Value of positron emission tomography in staging ocular adnexal lymphomas and evaluating their response to therapy.

BACKGROUND AND OBJECTIVE: An observational case series to assess the value of positron emission tomography (PET) in staging ocular adnexal lymphomas and evaluating their response to therapy. PATIENTS AND METHODS: The clinical records of 16 consecutive patients with ocular adnexal lymphoma for whom pretreatment and posttreatment PET scans and corresponding computed tomography (CT) and magnetic resonance imaging (MRI) scans were available were compared. RESULTS: Pretreatment PET scans demonstrated fluorine 18-fluorodeoxyglucose (FDG) positive lesions in 15 orbits of 12 patients. In 1 patient with low-grade follicular lymphoma of the orbit, PET revealed an additional focus of lymphoma in the deltoid muscle that was missed on clinical examination and conventional radiography. All of the posttreatment PET scans showed complete resolution of FDG uptake, suggesting good response to therapy. However, posttreatment CT and MRI scans demonstrated residual masses in 3 patients. CONCLUSIONS: PET is valuable for initial staging of ocular adnexal lymphomas and may be a good adjunct to conventional imaging in evaluation of response to therapy.     

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Augmentation of Shoulder Contour Using a Calf Implant

Sprengel deformity is a rare orthopedic condition that is associated with functional and cosmetic impairment. Results of orthopedic procedures are usually inconsistent and cosmetic results are far from satisfactory in these patients. A silicone-gel-filled calf prosthesis was used to correct the shoulder contour in a patient with Sprengel deformity. Cosmetically the deformity can be restored by using a calf implant for patients in whom orthopedic procedures are not likely to yield a satisfactory outcome.     

Toxicity of thallium on isolated rat liver mitochondria: The role of oxidative stress and MPT pore opening

Thallium(I) is a highly toxic heavy metal; however, up to now, its mechanisms are poorly understood. The authors' previous studies showed that this compound could induce reactive oxygen species (ROS) formation, reduced glutathione (GSH) oxidation, membrane lipid peroxidation, and mitochondrial membrane potential (MMP) collapse in isolated rat hepatocyte. Because the liver is the storage site of thallium, it seems that the liver mitochondria are one of the important targets for hepatotoxicity. In this investigation, the effects of thallium on mitochondria were studied to investigate its mechanisms of toxicity. Mitochondria were isolated from rat liver and incubated with different concentrations of thallium (25–200 µM). Thallium(I)‐treated mitochondria showed a marked elevation in oxidative stress parameters accompanied by MMP collapse when compared with the control group. These results showed that different concentrations of thallium (25–200 µM) induced a significant (P < 0.05) increase in mitochondrial ROS formation, ATP depletion, GSH oxidation, mitochondrial outer membrane rupture, mitochondrial swelling, MMP collapse, and cytochrome c release. In general, these data strongly supported that the thallium(I)‐induced liver toxicity is a result of the disruptive effect of this metal on the mitochondrial respiratory complexes (I, II, and IV), which are the obvious causes of metal‐induced ROS formation and ATP depletion. The latter two events, in turn, trigger cell death signaling via opening of mitochondrial permeability transition pore and cytochrome c expulsion. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 232–241, 2015.     

Surface Curvature as a Classifier of Abdominal Aortic Aneurysms: A Comparative Analysis

An abdominal aortic aneurysm (AAA) carries one of the highest mortality rates among vascular diseases when it ruptures. To predict the role of surface curvature in rupture risk assessment, a discriminatory analysis of aneurysm geometry characterization was conducted. Data was obtained from 205 patient-specific computed tomography image sets corresponding to three AAA population subgroups: patients under surveillance, those that underwent elective repair of the aneurysm, and those with an emergent repair. Each AAA was reconstructed and their surface curvatures estimated using the biquintic Hermite finite element method. Local surface curvatures were processed into ten global curvature indices. Statistical analysis of the data revealed that the L2-norm of the Gaussian and Mean surface curvatures can be utilized as classifiers of the three AAA population subgroups. The application of statistical machine learning on the curvature features yielded 85.5% accuracy in classifying electively and emergent repaired AAAs, compared to a 68.9% accuracy obtained by using maximum aneurysm diameter alone. Such combination of non-invasive geometric quantification and statistical machine learning methods can be used in a clinical setting to assess the risk of rupture of aneurysms during regular patient follow-ups.