Search

Simple Summary IDH1/2 mutations are a common event in acute myeloid leukemia (AML) and represent a therapeutic target. We designed the GIMEMA AML1516 observational protocol to examine the prevalence of IDH1/2 mutations and the associations between IDH mutations and clinico-biological parameters in a cohort of Italian patients affected by AML. By analyzing 284 consecutive adult AML patients, we confirmed that IDH1 and IDH2 mutations are frequently detected-14% and 18%, respectively-at diagnosis. IDH1/2 mutations were significantly associated with an inferior performance status and non-complex karyotype when compared to IDH1/2-WT. With regards to the outcome, in the subset of IDH1/2-mutated patients the rate of complete remission achievement was 60.5% and overall survival at 2 years was 44.5%: these percentages did not significantly differ from IDH1/2-WT patients. However, given the availability of IDH1/2 inhibitors, it is important to recognize IDH1/2-mutated cases up-front to offer patients the most appropriate therapeutic strategy. IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19-86). Of these, 38 (14%) harbored IDH1 and 51 (18%) IDH2 mutations. IDH1/2 mutations were significantly associated with WHO PS >2 (p < 0.001) and non-complex karyotype (p = 0.021) when compared to IDH1/2-WT. Furthermore, patients with IDH1 mutations were more frequently NPM1-mutated (p = 0.007) and had a higher platelet count (p = 0.036). At relapse, IDH1/2 mutations were detected in 6 (25%) patients. As per the outcome, 60.5% of IDH1/2-mutated patients achieved complete remission; overall survival and event-free survival at 2 years were 44.5% and 36.1%, respectively: these rates were similar to IDH1/2-WT. In IDH1/2-mutated patients, high WBC proved to be an independent prognostic factor for survival. In conclusion, the GIMEMA AML1516 confirms that IDH1/2 mutations are frequently detected at diagnosis and underlines the importance of recognizing IDH1/2-mutated cases up-front to offer the most appropriate therapeutic strategy, given the availability of IDH1/2 inhibitors.

Rare tumours such as penile carcinoma have been largely neglected by the urology scientific community in favour of more common — and, therefore, more easily fundable — diseases. Nevertheless, penile cancer represents a rising burden for health-care systems around the world, because a lack of widespread expertise, ineffective centralization of care and absence of research funds have hampered our ability to improve the global care of these patients. Moreover, a dichotomy has arisen in the field of penile cancer, further impeding care: the countries that are mainly supporting research on this topic through the development of epidemiological studies and design of clinical trials are not the countries that have the highest prevalence of the disease. This situation means that randomized controlled trials in developed countries often do not meet the minimum accrual and are intended to close before reaching their end points, whereas trials are almost completely absent in those areas with the highest disease prevalence and probability of successful recruitment, such as Africa, South America and South Asia. The scientific and organizational inaction that arises owing to this mismatch translates into a burdensome cost for our patients. A global effort to gather experts and pull together scientific data from around the world may be the best way to boost clinical research, to change clinical practice and, ultimately, to improve care for patients and their families., Penile cancer is a growing health-care concern worldwide. Despite its rarity, penile cancer has a disproportionate impact on some countries, as the location with the highest incidences are invariably those with low resources and few registries or trials. In this Perspective, the authors discuss how global collaboration and centralization of care can help to improve management of penile cancer worldwide, but especially in areas where resources are limited.

Fil: Pedernera, Tomas Ezequiel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mendoza. Instituto Argentino de Nivologia, Glaciologia y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivologia, Glaciologia y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivologia, Glaciologia y Ciencias Ambientales; Argentina

The 2017 version of the European LeukemiaNet (ELN) recommendations, by integrating cytogenetics and mutational status of specific genes, divides patients with acute myeloid leukemia into 3 prognostically distinct risk categories: favorable (ELN2017-FR), intermediate (ELN2017-IR), and adverse (ELN2017-AR). We performed a post hoc analysis of the GIMEMA (Gruppo Italiano Malattie EMatologiche dell’Adulto) AML1310 trial to investigate the applicability of the ELN2017 risk stratification to our study population. In this trial, after induction and consolidation, patients in complete remission were to receive an autologous stem cell transplant (auto-SCT) if categorized as favorable risk or an allogeneic stem cell transplant (allo-SCT) if adverse risk. Intermediate-risk patients were to receive auto-SCT or allo-SCT based on the postconsolidation levels of measurable residual disease as measured by using flow cytometry. Risk categorization was originally conducted according to the 2009 National Comprehensive Cancer Network recommendations. Among 500 patients, 445 (89%) were reclassified according to the ELN2017 criteria: ELN2017-FR, 186 (41.8%) of 455; ELN2017-IR, 179 (40.2%) of 445; and ELN2017-AR, 80 (18%) of 455. In 55 patients (11%), ELN2017 was not applicable. Two-year overall survival (OS) was 68.8%, 51.3%, 45.8%, and 42.8% for the ELN2017-FR, ELN2017-IR, ELN2017-not classifiable, and ELN2017-AR groups, respectively (P < .001). When comparing the 2 different transplant strategies in each ELN2017 risk category, a significant benefit of auto-SCT over allo-SCT was observed among ELN2017-FR patients (2-year OS of 83.3% vs 66.7%; P = .0421). The 2 transplant procedures performed almost equally in the ELN2017-IR group (2-year OS of 73.9% vs 70.8%; P = .5552). This post hoc analysis of the GIMEMA AML1310 trial confirms that the ELN2017 classification is able to accurately discriminate patients with different outcomes and who may benefit from different transplant strategies. This trial was registered as EudraCT number 2010-023809-36 and at www.clinicaltrials.gov as #NCT01452646.

This essay proposes an overview of the digital tools designed and developedby the EMoBookTrade project team to investigate the economic and legalframework of the late Renaissance and early Baroque European book mar-ket. In particular it illustrates the structure of the two databases developedto cross-reference the evolution of book prices in conjunction with the devel-opment of the system of book privileges. The article proposes a model forusers and developers interested in pursuing big-data-oriented investigationsin the field of book history with a focus on the economy of the book market.

We aimed to assess differences in the summer excess of mortality by COVID-19 history using data from the mortality and COVID-19 surveillances. We found 4% excess risk in 2022 summer, compared to 2015-2019. A mortality rate ratio of 1.59 (95%CI 1.39-1.82) for COVID-19 survivors compared to naïve, was found. Both were higher in people aged ≥75 years. During the July heat wave, the excess for COVID-19 survivors decreased and disappeared when excluding people living in nursing homes.Funding statementThis study was partially supported by the Italian Ministry of Health –CCM 2020 - “Sorveglianza epidemiologica e controllo del COVID-19 in aree urbane metropolitane e per il contenimento della circolazione del Sars-CoV-2 nella popolazione immigrata in Italia” and by the Ricerca Corrente 2023Highlightsthe excess of mortality in COVID-19 survivors is not exacerbated by heatwavesan excess of mortality during the whole summer in COVID-19 survivors aged over 75 suggest that no harvesting effect is appreciable in the older population that survived COVID-19For COVID-19 survivors aged over 75, a lower mortality than the naïve population was observed only during the July heat wave when we stratified by residency

Many efforts to persuade others politically employ interpersonal conversations. A recurring question is whether participants in such conversations are more readily persuaded by others who share their demographic characteristics (e.g., race). Echoing broader concerns that Americans have difficulties communicating across differences, research finds that individuals perceive demographically similar people as more trustworthy, suggesting shared demographics could facilitate persuasion. In a survey of practitioners and scholars, we find many share these expectations. However, dual-process theories suggest that messenger attributes are typically peripheral cues which should not influence persuasion when individuals are effortfully thinking, such as during interpersonal conversations. Supporting this view, we analyze data from eight experiments on interpersonal conversations across four topics (total N = 6,139) and find that shared demographics (age, gender, or race) do not increase their effects. These results are encouraging for the scalability of interpersonal conversation interventions, and suggest Americans are capable of persuading each other across difference.