Factors correlating with circulating T-zone-like cells of undetermined significance (TZUS) in dogs resident in Italy.

T-zone-like cells of undetermined significance (TZUS) share the same phenotypic pattern (CD45-CD5+) with T-zone lymphoma cells and were first described a few years ago in the peripheral blood (PB) of healthy aged American Golden retrievers (GR). History of bladder and eye disease increased the odd of circulating TZUS in the American GR population. Since differences among dogs may exist according to the geographical region of origin, herein we screened 489 PB samples to assess potential factors predisposing to the presence of circulating TZUS in dogs living in Italy. Overall, TZUS were found in 174 (35.6%) samples. Among 83 clinical variables, significant associations emerged with sex, age, diagnosis of neoplasia, history of neoplasia, history of infectious or parasitic disease, history of osteoarticular disease, presence of traumatic lesions or foreign bodies, and lymphocytes count. Only age and history of neoplasia retained significance at multivariate analysis (p=0.019 and p=0.036, respectively). Thus, older age and history of neoplasia are the main factors associated with circulating TZUS in Italian dogs. Future studies should focus on elucidating the biological role of TZUS and determining reproducible criteria for their identification, distinguishing them from infiltrating TZL.

Occupational health and psychological wellbeing in first line nurses during health crisis periods: reliability study of the SOIC tool.

Background: In 2020, the emergence of the new Coronavirus has put health professionals under enormous pressure, as they had to work in difficult and often disadvantaged situations. Prevention of symptoms such as stress, anxiety and burnout therefore become important health management goals. Aim: The aim of this pilot cross-sectional study was to assess the reliability and feasibility of a tool on Occupational Health Nurses after a Pandemic Period such as the COVID-19 pandemic (Salute Oc-cupazionale negli Infermieri in Periodo Pandemico Covid19 - SOIC) that aims to assess the occupational health and psychological wellbeing of nurses during periods of health crisis. Methods: This study was conducted from September to November 2022. The SOIC tool is composed by two preliminary sections and a third part including five validated questionnaires (measuring burnout, work engagement, psychological symptoms, resilience, and mindful awareness). An opportunistic sample of 202 nurses working in a Teaching Hospital of Rome and members of NurSind union were invited to participate: of these, 24 nurses completed the SOIC in two subsequent occasions (T1 and T2). Results: The test-retest assessment showed no differences between the two waves (T1 and T2) in terms of median scores for all questionnaires included in the SOIC tool. The Cronbach alphas, considering all items of each questionnaire included in the SOIC tool, showed good or excellent internal consistencies. Conclusion: The test-retest assessments and the reliability analyses encouraged the usability of the SOIC tool. Furthermore, consistent associations between the five questionnaires were obtained.

Sub-Lethal Concentrations of Graphene Oxide Trigger Acute-Phase Response and Impairment of Phase-I Xenobiotic Metabolism in Upcyte® Hepatocytes.

The impact of graphene oxide on hepatic functional cells represents a crucial evaluation step for its potential application in nanomedicine. Primary human hepatocytes are the gold standard for studying drug toxicity and metabolism; however, current technical limitations may slow down the large-scale diffusion of this cellular tool for in vitro investigations. To assess the potential hepatotoxicity of graphene oxide, we propose an alternative cell model, the second-generation upcyte® hepatocytes, which show metabolic and functional profiles akin to primary human hepatocytes. Cells were acutely exposed to sub-lethal concentrations of graphene oxide (≤80 µg/ml) for 24 h and stress-related cell responses (such as apoptosis, oxidative stress, and inflammatory response) were evaluated, along with a broad investigation of graphene oxide impact on specialized hepatic functions. Results show a mild activation of early apoptosis but not oxidative stress or inflammatory response in our cell model. Notably, while graphene oxide clearly impacted phase-I drug-metabolism enzymes (e.g., CYP3A4, CYP2C9) through the inhibition of gene expression and metabolic activity, conversely, no effect was observed for phase-II enzyme GST and phase-III efflux transporter ABCG2. The GO-induced impairment of CYP3A4 occurs concomitantly with the activation of an early acute-phase response, characterized by altered levels of gene expression and protein production of relevant acute-phase proteins (i.e., CRP, Albumin, TFR, TTR). These data suggest that graphene oxide induces an acute phase response, which is in line with recent in vivo findings. In conclusion, upcyte® hepatocytes appear a reliable in vitro model for assessing nanomaterial-induced hepatotoxicity, specifically showing that sub-lethal doses of graphene oxide have a negative impact on the specialized hepatic functions of these cells. The impairment of the cytochrome P450 system, along with the activation of an acute-phase response, may suggest potential detrimental consequences for human health, as altered detoxification from xenobiotics and drugs.

Impact of nursing students on the quality of care perceived by patients: a systematic review of the literature.

OBJECTIVE: The quality assessment process, based on customer satisfaction, is fundamental in the delivery of the best care services. This is most evident in care settings where trainee students are allowed to assist the patients. The purpose of this review is to clarify whether nursing students have an impact on patients' assessment of the quality of their nursing care. MATERIALS AND METHODS: A systematic literature search was carried out using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines in six databases: PubMed, CINAHL, Cochrane, Web of Science, Scopus, and PsycInfo. Two co-authors independently screened titles, abstracts, and full-text articles, following explicit exclusion and inclusion criteria. Analyses included non-randomized and non-homogeneous samples, involving both selected patients and methods for assessing their satisfaction. RESULTS: After full-text screening, 30 articles were identified, but only 11 were considered pertinent to the topic of the review. The trainee-patient relationship is based on mutual help and can improve the patient experience and trainee learning. The instruments used to measure perceived quality were found to be valid and reliable. CONCLUSIONS: The studies under review show high levels of satisfaction among patients when nursing care is delivered through training, particularly when the patients who agree to be treated by nursing trainees have previous experience of hospitalization and relationships with trainees. Educational background and the empathy and communication skills of both professional nurses and trainees influence patients' perception of the quality of care and their satisfaction with it.

Küntscher nails with static cement spacer: A simple technique in periprosthetic knee infections with massive bone loss and instability.

BACKGROUND: Two-stage revision for periprosthetic knee infection is challenging in cases of massive bone loss and instability. The present study aims to describe our experience with an alternative technique of reinforced cement spacer, usually necessary in these situations, focusing on its advantages and clinical results. METHODS: We retrospectively identified all patients who underwent a two-stage revision for periprosthetic knee infection using two intramedullary Küntscher nails as reinforcement from January 2010 to September 2018. From each medical record, we extracted the type of explanted prosthesis, isolated micro-organism, number of cement spacers before index procedure (and related episodes of spacer dislocation) and final treatment. RESULTS: Twelve patients were identified, mean age of 64.0 years (range 39-85). In four of them, the reinforced spacer was used twice for persistent infection, with a total of 16 procedures performed and no cases of dislocation. Ten patients were finally treated with reimplantation or arthrodesis with intramedullary nails, whereas an above-knee amputation was necessary for two patients. Infection was eradicated in 10 patients out of 12 (83%) at a mean follow up of 34.3 months (range 10-62). CONCLUSIONS: This technique is an effective alternative to traditional spacers in cases of massive bone loss, producing a mechanically stable joint and preserving adequate tissue tensions. The construct is technically easy to perform and, not less importantly, to remove during stage 2. Further studies, with larger groups, are necessary to determine its validity.

Flow Cytometric Characterization of S-phase Fraction and Ploidy in Lymph Node Aspirates from Dogs with Lymphoma.

Canine lymphoma is a multifaceted disease encompassing numerous entities with different prognosis. Objective assessment of the proliferation rate is of importance from the pathological and clinical perspectives. Different methods have been described in the literature to assess proliferation rate, including evaluation of Ki67 expression in fresh lymph node (LN) aspirates measured by flow cytometry (FC). This test has a high accuracy in discriminating between low- and high-grade lymphomas, and provides prognostic information among high-grade B-cell lymphomas. DNA content analysis is less expensive and suitable for well-preserved samples. We describe DNA-content analysis using LN aspirates from 112 dogs with lymphoma. S-phase fraction (SPF) accurately discriminated between low- and high-grade lymphomas, with 3.15% being the best discriminating cut-off value. SPF values strongly correlated with Ki67 expression as assessed by FC. Survival analyses were restricted to 33 dogs with high-grade B-cell lymphoma receiving standardized multi-agent chemotherapy, but no significant result was obtained for SPF. We also describe a subset of aneuploid cases and their respective follow-up. We conclude that DNA content analysis may be combined with morphological examination of LN aspirates to improve the objectivity in lymphoma subtype classification in dogs. Further studies are needed to assess the possible prognostic role of SPF and ploidy status within specific lymphoma subtypes in dogs.

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016.

OBJECTIVES: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. METHODS: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. RESULTS: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/µL [interquartile range (IQR) 169-521 cells/µL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1-5.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93-4.39; P < 0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75-0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40-0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91-0.99; P = 0.02). CONCLUSIONS: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy.

Health self-perception in patient with Crohn's disease: a web survey.

BACKGROUND: Crohn's Disease (CD) has an incidence on the physical and psychological autonomy of the patient, such as to alter their daily life. The impact of the disease on the daily life of the patients is related to the symptoms and complications of the disease. Patient autonomy and participation in social and work life are the goals that nurses must reach for patients with CD to improve their quality of life. AIM: To measure the perception of the health of people with a diagnosis of CD. METHOD: Review of the literature on PubMed, and internet sites. Administration on the web of the standardised questionnaire Short Form Health Survey (SF-12). RESULTS: A total of 228 patients with CD completed valid questionnaires and were enrolled. The SF-12 questionnaire scores make it possible to build a physical health index (PCS) with a median value of 36,10 (min 33,8; max 42,4) and mental health index (MCS) with a median value of 36,04 (min 28.5; max 38,4). There were statistically significant data related to the achievement of the degree with median 41.9 (min 35,1; max 48,4) compared to non-graduates with a p<0.001 and in relation to the employment level (median 37.9 min/max 34,7/46,7) compared to unemployed and inactive with a p = 0.03. CONCLUSION: Despite the inevitable complications of the disease (intestinal and extra-intestinal symptoms), most of our sample did not exhibit significant physical limitations (surgical intervention, stomach packaging which generally causes a decrease in libido in both male and female patients ). The nurse cares for a patient with CD must have not only technical skills and specialist skills, but a holistic vision of the patient. Despite some findings in this study, this research orientation deserves more attention.

Loss of CD45 cell surface expression in canine T-zone lymphoma results from reduced gene expression.

Canine T-zone lymphoma (TZL) is a peculiar lymphoma subtype characterized by an indolent clinical course and aberrant CD45-negative phenotype, commonly recognized by flow cytometry (FC). Recent studies have described clinical presentation and behavior, but to date the mechanisms behind the loss of CD45 protein expression have never been investigated. The aims of this study were: 1) to confirm the absence of CD45 in canine TZL via the concomitant use of FC and immunohistochemistry with two different sources of antibody; and 2) to investigate the amount of CD45 transcript and the presence of CD45 gene in the neoplastic cells of dogs affected by TZL. 57 lymph node aspirates were included in the present study: 40 (70.2%) TZLs, 7 (12.3%) high grade T-cell lymphomas and 10 (17.5%) reactive lymph nodes. Neoplastic cells and normal T-cells were isolated from TZL and reactive lymph nodes, respectively, via cell sorting. Immunohistochemistry was performed on 2 TZL, 2 reactive lymph nodes and 2 Peripheral T-cell Lymphomas. Total RNA and genomic DNA were extracted from lymph-nodes aspirates. Two different quantitative real-time PCR experiments were designed, to determine the amount of the CD45 transcript and of the corresponding gene fragment. All TZL cases were negative for CD45 at immunohistochemistry. CD45 transcript amount was significantly lower in TZL compared to controls (p<0.001). This difference was not significant (p=0.584) for CD45 DNA load, that was similar between TZL and controls. Moreover, CD45 transcript amount was inversely correlated with the percentage of neoplastic cells in each TZL sample (p=0.010). These results confirm that CD45 protein is lacking on cell surface irrespective of the technique and antibody source adopted. This phenotypic aberrancy is apparently due to the absence of gene transcription, as CD45 DNA was present, whereas CD45 transcript was virtually absent in the neoplastic cells. The data here reported support further studies investigating possible factors impairing CD45 gene transcription.

Prognostic significance of Ki67 evaluated by flow cytometry in dogs with high-grade B-cell lymphoma.

Ki67 can discriminate between high- and low-grade canine lymphomas, but its prognostic role in specific subtypes of the neoplasm is unknown. We assessed the prognostic significance of Ki67% (percentage of Ki67-positive cells), evaluated by flow cytometry, in 40 dogs with high-grade B-cell lymphoma, treated with a modified Wisconsin-Madison protocol (UW-25). The following variables were investigated for association with lymphoma specific survival (LSS) and relapse free interval (RFI): Ki67%, breed, sex, age, stage, substage, complete remission (CR). By multivariate analysis, Ki67% (P = 0.009) and achievement of CR (P = 0.001) were independent prognostic factors for LSS. Dogs with intermediate Ki67% (20.1-40%) presented longer LSS and RFI (median = 866 and 428 days, respectively) than dogs with low (median = 42 days, P < 0.001; median = 159 days, P = 0.014) or high (median = 173 days, P = 0.038; median = 100 days, P = 0.126) values. Determination of Ki67 is a prognostic tool that improves the clinical usefulness of flow cytometric analysis in canine high-grade B-cell lymphoma.

Chronic lymphocytic leukemia transformation into high-grade lymphoma: a description of Richter's syndrome in eight dogs.

Richter's syndrome (RS) is the development of an aggressive lymphoma in patients with chronic lymphocytic leukaemia (CLL). In humans, RS occurs in 2-20% of CLL, which transform into diffuse large B-cell lymphoma but reports in dogs are scarce. This study retrospectively describes eight dogs with CLL progressing into RS. A database including 153 dogs with CLL (93T CD8+ and 55 B-CLL) was interrogated and RS was demonstrated in eight cases (representing 5.2% of total CLL): two with T-cell (2.2% of T CLL) and six with a B-cell immunophenotype (10.9% of B-CLL). When RS occurred, lymphocytes were decreased compared to CLL. Five dogs had anaemia and two dogs thrombocytopenia. Frequent clinical signs included lymph node swelling, coughing, vomiting, neurological signs and weight loss. Independently from the therapy, RS was associated with a short survival (median 41 days). RS should be considered as an unfavourable evolution in canine CLL.

Identification of a suitable internal control for fluorescence analysis on canine peripheral blood samples.

Reliable detection of fluorescence intensity (FI) by flow cytometry (FC) is fundamental. FI depends on instrument settings and sample processing procedures: thus, measurements should be done using internal controls with known FI. Commercially available beads-based standards are expensive, thus reducing their usability in the veterinary practice. Cell subsets with stable mean FI (MFI) within the population have been proposed as acceptable surrogates in human medicine. In veterinary medicine, no data exist about stability of antigen expression among different subjects or upon sample storage. The aim of the present study was to evaluate MFI variability of main lymphocytes antigens among the lymphoid cells within each subject, among different subjects, and upon 24-h storage, in order to identify the antigen most suitable as stable internal control in MFI analyses. Peripheral blood samples from 18 healthy dogs were analysed by FC within 3h from sampling to assess the expression of CD3, CD5, CD4, CD8, CD21 and cyCD79b using conjugated monoclonal antibodies. Analyses were restricted to the lymphoid population. Fluorescent microbeads were added to each tube, and antigen MFI was calculated as Relative Fluorescence Intensity RFI (CD/beads). Fluorescence histogram CV (fhCV) for each CD was regarded as an index of the variability of expression among lymphocytes within each subject (cell-to-cell variability); whereas the CV of RFI was regarded as an index of inter-subjects variability (dog-to-dog variability). In 11 cases, FC analyses were repeated after 24h storage at 4°C and RFI and CVs of fresh and stored samples were compared to assess variability linked to storage. CD4 was identified as the best antigen to be used as an internal control for MFI analyses in canine peripheral blood samples because of low cell-to-cell and dog-to-dog variability, and optimal stability upon 24-h storage. Blood samples from a second group of 21 healthy dogs were labelled only with CD4, in order to assess the influence of breed, sex and age on the expression of CD4 in a larger case series. Based on univariate GLMs, none of these variables influenced CD4 RFI. Normalizing fluorescence data using lymphoid CD4 MFI as a reference would improve the comparison of results obtained by different laboratories, patients or times in diagnostic and research analyses of FI. Further studies are needed to confirm our results with different FC approaches.

Canine small clear cell/T-zone lymphoma: clinical presentation and outcome in a retrospective case series.

Published studies, taken together, suggest the existence of a single canine lymphoma entity, with a small clear cell appearance by cytological evaluation, a histopathological T-zone pattern and an aberrant CD45-negative T-cell phenotype, mostly characterized by long-term survival. We describe clinical presentation and outcome in a retrospective case series of canine small clear cell/T-zone lymphoma. Despite the reported predisposition of Golden retriever, this breed was not represented in our case series. Most dogs presented with stage V disease, whereas only few had clinical signs or peripheral cytopenias. Blood was almost always more infiltrated than bone marrow. Median survival confirmed the favourable prognosis described in literature, but a few dogs died within a short time. Also, a subgroup of dogs developed second malignancies, eventually leading to death. We did not investigate possible prognostic factors because of the wide variety in treatments, and further studies are needed to identify high-risk animals.

Flow cytometric evaluation of ki67 for the determination of malignancy grade in canine lymphoma.

Ki67 is a nuclear antigen significantly correlated with degree of malignancy in human non-Hodgkin lymphomas. We wanted to assess the ability of flow cytometric evaluation of Ki67 index (Ki67I) in differentiating the grade of malignancy in canine lymphomas. Ki67I was determined on lymph node aspirates of 90 immunophenotyped lymphomas classified according to the updated Kiel classification: 80 high grade (HG, 62 B cell and 18 T cell) and 10 low grade (LG, 3 B cell and 7 T cell) lymphomas. HG lymphomas showed significantly higher Ki67I compared with LG lymphomas (P < 0.0001). A significant difference in HG lymphomas was detected between B- and T-immunophenotypes. Receiver operating characteristic (ROC) curve highlighted a high accuracy of Ki67I in recognizing HG lymphomas [area under the curve (AUC) = 99.4] and a cut-off value of 12.2% was established (sensitivity = 96.3% and specificity = 100%). Thus, we suggest the combination of Ki67I flow cytometric determination and immunophenotype as a reliable tool to classify canine lymphomas.

Flow-cytometric detection of phenotypic aberrancies in canine small clear cell lymphoma.

Histopathology and immunohistochemistry are mandatory to solve the differential between canine low-grade lymphoma and reactive hyperplasia. However, clinicians and owners often show reluctance toward these invasive tests. However, molecular biology techniques are still not sensitive and specific enough to be regarded as a reliable tool for final diagnosis. In humans, flow cytometry (FC) allows a definitive diagnosis of T-cell lymphoma based on high prevalence of antigen aberrancies. We describe here the immunophenotype of 26 cases of suspect canine small-clear cell lymphoma, determined by multi-colour FC. All cases showed antigen aberrancies and therefore neoplasia was always confirmed. As a consequence, we argue that the combined use of cytology and FC allows solving the differential diagnosis between small clear cell lymphoma and non-neoplastic reactive conditions when histopathology is not available. Further studies are needed to establish if any aberrancy can be considered indicative of specific histotypes.

CD44 in canine leukemia: analysis of mRNA and protein expression in peripheral blood.

Hyaluronan receptor CD44 mediates interaction between cells and extracellular matrix. The expression of standard form and its variants is dysregulated in human leukemias and is associated with metastasis and prognosis. The aim of this work is the evaluation of CD44 mRNA and protein expression in canine leukemia. Peripheral blood from 20 acute leukemias (AL) (10 acute lymphoblastic, 6 acute myeloid and 4 acute undifferentiated leukemias), 21 chronic lymphocytic leukemias (CLL) and thirteen healthy dogs were collected. The mRNA expression of all CD44 variants presenting exons 1-5 and/or 16-20 (CD44_ex1-5 and CD44_ex16-20) and CD44 protein were determined by real-time RT-PCR and flow cytometry, using the mean fluorescent index (MFI), respectively. CD44 MFI was significantly higher in leukemic samples compared to controls and a higher expression was found in AL in respect with CLL. No significant differences were found when considering different phenotypic subtypes of AL and CLL. CD44_ex1-5 mRNA expression was significantly higher in AL compared to controls, whereas there was no difference in CLL compared to controls and AL. CD44_es16-20 showed the same trend, but without differences among groups. The high CD44 expression found in canine leukemias could be considered a step toward the definition of their molecular features.

Effect of a long-term oral l-arginine supplementation on glucose metabolism: a randomized, double-blind, placebo-controlled trial.

AIM: This study assessed the efficacy of long-term l-arginine (l-arg) therapy in preventing or delaying type 2 diabetes mellitus. METHODS: A mono-centre, randomized, double-blind, parallel-group, placebo-controlled, phase III trial (l-arg trial) was conducted on 144 individuals affected by impaired glucose tolerance (IGT) and metabolic syndrome (MS). l-Arg/placebo was administered (6.4 g/day) on a background structured lifestyle intervention for 18 months plus a 12-month extended follow-up period after study drug termination. Fasting glucose levels and glucose tolerance after oral glucose tolerance test were evaluated throughout the study. RESULTS: After 18 months, l-arg as compared with placebo did not reduce the cumulative incidence of diabetes [21.4 and 20.8%, respectively, hazard ratio (HR), 1.04; 95% confidence interval (CI), 0.58-1.86] while the cumulative probability to become normal glucose tolerant (NGT) increased (42.4 and 22.1%, respectively, HR, 2.60; 95% CI, 1.51-4.46, p < 0.001). The higher cumulative probability to become of NGT was maintained during the extended period in subjects previously treated with l-arg (HR, 3.21; 95% CI, 1.87-5.51; p < 0.001). At the end of the extended period, the cumulative incidence of diabetes in subjects previously treated with l-arg was reduced as compared with placebo (27.2 and 47.1%, respectively, HR, 0.42; 95% CI, 0.24-0.75, p < 0.05). During both periods, l-arg significantly improved insulin sensitivity and ß-cell function. CONCLUSION: Among persons with IGT and MS, the supplementation of l-arg for 18 months does not significantly reduce the incidence of diabetes but does significantly increase regression to NGT.

Modulating mesenchymal stromal cell function with cholesterol synthesis inhibitors.

There is increasing evidence that statins, inhibitors of 3-hydroxyl-3-methylglutaryl coenzyme A reductase, can effectively be used not only in the treatment of hypercholesterolemia, but also in other human disorders; indeed, statins have strong anti-inflammatory and immunomodulatory effects, so that they can influence the onset and outcome of inflammation and autoimmunity. On the other hand, it has been shown that statins can affect growth and survival of solid tumour and leukemic cells, thus they have been proposed in the treatment of neoplasias as multiple myeloma, in association with drugs, as thalidomide, known to act on the cancer microenvironment. In the current view, tumor microenvironment include many cell types that interact with tumor cells: among them, stromal and endothelial cells, macrophages and dendritic cells, the various types of lymphocytes such as NK cells, B and T cells. The interplay between all these cell populations, and the balance between these, determines whether there is a tumour cell growth promotion or inhibition. In haematological malignancies, such as multiple myeloma, chronic lymphocytic and myeloid leukemias and follicular lymphomas, the survival, drug-resistance and proliferation of leukemic cells have been shown to be largely dependent on a supportive microenvironment, so that some cellular components of it, mainly mesenchymal stromal cells, cancer associated fibroblasts and macrophages, are now proposed as targets of new therapies. Herein, we analyze the effects that statins can exert on cancer cells, stromal cells and human natural killer cells, to discuss whether they can be proposed as anti-cancer drugs.

MF-59 adjuvant influence on the functions of gammadelta T cells in HIV-1+ adults immunized with influenza seasonal vaccine.

INTRODUCTION: We previously reported that in HIV-1 infected patients circulating Vdelta1 T lymphocytes (Vdelta1) increase and proliferate in vitro in response to Candida albicans (Ca). Herein, we analysed the effects of MF59 adjuvant on the Vdelta1 T cell responses to hemagglutinin (HA) and Ca in HIV-1 seropositive and seronegative adults after influenzal vaccine, to clarify th molecular mechanisms triggered in vivo by an adjuvanted vaccine against influenza virus. MATERIALS AND METHODS: 58 seropositive (HIV-1+) and 48 seronegative (HIV-1-) subjects received influenzal vaccines containing or not the MF59 adjuvant. The follow-up of in vitro T cell proliferation and cytokine production (IL-17A, IL-22, IL-23, IL-6) to HA and Ca antigens were performed at different time points (at basal time and after 30 and 90 days from vaccination) by cytofluorimetric approaches. RESULTS: We confirmed that in HIV-1 infected individuals the Vdelta1 T cell subset is expanded in HIV-1 infected individuals and moreover the number of circulating Vdelta1 Tcells significantly enhanced in all HIV-1+ subjects on day 90 after influenza vaccination. Regard the follow-up of proliferative responses, the increments of CD3+ response to HA and Vdelta1 T cells to Ca in HIV-1+ individuals were detectable earlier on day 30 for MF59-vaccinated patients, instead on day 90 post-vaccination in HIV(+)-vaccinated without MF59 adjuvant. Of note, production of lL-17A and IL-22, two cytokines with anti-fungal activity, in response to Ca was enhanced (for IL-17A) or restored (for IL-22) by vaccination in HIV-1+ donors, mainly using the MF59-adjuvanted vaccine. Moreover, after vaccination IL-23 and IL-6 production increased in response to HA in the HIV+ and HIV- groups vaccinated with MF59 adjuvant. CONCLUSIONS: We suggest that in HIV-1 infected patients the circulating Vdelta1 T lymphocytes reactive to Ca upon challenge with influenza virus vaccine receive an activating/enhancing signal mediated by cytokines triggered by the boost with HA antigen particularly in presence of MF59 adjuvant.

Early stratification of patients with chest pain and suspected acute coronary syndrome in the Emergency Department.

AIM: The aim of this study was to investigate the accuracy of a critical pathway in the early stratification and management of patients with chest pain and suspected acute coronary syndrome (ACS) in the Emergency Department (ED). METHODS: An observational study was performed enrolling all patients with non-traumatic chest pain and suspected ACS who presented during a one-year period in the ED, where a critical pathway with five-level risk stratification, based on risk factors, characteristics of pain and ECG, was implemented. Patients were prospectively evaluated for rates of death, unstable angina, myocardial infarction or revascularization procedure occurring during admission or in the 30 days following discharge from the ED. Receiver-Operating Characteristics (ROC) curve was used to measure the accuracy of the stratification method. RESULTS: Overall, 1813 patients were enrolled: 475 patients (26.1%, 95% CI: 24.0-28.1 ) were admitted and 1338 (73.8%, 95% CI: 71.7-75.8) were discharged. Main outcomes occurred in 233 (49.9%, 95% CI: 47.5-52.2) of patients admitted and in 6 (0.4%, 95% CI: 0.06-0.7) of those discharged. The risk stratification system showed a good accuracy with an AUC-ROC curve of 0.90 (95% CI: 0.88-0.93). A total of 1541 (85%) patients were managed according to critical pathway. Adverse events were significantly fewer in patients discharged according to pathway criteria than in those who were not (0.27% vs. 1.37%, difference: 1.1% CI 95%: 0.06-2.1), without significant increase of inappropriate admissions. CONCLUSION: A critical pathway, based on clinical and ECG features, is a safe and accurate tool to stratify and manage the patients with non-traumatic chest pain and suspected ACS in the ED.