Plasma glycosaminoglycan scores in early stage renal cell carcinoma

Introduction & Objectives No diagnostic blood biomarker for RCC is currently used in the clinical routine. Using a systems biology approach, we previously developed a score based on circulating glycosaminoglycans (GAGs) that detected metastatic clear cell renal cell carcinoma (RCC) with 92.6%, 93.7%, and 100% accuracy vs. healthy subjects using either plasma, urine, or combined measurements in a validation cohort (Gatto et al., 2016, Cell Reports). It is still unknown if this test is accurate in early stage RCC or other RCC histologies. The primary endpoint of this study was the area-under-thecurve (AUC) in the use of plasma GAG scores to detect pre-operative RCC, any stage and any histology, versus healthy individuals

Manifolds with small Dirac eigenvalues are nilmanifolds

Consider the class of n-dimensional Riemannian spin manifolds with bounded sectional curvatures and diameter, and almost non-negative scalar curvature. Let r=1 if n=2,3 and r=2^{[n/2]-1}+1 if n\geq 4. We show that if the square of the Dirac operator on such a manifold has $r$ small eigenvalues, then the manifold is diffeomorphic to a nilmanifold and has trivial spin structure. Equivalently, if M is not a nilmanifold or if M is a nilmanifold with a non-trivial spin structure, then there exists a uniform lower bound on the r-th eigenvalue of the square of the Dirac operator. If a manifold with almost nonnegative scalar curvature has one small Dirac eigenvalue, and if the volume is not too small, then we show that the metric is close to a Ricci-flat metric on M with a parallel spinor. In dimension 4 this implies that M is either a torus or a K3-surface

Plasma Glycosaminoglycans as Diagnostic and Prognostic Biomarkers in Surgically Treated Renal Cell Carcinoma

Plasma glycosaminoglycan (GAG) measurements, when aggregated into diagnostic scores, accurately distinguish metastatic clear-cell renal cell carcinoma (RCC) from healthy samples and correlate with prognosis. However, it is unknown if GAG scores can detect RCC in earlier stages or if they correlate with prognosis after surgery. Objective: To explore the sensitivity and specificity of plasma GAGs for detection of early-stage RCC and prediction of recurrence and death after RCC surgery. Design, setting, and participants: This was a retrospective case-control study consisting of a consecutive series of 175 RCC patients surgically treated between May 2011 and February 2014 and 19 healthy controls. Outcome measurements and statistical analysis: Plasma GAGs in preoperative and postoperative RCC and healthy samples were measured using capillary electrophoresis with laser-induced fluorescence in a single blinded laboratory. A discovery set was first analyzed to update the historical GAG score. The sensitivity of the new GAG score for RCC detection versus healthy subjects was validated using the remaining samples. The correlation of the new GAG score to histopathologic variables, overall survival, and recurrence-free survival was evaluated using nonparametric and log-rank tests and multivariable Cox regression analyses. Results and limitations: The RCC cohort included 94 stage I, 58 stage II–III, and 22 stage IV cases. In the first discovery set (n = 67), the new GAG score distinguished RCC from healthy samples with an area under the receiver operating characteristic curve (AUC) of 0.999. In the validation set (n = 108), the GAG score achieved an AUC of 0.991, with 93.5% sensitivity. GAG scores were elevated in RCC compared to healthy samples, irrespective of and uncorrelated to stage, grade, histology, age, or gender. The total chondroitin sulfate concentration was an independent prognostic factor for both overall and recurrence-free survival (hazard ratios 1.51 and 1.25) with high concordance when combined with variables available at pathologic diagnosis (C-index 0.926 and 0.849) or preoperatively (C-index 0.846 and 0.736). Limitations of the study include its retrospective nature and moderate variability in GAG laboratory measurements. Conclusions: Plasma GAGs are highly sensitive diagnostic and prognostic biomarkers in surgically treated RCC independent of stage, grade, or histology. Prospective validation studies on GAG scores for early detection, prediction, and surveillance for RCC recurrence are thus warranted. Patient summary: In this study, we examined if a new molecular blood test can detect renal cell carcinoma in the early stages and predict if the cancer might relapse after surgery. The trial is registered on ClinicalTrial.gov as NCT03471897. Plasma glycosaminoglycan measurements aggregated into scores had higher sensitivity for the detection of any-stage renal cell carcinoma and high concordance with survival after surgery

Survey of culture and antibiogram in patients with impetigo

Background: Impetigo is a common infectious skin disease and most commonly occurs in children. Etiologic agents are Staphylococcus aureus or Beta-heamolytic Streptococcus group A or combination of these organisms. Adequacy of treatment is related on sensitivity of bacteria to common prescribed antibiotics.Methods: Study of the frequency of bacterial culture results from lesions and antibiograms for four systemic antibiotics cephalexin, erythromycin, cloxacillin and penicillin were assayed. Impetigo cases admitted to the dermatology clinic of Ghaem hospital in Mashhad for one year beginning from June 2001, were studied. These patients had no history of systemic or topical antimicrobial agents application. Results of antibiograms obtained from culture of skin lesions were analyzed with Chi-Square test.Findings: Twenty two (88%) patients were younger than 20 years. Twenty one cases (84%) had non bullous impetigo. In 17 (68%) cases lesions were localized on the face. Because of secondary contamination in 3 cases, statistical analysis was performed on 22 cases. The most common bacteria (95.5%) was Staphylococcus aureus. Antibiograms of S.aureus showed complete sensitivity to cephalxin in 85.3%, erythromycin in 63.6%, cloxacillin in 40.9%, and penicillin in 13.6% of cases. Conclusions: Staphylococcus aureus was the most common organism in 95.5% of cases and cephalexin was the first choice oral antibiotic followed by erythromycin

Cystic Renal Cell Carcinoma: A Report on Outcomes of Surgery and Active Surveillance in Patients Retrospectively Identified on Pretreatment Imaging

PURPOSE We evaluated the outcomes of surgical intervention and active surveillance in patients diagnosed with cystic renal cell carcinoma at our hypothesized radiological cutoff of greater than 50% cystic. MATERIALS AND METHODS We identified all 430 patients with a pathologically confirmed cystic renal mass that fit our criteria from 2000 to 2015. The 292 patients with a lack of computerized tomography, tumors less than 50% cystic on imaging, multifocal tumors and prior renal cell carcinoma were excluded from study. Patients were stratified into benign or malignant subgroups, and radiological, clinicopathological and oncologic features were determined. Univariate and multivariate associations between clinicoradiological parameters in each group were analyzed. We similarly reviewed the records of a separate cohort of patients treated with active surveillance for cystic renal cell carcinoma. RESULTS Of the 138 identified cases of cystic renal cell carcinoma 102 (73.9%) were renal cell carcinoma and 36 (26.1%) were benign masses. Of the tumors 77.5% were Fuhrman grade 1-2, 83.4% were stage pT2 or less and 65.9% showed clear cell histology. On univariate analysis male gender, a solid component and increasing Bosniak classification were significant for malignancy. In a separate cohort we identified 38 patients on active surveillance. The growth rate was 1.0 mm per year overall and 2.3 mm per year for the solid component. At a median followup of more than 4 years in all cohorts there was no evidence of recurrence or metastasis of cystic renal cell carcinoma. CONCLUSIONS Patients with unifocal cystic renal cell carcinoma evaluated using a standardized radiological threshold of greater than 50% cystic had an excellent prognosis on active surveillance and after surgical resection