Identification of Vertebral Fractures by Convolutional Neural Networks to Predict Nonvertebral and Hip Fractures: A Registry-based Cohort Study of Dual X-ray Absorptiometry.

Background Detection of vertebral fractures (VFs) aids in management of osteoporosis and targeting of fracture prevention therapies. Purpose To determine whether convolutional neural networks (CNNs) can be trained to identify VFs at VF assessment (VFA) performed with dual-energy x-ray absorptiometry and if VFs identified by CNNs confer a similar prognosis compared with the expert reader reference standard. Materials and Methods In this retrospective study, 12 742 routine clinical VFA images obtained from February 2010 to December 2017 and reported as VF present or absent were used for CNN training and testing. All reporting physicians were diagnostic imaging specialists with at least 10 years of experience. Randomly selected training and validation sets were used to produce a CNN ensemble that calculates VF probability. A test set (30%; 3822 images) was used to assess CNN agreement with the human expert reader reference standard and CNN prediction of incident non-VFs. Statistical analyses included area under the receiver operating characteristic curve, two-tailed Student t tests, prevalence- and bias-adjusted κ value, Kaplan-Meier curves, and Cox proportional hazard models. Results This study included 12 742 patients (mean age, 76 years ± 7; 12 013 women). The CNN ensemble demonstrated an area under the receiver operating characteristic curve of 0.94 (95% confidence interval [CI]: 0.93, 0.95) for VF detection that corresponded to sensitivity of 87.4% (534 of 611), specificity of 88.4% (2838 of 3211), and prevalence- and bias-adjusted κ value of 0.77. On the basis of incident fracture data available for 2813 patients (mean follow up, 3.7 years), hazard ratios adjusted for baseline fracture probability were 1.7 (95% CI: 1.3, 2.2) for CNN versus 1.8 (95% CI: 1.3, 2.3) for expert reader-detected VFs for incident non-VF and 2.3 (95% CI: 1.5, 3.5) versus 2.4 (95% CI: 1.5, 3.7) for incident hip fracture. Conclusion Convolutional neural networks can identify vertebral fractures on vertebral fracture assessment images with high accuracy, and these convolutional neural network-identified vertebral fractures predict clinical fracture outcomes. © RSNA, 2019 Online supplemental material is available for this article.

Vertebral Fracture Assessment Increases Use of Pharmacologic Therapy for Fracture Prevention in Clinical Practice.

The impact of vertebral fracture assessment (VFA) on lateral spine images in clinical practice on subsequent patient use of fracture prevention medication is unknown. Our objective was to determine the association of prevalent vertebral fracture identified on bone density lateral spine images (positive VFA) with subsequent use of fracture prevention therapy in usual clinical practice, using the Manitoba Bone Density Program database prospective observational cohort. Since 2010, targeted VFA imaging has been done at the time of bone densitometry in Manitoba for 21% of women and men meeting criteria based on age, bone mineral density (BMD), height loss, and glucocorticoid use. Among 6652 treatment-naive individuals with at least 90 days follow-up who had VFA imaging, 923 (13.9%) had one or more definite vertebral fractures identified using a modified algorithm-based qualitative (ABQ) method. For those with a positive VFA, their bone density reports stated the patient was at high risk of subsequent fracture and qualified for fracture prevention therapy. Subsequent osteoporosis treatment initiated within the next 12 months was identified using population-based pharmacy data. Logistic regression models were used to estimate the association of positive VFA with subsequent prescription (Rx), compared to negative VFA. Fracture prevention medication was started by 2127 (32%) individuals, 52.3% with positive versus 28.4% with negative VFA (p value <0.001). This association was substantially stronger in those designated (before VFA results were known) to have low or moderate fracture risk compared to high fracture risk (interaction p value <0.001), and in those with osteopenia (OR 4.51; 95% CI, 3.48 to 5.85) compared to those with osteoporosis by BMD criteria (OR 1.72; 95% CI, 1.43 to 2.08, interaction p value <0.001). Targeted VFA imaging at the time of bone densitometry substantially improves identification of those at high fracture risk and fracture prevention medication use among those with prevalent vertebral fracture. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.

Prevalent vertebral fracture on bone density lateral spine (VFA) images in routine clinical practice predict incident fractures.

PURPOSE: The predictive validity of vertebral fracture assessment (VFA) on bone density lateral spine images to identify prevalent vertebral fractures in routine clinical practice has not been established. Our objective was to estimate the associations of prevalent vertebral fracture identified on VFA images in routine practice with incident hip, all non-vertebral, major osteoporotic, and clinical vertebral fractures, using the Manitoba Bone Density database. METHODS: From 2010 onward, 9972 men and women (mean age [SD] 76 [6.9] years) had VFA images obtained at the time of bone densitometry that were interpreted for vertebral fracture by the clinicians reading the bone density tests. Definite and possible prevalent vertebral fractures, respectively, were identified in 1575 (15.8%) and 293 (2.9%) using a modified Algorithm Based Qualitative method. We ascertained incident fractures using Manitoba provincial health databases over a mean 2.8 (SD 1.7) years and used Cox proportional hazards models to estimate the associations of prevalent vertebral fractures with incident fractures. RESULTS: Compared to no prevalent vertebral fracture, those with definite prevalent vertebral fracture had higher hazard ratios for incident hip (HR 1.95, 95% C.I. 1.45 to 2.62), non-vertebral (HR 1.99, 95% C.I. 1.68 to 2.35), and clinical vertebral fracture (HR 2.68, 95% C.I. 1.69 to 4.23) adjusted for age, bone mineral density, body mass index, prior fracture, parental hip fracture, glucocorticoid use, alcohol use, smoking, and rheumatoid arthritis. These associations did not vary by FRAX fracture risk estimates or bone mineral density category. CONCLUSION: Prevalent vertebral fractures identified on densitometric VFA images in routine clinical practice are strongly associated with incident fractures, and this study is the first to show this using any lateral spine imaging modality outside of research settings. These findings are strong evidence supporting the targeted use of densitometric VFA imaging among post-menopausal women and older men referred for bone densitometry.

Carotid artery web and ischemic stroke: A case-control study.

OBJECTIVE: To determine whether there is an association between carotid artery web and ischemic stroke. METHODS: This was a single-center, age- and sex-matched, case-control study. Cases were consecutive patients with anterior circulation ischemic stroke of undetermined etiology (Trial of Org 10172 in Acute Stroke Treatment [TOAST] classification). Controls were consecutive patients with cerebral aneurysms, arteriovenous malformations, or primary intracerebral hemorrhages. Additional inclusion criteria were age <60 years and CT angiography of the neck. Two neuroradiologists diagnosed webs according to previously published criteria. One neuroradiologist also assessed for nonstenotic atherosclerotic plaque (carotid wall thickness ≥3 mm or intramural calcification). We used conditional logistic regression to estimate the odds ratio between carotid web and ischemic stroke and its 95% confidence interval. RESULTS: Fifty-three of 62 cases (85%) were matched by age (within 1 year) and by sex to 102 controls. There was a carotid web in 4 of 53 cases (9.4%) vs 1 of 102 controls (1.0%, odds ratio = 8.0, 95% confidence interval = 1.2-67, p = 0.032). There was no significant difference in the prevalence of nonstenotic carotid atherosclerotic plaque between the case and control groups. There was agreement on diagnosis of web for 163 of 164 patients (99%) and 7 of 8 webs (88%), and the Cohen κ for interobserver agreement was 0.93. CONCLUSIONS: There is an association between carotid artery web and ischemic stroke in patients who lack an alternative cause of stroke. Carotid web may be an underappreciated risk factor for stroke.

Nonstenotic carotid plaque on CT angiography in patients with cryptogenic stroke.

OBJECTIVE: To determine whether large (≥3 mm thick) but nonstenotic (<50%) carotid artery atherosclerotic plaque predominantly occurs ipsilateral rather than contralateral to cryptogenic stroke. METHODS: This was a cross-sectional observational study. Using a stroke registry, we identified consecutive patients with anterior circulation embolic stroke of undetermined source (ESUS). Using CT angiography, we measured carotid plaque size (thickness, mm) and carotid artery stenosis (North American Symptomatic Carotid Endarterectomy Trial method) for each patient. We dichotomized plaque size at several predefined thresholds and calculated the frequency of plaque size above each threshold ipsilateral vs contralateral to stroke. RESULTS: We included 85 patients with ESUS. Plaque with thickness ≥5 mm was present ipsilateral to stroke in 11% of patients, and contralateral in 1% (9/85 vs 1/85; p = 0.008). Plaque with thickness ≥4 mm was present ipsilateral to stroke in 19% of patients, and contralateral in 5% (16/85 vs 4/85; p = 0.002). Plaque with thickness ≥3 mm was present ipsilateral to stroke in 35% of patients, and contralateral in 15% (30/85 vs 13/85; p = 0.001). There was no difference in percentage stenosis ipsilateral vs contralateral to stroke (p = 0.98), and weak correlation between plaque size and stenosis (R(2) = 0.26, p < 0.001). CONCLUSIONS: Large but nonstenotic carotid artery plaque is considerably more common ipsilateral than contralateral to cryptogenic stroke, suggesting that nonstenotic plaque is an underrecognized cause of stroke. We measured plaque size using CT angiography, a method that could be easily implemented in clinical practice.

Development of Dural Arteriovenous Fistulas After Cerebral Venous Sinus Thrombosis.

A 57-year-old man presented with papilledema due to partially recanalized dural sinus thrombosis and was treated with anticoagulation and acetazolamide. One year after treatment and resolution of his symptoms, he had an increase in his optic disc edema accompanied by headaches. Subsequent neuroimaging indicated development of arteriovenous fistulas resulting in cortical and deep venous reflux. Given the high risk of mortality from intracranial hemorrhage, the patient underwent urgent treatment with a liquid embolic agent, which resulted in the resolution of his optic disc edema. Our case is unique in that recurrence of bilateral optic disc edema led to discovery of the rare complication of dural arteriovenous fistulas developing after dural sinus thrombosis. Ongoing monitoring of patients after cerebral venous sinus thrombosis is, therefore, important.

Pharmacodynamic activity of ertapenem versus penicillin-susceptible and penicillin-non-susceptible Streptococcus pneumoniae using an in vitro model.

BACKGROUND: Ertapenem is a novel carbapenem with activity against both penicillin-susceptible (MIC < or = 0.06 mg/L) and penicillin-non-susceptible (MIC > or = 0.12 mg/L) Streptococcus pneumoniae. This study assessed the pharmacodynamic activity of ertapenem against penicillin-susceptible and penicillin-non-susceptible S. pneumoniae using an in vitro pharmacodynamic model. METHODS: Fifteen S. pneumoniae strains including 3 penicillin-susceptible and 12 penicillin-non-susceptible [4 penicillin-intermediate (MIC 0.12-1 mg/L) and 8 penicillin-resistant (MIC > or = 2 mg/L); with different resistance phenotypes including erythromycin-resistant (MIC > or = 1 mg/L), ciprofloxacin-resistant (MIC > or = 4 mg/L) and doxycycline-resistant (MIC > or = 8 mg/L)] were studied. The in vitro pharmacodynamic model was inoculated with 1 x 10(6) cfu/mL and ertapenem was dosed once daily at 0 and 24 h to simulate f (free) Cmax and t(1/2) obtained after a standard 1 g intravenous once daily dose in healthy volunteers (fCmax 15 mg/L, t(1/2) 4 h). Sampling was performed for 48 h to assess viable growth. RESULTS: Ertapenem T(> MIC) > or = 80% (ertapenem MICs < or = 0.5 mg/L) resulted in bactericidal (> or = 3 log10 killing) activity at 12, 24 and 48 h with complete eradication of penicillin-susceptible and penicillin-non-susceptible S. pneumoniae from the model with no regrowth over the 48 h study period. Ertapenem T(> MIC) < or = 63% (ertapenem MIC > or = 1 mg/L) resulted in bactericidal activity at 12 h with regrowth at 24 and 48 h. The observed MICs for S. pneumoniae of ertapenem studied in the in vitro model did not change during the 48 h period, even for strains where regrowth occurred. CONCLUSIONS: Ertapenem is bactericidal against both penicillin-susceptible and penicillin-non-susceptible S. pneumoniae (ertapenem MICs < or = 0.5 mg/L) when simulating free drug after 1 g intravenous once daily dosing.

Pharmacodynamic activity of garenoxacin against ciprofloxacin-resistant Streptococcus pneumoniae.

BACKGROUND: The pharmacodynamic parameter that best correlates with bacteriological eradication for fluoroquinolones is the free (f) area under the 24 h serum concentration curve (AUC24) to MIC (fAUC24/MIC) ratio. This study assessed garenoxacin fAUC24/MIC against ciprofloxacin-resistant Streptococcus pneumoniae using an in vitro pharmacodynamic model. METHODS: A total of 14 S. pneumoniae including 1 fluoroquinolone-susceptible and 13 ciprofloxacin-resistant S. pneumoniae (ParC, efflux, ParC with efflux, and ParC and GyrA) were studied. The quinolone-resistance determining regions (QRDRs) of parC and gyrA were sequenced and efflux was assessed using a reserpine assay. S. pneumoniae with garenoxacin MICs (mg/L) [number of strains] studied were: 0.03 [1], 0.06 [2], 0.12 [2], 0.25 [2], 0.5 [3], 1 [2] and 2 [2]. The in vitro pharmacodynamic model was inoculated with 1 x 10(6) cfu/mL and garenoxacin was dosed once daily at 0 and 24 h to simulate fAUC24 and t1/2 obtained after standard oral doses in healthy volunteers (400 mg once daily, free AUC24 20 mg.h/L, t1/2 16 h). Sampling was performed over 48 h to assess viable growth. RESULTS: Garenoxacin fAUC24/MIC achieved in the model ranged from 12 to 800. Garenoxacin fAUC24/MIC 200-800 was bactericidal (> or = 3 log(10) killing) at 6, 24 and 48 h against ciprofloxacin-resistant S. pneumoniae mutants including ParC mutants only, efflux mutants only and ParC/efflux mutants. Garenoxacin fAUC24/MIC 48-96 was bactericidal (> or = 3 log(10) killing) at 24 and 48 h against all ciprofloxacin-resistant S. pneumoniae mutants. Garenoxacin fAUC24/MIC < or = 24 (against ParC and GyrA mutants) resulted in a bacteriostatic effect with regrowth at 24 and 48 h. CONCLUSIONS: Garenoxacin was bactericidal against ciprofloxacin-resistant S. pneumoniae at fAUC24/MIC > or = 48. Garenoxacin fAUC24/MIC < or = 24 resulted in a bacteriostatic effect with regrowth at 24 and 48 h.