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The lysine-specific histone demethylase 1 A (LSD1) is involved in antitumor immunity; however, its role in shaping CD8 + T cell (CTL) differentiation and function remains largely unexplored. Here, we show that pharmacological inhibition of LSD1 (LSD1i) in CTL in the context of adoptive T cell therapy (ACT) elicits phenotypic and functional alterations, resulting in a robust antitumor immunity in preclinical models in female mice. In addition, the combination of anti-PDL1 treatment with LSD1i-based ACT eradicates the tumor and leads to long-lasting tumor-free survival in a melanoma model, complementing the limited efficacy of the immune or epigenetic therapy alone. Collectively, these results demonstrate that LSD1 modulation improves antitumoral responses generated by ACT and anti-PDL1 therapy, providing the foundation for their clinical evaluation., (© 2024. The Author(s).)

Objective: Diagnosis of cancer is challenging in primary care due to the low incidence of cancer cases in primary care practice. A prolonged diagnostic interval may be due to doctor, patient or system factors, or may be due to the characteristics of the cancer itself. The objective of this study was to learn from Primary Care Physicians' (PCP) experiences of incidents when they had failed to think of, or act on, a cancer diagnosis., Design: A qualitative, online survey eliciting PCP narratives. Thematic analysis was used to analyse the data., Setting and Subjects: A primary care study, with narratives from 159 PCPs in 23 European countries., Main Outcome Measures: PCPs' narratives on the question 'If you saw this patient with cancer presenting in the same way today, what would you do differently?, Results: The main themes identified were: thinking broadly; improvement in communication and clinical management; use of other available resources and 'I wouldn't do anything differently'., Conclusion (implications): To achieve more timely cancer diagnosis, PCPs need to provide a long-term, holistic and active approach with effective communication, and to ensure shared decision-making, follow-up and continuing re-assessment of the patients' clinical conditions.

Background: While primary care physicians (PCPs) play a key role in cancer detection, they can find cancer diagnosis challenging, and some patients have considerable delays between presentation and onward referral., Aim: To explore European PCPs' experiences and views on cases where they considered that they had been slow to think of, or act on, a possible cancer diagnosis., Design & Setting: A multicentre European qualitative study, based on an online survey with open-ended questions, asking PCPs for their narratives about cases when they had missed a diagnosis of cancer., Method: Using maximum variation sampling, PCPs in 23 European countries were asked to describe what happened in a case where they were slow to think of a cancer diagnosis, and for their views on why it happened. Thematic analysis was used to analyse the data., Results: A total of 158 PCPs completed the questionnaire. The main themes were as follows: patients' descriptions did not suggest cancer; distracting factors reduced PCPs' cancer suspicions; patients' hesitancy delayed the diagnosis; system factors not facilitating timely diagnosis; PCPs felt that they had acted wrongly; and problems with communicating adequately., Conclusion: The study identified six overarching themes that need to be addressed. Doing so should reduce morbidity and mortality in the small proportion of patients who have a significant, avoidable delay in their cancer diagnosis. The 'Swiss cheese' model of accident causation showed how the themes related to each other., (Copyright © 2023, The Authors.)

Patients with schizophrenia spectrum disorders have a higher prevalence and frequency of smoking rates when compared to the rest of the population; to this, it must be added that they develop a greater dependence and have some worse health consequences than the general population. This is qualitative research on the perception of smoking in healthcare professionals assigned to psycho-rehabilitation programs for patients with schizophrenia spectrum disorders. The point of view of health personnel (Psychologists, Psychiatrists, Pedagogists, and Nurses) about cigarette smoking in these patients was analyzed, focusing on their implications in disturbance and comparing them with e-cigarettes too. The methodology used to collect the data was a semi-structured interview with five questions. The research path was carried out in two assisted therapeutic communities that are clinics for the rehabilitation of serious mental illness in the period between November and July 2022. The results showed that the opinion of health professionals on smoking is very negative. Research has also shown that nearly all patients are smokers; however, their high grade of addiction is caused by periods of high stress due to various factors that lead patients to consume a greater number of cigarettes. Almost all respondents have a positive opinion of the e-cigarette, which was defined as an excellent substitute for traditional cigarettes.

We prospectively evaluated changes in cardiac and hepatic iron overload (IO) and in morpho-functional cardiac parameters and myocardial fibrosis by magnetic resonance imaging (MRI) in patients with low-risk and intermediate-1-risk myelodysplastic syndromes (MDS). Fifty patients enrolled in the Myocardial Iron Overload in MyElodysplastic Diseases (MIOMED) study were followed for 12 months. IO was quantified by the T2* technique and biventricular function parameters by cine images. Macroscopic myocardial fibrosis was detected by late gadolinium enhancement technique. Twenty-eight patients (71.89±8.46 years; 8 females) performed baseline and follow-up MRIs. Thirteen patients had baseline hepatic IO, with a higher frequency among transfusion-dependent patients. Out of the 15 patients with a baseline MRI liver iron concentration <3 mg/g/dw, two (non-chelated) developed hepatic IO. Thirteen (46.4%) patients had an abnormal T2* value in at least one myocardial segment. One patient without hepatic IO and non-transfused had baseline global T2* <20 ms. Among the 15 patients with no baseline myocardial IO (MIO), 2 worsened. There was a significant increase in both left and right ventricular end-diastolic volume indexes. Thirty-six percent of patients showed myocardial fibrosis correlating with aging. Two new occurrences were detected at the follow-up. In conclusion, by a more sensitive segmental approach, MIO is quite frequent in MDS patients and it can be present also in non-transfused patients and in absence of detectable hepatic iron. The incidence of cardiac and hepatic IO and of myocardial fibrosis and the increase in biventricular volumes after a 12-month interval suggest performing periodic MRI scans to better manage MDS patients.

Background: The causes and effects of genotypic heterogeneity in beta-thalassemia major (β-TM) have not been fully investigated. The aim of this multicentre study was to determine whether different genotype groups could predict the development of cardiovascular magnetic resonance abnormalities and cardiac complications., Materials and Methods: We considered 708 β-TM patients (373 females, age 30.05±9.47 years) consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network. Data were collected from birth to the first cardiac magnetic resonance scan. Myocardial iron overload was assessed using a T2* technique. Biventricular function was quantified by cine images. Macroscopic myocardial fibrosis was evaluated by a late gadolinium enhancement technique., Results: Three groups of patients were identified: β + homozygotes (n=158), β + /β° heterozygotes (n=298) and β° homozygotes (n=252). Compared to β + homozygotes, the other two groups showed a significantly higher risk of myocardial iron overload and left ventricular dysfunction. We recorded 90 (13.0%) cardiac events: 46 episodes of heart failures, 38 arrhythmias (33 supraventricular, 3 ventricular and 2 hypokinetic) and 6 cases of pulmonary hypertensions. β° homozygotes showed a significantly higher risk than β + homozygotes of arrhythmias and cardiac complications considered globally., Discussion: Different genotype groups predicted the development of myocardial iron overload, left ventricular dysfunction, arrhythmias and cardiac complications in β-TM patients. These data support the importance of genotype knowledge in the management of β-TM patients.

We prospectively assessed by magnetic resonance imaging (MRI) the advantages of desferrioxamine (DFO) with respect to the absence of chelation therapy in non transfusion-dependent thalassaemia (NTDT) patients. We considered 18 patients non-chelated and 33 patients who received DFO alone between the two MRI scans. Iron overload was assessed by the T2* technique. Biventricular function parameters were quantified by cine sequences. No patient treated with DFO had cardiac iron. At baseline, only one non-chelated patient showed a pathological heart T2* value (< 20 ms) and he recovered at the follow-up. The percentage of patients who maintained a normal heart T2* value was 100% in both groups. A significant increase in the right ventricular ejection fraction was detected in DFO patients (3.48 ± 7.22%; P = 0.024). The changes in cardiac T2* values and in the biventricular function were comparable between the two groups. In patients with hepatic iron at baseline (MRI liver iron concentration (LIC) ≥ 3 mg/g/dw), the reduction in MRI LIC values was significant only in the DFO group (- 2.20 ± 4.84 mg/g/dw; P = 0.050). The decrease in MRI LIC was comparable between the groups. In conclusion, in NTDT patients, DFO therapy showed no advantage in terms of cardiac iron but its administration allowed an improvement in right ventricular function. Moreover, DFO reduced hepatic iron in patients with significant iron burden at baseline.

Collaborative and multicenter studies permit a large number of patients to be enrolled within a reasonable time and providing the opportunity to collect different data. Informatics platforms play an important role in management, storage, and exchange of data between the participants involved in the study. In this article, we describe a modular informatics platform designed and developed to support collaborative and multicenter studies in cardiology. In each developed module, data management is implemented following local defined protocols. The modular characteristic of the developed platform allows independent transfer of different kinds of data, such as biological samples, imaging raw data, and patients' digital information. Moreover, it offers safe central storage of the data collected during the study. The developed platform was successfully tested during a European collaborative and multicenter study, focused on evaluating multimodal non-invasive imaging to diagnose and characterize ischemic heart disease., (© The Author(s) 2015.)

Aims: Hybrid imaging provides a non-invasive assessment of coronary anatomy and myocardial perfusion. We sought to evaluate the added clinical value of hybrid imaging in a multi-centre multi-vendor setting., Methods and Results: Fourteen centres enrolled 252 patients with stable angina and intermediate (20-90%) pre-test likelihood of coronary artery disease (CAD) who underwent myocardial perfusion scintigraphy (MPS), CT coronary angiography (CTCA), and quantitative coronary angiography (QCA) with fractional flow reserve (FFR). Hybrid MPS/CTCA images were obtained by 3D image fusion. Blinded core-lab analyses were performed for CTCA, MPS, QCA and hybrid datasets. Hemodynamically significant CAD was ruled-in non-invasively in the presence of a matched finding (myocardial perfusion defect co-localized with stenosed coronary artery) and ruled-out with normal findings (both CTCA and MPS normal). Overall prevalence of significant CAD on QCA (>70% stenosis or 30-70% with FFR≤0.80) was 37%. Of 1004 pathological myocardial segments on MPS, 246 (25%) were reclassified from their standard coronary distribution to another territory by hybrid imaging. In this respect, in 45/252 (18%) patients, hybrid imaging reassigned an entire perfusion defect to another coronary territory, changing the final diagnosis in 42% of the cases. Hybrid imaging allowed non-invasive CAD rule-out in 41%, and rule-in in 24% of patients, with a negative and positive predictive value of 88% and 87%, respectively., Conclusion: In patients at intermediate risk of CAD, hybrid imaging allows non-invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

The aim of this study was to evaluate, in a large cohort of chronically transfused patients, whether the presence of extramedullary hematopoiesis (EMH) accounts for the typical patterns of cardiac iron distribution and/or cardiac function parameters. We retrospectively selected 1,266 thalassemia major patients who had undergone regular transfusions (611 men and 655 women; mean age: 31.3 ± 8.9 years, range: 4.2-66.6 years) and were consecutively enrolled within the Myocardial Iron Overload in Thalassemia network. The presence of EMH was evaluated based on steady-state free precession sequences; cardiac and liver iron overloads were quantified using a multiecho T2* approach; cardiac function parameters and pulmonary diameter were quantified using the steady-state free precession sequences; and myocardial fibrosis was evaluated using the late gadolinium enhancement technique. EMH was detected in 167 (13.2%) patients. The EMH+ patients had significantly lower cardiac iron overload than that of the EMH- patients (P = 0.003). The patterns of cardiac iron distribution were significantly different in the EMH+ and EMH- patients (P < 0.0001), with a higher prevalence of patients with no myocardial iron overload and heterogeneous myocardial iron overload and no significant global heart iron in the EMH+ group EMH+ patients had a significantly higher left ventricle mass index (P = 0.001) and a significantly higher pulmonary artery diameter (P = 0.002). In conclusion, in regularly transfused thalassemia patients, EMH was common and was associated with a thalassemia intermedia-like pattern of cardiac iron deposition despite regular transfusion therapy., (© 2015 Wiley Periodicals, Inc.)

Many fundamental biological processes are studied using the fission yeast, Schizosaccharomyces pombe. Here we report the construction of a set of 281 haploid gene deletion strains covering many previously uncharacterized genes. This collection of strains was tested for growth under a variety of different stress conditions. We identified new genes involved in DNA metabolism, completion of the cell cycle, and morphogenesis. This subset of nonessential gene deletions will add to the toolkits available for the study of biological processes in S. pombe., (Copyright © 2015 Chen et al.)