Citations

Study Design: Multicenter retrospective case series and review of the literature. Objective: To determine the rate of esophageal perforations following anterior cervical spine surgery. Methods: As part of an AOSpine series on rare complications, a retrospective cohort study was conducted among 21 high-volume surgical centers to identify esophageal perforations following anterior cervical spine surgery. Staff at each center abstracted data from patients’ charts and created case report forms for each event identified. Case report forms were then sent to the AOSpine North America Clinical Research Network Methodological Core for data processing and analysis. Results: The records of 9591 patients who underwent anterior cervical spine surgery were reviewed. Two (0.02%) were found to have esophageal perforations following anterior cervical spine surgery. Both cases were detected and treated in the acute postoperative period. One patient was successfully treated with primary repair and debridement. One patient underwent multiple debridement attempts and expired. Conclusions: Esophageal perforation following anterior cervical spine surgery is a relatively rare occurrence. Prompt recognition and treatment of these injuries is critical to minimizing morbidity and mortality.

Background: Osteochondritis dissecans (OCD) is a disorder of subchondral bone that causes adverse effects on the overlying cartilage and commonly affects the knee. The incidence of OCD and its long-term effect on the knee joint are controversial. Hypothesis/Purpose: The purpose of this study was to (1) evaluate the rate of osteoarthritis and knee arthroplasty in a population-based cohort of patients with OCD lesions treated operatively and (2) evaluate factors that may predispose patients to knee osteoarthritis and arthroplasty. The investigators hypothesized that OCD lesions diagnosed after skeletal maturity and treatment with fragment excision would be predictive of a diagnosis of osteoarthritis. Study Design: Cohort study; Level of evidence, 3. Methods: The investigators identified 221 patients (mean ± SD age, 26.1 ± 13.6 years) with OCD lesions treated operatively between 1976 and 2010 and followed for 16.3 ± 11.4 years (mean ± SD) from diagnosis. Information related to the diagnosis, laterality of lesion, details of treatment, and progression to osteoarthritis was obtained from the medical record. Surgical treatment was classified as fragment excision, fragment preservation (lesion drilling and/or fragment fixation), or chondral defect grafting (osteochondral allograft or autograft). Factors predictive of osteoarthritis and arthroplasty were examined. Results: There were 134 patients in the fragment excision group, 78 patients in the fragment preservation group, and 9 patients in the chondral defect grafting group. In the fragment excision group, the cumulative incidence of osteoarthritis was 12.0% at 5 years, 17.0% at 10 years, 26.0% at 15 years, 39.0% at 20 years, and 70% at 30 years. The cumulative incidence of arthroplasty was 2.0% at 5 years, 4.0% at 10 years, 4.0% at 15 years, 10.0% at 20 years, and 32.0% at 30 years. In the fragment preservation group, the cumulative incidence of osteoarthritis was 3.0% at 5 years, 7.0% at 10 years, 16.0% at 15 years, 25.0% at 20 years, and 51% at 30 years. The cumulative incidence of arthroplasty was 0.0% at 5 years, 0.0% at 10 years, 3.0% at 15 years, 6.0% at 20 years, and 11.0% at 30 years. No patients in the chondral defect grafting group developed osteoarthritis or underwent arthroplasty. Body mass index (BMI) greater than 25 kg/m 2 (hazard ratio [HR] 3.3; 95% CI, 1.6-7.0), older age at diagnosis (HR 4.9; 95% CI, 1.8-17.3), and fragment excision (HR 2.3; 95% CI, 1.2-4.6) were predictive of osteoarthritis. Conclusion: OCD patients treated with fragment excision have a high rate of osteoarthritis and knee arthroplasty at long-term follow-up. In contrast, patients treated with fragment preservation or chondral defect grafting have lower rates of osteoarthritis and arthroplasty. BMI greater than 25 kg/m 2 , older age at diagnosis, and fragment excision were predictive of osteoarthritis.

Abstract Background The American Board of Anesthesiology administers written and oral examinations for its primary certification. This retrospective cohort study tested the hypothesis that the risk of a disciplinary action against a physician’s medical license is lower in those who pass both examinations than those who pass only the written examination. Methods Physicians who entered anesthesiology training from 1971 to 2011 were followed up to 2014. License actions were ascertained via the Disciplinary Action Notification Service of the Federation of State Medical Boards. Results The incidence rate of license actions was relatively stable over the study period, with approximately 2 to 3 new cases per 1,000 person-years. In multivariable models, the risk of license actions was higher in men (hazard ratio = 1.88 [95% CI, 1.66 to 2.13]) and lower in international medical graduates (hazard ratio = 0.73 [95% CI, 0.66 to 0.81]). Compared with those passing both examinations on the first attempt, those passing neither examination (hazard ratio = 3.60 [95% CI, 3.14 to 4.13]) and those passing only the written examination (hazard ratio = 3.51 [95% CI, 2.87 to 4.29]) had an increased risk of receiving an action from a state medical board. The risk was no different between the latter two groups ( P = 0.81), showing that passing the oral but not the written primary certification examination is associated with a decreased risk of subsequent license actions. For those with residency performance information available, having at least one unsatisfactory training record independently increased the risk of license actions. Conclusions These findings support the concept that an oral examination assesses domains important to physician performance that are not fully captured in a written examination.

Background: The rate of patellofemoral arthritis after lateral patellar dislocation is unknown. Purpose/Hypothesis: The purpose of this study was to compare the risk of patellofemoral arthritis and knee arthroplasty between patients who experienced a lateral patellar dislocation and matched individuals without a patellar dislocation. Additionally, factors predictive of arthritis after patellar dislocation were examined. The hypothesis was that the rate of arthritis is likely higher among patients who experience a patellar dislocation compared with those who do not. Study Design: Cohort study; Level of evidence, 3. Methods: In this study, 609 patients who had a first-time lateral patellar dislocation between 1990 and 2010 were compared with an age- and sex-matched cohort of patients who did not have a patellar dislocation. Medical records were reviewed to collect information related to the initial injury, recurrent dislocation, treatment, and progression to clinically significant patellofemoral arthritis (defined as symptoms with degenerative changes on patellar sunrise radiographs). Factors associated with arthritis (age, sex, recurrence, osteochondral injury, trochlear dysplasia) were examined. Results: At a mean follow-up of 12.3 ± 6.5 years from initial dislocation, 58 patients (9.5%) in the dislocation cohort were diagnosed with patellofemoral arthritis, corresponding to a cumulative incidence of arthritis of 1.2% at 5 years, 2.7% at 10 years, 8.1% at 15 years, 14.8% at 20 years, and 48.9% at 25 years. In the control cohort, 8 patients (1.3%) were diagnosed with arthritis, corresponding to a cumulative incidence of arthritis of 0% at 5 years, 0% at 10 years, 1.3% at 15 years, 2.9% at 20 years, and 8.3% at 25 years. Therefore, patients who experienced a lateral patellar dislocation had a significantly higher risk of developing arthritis (hazard ratio [HR], 7.8; 95% CI, 3.9-17.6; P < .001) than individuals without a patellar dislocation. However, the risk of knee arthroplasty was similar between groups (HR, 2.8; 95% CI, 0.6-19.7; P = .2). Recurrent patellar dislocations (HR, 4.5; 95% CI, 1.6-12.6), osteochondral injury (HR, 11.3; 95% CI, 5.0-26.6), and trochlear dysplasia (HR, 3.6; 95% CI, 1.3-10.0) were associated with arthritis after patellar dislocation. Conclusion: Patellar dislocation is a significant risk factor for patellofemoral arthritis, as nearly half of patients have symptoms and radiographic changes consistent with arthritis at 25 years after lateral patellar dislocation. Osteochondral injury, recurrent patellar instability, and trochlear dysplasia are associated with the development of arthritis.

SummaryThe Glivec International Patient Assistance Programme makes Glivec (Imatinib mesylate) available to Philadelphia chromosome/BCR‐ABL1 positive patients with chronic myeloid leukaemia (CML) in Lower and Middle Income Countries (LMIC). We have established a large cohort of 211 CML patients who are eligible for Imatinib, in Kathmandu, Nepal. Thirty‐one patients were lost to follow‐up. We report on 180 CML patients with a median age of 38 years (range 9–81). Of these 180 patients, 162 underwent cytogenetic testing and 110 were investigated by reverse transcription polymerase chain reaction. One hundred and thirty‐nine of the 180 patients (77·2%) had at least one optimal response. Taken together, our cohort has a 95% overall survival rate and 78% of the patients were still taking Glivec at a median time of 48·8 months (range 3–140 months). The number of patients who actually failed therapy, as defined by the LeukaemiaNet 2013 criteria, was 39 (21·7%). While our cohort has some differences with those in North America or Europe, we have shown Glivec is effective in inducing an optimal response in our patients in Nepal and that it is possible to deliver a clinical service for CML patients using tyrosine kinase inhibitors in resource‐poor settings.

609 Background: Targeting MEK is of interest in the development of novel agents for treatment of many malignancies. However, better strategies are needed to overcome acquired resistance to MEK inhibitors. Preclinical studies have shown Wnt pathway overexpression in KRAS mutant cell lines resistant to the MEK inhibitor, Selumetinib. The combination of selumetinib and cyclosporin A (CsA), a non-canonical WnT pathway modulator, demonstrated antitumor activity in patient-derived xenograft (PDX) models. We are conducting an NCI CTEP-approved Phase I/IB trial (NCI # 9571/COMIRB # 13-2628) of selumetinib and CsA combination. Biomarkers of response to therapy are being co-developed. We hypothesize that this combination will be safe and potentially effective in patients with mCRC and that upregulation of FZD2 may predict for sensitivity. Methods: Phase I trial with initial dose escalation investigating the combination of selumetinib and CsA in patients with advanced solid tumors (n = 18) followed by an expansion cohort in patients with irinotecan and oxaliplatin-refractory mCRC (n = 20). The expansion cohort utilizes a selumetinib “run-in” to evaluate efficacy in RAS-WT and RAS-MT mCRC to identify those patients most likely to respond to the combination. Results: 18 patients were enrolled in the dose escalation phase and 10 patients have been enrolled in the dose expansion phase as of September 2016. Grade 1 or 2 nausea and rash were reported as the most common AEs. Most commonly reported Grade 3 or 4 toxicities were hypertension, elevated liver enzymes and rash. Three DLTs were reported with Grade 3 hypertension noted at dose level 1 and 2 and grade 3 rash reported at dose level 2. The maximum tolerated dose was defined as Selumetinib 75 mg BID and CsA 2 mg/kg BID on a 28-day cycle. Two partial responses and sixteen stable disease responses have been observed. Six patients have exhibited progressive disease. Conclusions: Selumetinib in combination with cyclosporin A appears to be well-tolerated with evidence of activity in solid tumors. Expansion cohort will complete enrollment this month. Clinical trial information: NCT02188264.

ABSTRACTHuman cerebral malaria (HCM) is a serious complication ofPlasmodium falciparuminfection. The most severe outcomes for patients include coma, permanent neurological deficits, and death. Recently, a large-scale magnetic resonance imaging (MRI) study in humans identified brain swelling as the most prominent predictor of fatal HCM. Therefore, in this study, we sought to define the mechanism controlling brain edema through the use of the murine experimental cerebral malaria (ECM) model. Specifically, we investigated the ability of CD8 T cells to initiate brain edema during ECM. We determined that areas of blood-brain barrier (BBB) permeability colocalized with a reduction of the cerebral endothelial cell tight-junction proteins claudin-5 and occludin. Furthermore, through small-animal MRI, we analyzed edema and vascular leakage. Using gadolinium-enhanced T1-weighted MRI, we determined that vascular permeability is not homogeneous but rather confined to specific regions of the brain. Our findings show that BBB permeability was localized within the brainstem, olfactory bulb, and lateral ventricle. Concurrently with the initiation of vascular permeability, T2-weighted MRI revealed edema and brain swelling. Importantly, ablation of the cytolytic effector molecule perforin fully protected against vascular permeability and edema. Furthermore, perforin production specifically by CD8 T cells was required to cause fatal edema during ECM. We propose that CD8 T cells initiate BBB breakdown through perforin-mediated disruption of tight junctions. In turn, leakage from the vasculature into the parenchyma causes brain swelling and edema. This results in a breakdown of homeostatic maintenance that likely contributes to ECM pathology.

Background: Second anterior cruciate ligament (ACL) tears after reconstruction occur at a reported rate of 20% to 30%. This high frequency indicates that there may be factors that predispose an athlete to graft failure and ACL tears of the contralateral knee. Purpose: To determine the incidence of second ACL injuries in a geographic population-based cohort over a 10-year observation period. Study Design: Descriptive epidemiological study. Methods: International Classification of Diseases, 9th Revision (ICD-9) codes relevant to the diagnosis of an ACL tear and the procedure code for ACL reconstruction were searched across the Rochester Epidemiology Project, a multidisciplinary county database, between the years of 1990 and 2000. This cohort of patients was tracked for subsequent ACL injuries through December 31, 2015. The authors identified 1041 patients with acute, isolated ACL tears. These patients were stratified by primary and secondary tears, sex, age, activity level, side of injury, sex by side of injury, and graft type. Results: Of the 1041 unique patients with a diagnosed ACL tear in Olmsted County, Minnesota, from 1990 to 2000, there were 66 (6.0%) second ACL tears; 66.7% of these tears occurred on the contralateral side. A second ACL injury was influenced by graft type ( P < .0001), election of ACL reconstruction ( P = .0060), and sex by side of injury ( P = .0072). Nonparametric analysis of graft disruption by graft type demonstrated a higher prevalence of second ACL tears with allografts compared with hamstring ( P = .0499) or patellar tendon autografts ( P = .0012). Conclusion: The incidence of second ACL tears in this population-based cohort was 6.0%, with 66.7% of these tears occurring on the contralateral side from the original injury. There was a high population incidence of second ACL injuries in female patients younger than age 20 years. The utilization of patellar tendon autografts significantly reduced the risk of second ACL injuries compared with allografts or hamstring autografts in this cohort.