Metronomic Oral Vinorelbine: An Alternative Schedule in Elderly and Patients PS2 With Local/Advanced and Metastatic NSCLC Not Oncogene-addicted

The MILES and ELVIS studies showed that vinorelbine is one of the best options for elderly patients with advanced non-small-cell-lung cancer (NSCLC). Oral vinorelbine at standard schedule (60-80 mg/m2/weekly) has good activity in terms of response rates and progression-free survival. In recent years, a metronomic schedule of oral vinorelbine (40-50 mg/m2 three times a week, continuously) has been studied in phase II trials, especially in unfit and elderly patients. In the MOVE trial metronomic oral vinorelbine had a clinical benefit [partial response (PR)+stable disease (SD) >12 weeks] in 58.1% of patients with mild toxicity. On this basis, in 2017 we started a phase II study with metronomic oral vinorelbine in elderly (over 70 years) or unfit [Eastern Cooperative Oncology Group performance score (ECOG-PS) of 2] patients with locally/advanced and metastatic NSCLC. Primary aims were clinical benefit (PR+SD ≥6 months) and toxicity; secondary aims were progression-free survival and overall survival

Clinical impact of first-line bevacizumab plus chemotherapy in metastatic colorectal cancer of mucinous histology: a multicenter, retrospective analysis on 685 patients

In metastatic colorectal cancer (MCRC), mucinous histology has been associated with poor response rate and prognosis. We investigated whether bevacizumab combined with different chemotherapy regimens may have an impact on clinical outcomes of MCRC patients with mucinous histology

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner

Association of dopamine D4 receptor (DRD4) exon III repeat polymorphism with temperament in 3-year-old infants

The long forms of the dopamine D4 receptor (DRD4) exon III repeat polymorphism (L-DRD4) have been linked in some studies to the adult personality trait of novelty seeking (NS), as well as to infant personality traits related to interest and activity. The current investigation extends the results of our previous longitudinal study on 1- to 5-month-old neonates assessed by the Early and Revised Infancy Temperament Questionnaire (EITQ/RITQ), in which we found a significant correlation between the DRD4 polymorphism and the adaptability trait at 1 month of age. In this study, we examined the relationship between children's behavior at 3 years of age, measured with the Toddler Temperament Scale (TTS), and DRD4 exon III repeat polymorphism. We found a significant association between the behavioral dimension of intensity of reaction and DRD4 genotypes. Current data failed to confirm the association with the adaptability trait. None of the extraversion and/or exploratory behavior measures was related to the L-DRD4 allele, as expected. In contrast, children with 4/7 genotypes showed worse response to new stimuli compared with 4/4 genotypes. This study corroborates only in part previous results on the link between the DRD4 gene and human temperament

ELECTROKINETIC REMEDIATION OF SOILS CONTAMINATED BY MERCURY

The electrokinetic approach, for the extraction of metal ions from dispersed solid matrixes, has received extensive description in the scientific literature of the last twenty years. The application of electric fields of suitable intensity, through saturated portions of soils, can determine the displacement of charged species. In principle, this effect has two components: one is the electromigration, the other is the component due to the electroosmotic drag of the spatial ionic charge facing the charged surface of soil particles. In the case of electromigration, the electric field has essentially the role of “driving force” for the movement of ionic species through the water impregnating the dispersed solids and the soil in particular. The effect remains even if the solid matrix is finely divided. The application of this technology, when aimed to the removal of mercury present in metallic form, requires its prior dissolution, which can be facilitated by adding appropriate chemicals. Designing an intervention requires a preliminary speciation of the contaminant in the soil, as well as the execution of electrochemical tests at a laboratory scale. The analysis of soil with speciation of the pollutant was carried out following the approach proposed by Boszke et al. “Mercury mobility and bioavailability in soil from contaminated area”, Environmental Geology (2008) 55: 1075-1087. The soil analysis was repeated after the electrochemical laboratory test, for an assessment of the amount of removed Hg. In addition, results obtained with this method were compared with those acquired using the alternative EPA 3200 procedure for speciation. The electrochemical laboratory test was performed on approximately 400 kg of soil, and for a period of about three months. After treatment, the soil analysis showed a significant reduction of total Hg (approximately 60% of the total). Basing on these results, an intervention in the field is being planned: estimation of time required to achieve the objective of remediation has been based on the removal of mobile and mobilizable forms of Hg

Comparison of patients' and providers' severity evaluation of oral mucosal conditions

BACKGROUND: In dental diseases, significant discrepancies were observed in the oral health-related quality of life evaluation between patients and providers. Few studies have been performed specifically on the impact of oral mucosal diseases on patients' health. OBJECTIVE: We sought to compare the evaluation of the severity of oral mucosal conditions in providers and patients. METHODS: Patients with an oral mucosal condition were recruited at the oral health care unit of a dermatologic hospital. Severity was evaluated both by the physician and by the patient, using a global severity assessment score on a 5-point scale. The 14-item Oral Health Impact Profile was used to evaluate oral health-related quality of life, the 12-item General Health Questionnaire for psychologic problems, and the 20-item Toronto Alexithymia Scale for alexithymia (ie, the difficulty in identifying and expressing feelings). RESULTS: Data were complete for 206 patients. The agreement between patients' and providers' evaluation was very low (Cohen κ = 0.18). Severity was particularly underestimated by the physician in patients with alexithymia (43% compared with 25% of patients with no alexithymia) and with psychologic problems (44% vs 25%). LIMITATIONS: Because of the high number of different conditions, and thus the small figures in each group, it was not possible to analyze the concordance between patient and provider in each single condition. CONCLUSION: Even in the severity assessment of his or her own disease, it is plausible that a patient does not provide a simple clinical evaluation, but includes subjective aspects. It is important for the physician to take into account the severity the patient perceives in making treatment decisions, and in evaluating clinical improvemen

RFID as a new ICT tool to monitor specimen life cycle and quality control in a biobank

Background: Biospecimen quality is crucial for clinical and translational research and its loss is one of the main obstacles to experimental activities. Beside the quality of samples, preanalytical variations render the results derived from specimens of different biobanks or even within the same biobank incomparable. Specimens collected along the years should be managed with a heterogeneous life cycle. Hence, we propose to collect detailed data concerning the whole life cycle of stored samples employing radio-frequency identification (RFID) technology. Methods: We describe the processing chain of blood biosamples that is operative at the biobank of IRCSS San Raffaele, Rome, Italy (BioBIM). We focus on the problem of tracing the stages following automated preanalytical processing: we collected the time stamps of all events that could affect the biological quality of the specimens by means of RFID tags and readers. Results: We developed a pilot study on a fragment of the life cycle, namely the storage between the end of the preanalytics and the beginning of the analytics, which is usually not traced by automated tools because it typically includes manual handling. By adopting RFID devices we identified the possible critical time delays. At 1, 3 and 6 months RFID-tagged specimens cryopreserved at -80 degrees C were successfully read. Conclusions: We were able to record detailed information about the storage phases and a fully documented specimen life cycle. This will allow us to promote and tune up the best practices in biobanking because i) it will be possible to classify sample features with a sharper resolution, which allows future utilization of stored material; ii) cost-effective policies can be adopted in processing, storing and selecting specimens; iii) after using each aliquot, we can study the life cycle of the specimen with a possible feedback on the procedures

HtrA1, a potential predictor of response to cisplatin-based combination chemotherapy in gastric cancer

Aims: HtrA1 is a member of the HtrA (high-temperature requirement factor A) family of serine proteases. HtrA1 plays a protective role in various malignancies due to its tumour suppressive properties. The aim of this study was to determine HtrA1 expression as a predictor of chemoresponse in patients with advanced gastric cancer. Methods and results: HtrA1 expression was determined by immunohistochemistry on specimens of primary gastric cancer from 80 patients treated consecutively with cisplatin-based combination chemotherapy. Response to chemotherapy was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria. Our population consisted of males/females [51/29; median age 64 years (range 32-82)]. A complete or partial response was observed in 71.4% [95% confidence interval (CI) 54.7-88.2], 66.7% (95% CI 47.8-85.5) and 28.6% (95 CI 11.8-45.3) of tumours showing high, medium and low HtrA1 expression, respectively. A statistically significant association between HtrA1 expression and the clinical response was observed (P = 0.002). The median overall survival for patients with high/medium expression was 17 months compared to 9.5 months for patients with low HtrA1 expression (P = 0.037). Conclusions: Identification of HtrA1 in gastric cancer prior to chemotherapy indicates that levels of HtrA1 could be used to predict response to platinum-based combination therapies. Further assessment of HtrA1 expression is highly warranted in large, prospective studies