Association Between Lateral Posterior Tibial Slope, Body Mass Index, and ACL Injury Risk.

BACKGROUND: While body mass index (BMI), a modifiable parameter, and knee morphology, a nonmodifiable parameter, have been identified as risk factors for anterior cruciate ligament (ACL) rupture, the interaction between them remains unknown. An understanding of this interaction is important because greater compressive axial force (perhaps due to greater BMI) applied to a knee that is already at an increased risk because of its geometry, such as a steep lateral posterior tibial slope, could further increase the probability of ACL injury. PURPOSE: To quantify the relationship between BMI and select knee morphological parameters as potential risk factors for ACL injury. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Sagittal knee magnetic resonance imaging (MRI) files from 76 ACL-injured and 42 uninjured subjects were gathered from the University of Michigan Health System's archive. The posterior tibial slope (PTS), middle cartilage slope (MCS), posterior meniscus height (PMH), and posterior meniscus bone angle (MBA) in the lateral compartment were measured using MRI. BMI was calculated from demographic data. The association between the knee structural factors, BMI, and ACL injury risk was explored using univariate and multivariate logistic regression. RESULTS: PTS (P = .043) and MCS (P = .037) significantly predicted ACL injury risk. As PTS and MCS increased by 1°, odds of sustaining an ACL injury increased by 12% and 13%, respectively. The multivariate logistic regression analysis, which included PTS, BMI centered around the mean (cBMI), and their interaction, showed that this interaction predicted the odds of ACL rupture (P = .050; odds ratio, 1.03). For every 1-unit increase in BMI from the average that is combined with a 1° increase in PTS, the odds of an ACL tear increased by 15%. CONCLUSION: An increase in BMI was associated with increased risk of ACL tear in the presence of increased lateral posterior tibial slope. Larger values of PTS or MCS were associated with an increased risk of ACL tear.

RasIns: Genetically Encoded Intrabodies of Activated Ras Proteins.

K- and H-Ras are the most commonly mutated genes in human tumors and are critical for conferring and maintaining the oncogenic phenotype in tumors with poor prognoses. Here, we design genetically encoded antibody-like ligands (intrabodies) that recognize active, GTP-bound K- and H-Ras. These ligands, which use the 10th domain of human fibronectin as their scaffold, are stable inside the cells and when fused with a fluorescent protein label, the constitutively active G12V mutant H-Ras. Primary selection of ligands against Ras with mRNA display resulted in an intrabody (termed RasIn1) that binds with a KD of 2.1µM to H-Ras(G12V) (GTP), excellent state selectivity, and remarkable specificity for K- and H-Ras. RasIn1 recognizes residues in the Switch I region of Ras, similar to Raf-RBD, and competes with Raf-RBD for binding. An affinity maturation selection based on RasIn1 resulted in RasIn2, which binds with a KD of 120nM and also retains excellent state selectivity. Both of these intrabodies colocalize with H-Ras, K-Ras, and G12V mutants inside the cells, providing new potential tools to monitor and modulate Ras-mediated signaling. Finally, RasIn1 and Rasin2 both display selectivity for the G12V mutants as compared with wild-type Ras providing a potential route for mutant selective recognition of Ras.

Validation of the Preoperative Platelet-to-Lymphocyte Ratio as a Prognostic Factor in a European Cohort of Patients with Upper Tract Urothelial Carcinoma.

INTRODUCTION: This study is aimed at investigating the potential prognostic impact of the preoperatively assessed platelet-to-lymphocyte ratio (PLR) in a European cohort of patients with non-metastatic upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Clinicopathological data from 180 consecutive non-metastatic UTUC patients, operated between 1990 and 2012 at a single tertiary academic center, were evaluated retrospectively. The preoperative PLR was assessed one day before surgery. Patients were categorized using a PLR cut-off value according to receiver-operating curve analysis. Cancer-specific survival (CSS) and overall survival (OS) were assessed using the Kaplan-Meier method. Additionally, multivariate proportional Cox regression models were applied. RESULTS: In multivariate analyses, age at the date of surgery (<65 vs. ≥65 years, hazard ratio (HR) 1.827, 95% CI 1.051-3.175, p = 0.033), pathologic T-stage (pT1 vs. pT2-4, HR 1.873, 95% CI 1.066-3.292, p = 0.029), and pretreatment PLR (<150.0 vs. ≥150.0, HR 1.782, 95% CI 1.041-3.050, p = 0.035) were independent predictors of OS. Regarding CSS, pathologic T-stage (pT1 vs. pT2-4, HR 2.176, 95% CI 1.062-4.460, p = 0.034) and pretreatment PLR (<150.0 vs. ≥150.0, HR 2.026, 95% CI 1.045-3.930, p = 0.037) were considered independent predictors. CONCLUSIONS: In the cohort studied, patients with an elevated (≥150.0) preoperative PLR had a higher cancer-specific mortality and overall mortality after radical surgery for UTUC, compared with those with a low pretreatment PLR.

A radiologist's guide to the clinical scales used in the 2015 Endovascular Stroke Trials and the Revised American Heart Association/American Stroke Association Guidelines for Endovascular Stroke Treatment.

In 2015, five trials demonstrated the efficacy of endovascular treatment for acute stroke, culminating in the revised American Heart Association/American Stroke Association (AHA/ASA) recommendations for stroke management. The different clinical scales used in these trials may be unfamiliar to emergency and on-call radiologists. The modified Rankin Scale was used to describe patient disability for prestroke assessment in three of the trials and for the 90-day follow up in all five trials. The Barthel index was used in one trial to score prestroke ability to perform activities of daily living. The NIH Stroke Scale was used as part of eligibility criteria in four of the stroke trials to assess pre-existing neurological deficits. Also, the modified Rankin Scale and the NIH Stroke Scale are used in the revised AHA/ASA recommendations. By understanding these scales, emergency and on-call radiologists will better appreciate the stroke patient's condition and will be able to more actively collaborate in the care of acute stroke patients.

Magnetic Resonance Imaging in Ischemic Stroke and Cerebral Venous Thrombosis.

Imaging is indispensable in the evaluation of patients presenting with central nervous system emergencies. Although computed tomography (CT) is the mainstay of initial assessment and triage, magnetic resonance imaging (MRI) has become vital in expanding diagnostic capabilities, refining management strategies, and developing our understanding of disease processes. Ischemic stroke and cerebral venous thrombosis are 2 areas wherein MRI is actively revolutionizing patient care. Familiarity with the imaging manifestations of these 2 disease processes is crucial for any radiologist reading brain MR studies. In this review, the fundamentals of image interpretation will be addressed in-depth. Furthermore, advanced imaging techniques which are redefining the role of emergency MRI will be outlined, with a focus on the pathophysiological mechanisms that underlie image interpretation. In particular, emerging data surrounding the use of MR perfusion imaging in acute stroke management portend dramatic shifts in neurointerventional management. To this end, a review of the recent stroke literature will hopefully enhance the radiologist's role in both meaningful reporting and multidisciplinary teamwork.

Preoperative Leucocytosis, Thrombocytosis and Anemia as Potential Prognostic Factors in Non-metastatic Renal Cell Carcinoma.

BACKGROUND: To validate the potential prognostic significance of preoperatively assessed inflammatory parameters leucocytosis, thrombocytosis and anemia in patients with non-metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: We retrospectively evaluated a cohort comprising 736 consecutive patients with non-metastatic RCC, operated on between 2004 and 2012 with curative radical or partial nephrectomy at a single tertiary academic centre. Laboratory parameters were assessed within one week before surgical intervention. Patients were categorized using laboratory parameter cut-off values according to receiver operating characteristics (ROC) analyses. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. To evaluate the potential prognostic significance of the preoperative laboratory parameters, multivariate Cox regression models were applied. RESULTS: Multivariable analysis identified preoperative thrombocytosis (≥285,000/µl) as an independent prognostic factor for CSS (Hazard ratio=2.28, 95% confidence interval=1.24-4.20, p=0.008). CONCLUSION: Regarding CSS, an elevated preoperative platelet count represented an independent prognostic factor of poor survival. Our findings strengthen the potential prognostic significance of preoperative thrombocytosis in patients with non-metastatic RCC.

Preoperative serum-gamma-glutamyltransferase (GGT) does not represent an independent prognostic factor in a European cohort of patients with non-metastatic renal cell carcinoma.

AIMS: Increasing evidence suggests that the serum-gamma-glutamyltransferase (GGT) might correlate with tumour development and growth rates in various human cancer types. Thus, we decided to investigate the potential prognostic impact of the preoperatively assessed serum-GGT in a European cohort of patients with non-metastatic renal cell carcinoma (RCC). METHODS: Clinicopathological data from 700 consecutive patients with non-metastatic RCC, operated between 2000 and 2010 at a single tertiary academic centre, were evaluated retrospectively. Preoperative serum-GGT was assessed 1 day before surgery. Patients were categorised using a serum-GGT cut-off value of 40 U/L according to a calculation by receiver operating curve analysis. Patients' cancer-specific survival (CSS), metastasis-free survival (MFS), as well as overall survival (OS) were assessed using the Kaplan-Meier method and Cox proportional models. RESULTS: In univariate analysis, an elevated preoperative serum-GGT level (<40 U/L vs ≥40 U/L) was statistically significantly associated with a shorter MFS (HR=1.517, 95% CI 1.047 to 2.197, p=0.027). In multivariate analyses, pathological T-Stage (pT-1 vs pT-2-4, HR=2.065, 95% CI 1.665 to 2.560), tumour grade (G-1+G-2 vs G-3+G-4, HR=1.671, 95% CI 1.261 to 2.213), as well as the presence of histological tumour necrosis (No vs Yes, HR=2.031, 95% CI 1.355 to 3.046) were independent predictors of MFS in patients with RCC, whereas the preoperative serum-GGT failed to reach independent predictor status (<40 U/L vs ≥40 U/L, HR=1.156, 95% CI 0.791 to 1.690). No prognostic role for GGT in OS or CSS could be identified. CONCLUSIONS: In the cohort studied, patients with an elevated (≥40 U/L) preoperative serum-GGT had a subsequently shorter MFS only in univariate analysis. In contrast to previous studies, our data failed to demonstrate preoperatively assessed serum-GGT as an independent prognostic factor in patients with non-metastatic RCC.

The Preoperative AST/ALT (De Ritis) Ratio Represents a Poor Prognostic Factor in a Cohort of Patients with Nonmetastatic Renal Cell Carcinoma.

PURPOSE: Aminotransaminases, which are strongly involved in cellular metabolism and cancer cell turnover, represent easily measureable, potential blood based biomarkers. We evaluated the prognostic value of the preoperatively assessed AST/ALT (De Ritis) ratio on clinically meaningful end points in a large European cohort of patients with nonmetastatic renal cell carcinoma. MATERIALS AND METHODS: We retrospectively evaluated clinicopathological data on 698 patients with nonmetastatic renal cell carcinoma operated on between 2005 and 2013 at a single tertiary academic center. The potential prognostic value of the AST/ALT ratio was analyzed using the Kaplan-Meier method, and univariate and multivariate Cox proportional regression models. The impact of the ratio on the predictive accuracy of the Leibovich prognosis score was determined by the Harrell c-index. RESULTS: An increased (1.26 or greater) preoperative AST/ALT ratio was statistically significantly associated with several well established prognostic factors, including pathological T stage, as well as with histological tumor necrosis (p <0.05). On multivariate analysis an increased preoperative AST/ALT ratio was an independent prognostic factor for metastasis-free survival (HR 1.61, 95% CI 1.25-2.07, p <0.001) and overall survival (HR 1.76, 95% CI 1.34-2.32, p <0.001). The Harrell c-index was 0.77 using the Leibovich prognosis score and 0.81 when AST/ALT was added. CONCLUSIONS: In our study cohort with nonmetastatic renal cell carcinoma the preoperatively assessed AST/ALT ratio represented an independent prognostic factor. This ratio might further improve the predictive accuracy of well established prognosis scores.

The role of HIV serostatus disclosure in antiretroviral medication adherence.

This study examined the relationship between HIV serostatus disclosure and adherence to antiretroviral therapy (ART). The study was conducted with 215 HIV-seropositive patients who demonstrated poor adherence (<80%) and who were in serodiscordant relationships. Participants completed self-report measures regarding HIV serostatus disclosure and reasons for missing ART doses, as well as electronic monitoring of ART adherence (MEMS caps). Overall, 19% of the sample reported missing medication doses in the last two months due to concerns regarding serostatus disclosure. Participants who reported greater serostatus disclosure to others demonstrated higher rates of adherence, and this relationship remained after controlling for other explanatory variables. The relationship between disclosure and adherence was not mediated by practical support for adherence from others. Interventions to improve ART adherence should address the role of serostatus disclosure by providing patients with skills to maintain adherence in contexts of non-disclosure and to make informed choices regarding selective disclosure.