Risk Stratification in Older Intensively Treated Patients With AML

\ua9 2024 by American Society of Clinical Oncology.PURPOSE AML is a genetically heterogeneous disease, particularly in older patients. In patients older than 60 years, survival rates are variable after the most important curative approach, intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HCT). Thus, there is an urgent need in clinical practice for a prognostic model to identify older patients with AML who benefit from curative treatment. METHODS We studied 1,910 intensively treated patients older than 60 years with AML and high-risk myelodysplastic syndrome (HR-MDS) from two cohorts (NCRIAML18 and HOVON-SAKK). The median patient age was 67 years. Using a random survival forest, clinical, molecular, and cytogenetic variables were evaluated in an AML development cohort (n = 1,204) for association with overall survival (OS). Relative weights of selected variables determined the prognostic model, which was validated in AML (n = 491) and HR-MDS cohorts (n = 215). RESULTS The complete cohort had a high frequency of poor-risk features, including 2022 European LeukemiaNet adverse-risk (57.3%), mutated TP53 (14.4%), and myelodysplasia-related genetic features (65.1%). Nine variables were used to construct four groups with highly distinct 4-year OS in the (1) AML development, (2) AML validation, and (3) HR-MDS test cohorts ([1] favorable: 54% \ub1 4%, intermediate: 38% \ub1 2%, poor: 21% \ub1 2%, very poor: 4% \ub1 1%; [2] 54% \ub1 9%, 43% \ub1 4%, 27% \ub1 4%, 4% \ub1 3%; and [3] 54% \ub1 10%, 33% \ub1 6%, 14% \ub1 5%, 0% \ub1 3%, respectively). This new AML60+ classification improves current prognostic classifications. Importantly, patients within the AML60+ intermediate- and very poor-risk group significantly benefited from allo-HCT, whereas the poor-risk patients showed an indication, albeit nonsignificant, for improved outcome after allo-HCT. CONCLUSION The new AML60+ classification provides prognostic information for intensively treated patients 60 years and older with AML and HR-MDS and identifies patients who benefit from intensive chemotherapy and allo-HCT

The effect of interventions on Twitter in four target groups using different measures of influence

In this paper, the influence of interventions on Twitter users is studied. We define influence in (a) number of participants, (b) size of the audience, (c) amount of activity, and (d) reach. Influence is studied for four different target groups: (a) politicians, (b) journalists, (c) employees and (d) the general public. Furthermore, two types of interventions are studied: (a) by all Twitter users (i.e., uncontrolled interventions), and (b) those tweeted by an organization that benefits from any resulting influence (i.e., controlled interventions). As a case study, tweets about a large Dutch governmental organization are used. Results show a relation between the number of uncontrolled interventions and influence in all four target groups, for each of the defined types of influence. Controlled interventions show less influence: significant influence was found for the general public, but influence for politicians and employees was only mildly significant, and no influence was found for journalists. The effect found for uncontrolled interventions, however, suggests that this influence is indeed reachable for some target groups, even when the number of interventions is small, and very well reachable for all target groups, provided the number of interventions is large enough. In addition to this, we found that interventions influence groups to a different extent. Own employees were influenced strongest, differing significantly from the other groups. © 2014, Springer-Verlag Wien

Bekalking en toevoegen van nutriënten; evaluatie van de effecten op de vitaliteit van het bos; een veldonderzoek naar boomgroei

Dit rapport doet verslag van een deelonderzoek uit de Evaluatie van effectgerichte maatregelen in multifunctionele bossen 2004-2005 en is gericht op de effecten van de maatregelen bemes-ting en bekalking in bossen als overbruggingsmaatregel in het kader van het Overlevingsplan Bos en Natuur (OBN). In dit rapport worden de effecten besproken van de EGM maatregelen bekalking en mineralengiften (`bemesting¿) op de groei en vitaliteit van de bosopstanden aan de hand van aanwasboringen. Enerzijds valt het op dat er in de 4 of 5 jaar na behandeling zowel bij bekalking bij `bemesting¿ meestal geen verandering in boomgroei is opgetreden. Groeiverbe-tering na behandeling trad alleen op kleine schaal (een beperkt deel van de gemeten bomen) op in een beperkt aantal opstanden. Anderzijds is het ook opmerkelijk dat er meestal geen sprake was van slechte boomgroei in de periode die aan de uitvoering van bekalking of `bemes-ting¿ voorafging. Uitgaand van de aanname dat een toegenomen groei van de bomen een goe-de indicatie geeft voor een verbetering van de vitaliteit, zou dit betekenen dat er in de behan-delde bossen over het algemeen geen (grote) vitaliteitsproblemen waren en dat de groei en vi-taliteit door de behandeling bekalking of `bemesting¿ daarom ook niet zodanig is verbeterd dat dit aantoonbaar was. Er worden een aantal aanbevelingen voor vervolgonderzoek gedaan in oude bemestingsproefvelden

von Willebrand factor propeptide in vascular disorders: A tool to distinguish between acute and chronic endothelial cell perturbation

Before de novo synthesized von Willebrand factor (vWF) leaves the endothelial cell, it undergoes endoproteolytic cleavage of its propeptide (vW antigen II). The processed vWF and propeptide are either released constitutively or, following activation of the endothelium, released through the regulated pathway. In a recent study (Borchiellini et al, Blood 88:2951, 1996), we showed that the half-life of mature vWF and of its propeptide differ fourfold to fivefold. We postulated that the molar ratio of the propeptide to mature vWF could serve as a tool to assess the extent of endothelial cell activation under physiologic and clinical conditions. To test this hypothesis, we measured mature vWF and propeptide in patients with documented acute and chronic vascular disease, including patients with thrombotic thrombocytopenic purpura (TTP), acute septicemia, and diabetes mellitus. These data were compared with experimental conditions in healthy subjects in which perturbation of the endothelium was simulated by physical exercise or by administration of 1-deamino-8-D-arginine vasopressin (DDAVP) or endotoxin. In all individuals of the latter study group, both vWF and propeptide levels were elevated during the acute phase of the experimentally induced vascular perturbation; at later time points after stimulation, only vWF levels remained elevated. In patients with sepsis and TTP, both vWF and propeptide were elevated several-fold. Thus, this pattern can readily be explained in terms of acute perturbation of the endothelium. In contrast, in patients with diabetes mellitus propeptide levels were only slightly elevated, whereas vWF levels were elevated twofold to threefold. This pattern is a typical feature of chronic, low-grade activation of the endothelium. These observations support our hypothesis that measurement of both propeptide and vWF levels allows to discriminate between chronic and acute phases of endothelial cell activation in vivo. Measurement of only vWF is less indicative in this respec

Fishualization: a group feedback display

In this contribution1 we present a novel psychological intervention that maps human computer activity to a group feedback device on the basis of a combination of various types of unobtrusive, low-level sensors. The goal is to enable employees to gain insights into their working habits, to reduce stress levels and increase productivity. The unique approach taken is a social feedback board (fishualization), which gives collective feedback to employees of an entire department to stimulate social interactions, group awareness and openness, which are all beneficial for well-being at work. Fishualization is set up with a reconfigurable and modular approach to visualization and reasoning components to allow future additions and improvements