Tissue immune profile: a tool to predict response to neoadjuvant therapy in triple negative breast cancer

Abstract: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) can predict better survival outcomes in patients with early triple negative breast cancer (TNBC). Tumor infiltrating lymphocytes (TILs), Programmed Death-Ligand 1 (PD-L1), and Cluster of Differentiation 73 (CD73) are immune-related biomarkers that can be evaluated in the tumor microenvironment. We investigated if the contemporary expression of these biomarkers combined in a tissue immune profile (TIP) can predict pCR better than single biomarkers in TNBC. Tumor infiltrating lymphocytes (TILs), CD73 expression by cancer cells (CC), and PD-L1 expression by immune cells (IC) were evaluated on pre-NACT biopsies. We defined TIP positive (TIP+) as the simultaneous presence of TILS ≥ 50%, PD-L1 ≥ 1%, and CD73 ≤ 40%. To consider the effects of all significant variables on the pCR, multivariate analysis was performed. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used for model selection. We retrospectively analyzed 60 biopsies from patients with TNBC who received standard NACT. Pathological complete response was achieved in 23 patients (38.0%). Twelve (20.0%) cases resulted to be TIP+. The pCR rate was significantly different between TIP+ (91.7%) and TIP− (25.0%) (p < 0.0001). Using a multivariate analysis, TIP was confirmed as an independent predictive factor of pCR (OR 49.7 (6.30–392.4), p < 0.0001). Finally, we compared the efficacy of TIP versus each single biomarker in predicting pCR by AIC and BIC. The combined immune profile is more accurate in predicting pCR (AIC 68.3; BIC 74.5) as compared to single biomarkers. The association between TIP+ and pCR can be proposed as a novel link between immune background and response to chemotherapy in TNBC, highlighting the need to consider an immunological patients’ profile rather than single biomarkers

Full-length TrkB variant in NSCLC is associated with brain metastasis

Despite remarkable therapeutic advances have been made in the last few decades, non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies and in particular NSCLC. Brain-derived neurotrophic factor (BDNF), binding its high-affinity tyrosine kinase B receptor, has been shown to promote cancer progression and metastasis. We hereby investigated the expression of the BDNF and its TrkB receptor in its full-length and truncated isoform T1, in samples from primary adenocarcinomas (ADKs) of the lung and in their metastasis to evaluate if their expression was related to preferential tumor entry into the central nervous system (CNS). By immunohistochemistry, 80% of the ADKs that metastasize to central nervous system expressed TrkB receptor compared to 33% expressing of ADKs without CNS metastasis. Moreover, ADKs with CNS metastasis showed an elevated expression of the full-length TrkB receptor. The TrkB receptor FL/T1 ratio was statistically higher in primary ADKs with brain metastasis compared to ADKs without brain metastasis. Our data indicate that TrkB full-length isoform expression in primary ADK cells may be associated with higher risk to develop brain metastasis. Therefore, TrkB receptor may possess prognostic and therapeutic implications in lung ADK

A pilot study on the epidemiological status of Equine Infectious Anaemia, Equine Viral Arteritis, Glanders and Dourine in Turkey.

A serological investigation of equine infectious anaemia (EIA), equine viral arteritis (EAV), glanders, and dourine was conducted on the sera of 346 Turkish horses using a combination of tests in series (ELISA and agar gel immunodiffusion) for EIA, virus neutralisation for EAV, and complement fixation (CF) for glanders and dourine. Fortynine sera showed anticomplementary reactions and were not assessable in the CF test for glanders and dourine. No positive samples were detected for EIA, dourine, and glanders. Fifty-seven sera were positive for EAV. A systematic review of the distribution of these diseases in Turkey was conducted to describe their epidemiological status in the country. The serological results of this investigation confirm those of the published reports for EAV and glanders, whereas different results were reported for dourine and EIA. In fact, no previous data were found for dourine. Furthermore, all sera tested for EIA in the literature were negative, but 3 outbreaks were reported on an international official site in 2005 without details. Further studies and reports of the outbreaks are needed to better understand the real status of infections and the transmission of the diseases. The systematic review is a useful tool to improve the knowledge of public health disease in a country

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort.

Randomized trials and observational cohorts reported higher rates of virological suppression after highly active antiretroviral therapy (HAART) including efavirenz (EFV), compared with boosted protease inhibitors (PIs). Correlations with immunological and clinical outcomes are unclear. Patients of the Italian MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding outcome (composite outcome for success (COS)) was introduced. We evaluated predictors of COS (no AIDS plus CD4+ count >500/ mm3 plus HIV-RNA <500 copies/mL) and of eight single outcomes either at month 6 or at year 3. Multivariable logistic regression was conducted. There were 6259 patients selected. Patients on EFV (43%) were younger, had greater CD4+ count, presented with AIDS less frequently, and more were Italians. At year 3, 90% of patients had HIV RNA <500 copies/mL, but only 41.4% were prescribed EFV, vs. 34.1% prescribed boosted PIs achieved COS (p <0.0001). At multivariable analysis, patients on lopinavir/ritonavir had an odds ratio of 0.70 for COS at year 3 (p <0.0001). Foreign origin and positive hepatitis C virus-Ab were independently associated with worse outcome (OR 0.54, p <0.0001 and OR 0.70, p 0.01, respectively). Patients on boosted PIs developed AIDS more frequently either at month 6 (13.8% vs. 7.6%, p <0.0001) or at year 3 (17.1% vs. 13.8%, p <0.0001). At year 3, deaths of patients starting EFV were 3%, vs. 5% on boosted PIs (p 0.008). In this study, naïve patients on EFV performed better than those on boosted PIs after adjustment for imbalances at baseline. Even when virological control is achieved, COS is relatively rare. Hepatitis C virus-positive patients and those of foreign origin are at risk of not obtaining COS. Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Exploring the role of Emotional Intelligence on disorder eating psychopathology

Purpose: This study aims to explore the role of emotional intelligence (EI) and specific facets that may underpin the aetiology of disordered eating attitudes and behaviours, as a means to understand what aspects of these deficits to target within treatments. Methods: Participants were recruited from the UK and Ireland. Among the sample of 355 participants, 84% were women and 16% were men. Regarding age, 59% were between 18 and 29, 30% were between 30 and 49, and 11% were 50 or older. Using a cross-sectional design, participants completed the Schutte Self-Report Emotional Intelligence Test to measure levels of trait EI and The Eating Attitudes Test (EAT-26) as a measure of eating disorder risk and presence of disordered eating attitudes. Results: EAT-26 scores were negatively correlated with total EI scores and with the following EI subscales: appraisal of own emotions, regulation of emotions, utilization of emotions, and optimism. Also, compared to those without an eating disorder history, participants who reported having had an eating disorder had significantly lower total EI scores and lower scores on four EI subscales: appraisal of others emotions, appraisal of own emotions, regulation of emotions, and optimism. Conclusions: Considering these findings, EI (especially appraisal of own emotions, regulation of emotions, and optimism) may need to be addressed by interventions and treatments for eating disorders

Risk of Severe Non AIDS Events Is Increased among Patients Unable to Increase their CD4+ T-Cell Counts >200+/μl Despite Effective HAART

Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE)

Different healthy habits between northern and southern Spanish school children

Aim: Healthy habits are influenced by several factors such as, geographical location. The aims of this study were to describe and compare healthy habits within two populations of sixth-grade primary school children (aged 11-12 years) from Northern and Southern Spain. Subject and Methods: A cross-sectional study using two representative samples of school children was conducted. Participants came from Logroño (n=329), in the North and Granada (n=284), in the South of Spain. Socio-demographic and anthropometric variables, adherence to the Mediterranean diet, aerobic fitness, and healthy lifestyles were recorded. Results: Boys reported higher level of physical activity and aerobic fitness than girls (p=0.000). Southern school children reported significantly higher adherence to the Mediterranean diet (♀: p=0.041; ♂: p=0.008), and lower aerobic fitness (♀: p=0.000; ♂: p=0.042) and hours of nightly sleep (♀: p=0.008, ♂: p=0.007) than Northern school children. Southern boys also reported lower levels of physical activity (p=0.013). There were slight or moderate correlations among all habits measured (physical activity, diet, screen and sleep time). Additionally, physical activity level was inversely related to body mass index in Northern boys (p=0.020) and Southern girls (p=0.024). Conclusions: Results showed differences in physical activity, eating and sleep habits, and aerobic fitness, according to geographical location. The relationships found among lifestyle habits indicate the need of health promotion interventions nationally and considering the differences discussed here

Risk of Chronic Kidney Disease among Patients Developing Mild Renal Impairment during Tenofovir-Containing Antiretroviral Treatment

BACKGROUND: Tenofovir (TDF) can cause kidney injury through tubular dysfunction, with or without drop of estimated glomerular filtration rate (eGFR). Whether mild eGFR reductions during treatment should be considered a reason for prompt TDF discontinuation, however, remains unclear. METHODS: Patients with normal pre-TDF eGFR levels, who had developed mild renal impairment (i.e., two consecutive eGFR results between 89-60 ml/min) on TDF, were observed until onset of chronic kidney disease (CKD), defined as two eGFR<60 ml/min 3 to 6 months apart. Multivariable Poisson regression analysis was used to investigate whether outcome was associated with current and cumulative use of TDF (modeled as time-varying covariates). RESULTS: 2023 (29%) out of 6984 patients developed mild renal impairment on TDF. Among them, 191 progressed to CKD. The incidence of CKD did not significantly differ during TDF treatment (2.6 per 100 PYFU; 95%CI 2.2-3.2) or after its discontinuation (2.2 per 100 PYFU; 95%CI 1.8-2.6). However, the rate of CKD was significantly higher among patients continuing with TDF treatment compared to those who had discontinued it within 6 months of occurrence of mild renal impairment (aIRR 4, 95%CI 2.4-6.8). In contrast, among patients who had maintained TDF >6 months despite mild renal impairment, current TDF use was not associated with a significantly higher rate of CKD. Other significant predictors of CKD were older age, intravenous drug use, diabetes, hypertension, lower pre-TDF eGFR, higher eGFR drop since TDF introduction and longer exposure to TDF. CONCLUSIONS: Prompt discontinuation of TDF among patients developing mild renal impairment may prevent further progression of renal damag

Zinc-bound metallothioneins and immune plasticity: lessons from very old mice and humans

The capacity of the remodelling immune responses during stress (named immune plasticity) is fundamental to reach successful ageing. We herein report two pivotal experimental models in order to demonstrate the relevance of the immune plasticity in ageing and successful ageing. These two experimental models will be compared with the capacity in remodelling the immune response in human centenarians. With regard to experimental models, one model is represented by the circadian rhythms of immune responses, the other one is the immune responses during partial hepatectomy/liver regeneration (pHx). The latter is suggestive because it mimics the immunosenescence and chronic inflammation 48 h after partial hepatectomy in the young through the continuous production of IL-6, which is the main cause of immune plasticity lack in ageing. The constant production of IL-6 leads to abnormal increments of zinc-bound Metallothionein (MT), which is in turn unable in zinc release in ageing. As a consequence, low zinc ion bioavailability appears for thymic and extrathymic immune efficiency, in particular of liver NKT cells bearing TCR γδ. The remodelling during the circadian cycle and during pHx of zinc-bound MT confers the immune plasticity of liver NKT γδ cells and NK cells in young and very old mice, not in old mice. With regard to human centenarians and their capacity in remodelling the immune response with respect to elderly, these exceptional individuals display low zinc-bound MT associated with: a) satisfactory intracellular zinc ion availability, b) more capacity in zinc release by MT, c) less inflammation due to low gene expression of IL-6 receptor (gp130), d) increased levels of IFN-gamma and number of NKT cell bearing TCR γδ. Moreover, some polymorphisms for MT tested in PBMCs from human donors are related to successful ageing. In conclusion, zinc-bound MT homeostasis is fundamental to confer the immune plasticity that is a condition "sine qua non" to achieve healthy ageing and longevity

Prevalence of obesity in preschool Greek children, in relation to parental characteristics and region of residence

<p>Abstract</p> <p>Background</p> <p>The aim of this retrospective cohort study was to record the prevalence of overweight and obesity in relation to parental education level, parental body mass index and region of residence, in preschool children in Greece.</p> <p>Methods</p> <p>A total of 2374 children (1218 males and 1156 females) aged 1–5 years, stratified by parental educational level (Census 1999), were examined from 105 nurseries in five counties, from April 2003 to July 2004, Weight (kg) and height (cm) were obtained and BMI (kg/m²) was calculated. Both the US Centers for Disease Control (CDC) and the International Obesity Task Force (IOTF) methods were used to classify each child as "normal", "at risk of overweight" and "overweight". Parental demographic characteristics, such as age and educational level and parental anthropometrical data, such as stature and body weight, were also recorded with the use of a specifically designed questionnaire.</p> <p>Results</p> <p>The overall estimates of at risk of overweight and overweight using the CDC method was 31.9%, 10.6 percentage points higher than the IOTF estimate of 21.3% and this difference was significant (p < 0.001). Children with one obese parent had 91% greater odds for being overweight compared to those with no obese parent, while the likelihood for being overweight was 2.38 times greater for children with two obese parents in the multivariate model.</p> <p>Conclusion</p> <p>Both methods used to assess prevalence of obesity have demonstarted that a high percentage of the preschool children in our sample were overweight. Parental body mass index was also shown to be an obesity risk factor in very young children.</p