67 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
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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.
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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
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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.
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- 2023
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4. 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.
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- 2024
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5. 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
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Medicine ,Science - Published
- 2024
6. 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
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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.
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- 2023
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7. 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
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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.
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- 2023
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8. 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
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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.
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- 2023
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9. 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
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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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10. 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
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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.
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- 2023
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11. 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
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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12. 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
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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13. 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
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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).
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- 2024
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14. Easy Anthropometric Measurements Are Representative of Baseline Values of Breast Q Values in Asymptomatic Women
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Giuseppe Catanuto, Nicola Rocco, Concetta G. Fichera, Ada Cinquerrui, Martina Rapisarda, Paolo Chiodini, Francesca Magnoni, Patrizia Dorangricchia, Valeria Sebri, Gabriella Pravettoni, Maurizio Bruno Nava, and Francesco Caruso
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breast cancer ,breast measurements ,quality of life ,Medicine - Abstract
Background: Measurements of breast morphology are a determinant of the assessment of any surgical procedure, either reconstructive or cosmetic. This study aims to investigate the association between easy anthropometric measurements and values of quality of life assessed in a sample of asymptomatic women. Methodology: Healthy asymptomatic women were admitted for this study. The following measurements were assessed: height, weight, nipple to sternal notch distance, areola to infra-mammary fold distance (right vs. left), right–left nipple distance. The Breast Q questionnaire (Italian translation V.1, pre-op breast conservation surgery) in the following domains: satisfaction with breasts; psycho-social satisfaction; physical satisfaction; sexual satisfaction, which was used to assess breast-related quality of life. Results: One hundred and forty-five women responded to the breast Q questionnaire. The mean age of the sample was 44.3 years; the medium BMI was 24.1; Spearman correlation coefficients revealed that all the investigated values were negatively correlated to the “satisfaction with breasts” domain. Psychosexual satisfaction was associated with age; BMI; nipple to sternal notch distance. After normalization for age values, we observed that “satisfaction with breast” was, once again, highly correlated to BMI; nipple to sternal notch distance; areola to IMF distance. In all cases, the higher the values, the lower the scores. Conclusions: Distances between easy relevant anatomical landmarks are representative of patients’ breast-related quality of life in a population of asymptomatic women. These findings allow us to identify an ideal anthropometric framework that can be used as a validated surgical endpoint for cosmetic and oncological procedures.
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- 2024
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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
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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.
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- 2023
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16. 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
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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
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- 2022
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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]).
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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.
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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
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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
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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
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- 2021
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22. 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.
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- 2022
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23. 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.
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- 2023
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24. Association between Renal Function at Admission and COVID-19 in-Hospital Mortality in Southern Italy: Findings from the Prospective Multicenter Italian COVOCA Study
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Raffaele Galiero, Vittorio Simeon, Giuseppe Loffredo, Alfredo Caturano, Luca Rinaldi, 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 Giuliano Numis, Carolina Bologna, Mariagrazia Nunziata, Vincenzo Esposito, Nicola Coppola, Nicola Maturo, Rodolfo Nasti, Pierpaolo Di Micco, Alessandro Perrella, Miriam Lettieri, Luigi Elio Adinolfi, Paolo Chiodini, Ferdinando Carlo Sasso, and on behalf of COVOCA Study Group
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COVID-19 ,chronic kidney diseases ,in-hospital mortality ,Medicine - Abstract
Background. Evidence has shown a close association between COVID-19 infection and renal complications in both individuals with previously normal renal function and those with chronic kidney disease (CKD). Methods. The aim of this study is to evaluate the in-hospital mortality of SARS-CoV-2 patients according to their clinical history of CKD or estimated glomerular filtration rate (eGFR). This is a prospective multicenter observational cohort study which involved adult patients (≥18 years old) who tested positive with SARS-CoV-2 infection and completed their hospitalization in the period between November 2020 and June 2021. Results. 1246 patients were included in the study, with a mean age of 64 years (SD 14.6) and a median duration of hospitalization of 15 days (IQR 9–22 days). Cox’s multivariable regression model revealed that mortality risk was strongly associated with the stage of renal impairment and the Kaplan–Meier survival analysis showed a progressive and statistically significant difference (p < 0.0001) in mortality according to the stage of CKD. Conclusion. This study further validates the association between CKD stage at admission and mortality in patients hospitalized for COVID-19. The risk stratification based on eGFR allows clinicians to identify the subjects with the highest risk of intra-hospital mortality despite the duration of hospitalization.
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- 2022
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25. The opportunity of patient-journey studies for academic clinical research in oncology
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Raimondo Di Liello, Paolo Chiodini, and Piera Gargiulo
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Medicine - Published
- 2021
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26. 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
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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.
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- 2022
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27. 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.
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- 2022
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28. Biological Role of Tumor/Stromal CXCR4-CXCL12-CXCR7 in MITO16A/MaNGO-OV2 Advanced Ovarian Cancer Patients
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Crescenzo D’Alterio, Anna Spina, Laura Arenare, Paolo Chiodini, Maria Napolitano, Francesca Galdiero, Luigi Portella, Vittorio Simeon, Simona Signoriello, Francesco Raspagliesi, Domenica Lorusso, Carmela Pisano, Nicoletta Colombo, Gian Franco Zannoni, Nunzia Simona Losito, Rossella De Cecio, Giosuè Scognamiglio, Daniela Califano, Daniela Russo, Valentina Tuninetti, Maria Carmela Piccirillo, Piera Gargiulo, Francesco Perrone, Sandro Pignata, and Stefania Scala
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chemokine ,CXCR4-CXCL12-CXCR7 axis ,ovarian cancer ,prognosis ,tumor microenvironment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
This study investigated the prognostic role of the CXCR4-CXCL12-CXCR7 axis in advanced epithelial ovarian cancer (EOC) patients receiving first-line treatment within the MITO16A/MaNGO-OV2 phase-IV trial. CXCR4-CXCL12-CXCR7 expression was evaluated in the epithelial and stromal component of 308 EOC IHC-stained tumor samples. The statistical analysis focused on biomarkers’ expression, their association with other variables and prognostic value. Zero-inflated tests, shrinkage, bootstrap procedures, and multivariable models were applied. The majority of EOC (75.0%) expressed CXCR4 and CXCR7, 56.5% expressed the entire CXCR4-CXCL12-CXCR7 axis, while only 4.6% were negative for CXCL12 and its cognate receptors, in regard to the epithelial component. Stromal CXCL12 and CXCR7, expressed in 11.2% and 65.5%, respectively, were associated with the FIGO stage. High CXCL12 in epithelial cancer cells was associated with shorter progression-free and overall survival. However, after adjusting for overfitting due to best cut-off multiplicity testing, the significance was lost. This is a wide-ranging, prospective study in which CXCR4-CXCL12-CXCR7 were systematically evaluated in epithelial and stromal components, in selected stage III-IV EOC. Although CXCL12 was not prognostic, epithelial expression identified high-risk FIGO stage III patients for PFS. These data suggest that it might be worth studying the CXCL12 axis as a therapeutic target to improve treatment efficacy in EOC patients.
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- 2022
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29. Evaluation of Angiogenesis-Related Genes as Prognostic Biomarkers of Bevacizumab Treated Ovarian Cancer Patients: Results from the Phase IV MITO16A/ManGO OV-2 Translational Study
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Daniela Califano, Daniela Gallo, Gian Luca Rampioni Vinciguerra, Rossella De Cecio, Laura Arenare, Simona Signoriello, Daniela Russo, Gabriella Ferrandina, Francesca Citron, Nunzia Simona Losito, Piera Gargiulo, Vittorio Simeon, Giovanni Scambia, Sabrina Chiara Cecere, Marco Montella, Nicoletta Colombo, Germana Tognon, Eliana Bignotti, Gian Franco Zannoni, Vincenzo Canzonieri, Alessandra Ciucci, Anna Spina, Giosuè Scognamiglio, Michele Del Sesto, Clorinda Schettino, Maria Carmela Piccirillo, Francesco Perrone, Paolo Chiodini, Sandro Pignata, and Gustavo Baldassarre
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ovarian cancer ,Bevacizumab treatment ,angiogenesis ,microRNAs ,vessel density ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background. Epithelial ovarian cancer (EOC) is a rare, highly lethal disease. In a subset of high grade EOC patients, maintenance therapy with the antiangiogenic drug Bevacizumab (BEV) is a valuable option. To date, no validated predictive or prognostic biomarkers exist for selecting EOC patients that might benefit from BEV treatment. Methods. Immunohistochemistry and RT-qPCR evaluated the expression of seven angiogenesis-related proteins and of a twelve microRNAs angio-signature in EOC patients, treated in first line with chemotherapy plus BEV (MITO16A/ManGO OV-2 phase IV trial). Centralized statistical analyses assessed the associations between each biomarker, clinical prognostic factors and survival outcomes. Results. High miR-484 expression was associated with longer progression-free and overall survival. Notably, the combined expression of miR-484 and its target VEGFB identified a subset of patients that might mostly benefit from BEV treatment. No other significant correlations were found between the other analyzed biomarkers and patients’ survival. The application of a shrinkage procedure to adjust for over-fitting hazard ratio estimates reduced the association significance. Conclusions. The analysis of angiogenesis related biomarkers in EOC patients homogenously treated with BEV in first line provides novel insight in their prognostic value and suggests that some of them might merit to be tested as predictive markers of drug activity in dedicated randomized trials.
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- 2021
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30. 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
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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.
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- 2023
31. 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
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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.
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- 2022
32. 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
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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
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- 2022
33. 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
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Pharmacology ,Pharmacology (medical) - Published
- 2023
34. 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.
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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
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- 2022
35. 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
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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.
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- 2022
36. 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
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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.
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- 2022
37. 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.
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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.
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- 2022
38. 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
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- 2022
39. Prevalence and renal prognosis of left ventricular diastolic dysfunction in non-dialysis chronic kidney disease patients with preserved systolic function
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Silvio Borrelli, Luca De Nicola, Carlo Garofalo, Ernesto Paoletti, Sergio Lucà, Paolo Chiodini, Stefano Lucà, Nicola Peruzzu, Antonella Netti, Eugenio Lembo, Giovanna Stanzione, Giuseppe Conte, Roberto Minutolo, Borrelli, Silvio, De Nicola, Luca, Garofalo, Carlo, Paoletti, Ernesto, Lucà, Sergio, Chiodini, Paolo, Lucà, Stefano, Peruzzu, Nicola, Netti, Antonella, Lembo, Eugenio, Stanzione, Giovanna, Conte, Giuseppe, and Minutolo, Roberto
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Aged, 80 and over ,Male ,Physiology ,Middle Aged ,Prognosis ,Ventricular Function, Left ,Ventricular Dysfunction, Left ,Diastole ,Renal Dialysis ,Prevalence ,Internal Medicine ,Humans ,Female ,Renal Insufficiency, Chronic ,Cardiology and Cardiovascular Medicine ,Aged - Abstract
Background: Left ventricular (LV) diastolic dysfunction is common in non-dialysis chronic kidney disease (ND-CKD) patients; however, the prevalence estimated according to the new diagnostic criteria as well as the prognostic role of diastolic dysfunction on CKD progression remain unknown. Method: We longitudinally evaluated consecutive ND-CKD patients and preserved systolic function (LV ejection fraction > 50%). According to the recently updated guidelines, LV diastolic dysfunction was assessed by four echocardiographic variables (annular e' velocity, average mitral valve E-wave/e' ratio, left atrial volume index and tricuspid regurgitation). Patients were classified as diastolic dysfunction, indeterminate and normal. Time-dependent estimated glomerular filtration rate (eGFR) change was assessed by mixed-effects regression model. Cumulative incidence of composite renal outcome (eGFR decline > 50% or chronic dialysis) was also estimated. Results: Among 140 patients (age 66.2 ± 14.5 years; 61% males; eGFR 39.8 ± 21.8 ml/min per 1.73m2; 43.6% diabetics), diastolic dysfunction occurred in 22.9%, indeterminate in 45.7% and normal in 31.4%. Prevalence of diastolic dysfunction was much lower than that estimated with older criteria (62.7%). Logistic regression (odds ratio, 95% confidence interval [CI]) showed that diastolic dysfunction was associated with lower eGFR (0.97, 0.94-0.99), older age (1.08, 1.01-1.06) and night-time systolic blood pressure (1.04, 1.00-1.07). Across 1702 eGFR measurements collected during a median follow-up of 4.6 years, eGFR decline (ml/min per 1.73m2; per year) was faster in patients with diastolic dysfunction (-2.12, 95% CI from -2.68 to -1.56) and in the indeterminate (11.2/100 pts per year) as compared to normal (-1.14, 95% CI from -1.64 to -0.63). Incidence of composite renal outcome was significantly higher in diastolic dysfunction (13.8/100 pts/year) than in normal group (3.5/100 pts per year)'. Conclusion: In ND-CKD population, LV diastolic dysfunction is less frequent than previously described and acts as independent predictor of CKD progression.
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- 2021
40. Improvement of glycemic control and reduction of major cardiovascular events in 18 cardiovascular outcome trials: an updated meta-regression
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Lorenzo Scappaticcio, Katherine Esposito, Giuseppe Bellastella, Maria Ida Maiorino, Paolo Chiodini, Dario Giugliano, Miriam Longo, Maiorino, M. I., Longo, M., Scappaticcio, L., Bellastella, G., Chiodini, P., Esposito, K., and Giugliano, D.
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Blood Glucose ,Male ,Time Factors ,Endocrinology, Diabetes and Metabolism ,Meta-regression ,Type 2 diabetes ,Review ,DPP-4i ,Cardiovascular outcome trials ,Glycemic control ,Risk Factors ,Cause of Death ,Stroke ,Randomized Controlled Trials as Topic ,Hazard ratio ,Cardiorenal outcome ,Middle Aged ,GLP-1RA ,Hospitalization ,Treatment Outcome ,Cardiovascular Diseases ,Female ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,MACE ,Incretins ,Risk Assessment ,Glucagon-Like Peptide-1 Receptor ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Diseases of the circulatory (Cardiovascular) system ,Sodium-Glucose Transporter 2 Inhibitors ,Glycemic ,Aged ,Glycated Hemoglobin ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Cardiorenal outcomes ,SGLT-2i ,Protective Factors ,medicine.disease ,Confidence interval ,Cardiovascular outcome trial ,Diabetes Mellitus, Type 2 ,RC666-701 ,business ,Mace ,Biomarkers - 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 2 = 45.2%, Q statistic P = 0.040). In meta-regression, there was an association between the reduction in HbA1c at the end of the trial and the HR reduction for MACE (beta = − 0.298, P = 0.007), with significant heterogeneity (I2 = 40%, Q statistic P = 0.04); this association was totally driven by the risk reduction of non-fatal stroke, which explained 100% of between-study variance (beta = − 0.531, R2 = 100%), without heterogeneity (I2 = 24%, Q statistic P = 0.206). There was no association between the reduction in HbA1c and the HR for heart failure or all-cause death. Conclusions The reduction of HbA1c in eighteen CVOTs was significantly associated with reduction of non-fatal stroke, explaining all (R2 = 100%) of the between-study variance. While the contribution of glucose lowering in some CV benefits of newer agents does not influence their indications for the patient with type 2 diabetes, it may hopefully facilitate their use.
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- 2021
41. Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses
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Liam Gaziano, Luanluan Sun, Matthew Arnold, Steven Bell, Kelly Cho, Stephen K. Kaptoge, Rebecca J. Song, Stephen Burgess, Daniel C. Posner, Katja Mosconi, Cassianne Robinson-Cohen, Amy M. Mason, Thomas R. Bolton, Ran Tao, Elias Allara, Petra Schubert, Lingyan Chen, James R. Staley, Natalie Staplin, Servet Altay, Pilar Amiano, Volker Arndt, Johan Ärnlöv, Elizabeth L.M. Barr, Cecilia Björkelund, Jolanda M.A. Boer, Hermann Brenner, Edoardo Casiglia, Paolo Chiodini, Jackie A. Cooper, Josef Coresh, Mary Cushman, Rachel Dankner, Karina W. Davidson, Renate T. de Jongh, Chiara Donfrancesco, Gunnar Engström, Heinz Freisling, Agustín Gómez de la Cámara, Vilmundur Gudnason, Graeme J. Hankey, Per-Olof Hansson, Alicia K. Heath, Ewout J. Hoorn, Hironori Imano, Simerjot K. Jassal, Rudolf Kaaks, Verena Katzke, Jussi Kauhanen, Stefan Kiechl, Wolfgang Koenig, Richard A. Kronmal, Cecilie Kyrø, Deborah A. Lawlor, Börje Ljungberg, Conor MacDonald, Giovanna Masala, Christa Meisinger, Olle Melander, Conchi Moreno Iribas, Toshiharu Ninomiya, Dorothea Nitsch, Børge G. Nordestgaard, Charlotte Onland-Moret, Luigi Palmieri, Dafina Petrova, Jose Ramón Quirós Garcia, Annika Rosengren, Carlotta Sacerdote, Masaru Sakurai, Carmen Santiuste, Matthias B. Schulze, Sabina Sieri, Johan Sundström, Valérie Tikhonoff, Anne Tjønneland, Tammy Tong, Rosario Tumino, Ioanna Tzoulaki, Yvonne T. van der Schouw, W.M. Monique Verschuren, Henry Völzke, Robert B. Wallace, S. Goya Wannamethee, Elisabete Weiderpass, Peter Willeit, Mark Woodward, Kazumasa Yamagishi, Raul Zamora-Ros, Elvis A. Akwo, Saiju Pyarajan, David R. Gagnon, Philip S. Tsao, Sumitra Muralidhar, Todd L. Edwards, Scott M. Damrauer, Jacob Joseph, Lisa Pennells, Peter W.F. Wilson, Seamus Harrison, Thomas A. Gaziano, Michael Inouye, Colin Baigent, Juan P. Casas, Claudia Langenberg, Nick Wareham, Elio Riboli, J.Michael Gaziano, John Danesh, Adriana M. Hung, Adam S. Butterworth, Angela M. Wood, Emanuele Di Angelantonio, Anna Koettgen, Jonathan Shaw, Robert Atkins, Paul Zimmet, Peter Whincup, Johann Willeit, Christoph Leitner, Anne Tybjaerg-Hansen, Peter Schnohr, Shoaib Afzal, David Lora Pablos, Cristina Martin Arriscado, Carmen Romero Ferreiro, Hannah Stocker, Ben Schöttker, Bernd Holleczek, Angela Chetrit, Lennart Welin, Kurt Svärdsudd, Lauren Lissner, Dominique Hange, Kirsten Mehlig, Dorothea Nagel, Paul E. Norman, Osvaldo Almeida, Leon Flicker, Jun Hata, Takanori Honda, Yoshihiko Furuta, Hiroyasu Iso, Akihiko Kitamura, Isao Muraki, Jukka T. Salonen, Tomi-Pekka Tuomainen, E. M. van Zutphen, N. M. van Schoor, Cinzia Lo Noce, Richard Kronmal, Georg Lappas, Peter M. Nilsson, Bo Hedblad, Jonathan Shaffer, Joseph Schwartz, Daichi Shimbo, Shinichi Sato, Mina Hayama-Terada, Simerjot Jassal, Thor Aspelund, Bolli Thorsson, Gunnar Sigurdsson, Layal Chaker, Kamran M. Ikram, Maryam Kavousi, Hugh Tunstall-Pedoe, Günay Can, Hüsniye Yüksel, Uğur Özkan, Hideaki Nakagawa, Yuko Morikawa, Masao Ishizaki, Edith Feskens, Johanna M Geleijnse, Daan Kromhout, Internal Medicine, Neurology, Epidemiology, Bell, Steven [0000-0001-6774-3149], Posner, Daniel C [0000-0002-3056-6924], Mason, Amy M [0000-0002-8019-0777], Allara, Elias [0000-0002-1634-8330], Staplin, Natalie [0000-0003-4482-4418], Arndt, Volker [0000-0001-9320-8684], Ärnlöv, Johan [0000-0002-6933-4637], Barr, Elizabeth LM [0000-0003-4284-1716], Boer, Jolanda MA [0000-0002-9714-4304], Brenner, Hermann [0000-0002-6129-1572], Casiglia, Edoardo [0000-0002-0003-3289], Chiodini, Paolo [0000-0003-0139-2264], Coresh, Josef [0000-0002-4598-0669], Cushman, Mary [0000-0002-7871-6143], Davidson, Karina W [0000-0002-9162-477X], de Jongh, Renate T [0000-0001-8414-3938], Engström, Gunnar [0000-0002-8618-9152], de la Cámara, Agustín Gómez [0000-0001-6827-6319], Gudnason, Vilmundur [0000-0001-5696-0084], Hankey, Graeme J [0000-0002-6044-7328], Hansson, Per-Olof [0000-0001-6323-0506], Heath, Alicia K [0000-0001-6517-1300], Hoorn, Ewout J [0000-0002-8738-3571], Imano, Hironori [0000-0002-6661-4254], Katzke, Verena [0000-0002-6509-6555], Kiechl, Stefan [0000-0002-9836-2514], Koenig, Wolfgang [0000-0002-2064-9603], Kronmal, Richard A [0000-0002-9897-7076], Kyrø, Cecilie [0000-0002-9083-8960], Ljungberg, Börje [0000-0002-4121-3753], MacDonald, Conor [0000-0002-4989-803X], Masala, Giovanna [0000-0002-5758-9069], Ninomiya, Toshiharu [0000-0003-1345-9032], Nordestgaard, Børge G [0000-0002-1954-7220], Onland-Moret, Charlotte [0000-0002-2360-913X], Palmieri, Luigi [0000-0002-4298-2642], Rosengren, Annika [0000-0002-5409-6605], Schulze, Matthias B [0000-0002-0830-5277], Sieri, Sabina [0000-0001-5201-172X], Sundström, Johan [0000-0003-2247-8454], Tikhonoff, Valérie [0000-0001-7846-0101], Tong, Tammy [0000-0002-0284-8959], Tzoulaki, Ioanna [0000-0002-4275-9328], van der Schouw, Yvonne T [0000-0002-4605-435X], Wannamethee, S Goya [0000-0001-9484-9977], Weiderpass, Elisabete [0000-0003-2237-0128], Willeit, Peter [0000-0002-1866-7159], Woodward, Mark [0000-0001-9800-5296], Yamagishi, Kazumasa [0000-0003-3301-5519], Zamora-Ros, Raul [0000-0002-6236-6804], Gagnon, David R [0000-0002-6367-3179], Tsao, Philip S [0000-0001-7274-9318], Edwards, Todd L [0000-0003-4318-6119], Damrauer, Scott M [0000-0001-8009-1632], Joseph, Jacob [0000-0002-7279-4896], Pennells, Lisa [0000-0002-8594-3061], Gaziano, Thomas A [0000-0002-5985-345X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nick [0000-0003-1422-2993], Hung, Adriana M [0000-0002-3203-1608], Butterworth, Adam S [0000-0002-6915-9015], Di Angelantonio, Emanuele [0000-0001-8776-6719], Apollo - University of Cambridge Repository, Gaziano, Liam, Sun, Luanluan, Arnold, Matthew, Bell, Steven, Cho, Kelly, Kaptoge, Stephen K, Song, Rebecca J, Burgess, Stephen, Posner, Daniel C, Mosconi, Katja, Robinson-Cohen, Cassianne, Mason, Amy M, Bolton, Thomas R, Tao, Ran, Allara, Elia, Schubert, Petra, Chen, Lingyan, Staley, James R, Staplin, Natalie, Altay, Servet, Amiano, Pilar, Arndt, Volker, Ärnlöv, Johan, Barr, Elizabeth L M, Björkelund, Cecilia, Boer, Jolanda M A, Brenner, Hermann, Casiglia, Edoardo, Chiodini, Paolo, Cooper, Jackie A, Coresh, Josef, Cushman, Mary, Dankner, Rachel, Davidson, Karina W, de Jongh, Renate T, Donfrancesco, Chiara, Engström, Gunnar, Freisling, Heinz, de la Cámara, Agustín Gómez, Gudnason, Vilmundur, Hankey, Graeme J, Hansson, Per-Olof, Heath, Alicia K, Hoorn, Ewout J, Imano, Hironori, Jassal, Simerjot K, Kaaks, Rudolf, Katzke, Verena, Kauhanen, Jussi, Kiechl, Stefan, Koenig, Wolfgang, Kronmal, Richard A, Kyrø, Cecilie, Lawlor, Deborah A, Ljungberg, Börje, Macdonald, Conor, Masala, Giovanna, Meisinger, Christa, Melander, Olle, Moreno Iribas, Conchi, Ninomiya, Toshiharu, Nitsch, Dorothea, Nordestgaard, Børge G, Onland-Moret, Charlotte, Palmieri, Luigi, Petrova, Dafina, Garcia, Jose Ramón Quiró, Rosengren, Annika, Sacerdote, Carlotta, Sakurai, Masaru, Santiuste, Carmen, Schulze, Matthias B, Sieri, Sabina, Sundström, Johan, Tikhonoff, Valérie, Tjønneland, Anne, Tong, Tammy, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T, Monique Verschuren, W M, Völzke, Henry, Wallace, Robert B, Wannamethee, S Goya, Weiderpass, Elisabete, Willeit, Peter, Woodward, Mark, Yamagishi, Kazumasa, Zamora-Ros, Raul, Akwo, Elvis A, Pyarajan, Saiju, Gagnon, David R, Tsao, Philip S, Muralidhar, Sumitra, Edwards, Todd L, Damrauer, Scott M, Joseph, Jacob, Pennells, Lisa, Wilson, Peter W F, Harrison, Seamu, Gaziano, Thomas A, Inouye, Michael, Baigent, Colin, Casas, Juan P, Langenberg, Claudia, Wareham, Nick, Riboli, Elio, Gaziano, J Michael, Danesh, John, Hung, Adriana M, Butterworth, Adam S, Wood, Angela M, Di Angelantonio, Emanuele, Internal medicine, AMS - Ageing & Vitality, AMS - Musculoskeletal Health, Amsterdam Gastroenterology Endocrinology Metabolism, Epidemiology and Data Science, APH - Aging & Later Life, and APH - Personalized Medicine
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kidney disease ,General Practice ,Emerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program ,Coronary Disease ,coronary disease ,Kidney ,Malalties coronàries ,1117 Public Health and Health Services ,Coronary diseases ,SDG 3 - Good Health and Well-being ,cardiovascular disease ,Risk Factors ,Physiology (medical) ,Diabetes Mellitus ,Humans ,Cardiac and Cardiovascular Systems ,Prospective Studies ,1102 Cardiorespiratory Medicine and Haematology ,Kardiologi ,Kidney diseases ,Malalties cardiovasculars ,Cardiovascular Diseases ,Kidney Diseases ,Stroke ,1103 Clinical Sciences ,Mendelian Randomization Analysis ,kidney diseases ,stroke ,Allmänmedicin ,Cardiovascular diseases ,Cardiovascular System & Hematology ,Malalties del ronyó ,Cardiology and Cardiovascular Medicine ,cardiovascular diseases - Abstract
Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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- 2022
42. Salt intake correlates with night systolic blood pressure in non-dialytic chronic kidney disease
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Silvio Borrelli, Francesca Mallamaci, Paolo Chiodini, Carlo Garofalo, Patrizia Pizzini, Rocco Tripepi, Graziella D'Arrigo, Giovanni Tripepi, Giuseppe Conte, Luca De Nicola, Carmine Zoccali, Roberto Minutolo, Borrelli, S., Mallamaci, F., Chiodini, P., Garofalo, C., Pizzini, P., Tripepi, R., D'Arrigo, G., Tripepi, G., Conte, G., De Nicola, L., Zoccali, C., and Minutolo, R.
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Transplantation ,Nephrology ,Hypertension ,Blood Pressure ,Sodium Chloride, Dietary ,Renal Insufficiency, Chronic ,Human - Published
- 2022
43. A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events
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Andrea Cappozzo, Cathal McCrory, Oliver Robinson, Anna Freni Sterrantino, Carlotta Sacerdote, Vittorio Krogh, Salvatore Panico, Rosario Tumino, Licia Iacoviello, Fulvio Ricceri, Sabina Sieri, Paolo Chiodini, Rose Anne Kenny, Aisling O’Halloran, Silvia Polidoro, Giuliana Solinas, Paolo Vineis, Francesca Ieva, and Giovanni Fiorito
- Abstract
Background: Recent evidence highlights the epidemiological value of blood DNA methylation (DNAm) as surrogate biomarker for exposures to risk factors for non-communicable diseases (NCD). DNAm surrogate of exposures predict diseases and longevity better than self-reported or measured exposures in many cases. Consequently, disease prediction models based on blood DNAm surrogates may outperform current state-of-art prediction models. This study aims to develop novel DNAm surrogates for cardiovascular diseases (CVD) risk factors and develop a composite biomarker predictive of CVD risk. We compared the prediction performance of our newly developed risk score with the state-of-art DNAm risk scores for cardiovascular diseases, the ‘next-generation’ epigenetic clock DNAmGrimAge, and the prediction model based on traditional risk factors SCORE2.Results: Using data from the EPIC Italy cohort, we derived novel DNAm surrogates for BMI, blood pressure, fasting glucose and insulin, cholesterol, triglycerides, and coagulation biomarkers. We validated them in four independent datasets from Europe and the US. Further, we derived a DNAmCVDscore predictive of the time-to-CVD event as a combination of several DNAm surrogates. ROC curve analyses show that DNAmCVDscore outperforms previously developed DNAm scores for CVD risk and SCORE2 for short-term CVD risk. Interestingly, the performance of DNAmGrimAge and DNAmCVDscore was comparable (slightly lower for DNAmGrimAge, although the differences were not statistically significant).Conclusions: We described novel DNAm surrogates for CVD risk factors useful for future molecular epidemiology research, and we described a blood DNAm-based composite biomarker, DNAmCVDscore, predictive of short-term cardiovascular events. Our results highlight the usefulness of DNAm surrogate biomarkers of risk factors in epigenetic epidemiology to identify high-risk populations. In addition, we provide further evidence on the effectiveness of prediction models based on DNAm surrogates and discuss methodological aspects for further improvements. Finally, our results encourage testing this approach for other NCD diseases by training and developing DNAm surrogates for disease-specific risk factors and exposures.
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- 2022
44. The bidirectional relationship between testosterone and metabolic disorders: testosterone deficiency as an early marker of cardiovascular risk in young men
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Davide Menafra, Angelis Cristina De, Francesco Garifalos, Michele Castoro, Nunzia Verde, Mariangela Piscopo, Giacomo Galdiero, Claudia Pivonello, Auriemma Renata Simona, Paolo Chiodini, Annamaria Colao, and Rosario Pivonello
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- 2022
45. Morphostructural characterization of the testis in a large cohort of men living in highly polluted areas of Campania Region in south Italy: a focus on cadmium exposure
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Francesco Garifalos, Angelis Cristina De, Nunzio Aldo Di, Davide Menafra, Michele Castoro, Nunzia Verde, Giacomo Galdiero, Mariangela Piscopo, Claudia Pivonello, Renata Simona Auriemma, Paolo Chiodini, Marco Trifuoggi, Annamaria Colao, and Rosario Pivonello
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- 2022
46. MO092: Prevalence and Renal Prognosis of Left Ventricular Diastolic Dysfunction in Nondialysis Chronic Kidney Disease Patients With Preserved Systolic Function
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Silvio Borrelli, Luca De Nicola, Carlo Garofalo, Eugenio Lembo, Antonella Netti, Sergio Lucà, Stefano Lucà, Paolo Chiodini, Ernesto Paoletti, Giovanna Stanzione, Giuseppe Conte, and Roberto Minutolo
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Transplantation ,Nephrology - Abstract
BACKGROUND AND AIMS Left ventricular (LV) diastolic dysfunction is common in nondialysis chronic kidney disease (ND-CKD) patients; however, the prevalence estimated according to the new diagnostic criteria as well as the prognostic role of diastolic dysfunction on CKD progression remain unknown. METHOD We longitudinally evaluated consecutive ND-CKD patients and preserved systolic function (LV ejection fraction > 50%). According to the recently updated guidelines, LV diastolic dysfunction was assessed by four echocardiographic variables (annular e’ velocity, average mitral valve E-wave/e’ ratio, left atrial volume index and tricuspid regurgitation). Patients were classified as diastolic dysfunction, indeterminate and normal. Time-dependent eGFR change was assessed by mixed-effects regression model. Cumulative incidence of composite renal outcome (eGFR decline > 50% or chronic dialysis) was also estimated. RESULTS Among 140 patients (age 66.2 ± 14.5 years; 61% males; eGFR 39.8 ± 21.8 mL/min/1.73 m2; 43.6% diabetics), diastolic dysfunction occurred in 22.9%, indeterminate in 45.7% and normal in 31.4%. Prevalence of diastolic dysfunction was much lower than that estimated with older criteria (62.1%). Logistic regression (OR, 95%CI) showed that diastolic dysfunction was associated with lower eGFR (0.97, 0.94–0.99), older age (1.08, 1.01–1.06) and nighttime systolic blood pressure (1.04, 1.00–1.07). Across 1702 eGFR measurements collected during a median follow-up of 4.6 years, eGFR decline (mL/min/1.73 m2/year) was faster in patients with diastolic dysfunction (−2.12, 95%CI from −2.68 to −1.56) and in the indeterminate (11.2/100 pts/year) as compared with normal (−1.14, 95%CI from −1.64 to −0.63) (Figur 2). Incidence of composite renal outcome was significantly higher in diastolic dysfunction (13.8/100 pts/year) than in normal group (3.5/100 pts/year). CONCLUSION In ND-CKD population, LV diastolic dysfunction is less frequent than previously described and acts as independent predictor of CKD progression. Mixed-effect regression was adjusted for age, gender, diabetes, prior cardiovascular disease, log(proteinuria), systolic office blood pressure (BP), diurnal and nocturnal systolic ambulatory BP and left ventricular hypertrophy.
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- 2022
47. Reply to Mocanu CA et al
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Vincenzo Bellizzi, Simona Signoriello, Paolo Chiodini, Luca De Nicola, Bellizzi, Vincenzo, Signoriello, Simona, Chiodini, Paolo, and De Nicola, Luca
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Nutrition and Dietetics ,Medicine (miscellaneous) - Published
- 2022
48. Machine learning in neuro-oncology: toward novel development fields
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Vincenzo Di Nunno, Mario Fordellone, Giuseppe Minniti, Sofia Asioli, Alfredo Conti, Diego Mazzatenta, Damiano Balestrini, Paolo Chiodini, Raffaele Agati, Caterina Tonon, Alicia Tosoni, Lidia Gatto, Stefania Bartolini, Raffaele Lodi, Enrico Franceschi, Di Nunno, V., Fordellone, M., Minniti, G., Asioli, S., Conti, A., Mazzatenta, D., Balestrini, D., Chiodini, P., Agati, R., Tonon, C., Tosoni, A., Gatto, L., Bartolini, S., Lodi, R., and Franceschi, E.
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Brain tumor ,Machine Learning ,Cancer Research ,Central nervous system malignancie ,Oncology ,Neurology ,Artificial Intelligence ,Humans ,Deep learning ,Neurology (clinical) ,Radiology - Abstract
Purpose: Artificial Intelligence (AI) involves several and different techniques able to elaborate a large amount of data responding to a specific planned outcome. There are several possible applications of this technology in neuro-oncology. Methods: We reviewed, according to PRISMA guidelines, available studies adopting AI in different fields of neuro-oncology including neuro-radiology, pathology, surgery, radiation therapy, and systemic treatments. Results: Neuro-radiology presented the major number of studies assessing AI. However, this technology is being successfully tested also in other operative settings including surgery and radiation therapy. In this context, AI shows to significantly reduce resources and costs maintaining an elevated qualitative standard. Pathological diagnosis and development of novel systemic treatments are other two fields in which AI showed promising preliminary data. Conclusion: It is likely that AI will be quickly included in some aspects of daily clinical practice. Possible applications of these techniques are impressive and cover all aspects of neuro-oncology.
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- 2022
49. Dipping Status, Ambulatory Blood Pressure Control, Cardiovascular Disease, and Kidney Disease Progression: A Multicenter Cohort Study of CKD
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Silvio Borrelli, Carlo Garofalo, Francis B. Gabbai, Paolo Chiodini, Simona Signoriello, Ernesto Paoletti, Maura Ravera, Elisabetta Bussalino, Vincenzo Bellizzi, Maria Elena Liberti, Luca De Nicola, Roberto Minutolo, Borrelli, Silvio, Garofalo, Carlo, Gabbai, Francis B, Chiodini, Paolo, Signoriello, Simona, Paoletti, Ernesto, Ravera, Maura, Bussalino, Elisabetta, Bellizzi, Vincenzo, Liberti, Maria Elena, De Nicola, Luca, and Minutolo, Roberto
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cardiovascular risk ,dipping statu ,ESKD ,hypertension ,nocturnal hypertension ,renal risk ,Nephrology ,ABPM ,CKD ,circadian profile ,Ambulatory blood pressure monitoring ,daytime blood pressure ,nighttime blood pressure - Abstract
Ambulatory blood pressure (BP) monitoring allows concurrent evaluation of BP control and nocturnal BP dipping status, both related to adverse outcomes. However, few studies have assessed the prognostic role of combining information on dipping status and achieved ambulatory BP in patients with chronic kidney disease (CKD).Prospective observational cohort study.906 patients with hypertension and CKD attending 1 of 3 Italian nephrology clinics.Four groups were defined by simultaneously classifying systolic ambulatory BP levels as being at goal (daytime SBP 135 and nighttime SBP 120 mm Hg) or above goal, and the presence or absence of nocturnal dipping (nighttime to daytime SBP ratio of 0.9 versus ≥0.9).The composite of time to initiation of maintenance dialysis or estimated glomerular filtration rate (eGFR) decline ≥50%, and the composite of fatal and nonfatal cardiovascular events.Multivariable Cox proportional hazards models were used to estimate risks of kidney disease progression and cardiovascular disease in the 4 exposure groups where nocturnal dipping with systolic ambulatory BP at goal was the reference group.The mean patient age was 63.8 years, 61% were male, and 26.4% had diabetes; eGFR was 41.1 ± 20.8 mL/min/1.73 mLack of a diverse cohort (all those enrolled were White). Residual uncontrolled confounding.Systolic ambulatory BP above goal or the absence of nocturnal dipping, regardless of ambulatory BP, is associated with higher risks of cardiovascular disease and kidney disease progression among patients with CKD.Among patients with chronic kidney disease (CKD), ambulatory blood pressure (BP) monitoring improves the identification of individuals at high risk of clinical disease outcomes. Those with uncontrolled ambulatory BP are known to have a higher risk of developing cardiovascular disease and kidney disease progression, particularly when their ambulatory BP does not decline by at least 10% at night. Whether this is also true for patients with presence of optimal ambulatory BP levels but a BP pattern of no nighttime decline is largely unknown. We measured ambulatory BP in 900 Italian patients with CKD and followed them for several years. We found that, independent of ambulatory BP level, the absence of nighttime reductions in BP was associated with worsening of CKD and more frequent cardiovascular events. The absence of nighttime declines in BP is an independent risk factor for adverse events among patients with CKD. Future studies are needed to examine whether treating the absence of nighttime declines in BP improves clinical outcomes.
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- 2022
50. Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
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Joanna L. Clasen, Alicia K. Heath, Heleen Van Puyvelde, Inge Huybrechts, Jin Young Park, Pietro Ferrari, Ghislaine Scelo, Arve Ulvik, Øivind Midttun, Per Magne Ueland, Kim Overvad, Anne Kirstine Eriksen, Anne Tjønneland, Rudolf Kaaks, Verena Katzke, Matthias B. Schulze, Domenico Palli, Claudia Agnoli, Paolo Chiodini, Rosario Tumino, Carlotta Sacerdote, Raul Zamora‐Ros, Miguel Rodriguez‐Barranco, Carmen Santiuste, Eva Ardanaz, Pilar Amiano, Julie A. Schmidt, Elisabete Weiderpass, Marc Gunter, Elio Riboli, Amanda J. Cross, Mattias Johansson, David C. Muller, Clasen, J. L., Heath, A. K., Van Puyvelde, H., Huybrechts, I., Park, J. Y., Ferrari, P., Scelo, G., Ulvik, A., Midttun, O., Ueland, P. M., Overvad, K., Eriksen, A. K., Tjonneland, A., Kaaks, R., Katzke, V., Schulze, M. B., Palli, D., Agnoli, C., Chiodini, P., Tumino, R., Sacerdote, C., Zamora-Ros, R., Rodriguez-Barranco, M., Santiuste, C., Ardanaz, E., Amiano, P., Schmidt, J. A., Weiderpass, E., Gunter, M., Riboli, E., Cross, A. J., Johansson, M., Muller, D. C., and Cancer Research UK
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Cancer Research ,dietary biomarkers ,transsulfuration ,dietary biomarker ,HOMOCYSTEINE ,METABOLISM ,urologic and male genital diseases ,vitamin B6 ,SERUM ,INFLAMMATION ,Humans ,1112 Oncology and Carcinogenesis ,ASSAY ,AMINO-ACIDS ,Oncology & Carcinogenesis ,Cysteine ,Prospective Studies ,Carcinoma, Renal Cell ,Homocysteine ,Carcinoma, Renal Cell/epidemiology ,Science & Technology ,Kidney Neoplasms/epidemiology ,PLASMA ,kidney cancer ,Bayes Theorem ,Kidney Neoplasms ,Vitamin B 6 ,Oncology ,VITAMIN-B-12 ,Case-Control Studies ,Pyridoxal Phosphate ,CYSTEINE ,Life Sciences & Biomedicine ,Biomarkers ,FOLATE - Abstract
Previous studies have suggested that components of one-carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case-control study (455 RCC cases and 455 matched controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Plasma samples from the baseline visit were analyzed for metabolites of the transsulfuration pathway, including pyridoxal 5'-phosphate (PLP, the biologically active form of vitamin B6), homocysteine, serine, cystathionine, and cysteine, in addition to folate. Bayesian conditional logistic regression was used to estimate associations of metabolites with RCC risk as well as interactions with established RCC risk factors. Circulating PLP and cysteine were inversely associated with RCC risk, and these associations were not attenuated after adjustment for other transsulfuration metabolites (odds ratio (OR) and 90% credible interval (CrI) per 1 SD increase in log concentration: 0.76 [0.66, 0.87]; 0.81 [0.66, 0.96], respectively). A comparison of joint metabolite profiles suggested substantially greater RCC risk for the profile representative of low overall transsulfuration function compared to high function (OR 2.70 [90% CrI 1.26, 5.70]). We found some statistical evidence of interactions of cysteine with body mass index, and PLP and homocysteine with smoking status, on their associations with RCC risk. In conclusion, we found evidence suggesting that the transsulfuration pathway may play a role in metabolic dysregulation leading to RCC development. ispartof: INTERNATIONAL JOURNAL OF CANCER vol:151 issue:5 pages:708-716 ispartof: location:United States status: published
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- 2022
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