Dealing with death in cancer care: should the oncologist be an amicus mortis?

The way death is (not) dealt with is one of the main determinants of the current crisis of cancer care. The tendency to avoid discussions about terminal prognoses and to create unrealistic expectations of fighting death is seriously harming patients, families and healthcare professionals, and the delivery of high-quality and equitable care. Drawing on different literature sources, we explore key dimensions of the taboo of death: medical, policy, cultural. We suggest that the oncologist, from a certain moment, could take on the role of amicus mortis, a classical figure in the past times, and thus accompanying patients towards the end of their life through palliation and linking them to psychosocial and ethical/existential resources. This presupposes the implementation of Supportive Care in Cancer and the ethical idea of relational autonomy based on understanding patients' needs considering their sociocultural contexts. It is also key to encourage public conversations beyond the area of medicine to re-integrate death into life.

Molecular evaluation of tissue proteins in vivo during controlled orthodontic movement.

Orthodontic tooth movement determines a biological response of all the tissues surrounding the teeth to which force is applied. The aim of this study is to evaluate which ideal orthodontic force, at the biological level, arouses an acute inflammatory response on periodontal tissues, and the duration of the force in order to establish an ideal experimental model of dental movement. The periodontal ligament and the alveolar bone change abruptly due to the biochemical adaptive response, resulting in a re-organization of the intracellular and the extracellular matrix. There is a modification of the local vascularization which stimulates a cascade production, synthesis and the release of arachidonic acid, metabolites, proteins, such as cytokines, and growth factors. Every dentist can control and should know the above-mentioned mechanism. Moreover, the production of proteins by modulating the direction and the intensity of the force can be changed but, above all, the duration.

The use of antidepressants in oncology: a review and practical tips for oncologists.

Background: The use of psychotropic drugs, namely those with an antidepressant profile (ADs), is a mandatory part of an integrated treatment of psychiatric disorders among cancer patients. We aimed to synthetize the most relevant data emerging from published studies to provide tips about the use of ADs in oncology. Design: A search was made of the major databases over the last 30 years (Embase/Medline, PsycLIT, PsycINFO, the Cochrane Library), including narrative reviews, systematic reviews and meta-analyses summarizing the results from observational studies and randomized clinical trials assessing effectiveness, safety profile, interactions, contraindications and use of ADs in oncology with regard to both psychiatric (depressive spectrum, stress-related, anxiety disorders) and cancer-related symptoms (e.g. pain, hot flashes and fatigue). Results: The weight of evidence supports the efficacy of ADs for more severe major depression in individuals with cancer and as an adjuvant treatment in cancer-related symptoms, although the methodological limitations of reported randomized controlled trials do not permit definite conclusions. Data also indicate that there should be caution in the use of ADs in cancer patients in terms of their safety profile and potential clinically significant interactions with other prescribed medications. Practical recommendations that have been made for the use of ADs in cancer patients, in the context of a multimodal approach to depression treatment, have been summarized here. Conclusions: ADs are a relatively safe and effective treatment for more severe major depression in cancer patients. However, more research is urgently needed regarding the efficacy of ADs in different cancer types and cancer settings, their interactions with anticancer agents and their additive benefit when integrated with psychosocial interventions.

Depressive spectrum disorders in cancer: prevalence, risk factors and screening for depression: a critical review.

BACKGROUND: Although depression and mood-related disorders are common in persons with cancer, these conditions remain frequently overlooked in clinical practice. Negative consequences of depressive disorder spectrum have been reported (e.g. suicidal ideation, increase physical complications and somatic symptoms, negative influence on prognosis), indicating the need for routine screening, assessment and management. METHODS: A search of the major databases (Medline, Embase, PsycLIT, PsycINFO, and the Cochrane Library) was conducted on the reviews and meta-analyses available in order to summarize relevant data concerning depressive disorders spectrum in terms of prevalence, risk factors, and screening and assessment among patients with cancer across the trajectory of the disease. RESULTS: The data show a prevalence of depression and depressive disorders between 5% and 60% according to the different diagnostic criteria, the tools used in the studies (e.g. semi-structured psychiatric interview and psychometric questionnaires), as well as the stage and type of cancer. Furthermore, despite the significant health care resources devoted to cancer care and the importance of addressing depressive symptoms, assessment and management of depressive spectrum disorders in cancer patients remains suboptimal. CONCLUSIONS: Routine screening and adequate assessment of depressive spectrum disorders is necessary in patients with cancer in order to effectively manage the multifaceted and complex consequences on cancer care.

Risk for Depression, Burnout and Low Quality of Life Among Personnel of a University Hospital in Italy is a Consequence of the Impact One Economic Crisis in the Welfare System?

BACKGROUND: Research literature suggests that burnout, depression, and a low mental quality of life (QOL) are common among health care workers. Economic crisis might have increased the burden of burnout, depression and low QOL in health care workers. OBJECTIVES: To identify depression risk, burnout levels, and quality of life in a sample of workers of an Italian university hospital. METHOD: Cross sectional study with comparison with two community surveys database results (n = 2000 and 1500, respectively). Overall, 522 workers accepted to take part in the study, representing a 78% response rate (out of 669 individuals). RESULTS: The frequency of positivity at the screener for Major Depressive Disorder among health care workers was more than double than that in the standardized community sample (33.3% vs 14.1%, p<0.0001). All professionals, except the administrative staff and technicians (i.e. those who do not have contact with patients), showed a statistically higher frequency of positivity for depressive episodes compared to the controls. Among the medical staff, the highest risk was found in the surgeon units, while the lowest one was in the laboratories. Surgeons also were those most exposed to high risk of burnout, as measured by the Maslach Burnout Inventory. CONCLUSION: Since burnout is linked to patient safety and quality of patient care, and contribute to medical errors, dedicated interventions aimed at reducing poor mental health and low quality of life in medical staff are indicated.

2013 President's Plenary International Psycho-oncology Society: embracing the IPOS standards as a means of enhancing comprehensive cancer care.

BACKGROUND: The second President's Plenary at the 2013 International Psycho-oncology Society's World Congress in Rotterdam, the Netherlands aimed to progress and, where needed, initiate changes to achieve comprehensive cancer care. Recent initiatives have been driven by the need to see psychosocial care as an integrated part of holistic multidisciplinary quality cancer care. The President's Plenary session covered the need for the following: An internationally agreed standard of quality cancer care, which includes psychosocial care for patients and their families and caregivers. An endorsement to assess distress as the 6th vital sign. Psycho-oncology professionals to integrate into a federation promoting better national and international outcomes. CONCLUSION: This overview highlights progress in terms of enhanced communication between and within different professionals groups supporting the implementation of a model of comprehensive patient care that is inclusive of psychosocial support and screening for distress. Tasks and challenges for the future are set out but the primary message is of the importance of collaboration in order to achieve recognition that psychosocial care is integrated into comprehensive cancer care; in this way, patient, family and carer needs can be more appropriately met.

Maladaptive coping styles moderate the relationship between information on cancer treatment and psychosocial symptoms: an Italian multicenter study.

Objectives: Disclosing information on diagnosis, prognosis and treatment is a delicate process in oncology, although awareness levels have over time increased in people with cancer. However, individual characteristics should be considered when communicating difficult information. We conducted a multicentric study to explore the moderating role of coping styles on the relationship between information about cancer, quality of life and psychological distress. Methods: In the period between October 2015 and February 2016, 288 patients with a diagnosis of a solid tumor were recruited from seven Italian oncology units. All participants were administered the Distress Thermometer (DT), the Mini-Mental Adjustment to Cancer (Mini-MAC), the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), and the EORTC QLQ 25-item information module (INFO25). We explored the moderating effect of coping style with quality of life (QoL) and distress (DT) as dependent variables and information on cancer treatment as independent variable. Results: Low levels of anxious preoccupation significantly moderated the relationship between information on treatment and QoL (R2 6%, p < 0.001), while low and medium levels of hopelessness significantly moderated the relationship between information on treatment and DT (R2 = 14%, p = 0.033). Adaptive coping strategies, such as fighting spirit and fatalism, and borderline strategies such as avoidance, did not play a role in this relationship. Conclusion: Taking into account and evaluating coping mechanisms in cancer care is a priority when disclosing information on treatments, in order to tailor communication style to individual features.

A cluster analysis-derived classification of psychological distress and illness behavior in the medically ill.

BACKGROUND: The classification of psychological distress and illness behavior in the setting of medical disease is still controversial. Current psychiatric nosology does not seem to cover the spectrum of disturbances. The aim of this investigation was to assess whether the joint use of DSM-IV categories and the Diagnostic Criteria for Psychosomatic Research (DCPR), that provide identification of syndromes related to somatization, abnormal illness behavior, irritable mood, type A behavior, demoralization and alexithymia, could yield subtyping of psychosocial variables in the medically ill. METHOD: A cross-sectional assessment using both DSM-IV and the DCPR was conducted in eight medical centers in the Italian Health System. Data were submitted to cluster analysis. Participants were consecutive medical out-patients and in-patients for whom a psychiatric consultation was requested. A total of 1700 subjects met eligibility criteria and 1560 agreed to participate. RESULTS: Three clusters were identified: non-specific psychological distress, irritability and affective disturbances with somatization. CONCLUSIONS: Two-step cluster analysis revealed clusters that were found to occur across clinical settings. The findings indicate the need of expanding clinical assessment in the medically ill to include the various manifestations of somatization, illness behavior and subclinical distress encompassed by the DCPR.

Type A behaviour: a reappraisal of its characteristics in cardiovascular disease.

AIMS: The role of type A behaviour in cardiovascular disease is controversial and most of the research is based on self-rating scales. The aim of this study was to assess the prevalence of type A behaviour in cardiology and in other medical settings using reliable interview methods that reflect its original description. METHODS: A sample of 1398 consecutive medical patients (198 with heart transplantation, 153 with a myocardial infarction, 190 with functional gastrointestinal disorders, 104 with cancer, 545 with skin disorders and 208 referred for psychiatric consultation) was administered the Structured Clinical Interview for the DSM-IV and the Structured Interview for the Diagnostic Criteria for Psychosomatic Research (DCPR) which identifies 12 clusters, including type A behaviour. RESULTS: A cardiac condition was present in 366 patients. There was a significant difference in the prevalence of type A behaviour in cardiovascular disease (36.1%) compared with other medical disorders (10.8%). Type A behaviour frequently occurred together with psychiatric and psychosomatic disturbances, particularly irritable mood, even though in the majority of cases it was not associated with DSM-IV diagnoses. Among cardiac patients, those with type A behaviour were less depressed, demoralised and worried about their illness. CONCLUSIONS: Type A behaviour was found to occur in about a third of cases of patients with cardiovascular disease. Only in a limited number of cases was it associated with depression. It has a lifestyle connotation that may have important clinical consequences as to stress vulnerability and illness behaviour.

Adherence to a guided walking program with amelioration of cognitive functions in subjects with schizophrenia even during COVID-19 pandemic.

BACKGROUND: Aim of the study was to enrol a group of individuals with schizophrenia in a long-term moderate-intensity physical activity program and to evaluate its effects on their cognitive functions and cardiovascular risk factors. An additional aim of the study was the comparison of the adherence to the physical activity program before and during the COVID-19 pandemic. METHODS: Forty sedentary patients diagnosed with schizophrenia (mean age 46.4 ± 9.6) followed by the Public Mental Health Department of Ferrara were included in the study. 28 of them followed a 1-year walking program consisting of two guided walking sessions/week, while 12 maintained their sedentary lifestyle and followed the usual Cognitive Rehabilitation program. To the participants following the walking program VO2 peak and walking speed were assessed at baseline and at the end of the program. All participants were evaluated on blood pressure and anthropometric variable. Cognitive functions were assessed with the Screen for Cognitive Impairment in Psychiatry (SCIP) and with the Frontal Assessment Battery (FAB) questionnaires. RESULTS: The 20 participants completing the walking program displayed significant improvements in cognitive functions (dppc2 0.35 for SCIP and 0.26 for FAB), with a positive correlation between SCIP score and the number of sessions attended (R = 0.86, p < 0.001), evident in the patients attending to at least 75 of the 100 walking sessions. Walking speed and VO2peak increased significantly and a decrease of body weight, BMI, systolic and diastolic blood pressure was also observed. The adherence to the walking program registered during Covid-19 period did not differ from that observed before the pandemic. The 12 CG (Control Group) patients maintaining the sedentary lifestyle did not display improvements of cognitive functions. CONCLUSIONS: The main finding of this study is the improvement of cognitive functions which is significantly related to the number of walking sessions attended by participants with schizophrenia. The walking program, guided by exercise specialists, proved to be an enjoyable activity for people with mental disorder feasible even during the COVID-19 pandemic. Trial registration Retrospectively registered on ISRCTN as non-randomized trial (n. ISRCTN14763786).

Communication training in oncology: results of intensive communication workshops for Italian oncologists.

The primary aim of this study was to evaluate the efficacy of a 3-day communication course model for senior Italian oncologists. The course, initially designed for US oncologists, was modified to address specific educational areas expected to be relevant to the targeted participants. Five 3-day intensive communication courses were held for oncologists from different geographical regions in Italy. The courses included formal lectures, small group work, role play and interviews with simulated patients. Participants completed questionnaires before and after the 3-day workshop. An improvement in self-efficacy, knowledge of communication skills, favourable changes in attitudes towards disclosure of medical information and assessing patients' concerns and fears were demonstrated at the end of the course. The course was feasible and succeeded in improving parameters associated with effective communication behaviours.

The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition.

The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.

Tissue viscoelasticity is related to tissue composition but may not fully predict the apparent-level viscoelasticity in human trabecular bone - An experimental and finite element study.

Trabecular bone is viscoelastic under dynamic loading. However, it is unclear how tissue viscoelasticity controls viscoelasticity at the apparent-level. In this study, viscoelasticity of cylindrical human trabecular bone samples (n=11, male, age 18-78 years) from 11 proximal femurs were characterized using dynamic and stress-relaxation testing at the apparent-level and with creep nanoindentation at the tissue-level. In addition, bone tissue elasticity was determined using scanning acoustic microscope (SAM). Tissue composition and collagen crosslinks were assessed using Raman micro-spectroscopy and high performance liquid chromatography (HPLC), respectively. Values of material parameters were obtained from finite element (FE) models by optimizing tissue-level creep and apparent-level stress-relaxation to experimental nanoindentation and unconfined compression testing values, respectively, utilizing the second order Prony series to depict viscoelasticity. FE simulations showed that tissue-level equilibrium elastic modulus (Eeq) increased with increasing crystallinity (r=0.730, p=.011) while at the apparent-level it increased with increasing hydroxylysyl pyridinoline content (r=0.718, p=.019). In addition, the normalized shear modulus g1 (r=-0.780, p=.005) decreased with increasing collagen ratio (amide III/CH2) at the tissue-level, but increased (r=0.696, p=.025) with increasing collagen ratio at the apparent-level. No significant relations were found between the measured or simulated viscoelastic parameters at the tissue- and apparent-levels nor were the parameters related to tissue elasticity determined with SAM. However, only Eeq, g2 and relaxation time τ1 from simulated viscoelastic values were statistically different between tissue- and apparent-levels (p<.01). These findings indicate that bone tissue viscoelasticity is affected by tissue composition but may not fully predict the macroscale viscoelasticity in human trabecular bone.

HLA-DRB1*15 association with multiple sclerosis is confirmed in a multigenerational Italian family.

Environmental and genetic factors seem to play a pathogenetic role in multiple sclerosis (MS). The genetic component is partly suggested by familial aggregation of cases; however, MS families with affected subjects over different generations have rarely been described. The aim of this study was to report clinical and genetic features of a multigenerational MS family and to perform a review of the literature on this topic. We describe a multigenerational Italian family with six individuals affected by MS, showing different clinical and neuroradiological findings. HLA-DRB1* typing revealed the presence of the DRB1*15:01 allele in all the MS cases and in 4/5 non-affected subjects. Reports on six multigenerational MS families have previously been published, giving similar results. The HLA-DRB1*15:01 allele was confirmed to be linked to MS disease in this family; moreover, its presence in non-affected subjects suggests the involvement of other susceptibility factors in the development and expression of the disease, in accordance with the complex disease model now attributed to MS.

C-Met/miR-130b axis as novel mechanism and biomarker for castration resistance state acquisition.

Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy. The relevance of these findings was confirmed on patients' samples and by in silico analysis on an independent patient cohort from Taylor's platform. Data suggest c-Met/miR-130b axis as a new prognostic marker for patients' risk assessment and as an indicator of therapy resistance. Our results propose new biomarkers for therapy decision-making in all phases of the pathology. Data may help identify high-risk patients to be treated with adjuvant therapy together with alternative cure for castration-resistant forms while facilitating the identification of possible patients candidates for anti-Met therapy. In addition, we demonstrated that it is possible to evaluate Met/miR-130b axis expression in exosomes isolated from peripheral blood of surgery candidates and advanced patients offering a new non-invasive tool for active surveillance and therapy monitoring.

The Neurobiological Basis of the Distress Thermometer: A PET Study in Cancer Patients.

The objective of this study was to investigate the possible associations between the Distress Thermometer (DT) scores and the brain metabolism of structures involved in stress response. Twenty-one cancer patients were assessed using the DT, Problem Checklist and Hospital Anxiety and Depression Scale (HADS). The psychological measures were correlated with [18 F]PET-FDG brain glucose metabolism. Multiple and linear regression and binary logistic regression were run to analyse data. The DT and HADS scores illustrated that 48% of patients were distressed, 19% were depressed and 48% were anxious. Results showed that some subcortical areas activity, such as part of midbrain and of hypothalamus, was correlated with the DT scores. The Problem Checklist scores correlated with the activity of the same areas and included more regions in the limbic forebrain and brainstem. Compared with the DT and Problem Checklist, HADS-Depression scores showed a more extensive pattern of correlation with brain activity, including limbic and cortical areas. The results highlighted that the DT scores correlated with the activity of brain areas typically involved in stress response. Indeed, hypothalamus metabolism was found to be the best predictor of distressed patients.