Adherence to oral anticancer treatments: network and sentiment analysis exploring perceived internal and external determinants in patients with metastatic breast cancer.

PURPOSE: Adherence to oral anticancer treatments (OATs) is a critical issue in metastatic breast cancer (MBC) to enhance survivorship and quality of life. The study is aimed to analyze the main themes and attributes related to OATs in MBC patients. This research is part of a project titled "Enhancing Therapy Adherence Among Metastatic Breast Cancer Patients" designed to produce a predictive model of non-adherence, a decision support system, and guidelines to improve adherence to OATs. METHODS: The study consists of an exploratory observational and qualitative analysis using a focus group method. A semi-structured interview guide was developed to handle relevant OAT themes. Wordcloud plots, network analysis, and sentiment analysis were performed. RESULTS: Nineteen female MBC patients participated in the protocol (age mean 55.95, SD = 6.87). Four main themes emerged: (theme 1) individual clinical pathway; (theme 2) barriers to adherence; (theme 3) resources to adherence; (theme 4) patients' perception of new technologies. The Wordcloud and network analysis highlighted the important role of treatment side effects and the relationship with the clinician in the modulation of adherence behavior. This result is consistent with the sentiment analysis underscoring patients experience fear of issues related to clinical values and ineffective communication and discontinuity of the doctor in charge of the patient care. CONCLUSION: The study highlighted the key role of the individual, relational variables, and side effects as internal and external determinants influencing adherence to MBC. Finally, the opportunity offered by eHealth technology to connect with other patients with similar conditions and share experiences could be a relief for MBC patients.

Predictive Models of Psychological Distress, Quality of Life, and Adherence to Medication in Breast Cancer Patients: A Scoping Review.

Purpose: An interplay of clinical and psychosocial variables affects breast cancer patients' experiences and clinical trajectories. Several studies investigated the role of socio-demographic, clinical, and psychosocial factors in predicting relevant outcomes in breast cancer care, thus developing predictive models. Our aim is to summarize predictive models for specific psychological and behavioral outcomes: psychological distress, quality of life, and medication adherence. Specifically, we aim to map the determinants of the outcomes of interest, offering a thorough overview of these models. Methods: Databases (PubMed, Scopus, Embase) have been searched to identify studies meeting the inclusion criteria: a breast cancer patients' sample, development/validation of a predictive model for selected psychological/behavioral outcomes (ie, psychological distress, quality of life, and medication adherence), and availability of English full-text. Results: Twenty-one papers describing predictive models for psychological distress, quality of life, and adherence to medication in breast cancer were included. The models were developed using different statistical approaches. It has been shown that treatment-related factors (eg, side-effects, type of surgery or treatment received), socio-demographic (eg, younger age, lower income, and inactive occupational status), clinical (eg, advanced stage of disease, comorbidities, physical symptoms such as fatigue, insomnia, and pain) and psychological variables (eg, anxiety, depression, body image dissatisfaction) might predict poorer outcomes. Conclusion: Predictive models of distress, quality of life, and adherence, although heterogeneous, showed good predictive values, as indicated by the reported performance measures and metrics. Many of the predictors are easily available in patients' health records, whereas others (eg, coping strategies, perceived social support, illness perceptions) might be introduced in routine assessment practices. The possibility to assess such factors is a relevant resource for clinicians and researchers involved in developing and implementing psychological interventions for breast cancer patients.

ESMO Expert Consensus Statements on Cancer Survivorship: promoting high-quality survivorship care and research in Europe.

BACKGROUND: The increased number of cancer survivors and the recognition of physical and psychosocial challenges, present from cancer diagnosis through active treatment and beyond, led to the discipline of cancer survivorship. DESIGN AND METHODS: Herein, we reflected on the different components of survivorship care, existing models and priorities, in order to facilitate the promotion of high-quality European survivorship care and research. RESULTS: We identified five main components of survivorship care: (i) physical effects of cancer and chronic medical conditions; (ii) psychological effects of cancer; (iii) social, work and financial effects of cancer; (iv) surveillance for recurrences and second cancers; and (v) cancer prevention and overall health and well-being promotion. Survivorship care can be delivered by structured care models including but not limited to shared models integrating primary care and oncology services. The choice of the care model to be implemented has to be adapted to local realities. High-quality care should be expedited by the generation of: (i) focused and shared European recommendations, (ii) creation of tools to facilitate implementation of coordinated care and (iii) survivorship educational programs for health care teams and patients. The research agenda should be defined with the participation of health care providers, researchers, policy makers, patients and caregivers. The following patient-centered survivorship research areas were highlighted: (i) generation of a big data platform to collect long-term real-world data in survivors and healthy controls to (a) understand the resources, needs and preferences of patients with cancer, and (b) understand biological determinants of survivorship issues, and (ii) develop innovative effective interventions focused on the main components of survivorship care. CONCLUSIONS: The European Society for Medical Oncology (ESMO) can actively contribute in the efforts of the oncology community toward (a) promoting the development of high-quality survivorship care programs, (b) providing educational material and (c) aiding groundbreaking research by reflecting on priorities and by supporting research networking.

Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance.

Resulting from impaired collagen turnover, fibrosis is a hallmark of adipose tissue (AT) dysfunction and obesity-associated insulin resistance (IR). Prolidase, also known as peptidase D (PEPD), plays a vital role in collagen turnover by degrading proline-containing dipeptides but its specific functional relevance in AT is unknown. Here we show that in human and mouse obesity, PEPD expression and activity decrease in AT, and PEPD is released into the systemic circulation, which promotes fibrosis and AT IR. Loss of the enzymatic function of PEPD by genetic ablation or pharmacological inhibition causes AT fibrosis in mice. In addition to its intracellular enzymatic role, secreted extracellular PEPD protein enhances macrophage and adipocyte fibro-inflammatory responses via EGFR signalling, thereby promoting AT fibrosis and IR. We further show that decreased prolidase activity is coupled with increased systemic levels of PEPD that act as a pathogenic trigger of AT fibrosis and IR. Thus, PEPD produced by macrophages might serve as a biomarker of AT fibro-inflammation and could represent a therapeutic target for AT fibrosis and obesity-associated IR and type 2 diabetes.

The psychometric properties of the Italian adaptation of the Health Orientation Scale (HOS).

BACKGROUND: A novel approach suggested that cognitive and dispositional features may explain in depth the health behaviors adoption and the adherence to prevention programs. The Health Orientation Scale (HOS) has been extensively used to map the adoption of health and unhealthy behaviors according to cognitive and dispositional features. Coherently, the main aim of the current research was to assess the factor structure of the Italian version of the HOS using exploratory and confirmatory factor analysis and testing the construct validity of the scale by assessing differences in health orientations between tobacco cigarette smokers and nonsmokers. METHOD: The research protocol was organized in two studies. Study 1 evaluated the dimensionality of the HOS in a sample of Northern Italian healthy people. Three hundred and twenty-one participants were enrolled; they were 229 women (71.3%) and 92 men (28.7%). In Study 2, the factor structure and construct validity of the HOS Italian version was assessed trough confirmatory factor analysis using a tobacco cigarette smokers and nonsmokers population. Two hundred and nineteen participants were enrolled; they were 164 women (75.2%) and 55 men (24.8%). RESULTS: In Study 1, a seven factors solution was obtained explaining 60% of cumulative variance instead of 10 factors solution of the original version of the HOS. In Study 2, the factor structure of the Italian version of the HOS was confirmed and applied to the smokers and nonsmokers; nonsmokers reported higher values than smokers in Factor 1 (MHPP) [t (208) = - 2.739 p < .007] (CI 95-4.96% to -.809), Factor 2 (HES) [t (209) = - 3.387 p < .001] (CI 95-3.93% to -. 1.03), Factor 3 (HIC) [t(213) = - 2.468 p < .014] (CI 95-2.56% to -.28) and Factor 7 (HEX) [t(217) = - 3.451 p < .001] (CI 95%- 1.45 to .39). CONCLUSIONS: Results of the Italian adaptation of HOS lead to a partial redistribution of items and confirmed 7 subscales to distinguish psycho-cognitive dispositional dimensions involved in health orientation styles.

Patient decision aids for prevention and treatment of cancer diseases: are they really personalised tools?

This article provides an analysis of cancer decision aids (DAs), instruments developed to support oncologic patients facing tough screening or treatment decisions, with a particular attention to their level of personalisation. As discussed in our previous works, we argue that the personalisation of medicine should regard not only the genetic and clinical aspects of diseases but also the different cognitive, psychological and social factors involved in clinical choices. According to this vision, we analysed the existing randomised controlled studies on cancer DAs concluding that only few of them take into account individual variables such as cultural level, individual risk attitudes, personal beliefs, and emotional state that are crucial to determine people's reactions and health-related choices. For these reasons, although quality standards have been published for these interventions, we suggest the need for further research in order to make these instruments more efficient in transforming and improving the actual clinical practice, improving patient empowerment and participation in health-related decisions.

Cognitive strategies and quality of life of patients with high-grade glioma.

The purpose of this study was to analyze the psychological well-being, quality of life, and cognitive strategies activated by patients with high-grade glioma. We hypothesized that the self-perceived quality of life is modulated by physical and psychological factors and that in order to understand this modulation more psychometric approaches are necessary. Data were collected from a sample of 73 consecutive patients with a histological diagnosis of primary malignant brain cancer (grade IV glioblastoma and grade III anaplastic astrocytoma) hospitalized in a specialized Italian center. The Functional Assessment of Cancer Therapy (FACT) scale and the Schedule of Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) scale were used to assess quality of life. The mean FACT-Brain (Br) score was 122.37. Similarly, the median SEIQoL-DW score was 72.9 out of a maximum value of 100. No gender effect was found in relation to overall quality of life. Patients with high depression and/or anxiety scores reported lower quality of life (QoL) scores in all the instruments considered. We did not find any gender effect concerning depression and anxiety levels. However, we found that men and women, though having similar physical and functional well-being, reported different QoL determinants, since men seem to rely more on physical adjustment, while women activate more introspective strategies. Positive actions, family issues, negative thoughts, health, and positive thoughts were found to be the most reported themes. In conclusion, the present study strongly suggests that a positive psychological adjustment is possible also in the event of a severe diagnosis and during aggressive treatments, but QoL determinants might be considered too in order to help health professionals to understand patients' experience and to meet their needs.

Methods for nutrition monitoring in cancer patients: a cognitive perspective.

In the present medical context, the evaluation and the monitoring of factors other than mere physical symptoms are an urgent demand. In particular, the issue of quality of life (QoL) has become a relevant target in the treatment of cancer. However, the approach towards these aspects is not well standardized and the actual applications in a concrete setting are fragmented, left to personal or local initiative. If this is true for QoL in general, it is particularly relevant in the specific field of nutrition. Indeed, though the growing awareness of a correlation between chronic diseases and dietary habits has led to an increased interest in nutrition, both before and after cancer, very little is still known about the methods that measure this important variable of the QoL. Indeed, good nutrition may have a relevant impact on QoL, positively affecting both the physical and psychological well-being. Targeting this issue implies using proper instruments to both monitor and educate the patients. Hence, we argue that it is vital for oncologists to be able to individuate the best tool available in a specified context, so as to achieve an important goal with little effort, also adopting standardized strategies proved to be efficacious. In this framework, we briefly reviewed the tools more frequently reported in the scientific literature. We suggest that through a cognitive approach, it is possible to achieve important clinical targets, initially by understanding the patients' needs, values, and psychosocial factors involved in nutritional behaviour and food-related decisions, in order to develop a personalized approach. Hence, this is the only way to support concrete actions for promoting healthier diets, thus preventing recurrences, monitoring chronic conditions, and supporting a good QoL.

Notch3-mediated regulation of MKP-1 levels promotes survival of T acute lymphoblastic leukemia cells.

Activation of the Notch pathway occurs commonly in T acute lymphoblastic leukemia (T-ALL) because of mutations in Notch1 or Fbw7 and is involved in the regulation of cell proliferation and survival. Deregulated Notch3 signalling has also been shown to promote leukemogenesis in transgenic mice, but the targets of Notch3 in human T-ALL cells remain poorly characterized. Here, we show that Notch3 controls levels of mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1). In a model of T-ALL cell dormancy, both Notch3 activation and MKP-1 expression were upregulated in aggressive compared with dormant tumors, and this inversely correlated with the levels of phosphorylated p38 and extracellular signal-regulated kinase1/2 (ERK1/2) MAPKs, two canonical MKP-1 targets. We demonstrate that MKP-1 protein levels are regulated by Notch3 in T-ALL cell lines because its silencing by RNA interference or treatment with γ-secretase inhibitors induced strong MKP-1 reduction whereas activation of Notch3 signalling had the opposite effect. Furthermore, MKP-1 has an important role in T-ALL cell survival because its attenuation by short hairpin RNA significantly increased cell death under stress conditions. This protective function has a key role in vivo, as MKP-1-deficient cells showed impaired tumorigenicity. These results elucidate a novel mechanism downstream of Notch3 that controls the survival of T-ALL cells.

Renal glomerular response to the inhibition of prostaglandin E2 synthesis and protein loading after the relief of unilateral ureteropelvic junction obstruction.

PURPOSE: We investigated glomerular filtration rate and renal function reserve after the surgical relief of partial obstruction. MATERIALS AND METHODS: We evaluated 4 boys and 1 girl 9 to 14 years old who underwent pyeloplasty because of unilateral ureteropelvic junction obstruction. Contralateral normal kidneys served as controls. The glomerular filtration rate (inulin clearance), and urinary excretion of prostaglandin E2, thromboxane B2 and endothelin were determined at baseline and after a meal of 4 gm./kg. cooked unsalted red meat on day 4 postoperatively. Tests were repeated the following day 1 hour after the oral administration of 20 mg./kg. aspirin, an inhibitor of prostaglandin E2 synthesis. Urine was collected separately through a bladder catheter and another catheter placed in the upper renal pelvis at surgery. RESULTS: Glomerular filtration rate at baseline was significantly greater in normal than in surgically treated kidneys (77.2 ml. per minute, range 60 to 98 versus 63.6, range 43 to 78, p = 0.04). Aspirin did not change baseline inulin clearance in normal kidneys but it significantly decreased the glomerular filtration rate in operated renal units (-4% versus -26.4%, p = 0.04). The concentration of all vasoactive compounds was not significantly different in the urine specimens of normal and operated kidneys. The administration of aspirin resulted in a significant decrease in mean urinary prostaglandin E2 excretion plus or minus standard error in operated but not in normal renal units (0.64+/-0.12 ng. per minute versus 0.27+/-0.06, p = 0.04). When expressed as mean versus baseline values, protein induced glomerular hyperfiltration seemed lower in operated than in contralateral intact kidneys (6.9% and 12.4%, respectively). CONCLUSIONS: In the immediate postoperative period previously obstructed kidneys maintain renal function via mechanisms that depend on the activation of prostaglandin, mimicking normal renal function. This effect is decreased by drugs that inhibit prostaglandin E2 production. Therefore, renal damage may be present when the glomerular filtration rate appears normal.

Renal impairment in chronic cigarette smokers.

To determine the effect of chronic cigarette smoking on renal function, a cross-sectional study was carried out with 30 subjects who had no known vascular disease risk factor other than cigarette smoking, and 24 age- and sex-matched controls without any vascular risk factor including cigarette smoking. Renal function by radionuclide studies of renal plasma flow, GFR, and plasma endothelin-1 concentration was determined. Compared with nonsmokers, smokers had a renal function impairment characterized by a normal GFR and a significant reduction in renal plasma flow as reflected by MAG3 clearance (199.20 +/- 58.85 ml/min per 1.73 m2 versus 256.54 +/- 60.14 ml/min per 1.73 m2; t = 3.52, P < 0.001). MAG3 clearance was significantly correlated with age and smoking. The renal dysfunction was associated with an increase in plasma endothelin-1 concentration (21.56 +/- 1.15 pmol/L versus 25.01 +/- 3.21 pmol/L; t = 5.00, P < 0.001). Former smokers as well had similar, although milder, abnormalities. In conclusion, cigarette smokers manifest an impairment of renal function, suggesting that smoke may have a detrimental effect on renal function.

Pepsinogen A/pepsinogen C or pepsinogen A multiplied by gastrin in the diagnosis of gastric cancer?

Being pepsinogen A (PGA) levels generally reduced and pepsinogen C (PGC) increased in gastric cancer patients, PGA/PGC ratio has been proposed as a useful marker of the tumour. We tested PGA, PGC and Gastrin (G) levels in patients with gastric cancer (39) and, as a control, in patients with epithelial dysplasia (21), chronic atrophic gastritis (57), gastric ulcer (11) or subjects lacking major or minor endoscopic and microscopic changes at gastroscopy (48). PGA and PGA/PGC levels were significantly reduced in gastric cancer patients (p less than 0.005 and p less than 0.0001 respectively with analysis of variance). Gastrin levels were also reduced in the same patients (p less than 0.005). We therefore adopted an index number (PGA x Gastrin) which was also dramatically reduced in gastric cancer (p less than 0.005); using an arbitrarily chosen cut-off, the "marker" showed very high sensitivity (76%), specificity (96%) and overall accuracy (74%, by Youden J test). We therefore suggest the use of the index number PGA x G in the diagnosis of gastric cancer, as the most useful gastrin presently available, to our knowledge.

CA 19-9 and CA 125 determination by immunoluminometric assay.

We evaluated a new immunoluminometric technique (ILMA) for the measurement of the cancer antigens, CA 19-9 and CA 125 in serum. A satisfactory reproducibility was found, coefficients of variation ranging from 4.2 to 7.3% in within-run and between-run assays. The linearity of tests was maintained over a wide concentration range. Mean analytical recovery was 94% for CA 19-9 and 98% for CA 125. A significant agreement between results obtained by immunoradiometric assays and evaluated methods was found both for CA 125 (ILMA = 0.917 IRMA + 1.048; r = 0.966; n = 98) and CA 19-9 (ILMA = 1.156 IRMA + 0.996; r = 0.995; n = 100).

Eicosanoid release from human bronchial epithelial cells upon exposure to toluene diisocyanate in vitro.

Epithelial injury and inflammation are involved in airway hyperresponsiveness and asthma induced by toluene diisocyanate. In that isocyanates are insoluble and highly reactive compounds, bronchial epithelial cells may represent the most important target cells of their toxic effect. We hypothesized that damage to airway epithelium by toluene diisocyanate may result in the release of metabolites of arachidonic acid, which are known to promote inflammation and to alter epithelial cell function and airway smooth muscle responsiveness. To test this hypothesis we examined eicosanoid products in the culture media of bronchial epithelial cells exposed in vitro to 8 and 18 ppb toluene diisocyanate. Epithelial cells derived from human bronchi obtained at surgery were cultured to confluency on collagen-coated microporous membranes. Those cells, which expressed differentiated characteristics of epithelial cells (they showed keratin-containing filaments and had a cobblestone appearance), were alternatively exposed to toluene diisocyanate or air for 30 min in a specially designed in vitro chamber. The production of metabolites of arachidonic acid was assessed by measuring the release of immunoreactive products into the cell medium at the end of the exposure and during a 2 hr period after exposure. This method revealed a predominant isocyanate-induced release of immunoreactive 15-hydroxyeicosatetraenoic acid. Release rate of this compound tended to be dose-related and was associated with cell damage as assessed by the release of lactate dehydrogenase in the medium.

Changes in the mitogenic activity of platelet-derived growth factor(s) in patients with myeloproliferative disease.

Platelet-derived growth factor (PDGF) is thought to take part in the genesis of bone marrow fibrosis that can be found in patients with myeloproliferative diseases. We evaluated platelet mitogenic activity as the difference between serum and plasma activity in 8 patients with myeloproliferative disease. We observed a trend of lower values in 2 cases of polycythemia vera and 2 cases of essential thrombocythemia, as seen by other authors. Two patients suffering from chronic myeloid leukemia were within the normal range. In contrast, our 2 cases of idiopathic myelofibrosis showed increased levels. If confirmed by further studies, this could suggest a pathogenetic relationship between increased levels of PDGF and bone marrow fibrosis, and give differential diagnostic significance to the PDGF mitogenic assay in myeloproliferative diseases.