Incidence of Newly HIV Diagnosed Cases among Foreign Migrants in Italy: 2006-2013

Objective: In Europe, during the last years the proportion of foreign migrants among AIDS and HIV cases is growing. In Italy, the number of new cases of HIV represented by foreign migrants has progressively increased, but the new HIV diagnoses incidence among foreign migrants has decreased, because of the increase in the total number of foreign migrants in recent years. Nevertheless, the new HIV diagnoses incidence among foreign migrants is still high if compared to that among Italians. The aim of the study was to analyze the characteristics of foreign migrants with a new HIV diagnosis and the new HIV diagnoses incidence among foreign migrants diagnosed in Italy between 2006 and 2013. Methods: The new diagnoses incidence was calculated as the ratio between the number of new HIV diagnoses among foreign migrants and the number of foreign migrants residing in Italy. The new HIV diagnoses incidence was compared with that among Italians using the standardized incidence ratio (SIR) adjusted by age and gender. Results: During the study period (2006-2013), of the 25,545 new diagnoses reported by the HIV surveillance system, 28.8% were among foreign migrants. The incidence of new HIV diagnoses among foreign migrants for the entire study period was 26.7 cases per 100,000 foreign migrant residents, compared to 5.1 per 100,000 among Italians. The incidence of new HIV diagnoses decreased over time for foreign migrants: from 42.5 per 100,000foreign migrant residents in 2006 to 20.0 per 100,000 foreign migrant residents in 2013, whereas for Italians it remained stable. The SIR confirmed the marked difference between the two populations: specifically the overall incidence of new diagnoses was more than four times higher among foreign migrants, compared to Italians.Conclusion: The results stress the need to reinforce the efforts aimed at reducing the circulation of HIV in this population

Genome-wide screening of copy number alterations and LOH events in renal cell carcinomas and integration with gene expression profile

<p>Abstract</p> <p>Background</p> <p>Clear cell renal carcinoma (RCC) is the most common and invasive adult renal cancer. For the purpose of identifying RCC biomarkers, we investigated chromosomal regions and individual genes modulated in RCC pathology. We applied the dual strategy of assessing and integrating genomic and transcriptomic data, today considered the most effective approach for understanding genetic mechanisms of cancer and the most sensitive for identifying cancer-related genes.</p> <p>Results</p> <p>We performed the first integrated analysis of DNA and RNA profiles of RCC samples using Affymetrix technology. Using 100K SNP mapping arrays, we assembled a genome-wide map of DNA copy number alterations and LOH areas. We thus confirmed the typical genetic signature of RCC but also identified other amplified regions (e.g. on chr. 4, 11, 12), deleted regions (chr. 1, 9, 22) and LOH areas (chr. 1, 2, 9, 13). Simultaneously, using HG-U133 Plus 2.0 arrays, we identified differentially expressed genes (DEGs) in tumor vs. normal samples. Combining genomic and transcriptomic data, we identified 71 DEGs in aberrant chromosomal regions and observed, in amplified regions, a predominance of up-regulated genes (27 of 37 DEGs) and a trend to clustering. Functional annotation of these genes revealed some already implicated in RCC pathology and other cancers, as well as others that may be novel tumor biomarkers.</p> <p>Conclusion</p> <p>By combining genomic and transcriptomic profiles from a collection of RCC samples, we identified specific genomic regions with concordant alterations in DNA and RNA profiles and focused on regions with increased DNA copy number. Since the transcriptional modulation of up-regulated genes in amplified regions may be attributed to the genomic alterations characteristic of RCC, these genes may encode novel RCC biomarkers actively involved in tumor initiation and progression and useful in clinical applications.</p

Increased phospho-mTOR expression in megakaryocytic cells derived from CD34+ progenitors of essential thrombocythaemia and myelofibrosis patients

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Laying the foundations for gene therapy in Italy for patients with haemophilia A: A Delphi consensus study

IntroductionCurrent treatment for haemophilia A involves factor VIII replacement or non-replacement (emicizumab) therapies, neither of which permanently normalise factor VIII levels. Gene therapy using adeno-associated viral (AAV) vectors is an emerging long-term treatment strategy for people with severe haemophilia A (PwSHA) that is likely to be available for clinical use in the near future. AimThis article proposes practical guidelines for the assessment, treatment, and follow-up of potential PwSHA candidates for AAV-based gene therapy. MethodUsing the Delphi method, a working group of Italian stakeholders with expertise in and knowledge of the care of adults with haemophilia A analysed literature for AAV-based gene therapy and drafted a list of statements that were circulated to a panel of Italian peers. During two rounds of voting, panel members voted on their agreement with each statement to reach a consensus. ResultsThe Delphi process yielded 40 statements regarding haemophilia A gene therapy, across five topics: (1) organisational model; (2) multidisciplinary team; (3) patient engagement; (4) laboratory surveillance; and (5) patient follow-up and gene therapy outcomes. The consensus was reached for all 40 statements, with the second round of voting needed for five statements. ConclusionUse of the hub-and-spoke organisational model and multidisciplinary teams are expected to optimise patient selection for gene therapy, as well as the management of dosing and patient follow-up, patient engagement, laboratory surveillance, and patient expectations regarding outcomes. This approach should allow the benefits of AAV-based gene therapy for haemophilia A to be maximised

Digital PCR improves the quantitation of DMR and the selection of CML candidates to TKIs discontinuation

Treatment-free remission (TFR) by tyrosine kinase inhibitors (TKI) discontinuation in patients with deep molecular response (DMR) is a paramount goal in the current chronic myeloid leukemia (CML) therapeutic strategy. The best DMR level by real-time quantitative PCR (RT-qPCR) for TKI discontinuation is still a matter of debate. To compare the accuracy of digital PCR (dPCR) and RT-qPCR for BCR-ABL1 transcript levels detection, 142 CML patients were monitored for a median time of 24\ua0months. Digital PCR detected BCR-ABL1 transcripts in the RT-qPCR undetectable cases. The dPCR analysis of the samples, grouped by the MR classes, revealed a significant difference between MR4.0 and MR4.5 (P\ua0=\ua00.0104) or MR5.0 (P\ua0=\ua00.0032). The clinical and hematological characteristics of the patients grouped according to DMR classes (MR4.0 vs MR4.5-5.0 ) were superimposable. Conversely, patients with dPCR values <0.468 BCR-ABL1 copies/\ub5L (as we previously described) showed a longer DMR duration (P\ua0=\ua00.0220) and mainly belonged to MR4.5-5.0 (P\ua0=\ua00.0442) classes compared to patients with higher dPCR values. Among the 142 patients, 111 (78%) discontinued the TKI treatment; among the 111 patients, 24 (22%) lost the MR3.0 or MR4.0 . RT-qPCR was not able to discriminate patients with higher risk of MR loss after discontinuation (P\ua0=\ua00.8100). On the contrary, according to dPCR, 12/25 (48%) patients with BCR-ABL1 values 650.468 and 12/86 (14%) patients with BCR-ABL1 values <0.468 lost DMR in this cohort, respectively (P\ua0=\ua00.0003). Treatment-free remission of patients who discontinued TKI with a dPCR <0.468 was significantly higher compared to patients with dPCR\ua0 65\ua00.468 (TFR at 2\ua0years 83% vs 52% P\ua0=\ua00.0017, respectively). In conclusion, dPCR resulted in an improved recognition of stable DMR and of candidates to TKI discontinuation

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin