Discovery of Two Novel Immunoepitopes and Development of Peptide-based Sarcoidosis Immunoassay.

RATIONALE: Sarcoidosis is a systemic granulomatous disorder associated with hypergammaglobulinemia and the presence of autoantibodies. The specific antigens initiating granulomatous inflammation in sarcoidosis are unknown and there is no specific test available to diagnose sarcoidosis. To discover novel sarcoidosis antigens, we developed a high-throughput T7 phage display library derived from the sarcoidosis cDNA and identified numerous clones differentiating sarcoidosis from other respiratory diseases. After clone sequencing and homology search, we identified two epitopes (Cofilinµ and Chain A) that specifically bind to serum IgGs of sarcoidosis patients. OBJECTIVES: To develop and validate an epitope-specific IgG-based immunoassay specific for sarcoidosis. METHODS: We chemically synthesized both immunoepitopes (Cofilinµ and Chain A), and generated rabbit polyclonal antibodies against both neoantigens. After extensive standardization, we developed a direct peptide ELISA and measured epitope-specific IgG in sera of 386 subjects including, healthy controls (n=100), three sarcoidosis cohorts (n=186), pulmonary tuberculosis (n=70) and lung cancer (n=30). MEASUREMENTS AND MAIN RESULTS: To develop a model to classify sarcoidosis from other groups, data were analyzed using five-fold cross-validation when adjusting for confounders. The Cofilinµ IgGs model yielded a mean sensitivity, specificity, and positive and negative predictive value (PPV, NPV) of 0.97, 0.9, 0.9 and 0.96, respectively. Those same measures for Chain A IgG antibody were 0.9, 0.83, 0.84 and 0.9 respectively. Combining both biomarkers improved AUC, sensitivity, specificity, PPV and NPV. CONCLUSIONS: These results provide a novel immunoassay for sarcoidosis. The discovery of two neoantigens facilitates the development of biospecific drug discovery and the sarcoidosis-specific model.

A new prediction model for total body water estimation by BIA in children with normal and excessive weight.

BACKGROUND: Various methods, including bioelectrical impedance analysis (BIA), are used for total body water (TBW) estimation. The objective of our study by BIA was to develop a new predication model based on corrected TBW for normal adult BMI, a concept similar to the standardization of glomerular filtration rate by relating it to the average adult body surface area. METHOD: We measured TBW by BIA in 335 children 3-21 years old with normal or excessive body weight. Based on our data, we derived a new prediction model for TBW (L) for females {[(72.784 + 0.4093 × weight)∗Corrected TBW]/100} and males {[(57.944 + 0.6551 × weight)∗Corrected TBW]/100}. For validation, we compared our prediction model with three other models on TBW by BIA and dilution methods. RESULTS: Our model's error size to predict TBW showed lower cross-validated root mean square error (CV-RMSE) as compared to three other models versus our dataset by BIA and two other datasets by dilution methods. Our model also showed a smaller error (2.059) in CV-RMSE as compared to other models by dilution methods (2.126, 2.873, and 4.384) for normal and excessive weight combined. This implies that our model is more robust when excessive weight individuals are included in the data.. CONCLUSION: Our prediction model for TBW estimation by BIA performs better as compared to some other models based on BIA and dilution method datasets. Furthermore, our prediction model is the only one that is devised to be applicable to children and young adults with both normal as well as excessive weight.

Validation of MRI classification system for tibial stress injuries.

OBJECTIVE: The purpose of our study was to compare an MRI classification system for tibial stress injuries with semiquantitative MR features of injury severity and clinical outcome. MATERIALS AND METHODS: Two musculoskeletal radiologists retrospectively reviewed in consensus the MR findings of 142 tibial stress injuries to quantify the degree of periosteal and bone marrow edema and grade the injuries using the Fredericson classification system (grade 1 = periosteal edema only, grade 2 = bone marrow edema visible on T2-weighted images, grade 3 = bone marrow edema visible on T1-weighted and T2-weighted images, grade 4a = multiple focal areas of intracortical signal abnormality, and grade 4b = linear areas of intracortical signal abnormality). Kruskal-Wallis tests were used to determine the relationship between the grade of stress injury and the degree of periosteal and bone marrow edema and the time to return to sports activity. RESULTS: Grade 4b injuries had significantly (p < 0.002) more severe and grade 1 injuries less severe periosteal and bone marrow edema than grades 2, 3, and 4a injuries. Grade 4b injuries had significantly (p < 0.002) longer time and grade 1 injuries shorter time to return to sports activity than grades 2, 3, and 4a injuries. There was no significant difference (p = 0.06-0.79) among grades 2, 3, and 4a injuries in the degree of periosteal and bone marrow edema and the time to return to sports activity. CONCLUSION: Grades 2, 3, and 4a stress injuries had similar degrees of periosteal and bone marrow edema and similar time to return to sports activity, which suggests that these three grades can be combined into a single category in an abbreviated Fredericson classification system.

The mammographic density of a mass is a significant predictor of breast cancer.

PURPOSE: To determine whether the mammographic density of noncalcified solid breast masses is associated with malignancy and to measure the agreement between prospective and retrospective assessment. MATERIALS AND METHODS: The institutional review board approved this study and waived informed consent. Three hundred forty-eight consecutive breast masses in 328 women who underwent image-guided or surgical biopsy between October 2005 and December 2007 were included. All 348 biopsy-proved masses were randomized and assigned to a radiologist who was blinded to biopsy results for retrospective assessment by using the Breast Imaging Reporting and Data System (retrospectively assessed data set). Clinical radiologists prospectively assessed the density of 180 of these masses (prospectively assessed data set). Pathologic result at biopsy was the reference standard. Benign masses were followed for at least 1 year by linking each patient to a cancer registry. Univariate analyses were performed on the retrospectively assessed data set. The association of mass density and malignancy was examined by creating a logistic model for the prospectively assessed data set. Agreement between prospective and retrospective assessments was calculated by using the κ statistic. RESULTS: In the retrospectively assessed data set, 70.2% of high-density masses were malignant, and 22.3% of the isodense or low-density masses were malignant (P < .0001). In the prospective logistic model, high density (odds ratio, 6.6), irregular shape (odds ratio, 9.9), spiculated margin (odds ratio, 20.3), and age (ß = 0.09, P < .0001) were significantly associated with the probability of malignancy. The κ value for prospective-retrospective agreement of mass density was 0.53. CONCLUSION: High mass density is significantly associated with malignancy in both retrospectively and prospectively assessed data sets, with moderate prospective-retrospective agreement. Radiologists should consider mass density as a valuable descriptor that can stratify risk. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100328/-/DC1.

MR arthrography of the hip: comparison of IDEAL-SPGR volume sequence to standard MR sequences in the detection and grading of cartilage lesions.

PURPOSE: To compare the diagnostic performance of iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL)-spoiled gradient-recalled echo (SPGR) with that of standard magnetic resonance (MR) arthrography sequences for detecting and grading cartilage lesions within the hip joint during MR arthrography. MATERIALS AND METHODS: Following institutional review board approval, 67 consecutive hip MR arthrograms were retrospectively reviewed independently by three musculoskeletal radiologists and one musculoskeletal fellow. IDEAL-SPGR images and the two-dimensional images, the latter from the routine MR arthrography protocol, were evaluated at separate sittings to grade each articular surface of the hip joint. By using arthroscopy as the reference standard, the sensitivity and specificity of the two techniques for detecting and grading cartilage lesions were determined. The McNemar test was used to compare diagnostic performance. Interreader agreement was calculated using Fleiss κ values. RESULTS: For all readers and surfaces combined, the sensitivity and specificity for detecting cartilage lesions was 74% and 77%, respectively, for IDEAL-SPGR and 70% and 84%, respectively, for the routine MR arthrography protocol. IDEAL-SPGR had similar sensitivity (P = .12) to and significantly lower specificity (P < .001) than the routine MR arthrography protocol for depicting cartilage lesions. When analyzing the differences in sensitivity and specificity by reader, the two readers who had experience with IDEAL-SPGR had no significant difference in sensitivity and specificity for detecting cartilage lesions between the two sequences. For all readers and surfaces combined, IDEAL-SPGR had a higher accuracy in correctly grading cartilage lesion (P = .012-.013). Interobserver agreement for detecting cartilage lesions did not differ between the two techniques. CONCLUSION: IDEAL-SPGR had similar sensitivity and significantly lower specificity for detecting cartilage lesions and higher accuracy for grading cartilage lesions than did a routine MR arthrography protocol; the lower specificity of IDEAL-SPGR for detecting cartilage lesions was not seen in experienced readers.

3.0-T evaluation of knee cartilage by using three-dimensional IDEAL GRASS imaging: comparison with fast spin-echo imaging.

PURPOSE: To compare the diagnostic performance of iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) gradient-recalled acquisition in steady-state (GRASS) imaging with a routine magnetic resonance (MR) imaging protocol for evaluating knee cartilage at 3.0 T in patients by using arthroscopy as the reference standard. MATERIALS AND METHODS: This prospective Health Insurance Portability and Accountability Act-compliant study was performed with a waiver of informed consent from the institutional review board. IDEAL GRASS was added to routine 3.0-T knee MR protocol performed in 95 symptomatic patients (48 males, mean age, 34.5 years; 47 females, mean age, 35.5 years) who underwent subsequent arthroscopic surgery. Radiologists used the routine MR protocol during the first review and IDEAL GRASS during the second to grade each articular surface and to determine the presence of meniscal tears. By using arthroscopy as the reference standard, the sensitivity, specificity, and accuracy of both imaging methods for detecting cartilage lesions and meniscal tears were determined. RESULTS: By using the z test to compare parameters between methods, the respective sensitivity, specificity, and accuracy for detecting all 192 cartilage lesions were 68.5%, 92.6%, and 84.5% for IDEAL GRASS and 66.1%, 92.9%, and 83.9% for the routine MR protocol. There was no significant difference (P = .34-.83) in parameters between methods for detecting cartilage lesions. The respective parameters for detecting 50 medial meniscal tears were 85.0%, 91.1%, and 87.9% for IDEAL GRASS and 94.0%, 90.0%, and 92.1% for the routine MR protocol. The parameters for detecting 31 lateral meniscal tears were 58.0%, 90.6%, and 80.0% for IDEAL GRASS and 80.1%, 91.4%, and 87.9% for the routine MR protocol. The routine MR protocol had a significantly higher sensitivity for detecting medial meniscal tears (P = .04) and lateral meniscal tears (P = .01) and significantly higher accuracy for detecting lateral meniscal tears (P = .03) than IDEAL GRASS. CONCLUSION: IDEAL GRASS has similar diagnostic performance as routine MR protocol for evaluating the articular cartilage of the knee in clinical patients at 3.0 T but has significantly lower sensitivity and accuracy for detecting meniscal tears.

Changing trends in serious extra-articular manifestations of rheumatoid arthritis among United State veterans over 20 years.

OBJECTIVES: The purpose of this study was to examine prevalence trends of serious extra-articular manifestations (EAMs) in a data set representing both hospitalized and ambulatory patients with RA. METHODS: This retrospective cohort study used serial cross-sectional data to examine the prevalence of serious EAMs in patients with RA from 1985 to 2006 across the United States (US) Veteran's Health Administration system. Serious EAMs included rheumatoid carditis, RA lung disease, FS and pooled EAM rates included previously reported vasculitis prevalence as queried by ICD-9 searches. Statistical analysis employed auto-regression and time series analysis using the Chow and Durbin-Watson tests to detect breakpoints and linear time-trends. RESULTS: Among 3 million veterans, including >35,000 RA patients annually, we noted declining RA hospitalizations emphasizing the importance of examining both the inpatient and outpatient settings to assess EAM prevalence. Individual EAM trends varied, demonstrating linear declines in FS, increases in RA lung disease and significant breakpoint declines in carditis and pooled serious EAMs. Pooled EAM prevalence dropped around 2000, from an early linear trend peak of 10% among inpatients, to <7% among both inpatients and outpatients by 2006. CONCLUSIONS: Overall, serious EAMs of RA have declined among US veterans in both the inpatient and outpatient settings, with the exception of RA lung disease likely reflecting improved detection. Breakpoints in pooled EAM prevalence appear to demonstrate consistent, true declines in severe RA extra-articular disease around 2000. Future work should explore the relationship between temporal EAM trends and specific RA therapies including adoption of biological agents.

Validation of results from knowledge discovery: mass density as a predictor of breast cancer.

The purpose of our study is to identify and quantify the association between high breast mass density and breast malignancy using inductive logic programming (ILP) and conditional probabilities, and validate this association in an independent dataset. We ran our ILP algorithm on 62,219 mammographic abnormalities. We set the Aleph ILP system to generate 10,000 rules per malignant finding with a recall >5% and precision >25%. Aleph reported the best rule for each malignant finding. A total of 80 unique rules were learned. A radiologist reviewed all rules and identified potentially interesting rules. High breast mass density appeared in 24% of the learned rules. We confirmed each interesting rule by calculating the probability of malignancy given each mammographic descriptor. High mass density was the fifth highest ranked predictor. To validate the association between mass density and malignancy in an independent dataset, we collected data from 180 consecutive breast biopsies performed between 2005 and 2007. We created a logistic model with benign or malignant outcome as the dependent variable while controlling for potentially confounding factors. We calculated odds ratios based on dichomotized variables. In our logistic regression model, the independent predictors high breast mass density (OR 6.6, CI 2.5-17.6), irregular mass shape (OR 10.0, CI 3.4-29.5), spiculated mass margin (OR 20.4, CI 1.9-222.8), and subject age (ß = 0.09, p < 0.0001) significantly predicted malignancy. Both ILP and conditional probabilities show that high breast mass density is an important adjunct predictor of malignancy, and this association is confirmed in an independent data set of prospectively collected mammographic findings.

Obesity and impaired barrier function after shock: A biomimetic in vitro model using microfluidics.

BACKGROUND: Impaired microvascular perfusion in the obese patient has been linked to chronic adverse health consequences. The impact on acute illnesses including trauma, sepsis, and hemorrhagic shock (HS) is uncertain. Studies have shown that endothelial glycocalyx and vascular endothelial derangements are causally linked to perfusion abnormalities. Trauma and HS are also associated with impaired microvascular perfusion in which glycocalyx injury and endothelial dysfunction are sentinel events. We postulate that obesity may impact the adverse consequences of HS on the vascular barrier. This was studied in vivo in a biomimetic model of HS using microfluidic technology. METHODS: Human umbilical vein endothelial cell monolayers were established in a microfluidic device. Cells were exposed to standard or biomimetic shock conditions (hypoxia plus epinephrine) followed by perfusion from plasma obtained from obese or nonobese subjects. Endothelial glycocalyx and endothelial cellular injury were then determined. RESULTS: Plasma from nonobese patients completely reversed glycocalyx and endothelial vascular barrier injury. Plasma from obese patients was only partially protective and was associated with differences in adipokines and other substances in the plasma of these patients. CONCLUSION: Our study supports that obesity impairs HS resuscitation. This may be due to microrheological differences between nonobese and obese individuals and may contribute to the poorer outcome in this patient population.

Vastly undersampled isotropic projection steady-state free precession imaging of the knee: diagnostic performance compared with conventional MR.

PURPOSE: To compare a vastly undersampled isotropic projection steady-state free precession (VIPR-SSFP) sequence and routine magnetic resonance (MR) imaging for evaluating the cartilage, ligaments, menisci, and osseous structures of the knee in symptomatic patients. MATERIALS AND METHODS: All subjects signed written informed consent prior to participation in this prospective, HIPAA-compliant, institutional review board-approved study. VIPR-SSFP was added to the routine 1.5-T MR imaging performed on 95 symptomatic patients (52 men, 43 women; average age, 41.6 years) who subsequently underwent arthroscopic knee surgery. All MR examinations were independently reviewed twice by two musculoskeletal radiologists to detect cartilage lesions, anterior and posterior cruciate ligament tears, meniscal tears, and bone marrow edema lesions, first by using routine MR and second by using VIPR-SSFP. By using arthroscopy as the reference standard, the sensitivity and specificity of both MR protocols were calculated. The z test was used to compare sensitivity and specificity values. RESULTS: VIPR-SSFP had significantly higher specificity (P < .01) for helping detect cartilage lesions (92.2% for VIPR-SSFP and 88.4% for routine MR), while routine MR had significantly higher sensitivity (P = .02) and accuracy (P = .05) for helping detect lateral meniscal tears (73.2% sensitivity and 88.4% accuracy for VIPR-SSFP and 87.5% specificity and 93.2% accuracy for routine MR). There was no significant difference (P = .14 to >.99) between VIPR-SSFP and routine MR in the remaining sensitivity and specificity values. VIPR-SSFP helped detect 69.3% of bone marrow edema lesions identified at routine MR. CONCLUSION: VIPR-SSFP can provide important clinical information regarding the cartilage, ligaments, menisci, and osseous structures of the knee, but is less sensitive than conventional MR imaging at helping detect lateral meniscal tears and bone marrow edema lesions.

Comparison of 1.5- and 3.0-T MR imaging for evaluating the articular cartilage of the knee joint.

PURPOSE: To retrospectively compare the diagnostic performance of 1.5- and 3.0-T magnetic resonance (MR) imaging protocols for evaluating the articular cartilage of the knee joint in symptomatic patients. MATERIALS AND METHODS: This HIPAA-compliant study was performed with a waiver of informed consent from the institutional review board. The study group consisted of 200 symptomatic patients undergoing MR examination of the knee at 1.5 T (61 men, 39 women; mean age, 38.9 years) or 3.0 T (52 men, 48 women; mean age, 39.1 years), who also underwent subsequent arthroscopic knee surgery. All MR examinations consisted of multiplanar fast spin-echo sequences with similar tissue contrast at 1.5 and 3.0 T. All articular surfaces were graded at arthroscopy by using the Noyes classification system. Three musculoskeletal radiologists retrospectively and independently graded all articular surfaces seen at MR imaging by using a similar classification system. The sensitivity, specificity, and accuracy of the 1.5- and 3.0-T MR protocols for detecting cartilage lesions were determined by using arthroscopy as the reference standard. The z test was used to compare sensitivity, specificity, and accuracy values at 1.5 and 3.0 T. RESULTS: For all readers combined, the respective sensitivity, specificity, and accuracy of MR imaging for detecting cartilage lesions were 69.3%, 78.0%, and 74.5% at 1.5 T (n = 241) and 70.5%, 85.9%, and 80.1% at 3.0 T (n = 226). The MR imaging protocol had significantly higher specificity and accuracy (P < .05) but not higher sensitivity (P = .73) for detecting cartilage lesions at 3.0 T than at 1.5 T. CONCLUSION: A 3.0-T MR protocol has improved diagnostic performance for evaluating the articular cartilage of the knee joint in symptomatic patients when compared with a 1.5-T protocol.

Endovascular abdominal aortic aneurysm repair: nonenhanced volumetric CT for follow-up.

PURPOSE: To evaluate the clinical usefulness of volumetric analysis at nonenhanced computed tomography (CT) as the sole method with which to follow up endovascular abdominal aortic aneurysm repair (EVAR) and to identify endoleaks causing more than 2% volumetric increase from the previous volume determination. MATERIALS AND METHODS: The study had institutional review board approval. Images were reviewed retrospectively in a HIPAA-compliant manner for 230 CT studies in 70 patients (11 women, 59 men; mean age, 74 years) who underwent EVAR. The scannning protocol consisted of three steps: (a) contrast material-enhanced CT angiography before endovascular stent placement, (b) contrast-enhanced CT angiography 0-3 months after repair to depict immediate complications, and (c) nonenhanced CT at 3, 6, and 12 months after repair. At each follow-up visit, immediate aortic volume analysis was performed. If the interval volumetric change was 2% or less, no further imaging was performed. If the volume increased by more than 2% on the nonenhanced CT image, contrast-enhanced CT angiography was performed immediately to identify the suspected endoleak. Confidence intervals (CIs) were obtained by using bootstrapping to account for repeated measurements in the same patients. RESULTS: Mean volume decrease was -3.2% (95% CI: -4.7%, -1.9%) in intervals without occurrence of a clinically relevant endoleak (n = 183). Types I and III high-pressure endoleaks (n = 10) showed a 10.0% (95% CI: 5.0%, 18.2%) interval volumetric increase. Type II low-pressure endoleaks (n = 37) showed a 5.4% (95% CI: 4.6%, 6.2%) interval volumetric increase. Endoleaks associated with minimal aortic volume increase of less than 2% did not require any intervention. This protocol reduced radiation exposure by approximately 57%-82% in an average-sized patient. CONCLUSION: Serial volumetric analysis of aortic aneurysm with nonenhanced CT serves as an adequate screening test for endoleak, causing volumetric increase of more than 2% from the volume seen at the previous examination.

Comparison of the accuracy rates of 3-T and 1.5-T MRI of the knee in the diagnosis of meniscal tear.

OBJECTIVE: The purpose of this study was to compare the accuracy of 3-T MRI with that of 1.5-T MRI of the knee in the diagnosis of meniscal tear and to analyze the causes of diagnostic error. MATERIALS AND METHODS: We reviewed the medical records and original MRI interpretations of 100 consecutive patients who underwent 3-T MRI of the knee and of 100 consecutive patients who underwent 1.5-T MRI of the knee to determine the accuracy of diagnoses of meniscal tear. Knee arthroscopy was the reference standard. We retrospectively reviewed all MRI diagnostic errors to determine the cause of the errors. RESULTS: At arthroscopy, 109 medial and 77 lateral meniscal tears were identified in the 200 patients. With two abnormal MR images indicating a meniscal tear, the sensitivity and specificity for medial tear were 92.7% and 82.2% at 1.5-T MRI and 92.6% and 76.1% at 3-T MRI (p = 1.0, p = 0.61). The sensitivity and specificity for lateral tears were 68.4% and 95.2% at 1.5-T MRI and 69.2% and 91.8% at 3-T MRI (p = 1.0, p = 0.49). Of the false-positive diagnoses of medial meniscal tear, five of eight at 1.5 T and seven of 11 at 3 T were apparent peripheral longitudinal tears of the posterior horn. Fifteen of the 26 missed medial and lateral meniscal tears were not seen in retrospect even with knowledge of the tear type and location. CONCLUSION: Allowing for sample size limitations, we found comparable accuracy of 3-T and 1.5-T MRI of the knee in the diagnosis of meniscal tear. The causes of false-positive and false-negative MRI diagnoses of meniscal tear are similar for 3-T and 1.5-T MRI.

MR diagnosis of posterior root tears of the lateral meniscus using arthroscopy as the reference standard.

OBJECTIVE: The purpose of our study was to determine whether tears of the posterior root of the lateral meniscus can be diagnosed using standard MR criteria of a meniscal tear in the presence or absence of an anterior cruciate ligament (ACL) tear. MATERIALS AND METHODS: From a series of 559 knee MR examinations with arthroscopic correlation, we selected all 16 proven tears isolated to the posterior root of the lateral meniscus for retrospective blinded review, along with 45 cases of arthroscopically intact lateral meniscal posterior roots. The reviewers categorized whether there was a torn, possibly torn, or intact root based on three specific coronal and three specific sagittal image locations. RESULTS: When all possibly torn roots were considered as torn, the sensitivity and specificity for diagnosis of a root tear were 93% and 89%, respectively. The observers' overall diagnosis of a tear based on all images gave a higher combined sensitivity and specificity than if the diagnosis of a tear had been based on one or any combination of the three coronal and three sagittal locations. Root tears were significantly more common in the presence of an ACL tear (p < 0.0001), but the presence or absence of an ACL tear did not change MR diagnostic accuracy. CONCLUSION: The standard MR criteria of meniscal distortion and signal to the surface can be used to diagnose lateral meniscal root tears. The presence or absence of an ACL tear did not change diagnostic accuracy.

Background fluctuation of kidney function versus contrast-induced nephrotoxicity.

OBJECTIVE: The reported incidence of contrast-induced acute kidney injury varies widely. Almost no studies have been conducted to quantify the background fluctuation of kidney function of patients receiving iodinated contrast medium. The purpose of this study was a retrospective comparison of the incidence of acute kidney injury among patients undergoing CT with low-osmolar (iohexol) or isoosmolar (iodixanol) contrast medium with the incidence among patients undergoing CT without contrast administration. MATERIALS AND METHODS: Creatinine concentration and estimated glomerular filtration rate were evaluated for 11,588 patients. Rates of acute kidney injury (defined as a 0.5 mg/dL increase in serum creatinine concentration or a 25% or greater decrease in estimated glomerular filtration rate within 3 days after CT) were compared among groups and stratified according to creatinine concentration and estimated glomerular filtration rate before the imaging examination. RESULTS: In all groups, the incidence of acute kidney injury increased with increasing baseline creatinine concentration. No significant difference in incidence of presumed contrast-induced kidney injury was identified between the isoosmolar contrast medium and the control groups. The incidence of acute kidney injury in the low-osmolar contrast medium cohort paralleled that of the control cohort up to a creatinine level of 1.8 mg/dL, but increases above this level were associated with a higher incidence of acute kidney injury. CONCLUSION: We identified a high incidence of acute kidney injury among control subjects undergoing unenhanced CT. The incidence of creatinine elevation in this group was statistically similar to that in the isoosmolar contrast medium group for all baseline creatinine values and all stages of chronic kidney disease. These findings suggest that the additional risk of acute kidney injury accompanying administration of contrast medium (contrast-induced nephrotoxicity) may be overstated and that much of the creatinine elevation in these patients is attributable to background fluctuation, underlying disease, or treatment.

Comparison of standard hip MR arthrographic imaging planes and sequences for detection of arthroscopically proven labral tear.

OBJECTIVE: The purpose of this study was to compare multiple imaging planes and two pulse sequences for detection of arthroscopically proven labral tears. MATERIALS AND METHODS: From March 2004 through June 2007, acetabular labral tear was diagnosed at hip arthroscopy of 189 patients. Preoperative MR arthrography of the affected hip was performed on 144 patients at our institution. These MR arthrograms were retrospectively reviewed by a musculoskeletal fellow and two musculoskeletal radiologists. The sequences used were coronal T1-weighted with fat saturation, coronal T2-weighted with fat saturation, sagittal T1-weighted with fat saturation, axial oblique T1-weighted with fat saturation, sagittal oblique T1-weighted with fat saturation, and axial T1-weighted. Using consensus, the reviewers evaluated images obtained with each sequence for the presence of a tear, number of slices on which a tear was seen, and the signal intensity of the tear. RESULTS: Among the 144 tears, 97.2% were identified as definitely present on images obtained with at least one of the sequences. The axial oblique sequence had the highest individual detection rate (85.0%). The detection rates for the sagittal T1-weighted (74.6%), coronal T1-weighted (67.4%), and coronal T2-weighted (63.6%) sequences were intermediate. Detection rates with the axial T1-weighted (29.9%) and sagittal oblique (18.2%) sequences were low. With the combination of three sequences (coronal T2-weighted with fat saturation, axial oblique T1-weighted with fat saturation, and sagittal T1-weighted with fat saturation), 95.8% of the 144 tears were identified as definitely present. Twenty-eight percent of tears had a signal intensity less than that of gadolinium or fluid. CONCLUSION: Imaging in the axial oblique plane has the highest rate of detection of acetabular labral tears. More than 95% of tears were identified with the use of three imaging planes. Signal intensity within a tear does not have to be equal to that of gadolinium or fluid to confirm the diagnosis of labral tear.

Live cell measurements of interaction forces and binding kinetics between Discoidin Domain Receptor 1 (DDR1) and collagen I with atomic force microscopy.

BACKGROUND: Discoidin Domain Receptors (DDRs) are membrane-tethered proteins of the receptor tyrosine kinase family, which signal in response to collagen. DDR expression is associated with human diseases, including fibrosis and cancer. The role of DDRs in human pathogenesis is mediated by dysregulated receptor function in response to the collagenous milieu. Thus, understanding DDR-collagen interactions is important for developing novel therapeutic strategies against DDRs. METHODS: We developed a biophysical method to isolate and measure specific interactions between DDR1 and collagen in live cells at the single molecule level using atomic force microscopy. This new method is capable of providing density and kinetics of membrane receptors in live cells. RESULTS: We isolated DDR1-collagen interactions and quantified the association and dissociation rates of the DDR1-collagen I complex. We estimated separate binding probabilities of collagen I to DDR and integrin, and by combining kinetic and binding probability data, we were able to estimate the density of receptors in two cancer cell types. We also tested the viability of a DDR1 blocking antibody and determined its efficacy in suppressing DDR1-collagen binding. CONCLUSIONS: The new method shows promise in quantifying receptor-ligand kinetics and receptor density on live cells. GENERAL SIGNIFICANCE: The new approach is applicable to other receptor-ligand systems and allows the determination of critical parameters at the single cell/single molecule level - in particular, the direct determination of kinetic and density differences of receptors in different cell types. This capability should prove to be useful in cancer research and drug design.

Juvenile versus adult osteochondritis dissecans of the knee: appropriate MR imaging criteria for instability.

PURPOSE: To retrospectively compare the sensitivity and specificity of previously described magnetic resonance (MR) imaging criteria for the detection of instability in patients with juvenile or adult osteochondritis dissecans (OCD) of the knee, with arthroscopic findings as the reference standard. MATERIALS AND METHODS: Informed consent was waived by the Institutional Review Board for this HIPAA-compliant study. The study group consisted of 32 skeletally immature patients (25 boys, seven girls; mean age, 14.4 years) with 36 juvenile OCD lesions of the knee and 33 skeletally mature patients (25 men, eight women; mean age, 26.2 years) with 34 adult OCD lesions of the knee. All patients had been evaluated with MR imaging and arthroscopy. MR studies were retrospectively reviewed by two radiologists in consensus to determine the presence of previously described MR imaging criteria for OCD instability (ie, high T2 signal intensity rim, surrounding cysts, high T2 signal intensity cartilage fracture line, and fluid-filled osteochondral defect). Sensitivity and specificity of the criteria were calculated separately for juvenile and adult OCD lesions. RESULTS: Separately, previously described MR imaging criteria for detection of OCD instability were 0%-88% sensitive and 21%-100% specific for juvenile OCD lesions and 27%-54% sensitive and 100% specific for adult OCD lesions. When used together, the criteria were 100% sensitive and 11% specific for instability in juvenile OCD lesions and 100% sensitive and 100% specific for instability in adult OCD lesions. CONCLUSION: Previously described MR imaging criteria for OCD instability have high specificity for adult but not juvenile lesions of the knee.

Aneurysm volume-to-ostium area ratio: a parameter useful for discriminating the rupture status of intracranial aneurysms.

BACKGROUND: Slow or stagnant flow is a hemodynamic feature that has been linked to the risk of aneurysm rupture. OBJECTIVE: To assess the potential value of the ratio of the volume of an aneurysm to the area of its ostium (VOR) as an indicator of intra-aneurysmal slow flow and, thus, in turn, the risk of rupture. METHODS: Using a sample defined from internal databases, a retrospective analysis of aneurysm size, aspect ratio (AR), and VOR was performed on a series of 155 consecutive aneurysms having undergone 3-dimensional digital subtraction angiography as a part of their evaluation. Measurements were obtained from 3-dimensional digital subtraction angiography studies using commercial software. Aneurysm size, AR, and VOR were correlated with rupture status (ruptured or unruptured). A multiple logistic regression model that best correlated with rupture status was generated to evaluate which of these parameters was the most useful to discriminate rupture status. This model was validated using an independent database of 62 consecutive aneurysms acquired outside the retrospective study interval. RESULTS: VOR showed better discrimination for rupture status than did size and AR. The best logistic regression model, which included VOR rather than size or AR, determined rupture status correctly in 80.6% of subjects. The reproducibility calculating AR and VOR was excellent. CONCLUSION: Determination of VOR was easily done and reproducible using widely available commercial equipment. It may be a more robust parameter to discriminate rupture status than AR.

Decline in rheumatoid vasculitis prevalence among US veterans: a retrospective cross-sectional study.

OBJECTIVE: To examine trends in the prevalence of rheumatoid vasculitis in a national US population comprising both hospitalized and ambulatory patients with rheumatoid arthritis (RA). METHODS: In this serial cross-sectional study, we analyzed data on hospitalized and ambulatory patients spanning 22 years (1985-2006) and 10 years (1997-2006), respectively, to determine the prevalence of rheumatoid vasculitis, as defined by the International Classification of Diseases, Ninth Revision. Our search encompassed data collected on a predominantly male study population during 10 million hospitalizations and outpatient visits, and included annual data on >37,000 RA patients. To test for a decrease in rheumatoid vasculitis prevalence, breakpoint analysis was performed using stepwise Chow and Durbin-Watson tests. RESULTS: There was a clear decline in the prevalence of rheumatoid vasculitis, and this decline remained evident even after accounting for a decreased number of hospitalizations among RA patients. Peak prevalence occurred among hospitalized patients in the 1980s, and prevalence gradually declined throughout the 1990s. Furthermore, simultaneous breakpoints representing a significant drop in rheumatoid vasculitis prevalence between the years 2000 and 2001 were demonstrated for both inpatients (P < 0.000) and outpatients (P < 0.003). The prevalence of vasculitis dropped 53% among inpatients and 31% among outpatients between 2000 and 2001. CONCLUSION: Our results demonstrate a significant decline in rheumatoid vasculitis prevalence after 2000 in this nationwide sample of hospitalized and ambulatory patients. The clear, consistent drop in prevalence provides an opportunity for the formulation of causal hypotheses, including consideration of the impact of biologic agents used to treat RA, on rheumatoid vasculitis.