Could the Combination of eGFR and mGPS Facilitate the Differential Diagnosis of Age-Related Renal Decline from Diseases? A Large Study on the Population of Western Sicily

The assessment of renal function is critical to diagnosing and managing renal age-related decline, disease (KD), and failure, which are prevalent in the elderly population. The glomerular filtration rate (GFR) is widely used as an indicator of kidney function, but its direct measurement is challenging, as are its age and gender caveats. This makes difficult the differential diagnosis between age-related physiological decline and KD and/or failure. Currently, the inflammation-based modified Glasgow prognostic score (mGPS) is emerging as a promising biomarker of several inflammatory acute/chronic diseases. In this study, the large variability of eGFR with age and gender was evaluated as the association of eGFR values with mGPS levels. A population of 57,449 adult participants (age >= 18 years) was enrolled. Appropriate circulating biomarkers were measured to detect eGFR and mGPS values. The data obtained demonstrated a significant decrease in eGFR in men vs. women across the four selected age classes (18-40, 40-60, 60-80, 80-100 years); eGFR classes were significantly associated with mGPS (p < 0.001), as were age classes and gender with mGPS categories. Accordingly, the percentage of people having an mGPS score = 2 significantly increased across the eGFR classes: with an 11% in the G1/eGFR class needed to achieve 44% in G5/eGFR. Thus, the combination of mGPS with eGFR could represent the best benchmark risk model for the differential diagnosis of kidney disease from the age-related eGFR reduction

Demographic and clinical features of the 132 HCV1 patients, stratified by presence of HCV defective particles or IL28B genotype.

<p>Continuous variables are expressed as median ± interquartile range (IQR). P values are calculated by Wilcoxon test and Fisher's test for continuous and categorised variables respectively; NS: not significant.</p><p>Demographic and clinical features of the 132 HCV1 patients, stratified by presence of HCV defective particles or IL28B genotype.</p

Multivariable logistic regression for Grading, ETR and Relapse.

<p>OR: odds ratio—CI: 95% confidence interval</p><p>^a: odds ratio and confidence intervals have been calculated considering an interval of 10 years.</p><p>^b: odds ratio and confidence intervals have been calculated considering an interval of 10⁵ units of viremia</p><p>^c: odds ratio and confidence intervals have been calculated considering an interval of 20 units of GGT</p><p>Multivariable logistic regression for Grading, ETR and Relapse.</p

Quantitative detection of total and defective HCV RNA in a subset of patients who carried defective HCV forms.

<p>Quantitative detection of total and defective HCV RNA in a subset of patients who carried defective HCV forms.</p

Virogical responses to PEG-IFNα/RBV stratified for HCV defective forms or IL28B genotype.

<p>RVR, EVR, ETR and SVR rates in the overall population as well as relapse rates in ETR-positive subjects, according to the presence of HCV deletions (A-B) or IL28B genotype (C-D), are reported. The presence of HCV defective particles does not have a significant effect on RVR, EVR, ETR or SVR rates, while it correlates with a higher probability of relapse in ETR-positive subjects (A-B). IL28B CT/TT genotypes are significantly associated with lower RVR, EVR, ETR and SVR rates and correlate with a higher probability of relapse (C-D).</p

Viral genome architecture of the defective forms identified in the serum of chronic hepatitis C patients (genotype 1 HCV).

<p>(A) Pictures of agarose-gel showing amplicons obtained after the second round of nested PCR for all the patients in which defective forms were identified (lanes 1–25) and a subset of patients negative for the defective form (lanes 26–36). Lanes M: molecular size markers. (B) Schematic representation of the architecture of the 25 defective variants identified in the sera of subjects chronically infected with genotype 1 HCV. (C) Picture of agarose gel showing amplicons obtained after nested PCR performed on synthetic HCV RNA mixtures assessing full-length/defective ratios from 1 to 1000 (lanes 3–12). FL: full-length RNA only (lane 1); D: deleted RNA only (lane 2). Lane M: molecular size markers.</p

Non-Small Cell Lung Cancer Testing on Reference Specimens: An Italian Multicenter Experience

Abstract Introduction Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. Methods Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. Results Overall, a median DNA concentration of 3.3 ng/µL (range 0.1–10.0 ng/µL) and 13.4 ng/µL (range 2.0–45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2–11.9 ng/µL) and 9.3 ng/µL (range 0.5–18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. Conclusions Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice