Exploring the immune-checkpoint inhibitors' efficacy/tolerability in special non-small cell lung cancer (NSCLC) populations: Focus on steroids and autoimmune disease

The advent of immune-checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis, both as monotherapy and in combination strategies, produced a paradigm change of the treatment algorithm for metastatic, non-oncogene addicted, non-small cell lung cancer (NSCLC) patients. Although the great efficacy and the optimal tolerability emerging from clinical studies has been confirmed for the majority of patients treated in the real-word scenario, however the potential activity and safety profile of these agents in uncommon NSCLC populations remains still controversial. Particularly, patients with previously diagnosed autoimmune disease or concomitant steroids treatment at the time of immunotherapy initiation represent two special subgroups of patients not unusual in the real-word practice, to whom the clinical implication of immune-checkpoint inhibitors administration is largely unknown. In this review we provided an updated literature overview, summarizing available evidence and reporting practical suggestions, which may guide physicians in their clinical management of these NSCLC sub-populations

Qualitative analysis of determinants of measles, mumps, rubella vaccine uptake in European parents

Background Parental concerns about measles, mumps and rubella (MMR) vaccination negatively influence decision to vaccinate their children, this leading to the recently reported vaccine coverage drop in Europe. The ESCULAPIO project, funded by the Italian National Centre for Disease Prevention and Control of the Ministry of Health (CCM), is investigating the main factors underlying decisions on vaccinations, in order to implement targeted campaigns and plan effective strategies. Methods A systematic literature review was carried out on studies describing the determinants underlying MMR vaccination uptake in European parents. Results A total of 45 studies were included in the analysis. The most common factors related with MMR vaccine uptake were knowledge, beliefs, perceptions on vaccines and diseases, reported in 44,4% of the articles. Parents showed doubts on vaccine efficacy, safety, side effects, while in other studies positive beliefs and perceptions were reported. Attitudes/ behaviours were often determinants of the uptake as well as demographic factors (40%). While higher no. of children in the household, lower income, temporary or lacking employment, and non-regular marital status were generally a barrier for vaccination, education level and house tenure were contradictory. Information source/advice and influence or trust of other people, institutions, media were often reported (31,1% and 17,8% respectively), but a clear direction was not showed. Conclusions These preliminary findings showed that communication strategies should provide parents with clear messages on vaccines and preventable infectious diseases, in order to build right knowledge and create correct beliefs and behaviours. Communication should be addressed mainly to more disadvantaged, larger and non-regular families. A quantitative analysis is been currently carrying out and will provide more information on the direction of the effect of the different factor

Epigenetic therapies for heart failure: Current insights and future potential

Despite the current reductionist approach providing an optimal indication for diagnosis and treatment of patients with heart failure with reduced ejection fraction (HFrEF), there are no standard pharmacological therapies for heart failure with preserved ejection fraction (HFpEF). Although in its infancy in cardiovascular diseases, the epigenetic-based therapy (“epidrugs”) is capturing the interest of physician community. In fact, an increasing number of controlled clinical trials is evaluating the putative beneficial effects of: 1) direct epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a possible indirect epigenetic interference, eg, metformin, statins, sodium glucose transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial has reported a reduction in first HF hospitalization (any EF value) and cardiovascular death in patients with type 2 diabetes and recent acute coronary syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF seem to benefit from supplementation to the standard therapy with statins, metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, the vasodilator hydralazine, with or without isosorbide dinitrate, did not provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk of incident HF and mortality in affected patients whereas clinical trials based on statins provided mixed results. Furthermore, PUFAs diet supplementation was significantly associated with reduced cardiovascular risk in both HFpEF and HFrEF. Future large trials will reveal whether direct and indirect epitherapy will remain a work in progress or become a useful way to customize the therapy in the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent advancement in the epitherapy as a possible way to improve personalized therapy of HF

Non-Markovian dynamics of interacting qubit pair coupled to two independent bosonic baths

The dynamics of two interacting spins coupled to separate bosonic baths is studied. An analytical solution in Born approximation for arbitrary spectral density functions of the bosonic environments is found. It is shown that in the non-Markovian cases concurrence "lives" longer or reaches greater values.Comment: 13 page

49Cr: Towards full spectroscopy up to 4 MeV

The nucleus 49Cr has been studied analysing gamma-gamma coincidences in the reaction 46Ti(alpha,n)49Cr at the bombarding energy of 12 MeV. The level scheme has been greatly extended at low excitation energy and several new lifetimes have been determined by means of the Doppler Shift Attenuation Method. Shell model calculations in the full pf configuration space reproduce well negative-parity levels. Satisfactory agreement is obtained for positive parity levels by extending the configuration space to include a nucleon-hole either in the 1d3/2 or in the 2s1/2 orbitals. A nearly one-to-one correspondence is found between experimental and theoretical levels up to an excitation energy of 4 MeV. Experimental data and shell model calculations are interpreted in terms of the Nilsson diagram and the particle-rotor model, showing the strongly coupled nature of the bands in this prolate nucleus. Nine values of K(pi) are proposed for the levels observed in this experiment. As a by-result it is shown that the values of the experimental magnetic moments in 1f7/2 nuclei are well reproduced without quenching the nucleon g-factors.Comment: 13 pages, 8 figure

The plants, rituals and spells that 'cured' helminthiasis in Sicily

<p>Abstract</p> <p>Background</p> <p>The author reports on the plants, rituals and spells used against worms and the so-called <it>scantu </it>(fright) in some areas of Sicily. The work is based on ethnobotanical research carried out, prevalently, between 2002-2006, in some areas of Eastern, South-Eastern, North-Central and South-Central Sicily.</p> <p>Methods</p> <p>This research is based on dialogue. Senior 'healers' were contacted; furthermore, doctors, teachers, farmers and in general 'experts' with herbs and 'magic' rituals. Information was collected about the way the plants of folk medicine are prepared. The interviewees were also invited to recite prayers and spells against helminthiasis.</p> <p>Results</p> <p>The author has highlighted the importance of how, in some parts of Sicily, some ailments like helminthiasis and other correlated pathologies like <it>scantu </it>are 'treated' and, especially within the rural social classes, by folk medicine remedies, herbal practises, particular prayers, rituals and spells.</p> <p>Conclusion</p> <p>As regards health/illness, it should be noted that in the last ten years conventional medicine has provided very satisfactory results even resolving potentially mortal pathologies. However, in certain social classes, there is no real collaboration between conventional and folk medicine; so for some senior citizens, the 'healer' with his rituals and empirical and magical herbs is still the person to turn to for the 'cure' of particular ailments. Interest in these practises from ancestral heritage in an advanced country like Italy, is only relevant if the aim is to recoup a cultural identity which is already in decline.</p> <p>It is significant to report a piece: on 14 October 2007 the news on a well-known national Italian TV channel reported an interview with a 94 year-old man from Arbatax (Sardinia) referred to as a 'healer' because both his townspeople and others from all over the world go to him for his cures. He is not paid except in kind and has been known to cure St. Anthony's fire, burns, scalding and marine fungal infections, by smearing his saliva over the infected part and reciting 'special words'.</p

Pathological characterization of tumor immune microenvironment (Time) in malignant pleural mesothelioma

SIMPLE SUMMARY: Tumor immune microenvironment is an important structural component of malignant pleural mesothelioma that contributes to disease growth support and progression. Its study and pathological characterization are important tools to find new biomarkers for advanced therapeutic strategies. ABSTRACT: Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13–15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients’ genetic predisposition and tumor genomic profile. The chronic inflammatory response to asbestos fibers leads to a unique tumor immune microenvironment (TIME) composed of a heterogeneous mixture of stromal, endothelial, and immune cells, and relative composition and interaction among them is suggested to bear prognostic and therapeutic implications. TIME in MPM is known to be constituted by immunosuppressive cells, such as type 2 tumor-associated macrophages and T regulatory lymphocytes, plus the expression of several immunosuppressive factors, such as tumor-associated PD-L1. Several studies in recent years have contributed to achieve a greater understanding of the pathogenetic mechanisms in tumor development and pathobiology of TIME, that opens the way to new therapeutic strategies. The study of TIME is fundamental in identifying appropriate prognostic and predictive tissue biomarkers. In the present review, we summarize the current knowledge about the pathological characterization of TIME in MPM

Lower All-Cause Mortality Risk in Females and Males with Peripheral Artery Disease following Pain-Free Home-Based Exercise: A 7-Year Observational Study

We evaluated the sex-specific difference in response upon participation in an exercise program with respect to the risk of adverse clinical outcomes among patients with peripheral artery disease (PAD) and claudication. The records of 400 PAD patients were assessed between 2012 and 2015. Two hundred of them were addressed to a walking program prescribed at the hospital and executed at home at symptom-free walking speed (Ex), while the remaining 200 acted as a control group (Co). The number and date of deaths, all-cause hospitalizations, and amputations for a 7-year period were collected from the regional registry. At baseline, no differences were observed (MEX n = 138; FEX n = 62; MCO n = 149; FCO n = 51). The 7-year survival rate was significantly higher in FEX (90%) than in MEX (82% hazard ratio, HR: 0.542 95% CI 0.331–0.885), FCO (45%, HR: 0.164 95% CI 0.088–0.305), and MCO (44%; HR: 0.157 95% CI 0.096–0.256). A significantly lower rate of hospitalization (p &lt; 0.001) and amputations (p = 0.016) was observed for the Ex group compared to the Co group, without differences by sex. In conclusion, in PAD patients, active participation in a home-based pain-free exercise program was associated with a lower rate of death and better long-term clinical outcomes, particularly among women

Survival and clinical outcomes of diabetic peripheral artery disease patients following a pain-free homebased walking program

Aim: We retrospectively examined the impact on the rate of survival of pain-free home-based exercise in diabetic peripheral artery disease patients compared to patients receiving usual care. Methods: In total, 202 patients at Fontaine's Stage II with diabetes were studied. Half were enrolled in a structured home-based exercise program (E), whereas the other half received walking advice as the active control group (C). Long-term clinical outcomes at five years were gathered from the Emilia-Romagna Health Service Registry, with survival probability selected as the primary outcome. Results: At baseline, the two groups did not differ for any demographic or clinical characteristics. High adherence to the program was recorded in Group E (88% of home-walking sessions executed, with an average distance walked during the program of 174 km). After five years, a survival rate of 90% for Group E and 60% for Group C was observed, with a significantly (P &lt; 0.001) higher mortality risk for Group C [Hazard ratio (HR) = 3.92]. Additionally, among secondary outcomes, Group E showed a significantly (P = 0.048) lower rate of peripheral revascularizations than Group C (15% vs. 24%, respectively; HR = 1.91), all-cause hospitalizations (P = 0.007; 61% vs. 80%, HR = 1.58), and amputations (P = 0.049; 6% vs. 13%, HR = 2.47). In a Cox multivariate-proportional regression model of the entire population, the predictors of survival probability were age (HR = 1.05), Charlson index (HR = 1.24), lower ankle-brachial index (HR = 6.66), and control group (HR = 4.99). Conclusion: A simple sustainable program aimed at improving mobility of diabetic patients with claudication at high cardiovascular risk was associated with better survival and long-term clinical outcomes

Potential clinical benefits of cell therapy in coronary heart disease: an update

Cell therapy is a central issue of regenerative medicine and is raising a growing interest in the scientific community, but its full therapeutic potential in coronary heart disease (CHD) has not been reached yet. Several different methods, cell types, delivery routes, and supporting techniques have been attempted and improved to elicit cardiac regeneration in CHD, but only some of them showed a really convincing potential for the use in clinical practice. Here we provide an update on approaches and clinical trials of cell therapy applied to CHD, which are ongoing or that have been realized in the last 5 years. Moreover, we discuss the evidence collected so far in favor or against the validity of stem cell therapy for CHD. In particular, we review and comment the recent advances in cell therapy applied to CHD, the most promising cell types, delivery strategies, biochemical and engineering techniques that have been adopted in this context