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.

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.

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.

From Individual To Social Trauma: Sources Of Everyday Trauma In Italy, The US And UK During The Covid-19 Pandemic.

The heterogeneity of COVID-19 experience and response for each individual is irrefutable; nevertheless, similarities can be observed between countries with respect to people's psychological responses. The main aim of this Commentary is to provide a cultural perspective of the sources of trauma, at the individual and social level, in three different countries: Italy, US and UK. The evidence from previous outbreaks, such as SARS, H1N1 flu, Ebola, and the ongoing Italian, the US, and the UK experience of COVID-19 shows that COVID-19 has introduced not only an individual trauma but also a collective trauma, that researchers should attend to now and in future global emergencies. Future clinical interventions should aim to reconnect dissociated parts both in the individual and in society. This commentary discusses four potential sources of trauma: high-stakes decision fatigue in healthcare professionals, traumatic grief, and bereavement in people who have lost loved ones, loss of roles and identity, and social divisions related to economic shutdown.

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.

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.

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.

Leukotriene B4 and late asthmatic reactions induced by toluene diisocyanate.

We investigated whether leukotriene B4 (LTB4) is released from the lungs of sensitized subjects during asthmatic reactions induced by toluene diisocyanate (TDI). We examined three groups of TDI-sensitized subjects, one after no exposure to TDI, the second 8 h after an exposure to TDI that caused an early asthmatic reaction, and the third 8 h after an exposure to TDI that caused a late asthmatic reaction. We analyzed bronchoalveolar lavage (BAL) fluid by reverse-phase high-performance liquid chromatography and by specific radioimmunoassay. The mean concentration of LTB4 was higher [0.31 +/- 0.09 (SE) ng/ml, range 0.15-0.51] in BAL fluid of sensitized subjects who developed a late asthmatic reaction than in BAL fluid of subjects who developed an early asthmatic reaction (0.05 +/- 0.04 ng/ml, range 0-0.224), and no LTB4 was detectable in the control subjects. We also performed BAL 8 h after TDI exposure on four TDI-sensitized late-dual reactors who were on steroid treatment. In this group of subjects no LTB4 was detectable. These results suggest that LTB4 may be involved in late asthmatic reactions induced by TDI.

Toluene diisocyanate-stimulated release of arachidonic acid metabolites in the organ bath from guinea-pig airways.

This study was designed to evaluate whether metabolites of arachidonic acid play a role in the contractile response to toluene diisocyanate in isolated guinea pig airways. In control experiments we collected the supernatant from an organ bath over a time period of 2 h, after the addition of toluene diisocyanate (100 and 300 microM), and after the addition of toluene diisocyanate (300 microM) in the presence of indomethacin (5 microM). We measured prostaglandin E2, 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, thromboxane B2, leukotriene B4, leukotriene C4/D4/E4/F4 by radioimmunoassays. Levels of prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha increased significantly after addition of toluene diisocyanate in the absence of indomethacin. These results suggest that prostaglandins are involved in toluene diisocyanate-induced contractions in guinea-pig airways.

Evaluation of the Incstar Cyclo-Trac sp kit for the determination of cyclosporine in blood.

We measured cyclosporine in whole blood samples from renal and heart transplant patients by high performance liquid chromatography and by two radioimmunoassays with use of specified monoclonal antibodies. In particular, we evaluated the analytical performance of a new specific radioimmunoassay with an iodinated tracer. The reproducibility of the method is satisfactory (within-run CV 7.1 to 9.5% and between-run CV 7.2 to 10.3%). The limit of detection is 10.3 micrograms/L and the analytical recovery between 99 and 114%. The results obtained with samples from both renal heart transplant patients agree well with those obtained by HPLC and by a specific RIA that uses a tritiated tracer.

Pepsinogen Group I radioimmunoassay and total serum pepsinogen colorimetric determination: a comparative study in normal subjects and in peptic ulcer patients.

Pepsinogens, proteolytic enzymes produced by peptic cells of the stomach and discharged into the gastric lumen as well as into the blood have been divided into two groups: PG-I, originating from chief cells, and PG-II, mainly from antrum peptic cells. Both total serum pepsinogen (s-Pg) and PG-I have been separately reported as being significantly increased in gastric (GU) and duodenal ulcer (DU) patients and related to maximal acid output. In order to ascertain the relationship between s-Pg measured by means of the colorimetric Uete method, and PG-I determined by RIA method, these were assayed in 72 control subjects, 35 GU and 95 DU patients. s-Pg was found to be significantly increased both in GU and DU patients in comparison with control subjects. Likewise PG-I was significantly enhanced in GU and DU patients as compared with controls. A significant direct correlation between s-Pg and PG-I was found in all the subjects studied (r = 0.732).

Renal immunohistochemical distribution, plasma levels and urinary excretion of endothelin after kidney transplantation.

We investigated the immunohistochemical distribution of endothelin (ET) in 22 graft biopsies from kidney-transplanted patients. Like normal kidney tissue, 6/22 biopsies showed either no or only very weak ET positivity in the vascular endothelium. In the other 16 cases ET staining was marked on the vascular endothelium and wall (9/16), inflammatory infiltrates (11/16), glomeruli (7/16) and tubules (5/16). ET positivity in glomeruli and inflammatory infiltrates correlated with the degree of glomerular damage and interstitial inflammation but no correlation was found between the immunohistochemical results and the clinical variables considered. ET plasma levels (ET-PL) in patients (5.13 + 1.77 pmol/L) did not differ significantly from age-matched healthy controls (3.76 + 0.93 pmol/L), nor did ET urinary excretion (ET-U/CR-U) (33.94 + 21.89 and 24.94 + 8.5 pmol/mmol/L respectively). Neither ET-PL nor ET-U/CR-U was correlated with histological and immunohistochemical data or with the clinical variables. Our study suggests a potential role of ET as a local pro-inflammatory and growth factor in renal allografts and confirms its importance in the sequence of events involved in the progression of kidney damage.

Urinary excretion of vasoactive substances in chronic renal failure.

To investigate the pathophysiological role of vasoactive substances in the progression of chronic renal disease, we measured the 24-hour urinary excretion of prostaglandin 6-keto F1alpha, thromboxane B2, NOx, cGMP and ET-1 in 26 patients with chronic renal failure under conservative treatment and in 40 control subjects. Urinary 6-keto PgF1alpha, TxB2 and cyclic GMP were evaluated by RIA, and ET-1 was assayed by EIA. NOx were evaluated using a colorimetric assay as nitrate/nitrite. Urinary excretion of prostaglandin 6-keto F1alpha averaged 18.1 +/- 20.9 ng/g Ucreat in patients vs. 240.9 +/- 257.3 in controls (p < 0.0001), thromboxane B2 422 +/- 374 ng/g Ucreat in patients vs. 967 +/- 589 in controls (p < 2x 10(-5)), NOx 7.07 +/- 5.54 mg/g Ucreat in patients vs. 9.79 +/- 3.77 in controls (p < 0.01), cGMP 310 +/- 200 pg/g Ucreat in patients vs. 488 +/- 241 in controls (p < 0.001). In contrast, ET-1 urinary excretion was almost doubled in patients (13.45 +/- 5.84 ng/g of Ucreat) in comparison with controls (6.84 +/- 2.81 p < 1x10(-5)). While in control subjects significant correlations between urinary excretions of prostaglandin 6-keto F1alpha and thromboxane B2 (r = 0.69, p < 0.001) or NOx and ET-1 (r = 0.54, p < 0.001) were present, in patients only the relationship between urinary excretions of prostaglandin 6-keto F1alpha and thromboxane B2 (r = 0.53, p < 0.01) was retained. Our data suggest that in the normal kidney a balance between prostaglandin I2 and thromboxane A2, or nitric oxide and endothelin-1 is present, which contributes to hemodynamic regulation and protects this organ from ischemic damage. This balance is abolished in CRF, where a large increment of vasopressor agent endothelin is present, which, joined to a prevalent decrease of prostaglandin I2 synthesis, could contribute to the ischemic and fibrogenetic damage of the kidney, leading to progression of renal disease.

[Thyroid function in the euthyroid elderly subject: evidence of low T3 syndrome]. / La funzionalità tiroidea negli anziani eutiroidei: evidenza di una "sindrome a bassa T3".

The presence of a low T3 syndrome was confirmed in elderly euthyroid patients. The condition is characterised by lower circulating total (TT3) and free triiodothyronin (FT3) than in adults with no clinical symptoms of hypothyroidism. A total of 133 subjects over 65 were studied as we used 204 adult controls aged 18-65. Among the indices of thyroid function studied only TT3 and FT3 were founded to be statistically reduced among the elderly.

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.