Posterior Cruciate Ligament and Patellar Tendon Can Predict Anterior Cruciate Ligament Size for Planning During ACL Reconstruction in Pediatric Patients.

Purpose: To establish correlations between the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and patellar tendon in normal pediatric knees to inform surgical planning for ACL reconstruction graft size. Methods: Magnetic resonance imaging scans of patients ages 8 to 18 years were assessed. Measurements included ACL and PCL length, thickness, and width, and ACL footprint thickness and width at the tibial insertion. Interrater reliability was assessed with a random set of 25 patients. Pearson correlation coefficients were used to assess the correlation between ACL, PCL, and patellar tendon measurements. Linear regression models were used to test whether the relationships differed by sex or age. Results: Magnetic resonance imaging scans of 540 patients were assessed. Interrater reliability was high for all measurements except PCL thickness at midsubstance. Sample equations for estimating ACL size are as follows: ACL length = 22.61 + 1.55∗PCL origin width (R2 = 0.46; 8- to 11-year-old male patients), ACL length = 12.37 + 0.58∗PCL length + 2.29∗PCL origin thickness - 0.90∗PCL insertion width (R2 = 0.68; 8- to 11-year-old female patients), ACL midsubstance thickness = 4.95 + 0.25∗PCL midsubstance thickness + 0.04∗PCL insertion thickness - 0.08∗PCL insertion width (R2 = 0.12; 12- to 18-year-old male patients), and ACL midsubstance width = 0.57 + 0.23∗PCL midsubstance thickness + 0.07∗PCL midsubstance width + 0.16∗PCL insertion width (R2 = 0.24; 12- to 18-year-old female patients). Conclusions: We found correlations between ACL, PCL, and patellar tendon measurements that can be used to create equations that predict ACL size in various dimensions based on PCL and patellar tendon measurements. Clinical Relevance: There is a lack of consensus on the ideal ACL graft diameter for pediatric ACL reconstruction. The findings from this study can assist orthopaedic surgeons to individualize ACL graft size for specific patients.

A sulfone-based strategy for the preparation of 2,4-disubstituted furan derivatives.

2,4-Disubstituted furans are prepared by treating 2,3-dibromo-1-phenylsulfonyl-1-propene (DBP, 2) with 1,3-diketones under basic conditions. The furan-forming step involves a deacetylation, and the selectivity of this process depends upon the steric demand of the R group. The substituent in position 4 is elaborated by reaction of sulfonyl carbanions with alkyl halides, acyl halides, and aldehydes. Oxidative or reductive desulfonylation produces the 2,4-disubstituted furans in 60-92% yield. This strategy has been used to prepare rabdoketone A (12) and the naturally occurring nematotoxic furoic acid 13.

Overexpression of EPH receptor B2 in malignant mesothelioma correlates with oncogenic behavior.

INTRODUCTION: Malignant pleural mesothelioma (MM) is an aggressive asbestos-associated malignancy with limited therapeutic options. This study describes the overexpression of Ephrin B2 receptor (EPHB2) in MM cell lines and tumors, and the effect of its manipulation on proliferative and invasive qualities of the disease. METHODS: Using expression arrays, we investigated EPHB2 in MM tumors compared with normal mesothelium. EPHB2 and downstream target expression were evaluated using reverse-transcriptase polymerase chain reaction and immunoblotting methods. The biological significance of EPHB2 in MM was evaluated using in vitro functional assays with and without targeting by EPHB2-short hairpin RNA or blocking peptide in two mesothelioma cell lines, HP-1 and H2595. RESULTS: EPHB2 is overexpressed in all MM cell lines, but not in benign mesothelial cells, and is significantly elevated in MM tumor tissue compared with matched normal peritoneum. Targeted knockdown of EPHB2 in HP-1 and H2595 cell lines reduced its expression and that of EPHB2 downstream targets such as matrix metalloproteinase (MMP-2) and vascular endothelial growth factor, whereas caspase 2 and caspase 8 had increased expression. Inhibition of EPHB2 resulted in a significant decrease in scratch closure (1.25-fold-1.8-fold), proliferation (1.5-fold), and invasion (1.7-fold-1.8-fold) compared with the controls. Most notably, however, EPHB2 silencing resulted in a significant increase in apoptotic proteins and activity. CONCLUSION: EPHB2 seems to play an important role in MM pathogenesis and these findings indicate that EPHB2 could serve as a potential novel therapeutic target for treatment of the disease.

Plasma osteopontin velocity differentiates lung cancers from controls in a CT screening population.

INTRODUCTION: As CT screening is integrated into non-small cell lung cancer (NSCLC) care, additional parameters are needed to help distinguish cancers from benign nodules. Osteopontin (OPN), a secreted phosphoprotein, has elevated plasma levels in NSCLC. We hypothesize that changes in plasma OPN over time (i.e., OPN velocity [OPNV]) can differentiate NSCLC patients from those without cancer in a CT screening population. METHODS: A nested case-control study was conducted within a NSCLC CT screening trial. Incident cancers with serial plasma were matched to controls. OPN was measured by ELISA. Demographic, OPN, and OPNV were compared between cancers and controls using Wilcoxon Signed Rank tests. RESULTS: Ten incident cancers were identified. The pack years distributions were similar, but cancers were older (median of the paired difference: 5.35 years; p=0.002) and their surveillance intervals were shorter (median of the paired difference: -2 months; p=0. 03) than matched controls. Baseline OPN was similar (median of the paired difference: -5.15 ng/ml, p=0.50), but OPNV in the cancers was significantly greater than that of matched controls, (median of the paired difference: 1.06 ng/ml/month, p=0.01). Accuracy rate for prediction of disease status based on OPNV (adjusted for age and surveillance) was 83%. CONCLUSIONS: These are early evidence for utility of monitoring plasma OPN during CT screening to assist in identification of NSCLCs.