Publications by authors named "Vittorio Simeon"

87 Publications

Ceftolozane-Tazobactam Combination Therapy Compared to Ceftolozane-Tazobactam Monotherapy for the Treatment of Severe Infections: A Systematic Review and Meta-Analysis.

Antibiotics (Basel) 2021 Jan 15;10(1). Epub 2021 Jan 15.

Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy.

Ceftolozane-tazobactam (C/T) is a combination of an advanced-generation cephalosporin (ceftolozane) with a β-lactamase inhibitor (tazobactam). It is approved for the treatment of complicated urinary-tract/intra-abdominal infections and hospital-acquired/ventilator-associated pneumonia. This systematic review and meta-analysis (registered prospectively on PROSPERO, no. CRD42019134099, on 20 January 2020) aimed to evaluate the effectiveness of C/T combination therapy compared to C/T monotherapy for the treatment of severe infections and to describe the prevalence of microorganisms in the included studies. We retrieved literature from PubMed, EMBASE, and CENTRAL, until 26 November 2020. Eligible studies were both randomised trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was all-cause mortality; secondary outcomes were (i) clinical improvement and (ii) microbiological cure. Eight nonrandomised studies were included in the qualitative synthesis: Seven retrospective cohort studies and one case-control study. The meta-analysis of the four studies evaluating all-cause mortality (in total 148 patients: 87 patients treated with C/T alone and 61 patients treated with C/T combination therapy) showed a significant reduction of mortality in patients receiving C/T combination therapy, OR: 0.31, 95% CI: 0.10-0.97, = 0.045. Conversely, the meta-analysis of the studies evaluating clinical improvement and microbiological cure showed no differences in C/T combination therapy compared to C/T monotherapy. The most consistent data come from the analysis of the clinical improvement, = 391 patients, OR: 0.97, 95% CI: 0.54-1.74, = 0.909. In 238 of the 391 patients included (60.8%), C/T was used for the treatment of infections caused by Pseudomonas aeruginosa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antibiotics10010079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830767PMC
January 2021

[Covid-19 and clinical-epidemiological research in Italy: proposal of a research agenda on priority topics by the Italian association of epidemiology].

Epidemiol Prev 2020 Sep-Dec;44(5-6 Suppl 2):51-59

Istituto per la ricerca e l'innovazione biomedica, Consiglio nazionale delle ricerche, Palermo.

Background: the Covid-19 pandemic has provoked a huge of clinical and epidemiological research initiatives, especially in the most involved countries. However, this very large effort was characterized by several methodological weaknesses, both in the field of discovering effective treatments (with too many small and uncontrolled trials) and in the field of identifying preventable risks and prognostic factors (with too few large, representative and well-designed cohorts or case-control studies).

Objectives: in response to the fragmented and uncoordinated research production on Covid-19, the   italian Association of Epidemiology (AIE) stimulated the formation of a working group (WG) with the aims of identifying the most important gaps in knowledge and to propose a structured research agenda of clinical and epidemiological studies considered at high priority on Covid-19, including recommendations on the preferable methodology.

Methods: the WG was composed by 25 subjects, mainly epidemiologists, statisticians, and other experts in specific fields, who have voluntarily agreed to the proposal. The agreement on a list of main research questions and on the structure of the specific documents to be produced were defined through few meetings and cycles of document exchanges.

Results: twelve main research questions on Covid-19 were identified, covering aetiology, prognosis, interventions, follow-up and impact on general and specific populations (children, pregnant women). For each of them, a two-page form was developed, structured in: background, main topics, methods (with recommendations on preferred study design and warnings for bias prevention) and an essential bibliography.

Conclusions: this research agenda represents an initial contribution to direct clinical and epidemiological research efforts on high priority topics with a focus on methodological aspects. Further development and refinements of this agenda by Public Health Authorities are encouraged.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19191/EP20.5-6.S2.103DOI Listing
January 2021

Impact of chronic liver disease upon admission on COVID-19 in-hospital mortality: Findings from COVOCA study.

PLoS One 2020 10;15(12):e0243700. Epub 2020 Dec 10.

Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

Background: Italy has been the first Western country to be heavily affected by the spread of SARS-COV-2 infection and among the pioneers of the clinical management of pandemic. To improve the outcome, identification of patients at the highest risk seems mandatory.

Objectives: Aim of this study is to identify comorbidities and clinical conditions upon admission associated with in-hospital mortality in several COVID Centers in Campania Region (Italy).

Methods: COVOCA is a multicentre retrospective observational cohort study, which involved 18 COVID Centers throughout Campania Region, Italy. Data were collected from patients who completed their hospitalization between March-June 2020. The endpoint was in-hospital mortality, assessed either from data at discharge or death certificate, whilst all exposure variables were collected at hospital admission.

Results: Among 618 COVID-19 hospitalized patients included in the study, 143 in-hospital mortality events were recorded, with a cumulative incidence of about 23%. At multivariable logistic analysis, male sex (OR 2.63, 95%CI 1.42-4.90; p = 0.001), Chronic Liver Disease (OR 5.88, 95%CI 2.39-14.46; p<0.001) and malignancies (OR 2.62, 95%CI 1.21-5.68; p = 0.015) disclosed an independent association with a poor prognosis, Glasgow Coma Scale (GCS) and Respiratory Severity Scale allowed to identify at higher mortality risk. Sensitivity analysis further enhanced these findings.

Conclusion: Mortality of patients hospitalized for COVID-19 appears strongly affected by both clinical conditions on admission and comorbidities. Originally, we observed a very poor outcome in subjects with a chronic liver disease, alongside with an increase of hepatic damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243700PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728173PMC
January 2021

Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Int J Cancer 2021 Apr 9;148(7):1637-1651. Epub 2020 Nov 9.

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33339DOI Listing
April 2021

Replacement of Red and Processed Meat With Other Food Sources of Protein and the Risk of Type 2 Diabetes in European Populations: The EPIC-InterAct Study.

Diabetes Care 2020 Nov 31;43(11):2660-2667. Epub 2020 Aug 31.

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, U.K.

Objective: There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact.

Research Design And Methods: The European Prospective Investigation into Cancer (EPIC)-InterAct case cohort included 11,741 individuals with type 2 diabetes and a subcohort of 15,450 participants in eight countries. We modeled the replacement of self-reported red and processed meat with poultry, fish, eggs, legumes, cheese, cereals, yogurt, milk, and nuts. Country-specific hazard ratios (HRs) for incident type 2 diabetes were estimated by Prentice-weighted Cox regression and pooled using random-effects meta-analysis.

Results: There was a lower hazard for type 2 diabetes for the modeled replacement of red and processed meat (50 g/day) with cheese (HR 0.90, 95% CI 0.83-0.97) (30 g/day), yogurt (0.90, 0.86-0.95) (70 g/day), nuts (0.90, 0.84-0.96) (10 g/day), or cereals (0.92, 0.88-0.96) (30 g/day) but not for replacements with poultry, fish, eggs, legumes, or milk. If a causal association is assumed, replacing red and processed meat with cheese, yogurt, or nuts could prevent 8.8%, 8.3%, or 7.5%, respectively, of new cases of type 2 diabetes.

Conclusions: Replacement of red and processed meat with cheese, yogurt, nuts, or cereals was associated with a lower rate of type 2 diabetes. Substituting red and processed meat by other protein sources may contribute to the prevention of incident type 2 diabetes in European populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc20-1038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576430PMC
November 2020

Area Deprivation and Risk of Death and CKD Progression: Long-Term Cohort Study in Patients under Unrestricted Nephrology Care.

Nephron 2020 20;144(10):488-497. Epub 2020 Aug 20.

Nephrology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy.

Background: Area deprivation index (ADI) associates with prognosis in non-dialysis CKD. However, no study has evaluated this association in CKD patients under unrestricted nephrology care.

Methods: We performed a long-term prospective study to assess the role of deprivation in CKD progression and mortality in stage 1-4 CKD patients under regular nephrology care, living in Naples (Italy). We used ADI calculated at census block levels, standardized to mean values of whole population in Naples, and linked to patients by georeference method. After 12 months of "goal-oriented" nephrology treatment, we compared the risk of death or composite renal outcomes (end-stage kidney disease or doubling of serum creatinine) in the tertiles of standardized ADI. Estimated glomerular filtration rate (eGFR) decline was evaluated by mixed effects model for repeated eGFR measurements.

Results: We enrolled 715 consecutive patients (age: 64 ± 15 years; 59.1% males; eGFR: 49 ± 22 mL/min/1.73 m2). Most (75.2%) were at the lowest national ADI quintile. At referral, demographic, clinical, and therapeutic features were similar across ADI tertiles; after 12 months, treatment intensification allowed better control of hypertension, proteinuria, hypercholesterolaemia, and anaemia with no difference across ADI tertiles. During the subsequent long-term follow-up (10.5 years [interquartile range 8.2-12.6]), 166 renal events and 249 deaths were registered. ADI independently associated with all-cause death (p for trend = 0.020) and non-cardiovascular (CV) mortality (p for trend = 0.045), while CV mortality did not differ (p for trend = 0.252). Risk of composite renal outcomes was similar across ADI tertiles (p for trend = 0.467). The same held true for eGFR decline (p for trend = 0.675).

Conclusions: In CKD patients under regular nephrology care, ADI is not associated with CKD progression, while it is associated with all-cause death due to an excess of non-CV mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509351DOI Listing
August 2020

AXL is a predictor of poor survival and of resistance to anti-EGFR therapy in RAS wild-type metastatic colorectal cancer.

Eur J Cancer 2020 10 17;138:1-10. Epub 2020 Aug 17.

Department of Precision Medicine, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy. Electronic address:

Background: RAS mutations are the only validated biomarkers in metastatic colorectal cancer (mCRC) for anti-epidermal growth factor receptor (EGFR) therapy. Limited clinical information is available on AXL expression, marker of epithelial to mesenchymal transition, in mCRC.

Methods: AXL was retrospectively assessed by immunohistochemistry in 307 patients. RAS wild-type (WT) patients (N = 136) received first-line anti-EGFR-based therapy; RAS mutant patients (N = 171) received anti-angiogenic-based regimens. Preclinical experiments were performed using human RAS WT CRC cell lines and xenograft models. AXL RNA levels were assessed in a cohort of patients with available samples at baseline and at progression to anti-EGFR treatment and in the GSE5851 dataset.

Results: AXL was expressed in 55/307 tumour tissues, correlating with worse survival in the overall population (AXL-positive, 23.7 months; AXL-negative, 30.8 months; HR, 1.455, P = 0.032) and in RAS WT patients (AXL-positive, 23.0 months; AXL-negative, 35.8 months; HR,1.780, P = 0.032). Progression-free survival (PFS) in the RAS WT cohort was shorter in the AXL-positive cohort (6.2 months versus 12.1 months; HR, 1.796, P = 0.013). Three-dimensional cultures obtained from a patient following anti-EGFR therapy resulted AXL-positive, showing resistance to anti-EGFR drugs and sensitivity to AXL inhibition. AXL transfection in CRC cell lines induced AXL overexpression and resistance to the EGFR blockade. At progression to cetuximab, 2/10 SW48-tumour xenograft mice showed AXL expression. Consistently, AXL RNA levels increased in 5/7 patients following anti-EGFR therapy. Moreover, in the GSE5851 dataset higher AXL RNA levels correlated with worse PFS with cetuximab in KRAS-exon2 WT chemorefractory patients.

Conclusions: AXL is a marker of poor prognosis in mCRC with consistent clinical and preclinical evidences of involvement in primary and acquired resistance to anti-EGFR drugs in RAS WT patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2020.07.010DOI Listing
October 2020

Ceftazidime-Avibactam Combination Therapy Compared to Ceftazidime-Avibactam Monotherapy for the Treatment of Severe Infections Due to Carbapenem-Resistant Pathogens: A Systematic Review and Network Meta-Analysis.

Antibiotics (Basel) 2020 Jul 7;9(7). Epub 2020 Jul 7.

Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.). Section of Anesthesia, Analgesia, Intensive Care and Emergency. Policlinico Paolo Giaccone, University of Palermo, 90127 Palermo, Italy.

Ceftazidime-avibactam (CZA) is a novel beta-lactam beta-lactamase inhibitor combination approved for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and for hospital-acquired/ventilator-associated pneumonia. The aim of this systematic review (PROSPERO registration number: CRD42019128927) was to evaluate the effectiveness of CZA combination therapy versus CZA monotherapy in the treatment of severe infections. The databases included in the search, until February 12th, 2020, were MEDLINE by PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials. We included both randomized controlled trials (RCTs) and non-randomized studies published in peer-reviewed journals and in the English language. The primary outcome was all-cause mortality (longest follow-up) evaluated in patients with the diagnosis of infection with at least one pathogen; secondary outcomes were clinical and microbiological improvement/cure. Thirteen studies were included in the qualitative synthesis: 7 RCTs and 6 retrospective studies All the six retrospective studies identified carbapenamase-producing Enterobacteriaceae (CRE) as the cause of infection and for this reason were included in the network meta-analysis (NMA); the quality of the studies, assessed using the New Castle-Ottawa Scale, was moderate-high. In all the six retrospective studies included in the NMA, CZA was used in large part for off-label indications (mostly blood stream infections: 80-100% of patients included). No difference in mortality rate was observed in patients undergoing CZA combination therapy compared to CZA monotherapy [ = 503 patients, direct evidence OR: 0.96, 95% CI: 0.65-1.41].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antibiotics9070388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400227PMC
July 2020

Temporomandibular disorders, neck disability, and oral parafunctions in tinnitus patients: A cross-sectional epidemiological study from Southern Italy.

Cranio 2020 Jun 19:1-9. Epub 2020 Jun 19.

Department of Neurosciences, Reproductive Sciences and Oral Science, School of Orthodontics and Temporomandibular Disorders, University of Naples Federico II , Naples, Italy.

Objective: To assess the prevalence of temporomandibular disorders (TMD) in a sample of tinnitus patients and to determine the association between tinnitus, TMD, neck disability, and oral parafunctions.

Methods: Seventy-nine tinnitus patients were enrolled and underwent standardized clinical examination for TMD. The tinnitus severity was measured with the Tinnitus Handicap Inventory (THI). The oral parafunctions were self-reported with the Oral Behavior Checklist (OBC). The neck disability was recorded with the Neck Disability Index (NDI).

Results: More than half of the sample presented TMD, and the most frequent diagnosis was TMD pain. Higher THI was observed in TMD-pain individuals, compared to TMD-free (β 18.4; 95%CI 6.7, 30.1; p = 0.002). The OBC showed a significant low-to-moderate positive correlation with the THI (rho= 0.368, p = 0.001), while the NDI did not.

Discussion: Standardized assessment of TMD and oral behaviors should be integrated into the routine diagnostic evaluations of tinnitus patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08869634.2020.1781499DOI Listing
June 2020

Antimicrobial Lock Therapy in Clinical Practice: A Scoping Review Protocol.

Methods Protoc 2020 Feb 12;3(1). Epub 2020 Feb 12.

Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", 80138 Naples 80138, Italy.

Our objective is to review the scientific literature on the use of antimicrobial lock therapy (ALT). To achieve this result, our scoping review will address the following seven key questions: 1) Who are the patients who will benefit from this technique? 2) What are the techniques utilized? 3) What are the settings in which the technique is performed? 4) When the technique is performed? 5) Why the technique is performed? 6) How the technique is performed? 7) In how much amount, of such technique performed? This review considers all studies published in full and in peer-reviewed journals, with no restrictions on language, on the year of publication and age of the participants. Both randomized controlled trials and observational studies will be included. This scoping review has been planned on a five-stage framework: 1. Identifying the review question; 2. identifying relevant studies; 3. study selection; 4. charting the data; 5. collating, summarizing, and reporting the results. It is conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. The databases utilized will include MEDLINE via PubMed, EMBASE and Cochrane Central Register of Controlled Trials and Grey Literature. SCOPING REVIEW REGISTRATION: Open Science Framework https://osf.io/vphwm/.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/mps3010016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189672PMC
February 2020

Changes in the relative prevalence of candidaemia due to non-albicans Candida species in adult in-patients: A systematic review, meta-analysis and meta-regression.

Mycoses 2020 Apr;63(4):334-342

Clinica Malattie Infettive, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy.

Background: Candidaemia remains associated with high mortality and increased costs worldwide.

Objective: To assess the changes over time in the relative prevalence of non-albicans candidaemia (NAC).

Methods: A systematic review, meta-analysis and meta-regression were performed. Observational studies investigating the epidemiology of consecutive, non-selected, candidaemia episodes were included. Two separated analyses were conducted: (a) whole hospital analysis and (b) intensive care unit (ICU) analysis.

Results: Starting from an initial total of 7726 records, 220 studies fulfilled inclusion criteria. The pooled prevalence of NAC in whole hospital analysis was 49.5% (95% confidence intervals [CI] 48.0-51.1, I 93.1%), while the pooled prevalence in ICU analysis was 50.6% (95% CI 46.6-54.6; I 86.7%). In meta-regression, a progressive increase in NAC prevalence was observed in whole hospital analysis, although it explained only a small portion of between-study variance (estimated yearly prevalence change +0.3%, 95% CI from +0.1% to +0.5%, P = .003; adjusted R 3.42%) and was observed only in some continents in subgroup analyses. No relevant changes over time were observed in NAC prevalence for ICU studies.

Conclusions: We registered an increasing trend in the relative prevalence of NAC, which, nonetheless, seems to be limited to some continents and to contribute only minimally to explain the observed differences in NAC prevalence across studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/myc.13054DOI Listing
April 2020

Comparative Gene Expression Profiling of Tobacco-Associated HPV-Positive versus Negative Oral Squamous Carcinoma Cell Lines.

Int J Med Sci 2020 1;17(1):112-124. Epub 2020 Jan 1.

Laboratory of Pre-Clinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.

HPV-positive oral squamous cell carcinomas (OSCCs) are specific biological and clinical entities, characterized by a more favorable prognosis compared to HPV-negative OSCCs and occurring generally in non-smoking and non-drinking younger individuals. However, poor information is available on the molecular and the clinical behavior of HPV-positive oral cancers occurring in smoking/drinking subjects. Thus, this study was designed to compare, at molecular level, two OSCC cell lines, both derived from drinking and smoking individuals and differing for presence/absence of HPV infection. HPV-negative UPCI-SCC-131 and HPV16-positive UPCI-SCC-154 cell lines were compared by whole genome gene expression profiling and subsequently studied for activation of Wnt/βCatenin signaling pathway by the expression of several Wnt-target genes, βCatenin intracellular localization, stem cell features and miRNA let-7e. Gene expression data were validated in head and neck squamous cell carcinoma (HNSCC) public datasets. Gene expression analysis identified Wnt/βCatenin pathway as the unique signaling pathway more active in HPV-negative compared to HPV-positive OSCC cells and this observation was confirmed upon evaluation of several Wnt-target genes (i.e., and ). Interestingly, HPV-negative OSCC cells showed higher levels of total βCatenin and its active form, increase of its nuclear accumulation and more prominent stem cell traits. Furthermore, miRNA let-7e was identified as potential upstream regulator responsible for the downregulation of Wnt/βCatenin signaling cascade since its silencing in UPCI-SCC-154 cell resulted in upregulation of Wnt-target genes. Finally, the analysis of two independent gene expression public datasets of human HNSCC cell lines and tumors confirmed that Wnt/βCatenin pathway is more active in HPV-negative compared to HPV-positive tumors derived from individuals with smoking habit. These data suggest that lack of HPV infection is associated with more prominent activation of Wnt/βCatenin signaling pathway and gain of stem-like traits in tobacco-related OSCCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.35133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945558PMC
October 2020

Impact of Fixed Orthodontic Appliance and Clear Aligners on the Periodontal Health: A Prospective Clinical Study.

Dent J (Basel) 2020 Jan 2;8(1). Epub 2020 Jan 2.

Department of Neuroscience, Reproductive Science and Oral Science, Division of Orthodontics, University of Naples Federico II, 80131 Naples, Italy.

This study aimed to evaluate the periodontal health of orthodontic patients with supportive periodontal therapy in a 3 month follow-up. The sample comprised 20 patients (mean age 20.6 ± 8.1 years) in treatment with multibracket fixed appliances (fixed group-FG) and 20 patients (mean age 34.7 ± 12.5 years) in treatment with clear aligners (clear aligners group-CAG). At baseline (T0) and after 3 months (T1), probing depth (PD), plaque index (PI), bleeding on probing (BOP), and gingival recession (REC) were measured. Patients were trained to perform an individualized tooth brushing technique, and every 2 weeks they were re-called to reinforce the oral hygiene instructions. The intra-group comparisons (T1 vs. T0) were calculated with the Wilcoxon signed-rank test, while a linear regression model was used for the inter-group comparisons (FG vs. CAG). The significance level was set at < 0.05. Statistically significant decrease in both groups was found for PD (FG: Δ, -9.2 inter-quartile range (IQR), -22.5, -5.5; CAG: Δ, -12.6 IQR, -25.4, -4.8), BOP (FG: Δ, -53.5 IQR, -70.5, -37; CAG: Δ, -37.5 IQR, -54.5, -23), and PI (FG: Δ, -17.5 IQR, -62.5, 14.5; CAG: Δ, -24 IQR, -49.5, -5). The result of the linear regression models suggested that the type of appliance did not have any effects on the improvement of periodontal variables. Therefore, patients undergoing orthodontic treatment with fixed appliances and clear aligners did not show differences in gingival health when followed by a dental hygienist.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/dj8010004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175220PMC
January 2020

Prospective validation of the International Warfarin Pharmacogenetics Consortium algorithm in high-risk elderly people (VIALE study).

Pharmacogenomics J 2020 06 5;20(3):451-461. Epub 2019 Dec 5.

Department of Mental Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138, Napoli, Italy.

We assessed the predictive accuracy of the Warfarin Pharmacogenetics Consortium (IWPC) algorithm in a prospective cohort of 376 high-risk elderly patients (≥65 years) who required new treatment with warfarin for either medical (non valvular atrial fibrillation) or surgical conditions (heart valve replacement), had ≥1 comorbid conditions, and regularly used ≥2 other drugs. Follow-up visits were performed according to clinical practice and lasted for a maximum of 1 year. Two hundred and eighty-three (75%) patients achieved a stable maintenance dose. Warfarin maintenance doses were low on average (median 20.3 mg/week, interquartile range, 14.1-27.7 mg/week) and were substantially overestimated by the IWPC algorithm. Overall the percentage of patients whose predicted dose of warfarin was within 20% of the actual stable dose was equal to 37.5%, (95% CI 32.0-43.3%). IWPC algorithm explained only 31% of the actual warfarin dose variability. Modifications of the IWPC algorithm are needed in high-risk elderly people.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41397-019-0129-6DOI Listing
June 2020

Distribution of the Condylion-Gonion-Menton (CoGoMe^) Angle in a Population of Patients from Southern Italy.

Dent J (Basel) 2019 Nov 3;7(4). Epub 2019 Nov 3.

Department of Neurosciences, Reproductive Sciences and Oral Sciences, Section of Orthodontics, University of Naples "Federico II", 80131 Naples, Italy.

The condylion-gonion-menton angle (CoGoMe^) is commonly used as a pre-treatment indicator of responsiveness in Class II patients treated with functional appliances. The distribution of this angle in the Caucasian population is still unknown. This study aimed to determine the distribution of the CoGoMe^ and its relationship with age, sagittal jaw relationship (ANPg^), and mandibular inclination (SN^GoGn) in patients from Southern Italy. The sample included 290 subjects (median14 years of age; Interquartile range, IQR, 12-17) with lateral cephalograms taken before the orthodontic treatment. The distribution of the CoGoMe^ was assessed with the Shapiro-Wilk test, and the differences according to the ANPg^ and the SN^GoGn were estimated using one-way ANOVA. Linear regression analysis was performed to evaluate how the CoGoMe^ varied according to age. The statistical significance was set at P < 0.05. The results showed that the CoGoMe^ was normally distributed (P = 0.290) with a mean value of 127.2° ± 7.7°. The distribution of the CoGoMe^ in groups with different SN^GoGn angles was significantly different (P < 0.001). These angles showed a positive association (Beta coefficient B = 0.6; 95% CI: 0.51, 0.67; P < 0.001). In growing patients, the CoGoMe^ decreased every year by 0.6° (B = -0.6; 95% CI: -1.05, -0.12; P = 0.014). In conclusion, the CoGoMe^ was associated with mandibular inclination and could be considered to be a predictor of vertical growth patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/dj7040104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960630PMC
November 2019

Lipoprotein (a) is an independent predictor of cardiovascular events in Mediterranean women (Progetto Atena).

Eur J Prev Cardiol 2020 Dec 22;27(19):2248-2250. Epub 2019 Oct 22.

Dipartimento di Medicina Clinica e Chirurgia, Università "Federico II" di Napoli, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2047487319884380DOI Listing
December 2020

Dexmedetomidine as adjunctive therapy for the treatment of alcohol withdrawal syndrome: a systematic review protocol.

JBI Database System Rev Implement Rep 2019 10;17(10):2159-2164

Department of Women, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy.

Objective: The purpose of this review is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care (benzodiazepines) compared to either the standard of care or other adjunctive treatment approaches (e.g. benzodiazepines plus propofol) for the treatment of alcohol withdrawal syndrome (AWS).

Introduction: Benzodiazepines have been the cornerstone of AWS therapy, but in some patients, AWS is refractory to high doses. Moreover, benzodiazepine use is burdened by excessive sedation, confusion and respiratory depression. Options for management of refractory AWS include the addition of phenobarbital, propofol and, more recently, dexmedetomidine to benzodiazepines therapy. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the intensive care unit.

Inclusion Criteria: This review will consider studies including patients who are 18 years or older and are diagnosed with AWS. The exclusion criteria are a history of psychoactive substances or withdrawal states and/or severe neurologic disorder (e.g. traumatic brain injury, acute stroke, severe dementia, seizure disorder).

Methods: This review will include only studies published in English, with no restrictions on the year of publication. Both randomized controlled trials and observational studies (including cohort and case-control studies) assessing the drug effectiveness and safety will be included. The databases utilized will include: PubMed, Embase and Cochrane Central Register of Controlled Trials. In addition, the trial registers to be searched will include: World Health Organization International Clinical Trials Registry Platform (ICTRP), U.S. National Library of Medicine Drug Information Portal and ClinicalTrials.gov.

Systematic Review Registration Number: PROSPERO CRD42018084370.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11124/JBISRIR-2017-003949DOI Listing
October 2019

Deferasirox drives ROS-mediated differentiation and induces interferon-stimulated gene expression in human healthy haematopoietic stem/progenitor cells and in leukemia cells.

Stem Cell Res Ther 2019 06 13;10(1):171. Epub 2019 Jun 13.

Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, PZ, Italy.

Background: Administration of the iron chelator deferasirox (DFX) in transfusion-dependent patients occasionally results in haematopoiesis recovery by a mechanism remaining elusive. This study aimed to investigate at a molecular level a general mechanism underlying DFX beneficial effects on haematopoiesis, both in healthy and pathological conditions.

Methods: Human healthy haematopoietic stem/progenitor cells (HS/PCs) and three leukemia cell lines were treated with DFX. N-Acetyl cysteine (NAC) and fludarabine were added as antioxidant and STAT1 inhibitor, respectively. In vitro colony-forming assays were assessed both in healthy and in leukemia cells. Intracellular and mitochondrial reactive oxygen species (ROS) as well as mitochondrial content were assessed by cytofluorimetric and confocal microscopy analysis; mtDNA was assessed by qRT-PCR. Differentiation markers were monitored by cytofluorimetric analysis. Gene expression analysis (GEA) was performed on healthy HS/PCs, and differently expressed genes were validated in healthy and leukemia cells by qRT-PCR. STAT1 expression and phosphorylation were assessed by Western blotting. Data were compared by an unpaired Student t test or one-way ANOVA.

Results: DFX, at clinically relevant concentrations, increased the clonogenic capacity of healthy human CD34 HS/PCs to form erythroid colonies. Extension of this analysis to human-derived leukemia cell lines Kasumi-1, K562 and HL60 confirmed DFX capacity to upregulate the expression of specific markers of haematopoietic commitment. Notably, the abovementioned DFX-induced effects are all prevented by the antioxidant NAC and accompanied with overproduction of mitochondria-generated reactive oxygen species (ROS) and increase of mitochondrial content and mtDNA copy number. GEA unveiled upregulation of genes linked to interferon (IFN) signalling and tracked back to hyper-phosphorylation of STAT1. Treatment of leukemic cell lines with NAC prevented the DFX-mediated phosphorylation of STAT1 as well as the expression of the IFN-stimulated genes. However, STAT1 inhibition by fludarabine was not sufficient to affect differentiation processes in leukemic cell lines.

Conclusions: These findings suggest a significant involvement of redox signalling as a major regulator of multiple DFX-orchestrated events promoting differentiation in healthy and tumour cells. The understanding of molecular mechanisms underlying the haematological response by DFX would enable to predict patient's ability to respond to the drug, to extend treatment to other patients or to anticipate the treatment, regardless of the iron overload.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-019-1293-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567456PMC
June 2019

Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer: HOBOE phase 3 randomised trial.

Eur J Cancer 2019 09 1;118:178-186. Epub 2019 Jun 1.

Medical Statistics, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy.

Aim: The aim of the study is to analyse whether letrozole (L) and zoledronic acid plus L (ZL) are more effective than tamoxifen (T) as adjuvant endocrine treatment of premenopausal patients with breast cancer with hormone receptor-positive (HR+) tumours.

Patients And Methods: In a phase 3 trial, 1065 premenopausal patients with HR + early breast cancer received triptorelin to suppress ovarian function and were randomly assigned (1:1:1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis.

Results: With a 64-month median follow-up and 134 reported events, the disease-free rate at 5 years was 85.4%, 93.2% and 93.3% with T, L and ZL, respectively (overall P = 0.008). The hazard ratio for a DFS event was 0.52 (95% confidence interval [CI], 0.34 to 0.80; P = 0.003) with ZL vs T, 0.72 (95% CI, 0.48 to 1.07; P = 0.06) with L vs T and 0.70 (95% CI, 0.44 to 1.12; P = 0.22) with ZL vs L. With 36 deaths, there was no significant difference in overall survival (P = 0.14). Treatment was stopped for toxicity or refusal in 7.3%, 7.3% and 16.6% patients, and in the safety population, grade 3-4 side-effects were reported in 4.2%, 6.9% and 9.1% patients treated with T, L or ZL, respectively.

Conclusion: HOBOE study shows that in premenopausal patients with early breast cancer undergoing ovarian function suppression with triptorelin, ZL significantly improves DFS, while worsening compliance and toxicity, as compared with T. (NCT00412022).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2019.05.004DOI Listing
September 2019

DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation.

Stem Cell Res Ther 2019 05 20;10(1):138. Epub 2019 May 20.

Laboratory of Preclinical and Translational Research, IRCCS - Referral Cancer Center of Basilicata (CROB), 85028, Rionero in Vulture, Italy.

Background: Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative therapeutic approach for different hematological malignancies (HMs), and epigenetic modifications, including DNA methylation, play a role in the reconstitution of the hematopoietic system after AHSCT. This study aimed to explore global DNA methylation dynamic of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) from donors and their respective recipients affected by acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and Hodgkin lymphoma (HL) during the first year after transplant.

Methods: We measured DNA methylation profile by Illumina HumanMethylationEPIC in BM HSPC of 10 donors (t0) and their matched recipients at different time points after AHSCT, at day + 30 (t1), + 60 (t2), + 120 (t3), + 180 (t4), and + 365 (t5). Differential methylation analysis was performed by using R software and CRAN/Bioconductor packages. Gene set enrichment analysis was carried out on promoter area of significantly differentially methylated genes by clusterProfiler package and the mSigDB genes sets.

Results: Results show significant differences in the global methylation profile between HL and acute leukemias, and between patients with mixed and complete chimerism, with a strong methylation change, with prevailing hyper-methylation, occurring 30 days after AHSCT. Functional analysis of promoter methylation changes identified genes involved in hematopoietic cell activation, differentiation, shaping, and movement. This could be a consequence of donor cell "adaptation" in recipient BM niche. Interestingly, this epigenetic remodeling was reversible, since methylation returns similar to that of donor HSPCs after 1 year. Only for a pool of genes, mainly involved in dynamic shaping and trafficking, the DNA methylation changes acquired after 30 days were maintained for up to 1 year post-transplant. Finally, preliminary data suggest that the methylation profile could be used as predictor of relapse in ALL.

Conclusions: Overall, these data provide insights into the DNA methylation changes of HSPCs after transplantation and a new framework to investigate epigenetics of AHSCT and its outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-019-1245-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528331PMC
May 2019

The rs17084733 variant in the 3' UTR disrupts a miR-221/222 binding site in gastrointestinal stromal tumour: a sponge-like mechanism conferring disease susceptibility.

Epigenetics 2019 06 13;14(6):545-557. Epub 2019 Apr 13.

a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.

Several miRNAs are dysregulated in gastrointestinal stromal tumours (GIST), and miR-221/222 appear to have a prominent role in GIST biology. Therefore, we investigated the role of DNA variants located in miR-221/222 precursor sequences and their target 3'UTR. Ninety-five polymorphisms were analysed in 115 GIST cases and 88 healthy controls. 3'UTR rs17084733 and pri-miR-222 rs75246947 were found significantly associated with GIST susceptibility. Specifically, rs17084733 A allele was more common in GIST, particularly in KIT wild-type (WT) patients (Padj = 0.017). rs17084733 variant is located within one of the three miR-221/222 binding sites in the 3'UTR, resulting in a mismatch in this seed region. Conversely, KIT mRNA levels were lower in patients carrying the variant allele, except for mutant GIST. Luciferase assay data in GIST cells, generated using a construct containing all the three miR-221/222 binding sites, are consistent with KIT mRNA levels in GIST patients. Reporter assay data, generated using a construct containing only the site encompassing rs17084733, confirmed that this is a functional variant disrupting the miR-221/222 binding site. In conclusion, this is the first study investigating the role of SNPs on miR-221/222 precursor sequences and their binding region on 3'UTR in GIST. We identified the variant rs17084733 as a possible novel genetic biomarker for risk of developing -WT GIST. Moreover, our findings suggest the role of one of the three miR-221/222 binding sites on 3'UTR as endogenous sponge, soaking up and subtracting miR-221/222 to the other two sites characterized by a higher affinity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15592294.2019.1595997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557610PMC
June 2019

Prevalence of malocclusion, oral parafunctions and temporomandibular disorder-pain in Italian schoolchildren: An epidemiological study.

J Oral Rehabil 2019 Jul 7;46(7):611-616. Epub 2019 May 7.

Division of Orthodontics, Department of Neurosciences, Reproductive Sciences and Oral Sciences, University of Naples 'Federico II', Naples, Italy.

Background: The prevalence of malocclusion, temporomandibular disorders (TMD) and oral parafunctions is highly debated in children population.

Objectives: To investigate the prevalence of malocclusion, self-reported oral parafunctions and TMD-pain in Italian schoolchildren and to assess the association between the examined factors.

Methods: A total of 700 children aged 9-11 years were selected among six public schools in Campania region (Italy). Molar relationship, overjet, overbite and cross-bite were assessed through a clinical examination. Furthermore, the subjects were demanded to fill in a validated questionnaire for TMD-pain screening and the short form of the Oral Behaviours Checklist. Descriptive statistics were used to report the frequencies. The associations between occlusal traits, oral parafunctions and TMD-pain were analysed with a Pearson chi-square test, as expressed by odds ratio and 95% confidence intervals. The significance level was set at P < 0.05.

Results: Molar Class I was the most frequently encountered molar relationship, followed by molar Class II, subdivision and molar Class III. Increased overjet was more common than negative overjet. Posterior cross-bite was observed in 12% of children. TMD-pain was recorded in 14.7% of subjects. High frequency of oral parafunctions was reported in 21.3% of subjects. A significant association was found between TMD-pain and negative overbite. Cross-bite and high frequency of oral parafunctions were associated with TMD-pain.

Conclusion: The current results show that malocclusion, self-reported oral parafunctions and TMD-pain are frequent findings among Italian schoolchildren and that some occlusal factors and high frequency of oral parafunctions might be associated with TMD-pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/joor.12794DOI Listing
July 2019

Evaluation of Allergic Diseases, Symptom Control, and Relation to Infections in a Group of Italian Elite Mountain Bikers.

Clin J Sport Med 2020 09;30(5):465-469

Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli," Naples, Italy.

Objectives: This study estimates the prevalence of allergic diseases in a group of Italian elite mountain bikers, compares the prevalence of infectious episodes between allergic and nonallergic athletes, and evaluates asthma and rhinitis symptom control in allergic athletes.

Design: Two hundred twenty-six Italian nonsmoking mountain bikers received by mail the Allergy Questionnaire for Athletes (AQUA) and completed it. The RhinAsthma Patient Perspective (RAPP) questionnaire was sent to the 108 participants with a positive AQUA score and 104 returned the questionnaire.

Methods: Athletes with an AQUA score ≥5 or <5 were defined AQUA+ (allergic) or AQUA- (nonallergic), respectively. RhinAsthma Patient Perspective questionnaire total score ≥15 was indicative of a poor control of symptoms.

Results: Of the 226 athletes, 47.8% were AQUA+, whereas 52.2% were AQUA-. A higher number of AQUA+ athletes reported frequent upper respiratory tract infections (URTIs) and herpes labialis than AQUA- athletes (P < 0.001), and the prevalence of URTI was greater in the subgroup of AQUA+ athletes who trained ≥3 hours per session. According to RAPP questionnaire score, 21.1% of AQUA+ mountain bikers had a poor control of asthma and rhinitis symptoms.

Conclusions: Our study shows a high prevalence of allergy among Italian elite mountain bikers whose asthma and rhinitis symptoms are poorly controlled in about a fifth of the sample. Allergic athletes, mainly those training more than 3 hours per session, are at higher risk of URTI and herpes labialis. Screening programs to detect allergic diseases and to evaluate symptom control in athletes should be strongly encouraged.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JSM.0000000000000678DOI Listing
September 2020

Is re-challenge still an option as salvage therapy in multiple myeloma? The case of REal-life BOrtezomib re-Use as secoND treatment for relapsed patients exposed frontline to bortezomib-based therapies (the REBOUND Study).

Ann Hematol 2019 Feb 23;98(2):361-367. Epub 2018 Oct 23.

Haematology Unit, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.

Therapeutic re-challenge is currently a debated issue in the field of multiple myeloma (MM), given the recent availability of several new drugs and combinations. However, very few specific evidences are available about bortezomib re-use at first relapse. This multicenter, observational, retrospective study enrolled 134 MM patients with significant response after bortezomib-based frontline regimens and who had received a first salvage treatment containing bortezomib at relapse. The overall response rate was 71%, including 40% partial responses, 24% very good partial responses, and 7% complete responses. Re-treatment was well-tolerated, with no significant new or unexpected toxicities observed. The median duration of second progression-free survival (PFS) was 15 months, while median PFS2 was 55 months. With a median follow-up of 56 months, overall survival was 94 months for the entire series, without significant differences between patients undergoing or not undergoing transplant procedures. This real-life survey indicates that re-treatment including bortezomib as a first salvage therapy could be still considered in MM patients achieving durable response after initial exposure to bortezomib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-018-3524-1DOI Listing
February 2019

The meshed biological matrix in immediate, definitive breast reconstruction.

J Plast Reconstr Aesthet Surg 2019 Jan 23;72(1):137-171. Epub 2018 Sep 23.

Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture (PZ), Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bjps.2018.09.004DOI Listing
January 2019

Global methylation patterns in primary plasma cell leukemia.

Leuk Res 2018 10 18;73:95-102. Epub 2018 Sep 18.

Unit of Hematology and Stem Cell Transplantation, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.

Primary plasma cell leukemia (pPCL) is a rare and very aggressive variant of multiple myeloma (MM). Specific clinical, biological and molecular patterns distinguish pPCL from MM. Here, we performed a genome-wide methylation analysis by high-density array in 14 newly diagnosed pPCL patients along with 60 MMs, and 5 patients affected by monoclonal gammopathy of uncertain significance (MGUS). Our analysis revealed a global hypomethylation profile associated with pPCL. Additionally, differential methylation patterns were found related to distinct chromosomal aberrations and DIS3 mutations, affecting genes with roles in bone metabolism, cell migration, transcription regulation or DNA damage response. When compared with MM patients, pPCL showed a distinct methylation profile mostly characterized by hypomethylated probes specific for genes involved in several processes like cell adhesion and migration. Furthermore, decreasing methylation levels were evidenced for genes significantly modulated in the progressive phases of plasma cell dyscrasias, from MGUS to MM and pPCL. Overall, our data provide new insights into the molecular characterization of pPCL, thus being potentially useful in the prognostic stratification or identification of novel molecular targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2018.09.007DOI Listing
October 2018

An exploratory study by DMET array identifies a germline signature associated with imatinib response in gastrointestinal stromal tumor.

Pharmacogenomics J 2019 08 20;19(4):390-400. Epub 2018 Sep 20.

"Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.

Imatinib represents the standard therapy for gastrointestinal stromal tumor (GIST) patients with metastatic/unresectable disease. Despite  the excellent results achieved with its introduction, the majority of patients quite invariably experience disease progression. The aim of this study was to understand the contribution of germline DNA polymorphisms in discriminating between imatinib clinical response [evaluated as progression free survival (PFS)] and toxicity. In particular, a discovery cohort (34 GIST with a KIT exon 11 primary mutation, and no toxicity) was analyzed through DMET array that interrogates 1936 variants in 231 genes of the ADME process. We further confirmed the genotype of selected variants in an extended cohort of 49 patients (the original cohort and 15 new cases, all with exon 11 primary mutation), identifying 6 SNPs- ABCB4 rs1202283, ABCC2 rs2273697, ABCG1 rs1541290, CYP11B1 rs7003319, CYP7B1 rs6987861, and NQO1 rs10517-significantly associated with response to imatinib. Three SNPs, ABCB4 rs1202283, ABCC2 rs2273697, and NQO1 rs10517, which had a significant association after adjusted multivariate analysis, were included in a genetic prediction model. We confirmed that these SNPs could stratify the cohort of 49 patients according to the risk of developing progression under imatinib treatment. In conclusion, we identified a genetic signature of response to imatinib therapy in GIST patients able to stratify patients at low and high risk to progress, according to their genotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41397-018-0050-4DOI Listing
August 2019

Clinical impact of nasal budesonide treatment on COPD patients with coexistent rhinitis.

Int J Chron Obstruct Pulmon Dis 2018 27;13:2025-2032. Epub 2018 Jun 27.

Department of Cardio-Thoracic and Respiratory Sciences, Monaldi Hospital, University of Campania "Luigi Vanvitelli", Naples, Italy,

Background: A high percentage of patients with COPD report chronic nasal symptoms. The study aims to evaluate the clinical impact of a 2-month treatment with inhaled nasal budesonide (100 µg per nostril twice daily) in patients affected by COPD with chronic rhinitis comorbidity.

Patients And Methods: Fifty-three stable COPD patients in therapy according to the Global initiative for chronic Obstructive Lung Disease recommendations were enrolled; 49 completed the study. At enrollment (visit 0), patients underwent skin prick test and rhinoscopy. At visit 0 and after 1 month (visit 1) and 2 months (visit 2) of therapy with nasal budesonide, patients underwent spirometry, and COPD assessment test (CAT), Sinonasal Outcome Test (SNOT 22), and modified Medical Research Council dyspnea scale were administered. Differences in continuous variables, after 2 months of treatment with nasal budesonide, were evaluated using a paired -test or Wilcoxon matched-pairs signed-ranks test.

Results: Two months of treatment with nasal budesonide showed a significant statistical improvement in the total scores of CAT, SNOT 22, and modified Medical Research Council (<0.001). A significant relationship between CAT and SNOT 22 total scores at baseline and after treatment was observed.

Conclusion: The results of the present study indicate the importance of careful evaluation of the presence of chronic nasal symptoms in all COPD patients and suggest beneficial clinical effect from treatment with nasal budesonide in terms of COPD symptoms and quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S165857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029594PMC
January 2019

IL6/STAT3 axis mediates resistance to BRAF inhibitors in thyroid carcinoma cells.

Cancer Lett 2018 10 2;433:147-155. Epub 2018 Jul 2.

Laboratory of Pre-Clinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture, PZ, Italy; Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. Electronic address:

Thyroid carcinomas (TCs) bearing BRAF mutations represent approximately 26-53% of human thyroid malignancies and, differently from melanomas, are poorly sensitive to BRAF inhibitors (BRAFi), and develop acquired resistance through activation of alternative signaling pathways. A whole-genome gene expression analysis of TC BRAF V600E cells exposed to PLX4032 identified JAK/STAT among the most significantly modulated signaling pathways. Interestingly, both transient exposure and chronic adaptation to PLX4032 resulted in upregulation of IL6/STAT3 axis and this impaired the cytostatic activity of PLX4032. Mechanistically, exposure to PLX4032 enhanced IL6 secretion and this, in turn, was responsible for STAT3 upregulation, activation of ERK signaling and poor sensitivity to BRAF inhibition. Consistently, the dual blockade of STAT3 (by siRNA or pharmacological inhibition) or IL6 signaling (by the humanized anti-human IL6 receptor antibody, tocilizumab) and BRAF (by PLX4032) improved the inhibition of cell cycle progression compared to PLX4032 single agent. These data support the role of IL6/STAT3 signaling pathway in modulating TC cell response to PLX4032 and candidate IL6 targeting as a strategy to improve the activity of PLX4032 in BRAF V600E TC cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2018.06.038DOI Listing
October 2018

Are third-generation cephalosporins still the empirical antibiotic treatment of community-acquired spontaneous bacterial peritonitis? A systematic review and meta-analysis.

Eur J Gastroenterol Hepatol 2018 Mar;30(3):329-336

Intensive Care, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.

Background: Spontaneous bacterial peritonitis (SBP) is a common complication among cirrhotic patients. Guidelines recommend third-generation cephalosporins (3GCs) as empiric antibiotic therapy (EAT) of SBP. Recently, a broad-spectrum EAT was shown to be more effective than cephalosporins in the treatment of nosocomial spontaneous bacterial peritonitis (N-SBP); however, the prevalence of 3GCs-resistant bacteria is high in the nosocomial setting and broad-spectrum EAT cannot be used in all cases of SBP.

Aim: The aim of this study was to evaluate the 3GCs resistance distribution between N-SBP and community-acquired spontaneous bacterial peritonitis (CA-SBP) to clarify whether 3GCs are still an effective therapeutic intervention for CA-SBP.

Methods: We searched for studies that reported the aetiology of SBP and the resistance profile of both gram-positive and gram-negative bacteria in MEDLINE and Google Scholar databases (since 1 January 2000 to 30 April 2017). A meta-analysis was carried out to estimate the risk difference [relative risk (RR) and 95% confidence intervals (CIs)] for 3GCs resistance in N-SBP and CA-SBP. Heterogeneity was assessed using the I-test.

Results: A total of eight studies were included, including 1074 positive cultures of ascitic fluid in cirrhotic patients; 462 positive cultures were from N-SBP and, among these, 251 (54.3%) were 3GCs resistant. Six hundred and twelve positive cultures were from CA-SBP and, among these, 207 (33.8%) were 3GCs-resistant SBP. A pooled RR of 3GCs resistance in N-SBP compared with CA-SBP showed a significant difference (RR=1.67, 95% CI: 1.14-2.44; P=0.008). We carried out two subgroup analyses: the first according to the median year of study observation (before vs. since 2008) and the second according to the country of the study (China vs. others). The studies carried out before 2008 (327 SBP-positive culture) showed a significantly higher risk for 3GCs-resistant strains in N-SBP compared with CA-SBP (RR=2.36, 95% CI: 1.39-3.99; P=0.001), whereas this was not found in SBP acquired after 2008 (RR=1.24, 95% CI: 0.83-1.84; P=0.29). N-SBP occurring in China had no significantly higher risk for 3GCs-resistant strains compared with CA-SBP (RR=1.44, 95% CI: 0.87-2.37; P=0.16).

Conclusion: Our findings suggest that although the pooled RR of 3GCs resistance in N-SBP compared with CA-SBP show that 3GCs are still an effective option for the treatment of CA-SBP, the subanalysis of studies that enroled patients in the last decade did not show a significant higher RR of 3GCs resistance in N-SBP compared with CA-SBP. Therefore, in centres where local patterns of antimicrobial susceptibility (with low rates of 3GCs resistance) are not available, 3GCs should not be used initially for CA-SBP treatment. Future studies are needed to confirm this trend of 3GCs resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0000000000001057DOI Listing
March 2018