IMPIEGO DI METODI MOLECOLARI (16SrRNA) PER L'IDENTIFICAZIONE DI AGENTI INFETTIVI RESPONSABILI DI INFEZIONI CATETERECORRELATE IN PAZIENTI EMODIALIZZATI

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Impact of Previous Nephrectomy on Clinical Outcome of Metastatic Renal Carcinoma Treated With Immune-Oncology: A Real-World Study on Behalf of Meet-URO Group (MeetUro-7b)

Background: Immune-Oncology (IO) improves Overall Survival (OS) in metastatic Renal Cell Carcinoma (mRCC). The prognostic impact of previous Cytoreductive Nephrectomy (CN) and radical nephrectomy (RN), with curative intent, in patients treated with IO is not well defined. The aim of our paper is to evaluate the impact of previous nephrectomy on outcome of mRCC patients treated with IO. Methods: 287 eligible patients were retrospectively collected from 16 Italian referral centers adhering to the MeetUro association. Patients treated with IO as second and third line were included, whereas patients treated with IO as first line were excluded. Kaplan–Meier method and log-rank test were performed to compare Progression Free Survival (PFS) and OS between groups. In our analysis, both CN and RN were included. The association between nephrectomy and other variables was analyzed in univariate and multivariate setting using the Cox proportional hazard model. Results: 246/287 (85.7%) patients had nephrectomy before IO treatment. Median PFS in patients who underwent nephrectomy (246/287) was 4.8 months (95%CI 3.9–5.7) vs 3.7 months (95%CI 1.9–5.5) in patients who did not it (HR log rank 0.78; 95%CI 0.53 to 1.15; p = 0.186). Median OS in patients who had previous nephrectomy (246/287) was 20.9 months (95%CI 17.6–24.1) vs 13 months (95%CI 7.7–18.2) in patients who did not it (HR log rank 0.504; 95%CI 0.337 to 0.755; p = 0.001). In the multivariate model, nephrectomy showed a significant association with OS (HR log rank 0.638; 95%CI 0.416 to 0.980), whereas gland metastases were still associated with better outcome in terms of both OS (HR log rank 0.487; 95%CI 0.279 to 0.852) and PFS (HR log rank 0.646; 95%CI 0.435 to 0.958). Conclusions: IO treatment, in patients who had previously undergone nephrectomy, was associated with a better outcome in terms of OS. Further prospective trials would assess this issue in order to guide clinicians in real word practice

The color of cancer: margin guidance for oral cancer resection using elastic scattering spectroscopy

Published in final edited form as: Laryngoscope. 2017 September ; 127(Suppl 4): S1–S9. doi:10.1002/lary.26763.OBJECTIVES/HYPOTHESIS: To evaluate the usefulness of elastic scattering spectroscopy (ESS) as a diagnostic adjunct to frozen section analysis in patients with diagnosed squamous cell carcinoma of the oral cavity. STUDY DESIGN: Prospective analytic study. METHODS: Subjects for this single institution, institutional review board-approved study were recruited from among patients undergoing surgical resection for squamous cell cancer of the oral cavity. A portable ESS device with a contact fiberoptic probe was used to obtain spectral signals. Four to 10 spectral readings were obtained on each subject from various sites including gross tumor and normal-appearing mucosa in the surgical margin. Each reading was correlated with the histopathologic findings of biopsies taken from the exact location of the spectral readings. A diagnostic algorithm based on multidimensional pattern recognition/machine learning was developed. Sensitivity and specificity, error rate, and area under the curve were used as performance metrics for tests involving classification between disease and nondisease classes. RESULTS: Thirty-four (34) subjects were enrolled in the study. One hundred seventy-six spectral data point/biopsy specimen pairs were available for analysis. ESS distinguished normal from abnormal tissue, with a sensitivity ranging from 84% to 100% and specificity ranging from 71% to 89%, depending on how the cutoff between normal and abnormal tissue was defined (i.e., mild, moderate, or severe dysplasia). There were statistically significant differences in malignancy scores between histologically normal tissue and invasive cancer and between noninflamed tissue and inflamed tissue. CONCLUSIONS: This is the first study to evaluate the effectiveness of ESS in guiding mucosal resection margins in oral cavity cancer. ESS provides fast, real-time assessment of tissue without the need for pathology expertise. ESS appears to be effective in distinguishing between normal mucosa and invasive cancer and between "normal" tissue (histologically normal and mild dysplasia) and "abnormal" tissue (severe dysplasia and carcinoma in situ) that might require further margin resection. Further studies, however, are needed with a larger sample size to validate these findings and to determine the effectiveness of ESS in distinguishing visibly and histologically normal tissue from visibly normal but histologically abnormal tissue. LEVEL OF EVIDENCE: NA Laryngoscope, 127:S1-S9, 2017.R21 DE023192 - NIDCR NIH HHSAccepted manuscrip

Axitinib after Sunitinib in Metastatic Renal Cancer: Preliminary Results from Italian "Real-World" SAX Study.

Axitinib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) after failure of prior treatment with Sunitinib or cytokine. The present study is an Italian Multi-Institutional Retrospective Analysis that evaluated the outcomes of Axitinib, in second-line treatment of mRCC. The medical records of 62 patients treated with Axitinib, were retrospectively reviewed. The Progression Free Survival (PFS), the Overall Survival (OS), the Objective Response Rate (ORR), the Disease Control Rate (DCR), and the safety profile of axitinib and sunitinib–axitinib sequence, were the primary endpoint. The mPFS was 5.83 months (95% CI 3.93–7.73 months). When patients was stratified by Heng score, mPFS was 5.73, 5.83, 10.03 months according to poor, intermediate, and favorable risk group, respectively. The mOS from the start of axitinib was 13.3 months (95% CI 8.6–17.9 months); the observed ORR and DCR were 25 and 71%, respectively. When stratified patients by subgroups defined by duration of prior therapy with Sunitinib (≤ vs. >median duration), there was a statistically significant difference in mPFS with 8.9 (95% CI 4.39–13.40 months) vs. 5.46 months (95% CI 4.04–6.88 months) for patients with a median duration of Sunitinib >13.2 months. DCR and ORR to previous Sunitinib treatment was associated with longer statistically mPFS, 7.23 (95% CI 3.95–10.51 months, p = 0.01) and 8.67 (95% CI 4.0–13.33 months, p = 0.008) vs. 2.97 (95% CI 0.65–5.27 months, p = 0.01) and 2.97 months (95% CI 0.66–5.28 months, p = 0.01), respectively. Overall Axitinib at standard schedule of 5 mg bid, was well-tolerated. The most common adverse events of all grades were fatig (25.6%), hypertension (22.6%), gastro-intestinal disorders (25.9%), and hypothyroidism (16.1%). The sequence Sunitinib–Axitinib was well-tolerated without worsening in side effects, with a median OS of 34.7 months (95% CI 18.4–51.0 months). Our results are consistent with the available literature; this retrospective analysis confirms that Axitinib is effective and safe in routine clinical practice

Cyclin-Dependent Kinase Activity Controls the Onset of the HCMV Lytic Cycle

The onset of human cytomegalovirus (HCMV) lytic infection is strictly synchronized with the host cell cycle. Infected G0/G1 cells support viral immediate early (IE) gene expression and proceed to the G1/S boundary where they finally arrest. In contrast, S/G2 cells can be infected but effectively block IE gene expression and this inhibition is not relieved until host cells have divided and reentered G1. During latent infection IE gene expression is also inhibited, and for reactivation to occur this block to IE gene expression must be overcome. It is only poorly understood which viral and/or cellular activities maintain the block to cell cycle or latency-associated viral IE gene repression and whether the two mechanisms may be linked. Here, we show that the block to IE gene expression during S and G2 phase can be overcome by both genotoxic stress and chemical inhibitors of cellular DNA replication, pointing to the involvement of checkpoint-dependent signaling pathways in controlling IE gene repression. Checkpoint-dependent rescue of IE expression strictly requires p53 and in the absence of checkpoint activation is mimicked by proteasomal inhibition in a p53 dependent manner. Requirement for the cyclin dependent kinase (CDK) inhibitor p21 downstream of p53 suggests a pivotal role for CDKs in controlling IE gene repression in S/G2 and treatment of S/G2 cells with the CDK inhibitor roscovitine alleviates IE repression independently of p53. Importantly, CDK inhibiton also overcomes the block to IE expression during quiescent infection of NTera2 (NT2) cells. Thus, a timely block to CDK activity not only secures phase specificity of the cell cycle dependent HCMV IE gene expression program, but in addition plays a hitherto unrecognized role in preventing the establishment of a latent-like state

Curve Number: Empirical Evaluation and Comparison with Curve Number Handbook Tables in Sicily

The curve number (CN) method is widely used for estimating direct runoff depth from rainstorms. The procedure is on the basis of the parameter CN, a lumped expression of basin absorption and runoff potential, and a second parameter, initial abstraction (IA), which represents the interception, infiltration, and surface depression during the early part of a storm. The evaluation of CN in Sicily at a basin scale from rainfall-runoff multiday events is done using rainfall-runoff observations during the period 1940–1997 (mean record length of 20 years) in 61 Sicilian watersheds using three different methods: (1) the national engineering handbook, section 4 hydrology (NEH4) method (NEH4M) (the median CN for the annual flood events); (2) asymptotic fitting of ordered and natural data; and (3) least-squares method using rainfall-runoff using both ordered and natural data. Asymptotic fitting showed a major occurrence of the standard CN response (43 basins), with a lesser complacent response (10 basins), and a few cases of violent behavior (three basins). For five basins, the data quality and/or small sample size did not allow the identification of a CN. The least-squares and asymptotic fittings furnished similar results but showed that the original assumption of the initial abstraction ratio (IA/S or λ) of 0.20 in watersheds with a standard and violent CN response is unusually high. Using both natural and ordered rainfall-runoff data, a median λ value of 0 and 0.05 was found for natural data and ordered data, respectively. The CNs found by the recommended handbook method (NEH4 method) were higher than those found from the handbook tables. The asymptotic fitting and least-squares fitting methods were all lower than the table values. Comparisons were made between the CNs estimated using hydrologic soil-cover complexes on the basis of Soil Conservation Service (SCS)–National Resources Conservation Service (NRCS) handbook tables and the CN evaluated from rainfall-runoff multiday events in 36 of the basins. Overall, although comparisons were poor, the NEH4 method and asymptotic fitting method that used all of the ordered data were closest to the CNs from the handbook tables. The link between the CN estimated with the asymptotic fitting method (AFM) (T-series, ordered data) and the watersheds’ morphoclimatic and hydrologic characteristics was also investigated, and a useful relationship for basins with a larger drainage area (SDA>160  km2) was found

CHANGES OF MICROFLORA DURING STORAGE OF ‘NDUJA, A VERY TYPICAL SAUSAGE OF CALABRIA (ITALY)

The ‘nduja is one of the most typical and appreciated Calabrian raw seasoned sausages. As well as other Calabrian meat products, the ‘nduja contains a high quantity of hot red chilli pepper. The ‘nduja is a seasoned, very savoury but yet spreadable sausage; it is traditionally spread on bread or used as natural flavour enhancer of pasta, pizza and other similar kind of food. 27 samples of ‘nduja were sampled, 15 coming from artisanal production and the remaining 12 from industrial production, in order to establish if they were differences between the two kind of production from the hygienic point of view. The samples were stored up to 6 month and analyzed at 1 day of storage and then at 3 and 6 month of storage. Our results show that the ‘nduja is a meat product of good hygienic quality; the sausages made in artisanal manner showed a more variable microbial quality as the ones made in industrial factories. The microbial flora of ‘nduja is mainly composed by lactobacilli, yeasts and moulds; only in rare cases we have found quite high numbers of micrococci and/od pseudomonads. Total and faecal coliforms are in general very low, in the product ready to eat. No Salmonella enterica nor Listeria monocytogenes nor enterotoxigenic strains of S. aureus or B. cereus were found in the samples analysed

Standard Asymptotic Response and Expected Runoff from Curve Number Theory

The Standard Asymptotic response is a common finding with rainfall-runoff analysis with the Curve Number method. Widely-observed in data analyses, it is the secondary relationship between the data-defined CN and the causative rainfall P, for which the empirical fitting equation CN(P) = CN 1e+ (100-CN 1e)exp(-kP) has been found to fit well. This is an unexpected variation in the handbook methodology. It is investigated here on a \u201ctheoretical\u201d basis by using the handbook tabled values of CN for the three AMC classes, I, II, and III; the storm-to-storm S (=1000/CN-10); and the observed 12-50-88 percent conditional probabilities for the ARC classes. With this, and treating S as a variable across the AMC classes, the standardized values of S, or S/SII =S*, are found to well describe a lognormal distribution with \u3c3n=0.713. Using standardized (dimensionless) values of P (P*=P/SII) and the found lognormal distribution, the expected values of Q* (or E(Q/SII)) are calculated for an array of P*. Converting back to dimensioned rainfall and E(Q), resulting CNs generate the standard asymptotic phenomenon. The effects are most prominent for smaller storms, in the range of P/S0 for any P>0. This simple shift to expected values from medians allows 1) explanation of the Standard response, and 2) an alternate and more enlightened application of the Curve Number method, especially with smaller runoff-producing rainstorms