goal of lessening the associated morbidity and economic burden.

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OBJECTIVE: Approximately 12% of intracerebral hemorrhages (ICHs) occur in the thalamus. Understanding the anatomic regions involved with thalamic hemorrhages is potentially useful, offering the physician a more accurate prognosis for patient outcomes. This study was performed to determine if thalamic hemorrhage location observed on a computed tomography (CT) scan was predictive of neurologic outcomes. METHODS: A sample of 168 thalamic hemorrhage patients admitted to a tertiary care center were analyzed. Axial CT scans of thalamic hemorrhages were classified into 1 of 6 possible categories based on thalamic nuclei anatomy: anterior, posterior, medial, lateral, central, or global. For each classification, patient clinical characteristics were collected to identify variables indicative of clinical outcome. Outcome measures used in this study included mortality, hospital length of stay, readmission within 30 days, ICH score, Glasgow Coma Scale score, neurologic deterioration (calculated as a change in modified Rankin scale score from admission to discharge), and discharge disposition. RESULTS: On multivariable analysis, patients with posterior and lateral thalamic hemorrhages demonstrated a decreased likelihood of mortality; patients with posterior hemorrhages were less likely to have neurologic deterioration relative to global thalamic hemorrhages when controlling for hemorrhage volume and ventriculomegaly. Ventriculomegaly and hemorrhage volume were also predictive of both mortality and neurologic deterioration. CONCLUSIONS: In thalamic hemorrhages, patient prognosis may be influenced by hemorrhage location, with posterior and lateral hemorrhages demonstrating better clinical outcome versus hemorrhages in other locations. This is potentially valuable because hemorrhage location affords the treating physician a readily available prognostic factor when assessing intracranial hemorrhages.

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BACKGROUND: There is a dearth of advocacy training in graduate medical education in the United States. To address this void, the Legislative Education and Advocacy Development (LEAD) course was developed as an interprofessional experience, partnering a cohort of pediatrics residents, fourth-year medical students, and public health students to be trained in evidence-informed health policy making. OBJECTIVE: The objective of our study was to evaluate the usefulness and acceptability of a service-based legislative advocacy course. METHODS: We conducted a pilot study using a single-arm pre-post study design with 10 participants in the LEAD course. The course's didactic portion taught learners how to define policy problems, research the background of the situation, brainstorm solutions, determine evaluation criteria, develop communication strategies, and formulate policy recommendations for state legislators. Learners worked in teams to create and present policy briefs addressing issues submitted by participating Illinois State legislators. We compared knowledge and attitudes of learners from pre- and postcourse surveys. We obtained qualitative feedback from legislators and pediatric residency directors. RESULTS: Self-reported understanding of the health care system increased (mean score from 4 to 3.3, P=.01), with answers scored from 1=highly agree to 5=completely disagree. Mean knowledge-based scores improved (6.8/15 to 12.0/15 correct). Pediatric residency program directors and state legislators provided positive feedback about the LEAD course. CONCLUSIONS: Promising results were demonstrated for the LEAD approach to incorporate advocacy training into graduate medical education.

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Gibbus deformities are characterized by anterior collapse of one or more vertebral bodies resulting in kyphosis. These deformities usually arise from spinal infections, and are traditionally associated with tuberculosis; other pathogens are rarely reported in the literature. In this case report, the authors describe a patient with a sharp, angulated Gibbus deformity presenting with back pain and myelopathy. The patient was placed on antibiotics, underwent T11-T12 corpectomy, placement of an expandable cage, and T8-L3 fusion with improvement of symptoms. Microbiology returned positive for non-tuberculosis osteomyelitis, and the postoperative course was uneventful. This report further reviews the presentation, pathology, development, and neurosurgical treatment of Gibbus deformities. Although they have become rare as rates of tuberculosis have declined, Gibbus deformities remain an important surgical entity that should be recognized by the spine surgeon.

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A sensitive reporter assay to measure human immunodeficiency virus type 1 (HIV-1) protease (PR) activity is described in this manuscript. This assay measures PR activity as a function of the resonance energy transfer (RET) between a donor molecule [humanized sea pansy Renilla reniformis luciferase (hRLuc)] and an energy acceptor molecule, humanized green fluorescent protein (hGFP2) when expressed in mammalian cells. This is a naturally occurring phenomenon and is an emerging and powerful technology that has significant advantages over alternative in vitro PR assays. The HIV-1 Gag-p2/Gag-p7 (p2/p7) PR site was inserted between hGFP2 and hRLuc. The newly created vector, hRLuc-p2/p7-hGFP2 was co-expressed with an HIV-1 codon-optimized PR+ or PR- Gag/Pol expressor. Expression of the hRLuc-p2/p7-hGFP2 alone or with the PR- Gag-Pol expressor generated a BRET2 indicating that the PR cleavage site was not cleaved, whereas the inclusion of the PR+ Gag-Pol produced a significant reduction in the BRET2. The inclusion of PR inhibitors Saquinavir or Amprenavir, or the expression of a p2/p7 PR substrate mutant also blocked the cleavage to result in a stable BRET2 signal. Because the HIV-1 auxiliary protein Vif has been shown to modulate the HIV-1p2/p7 cleavage, this assay was then validated in studies in which Vif was expressed. When Vif was overexpressed along with hRLuc-p2/p7-hGFP2 and PR+ Gag-Pol, the decrease in BRET2 was abrogated in a dose-dependent manner, demonstrating that supraphysiologic levels of Vif block p2/p7 cleavage. An accumulation of a Gag processing intermediate was observed, indicating that p2/p7 cleavage was negatively affected. Overexpression of an RNA-binding-defective Staufen protein or a related dsRNA-binding protein TRBP had no effect on PR cleavage activity as shown by Western and BRET2 analyses. The p2/p7 processing data were confirmed by Western blot analyses. BRET is non-invasive and occurs within live cells, is measured in real time, and is not restricted to cellular compartments making it an especially attractive technology to identify small bioactive inhibitory molecules. This PR BRET2 biosensor assay can be adapted for high throughput screening of new HIV-1 PR inhibitors. It can be employed to screen for antiviral compounds that also target the proteases of other viruses.

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During early assembly of human immunodeficiency virus type 1 (HIV-1), an assembly complex is formed, the components of which include genomic RNA, Gag, GagPol, tRNA(Lys), and lysyl tRNA synthetase (LysRS). Directly increasing or decreasing cellular expression of LysRS results in corresponding changes in viral infectivity and in the viral concentrations of LysRS, tRNA(Lys), and, surprisingly, reverse transcriptase (RT). Since altering the cellular expression of LysRS does not lead to a change in the incorporation of the RT precursor protein, GagPol, in protease-negative HIV-1, we propose that the altered viral content of RT resulting from alterations in cellular LysRS concentration results from the ability of LysRS to inhibit premature activation of Gag-Pol viral protease within the complex. Supporting this hypothesis, we find that increases and decreases in cellular LysRS expression are accompanied by 5-8-fold increases and 5-fold decreases, respectively, in the cytoplasmic proteolysis of Gag and GagPol to mature viral proteins. Using a novel bioluminescence resonance energy transfer assay to directly measure HIV-1 protease activity in vivo also indicates that the overexpression of LysRS in the cell reduces viral protease activity.

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