Citations

Background— The pathogenesis of sudden cardiac death in college athletes has not been defined by systematic case identification. Methods and Results— A total of 45 cases of sudden cardiac death were identified in National Collegiate Athletic Association (NCAA) athletes from 2004 to 2008 based on an internal reporting system and review of media reports. Autopsy reports were reviewed and adjudicated by a multidisciplinary panel. Cause of death could be reasonably determined in 36 cases; 3 athletes had no autopsy, 5 autopsy reports could not be obtained, and 1 autopsy had insufficient information to determine cause of death. The most common finding at death was a structurally normal heart or autopsy-negative sudden unexplained death (11, 31%), followed by coronary artery abnormalities (5, 14%), dilated cardiomyopathy (3, 8%), myocarditis related (3, 8%), aortic dissection (3, 8%), and idiopathic left ventricular hypertrophy/possible hypertrophic cardiomyopathy (HCM; 3, 8%). There was 1 case each (3%) of hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, commotio cordis, and Kawasaki disease. There was 1 case of death in a sickle cell positive athlete who also had left ventricular hypertrophy. The adjudicated diagnosis agreed with the official pathology report in only 59% of cases. Conclusions— Unexplained death with a structurally normal heart is the most common finding after suspected sudden cardiac death in NCAA athletes. Hypertrophic cardiomyopathy is infrequently seen, and conclusions in autopsy reports may not accurately reflect the pathological findings. Standardized protocols for cardiovascular autopsies in athletes are needed, including postmortem genetic testing, particularly in autopsy-negative cases.

Spinal instrumentation has made significant advances in the last two decades, with transpedicular constructs now widely used in spinal fixation. Pedicle screw constructs are routinely used in thoracolumbar-instrumented fusions, and in recent years, the cervical spine as well. Three-column fixations with pedicle screws provide the most rigid form of posterior stabilization. Surgical landmarks and fluoroscopy have been used routinely for pedicle screw insertion, but a number of studies reveal inaccuracies in placement using these conventional techniques (ranging from 10% to 50%). The ability to combine 3D imaging with intraoperative navigation systems has improved the accuracy and safety of pedicle screw placement, especially in more complex spinal deformities. However, in the authors' experience with image guidance in more than 1500 cases, several potential pitfalls have been identified while using intraoperative spinal navigation that could lead to suboptimal results. This article summarizes the authors' experience with these various pitfalls using spinal navigation, and gives practical tips on their avoidance and management.

Background: Because both daptomycin and statins may increase creatine phosphokinase (CPK) levels, the manufacturer of daptomycin suggests considering holding statins during daptomycin therapy. Published evidence suggests potential detrimental effects of withdrawing statin therapy. Objectives: The objectives of this study were to determine the impact of concurrent statin therapy on peak CPK values, incidence of CPK elevation in patients receiving daptomycin therapy, and clinical factors associated with increased risk of developing CPK elevation. Methods: This was a single-center, retrospective cohort study of patients ≥18 years of age who received daptomycin for ≥72 hours and had ≥1 follow-up CPK during a 5-year period. A Kaplan-Meier curve was used to evaluate time to CPK elevation. Cox regression analyses were used to compare the risk of developing elevated CPK between 3 study groups: those receiving daptomycin alone, daptomycin with concurrent statin therapy, and statin therapy held while on daptomycin. Results: 498 patients were included in the study—384 received daptomycin alone, 63 received daptomycin concurrent with statin, and 51 with statin held during daptomycin therapy. Cumulative incidence of CPK elevation was 5.1% and 12% at 7 and 14 days. Those on daptomycin and statin concurrent therapy demonstrated an approximately 2-fold risk of CPK elevation compared with those having their statin therapy held, but the overall group effect was not statistically significant ( P = .17). Conclusions: Our findings suggest that holding statin during daptomycin therapy may not be necessary, but may indicate need for increased frequency of CPK monitoring when these medications are used concurrently.

ABSTRACTThe chromatin remodeling complex SWI/SNF and the transcription factor C/EBPβ play critical roles in osteoblastic cells as they jointly control transcription of a number of bone‐related target genes. The largest C/EBPβ isoform, LAP*, possesses a short additional N‐terminal domain that has been proposed to mediate the interaction of this factor with SWI/SNF in myeloid cells. Here we examine the requirement of a functional N‐terminus in C/EBPβ‐LAP* for binding SWI/SNF and for recruiting this complex to the Ric‐8B gene to mediate transcriptional repression. We find that both C/EBPβ‐LAP* and SWI/SNF simultaneously bind to the Ric‐8B promoter in differentiating osteoblasts that repress Ric‐8B expression. This decreased expression of Ric‐8B is not accompanied by significant changes in histone acetylation at the Ric‐8B gene promoter sequence. A single aminoacid change at the C/EBPβ‐LAP* N‐terminus (R3L) that inhibits C/EBPβ‐LAP*‐SWI/SNF interaction, also prevents SWI/SNF recruitment to the Ric‐8B promoter as well as C/EBPβ‐LAP*‐dependent repression of the Ric‐8B gene. Inducible expression of the C/EBPβ‐LAP*R3L protein in stably transfected osteoblastic cells demonstrates that this mutant protein binds to C/EBPβ‐LAP*‐target promoters and competes with the endogenous C/EBPβ factor. Together our results indicate that a functional N‐terminus in C/EBPβ‐LAP* is required for interacting with SWI/SNF and for Ric‐8B gene repression in osteoblasts. J. Cell. Physiol. 229: 1521–1528, 2014. © 2014 Wiley Periodicals, Inc.

Background: Glucose control can be problematic in critically ill patients. We evaluated the impact of statistical transformation on interpretation of intensive care unit inpatient glucose control data. Methods: Point-of-care blood glucose (POC-BG) data derived from patients in the intensive care unit for 2011 was obtained. Box–Cox transformation of POC-BG measurements was performed, and distribution of data was determined before and after transformation. Different data subsets were used to establish statistical upper and lower control limits. Exponentially weighted moving average (EWMA) control charts constructed from April, October, and November data determined whether out-of-control events could be identified differently in transformed versus nontransformed data. Results: A total of 8679 POC-BG values were analyzed. POC-BG distributions in nontransformed data were skewed but approached normality after transformation. EWMA control charts revealed differences in projected detection of out-of-control events. In April, an out-of-control process resulting in the lower control limit being exceeded was identified at sample 116 in nontransformed data but not in transformed data. October transformed data detected an out-of-control process exceeding the upper control limit at sample 27 that was not detected in nontransformed data. Nontransformed November results remained in control, but transformation identified an out-of-control event less than 10 samples into the observation period. Conclusions: Using statistical methods to assess population-based glucose control in the intensive care unit could alter conclusions about the effectiveness of care processes for managing hyperglycemia. Further study is required to determine whether transformed versus nontransformed data change clinical decisions about the interpretation of care or intervention results.

ABSTRACT Objectives To determine whether α‐synuclein dinucleotide repeat (REP1) genotypes are associated with survival in Parkinson's disease (PD). Methods Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium provided REP1 genotypes and baseline and follow‐up clinical data for cases. The primary outcome was time to death. Cox proportional hazards regression models were used to assess the association of REP1 genotypes with survival. Results Twenty‐one sites contributed data for 6,154 cases. There was no significant association between α‐synuclein REP1 genotypes and survival in PD. However, there was a significant association between REP1 genotypes and age at onset of PD (hazard ratio: 1.06; 95% confidence interval: 1.01‐1.10; P value = 0.01). Conclusions In our large consortium study, α‐synuclein REP1 genotypes were not associated with survival in PD. Further studies of α‐synuclein's role in disease progression and long‐term outcomes are needed. © 2014 International Parkinson and Movement Disorder Society

Objectives: We evaluated relapse patterns after transoral laser microsurgery (TLM) in squamous cell carcinoma (SCC) of the tonsil and tongue base and evaluated the indications for adjuvant irradiation. Methods: Between December 1, 1996, and December 31, 2005, 79 patients with previously untreated SCC of the tonsil or tongue base underwent TLM with or without neck dissection. Thirty-eight patients (48%) underwent postoperative irradiation (median, 62 Gy) to the primary site and the neck. Analysis of relapse patterns was performed on the basis of adverse risk factors and the presence or absence of adjuvant irradiation. Results: The median follow-up for living patients was 47 months (range, 10 to 107 months), and patients were monitored for at least 2 years or until recurrence or death. Local, regional, and distant treatment failures numbered 4, 6, and 4 for surgery alone (n = 41) and 0, 2, and 6 for adjuvant irradiation (n = 38), respectively. Patients with high-risk features (extracapsular extension or at least 2 adverse factors) had locoregional control rates at 2 or more years of 66% and 94% for TLM alone and TLM plus adjuvant irradiation, respectively. Conclusions: Adjuvant irradiation after TLM resection of oropharyngeal SCC with intermediate- or high-risk features improves locoregional control compared with TLM alone.