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1.  Obstructive sleep apnea and the prevalence and incidence of cancer 
A link between obstructive sleep apnea and cancer development or progression has been suggested, possibly through chronic hypoxemia, but supporting evidence is limited. We examined the association between the severity of obstructive sleep apnea and prevalent and incident cancer, controlling for known risk factors for cancer development.
We included all adults referred with possible obstructive sleep apnea who underwent a first diagnostic sleep study at a single large academic hospital between 1994 and 2010. We linked patient data with data from Ontario health administrative databases from 1991 to 2013. Cancer diagnosis was derived from the Ontario Cancer Registry. We assessed the cross-sectional association between obstructive sleep apnea and prevalent cancer at the time of the sleep study (baseline) using logistic regression analysis. Cox regression models were used to investigate the association between obstructive sleep apnea and incident cancer among patients free of cancer at baseline.
Of 10 149 patients who underwent a sleep study, 520 (5.1%) had a cancer diagnosis at baseline. Over a median follow-up of 7.8 years, 627 (6.5%) of the 9629 patients who were free of cancer at baseline had incident cancer. In multivariable regression models, the severity of sleep apnea was not significantly associated with either prevalent or incident cancer after adjustment for age, sex, body mass index and smoking status at baseline (apnea–hypopnea index > 30 v. < 5: adjusted odds ratio [OR] 0.96, 95% confidence interval [CI] 0.71–1.30, for prevalent cancer, and adjusted hazard ratio [HR] 1.02, 95% CI 0.80–1.31, for incident cancer; sleep time spent with oxygen saturation < 90%, per 10-minute increase: adjusted OR 1.01, 95% CI 1.00–1.03, for prevalent cancer, and adjusted HR 1.00, 95% CI 0.99–1.02, for incident cancer).
In a large cohort, the severity of obstructive sleep apnea was not independently associated with either prevalent or incident cancer. Additional studies are needed to elucidate whether there is an independent association with specific types of cancer.
PMCID: PMC4162778  PMID: 25096668
2.  Murine Cell Line Model of Proneural Glioma for Evaluation of Anti-Tumor Therapies 
Journal of neuro-oncology  2013;112(3):375-382.
Molecular subtypes of glioblastoma (GBM) with distinct alterations have been identified. There is need for reproducible, versatile preclinical models that resemble specific GBM phenotypes to facilitate preclinical testing of novel therapies. We present a cell line-based murine Proneural GBM model and characterize its response to radiation therapy.
Proneural gliomas were generated by injecting PDGF-IRES-Cre retrovirus into the subcortical white matter of adult mice that harbor floxed tumor suppressors (Pten and p53) and stop-floxed reporters. Primary cell cultures were generated from the retrovirus induced tumors and maintained in vitro for multiple passages. RNA sequencing-based expression profiling of the resulting cell lines was performed. The tumorigenic potential of the cells was assessed by intracranial injection into adult naïve mice from different strains. Tumor growth was assessed by bioluminescence imaging (BLI). BLI for tumor cells and brain slices were obtained and compared to in vivo BLI. Response to whole-brain radiation was assessed in glioma-bearing animals.
Intracranial injection of Pdgf+Pten−/−p53−/−luciferase+ glioma cells led to formation of GBM-like tumors with 100% efficiency (n=48) and tumorigenesis was retained for more than 3 generations. The cell lines specifically resembled Proneural GBM based on expression profiling by RNA-Seq. Pdgf+Pten−/−p53−/−luciferase+ cell number correlated with BLI signal. Serial BLI measured tumor growth and correlated with size and location by ex-vivo imaging. Moreover, BLI predicted tumor-related mortality with a 93% risk of death within 5 days following a BLI signal between 1×108−5×108 photons/sec/cm2. BLI signal had transient but significant response following radiotherapy, which corresponded to a modest survival benefit for radiated mice (p<0.05).
Intracranial injection of Pdgf+Pten−/−p53−/−luciferase+ cells constitutes a novel and highly reproducible model, recapitulating key features of human Proneural GBM, and can be used to evaluate tumor-growth and response to therapy.
PMCID: PMC3694577  PMID: 23504257
glioma; proneural; murine; radiotherapy; cell line
3.  Obstructive Sleep Apnea and Risk of Cardiovascular Events and All-Cause Mortality: A Decade-Long Historical Cohort Study 
PLoS Medicine  2014;11(2):e1001599.
Tetyana Kendzerska and colleagues explore the association between physiological measures of obstructive sleep apnea other than the apnea-hypopnea index and the risk of cardiovascular events.
Please see later in the article for the Editors' Summary
Obstructive sleep apnea (OSA) has been reported to be a risk factor for cardiovascular (CV) disease. Although the apnea-hypopnea index (AHI) is the most commonly used measure of OSA, other less well studied OSA-related variables may be more pathophysiologically relevant and offer better prediction. The objective of this study was to evaluate the relationship between OSA-related variables and risk of CV events.
Methods and Findings
A historical cohort study was conducted using clinical database and health administrative data. Adults referred for suspected OSA who underwent diagnostic polysomnography at the sleep laboratory at St Michael's Hospital (Toronto, Canada) between 1994 and 2010 were followed through provincial health administrative data (Ontario, Canada) until May 2011 to examine the occurrence of a composite outcome (myocardial infarction, stroke, congestive heart failure, revascularization procedures, or death from any cause). Cox regression models were used to investigate the association between baseline OSA-related variables and composite outcome controlling for traditional risk factors. The results were expressed as hazard ratios (HRs) and 95% CIs; for continuous variables, HRs compare the 75th and 25th percentiles. Over a median follow-up of 68 months, 1,172 (11.5%) of 10,149 participants experienced our composite outcome. In a fully adjusted model, other than AHI OSA-related variables were significant independent predictors: time spent with oxygen saturation <90% (9 minutes versus 0; HR = 1.50, 95% CI 1.25–1.79), sleep time (4.9 versus 6.4 hours; HR = 1.20, 95% CI 1.12–1.27), awakenings (35 versus 18; HR = 1.06, 95% CI 1.02–1.10), periodic leg movements (13 versus 0/hour; HR = 1.05, 95% CI 1.03–1.07), heart rate (70 versus 56 beats per minute [bpm]; HR = 1.28, 95% CI 1.19–1.37), and daytime sleepiness (HR = 1.13, 95% CI 1.01–1.28).The main study limitation was lack of information about continuous positive airway pressure (CPAP) adherence.
OSA-related factors other than AHI were shown as important predictors of composite CV outcome and should be considered in future studies and clinical practice.
Please see later in the article for the Editors' Summary
Editors' Summary
Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder, particularly among middle-aged and elderly people. It is characterized by apnea—a brief interruption in breathing that lasts at least 10 seconds—and hypopnea—a decrease of more than 50% in the amplitude of breathing that lasts at least 10 seconds or clear but smaller decrease in amplitude associated with either oxygen desaturation or an arousal. Patients with OSA experience numerous episodes of apnea and hypopnea during the night; severe OSA is defined as having 30 or more episodes per hour (an apnea-hypopnea index [AHI] of >30). These breathing interruptions occur when relaxation of the upper airway muscles decreases the airflow, which lowers the amount of oxygen in the blood. As a result, affected individuals frequently wake from deep sleep as they struggle to breathe. Symptoms of OSA include loud snoring and daytime sleepiness. Treatments include lifestyle changes such as losing weight (excess fat around the neck increases airway collapse) and smoking cessation. For severe OSA, doctors recommend continuous positive airway pressure (CPAP), in which a machine blows pressurized air through a face mask into the airway to keep it open.
Why Was This Study Done?
OSA can be life-threatening. Most directly, daytime sleepiness can cause accidents, but OSA is also associated with an increased risk of developing cardiovascular disease (CVD, disease that affects the heart and the circulation). To date, studies that have investigated the association between OSA and the risk of myocardial infarction (heart attack), congestive heart failure, stroke, and other CVDs have used the AHI to diagnose and categorize the severity of OSA. However, by focussing on AHI, clinicians and researchers may be missing opportunities to improve their ability to predict which patients are at the highest risk of CVD. In this historical cohort study, the researchers investigate the association between other OSA-related variables (for example, blood oxygen saturation and sleep fragmentation) and the risk of cardiovascular events and all-cause mortality (death). A historical cohort study examines the medical records of groups of individuals who have different characteristics at baseline for the subsequent occurrence of specific outcomes.
What Did the Researchers Do and Find?
The researchers used administrative data (including hospitalization records and physicians' claims for services supplied to patients) to follow up adults referred for suspected OSA who underwent diagnostic polysomnography (a sleep study) at a single Canadian hospital between 1994 and 2010. A database of the polysomnography results provided information on OSA-related variables for all the study participants. Over an average follow-up of about 6 years, 11.5% of the 10,149 participants were hospitalized for a myocardial infarction, stroke, or congestive heart failure, underwent a revascularization procedure (an intervention that restores the blood supply to an organ or tissue after CVD has blocked a blood vessel), or had died from any cause. After adjusting for multiple established risk factors for CVD such as smoking and age in Cox regression models (a statistical approach that examines associations between patient variables and outcomes), several OSA-related variables (but not AHI) were significant predictors of CVD. The strongest OSA-related predictor of cardiovascular events or all-cause mortality was total sleep time spent with oxygen saturation below 90%, which increased the risk of a cardiovascular event or death by 50%. Other statistically significant OSA-related predictors (predictors that were unlikely to be associated with the outcome through chance) of cardiovascular events or death included total sleep time, number of awakenings, frequency of periodic leg movements, heart rate, and daytime sleepiness.
What Do These Findings Mean?
These findings indicate that OSA-related factors other than AHI are important predictors of the composite outcome of a cardiovascular event or all-cause mortality. Indeed, although AHI was significantly associated with the researchers' composite outcome in an analysis that did not consider other established risk factors for CVD (“confounders”), the association became non-significant after controlling for potential confounders. The accuracy of these findings, which need to be confirmed in other settings, is likely to be limited by the lack of information available about the use of CPAP by study participants and by the lack of adjustment for some important confounders. Importantly, however, these findings suggest that OSA-related factors other than AHI should be considered as predictors of CVD in future studies and in clinical practice.
Additional Information
Please access these websites via the online version of this summary at
The US National Heart Lung and Blood Institute has information (including several videos) about obstructive sleep apnea (in English and Spanish), sleep studies, heart disease, and other cardiovascular diseases (some information in English and Spanish)
The UK National Health Service Choices website provides information (including personal stories) about sleep apnea and about cardiovascular disease
The not-for-profit American Sleep Apnea Association provides detailed information about sleep apnea for patients and health-care professionals, including personal stories about the condition
The MedlinePlus encyclopedia has pages on obstructive sleep apnea and on polysomnography; MedlinePlus provides links to further information and advice about obstructive sleep apnea, heart diseases, and vascular diseases (in English and Spanish)
PMCID: PMC3913558  PMID: 24503600
4.  Sensitivity and specificity of time-domain versus spectral-domain optical coherence tomography in diabetic macular edema 
Indian Journal of Ophthalmology  2013;61(5):208-212.
The purpose was to evaluate the sensitivity and specificity of measurements of central macular thickness (CMT) in diabetic macular edema using stratus time-domain and cirrus spectral-domain optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, CA).
Materials and Methods:
A total of 36 eyes from 19 patients with clinically significant diabetic macular edema (DME) were included. All participants underwent automated scanning patterns using cirrus HD-OCT and stratus OCT examinations on the same day. The sensitivity/specificity of retinal thickness measurements was calculated from published normative data. Agreement was calculated using Bland--Altman method. The receiver operating characteristic curves (ROC) and areas under the ROC were plotted.
The mean difference between the cirrus HD-OCT and stratus OCT in the central foveal zone was 49.89 μm. Bland--Altman analysis confirmed that the retinal thickness measurements had poor agreement in patients with DME. The areas under the ROC for retinal thickness measurements were 0.88 using cirrus HD-OCT and 0.94 with stratus.
In patients with DME, the cirrus HD-OCT gives a higher reading than stratus OCT with poor agreement between the devices in most regions within the nine subfield zones. The sensitivity and specificity of the stratus OCT was comparable to the cirrus.
PMCID: PMC3730503  PMID: 23571234
Diabetic macular edema; optical coherence tomography; sensitivity; specificity
5.  Medial lenticulostriate artery aneurysm presenting with isolated intraventricular hemorrhage 
Isolated intraventricular hemorrhage (IVH) secondary to lenticulostriate artery aneurysm rupture is extremely rare. Thus, the diagnostic imaging modalities and therapeutic interventions utilized in the management of such cases are not clearly defined.
Case Description:
Here we describe a case of isolated or primary IVH (PIVH) in a 71-year-old woman presenting with severe headache. Emergent catheter cerebral angiography, performed after nondiagnostic computed tomography angiography (CTA), revealed the bleeding source to be a 4 × 2.6 mm distal medial lenticulostriate artery aneurysm that ruptured directly into the lateral ventricle. The poorly accessible location of the aneurysm for both endovascular and direct surgical treatment argued for conservative management. A good clinical outcome was obtained with rapid angiographic resolution of the ruptured aneurysm.
Thus, lenticulostriate artery aneurysm rupture must be given diagnostic consideration in cases of isolated IVH. Emergent catheter cerebral angiography should be performed in cases such as this when noninvasive imaging is unrevealing. Conservative management may be a reasonable therapeutic option in patients with this kind of aneurysm, and spontaneous resolution can be observed.
PMCID: PMC3130466  PMID: 21748044
Angiography; cerebral aneurysm; fibromuscular dysplasia; intraventricular hemorrhage; lenticulostriate artery; pseudoaneurysm
6.  Utility of routine chest radiographs in a medical–surgical intensive care unit: a quality assurance survey 
Critical Care  2001;5(5):271-275.
To determine the utility of routine chest radiographs (CXRs) in clinical decision-making in the intensive care unit (ICU).
A prospective evaluation of CXRs performed in the ICU for a period of 6 months. A questionnaire was completed for each CXR performed, addressing the indication for the radiograph, whether it changed the patient's management, and how it did so.
A 14-bed medical–surgical ICU in a university-affiliated, tertiary care hospital.
A total of 645 CXRs were analyzed in 97 medical patients and 205 CXRs were analyzed in 101 surgical patients.
Of the 645 CXRs performed in the medical patients, 127 (19.7%) led to one or more management changes. In the 66 surgical patients with an ICU stay <48 hours, 15.4% of routine CXRs changed management. In 35 surgical patients with an ICU stay ≥ 48 hours, 26% of the 100 routine films changed management. In both the medical and surgical patients, the majority of changes were related to an adjustment of a medical device.
Routine CXRs have some value in guiding management decisions in the ICU. Daily CXRs may not, however, be necessary for all patients.
PMCID: PMC83854  PMID: 11737902
chest radiograph; intensive care unit; quality assurance; routine radiography

Results 1-6 (6)