Associations of cumulative voriconazole dose, treatment duration, and alkaline phosphatase with voriconazole-induced periostitis.

OBJECTIVE: To investigate the associations of cumulative voriconazole dose, treatment duration, and alkaline phosphatase with voriconazole-induced periostitis. MATERIALS AND METHODS: One hundred and thirty-one patients with voriconazole use were identified using a clinical informatics tool. Health record data including age, sex, immune status, alkaline phosphatase, voriconazole levels, voriconazole dose, frequency, and treatment duration were collected. Imaging studies during the duration of treatment were reviewed by two radiology trainees and imaging features of voriconazole-induced periostitis were confirmed by a board-certified musculoskeletal radiologist. The length, location in the body, location in the bone, type, and morphology of periostitis lesions were recorded. Incident voriconazole-induced periostitis was defined as new periostitis on imaging after 28 days or more of voriconazole treatment in the absence of an alternative diagnosis. Univariate Firth's logistic regression models were performed using cumulative voriconazole dose, treatment duration, and average ALP as predictors and incident VIP as the outcome. RESULTS: There were nine patients with voriconazole-induced periostitis and 122 patients without voriconazole-induced periostitis. The most common lesion location in the body was the ribs (37%) and morphology was solid (44%). A 31.5-g increase in cumulative voriconazole dose was associated with 8% higher odds of incident periostitis. Increased treatment duration (63 days) and higher average alkaline phosphatase (50 IU/L) were associated with 7% higher odds of periostitis and 34% higher odds of periostitis, respectively. CONCLUSION: Increased cumulative voriconazole dose, treatment duration, and average alkaline phosphatase were associated with higher odds of voriconazole-induced periostitis.

Patients with Type 2 Diabetes Exhibit a More Mineralized Deep Cartilage Layer Compared with Nondiabetic Controls: A Pilot Study.

OBJECTIVE: To assess differences in biochemical composition of the deep cartilage layer in subjects with type 2 diabetes mellitus (T2DM) and nondiabetic controls using UTE (ultra-short echo time) T2* mapping and to investigate the association of vascular health and UTE T2* measurements. DESIGN: Ten subjects with T2DM matched for age, sex, and body mass index with 10 nondiabetic controls. A 3D UTE sequence with 6 echo times was acquired using 3T magnetic resonance imaging of the knee. For UTE T2* analysis, the deep cartilage layer was segmented and analyzed in 5 compartments (patella, medial, and lateral femur and tibia). The ankle brachial index (ABI) was obtained in all subjects. Linear regression analyses were used to assess associations of T2DM and UTE T2* relaxation times and the associations of ABI measurements and UTE measurements. RESULTS: Compared with nondiabetic controls, T2DM subjects had significantly lower mean T2*-UTE in the patella (mean difference 4.87 ms; 95% confidence interval [CI] 1.09-8.65; P = 0.015), the lateral tibia (mean difference 2.26 ms; 95% CI 0.06-4.45; P = 0.045), and the lateral femur (mean difference 4.96 ms; 95% CI 0.19-9.73; P = 0.043). Independent of diabetic status, subjects with higher ABI values, indicating better vascular health, had higher T2*-UTE of the patella (coefficient 15.2; 95% CI 3.3-21.4; P = 0.017), the medial tibia (coefficient 9.8; 95% CI 1.0-18.6; P = 0.031), and the lateral femur (coefficient 18.8; 95% CI 3.3-34.3; P = 0.021). CONCLUSIONS: T2*-UTE measurements of the deep cartilage layer were consistently lower in subjects with T2DM and in subjects with impaired vascular health, likely indicating increased mineralization of this layer.

Investigating the Association of Metabolic Biomarkers With Knee Cartilage Composition and Structural Abnormalities Using MRI: A Pilot Study.

OBJECTIVE: The goal of this study was to explore the metabolic syndrome-associated phenotype of osteoarthritis by investigating the cross-sectional associations of glycemic markers and serum lipids with knee cartilage composition and structural abnormalities in middle-aged adults. DESIGN: Twenty participants between 40 to 70 years of age with Kellgren-Lawrence score 0-1 in at least one knee were recruited at a single center. Knee cartilage composition was assessed using 3.0 T cartilage T2 and T1ρ mapping. Evaluation of structural knee abnormalities was performed using the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Linear regression was used to assess the associations of standardized fasting glucose (FG), hemoglobin A1c (HbA1c), insulin, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL cholesterol, and triglycerides with cartilage T2 and T1ρ as well as WORMS subscores, adjusting for body mass index. RESULTS: Higher FG and higher HbA1c were associated with higher WORMS meniscus sum (beta coefficient 1.31 [95% confidence interval (CI): 0.57, 2.05], P = 0.002 per standard deviation [SD] increase in FG; beta coefficient 0.90 [95% CI: 0.07, 1.73], P = 0.035 per SD increase in HbA1c). Also, higher total cholesterol and higher non-HDL cholesterol were associated with higher WORMS cartilage sum (beta coefficient 0.94 [95% CI: 0.01, 1.86], P = 0.048 per SD increase in total cholesterol; beta coefficient 1.05 [95% CI: 0.14, 1.96], P = 0.03 per SD increase in non-HDL cholesterol). CONCLUSIONS: Higher FG and HbA1c were associated with increased meniscal degeneration while higher total and non-HDL cholesterol were associated with increased cartilage degeneration.

Association of blood pressure with knee cartilage composition and structural knee abnormalities: data from the osteoarthritis initiative.

OBJECTIVE: To investigate the associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with changes in knee cartilage composition and joint structure over 48 months, using magnetic resonance imaging (MRI) data from the Osteoarthritis Initiative (OAI). MATERIALS AND METHODS: A total of 1126 participants with right knee Kellgren-Lawrence (KL) score 0-2 at baseline, no history of rheumatoid arthritis, blood pressure measurements at baseline, and cartilage T2 measurements at baseline and 48 months were selected from the OAI. Cartilage composition was assessed using MRI T2 measurements, including laminar and gray-level co-occurrence matrix texture analyses. Structural knee abnormalities were graded using the whole-organ magnetic resonance imaging score (WORMS). We performed linear regression, adjusting for age, sex, body mass index, physical activity, smoking status, alcohol use, KL score, number of anti-hypertensive medications, and number of nonsteroidal anti-inflammatory drugs. RESULTS: Higher baseline DBP was associated with greater increases in global T2 (coefficient 0.22 (95% CI 0.09, 0.34), P = 0.004), global superficial layer T2 (coefficient 0.39 (95% CI 0.20, 0.58), P = 0.001), global contrast (coefficient 15.67 (95% CI 8.81, 22.53), P < 0.001), global entropy (coefficient 0.02 (95% CI 0.01, 0.03) P = 0.011), and global variance (coefficient 9.14 (95% CI 5.18, 13.09), P < 0.001). Compared with DBP, the associations of SBP with change in cartilage T2 parameters and WORMS subscores showed estimates of smaller magnitude. CONCLUSION: Higher baseline DBP was associated with higher and more heterogenous cartilage T2 values over 48 months, indicating increased cartilage matrix degenerative changes.