Comparison of two audit and feedback approaches: descriptive analysis of personal and contextual dynamics.

INTRODUCTION: Audit and feedback (A&F) is a systematic intervention that can be used to improve the quality of health care. The EASY-NET Network Project proposes an innovative A&F model. AIM: This study aimed to describe the newly proposed A&F model. An analysis was conducted, examining the participants' attitudes and their individual and interpersonal mechanisms to understand how they influence the work context and vice versa. METHODS: Two A&F models were compared, involving emergency and rehabilitation health workers, who were divided into two groups. The classic A&F model was compared with a new model, using a desk audit followed by interactive feedback. Communication training was provided to the audit team by psychologists before commencement of the project. The experimental group underwent psychological screening using two standardized tools (COPE-NVI and ProQoL) to evaluate personal and relational dynamics using the context-mechanism-outcome (CMO) paradigm. RESULTS: The exchange of ideas among health professionals is more effective when using face-to-face feedback than written feedback. The COPE-NVI and ProQoL questionnaires highlighted the difficulties experienced by health care professionals in implementing effective coping strategies to deal with stressful events. CONCLUSIONS: Identifying signs of stress in health care workers is essential for improvement strategies to be implemented and for establishing new, optimal conditions. Remote feedback makes it possible to overcome logistical barriers and, in the future, this method can be used for inter-organizational collaboration. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A203.

Rare Driver Mutations in Advanced, Oncogene-Addicted Non-Small Cell Lung Cancer: A North Italian, Real-World, Registry Experience.

The real-world, retrospective, NEROnE registry investigated the impact of next-generation sequencing (NGS) in advanced non-small-cell lung cancer (NSCLC) patients (pts) at three oncology units in the north of Italy between January 2020 and December 2022. We focused on the clinical characterization and outcomes of NSCLC with rare molecular alterations: EGFR exon 20 insertion, non-activating EGFR mutations, BRAF V600E and non-V600, ROS1 and RET rearrangements, MET, ErbB2, and FGFR mutations. Overall, these represented 6.4% (62/970) of the pts analysed with NGS in the daily practice. The most heavily represented rare alterations were ROS1 rearrangement (15 pts-24%) and MET exon 14 skipping mutation (11 pts-18%). No associations were found with the demographic and clinical features. Forty-nine pts received targeted therapies, of which 38.8% were first- and 9.8% were second-line. The remaining pts received chemotherapy and/or immunotherapy. In terms of the clinical outcomes, although not statistically significant, a tendency toward shorter OS was seen when therapies other than specific targeted therapies were used (HR: 1.84, 95% CI: 0.79-4.33, p = 0.158). The pts with co-mutations (19.4%) seemed to receive an advantage from the front-line chemotherapy-based regimen. Finally, an NLR score (a well-known inflammatory index) ≥ 4 seemed to be related to shorter OS among the pts treated with immunotherapy alone or in combination with chemotherapy (HR: 2.83, 95% CI: 1.08-7.40, p = 0.033). Prospective evaluations need to be performed to clarify whether these indexes may help to identify patients with oncogene-addicted NSCLC who could benefit from immunotherapy.

A systematic review about the importance of neuropsychological features in heart failure: is at heart the only failure?

Heart failure can lead to cognitive impairment that is estimated to be present in over a quarter of patients. It is important to intervene at a cognitive level to promote brain plasticity through cognitive training programs. Interventions transformed by technology offer the promise of improved cognitive health for heart failure patients. This review was conducted on studies evaluating the role of cognitive rehabilitation in patients with heart failure. We examined clinical trials involving patients with heart failure. Our search was performed on Pubmed, Web of Science and Cochrane library databases. Of the initial 256 studies, 10 studies met the inclusion criteria. Cognitive rehabilitation training has important implications for the treatment and prevention of cognitive decline in heart failure patients with significant recovery for delayed recall memory and a significant time effect for total recall memory and delayed, psychomotor speed and IADL performance. It is important to include the assessment of cognitive functioning in the routine clinical examinations of patients with heart failure, discover the relationship between cognitive function and heart failure, and target cognitive rehabilitation programs that promote brain plasticity.

A Set of Possible Markers for Monitoring Heart Failure and Cognitive Impairment Associated: A Review of Literature from the Past 5 Years.

BACKGROUND: Heart failure is an epidemiologically relevant disease because of the aging population and widespread lifestyles that promote it. In addition to the acute event, it is possible for the disease to become chronic with periodic flare-ups. It is essential to study pathology from a diagnostic and prognostic point of view and to identify parameters for effective monitoring. In addition, heart failure is associated with multiple comorbidities, including cognitive impairment, which is monitored clinically but not through specific biomarkers in these patients. The purpose of this review is to gather the most recent scientific evidence on a few possible biomarkers previously identified for monitoring heart failure and associated cognitive impairment. METHODS: We surveyed studies inherent to a set of previously identified markers, evaluating English-language articles from the past five years conducted in adult heart failure patient populations. We used the databases PubMed, Web of Sciences, and Cochrane Library for search studies, and we considered articles published in journals with an impact factor greater than five in the publication year. RESULTS: Among the biomarkers evaluated, a concordant indication for serial measurements for heart failure monitoring emerged only for interleukin-6. For the other markers, there is still little evidence available, which is interesting but sometimes conflicting. Interesting studies have also emerged for biomarkers of cognitive decline assessed in patients with heart failure, confirming the hypotheses of the increasingly studied heart-brain correlation. CONCLUSION: Certainly, further studies in large populations are needed to identify effective biomarkers for monitoring heart failure and associated cognitive impairment.

Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial.

BACKGROUND: Pleural mesothelioma usually presents at an advanced, incurable stage. Chemotherapy with platinum-pemetrexed is a standard treatment. We hypothesised that the addition of pembrolizumab to platinum-pemetrexed would improve overall survival in patients with pleural mesothelioma. METHODS: We did this open-label, international, randomised phase 3 trial at 51 hospitals in Canada, Italy, and France. Eligible participants were aged 18 years or older, with previously untreated advanced pleural mesothelioma, with an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) to intravenous chemotherapy (cisplatin [75 mg/m2] or carboplatin [area under the concentration-time curve 5-6 mg/mL per min] with pemetrexed 500 mg/m2, every 3 weeks for up to 6 cycles), with or without intravenous pembrolizumab 200 mg every 3 weeks (up to 2 years). The primary endpoint was overall survival in all randomly assigned patients; safety was assessed in all randomly assigned patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02784171, and is closed to accrual. FINDINGS: Between Jan 31, 2017, and Sept 4, 2020, 440 patients were enrolled and randomly assigned to chemotherapy alone (n=218) or chemotherapy with pembrolizumab (n=222). 333 (76 %) of patients were male, 347 (79%) were White, and median age was 71 years (IQR 66-75). At final analysis (database lock Dec 15, 2022), with a median follow-up of 16·2 months (IQR 8·3-27·8), overall survival was significantly longer with pembrolizumab (median overall survival 17·3 months [95% CI 14·4-21·3] with pembrolizumab vs 16·1 months [13·1-18·2] with chemotherapy alone, hazard ratio for death 0·79; 95% CI 0·64-0·98, two-sided p=0·0324). 3-year overall survival rate was 25% (95% CI 20-33%) with pembrolizumab and 17% (13-24%) with chemotherapy alone. Adverse events related to study treatment of grade 3 or 4 occurred in 60 (27%) of 222 patients in the pembrolizumab group and 32 (15%) of 211 patients in the chemotherapy alone group. Hospital admissions for serious adverse events related to one or more study drugs were reported in 40 (18%) of 222 patients in the pembrolizumab group and 12 (6%) of 211 patients in the chemotherapy alone group. Grade 5 adverse events related to one or more drugs occurred in two patients on the pembrolizumab group and one patient in the chemotherapy alone group. INTERPRETATION: In patients with advanced pleural mesothelioma, the addition of pembrolizumab to standard platinum-pemetrexed chemotherapy was tolerable and resulted in a significant improvement in overall survival. This regimen is a new treatment option for previously untreated advanced pleural mesothelioma. FUNDING: The Canadian Cancer Society and Merck & Co.

Coping and Quality of Life Differences between Emergency and Rehabilitation Healthcare Workers.

Audit and Feedback (A&F) is a systematic process involving the collection of data, which are subsequently compared with the established reference standards and then subsequently disseminated to healthcare providers through feedback meetings. This allows continuous improvement to be ensured in the quality of care processes. Often, the parameters taken into account concern only the patient and the treatment processes, neglecting other variables. Quality of life in the workplace and coping skills are determining variables for the clinical performance of all healthcare professionals. For this reason, in this study, these variables were investigated and differences were highlighted in two different role categories and context: cardiovascular emergency and neurological rehabilitation. A psychological screening was carried out by sending the computerized Coping Orientation to Problems Experienced-Nuova Versione Italiana (COPE-NVI) and Professional Quality of Life Scale-5 (ProQoL) questionnaires to all healthcare workers involved. Ninety-five healthcare providers (mean ± SD age: 47 ± 10.4 years; 37.9% male) answered the questionnaire and were assigned into two groups (G1 and G2) based on the ward in which they worked. These were further divided into two subgroups (R1 and R2) based on their role. The obtained results show that avoidance strategies are used more by health professionals working in rehabilitation (G2) wards than in intensive-care units (G1). Moreover, in G1 nurses, physical therapists and speech therapists (R2) obtained higher scores in terms of turning to religion (TR) and compassion satisfaction (CS), while physicians and psychologists (R1) obtained higher scores on the burnout scale (BO). The TR score for R2 was found to be higher, even in G2. The response trend of the two groups in the different departments was analyzed and commented on.

The Role of Sex Differences in Bone Health and Healing.

Fracture healing is a long-term and complex process influenced by a huge variety of factors. Among these, there is a sex/gender disparity. Based on significant differences observed in the outcome of bone healing in males and females, in the present review, we report the main findings, hypotheses and pitfalls that could lead to these differences. In particular, the role of sex hormones and inflammation has been reported to have a role in the observed less efficient bone healing in females in comparison with that observed in males. In addition, estrogen-induced cellular processes such as autophagic cell cycle impairment and molecular signals suppressing cell cycle progression seem also to play a role in female fracture healing delay. In conclusion, it seems conceivable that a complex framework of events could contribute to the female bias in bone healing, and we suggest that a reappraisal of the compelling factors could contribute to the mitigation of sex/gender disparity and improve bone healing outcomes.

Improving Knowledge of Audit and Feedback among Health Care Professionals in Sicily.

Audit and Feedback (A&F) is considered one of the most significant tools for implementing continuous Quality Improvement (QI) in the healthcare field. The audit process is a structured inspection of professional practice against known standards or targets. The results of this inspection are subsequently feedback from professionals in order to implement an improvement process. The Italian Ministry of Health has recently funded the network project EASY-NET, with the main objective of evaluating the effectiveness of A&F strategies to improve healthcare practice and equity in various clinical and organizational settings in seven Italian regions. The Sicily region is represented within the EASY-NET project by the IRCCS Centro Neurolesi Bonino-Pulejo of Messina as the Work Package 7 (WP7). One of the objectives of the WP7 is to assess mechanisms and tools to enhance the effectiveness of A&F strategies. The purpose of this study is to investigate the influence that training interventions can have on improving knowledge of A&F strategies among healthcare professionals. The study employed a quasi-experimental design with a pretest-posttest evaluation strategy. The participants' initial knowledge of A&F strategies was evaluated through a baseline survey. Subsequently, the participants attended an online training workshop led by A&F experts, and a follow-up survey consisting of the same set of questions was conducted at the end of the process. Results showed statistically significant positive changes in the level of knowledge of A&F among participants following the training intervention. Furthermore, dividing the participants into two subgroups based on their professional background revealed significant differences in the level of knowledge of A&F methodologies between the observed categories of healthcare professionals. In conclusion, the study revealed that training interventions can be facilitators to implementing effective A&F programs.

Changes in the Histology of Lung Cancer in Northern Italy: Impact on Incidence and Mortality.

This study assessed the incidence, mortality, and survival of lung cancer subtypes of NSCSLC (non-small-cell lung cancer), SCLC (small-cell lung cancer), and other morphologies. It is an observational epidemiological study using 7197 cases from the Reggio Emilia Cancer Registry recorded between 2001 and 2020 in males and females. The incidence of NSCLC in 5104 males indicates a significant 3% annual increase until 2013 and then a decline of -3.2% that is not statistically significant; until 2014, mortality increased significantly (3.2%), but it then decreased non-significantly (-12.1%), especially squamous cell cancer. In 2093 females, the incidence and mortality trends continued to rise significantly through 2012, and then they began to slightly decline (not statistically significant). The two-year relative survival of NSCLC increased from 32% to 38% in males and from 42% to 56% in females. SCLC in males decreased significantly both in incidence and mortality, while in women, it showed a slight increase (significantly for incidence but not for mortality). This study is important because it analyzes the decrease in lung cancer in males and the increase in females in relation to the different histotypes. Our study's findings confirmed a decline in male incidence and death beginning in 2013. We were unable to determine if the drop in cigarette smoking and the introduction of new drugs such as EGFR in first-line therapy were responsible for the lower incidence.

Brief Report: Canadian Cancer Trials Group IND.227: A Phase 2 Randomized Study of Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma (NCT02784171).

Immune checkpoint inhibitors have activity in mesothelioma. IND.227 was a phase 2 trial (120 patients planned) comparing progression-free survival of standard platinum and pemetrexed (CP) versus CP + pembrolizumab (pembro) versus pembro. Accrual to the pembro arm was discontinued on the basis of interim analysis (IA-16 wk disease control rate). CP + pembro was tolerable, with progression-free survival similar between arms and median survival and overall response rate higher than those of CP alone (19.8 mo [95% confidence interval or CI: 8.4-41.36] versus 8.9 mo [95% CI: 5.3-12.8] and 47% [95% CI: 24%-71%] versus 19% [95% CI: 5%-42%], respectively). The subsequent phase 3 trial has completed accrual; results are expected in 2023.

Multi-characteristic toxicity of enantioselective chiral fungicide tebuconazole to a model organism Mediterranean mussel Mytilus galloprovincialis Lamarck, 1819 (Bivalve: Mytilidae).

The survey of available scientific literature shows a lack of data on the chronic effects of tebuconazole (TEB) on non-target aquatic organisms. Therefore, this study evaluates toxicity (10 and 20 days) of two considered concentrations 2 ng/L (E1) and 2 µg/L (E2) of TEB to bioindicator species Mytilus galloprovincialis. To this end, the TEB concentrations measured in soft mussel tissues showed a time-dependent increasing trend. The viability of haemocyte and digestive gland (DG) cells was higher than 95 % during the experiment. However, DG cells lost the ability to regulate their volume in both groups after 20-d. The E1 treatment increased Cl- and Na+ levels, and E2 decreased Na+ levels in the haemolymph. In addition, levels of superoxide dismutase (SOD) activity and oxidatively modified protein (OMP) increased after 10- and 20-d in both treatments. Histopathological findings showed abnormalities in the E2, e.g., haemocyte infiltration, hypertrophy, and hyperplasia in gills and DG. This study reveals the potential risks of TEB usage in the model organism M. galloprovincialis, primarily via bioaccumulation of TEB in food web links, and improves knowledge about its comprehensive toxicity.

A first insight into haemocytes of Pinctada imbricata radiata: A morpho-functional characterization.

The pearl oyster Pinctada imbricata radiata (Leach, 1814), from the Pacific Ocean, was one of the first species to reach via Suez the Mediterranean, colonizing the eastern basin and recently spreading to the western. The species showed to be able to adapt to a wide range of climatic, hydrological, and ecological conditions. Since 2000 it reached the Strait of Messina, where is now infesting the transitional waters of the oriented natural reserve "Laguna di Capo Peloro." Due to such resistance and adaptation ability, various assays were performed. Haemocyte morpho-functional aspects were evaluated in haemolymph samples fixed with 1% and 2% glutaraldehyde for optical and electron microscopy (TEM). The following assays were carried out: cell characterization using several dyes, detection of intra- and extracellular lipids, the capability of phagocytosis using the yeast Saccharomyces cerevisiae and to produce superoxide anion (O2- ). Detection of several enzymes, such as acid and alkaline phosphatase, arylsulfatase, chloro-acetylesterase and ß-glucuronidase was also assessed. Cell count was demonstrated to be abundant with a mean of 8.263 × 106 mm2 ± 0.935 × 106 (SD). Two main cell populations were noticed: granulocytes and hyalocytes, both competent for phagocytosis, to produce O2- , and characterized by lipids. Based on the granule analysis, enzymatic activity was also demonstrated. The observations under TEM confirmed all the results obtained. This study supports the hypothesis that P. imbricata radiata can be usefully employed as a model organism in environmental biomonitoring. Moreover, since the species represent potential threats to native species and ecosystems, further insights into its biological adaptations in invaded ecosystems are recommended.

Impact of low skeletal muscle mass and quality on clinical outcomes in patients with head and neck cancer undergoing (chemo)radiation.

The study aimed to explore the impact of low skeletal muscle mass and quality on survival outcomes and treatment tolerance in patients undergoing radical chemo-radiation therapy for head and neck cancer (HNC). This is significant given the growing interest in sarcopenia as a possible negative predictive/prognostic factor of disease progression and survival. From 2010 to 2017, 225 patients were included in the study. Pre-treatment computed tomography (CT) scans of HNC patients undergoing (chemo)radiation therapy were retrospectively reviewed. The skeletal muscle area, normalized for height to obtain the skeletal muscle index (SMI), the skeletal muscle density (SMD) and the intramuscular adipose tissue area (IMAT) were measured at the level of the L3 vertebra. Low SMD and low SMI were defined according to previously reported thresholds, while high IMAT was defined using population-specific cut-point analysis. SMI, SMD, and IMAT were also measured at the proximal thigh (PT) level and tested as continuous variables. Clinical morpho-functional parameters, baseline nutritional markers with a known or suspected impact on HNC treatment, clinical outcomes and sarcopenia were also collected. In multivariate analyses, adjusted by age, sex, stage, diabetes, body mass index (BMI), and weight loss, L3-SMI was not significantly associated with survival, while poor muscle quality was negatively associated with overall survival (OS) (HR = 1.88, 95% CI = 1.09-3.23, p = 0.022 and HR = 2.04, 95% CI = 1.27-3.27, p = 0.003, for low L3-SMD and high L3-IMAT, respectively), progression-free survival (PFS) (HR = 2.26, 95% CI = 1.39-3.66, p = 0.001 and HR = 1.97, 95% CI = 1.30-2.97, p = 0.001, for low L3-SMD and high L3-IMAT, respectively) and cancer-specific survival (CSS) (HR = 2.40, 95% CI = 1.28-4.51, p = 0.006 and HR = 1.81, 95% CI = 1.04-3.13, p = 0.034, for low L3-SMD and high L3-IMAT, respectively). Indices at the PT level, tested as continuous variables, showed that increasing PT-SMI and PT-SMD were significant protective factors for all survival outcomes (for OS: HR for one cm2/m2 increase in PT-SMI 0.96; 95% CI = 0.94-0.98; p = 0.001 and HR for one HU increase in PT-SMD 0.90; 95% CI = 0.85-0.94; p < 0.001, respectively). PT-IMAT was a significant risk factor only in the case of CSS (HR for one cm2 increase 1.02; 95% CI = 1.00-1.03; p = 0.046). In conclusion, pre-treatment low muscle quality is a strong prognostic indicator of death risk in patients affected by HNC and undergoing (chemo)radiotherapy with curative intent.

Identification of haemocytes and histological examination of gills of the spiny oyster Spondylus gaederopus (Linnaeus, 1758).

In the framework of investigations aimed to detect new available bioindicators in marine environment, haemolymph cells and ctenidia of the Mediterranean spiny oyster, Spondylus gaederopus, have been investigated. Haemocyte count and characterisation, phagocytosis and superoxide anion production and enzyme activity assays, have been carried out. TEM observations have been performed. After gross anatomy observations, cito-histological determinations have been carried out, especially focused on ctenidia structure and function. Main results concerned the relatively low number of circulating cells, and the rich in granules granulocytes, most of which were lysosomes. Release of lysosomal enzymes was confirmed a shared trait inside bivalves. Glycogen deposits as probable result of conversion of bacteria carbohydrates, have been detected, as well as the occurrence of both acidophilic and basophilic haemocytes. Phagocytosis, both in granulocytes and agranulocytes, has been recorded, together with the production of superoxide anion. Haemocytes were found positive to acid phosphatase, alkaline phosphatase, ß-glucuronidase, chloroacetylesterase and arylsulphatase. Ctenidia showed a complex organization, including two demibranch to each ctenidium, two different kinds of lamellae filament and specialized structures as ciliated disks connecting filaments in "eutherorhabdic ctenidia". The occurrence of three different types of mucous cells in the same region of ordinary filaments has been underlined. Such features, suggesting high resistance to environmental stress and disease, allow to consider spiny oysters as promising bioindicators, although deserving of further investigations to evaluate the physiological responses to stress in controlled conditions. Present data, moreover, providing basic information on the biology of S. gaederopus, notably implement the present knowledge on the Mediterranean spiny oysters, whose under-evaluated ecological role should be carefully considered.

Human Monocyte-Derived Dendritic Cells Are the Pharmacological Target of the Immunosuppressant Flavonoid Silibinin.

Silibinin, a natural polyphenolic flavonoid, is known to possess anti-inflammatory, anticancer, antioxidant, and immunomodulatory properties. However, the effects of Silibinin on the maturation and immunostimulatory functions of human dendritic cells (DC) remain to be elucidated. In this study, we have attempted to ascertain whether Silibinin influences the maturation, cytokine production, and antigen-presenting capacity of human monocyte-derived DC. We show that Silibinin significantly suppresses the upregulation of costimulatory and MHC molecules in LPS-stimulated mature DC and inhibits lipopolysaccharide (LPS)-induced interleukin (IL)-12, IL-23, and TNF-α production. Furthermore, Silibinin impairs the proliferation response of the allogenic memory CD4 T lymphocytes elicited by LPS-matured DC and their Th1/Th17 profile. These findings demonstrate that Silibinin displays immunosuppressive activity by inhibiting the maturation and activation of human DC and support its potential application of adjuvant therapy in the treatment of autoimmune diseases.

Therapeutic Outcomes and Clinical Features of Advanced Non-Small Cell Lung Cancer Carrying KRAS Mutations: A Multicenter Real-life Retrospective Study.

INTRODUCTION: Targeting Kirsten Rat Sarcoma (KRAS) has been deemed impossible for long time, but new drugs have recently demonstrated promising results. Evidence on the outcome of KRAS-mutant advanced-NSCLC treated with new standard regimens are still scarce. Thus, we aimed at assessing the incidence and clinical impact of KRAS mutations in a real-life population of advanced-NSCLC, exploring the prognostic significance of distinct alterations. MATERIALS AND METHODS: The present multicenter retrospective study, conducted by 5 Italian Centers from January 2018 to February 2020, involved 297 advanced KRAS mutant NSCLC. Complete clinico-pathological data were evaluated. RESULTS: Out of 297 patients, 130 carried KRAS_G12C mutation, while 167 presented with mutations other than G12C. Within KRAS_non-G12C group, 73%, 16.8% and 8.9% harboured G12X, codon 13 and Q61H alterations, respectively. No significant differences in survival outcome and treatment response were documented according to KRAS_G12C versus non-G12C, nor KRAS_G12C versus G12X versus other mutations. On univariate analysis ECOG PS, number and sites of metastatic lesions and PD-L1 status significantly impacted on survival. A clear trend towards worse prognosis was apparent in chemotherapy-treated patients, while immunotherapy-based regimens were associated to prolonged survival. Investigating the outcome of PD-L1 ≥ 50% population, we did not detect any significant difference between KRAS_G12C and non-G12C subsets. CONCLUSION: Here, we report on real-life data from a large retrospective cohort of advanced NSCLC harbouring KRAS alterations, with particular attention to G12C mutation. Our study offers useful clues on survival outcome, therapeutic response and clinico-pathological correlations in KRAS-mutant setting, especially in the upcoming era of KRAS G12C targeting therapy.

Anti-Inflammatory Effects of 1,25(OH)2D/Calcitriol in T Cell Immunity: Does Sex Make a Difference?

Hypovitaminosis D is involved in various inflammatory, infectious and autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Moreover, the active form of vitamin D, calcitriol, has been shown to modulate the immune response, playing an anti-inflammatory effect. However little is known about the mechanisms underlying this anti-inflammatory effect and the potential sex differences of calcitriol immune regulation. Hence, the aim of this study was to investigate whether calcitriol could act differently in modulating T cell immunity of age-matched male and female healthy donors. We analyzed the effects of calcitriol in T lymphocytes from healthy women and men on the expression levels of the vitamin D receptor (VDR) and pro- and anti-inflammatory cytokine production. We showed that a treatment with calcitriol induced a significant increase in the VDR expression levels of activated T lymphocytes from male and female healthy subjects. Moreover, we found that calcitriol significantly reduced the expression level of pro-inflammatory cytokines IL-17, INF-γ and TNF-α in the T lymphocytes of both sexes. Notably, we observed that calcitriol induced a significant increase in the expression level of anti-inflammatory cytokine IL-10 only in the T lymphocytes from female healthy donors. In conclusion, our study provides new insights regarding the sex-specific anti-inflammatory role of calcitriol in T cell immunity.

Multicenter Observational Study on Metastatic Non-Small Cell Lung Cancer Harboring BRAF Mutations: Focus on Clinical Characteristics and Treatment Outcome of V600E and Non-V600E Subgroups.

INTRODUCTION: BRAF mutation involved 2-4% of lung adenocarcinoma. Differences in clinicopathologic features and patient outcome exist between V600E and non-V600E BRAF mutated NSCLC. Thus, we sought to assess the frequency and clinical relevance of BRAF mutations in a real-life population of advanced-NSCLC, investigating the potential prognostic significance of distinct genetic alterations. MATERIALS AND METHODS: The present multicenter Italian retrospective study involved advanced BRAF mutant NSCLC. Complete clinicopathologic data were evaluated for BRAF V600E and non-V600E patients. RESULTS: A total of 44 BRAFmut NSCLC patients were included (V600E, n = 23; non-V600E, n = 21). No significant differences in survival outcome and treatment response were documented, according to V600E vs. non-V600E mutations, although a trend towards prolonged PFS was observed in the V600E subgroup (median PFS = 11.3 vs. 6.0 months in non-V600E). In the overall population, ECOG PS and age significantly impacted on OS, while bone lesions were associated with shorter PFS. Compared to immunotherapy, first-line chemotherapy was associated with longer OS in the overall population, and especially in the BRAF V600E subtype. CONCLUSIONS: Here, we report on real-life data from a retrospective cohort of advanced-NSCLC harboring BRAF alterations. Our study offers relevant clues on survival outcome, therapeutic response, and clinicopathologic correlations of BRAF-mutant NSCLC.

The Natural Estrogen Receptor Beta Agonist Silibinin as a Promising Therapeutic Tool in Diffuse Large B-cell Lymphoma.

BACKGROUND/AIM: About 40% of patients with diffuse large cell lymphoma (DLBCL) still have a poor prognosis. Additionally, DLBCL patients treated with doxorubicin are at risk of cardiac failure. Growing evidence suggests an antitumor and cardioprotective activity exerted by estrogen via its binding to estrogen receptor (ER) ß. The aim of this study was to evaluate the anticancer activity of the phytoestrogen silibinin, an ERß selective agonist, on DLBCL growth, and its potential cardioprotective effect. MATERIALS AND METHODS: DLBCL cell lines SUDHL-8, SUDHL-6, and RIVA were used. The anti-tumor activity of silibinin was also evaluated in vivo in NOD/SCID/IL2Rg-/- (NSG) xenografted mice. AC16 human ventricular cardiomyocytes were used to investigate the cardioprotective effects of silibinin. RESULTS: In vitro silibinin induced apoptosis and autophagy, and blocked tumor cell proliferation, also protecting AC16 cardiomyocytes from doxorubicin-induced toxicity. In vivo silibinin induced cell death and autophagy, and reduced tumor volume. CONCLUSION: Silibinin represents a promising therapeutic tool.