335 results on '"Paolo, Chiodini"'
Search Results
2. Efficacy of erythropoietin as a neuroprotective agent in CKD-associated cognitive dysfunction: A literature systematic review
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Michelangela Barbieri, Paolo Chiodini, Piergiacomo Di Gennaro, Gaye Hafez, Sophie Liabeuf, Jolanta Malyszko, Laila-Yasmin Mani, Francesco Mattace-Raso, Marion Pepin, Norberto Perico, Mariadelina Simeoni, Carmine Zoccali, Giovanni Tortorella, Annalisa Capuano, Giuseppe Remuzzi, Giovambattista Capasso, and Giuseppe Paolisso more...
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Erythropoietin ,rHuEPO ,CKD ,Cognition ,Darbepoetin ,Neuroprotection ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Patients with chronic kidney disease (CKD) often experience mild cognitive impairment and other neurocognitive disorders. Studies have shown that erythropoietin (EPO) and its receptor have neuroprotective effects in cell and animal models of nervous system disorders. Recombinant human EPO (rHuEPO), commonly used to treat anemia in CKD patients, could be a neuroprotective agent. In this systematic review, we aimed to assess the published studies investigating the cognitive benefits of rHuEPO treatment in individuals with reduced kidney function. We comprehensively searched Pubmed, Cochrane Library, Scopus, and Web of Science databases from 1990 to 2023. After selection, 24 studies were analyzed, considering study design, sample size, participant characteristics, intervention, and main findings. The collective results of these studies in CKD patients indicated that rHuEPO enhances brain function, improves performance on neuropsychological tests, and positively affects electroencephalography measurements. These findings suggest that rHuEPO could be a promising neuroprotective agent for managing CKD-related cognitive impairment. more...
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- 2024
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3. Oligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION study
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Alessandro Ottaiano, Antonella De Luca, Mariachiara Santorsola, Giosuè Scognamiglio, Annabella Di Mauro, Paolo Chiodini, Matilde Lambiase, Alessandra Sacco, Antonella Petrillo, Vincenza Granata, Roberta Fusco, Edoardo Mercadante, Nicola Martucci, Giuseppe De Luca, Antonello La Rocca, Egidio Celentano, Anna Crispo, Piergiacomo Di Gennaro, Fabiana Tatangelo, Gerardo Ferrara, Francesco Izzo, Andrea Belli, Renato Patrone, Paolo Delrio, Daniela Rega, Silvia De Franciscis, Paolo Muto, Vincenzo Ravo, Rossella Di Franco, Valentina Borzillo, Sara Santagata, Giuseppina Rea, Daniela Castaldo, Ugo Pace, Gianfranco De Feo, Stefania Scala, Guglielmo Nasti, and Nicola Normanno more...
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Oligometastatic diseases ,Colorectal cancer ,Biomarkers ,Genetics ,Prognosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, characterized by a limited number of metastatic sites, referred to as “oligo-metastatic disease” (OMD). The precise biological characteristics that define the oligometastatic behavior remain uncertain. In this study, we present a protocol designed to prospectively identify OMD, with the aim of proposing novel therapeutic approaches and monitoring strategies. Methods The PREDICTION study is a monocentric, prospective, observational investigation. Enrolled patients will receive standard treatment, while translational activities will involve analysis of the tumor microenvironment and genomic profiling using immunohistochemistry and next-generation sequencing, respectively. The first primary objective (descriptive) is to determine the prevalence of biological characteristics in OMD derived from gastrointestinal tract neoplasms, including high genetic concordance between primary tumors and metastases, a significant infiltration of T lymphocytes, and the absence of clonal evolution favoring specific driver genes (KRAS and PIK3CA). The second co-primary objective (analytic) is to identify a prognostic score for true OMD, with a primary focus on metastatic colorectal cancer. The score will comprise genetic concordance (> 80%), high T-lymphocyte infiltration, and the absence of clonal evolution favoring driver genes. It is hypothesized that patients with true OMD (score 3+) will have a lower rate of progression/recurrence within one year (20%) compared to those with false OMD (80%). The endpoint of the co-primary objective is the rate of recurrence/progression at one year. Considering a reasonable probability (60%) of the three factors occurring simultaneously in true OMD (score 3+), using a significance level of α = 0.05 and a test power of 90%, the study requires a minimum enrollment of 32 patients. Discussion Few studies have explored the precise genetic and biological features of OMD thus far. In clinical settings, the diagnosis of OMD is typically made retrospectively, as some patients who undergo intensive treatment for oligometastases develop polymetastatic diseases within a year, while others do not experience disease progression (true OMD). In the coming years, the identification of true OMD will allow us to employ more personalized and comprehensive strategies in cancer treatment. Trial registration ClinicalTrials.gov ID NCT05806151. more...
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- 2023
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4. Dexmedetomidine as Adjunctive Therapy for the Treatment of Alcohol Withdrawal Syndrome: A Systematic Review and Meta-Analysis
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Marco Fiore, Aniello Alfieri, Giacomo Torretta, Maria Beatrice Passavanti, Pasquale Sansone, Vincenzo Pota, Vittorio Simeon, Paolo Chiodini, Antonio Corrente, and Maria Caterina Pace
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dexmedetomidine ,alcohol withdrawal syndrome ,intensive care ,sedatives ,systematic review ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Alcohol withdrawal syndrome (AWS) is defined as the cessation or reduction in heavy and prolonged alcohol use within several hours to a few days of cessation. The recommended first-line therapy for AWS ranging from mild to severe or complicated remains benzodiazepines; in cases where benzodiazepines are not adequate in controlling persistent autonomic hyperactivity or anxiety, dexmedetomidine could be utilized. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the ICUs, with the potential reduction in healthcare costs. The purpose of this systematic review and meta-analysis (PROSPERO CRD42018084370) is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care for the treatment of AWS. We retrieved literature from PubMed, EMBASE, and CENTRAL until 10 January 2024. Eligible studies were both randomized trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was tracheal intubation; secondary outcomes were (i) bradycardia and (ii) hypotension. A total of 3585 papers were retrieved: 2635 from EMBASE, 930 from Medline, and 20 from CENTRAL. After eliminating duplicates, 2960 papers were screened by title and abstract; 75 out of the 2960 papers were read in full text. The qualitative synthesis included nine of all manuscripts read in full text. The quantitative synthesis included eight studies for the primary outcome (tracheal intubation), seven for the secondary outcome bradycardia, and six for the secondary outcome hypotension. The meta-analysis showed that Dexmedetomidine, as adjunctive therapy, is not more effective than standard therapy in reducing the risk of tracheal intubation in AWS [RR: 0.57, 95% CI: 0.25–1.3, p = 0.15]. It also appears to be less safe than sedative therapy as it significantly increases the risk of bradycardia [RR: 2.68, 95% CI: 1.79–4.16, p = 0.0016]. Hypotension was not significantly different in patients who received dexmedetomidine [RR: 1.5, 95% CI: 0.69–3.49, p = 0.21]. more...
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- 2024
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5. CD39 and LDHA affects the prognostic role of NLR in metastatic melanoma patients treated with immunotherapy
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Domenico Mallardo, Mario Fordellone, Andrew White, Margaret Ottaviano, Francesca Sparano, Michael Bailey, Arianna Bianca Facchini, Sufey Ong, Piera Maiolino, Corrado Caracò, Sarah Church, Ernesta Cavalcanti, Sarah Warren, Alfredo Budillon, Alessandra Cesano, Ester Simeone, Paolo Chiodini, and Paolo Antonio Ascierto more...
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Melanoma ,NLR ,CD39 ,HDLA ,TGFβ ,Biomarker ,Medicine - Abstract
Abstract Background Identifying response markers is highly needed to guide the treatment strategy in patients with metastatic melanoma. Methods A retrospective study was carried out in patients with unresectable/metastatic melanoma (stage IIIb–IV), treated with anti-PD-1 in the first line setting, to better explore the role and the timing of neutrophil/lymphocyte ratio (NLR) as potential biomarker of response. The relationship of NLR with inflammation-immune mediators and the underlying negative effect of raising NLR during immunotherapy, have been investigated with transcriptomic gene analysis. Results The results confirmed previous findings that a high baseline NLR is associated with a poorer prognosis and with higher serum level of lactate dehydrogenase (LDH), regardless of the presence of brain metastases. The transcriptomic analysis showed that high baseline NLR is associated with a characteristic gene signature CCNA1, LDHA and IL18R1, which correlates with inflammation and tumorigenesis. Conversely, low baseline NLR is associated with the signature CD3, SH2D1A, ZAP70 and CD45RA, linked to the immune-activation. The genes positively associated with NLR (CD39 (ENTPD1), PTEN, MYD88, MMP9 and LDH) are involved in processes of immunosuppression, inflammation and tumor-promoting activity. Increased expression of CD39 correlated with TGFβ2, a marker of the N2 neutrophils with immunosuppressive activity. Conclusions These results suggest that increasing NLR is associated with an increased neutrophil population, with polarization to the N2 phenotype, and this process may be the basis for the negatively prognostic role of NLR. more...
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- 2023
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6. Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition
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Joanna L. Clasen, Rita Mabunda, Alicia K. Heath, Rudolf Kaaks, Verena Katzke, Matthias B. Schulze, Anna Birukov, Giovanna Tagliabue, Paolo Chiodini, Rosario Tumino, Lorenzo Milani, Tonje Braaten, Inger Gram, Marko Lukic, Leila Luján‐Barroso, Miguel Rodriguez‐Barranco, María‐Dolores Chirlaque, Eva Ardanaz, Pilar Amiano, Jonas Manjer, Linnea Huss, Börje Ljungberg, Ruth Travis, Karl Smith‐Byrne, Marc Gunter, Matthias Johansson, Sabina Rinaldi, Elisabete Weiderpass, Elio Riboli, Amanda J. Cross, and David C. Muller more...
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. Materials & Methods We investigated associations of age at menarche and age at menopause, pregnancy‐related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Results During 15 years of follow‐up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. more...
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- 2023
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7. Harmonization of tumor mutation burden testing with comprehensive genomic profiling assays: an IQN Path initiative
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Nicola Normanno, Paolo Chiodini, Riziero Esposito Abate, Raffaella Pasquale, Alessandra Sacco, Vittorio Simeon, Monica Rosaria Maiello, and Daniela Frezzetti
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Although conflicting results emerged from different studies, the tumor mutational burden (TMB) appears as one of most reliable biomarkers of sensitivity to immune checkpoint inhibitors. Several laboratories are reporting TMB values when performing comprehensive genomic profiling (CGP) without providing a clinical interpretation, due to the lack of validated cut-off values. The International Quality Network for Pathology launched an initiative to harmonize TMB testing with CGP assay and favor the clinical implementation of this biomarker.Methods TMB evaluation was performed with three commercially available CGP panels, TruSight Oncology 500 (TSO500), Oncomine Comprehensive Plus Assay (OCA) and QIAseq Multimodal Panel (QIA), versus the reference assay FoundationOne CDx (F1CDx). Archived clinical samples derived from 60 patients with non-small cell lung cancer were used for TMB assessment. Adjusted cut-off values for each panel were calculated.Results Testing was successful for 91.7%, 100%, 96.7% and 100% of cases using F1CDx, TSO500, OCA and QIA, respectively. The matrix comparison analysis, between the F1CDx and CGP assays, showed a linear correlation for all three panels, with a higher correlation between F1CDx and TSO500 (rho=0.88) than in the other two comparisons (rho=0.77 for QIA; 0.72 for OCA). The TSO500 showed the best area under the curve (AUC, value 0.96), with a statistically significant difference when compared with the AUC of OCA (0.83, p value=0.01) and QIA (0.88, p value=0.028). The Youden Index calculation allowed us to extrapolate TMB cut-offs of the different panels corresponding to the 10 mutations/megabase (muts/Mb) cut-off of F1CDx: 10.19, 10.4 and 12.37 muts/Mb for TSO500, OCA and QIA, respectively. Using these values, we calculated the relative accuracy measures for the three panels. TSO500 showed 86% specificity and 96% sensitivity, while OCA and QIA had lower yet similar values of specificity and sensitivity (73% and 88%, respectively).Conclusion This study estimated TMB cut-off values for commercially available CGP panels. The results showed a good performance of all panels on clinical samples and the calculated cut-offs support better accuracy measures for TSO500. The validated cut-off values can drive clinical interpretation of TMB testing in clinical research and clinical practice. more...
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- 2024
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8. Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy
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Raffaele Galiero, Giuseppe Loffredo, Vittorio Simeon, Alfredo Caturano, Erica Vetrano, Giulia Medicamento, Maria Alfano, Domenico Beccia, Chiara Brin, Sara Colantuoni, Jessica Di Salvo, Raffaella Epifani, Riccardo Nevola, Raffaele Marfella, Celestino Sardu, Carmine Coppola, Ferdinando Scarano, Paolo Maggi, Cecilia Calabrese, Pellegrino De Lucia Sposito, Carolina Rescigno, Costanza Sbreglia, Fiorentino Fraganza, Roberto Parrella, Annamaria Romano, Giosuele Calabria, Benedetto Polverino, Antonio Pagano, Fabio Numis, Carolina Bologna, Mariagrazia Nunziata, Vincenzo Esposito, Nicola Coppola, Nicola Maturo, Rodolfo Nasti, Pierpaolo Di Micco, Alessandro Perrella, Luigi Elio Adinolfi, Paolo Chiodini, Marina Di Domenico, Luca Rinaldi, and Ferdinando Carlo Sasso more...
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Medicine ,Science - Published
- 2024
9. Biological and clinical impact of membrane EGFR expression in a subgroup of OC patients from the phase IV ovarian cancer MITO-16A/MANGO-OV2A trial
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Luca Forlani, Loris De Cecco, Vittorio Simeon, Biagio Paolini, Marina Bagnoli, Sabrina Chiara Cecere, Anna Spina, Eleonora Citeroni, Eliana Bignotti, Domenica Lorusso, Laura Arenare, Daniela Russo, Carmine De Angelis, Laura Ardighieri, Giosuè Scognamiglio, Michele Del Sesto, Germana Tognon, Daniela Califano, Clorinda Schettino, Paolo Chiodini, Francesco Perrone, Delia Mezzanzanica, Sandro Pignata, and Antonella Tomassetti more...
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Ovarian cancer ,Bevacizumab ,EGFR ,Immunohistochemistry ,Microarray ,Bioinformatics ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Validated prognostic biomarkers for anti-angiogenic therapy using the anti-VEGF antibody Bevacizumab in ovarian cancer (OC) patients are still an unmet clinical need. The EGFR can contribute to cancer-associated biological mechanisms in OC cells including angiogenesis, but its targeting gave disappointing results with less than 10% of OC patients treated with anti-EGFR compounds showing a positive response, likely due to a non adequate selection and stratification of EGFR-expressing OC patients. Methods EGFR membrane expression was evaluated by immunohistochemistry in a cohort of 310 OC patients from the MITO-16A/MANGO-OV2A trial, designed to identify prognostic biomarkers of survival in patients treated with first line standard chemotherapy plus bevacizumab. Statistical analyses assessed the association between EGFR and clinical prognostic factors and survival outcomes. A single sample Gene Set Enrichment-like and Ingenuity Pathway Analyses were applied to the gene expression profile of 195 OC samples from the same cohort. In an OC in vitro model, biological experiments were performed to assess specific EGFR activation. Results Based on EGFR-membrane expression, three OC subgroups of patients were identified being the subgroup with strong and homogeneous EGFR membrane localization, indicative of possible EGFR out/in signalling activation, an independent negative prognostic factor for overall survival of patients treated with an anti-angiogenic agent. This OC subgroup resulted statistically enriched of tumors of histotypes different than high grade serous lacking angiogenic molecular characteristics. At molecular level, among the EGFR-related molecular traits identified to be activated only in this patients’ subgroup the crosstalk between EGFR with other RTKs also emerged. In vitro, we also showed a functional cross-talk between EGFR and AXL RTK; upon AXL silencing, the cells resulted more sensitive to EGFR targeting with erlotinib. Conclusions Strong and homogeneous cell membrane localization of EGFR, associated with specific transcriptional traits, can be considered a prognostic biomarker in OC patients and could be useful for a better OC patients’ stratification and the identification of alternative therapeutic target/s in a personalized therapeutic approach. more...
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- 2023
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10. Chocolate Eaters Do Not Necessarily Win a Nobel Prize—Authors in Special Issues Do Not Necessarily Publish Lower Quality Papers
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Nino Künzli, Christopher Woodrow, Anke Berger, Katarzyna Czabanowska, Licia Iacoviello, Raquel Lucas, Andrea Madarasova Geckova, Sonja Merten, Olaf von dem Knesebeck, Sarah Mantwill, Salvatore Panico, Lyda Osorio, Ana Isabel Ribeiro, Paolo Chiodini, L. Suzanne Suggs, and Jean Coulibaly more...
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editorial policies ,science funding policies ,peer review ,special issues ,regular issues ,Public aspects of medicine ,RA1-1270 - Published
- 2023
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11. A 52-week multicenter retrospective real-world study on effectiveness and safety of dupilumab in children with atopic dermatitis aged from 6 to 11 years
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Cataldo Patruno, Gabriella Fabbrocini, Giuseppe Lauletta, Valeria Boccaletti, Cristiana Colonna, Riccardo Cavalli, Iria Neri, Michela Ortoncelli, Donatella Schena, Luca Stingeni, Katharina Hansel, Vincenzo Piccolo, Veronica Di Brizzi, Concetta Potenza, Ersilia Tolino, Luca Bianchi, Sara Manti, Rocco De Pasquale, Vito Di Lernia, Lucia Caminiti, Elena Galli, Paola Coppo, Andrea Chiricozzi, Clara De Simone, Cristina Guerriero, Fabrizio Giuseppe Amoruso, Eugenio Provenzano, Salvatore Leonardi, Amelia Licari, Gian Luigi Marseglia, Antonino Palermo, Sabrina Di Pillo, Daniele Russo, Viviana Moschese, Vincenzo Patella, Tiziana Peduto, Caterina Ferreli, Paola Zangari, Federica Veronese, Samantha Federica Berti, Michaela Gruber, Elena Pezzolo, Stefania Termine, Rosanna Satta, Federica Dragoni, Maria Esposito, Maria Concetta Fargnoli, Paolo Chiodini, Ylenia Vallone, Francesca di Vico, Vincenzo Picone, and Maddalena Napolitano more...
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atopic dermatitis ,children ,dupilumab ,real-world data ,Dermatology ,RL1-803 - Abstract
Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years. Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled. Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52. Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time. more...
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- 2023
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12. 41 CD39 affect the prognostic role of NLR via N2 neutrophils in metastatic melanoma patients treated with immunotherapy
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Michael Bailey, Andrew White, Francesca Sparano, Alessandra Cesano, Corrado Caracò, Ester Simeone, Alfredo Budillon, Sarah Warren, SuFey Ong, Domenico Mallardo, Sarah Church, Ernesta Cavalcanti, Paolo Ascierto, Margaret Ottaviano, Paolo Chiodini, Piera Maiolino, Mario Fordellone, and Bianca Arianna Facchini more...
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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13. 1247 Gene signature predict autoimmune toxicity in patients with metastatic melanoma
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Michael Bailey, Andrew White, Francesca Sparano, Alessandra Cesano, Corrado Caracò, Ester Simeone, Lucia Festino, Alfredo Budillon, Sarah Warren, Domenico Mallardo, Sarah Church, Vito Vanella, Ernesta Cavalcanti, Paolo Ascierto, Claudia Trojaniello, Maria Grazia Vitale, Margaret Ottaviano, Paolo Chiodini, Marilena Tuffanelli, Mario Fordellone, and Bianca Arianna Facchini more...
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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14. The number of risk factors not at target is associated with cardiovascular risk in a type 2 diabetic population with albuminuria in primary cardiovascular prevention. Post-hoc analysis of the NID-2 trial
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Ferdinando Carlo Sasso, Vittorio Simeon, Raffaele Galiero, Alfredo Caturano, Luca De Nicola, Paolo Chiodini, Luca Rinaldi, Teresa Salvatore, Miriam Lettieri, Riccardo Nevola, Celestino Sardu, Giovanni Docimo, Giuseppe Loffredo, Raffaele Marfella, Luigi Elio Adinolfi, Roberto Minutolo, and NID-2 study group Investigators more...
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Type 2 diabetes mellitus ,Cardiovascular risk ,Diabetes complications ,Multifactorial treatment ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Nephropathy in Diabetes type 2 (NID-2) study is an open-label cluster randomized clinical trial that demonstrated that multifactorial intensive treatment reduces Major Adverse Cardiac Events (MACEs) and overall mortality versus standard of care in type 2 diabetic subjects with albuminuria and no history of cardiovascular disease. Aim of the present post-hoc analysis of NID- 2 study is to evaluate whether the number of risk factors on target associates with patient outcomes. Methods Intervention phase lasted four years and subsequent follow up for survival lasted 10 years. To the aim of this post-hoc analysis, the whole population has been divided into 3 risk groups: 0–1 risk factor (absent/low); 2–3 risk factors (intermediate); 4 risk factors (high). Primary endpoint was a composite of fatal and non-fatal MACEs, the secondary endpoint was all-cause death at the end of the follow-up phase. Results Absent/low risk group included 166 patients (52.4%), intermediate risk group 128 (40.4%) and high-risk group 23 (7.3%). Cox model showed a significant higher risk of MACE and death in the high-risk group after adjustment for confounding variables, including treatment arm (HR 1.91, 95% CI 1.04–3.52, P = 0.038 and 1.96, 95%CI 1.02–3.8, P = 0,045, respectively, vs absent/low risk group). Conclusions This post-hoc analysis of the NID-2 trial indicates that the increase in the number of risk factors at target correlates with better cardiovascular-free survival in patients with type 2 diabetes at high CV risk. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925 more...
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- 2022
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15. Hyperkalemia in CKD: an overview of available therapeutic strategies
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Davide Costa, Gemma Patella, Michele Provenzano, Nicola Ielapi, Teresa Faga, Mariateresa Zicarelli, Franco Arturi, Giuseppe Coppolino, Davide Bolignano, Giovambattista De Sarro, Umberto Marcello Bracale, Luca De Nicola, Paolo Chiodini, Raffaele Serra, and Michele Andreucci more...
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serum potassium ,chronic kidney disease ,RAAS-blockade ,potassium binder ,hypokalemic agents ,Medicine (General) ,R5-920 - Abstract
Hyperkalemia (HK) is a life-threatening condition that often occurs in patients with chronic kidney disease (CKD). High serum potassium (sKsK) is responsible for a higher risk of end-stage renal disease, arrhythmias and mortality. This risk increases in patients that discontinue cardio-nephroprotective renin–angiotensin–aldosterone system inhibitor (RAASi) therapy after developing HK. Hence, the management of HK deserves the attention of the clinician in order to optimize the therapeutic strategies of chronic treatment of HK in the CKD patient. The adoption in clinical practice of the new hypokalaemic agents patiromer and sodium zirconium cyclosilicate (SZC) for the prevention and chronic treatment of HK could allow patients, suffering from heart failure and chronic renal failure, to continue to benefit from RAASi therapy. We have updated a narrative review of the clear variables, correct definition, epidemiology, pathogenesis, etiology and classifications for HK among non-dialysis CKD (ND CKD) patients. Furthermore, by describing the prognostic impact on mortality and on the progression of renal damage, we want to outline the strategies currently available for the control of potassium (K+) plasma levels. more...
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- 2023
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16. A Retrospective Study (2015–2020) on the Risk Factors Associated with the Persistence and Spread of Brucellosis in Buffalo Farms in Caserta Province, Italy
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Maria Ottaiano, Roberta Brunetti, Antonio Limone, Maria Rosaria Capone, Alessandra Di Giuseppe, Annamaria Conte, Fabrizio De Massis, Paolo Chiodini, Simona Signoriello, Loredana Baldi, and E. De Carlo more...
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brucellosis ,risk factors ,regression model ,statistical association ,buffalo ,Caserta ,Veterinary medicine ,SF600-1100 - Abstract
Bovine and bubaline brucellosis is still present in some regions of Italy. Although control and eradication measures have been implemented for several years, the brucellosis situation remains problematic in the Campania region. The infection is present in the provinces of Salerno and Caserta, with the latter experiencing a drastic increase in the prevalence and incidence of infection in buffalo species (Bubalus bubalis) in recent years. The brucellosis eradication plan in Italy is subject to the European co-financing system, and failure to achieve the objectives of the plan has resulted in economic cuts for the Campania Region for years. This study aimed to evaluate the possible risk factors associated with the spread and persistence of brucellosis infection on buffalo farms in the Province of Caserta. The results of official controls carried out from 2015 to 2020 on the buffalo farms of the Province were analyzed. Statistical analysis was performed by means of the R software (version 4.1.0) on a final dataset consisting of 4583 observations. The possible association between covariates and outcome (presence/absence of infection) was evaluated (T-Fisher and Wilcoxon). A logistic regression model with mixed effects was carried out. The study shows that the risk of infection is statistically associated with the density of farms per square km and previous notifications of abortions on the same farms. Furthermore, animal movements constitute a risk factor for the permanence of infection over time (OR > 1), and herds already infected prior to 2015 were seen to have an almost three-fold higher risk of developing the disease (OR = 3.35). more...
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- 2024
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17. Risk Factors for the Spread of Brucellosis in Sheep and Goats in the Campania Region in the Years 2015–2020
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Roberta Brunetti, Maria Ottaiano, Mario Fordellone, Paolo Chiodini, Simona Signoriello, Federica Gargano, Fabrizio De Massis, Loredana Baldi, and Esterina De Carlo
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brucellosis ,risk factors ,regression model ,statistical association ,sheep and goats ,Biology (General) ,QH301-705.5 - Abstract
Brucella is a Gram-negative facultative intracellular pathogen that causes infection in sheep and goats (B. melitensis.); B. melitensis can also infect other animals. Sheep and goat brucellosis is still present in some regions of Italy, including Campania, and causes considerable economic losses and health threats. The aim of this study was to evaluate the possible risk factors influencing the spread of brucellosis among sheep and goat farms in the Campania region in order to provide the local veterinary services with practical support in evaluating and planning diagnostic, preventive and control interventions. The results of official controls for brucellosis carried out from 2015 to 2020 in the sheep and goat farms of the Campania Region were analyzed. Data were extracted from the National Veterinary Information Systems and the Laboratory Management System of the Experimental Zooprophylactic Institute of Southern Italy. Statistical analysis was carried out through the software R version 4.1.0; the dataset consisted of 37,442 observations, and 9 qualitative and quantitative variables were evaluated on 8487 farms, 248 of which were positive. The association between covariates and the outcome (presence/absence of the disease) was evaluated (Fisher and Wilcoxon tests). A logistic regression model with mixed effects was carried out. This study confirmed that brucellosis in sheep and goats in the Campania region mostly occurs through contact with infected animals imported from other farms (OR = 3.41—IC 95% [1.82–6.41]). Farms with a greater number of animals were seen to be at the greatest risk of infection (OR = 1.04—IC 95% [1.03–1.05]); previous suspension of healthy status also proved to be a risk factor (OR = 55.8—IC 95% [26.7–117]). more...
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- 2023
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18. The effect of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors on cardiorenal outcomes: a network meta-analysis of 23 CVOTs
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Dario Giugliano, Miriam Longo, Simona Signoriello, Maria Ida Maiorino, Bruno Solerte, Paolo Chiodini, and Katherine Esposito
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Cardiovascular outcome trials ,DPP-4 inhibitors ,GLP-1 receptor agonists ,SGLT-2 inhibitors ,Network meta-analysis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors reduce cardiorenal outcomes. We performed a network meta-analysis to compare the effect on cardiorenal outcomes among GLP-1 RAs, SGLT-2 inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. Methods We searched the PUBMED, Embase and Cochrane databases for relevant studies published up until 10 December 2021. Cardiovascular and renal outcome trials reporting outcomes on GLP-1RA, SGLT-2 inhibitors and DPP-4 inhibitors in patients with or without type 2 diabetes mellitus were included. The primary outcome was major adverse cardiovascular events (MACE); other outcomes were cardiovascular and total death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure (HHF), and renal outcome. Results Twenty-three trials enrolling a total number of 181,143 participants were included. DPP-4 inhibitors did not lower the risk of any cardiorenal outcome when compared with placebo and were associated with higher risks of MACE, HHF, and renal outcome when compared with the other two drug classes. SGLT-2 inhibitors significantly reduced cardiovascular (RR = 0.88) and total (RR = 0.87) death, as compared with DPP-4 inhibitors, while GLP-1 RA reduced total death only (RR = 0.87). The comparison between GLP-1RA and SGLT-2 inhibitors showed no difference in their risks of MACE, nonfatal MI, nonfatal stroke, CV and total death; SGLT-2 inhibitors were superior to GLP-1RA in reducing the risk of HHF and the renal outcome (24% and 22% lower risk, respectively). Only GLP-1RA reduced the risk of nonfatal stroke (RR = 0.84), as compared with placebo. There was no head-to-head trial directly comparing these antidiabetic drug classes. Conclusions SGLT-2 inhibitors and GLP-1RA are superior to DPP-4 inhibitors in reducing the risk of most cardiorenal outcomes; SGLT-2 inhibitors are superior to GLP-1RA in reducing the risk of HHF and renal events; GLP-1RA only reduced the risk of nonfatal stroke. Both SGLT-2 inhibitors and GLP-1RA should be the preferred treatment for type 2 diabetes and cardiorenal diseases. more...
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- 2022
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19. Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial
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Francesco Perrone, Maria Carmela Piccirillo, Paolo Antonio Ascierto, Carlo Salvarani, Roberto Parrella, Anna Maria Marata, Patrizia Popoli, Laurenzia Ferraris, Massimiliano M. Marrocco-Trischitta, Diego Ripamonti, Francesca Binda, Paolo Bonfanti, Nicola Squillace, Francesco Castelli, Maria Lorenza Muiesan, Miriam Lichtner, Carlo Calzetti, Nicola Duccio Salerno, Luigi Atripaldi, Marco Cascella, Massimo Costantini, Giovanni Dolci, Nicola Cosimo Facciolongo, Fiorentino Fraganza, Marco Massari, Vincenzo Montesarchio, Cristina Mussini, Emanuele Alberto Negri, Gerardo Botti, Claudia Cardone, Piera Gargiulo, Adriano Gravina, Clorinda Schettino, Laura Arenare, Paolo Chiodini, Ciro Gallo, and the TOCIVID-19 investigators, Italy more...
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Medicine - Published
- 2021
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20. Improvement of glycemic control and reduction of major cardiovascular events in 18 cardiovascular outcome trials: an updated meta-regression
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Maria Ida Maiorino, Miriam Longo, Lorenzo Scappaticcio, Giuseppe Bellastella, Paolo Chiodini, Katherine Esposito, and Dario Giugliano
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Cardiovascular outcome trials ,Type 2 diabetes ,DPP-4i ,GLP-1RA ,SGLT-2i ,Cardiorenal outcomes ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Besides providing reassurance about cardiovascular (CV) safety of newer diabetes drugs, cardiovascular outcome trials (CVOTs) have also shown encouraging benefits on some CV endpoints. The contribution of the better glycemic control in the reduction of major cardiovascular events (MACE) remains an open question. The aim of this study is to evaluate the associations between the reduction of HbA1c and risk of MACE, MACE components, hospitalization for heart failure (HF) and all-cause death in CVOTs. Methods An electronic search up to July 2021 was conducted to determine eligible trials. Systematic review identified eighteen CVOTs reporting prespecified CV outcomes. Pooled summary estimates and 95% confidence intervals (CI) were calculated according to the random effects model using the Paule-Mandel method; restricted maximum likelihood estimators were used to estimate model parameters in the metaregression. Results The eighteen CVOTs evaluated 161,156 patients and included four trials with dipeptidyl-peptidase-4 inhibitors (DPP-4i), eight trials with glucagon-like peptide-1 receptor agonists (GLP-1RA) and six trials with sodium-glucose cotransporter-2 inhibitors (SGLT-2i). Random-effects model meta-analysis showed an association between treatment and risk of MACE (hazard ratio [HR] 0.90; 95% CI 0.86, 0.94, P more...
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- 2021
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21. GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs
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Dario Giugliano, Lorenzo Scappaticcio, Miriam Longo, Paola Caruso, Maria Ida Maiorino, Giuseppe Bellastella, Antonio Ceriello, Paolo Chiodini, and Katherine Esposito
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Cardiovascular outcome trials ,Type 2 diabetes ,GLP-1RA ,Cardiorenal outcomes ,Lixisenatide ,Liraglutide ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background A meta-analysis is presented of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) versus placebo on cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods We did an electronic search up to June 30, 2021, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). We included data from 8 CVOTs and 60,080 patients (72.4% with established cardiovascular disease). Results GLP-1RA reduced major cardiovascular events (MACE) by 14% (HR = 0.86, 95% CI 0.79–0.94, P = 0.006) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (P = 0.127). GLP-1RA also reduced the risk of cardiovascular death by 13% (P = 0.016), nonfatal stroke by 16% (P = 0.007), hospitalization for heart failure by 10% (P = 0.023), all-cause mortality by 12% (P = 0.012), and the broad composite kidney outcome by 17% (P = 0.012), which was driven by a reduction in macroalbuminuria only (HR = 0.74, 0.67–0.82, P more...
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- 2021
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22. Comparing the COVID-19 pandemic in space and over time in Europe, using numbers of deaths, crude rates and adjusted mortality trend ratios
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Valentina Gallo, Paolo Chiodini, Dario Bruzzese, Elias Kondilis, Dan Howdon, Jochen Mierau, and Raj Bhopal
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Medicine ,Science - Abstract
Abstract Comparison of COVID-19 trends in space and over time is essential to monitor the pandemic and to indirectly evaluate non-pharmacological policies aimed at reducing the burden of disease. Given the specific age- and sex- distribution of COVID-19 mortality, the underlying sex- and age-distribution of populations need to be accounted for. The aim of this paper is to present a method for monitoring trends of COVID-19 using adjusted mortality trend ratios (AMTRs). Age- and sex-mortality distribution of a reference European population (N = 14,086) was used to calculate age- and sex-specific mortality rates. These were applied to each country to calculate the expected deaths. Adjusted Mortality Trend Ratios (AMTRs) with 95% confidence intervals (C.I.) were calculated for selected European countries on a daily basis from 17th March 2020 to 29th April 2021 by dividing observed cumulative mortality, by expected mortality, times the crude mortality of the reference population. These estimated the sex- and age-adjusted mortality for COVID-19 per million population in each country. United Kingdom experienced the highest number of COVID-19 related death in Europe. Crude mortality rates were highest Hungary, Czech Republic, and Luxembourg. Accounting for the age-and sex-distribution of the underlying populations with AMTRs for each European country, four different patterns were identified: countries which experienced a two-wave pandemic, countries with almost undetectable first wave, but with either a fast or a slow increase of mortality during the second wave; countries with consistently low rates throughout the period. AMTRs were highest in Eastern European countries (Hungary, Czech Republic, Slovakia, and Poland). Our methods allow a fair comparison of mortality in space and over time. These might be of use to indirectly estimating the efficacy of non-pharmacological health policies. The authors urge the World Health Organisation, given the absence of age and sex-specific mortality data for direct standardisation, to adopt this method to estimate the comparative mortality from COVID-19 pandemic worldwide. more...
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- 2021
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23. Efficacy and durability of multifactorial intervention on mortality and MACEs: a randomized clinical trial in type-2 diabetic kidney disease
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Ferdinando Carlo Sasso, Pia Clara Pafundi, Vittorio Simeon, Luca De Nicola, Paolo Chiodini, Raffaele Galiero, Luca Rinaldi, Riccardo Nevola, Teresa Salvatore, Celestino Sardu, Raffaele Marfella, Luigi Elio Adinolfi, Roberto Minutolo, and NID-2 Study Group Investigators more...
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Diabetic nephropathy ,Multifactorial intervention ,Intensified treatment ,CV risk factors ,Very high CV risk ,MACE ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure 40/50 mg/dL for men/women and more...
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- 2021
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24. A scoping review of retracted publications in anesthesiology
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Marco Fiore, Aniello Alfieri, Maria Caterina Pace, Vittorio Simeon, Paolo Chiodini, Sebastiano Leone, Stefan Wirz, Arturo Cuomo, Vincenzo Stoia, and Marco Cascella
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anesthesiology ,duplicate publication ,fraud ,plagiarism ,scoping review ,Anesthesiology ,RD78.3-87.3 - Abstract
Context: Fraudulent publication is a scourge of scientific research. Objectives: This scoping review was aimed at characterizing retracted publications for fraud or plagiarism in the field of anesthesia. Does the reputation of the journal (Quartile and Impact Factor, IF) protect the reader from the risk of having the manuscript he read withdrawn for fraud/plagiarism? Methods/Design: This scoping review was planned following the Joanna Briggs Institute recommendations. Data sources: PubMed and the Retraction Watch Database (http://retractiondatabase.org/RetractionSearch.aspx?). Study selection: All types of publications retracted. Data extraction: Year, first author nationality, journal name, journal category, IF, Quartile, H index. Data analysis: The association with Quartile and IF was investigated. Results: No significant association between retraction of papers published in no-Quartile journals and retractions published in journals placed in the highest quartile. Conclusions: The quality of the surveillance in paper submission is not higher in journals of the first Quartile than in journals not placed in other Quartiles. (The protocol was prospectively registered in the Open Science Framework https://doi.org/10.17605/OSF.IO/TGKNE) more...
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- 2021
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25. Modeling for the Stringency of Lock-Down Policies: Effects of Macroeconomic and Healthcare Variables in Response to the COVID-19 Pandemic
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Giunio Santini, Mario Fordellone, Silvia Boffo, Simona Signoriello, Danila De Vito, and Paolo Chiodini
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lock-down modeling ,socio economic impact ,containment policies ,COVID-19 ,SARS-CoV-2 pandemic ,healthcare services ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundThe spread of COVID-19 has been characterized by unprecedented global lock-downs. Although, the extent of containment policies cannot be explained only through epidemic data. Previous studies already focused on the relationship between the economy and healthcare, focusing on the impact of diseases in countries with a precarious economic situation. However, the pandemic caused by SARS-CoV-2 drew most countries of the world into a precarious economic situation mostly caused by the global and local lock-downs policies.MethodsA discriminant analysis performed via partial least squares procedure was applied to evaluate the impact of economic and healthcare variables on the containment measures adopted by 39 countries. To collect the input variables (macroeconomic, healthcare, and medical services), we relied on official databases of international organizations, such as The World Bank and WHO.ResultsThe stringency lock-down policies could not only be influenced by the epidemical data, but also by previous features of the selected countries, such as economic and healthcare conditions.ConclusionsIndeed, economic and healthcare variables also contributed to shaping the implemented lock-down policies. more...
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- 2022
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26. Evaluation of the diagnostic accuracy of a new point-of-care rapid test for SARS-CoV-2 virus detection
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Leonardo Miscio, Antonio Olivieri, Francesco Labonia, Gianfranco De Feo, Paolo Chiodini, Giuseppe Portella, Luigi Atripaldi, Roberto Parrella, Rodolfo Conenna, Franco Maria Buonaguro, Ernesta Cavalcanti, Paolo Ascierto, Gerardo Botti, and Attilio Bianchi more...
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SARS-CoV-2 ,COVID-19 ,Point-of-care rapid test ,Health surveillance ,Medicine - Abstract
Abstract Background The easy access to a quick diagnosis of coronavirus disease 2019 (COVID-19) is a key point to improve the management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to contain its spread. Up to now, laboratory real-time PCR is the standard of care, but requires a fully equipped laboratory and significant infrastructure. Consequently, new diagnostic tools are required. Methods In the present work, the diagnostic accuracy of the point-of-care rapid test "bKIT Virus Finder COVID-19" (Hyris Ltd) is evaluated by a retrospective and a prospective analysis on SARS CoV-2 samples previously assessed with an FDA “authorized for the emergency use—EUA” reference method. Descriptive statistics were used for the present study. Results Results obtained with the Hyris Kit are the same as that of standard laboratory-based real time PCR methods for all the analyzed samples. In addition, the Hyris Kit provides the test results in less than 2 h, a significantly shorter time compared to the reference methods, without the need of a fully equipped laboratory. Conclusions To conclude, the Hyris kit represents a promising tool to improve the health surveillance and to increase the capacity of SARS-CoV-2 testing. more...
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- 2020
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27. A new 'hub and spoke' teledermoscopy system involving general practitioners and dermatologists for the early detection of cutaneous melanoma: a pilot study
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Gabriella Fabbrocini, Sara Cacciapuoti, Gaia De Fata Salvatores, Claudia Costa, Paolo Chiodini, Maria Antonietta Luciano, Serena Poggi, Silvestro Scotti, Luigi Sparano, Giuseppe Di Leo, Paolo Sommella, Matteo Ferro, and Massimiliano Scalvenzi more...
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teledermoscopy ,melanoma ,general practitioners ,early detection ,Chemical engineering ,TP155-156 ,Biotechnology ,TP248.13-248.65 ,Medical technology ,R855-855.5 - Abstract
The incidence of cutaneous melanoma has been increasing over the past few decades. The introduction of dermoscopy has enriched the diagnostic armamentarium of dermatologists improving diagnostic accuracy. The involvement of General Practitioners (GPs) and the use of telemedicine systems could constitute a new resource to make available early diagnosis to a larger population and to rationalize health resources in favor of patients at high risk of developing skin tumors. Aims: Primary aim of this study is to assess the feasibility of a “hub and spoke” model for the cooperation between high-specialty hospital units and GPs, using a new online teledermatology platform (I3DermoscopyApp®), that recently has been proved as a valid semiautomatic diagnostic image-based measurement system. Secondary aim is to evaluate the reliability of this semiautomatic diagnostic system in a clinical model of real life. Methods: An observational cross-sectional study using a “hub and spoke” model, was conducted at Dermatology Unit of Department of Clinical Medicine and Surgery of University Federico II of Naples. GPs and dermatologists were involved in this study after a demormoscopy traninig. Results: The system proved to be reliable in the triage phase and useful in the rationalization of highly specialized medical resources. Comparing patients diagnosed with malignant skin tumors through teledermoscopy system with patients with the same skin lesions of our department not participating to the study, we noticed that latency time between diagnosis and surgical excision were significantly decreased demonstrating the reliability of this semiautomatic diagnostic system in a clinical model of real life. Discussion: This study demonstrating the feasibility of a hub and spoke system based on a teledermatology cooperation between GPs and dermoscopy trained dermatologists. The use of teledermoscopy improves the ability of GPs selecting lesions suggestive of skin cancer without increasing the number of unnecessary expert consultations. more...
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- 2020
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28. Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial
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Francesco Perrone, Maria Carmela Piccirillo, Paolo Antonio Ascierto, Carlo Salvarani, Roberto Parrella, Anna Maria Marata, Patrizia Popoli, Laurenzia Ferraris, Massimiliano M. Marrocco-Trischitta, Diego Ripamonti, Francesca Binda, Paolo Bonfanti, Nicola Squillace, Francesco Castelli, Maria Lorenza Muiesan, Miriam Lichtner, Carlo Calzetti, Nicola Duccio Salerno, Luigi Atripaldi, Marco Cascella, Massimo Costantini, Giovanni Dolci, Nicola Cosimo Facciolongo, Fiorentino Fraganza, Marco Massari, Vincenzo Montesarchio, Cristina Mussini, Emanuele Alberto Negri, Gerardo Botti, Claudia Cardone, Piera Gargiulo, Adriano Gravina, Clorinda Schettino, Laura Arenare, Paolo Chiodini, Ciro Gallo, and the TOCIVID-19 investigators, Italy more...
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COVID-19 ,Pneumonia ,Coronavirus ,Tocilizumab ,IL-6 ,Phase 2 ,Medicine - Abstract
Abstract Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P more...
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- 2020
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29. Preventing major adverse cardiovascular events by SGLT-2 inhibition in patients with type 2 diabetes: the role of kidney
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Dario Giugliano, Luca De Nicola, Maria Ida Maiorino, Giuseppe Bellastella, Carlo Garofalo, Paolo Chiodini, Antonio Ceriello, and Katherine Esposito
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SGLT-2 inhibitors ,Type 2 diabetes ,MACE ,Diabetic kidney disease ,Statin therapy ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Cardiovascular outcome trials (CVOTs) have demonstrated a significant reduction of major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D) treated by SGLT-2 inhibitors. This holds true in the presence of background therapy with statins in most patients. Noteworthy, this SGLT-2 inhibitors effect is unique because, at variance with other components of cardiorenal protection, MACE prevention does not appear to be a class effect. Here, we present meta-analysis of the four key CVOTs indicating a major role of renal function in determining the extent of MACE prevention, with the benefit increasing in more severe kidney disease, that is, a high-risk condition where effectiveness of the traditional approach with statins is reduced. more...
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- 2020
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30. A Maximum-Entropy Fuzzy Clustering Approach for Cancer Detection When Data Are Uncertain
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Mario Fordellone, Ilaria De Benedictis, Dario Bruzzese, and Paolo Chiodini
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cancer detection ,cancer classification ,unsupervised classification ,entropy regularization procedure ,penalized classification model ,interval-valued data ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
(1) Background: Cancer is a leading cause of death worldwide and each year, approximately 400,000 children develop cancer. Early detection of cancer greatly increases the chances for successful treatment, while screening aims to identify individuals with findings suggestive of specific cancer or pre-cancer before they have developed symptoms. Precise detection, however, often mainly relies on human experience and this could suffer from human error and error with a visual inspection. (2) Methods: The research of statistical approaches to analyze the complex structure of data is increasing. In this work, an entropy-based fuzzy clustering technique for interval-valued data (EFC-ID) for cancer detection is suggested. (3) Results: The application on the Breast dataset shows that EFC-ID performs better than the conventional FKM in terms of AUC value (EFC-ID = 0.96, FKM = 0.88), sensitivity (EFC-ID = 0.90, FKM = 0.64), and specificity (EFC-ID = 0.93, FKM = 0.92). Furthermore, the application on the Multiple Myeloma data shows that EFC-ID performs better than the conventional FKM in terms of Chi-squared (EFC-ID = 91.64, FKM = 88.26), Accuracy rate (EFC-ID = 0.71, FKM = 0.60), and Adjusted Rand Index (EFC-ID = 0.33, FKM = 0.21). (4) Conclusions: In all cases, the proposed approach has shown good performance in identifying the natural partition and the advantages of the use of EFC-ID have been detailed illustrated. more...
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- 2023
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31. The opportunity of patient-journey studies for academic clinical research in oncology
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Raimondo Di Liello, Ciro Gallo, Francesco Perrone, Laura Arenare, Paolo Chiodini, Maria Carmela Piccirillo, Piera Gargiulo, and Lorenzo Guizzaro
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Medicine - Abstract
A wave of new treatments and treatment combinations are becoming available for solid tumours. Trials performed to obtain registration establish a positive benefit-risk but unavoidably leave many questions unanswered on place-in-therapy and the relative efficacy of different treatment sequences. Such limitations create problems in terms of strength of treatment guidelines and reimbursement (in countries where a public payer exists). Data on new drugs arriving during the last 10 years for the treatment of hepatocellular carcinoma and renal cancer are reported as an example of how the fortunate condition of having new effective treatments may translate into uncertainty regarding the optimal treatment plan. We suggest that academic research should react to such limitations and propose a model of patient-journey study (PJS), where patients are followed from the initial diagnosis across subsequent lines of treatment. A PJS master protocol might include at each node of clinical decision either the possibility of choosing treatment according to guidelines (generating prospective real-world evidence) or the possibility to randomise where uncertainty exists (generating comparative effectiveness data). PJS protocols might be adaptively modified every time a new drug arrives on the market. Overall, methodologically sound analyses of PJS will produce knowledge on the efficacy and the effectiveness of different treatment pathways and might significantly optimise treatment of patients in clinical practice. PJS would represent a jump from a few snapshots (trials performed to get regulatory approval) to a full movie (evidence on the relative value of treatment pathways). more...
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- 2021
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32. Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol
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Alessandro Ottaiano, Stefania Scala, Nicola Normanno, Maria Napolitano, Monica Capozzi, Anna Maria Rachiglio, Cristin Roma, Anna Maria Trotta, Crescenzo D’Alterio, Luigi Portella, Carmela Romano, Antonino Cassata, Rossana Casaretti, Lucrezia Silvestro, Anna Nappi, Salvatore Tafuto, Antonio Avallone, Alfonso De Stefano, Mario Tamburini, Carmine Picone, Antonella Petrillo, Francesco Izzo, Raffaele Palaia, Vittorio Albino, Alfonso Amore, Andrea Belli, Ugo Pace, Massimiliano Di Marzo, Paolo Chiodini, Gerardo Botti, Gianfranco De Feo, Paolo Delrio, and Guglielmo Nasti more...
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Colorectal Cancer ,Antibody-dependent cell-mediated cytotoxicity ,Cetuximab ,Irinotecan ,Fluorouracule ,FcγR ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Combination of chemotherapies (fluoropirimidines, oxaliplatin and irinotecan) with biologic drugs (bevacizumab, panitumumab, cetuximab) have improved clinical responses and survival of metastatic colorectal cancer (mCRC). However, patients’ selection thorough the identification of predictive factors still represent a challange. Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicite both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). ADCC is the cytotoxic killing of antibody-coated target cells by immunologic effectors. The effector cells express a receptor for the Fc portion of these antibodies (FcγR); genetic polymorphisms of FcγR modify the binding affinity with the Fc of IgG1. Interestingly, the high-affinity FcγRIIIa V/V is associated with increased ADCC in vitro and in vivo. Thus, ADCC could partially account for cetuximab activity. Methods/design CIFRA is a single arm, open-label, phase II study assessing the activity of cetuximab in combination with irinotecan and fluorouracile in FcγRIIIa V/V patients with KRAS, NRAS, BRAF wild type mCRC. The study is designed with a two-stage Simon model based on a hypothetical higher response rate (+ 10%) of FcγRIIIa V/V patients as compared to previous trials (about 60%) assuming ADCC as one of the possible mechanisms of cetuximab action. The test power is 95%, the alpha value of the I-type error is 5%. With these assumptions the sample for passing the first stage is 14 patients with > 6 responses and the final sample is 34 patients with > 18 responses to draw positive conclusions. Secondary objectives include toxicity, responses’ duration, progression-free and overall survival. Furthermore, an associated translational study will assess the patients’ cetuximab-mediated ADCC and characterize the tumor microenvironment. Discussion The CIFRA study will determine whether ADCC contributes to cetuximab activity in mCRC patients selected on an innovative immunological screening. Data from the translational study will support results’ interpretation as well as provide new insights in host-tumor interactions and cetuximab activity. Trial registration The CIFRA trial (version 0.0, June 21, 2018) has been registered into the NIH-US National Library of Medicine, ClinicalTrials.gov database with the identifier number (NCT03874062). more...
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- 2019
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33. Preventive skin analgesia with lidocaine patch for management of post‐thoracotomy pain: Results of a randomized, double blind, placebo controlled study
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Alfonso Fiorelli, Caterina Pace, Roberto Cascone, Annalisa Carlucci, Emanuele De Ruberto, Anna Cecilia Izzo, Beatrice Passavanti, Paolo Chiodini, Vincenzo Pota, Caterina Aurilio, Mario Santini, and Pasquale Sansone more...
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Lidocaine patch ,post‐thoracotomy pain ,pre‐emptive analgesia ,thoracic surgery ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background To evaluate whether pre‐emptive skin analgesia using a lidocaine patch 5% would improve the effects of systemic morphine analgesia for controlling acute post‐thoracotomy pain. Methods This was a double‐blind, placebo controlled, prospective study. Patients were randomly assigned to receive lidocaine 5% patch (lidocaine group) or a placebo (placebo group) three days before thoracotomy. Postoperative analgesia was induced in all cases with intravenous morphine analgesia. The intergroup differences were assessed in order to evaluate whether the lidocaine patch 5% would have effects on pain intensity when at rest and after coughing (primary end‐point) on morphine consumption, on the recovery of respiratory function, and on peripheral painful pathways measured with N2 and P2 laser‐evoked potential (secondary end‐points). Results A total of 90 patients were randomized, of whom 45 were allocated to the lidocaine group and 45 to the placebo group. Lidocaine compared with the placebo group showed a significant reduction in pain intensity both at rest (P = 0.013) and after coughing (P = 0.015), and in total morphine consumption (P = 0.001); and also showed a better recovery of flow expiratory volume in one second (P = 0.025) and of forced vital capacity (P = 0.037). The placebo group compared with the lidocaine group presented a reduction in amplitude of N2 (P = 0.001) and P2 (P = 0.03), and an increase in the latency of N2 (P = 0.023) and P2 (P = 0.025) laser‐evoked potential. Conclusions The preventive skin analgesia with lidocaine patch 5% seems to be a valid adjunct to intravenous morphine analgesia for controlling post‐thoracotomy pain. However, our initial results should be corroborated/confirmed by larger studies. more...
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- 2019
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34. Analysis of A Disintegrin and Metalloprotease 17 (ADAM17) Expression as a Prognostic Marker in Ovarian Cancer Patients Undergoing First-Line Treatment Plus Bevacizumab
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Marina Fabbi, Delfina Costa, Daniela Russo, Laura Arenare, Gabriele Gaggero, Simona Signoriello, Giovanni Scambia, Carmela Pisano, Nicoletta Colombo, Nunzia Simona Losito, Gilberto Filaci, Anna Spina, Daniela Califano, Giosuè Scognamiglio, Angiolo Gadducci, Delia Mezzanzanica, Marina Bagnoli, Silvano Ferrini, Vincenzo Canzonieri, Paolo Chiodini, Francesco Perrone, and Sandro Pignata more...
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ovarian cancer ,ADAM17 ,immunohistochemistry ,bevacizumab treatment ,prognostic biomarker ,Medicine (General) ,R5-920 - Abstract
To find prognostic factors for advanced ovarian cancer patients undergoing first-line therapy with carboplatin, paclitaxel and bevacizumab, we investigated the expression of a disintegrin and metalloprotease 17 (ADAM17) in cancer tissues. ADAM17 has been involved in ovarian cancer development, progression and cell resistance to cisplatin. Tissue microarrays from 309 ovarian cancer patients enrolled in the MITO16A/MANGO-OV2 clinical trial were analyzed by immunohistochemistry for ADAM17 protein expression. Intensity and extent of staining were combined into a semi-quantitative visual grading system (H score) which was related to clinicopathological characteristics of cases and the clinical outcome of patients by univariate and multivariate Cox regression models. ADAM17 immunostaining was detected in most samples, mainly localized in the tumor cells, with variable intensity across the cohort. Kaplan–Meier survival curves, generated according to the best cut-off value for the ADAM17 H score, showed that high ADAM17 expression was associated with worse prognosis for PFS and OS. However, after the application of a shrinkage procedure to adjust for overfitting hazard ratio estimates, the ADAM17 value as prognostic factor was lost. As subgroup analysis suggested that ADAM17 expression could be prognostically relevant in cases with no residual disease at baseline, further studies in this patient category may be worth planning. more...
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- 2022
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35. Unsupervised Hierarchical Classification Approach for Imprecise Data in the Breast Cancer Detection
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Mario Fordellone and Paolo Chiodini
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unsupervised classification ,hierarchical classification ,interval-valued data ,imprecise data ,cancer detection ,cancer classification ,Science ,Astrophysics ,QB460-466 ,Physics ,QC1-999 - Abstract
(1) Background: in recent years, a lot of the research of statistical methods focused on the classification problem in presence of imprecise data. A particular case of imprecise data is the interval-valued data. Following this research line, in this work a new hierarchical classification technique for multivariate interval-valued data is suggested for diagnosis of the breast cancer; (2) Methods: an unsupervised hierarchical classification method for imprecise multivariate data (called HC-ID) is performed for diagnosis of breast cancer (i.e., to discriminate between benign or malignant masses) and the results have been compared with the conventional (unsupervised) hierarchical classification approach (HC); (3) Results: the application on real data shows that the HC-ID procedure performs better HC procedure in terms of accuracy (HC-ID = 0.80, HC = 0.66) and sensitivity (HC-ID = 0.61, HC = 0.08). In the results obtained by the usual procedure, there is a high degree of false-negative (i.e., benign cancer diagnosis in malignant status) affected by the high degree of variability (i.e., uncertainty) characterizing the worst data. more...
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- 2022
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36. Aflibercept or bevacizumab in combination with FOLFIRI as second-line treatment of mRAS metastatic colorectal cancer patients: the ARBITRATION study protocol
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Alessandro Ottaiano, Stefania Scala, Mariachiara Santorsola, Anna Maria Trotta, Crescenzo D’Alterio, Luigi Portella, Ottavia Clemente, Anna Nappi, Nicoletta Zanaletti, Alfonso De Stefano, Antonio Avallone, Vincenza Granata, Carmen Notariello, Amalia Luce, Angela Lombardi, Carmine Picone, Antonella Petrillo, Francesco Perri, Fabiana Tatangelo, Annabella Di Mauro, Vittorio Albino, Francesco Izzo, Daniela Rega, Ugo Pace, Massimiliano Di Marzo, Paolo Chiodini, Gianfranco De Feo, Paola Del Prete, Gerardo Botti, Paolo Delrio, Michele Caraglia, and Guglielmo Nasti more...
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: The intensive study of predictive factors has strongly ameliorated the therapeutic flow-chart of metastatic colorectal cancer (mCRC) by allowing the selection of patients who benefit from specific therapies. For instance, in mRAS (mutated RAS) mCRC patients, anti-EGFR drugs (cetuximab and panitumumab) are not recommended; in this group of patients, the use of anti-angiogenic drugs (bevacizumab and aflibercept) is predominant. However, at progression to standard bevacizumab-based first-line chemotherapy, still to date, there are no studies to guide oncologists in the choice of the best second-line anti-angiogenic drug (bevacizumab beyond progression versus aflibercept). Methods: ARBITRATION is a prospective, observational study assessing efficacy differences between second-line fluorouracil/irinotecan (FOLFIRI)/bevacizumab versus FOLFIRI/aflibercept at progression to fluoropyrimidines, oxaliplatin and bevacizumab in mRAS mCRC patients. A test power of 80%, a median survival of 9 months from second-line treatment start and a hazard ratio of 0.67 between the two schedules were the basis for statistical design. The final sample will be 220 patients (110 per treatment). The significance will be verified with a two-tailed log-rank test with an alpha value of the I-type error of 5%. Time-to-outcome will be described by Kaplan–Meier curves and prognostic factors studied through multivariable analyses based on the Cox model. Secondary objectives include safety, responses’ duration and progression-free survival. A translational research will be conducted to measure several angiogenic proteins in patients’ serum before starting the therapy in order to evidence any angiogenic factor patterns related to outcome. Discussion: We present a large, prospective, observational study aiming to answer two scientific questions: (1) outcome differences between second-line treatments with FOLFIRI/bevacizumab beyond progression versus FOLFIRI/aflibercept in mRAS mCRC patients, (2) angiogenic factors’ patterns that could associate with efficacy and help oncologists to apply best the therapeutic anti-angiogenic strategies. Trial registration: The ARBITRATION trial (version 0.0, 13 April 2020) has been registered into the clinicaltrials.gov registry on 20 May 2020 with identifier NCT04397601. more...
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- 2021
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37. Lack of effect on in-hospital mortality of drugs used during COVID-19 pandemic: Findings of the retrospective multicenter COVOCA study.
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Pia Clara Pafundi, Raffaele Galiero, Vittorio Simeon, Luca Rinaldi, Alessandro Perrella, Erica Vetrano, Alfredo Caturano, Maria Alfano, Domenico Beccia, Riccardo Nevola, Raffaele Marfella, Celestino Sardu, Carmine Coppola, Ferdinando Scarano, Paolo Maggi, Pellegrino De Lucia Sposito, Laura Vocciante, Carolina Rescigno, Costanza Sbreglia, Fiorentino Fraganza, Roberto Parrella, Annamaria Romano, Giosuele Calabria, Benedetto Polverino, Antonio Pagano, Carolina Bologna, Maria Amitrano, Vincenzo Esposito, Nicola Coppola, Nicola Maturo, Luigi Elio Adinolfi, Paolo Chiodini, Ferdinando Carlo Sasso, and COVOCA Study Group more...
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Medicine ,Science - Abstract
IntroductionDuring COVID-19 pandemic, the use of several drugs has represented the worldwide clinical practice. However, though the current increase of knowledge about the disease, there is still no effective treatment for the usage of drugs. Thus, we retrospectively assessed use and effects of therapeutic regimens in hospitalized patients on in-hospital mortality.MethodsCOVOCA is a retrospective observational cohort study on 18 COVID centres throughout Campania Region Hospitals. We included adult patients with confirmed SARS-CoV-2 infection, discharged/dead between March/June 2020.Results618 patients were included, with an overall in-hospital cumulative mortality incidence of 23.1%. Most prescribed early treatments were antivirals (72%), antibiotics (65%) and hydroxychloroquine/anticoagulants (≈50%). Tocilizumab, indeed, was largely prescribed late during hospitalization. Multivariable models, with a cut-off at day 2 for early COVID-19 therapy administration, did not disclose any significant association of a single drug administration on the clinical outcome.DiscussionCOVOCA represents the first multicenter database in Campania region. None drug class used during the pandemic significantly modified the outcome, regardless of therapy beginning, both overall and net of those already in non-invasive ventilation (NIV)/ orotracheal intubation (OTI) at hospitalization. Our cumulative incidence of mortality seems lower than other described during the same period, particularly in Northern Italy. more...
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- 2021
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38. Carboplatin and paclitaxel plus avelumab compared with carboplatin and paclitaxel in advanced or recurrent endometrial cancer (MITO END-3): a multicentre, open-label, randomised, controlled, phase 2 trial
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Sandro Pignata, Giovanni Scambia, Clorinda Schettino, Laura Arenare, Carmela Pisano, Davide Lombardi, Ugo De Giorgi, Claudia Andreetta, Saverio Cinieri, Carmine De Angelis, Domenico Priolo, Claudia Casanova, Marta Rosati, Filippo Greco, Elena Zafarana, Ilaria Schiavetto, Serafina Mammoliti, Sabrina Chiara Cecere, Vanda Salutari, Simona Scalone, Alberto Farolfi, Marilena Di Napoli, Domenica Lorusso, Piera Gargiulo, Daniela Califano, Daniela Russo, Anna Spina, Rossella De Cecio, Paolo Chiodini, Francesco Perrone, Valentina Accinno, Chiara Altavilla, Giovanna Antonelli, Grazia Artioli, Francesco Avola, Bonifacio Barbara, Valentina Barbato, Michele Bartoletti, Simona Bevilacqua, Roberto Bordonaro, Oriana Borghese, Gaetano Buonfanti, Floriana Camarda, Giuliana Canzanella, Vittoria Carbone, Maria Rita Carbone, Giulia Carlo Stella, Chiara Cassani, Fabrizio Castagna, Monica Cattaneo, Margherita Cinefra, Nicoletta Colombo, Serena Corsetti, Monia Dall'Agata, Maria D'Amico, Gennaro Daniele, Elvira De Marino, Giovanni De Matteis, Sabino De Placido, Gabriella Del Bene, Antonia Del Giudice, Francesca Del Monte, Michele Del Sesto, Maddalena Donini, Giuliana Drudi, Gianluca Falcone, Adolfo Favaretto, Giulia Ferrera, Manuela Florio, Valeria Forestieri, Maria Stella Gallo, Ciro Gallo, Francesca Garibaldi, Fabiana Gerevini, Viola Ghizzoni, Maria Olga Giganti, Anna Gimigliano, Elena Giudice, Nicoletta Gnocchi, Adriano Gravina, Stefano Greggi, Maria Laura Iaia, Annalisa Ilardi, Gelsomina Iovine, Gabriella Ippoliti, Giulia Irollo, Ilenia Isidori, Mariateresa Lapresa, Giuseppe Lavenia, Laura Longhitano, Bortot Lucia, Gabriella Luzi, Sara Mariano, Valentina Marino, Giovanna Marrapese, Marilena Martino, Roberta Matocci, Enrica Mazzoni, Daniela Mercuri, Maria Mirto, Giovanna Mollo, Abbondanza Montinaro, Marta Moscatelli, Anna Maria Mosconi, Lucia Musacchio, Nicoletta Nanni, Pamela Natalucci, Milena Sabrina Nicoloso, Michele Orditura, Gabriella Maria Parma, Rodolfo Passalacqua, Michela Pelone, Maria Teresa Perri, Bruno Perrucci, Alessandra Piancastelli, Maria Carmela Piccirillo, Antonio Piccolo, Stefania Rapisardi, Giorgia Ravaglia, Teresa Ribecco, Caterina Ricci, Marianna Roccio, Fiorella Romano, Daniela Sambataro, Alfonso Savio, Ada Sbriglia, Cono Scaffa, Concetta Sergi, Francesca Sgandurra, Roberto Sorio, Stefano Stabile, Gianna Tabaro, Margherita Tambaro, Stefano Tamberi, Angelica Tecchiato, Angela Maria Trujillo, Eleonora Zaccarelli, Pignata, S, Scambia, G, Schettino, C, Arenare, L, Pisano, C, Lombardi, D, De Giorgi, U, Andreetta, C, Cinieri, S, De Angelis, C, Priolo, D, Casanova, C, Rosati, M, Greco, F, Zafarana, E, Schiavetto, I, Mammoliti, S, Cecere, S, Salutari, V, Scalone, S, Farolfi, A, Di Napoli, M, Lorusso, D, Gargiulo, P, Califano, D, Russo, D, Spina, A, De Cecio, R, Chiodini, P, Perrone, F, Accinno, V, Altavilla, C, Antonelli, G, Artioli, G, Avola, F, Barbara, B, Barbato, V, Bartoletti, M, Bevilacqua, S, Bordonaro, R, Borghese, O, Buonfanti, G, Camarda, F, Canzanella, G, Carbone, V, Carbone, M, Carlo Stella, G, Cassani, C, Castagna, F, Cattaneo, M, Cinefra, M, Colombo, N, Corsetti, S, Dall'Agata, M, D'Amico, M, Daniele, G, De Marino, E, De Matteis, G, De Placido, S, Del Bene, G, Del Giudice, A, Del Monte, F, Del Sesto, M, Donini, M, Drudi, G, Falcone, G, Favaretto, A, Ferrera, G, Florio, M, Forestieri, V, Gallo, M, Gallo, C, Garibaldi, F, Gerevini, F, Ghizzoni, V, Giganti, M, Gimigliano, A, Giudice, E, Gnocchi, N, Gravina, A, Greggi, S, Iaia, M, Ilardi, A, Iovine, G, Ippoliti, G, Irollo, G, Isidori, I, Lapresa, M, Lavenia, G, Longhitano, L, Lucia, B, Luzi, G, Mariano, S, Marino, V, Marrapese, G, Martino, M, Matocci, R, Mazzoni, E, Mercuri, D, and Mirto, M more...
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Oncology ,Carboplatin - Abstract
Background: Adding immunotherapy to first-line chemotherapy might improve outcomes for patients with advanced or recurrent endometrial cancer. We aimed to compare carboplatin and paclitaxel versus avelumab plus carboplatin and paclitaxel as first-line treatment with avelumab given concurrent to chemotherapy and as maintenance after the end of chemotherapy. Methods: MITO END-3 is an open-label, randomised, controlled, phase 2 trial conducted at 31 cancer institutes, hospitals, and universities in Italy. Eligible patients were aged 18 years or older with histologically confirmed advanced (FIGO stage III–IV) or recurrent endometrial cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and no previous systemic anticancer therapy as primary treatment for advanced or metastatic disease. Participants were randomly assigned (1:1) using a computerised minimisation procedure stratified by centre, histology, and stage at study entry, to either receive carboplatin (area under the curve [AUC] 5 mg/mL × min) and paclitaxel (175 mg/m2; standard group) intravenously every 3 weeks for six to eight cycles or avelumab (10 mg/kg intravenously) added to carboplatin and paclitaxel (experimental group) every 3 weeks and then every 2 weeks as a single maintenance treatment after the end of chemotherapy until disease progression or unacceptable toxicity. Patients, treating clinicians, and those assessing radiological examinations were not masked to study treatment. The primary endpoint was investigator-assessed progression-free survival, measured in the intention-to-treat (ITT) population. Patients who received at least one dose of study drug were included in the safety analysis. Experimental group superiority was tested with 80% power and one-tailed α 0·20. This trial is registered with ClinicalTrials.gov (NCT03503786) and EudraCT (2016–004403–31). Findings: From April 9, 2018, to May 13, 2021, 166 women were assessed for eligibility and 39 were excluded. 125 eligible patients were randomly assigned to receive carboplatin and paclitaxel (n=62) or avelumab plus carboplatin and paclitaxel (n=63) and included in the ITT population. The median follow-up was 23·3 months (IQR 13·2–29·6) and was similar between the two groups. 91 progression-free survival events were reported, with 49 events in 62 patients in the standard group and 42 events in 63 patients in the experimental group. The median progression-free survival was 9·9 months (95% CI 6·7–12·1) in the standard group and 9·6 months (7·2–17·7) in the experimental group (HR of progression or death 0·78 [60% CI 0·65–0·93]; one-tailed p=0·085). Serious adverse events were reported more frequently in the experimental group (24 vs seven events in the standard group); neutrophil count decrease was the most frequent grade 3–4 adverse event (19 [31%] of 61 patients in the experimental group vs 26 [43%] of 61 patients in the standard group). Two deaths occurred in the experimental group during treatment (one respiratory failure following severe myositis [possibly related to treatment] and one cardiac arrest [not related to treatment]). Interpretation: Adding avelumab to first-line chemotherapy deserves further testing in patients with advanced or recurrent endometrial cancer, although consideration of mismatch repair status is warranted. more...
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- 2023
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39. A phase 2, open label, multicenter, single arm study of tocilizumab on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia (TOCIVID-19 trial): Statistical analysis plan
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Paolo Chiodini, Laura Arenare, Maria Carmela Piccirillo, Francesco Perrone, and Ciro Gallo
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Statistical analysis plan ,COVID-19 pneumonia ,Tocilizumab ,Phase 2 trial ,Medicine (General) ,R5-920 - Abstract
Background: Tocilizumab, an IL-6 receptor antagonist, was suggested as a possible treatment of severe or critical COVID-19 pneumonia in a small Chinese study. The TOCIVID-19 trial evaluates efficacy and tolerability of tocilizumab in the treatment of patients with severe or critical COVID-19 pneumonia. Methods: TOCIVID-19 is an academic multicenter, single-arm, open-label, phase 2 study. All the patients are being offered a single shot of 8 mg/kg of Tocilizumab (up to a maximum of 800 mg), with an eventual second administration at the discretion of the Investigator. A companion prospective cohort, added to corroborate internal validity, includes either patients not eligible for phase 2 or subjects eligible for phase 2 but exceeding the planned sample size. 14- and 30-days lethality rates are the two co-primary endpoints in the intention-to-treat (ITT) population. Secondary objectives are to evaluate mortality and clinical improvement in the modified-ITT population of subjects who received the drug. Details of the methodological and statistical approaches are reported here reflecting the amendments impelled by the continuously increasing knowledge on COVID-19 progression and challenges in data collection. Conclusion: This paper provides details of planned statistical analyses for TOCIVID19 trial to reduce the risk of reporting bias and increase validity of the study findings.TOCIVID-19 trial is registered in the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092. more...
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- 2020
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40. Impact of chronic liver disease upon admission on COVID-19 in-hospital mortality: Findings from COVOCA study.
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Raffaele Galiero, Pia Clara Pafundi, Vittorio Simeon, Luca Rinaldi, Alessandro Perrella, Erica Vetrano, Alfredo Caturano, Maria Alfano, Domenico Beccia, Riccardo Nevola, Raffaele Marfella, Celestino Sardu, Carmine Coppola, Ferdinando Scarano, Paolo Maggi, Pellegrino De Lucia Sposito, Laura Vocciante, Carolina Rescigno, Costanza Sbreglia, Fiorentino Fraganza, Roberto Parrella, Annamaria Romano, Giosuele Calabria, Benedetto Polverino, Antonio Pagano, Carolina Bologna, Maria Amitrano, Vincenzo Esposito, Nicola Coppola, Nicola Maturo, Luigi Elio Adinolfi, Paolo Chiodini, Ferdinando Carlo Sasso, and COVOCA Study Group more...
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Medicine ,Science - Abstract
BackgroundItaly has been the first Western country to be heavily affected by the spread of SARS-COV-2 infection and among the pioneers of the clinical management of pandemic. To improve the outcome, identification of patients at the highest risk seems mandatory.ObjectivesAim of this study is to identify comorbidities and clinical conditions upon admission associated with in-hospital mortality in several COVID Centers in Campania Region (Italy).MethodsCOVOCA is a multicentre retrospective observational cohort study, which involved 18 COVID Centers throughout Campania Region, Italy. Data were collected from patients who completed their hospitalization between March-June 2020. The endpoint was in-hospital mortality, assessed either from data at discharge or death certificate, whilst all exposure variables were collected at hospital admission.ResultsAmong 618 COVID-19 hospitalized patients included in the study, 143 in-hospital mortality events were recorded, with a cumulative incidence of about 23%. At multivariable logistic analysis, male sex (OR 2.63, 95%CI 1.42-4.90; p = 0.001), Chronic Liver Disease (OR 5.88, 95%CI 2.39-14.46; pConclusionMortality of patients hospitalized for COVID-19 appears strongly affected by both clinical conditions on admission and comorbidities. Originally, we observed a very poor outcome in subjects with a chronic liver disease, alongside with an increase of hepatic damage. more...
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- 2020
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41. Safety and efficacy of abiraterone acetate in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: an Italian multicenter 'real life' study
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Luca Cindolo, Clara Natoli, Cosimo De Nunzio, Michele De Tursi, Maurizio Valeriani, Silvana Giacinti, Salvatore Micali, Mino Rizzo, Giampaolo Bianchi, Eugenio Martorana, Marcello Scarcia, Giuseppe Mario Ludovico, Pierluigi Bove, Anastasia Laudisi, Oscar Selvaggio, Giuseppe Carrieri, Maida Bada, Pietro Castellan, Stefano Boccasile, Pasquale Ditonno, Paolo Chiodini, Paolo Verze, Vincenzo Mirone, and Luigi Schips more...
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Prostate cancer ,Androgen deprivation therapy ,Abiraterone acetate ,Castration-resistant prostate cancer ,Androgen receptor ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background To evaluate the safety and efficacy of abiraterone acetate (AA) in the “real life” clinical practice for men with chemotherapy-naïve metastatic castration-resistant prostate. Methods A consecutive series of patients with mCRPC in 9 Italian tertiary centres treated with AA was collected. Demographics, clinical parameters, treatment outcomes and toxicity were recorded. The Brief Pain Inventory scale Q3 was tracked and patient treatment satisfaction was evaluated. Survival curves were estimated by the method of Kaplan-Meier and Cox regression and compared by the log-rank test statistic. Results We included 145 patients (mean age 76.5y). All patients were on androgen deprivation therapy. Patients had prior radiotherapy, radical prostatectomy, both treatments or exclusive androgen deprivation therapy in 17%, 33%, 9% and 40%, respectively. 57% of the patients had a Gleason score higher more than 7 at diagnosis. 62% were asymptomatic patients. The median serum total PSA at AA start was 17 ng/mL (range 0,4–2100). The median exposure to AA was 10 months (range 1–35). The proportion of patients achieving a PSA decline ≥50% at 12 weeks was 49%. Distribution of patient satisfaction was 32% “greatly improved”, 38% “improved”, 24% “not changed”, 5.5% “worsened”. Grade 3 and 4 toxicity was recorded in 17/145 patients 11.7% (70% cardiovascular events, 30% critical elevation of AST/ALT levels). At the last follow-up, median progression free and overall survival were 17 and 26.5 months, respectively. Both outcomes significantly correlated with the presence of pain, patient satisfaction, PSA baseline and PSA decline. Conclusions The AA is effective and well tolerated in asymptomatic or slightly symptomatic mCRPC in a “real life” setting. The survival outcomes are influenced by the presence of pain, patient satisfaction, baseline PSA and PSA decline. Trial registration The study was retrospectively registered at ISRCTN as DOI: 10.1186/ISRCTN 52513758 in date April the 30th 2016. more...
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- 2017
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42. Baseline and lifetime alcohol consumption and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort ( <scp>EPIC</scp> )
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Yahya Mahamat‐Saleh, Marie Al‐Rahmoun, Gianluca Severi, Reza Ghiasvand, Marit B. Veierod, Saverio Caini, Domenico Palli, Edoardo Botteri, Carlotta Sacerdote, Fulvio Ricceri, Marko Lukic, Maria J. Sánchez, Valeria Pala, Rosario Tumino, Paolo Chiodini, Pilar Amiano, Sandra Colorado‐Yohar, María‐Dolores Chirlaque, Eva Ardanaz, Catalina Bonet, Verena Katzke, Rudolf Kaaks, Matthias B. Schulze, Kim Overvad, Christina C. Dahm, Christian S. Antoniussen, Anne Tjønneland, Cecilie Kyrø, Bas Bueno‐de‐Mesquita, Jonas Manjer, Malin Jansson, Anders Esberg, Nagisa Mori, Pietro Ferrari, Elisabete Weiderpass, Marie‐Christine Boutron‐Ruault, Marina Kvaskoff, Mahamat-Saleh, Yahya, Al-Rahmoun, Marie, Severi, Gianluca, Ghiasvand, Reza, Veierod, Marit B, Caini, Saverio, Palli, Domenico, Botteri, Edoardo, Sacerdote, Carlotta, Ricceri, Fulvio, Lukic, Marko, Sánchez, Maria J, Pala, Valeria, Tumino, Rosario, Chiodini, Paolo, Amiano, Pilar, Colorado-Yohar, Sandra, Chirlaque, María-Dolore, Ardanaz, Eva, Bonet, Catalina, Katzke, Verena, Kaaks, Rudolf, Schulze, Matthias B, Overvad, Kim, Dahm, Christina C, Antoniussen, Christian S, Tjønneland, Anne, Kyrø, Cecilie, Bueno-de-Mesquita, Ba, Manjer, Jona, Jansson, Malin, Esberg, Ander, Mori, Nagisa, Ferrari, Pietro, Weiderpass, Elisabete, Boutron-Ruault, Marie-Christine, and Kvaskoff, Marina more...
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Male ,Cancer och onkologi ,Cancer Research ,Skin Neoplasms ,Alcohol Drinking ,alcohol ,keratinocyte cancers ,Public Health, Global Health, Social Medicine and Epidemiology ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,cutaneous melanoma ,cohort studies ,Oncology ,Carcinoma, Basal Cell ,Risk Factors ,Cancer and Oncology ,Carcinoma, Squamous Cell ,epidemiology ,Humans ,Female ,Prospective Studies ,Melanoma ,cohort studie - Abstract
Experimental evidence suggests that alcohol induces cutaneous carcinogenesis, yet epidemiological studies on the link between alcohol intake and skin cancer have been inconsistent. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort initiated in 1992 in 10 European countries. Alcohol intake at baseline and average lifetime alcohol intake were assessed using validated country-specific dietary and lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in Cox models. A total of 14 037 skin cancer cases (melanoma: n = 2457; basal-cell carcinoma (BCC): n = 8711; squamous-cell carcinoma (SCC): n = 1928; unknown: n = 941) were identified among 450 112 participants (average follow-up: 15 years). Baseline alcohol intake was positively associated with SCC (>15 vs 0.1-4.9 g/day: HR = 1.44, 95% CI = 1.17-1.77; Ptrend = .001), BCC (HR = 1.12, 95% CI = 1.01-1.23; Ptrend = .04), and melanoma risks in men (HR = 1.17, 95% CI = 0.95-1.44; Ptrend = .17), while associations were more modest in women (SCC: HR = 1.09, 95% CI = 0.90-1.30; Ptrend = .13; BCC: HR = 1.08, 95% CI = 1.00-1.17,Ptrend = .03; melanoma: HR = 0.93, 95% CI = 0.80-1.08, Ptrend = .13). Associations were similar for lifetime alcohol intake, with an attenuated linear trend. Lifetime liquor/spirit intake was positively associated with melanoma (fourth vs first quartile: HR = 1.47, 95% CI = 1.08-1.99; Ptrend = .0009) and BCC risks in men (HR = 1.17, 95% CI = 1.04-1.31;Ptrend = .14). Baseline and lifetime intakes of wine were associated with BCC risk (HR = 1.25 in men; HR = 1.11-1.12; in women). No statistically significant associations were found between beverage types and SCC risk. Intake of beer was not associated with skin cancer risk. Our study suggests positive relationships between alcohol intake and skin cancer risk, which may have important implications for the primary prevention of skin cancer. What's new? Drinking alcohol can make the skin more sensitive to sunlight and vulnerable to skin cancer. Here, the authors conducted a large prospective cohort study to evaluate whether alcohol consumption correlates with skin cancer risk. Among the 450 112 participants, there were 2457 cases of melanoma, 8711 of basal cell carcinoma, and 1928 of squamous cell carcinoma. There was a positive association between alcohol and all three cancer types, stronger in men than in women. The association varied somewhat by beverage type. more...
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- 2022
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43. Early predictors of clinical deterioration in a cohort of outpatients with COVID‐19 in southern Italy: A multicenter observational study
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Caterina, Monari, Mariantonietta, Pisaturo, Paolo, Maggi, Margherita, Macera, Giovanni, Di Caprio, Raffaella, Pisapia, Valeria, Gentile, Mario, Fordellone, Paolo, Chiodini, Nicola, Coppola, Monari, Caterina, Pisaturo, Mariantonietta, Maggi, Paolo, Macera, Margherita, Di Caprio, Giovanni, Pisapia, Raffaella, Gentile, Valeria, Fordellone, Mario, Chiodini, Paolo, and Coppola, Nicola more...
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Adult ,Male ,Clinical Deterioration ,Fever ,SARS-CoV-2 ,SARS-CoV-2 infection ,severe outcome ,COVID-19 ,Middle Aged ,Cohort Studies ,Hospitalization ,Infectious Diseases ,early predictor ,Virology ,Outpatients ,Humans ,Female ,Prospective Studies ,Aged - Abstract
Data regarding early predictors of clinical deterioration in patients with infection of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) is still scarce. The aim of the study is to identify early symptoms or signs that may be associated with severe coronavirus disease 2019(COVID-19).We conducted a multicentre prospective cohort study on a cohort of patients with COVID-19 in home isolation from March 2020 to April 2021. We assessed longitudinal clinical data (fever, dyspnea, need for hospitalization) through video calls at three specific time points: the beginning of symptoms or the day of the first positivity of the nasopharyngeal swab for SARS-CoV-2-RNA (t0 ), and 3 (t3 ) and 7 (t7 ) days after the onset of symptoms. We included 329 patients with COVID-19: 182 (55.3%) males, mean age 53.4 ± 17.4 years, median Charlson comorbidity index(CCI) of 1 (0-3). Of the 329 patients enrolled, 171 (51.98%) had a mild, 81 (24.6%) a moderate, and 77 (23.4%) a severe illness; 151 (45.9%) were hospitalized. Compared to patients with mild COVID-19, moderate and severe patients were older (p more...
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- 2022
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44. Glycemic Control, Preexisting Cardiovascular Disease, and Risk of Major Cardiovascular Events in Patients with Type 2 Diabetes Mellitus: Systematic Review With Meta‐Analysis of Cardiovascular Outcome Trials and Intensive Glucose Control Trials
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Dario Giugliano, Maria Ida Maiorino, Giuseppe Bellastella, Paolo Chiodini, and Katherine Esposito
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cardiovascular events ,cardiovascular outcome trial ,intensive glucose control ,type 2 diabetes mellitus ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background The value of glycemic control and preexisting cardiovascular disease in determining the risk of major cardiovascular events (MACE) in type 2 diabetes mellitus is uncertain. Intensive glucose control trials suggest that the 9% lower risk of MACE associated with intensive glycemic control, as compared with conventional glycemic control, is only driven by patients with type 2 diabetes mellitus without cardiovascular disease at baseline. Methods and Results We did a meta‐analysis of cardiovascular outcome trials dividing patients with or without preexisting cardiovascular disease; we found that the lower risk of MACE is confined to patients with cardiovascular disease at baseline. Compared with placebo, the use of both glucagon‐like peptide‐1 receptor agonists and sodium‐glucose cotransporter‐2 inhibitors was associated with a significant 14% lower MACE risk in patients with preexisting cardiovascular disease and with a nonsignificant 2% higher MACE risk in those without preexisting cardiovascular disease (P for interaction=0.021). The meta‐regression analysis of all 12 trials demonstrated a significant (P=0.002) association between reductions of glycated hemoglobin in glycated hemoglobin A1C. Accordingly, the reduction of MACE expected if all cardiovascular outcome trials had achieved a 0.9% glycated hemoglobin reduction would have been 33%. Routine clinical care data complement the results of cardiovascular outcome trials but with some differences: the lower risk of MACE with sodium‐glucose cotransporter‐2 inhibitor use is evident in patients with type 2 diabetes mellitus with or without preexisting cardiovascular disease. Conclusions Sodium‐glucose cotransporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists should be included in the therapeutic plan of patients with type 2 diabetes mellitus and overt cardiovascular disease, with due attention paid to improvement of glycemic control, which may amplify their benefit on MACE. more...
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- 2019
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45. Machine Learning Application Identifies Germline Markers of Hypertension in Ovarian Cancer Patients Treated with Carboplatin, Taxane and Bevacizumab
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Maurizio Polano, Luca Bedon, Michele Dal Bo, Roberto Sorio, Michele Bartoletti, Elena De Mattia, Erika Cecchin, Carmela Pisano, Domenica Lorusso, Andrea Alberto Lissoni, Andrea De Censi, Sabrina Chiara Cecere, Paolo Scollo, Sergio Marchini, Laura Arenare, Ugo De Giorgi, Daniela Califano, Elena Biagioli, Paolo Chiodini, Francesco Perrone, Sandro Pignata, and Giuseppe Toffoli more...
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Pharmacology ,Pharmacology (medical) - Published
- 2023
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46. Olaparib beyond progression compared with platinum chemotherapy after secondary cytoreductive surgery in patients with recurrent ovarian cancer: phase III randomized, open-label MITO 35b study, a project of the MITO-MANGO groups
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Clorinda Schettino, Lucia Musacchio, Michele Bartoletti, Paolo Chiodini, Laura Arenare, Gustavo Baldassarre, Daniela Califano, Ettore Capoluongo, Maria Paola Costi, Maurizio D'Incalci, Sergio Marchini, Delia Mezzanzanica, Nicola Normanno, Stefania Scala, Stefano Greggi, Francesco Perrone, Sandro Pignata, Schettino, C., Musacchio, L., Bartoletti, M., Chiodini, P., Arenare, L., Baldassarre, G., Califano, D., Capoluongo, E., Costi, M. P., D'Incalci, M., Marchini, S., Mezzanzanica, D., Normanno, N., Scala, S., Greggi, S., Perrone, F., and Pignata, S. more...
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Ovarian Neoplasms ,Mangifera ,BRCA1 protein ,BRCA2 protein ,ovarian cancer ,Adenosine Diphosphate ,Carcinoma, Ovarian Epithelial ,Cytoreduction Surgical Procedures ,Female ,Humans ,Neoplasm Recurrence, Local ,Phthalazines ,Piperazines ,Platinum ,Poly(ADP-ribose) Polymerase Inhibitors ,Ribose ,Antineoplastic Agents ,Carcinoma ,Obstetrics and Gynecology ,Neoplasm Recurrence ,Local ,Oncology ,Ovarian Epithelial - Abstract
BackgroundPoly (ADP-ribose) polymerase inhibitors have transformed the management landscape for patients with ovarian cancer, demonstrating remarkable improvements in progression-free survival and overall survival. Unfortunately, most relapses are due to an acquired mechanism of resistance to these agents. We hypothesize that secondary cytoreductive surgery, removing resistant clones, might help to overcome the development of resistance to poly (ADP-ribose) polymerase inhibitors, prolonging their therapeutic effect.Primary ObjectiveTo determine the efficacy of olaparib beyond progression compared with standard platinum-based chemotherapy in patients with recurrent ovarian cancer progressed during or after poly (ADP-ribose) polymerase inhibitor maintenance therapy after secondary cytoreductive surgery.Study HypothesisOlaparib administered beyond progression is more effective in increasing progression-free survival and progression-free survival 2 compared with second-line platinum-based chemotherapy in patients after secondary cytoreductive surgery.Trial DesignPhase III, randomized, open-label, multicenter trial. Eligible patients will be randomized in a 1:1 ratio to receive olaparib or platinum-based chemotherapy of the investigator’s choice.Major Eligibility CriteriaEligible patients must have high-grade serous or endometrioid ovarian cancer progressed during or after first-line poly (ADP-ribose) polymerase inhibitor maintenance therapy and must have undergone secondary cytoreductive surgery.Primary EndpointThe dual primary endpoints will include progression-free survival and progression-free survival 2. Progression-free survival is defined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as the time between randomization and progression or death from any cause. Progression-free survival 2 is defined by the investigator using RECIST version 1.1 as the time frame from randomization to the second progression or death from any cause after subsequent treatment.Sample SizeApproximately 200 patients will be enrolled in this study.Estimated Dates for Completing Accrual and Presenting ResultsEnrollment will be completed in 2024. Results will be presented in 2026.Trial RegistrationEudraCT 2021-000245-41NCT05255471 more...
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- 2022
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47. Risk of end-stage kidney disease in kidney transplant recipients versus patients with native chronic kidney disease: multicentre unmatched and propensity-score matched analyses
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Luca De Nicola, Raffaele Serra, Michele Provenzano, Roberto Minutolo, Ashour Michael, Nicola Ielapi, Stefano Federico, Rosa Carrano, Vincenzo Bellizzi, Carlo Garofalo, Carmela Iodice, Silvio Borrelli, Giuseppe Grandaliano, Giovanni Stallone, Loreto Gesualdo, Paolo Chiodini, Michele Andreucci, De Nicola, Luca, Serra, Raffaele, Provenzano, Michele, Minutolo, Roberto, Michael, Ashour, Ielapi, Nicola, Federico, Stefano, Carrano, Rosa, Bellizzi, Vincenzo, Garofalo, Carlo, Iodice, Carmela, Borrelli, Silvio, Grandaliano, Giuseppe, Stallone, Giovanni, Gesualdo, Loreto, Chiodini, Paolo, and Andreucci, Michele more...
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esrd ,chronic renal failure ,epidemiology ,kidney transplantation ,prognosis ,Transplantation ,Nephrology - Abstract
Background In kidney transplant recipients (KTR), the end-stage kidney disease (ESKD) risk dependent on the risk factors acting in native chronic kidney disease (CKD) remains undefined. Methods We compared risk and determinants of ESKD between 757 adult KTR and 1940 patients with native CKD before and after propensity-score (PS) analysis matched for unmodifiable risk factors [(age, sex, diabetes, cardiovascular disease and estimated glomerular filtration rate (eGFR)]. Results In unmatched cohorts, eGFR was lower in CKD versus KTR (45.9 ± 11.3 versus 59.2 ± 13.4 mL/min/1.73 m2, P < 0.001). During a median follow-up of 5.4 years, the unadjusted cumulative incidence of ESKD was consistently lower in unmatched KTR versus CKD. Conversely, in PS-matched analysis, the risk of ESKD in KTR was 78% lower versus CKD at 1 year of follow-up while progressively increased over time resulting similar to that of native CKD patients after 5 years and 2.3-fold higher than that observed in CKD at 10 years. R2 analysis in unmatched patients showed that the proportion of the outcome variance explained by traditional ESKD determinants was smaller in KTR versus native CKD (31% versus 70%). After PS matching, the risk of ESKD [hazard ratio (HR), 95% confidence interval (95% CI)] was significantly associated with systolic blood pressure (1.02, 1.01–1.02), phosphorus (1.31, 1.05–1.64), 24-h proteinuria (1.11, 1.05–1.17) and haemoglobin (0.85, 0.78–0.93) irrespective of KTR status. Similar data were obtained after matching also for modifiable risk factors. Conclusions In KTR, when compared with matched native CKD patients, the risk of ESKD is lower in the first 5 years and higher later on. Traditional determinants of ESKD account for one-third of the variability of time-to-graft failure. more...
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- 2022
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48. New-onset anemia and associated risk of ESKD and death in non-dialysis CKD patients: a multicohort observational study
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Roberto, Minutolo, Michele, Provenzano, Paolo, Chiodini, Silvio, Borrelli, Carlo, Garofalo, Michele, Andreucci, Maria Elena, Liberti, Vincenzo, Bellizzi, Giuseppe, Conte, Luca, De Nicola, V, Bellizzi, Minutolo, Roberto, Provenzano, Michele, Chiodini, Paolo, Borrelli, Silvio, Garofalo, Carlo, Andreucci, Michele, Liberti, Maria Elena, Bellizzi, Vincenzo, Conte, Giuseppe, and De Nicola, Luca more...
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Transplantation ,ESKD ,non-dialysis CKD ,Nephrology ,epidemiology ,anemia - Abstract
Background Anemia is a common complication of chronic kidney disease (CKD), but its incidence in nephrology settings is poorly investigated. Similarly, the risks of adverse outcomes associated with new-onset anemia are not known. Methods We performed a pooled analysis of three observational cohort studies including 1031 non-anemic CKD patients with eGFR Results The mean age was 63 ± 14 years, 60% were men and 20% had diabetes. The mean estimated glomerular filtration rate (eGFR) was 37 ± 13 mL/min/1.73 m2 and the median proteinuria was 0.4 g/day [interquartile range (IQR) 0.1–1.1]. The incidence of mild and severe anemia was 13.7/100 patients-year and 6.2/100 patients-year, respectively. Basal predictors of either mild or severe anemia were diabetes, lower hemoglobin, higher serum phosphate, eGFR 0.50 g/day. Male sex, moderate CKD (eGFR 30–44 mL/min/1.73 m2) and moderate proteinuria (0.15–0.50 g/day) predicted only mild anemia. The incidence of anemia increased progressively with CKD stages (from 8.77 to 76.59/100 patients-year) and the proteinuria category (from 13.99 to 25.02/100 patients-year). During a median follow-up of 3.1 years, 232 patients reached ESKD and 135 died. Compared with non-anemic patients, mild anemia was associated with a higher adjusted risk of ESKD {hazard ratio [HR] 1.42 [95% confidence interval (CI) 1.02–1.98]} and all-cause death [HR 1.55 (95% CI 1.04–2.32)]. Severe anemia was associated with an even higher risk of ESKD [HR 1.73 (95% CI 1.20–2.51)] and death [HR 1.83 (95% CI 1.05–3.19)]. Conclusions New-onset anemia is frequent, particularly in patients with more severe renal damage and in those with diabetes mellitus. The occurrence of anemia, even of a mild degree, is associated with mortality risk and faster progression towards ESKD. more...
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- 2022
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49. Validation of MiROvaR, a microRNA-based predictor of early relapse in early stage epithelial ovarian cancer as a new strategy to optimise patients' prognostic assessment
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Antonino Ditto, Loris De Cecco, Biagio Paolini, Paola Alberti, Fabio Martinelli, Umberto Leone Roberti Maggiore, Giorgio Bogani, Paolo Chiodini, Sandro Pignata, Antonella Tomassetti, Francesco Raspagliesi, Delia Mezzanzanica, Marina Bagnoli, Ditto, A., De Cecco, L., Paolini, B., Alberti, P., Martinelli, F., Leone Roberti Maggiore, U., Bogani, G., Chiodini, P., Pignata, S., Tomassetti, A., Raspagliesi, F., Mezzanzanica, D., and Bagnoli, M. more...
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Adult ,Aged, 80 and over ,Male ,microRNA signature ,Cancer Research ,Carcinoma, Ovarian Epithelial ,Middle Aged ,Prognosis ,Progression-Free Survival ,MicroRNAs ,Young Adult ,Oncology ,Early-stage ovarian cancer ,Disease Progression ,Humans ,Female ,Neoplasm Recurrence, Local ,Aged ,Neoplasm Staging ,Retrospective Studies - Abstract
Aim: Early-stage epithelial ovarian cancer (eEOC) patients have a generally favorable prognosis but unpredictable recurrence. Accurate prediction of risk of relapse is still a major concern, essentially to avoid overtreatment. Our robust tissue-based miRNA signature named MiROvaR, predicting early EOC recurrence in mostly advanced-stage EOC patients, is here challenged in an independent cohort to extend its classifying ability in the early-stage EOC setting. Methods: We retrospectively selected patients who underwent comprehensive surgical staging at our institution including stages from IA to IIB. miRNA expression profile was analysed in 89 cases and MiROvaR algorithm was applied using the previously validated cut-off for patients' classification. The primary endpoint was progression-free survival (PFS) at 5 years. Complete follow-up time (median = 112 months) was also considered as secondary analysis. Results: MiROvaR was assessable on 87 cases (19 events of disease progression) and classified 68 (78%) low-risk and 19 (22%) high-risk patients. Recurrence rate at primary end-point was 39% for high-risk patients as compared to 9.5% for low-risk ones. Accordingly, their Kaplan–Meier PFS curves were significantly different at both primary and secondary analysis (p = 0.0006 and p = 0.03, respectively). While none of the prominent clinical variables had prognostic relevance, MiROvaR significantly predicted disease recurrence at the 5-year assessment (primary endpoint analysis; HR:5.43, 95%CI:1.82–16.1, p = 0.0024; AUC = 0.78, 95%CI:0.53–0.82) and at complete follow-up time (HR:2.67, 95%CI:1.04–6.8, p = 0.041; AUC:0.68, 95%CI:0.52–0.82). Conclusions: We validated MiROvaR performance in identifying at diagnosis eEOC patients' at higher risk of early relapse thus enabling selection of the most effective therapeutic approach. more...
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- 2022
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50. Impact of Stress and Trait Anxiety on the Sensory and Jaw Motor Responses to a Tonic Orofacial Nociceptive Stimulus
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Jeffrey Chow, Paolo Chiodini, Ambra Michelotti, Richard Ohrbach, Iacopo Cioffi, Chow, J. C. F., Chiodini, P., Michelotti, A., Ohrbach, R., and Cioffi, I.
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Adult ,Nociception ,Occlusion ,Pain ,Masticatory muscle ,Anxiety ,Anesthesiology and Pain Medicine ,Humans ,Bruxism ,Dentistry (miscellaneous) ,Neurology (clinical) ,Sensory hreshold ,Stress, Psychological ,Human ,Pain Measurement - Abstract
Aims: To investigate how trait anxiety and stress jointly affect the sensory and jaw motor responses to a tonic orofacial nociceptive stimulus. Methods: Orthodontic separators were placed between the first molars in 45 adults with low (n = 14), intermediate (n = 17), and high (n = 14) trait anxiety. Tooth pain, occlusal discomfort, tooth clenching (as a jaw motor behavior), and situational stress were measured three times a day for 5 days using visual analog scales. Mixed-effects regression models were used to evaluate the sensory and motor outcome measures. Results: Pain, discomfort, and frequency of tooth-clenching trajectories were affected by trait anxiety (P =.007, P more...
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- 2022
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