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BackgroundErythrocytes (RBCs) hold a crucial role in hemostasis and their integrity is influenced by different stimuli including circulating inflammatory mediators. Even though RBCs do not have nuclei and mitochondria, they have developed a process allowing them to undergo a rapid self-destruction named eryptosis. The exact mechanism of erythrocytes cell death is not fully clarified yet but it seems to involve Ca2+ and ceramide formation, leading to cell shrinkage and externalization of phosphatidylserine (PS) (1). Interaction between platelets and erythrocytes could participate in an increasing risk of thrombotic episodes typical of several diseases including antiphospholipid syndrome (APS). In fact, not only signals triggering eryptosis are involved in thrombosis activation, but also recent studies have demonstrated how PS-exposing erythrocytes are able to adhere to the vascular wall causing an impairment of circulation (2,3).ObjectivesEnhanced eryptosis is known to contribute to several pathological conditions (1) but the involvement of this process in APS has not been investigated yet. For this reason the aim of the study was to evaluate eryptosis levels in APS, healthy subjects positive for antiphospolipid antibodies without clinical manifestations (aPL carriers), autoimmune haemolytic anaemia (AIHA) and healthy donors (HD).Methods27 patients with primary APS (M/F 5/22, mean age 51.1±7.6 years), 14 aPL carriers (M/F 3/11, mean age 48.9±8.4 years) were recruited after written informed consent. Moreover 10 AIHA patients and 12 HD were also enrolled as positive and negative control group respectively. RBCs were isolated from whole blood after centrifugation and eryptosis levels were analysed by flow cytometry, evaluating the percentage of annexin V-positive cells (PS-exposing cells). Flow cytometry was also use to estimated cellular volume from forward scatter (FSC).ResultsAPS patients showed higher levels of eryptosis compared to HD (p=0.01). Interestingly, the percentage of annexin V-positive RBCs was lower in aPL carriers respect to APS patients (p=0.001). Moreover, an inverse correlation between RBCs volume and eryptosis was found in APS patients (r=-0.4, p=0.03). No clinical correlation between eryptosis and clinical manifestations were noticed. As expected, eryptosis was upregulated in AIHA patients compared to all populations studied (p<0.0001).ConclusionsOur study provides for the first time evidence of eryptosis enhancement in APS patients suggesting a possible contribution of RBCs apoptosis in the pathogenesis of the disease.References Lang E, Lang F. Triggers, inhibitors, mechanisms, and significance of eryptosis: the suicidal erythrocyte death. Biomed Res Int. 2015;2015:513518.Borst O, Abed M, Alesutan I, Towhid ST, Qadri SM, Foller M, Gawaz M, Lang F. Dynamic adhesion of eryptotic erythrocytes to endothelial cells via CXCL16/SR-PSOX. Am J Physiol Cell Physiol. 2012;302:C644-C651.Pretorius E, du Plooy JN, Bester J. A Comprehensive Review on Eryptosis. Cell Physiol Biochem. 2016;39:1977–2000. Disclosure of InterestNone declared

B cell chronic lymphocytic leukaemia (CLL) shows evidence of familial aggregation, but the inherited basis is poorly understood. Mutations in the ATM gene have been demonstrated in CLL. This, coupled with a possibly increased risk of leukaemia in relatives of patients with Ataxia Telangiectasia, led us to question whether the ATM gene is involved in familial cases of CLL. To examine this proposition we typed five markers on chromosome 11q in 24 CLL families. No evidence for linkage between CLL and ATM in the 24 families studied and the best estimates of the proportion of sibling pairs that share no, one or both haplotypes at ATM were not different from their null expectations. This would imply that ATM is unlikely to make a significant contribution to the three-fold increase in risk of CLL seen in relatives of patients.

ARLTS1 is a member of a large family of genes that encode proteins with a variety of functions, such as membrane and vesicular transport. These investigators provide evidence that ARLTS1 is a tumor-suppressor gene and that a polymorphic variant of ARLTS1 is associated with familial cancer. The investigators provide evidence that ARLTS1 is a tumor-suppressor gene and that a polymorphic variant of ARLTS1 is associated with familial cancer. Homozygous or heterozygous deletions at chromosome 13q14.3 occur in a variety of hematopoietic and solid tumors. 1 – 5 In some cases of chronic lymphocytic leukemia (CLL), these deletions are the only detectable cytogenetic abnormality. 6 , 7 The 13 known genes in this region are expressed in hematopoietic cells and solid tissues, but none have been found to be inactivated in tumors. 2 , 8 – 10 Because of the absence of any detectable pathogenic mutation and the active transcription of all retained genes at 13q14.3 (except the microRNA genes miR-15a and miR-16-1 ), it is possible that haploinsufficiency, in which one allele is deleted and . . .

Recognition of biased immunoglobulin variable (IgV) gene usage in B-cell chronic lymphocytic leukemia (B-CLL) may yield insight into leukemogenesis and may help to refine prognostic categories. We explored Ig variable heavy (V H ) and light (V L ) chain gene usage in highly stable and indolent B-CLL ( n =25) who never required treatment over 10 or more years. We observed an unexpectedly high usage of mutated V H 3-72 (6/25; 24.0%), a gene that was otherwise rare in B-CLL (7/805; 0.87%; P <0.01), including mutated cases (6/432; 1.39%; P <0.01) and was exceptional among indolent (1/230, 0.435%; P <0.01), and aggressive B-cell lymphomas (0/105; P <0.01). Three of six V H 3-72 B-CLL cases utilized the same V L V κ 4-1 gene. Two V H 3-72 B-CLL cases had highly homologous V H complementarity determining regions 3 (CDR3s), encoding Cys-XXXX-Cys domains, and utilized V κ 4-1 genes with homologous IgV L CDR3s. An identical threonine to isoleucine change at codon 84 of V H 3-72 framework region 3 (FR3) recurred in four cases of highly stable V H 3-72 B-CLL. This mutation is expected to cause a conformational change of FR3 proximal to CDR3 that might critically affect high-affinity antigen binding. B-cell receptors encoded by V H 3-72 may identify a specific B-CLL group and be implicated in leukemogenesis through an antigen-driven expansion of B cells.

Handgrip strength (HGS) is a key diagnostic tool for sarcopenia, yet the comparative prognostic value of the hydraulic dynamometer and pneumatic vigorimeter in hospitalized older adults remains unclear. This study is the first to examine the vigorimeter as a predictor of in-hospital mortality in this setting. This prospective cohort study included 376 hospitalized older adults (mean age: 82.7 years) across acute, rehabilitation, and long-term care wards. HGS was assessed using both the dynamometer and vigorimeter, applying two sets of cut-offs per instrument. Sarcopenia was confirmed using bioelectrical impedance analysis to calculate the fat-free mass index (FFMI), with four diagnostic criteria combining HGS and FFMI thresholds. Associations between HGS, sarcopenia, and mortality were evaluated using logistic regression and Cox proportional hazards models, with Kaplan-Meier curves illustrating survival differences. Higher HGS measured by the vigorimeter was independently associated with reduced in-hospital mortality (OR 0.96, 95% CI 0.93-0.98, p = 0.001), whereas no significant association was found for dynamometer-measured HGS. Confirmed sarcopenia was significantly associated with mortality for two diagnostic criteria (criterion 2: vigorimeter with DO-HEALTH1 cut-offs: OR 1.77, 95% CI 1.01-3.10, p = 0.047; criterion 4: vigorimeter with DO-HEALTH2 cut-offs: OR 1.76, 95% CI 1.01-3.07, p = 0.048), although no significant association was observed with time-to-mortality. Kaplan-Meier curves demonstrated significant survival differences only for vigorimeter-based HGS cut-offs (p = 0.04). Male sex and falls during hospitalization were associated with increased mortality, while admission to rehabilitation or long-term care wards was associated with reduced mortality. Vigorimeter-based HGS, especially using DO-HEALTH1 cut-offs, demonstrated superior prognostic value for in-hospital mortality compared to the dynamometer. These findings support the clinical utility of the vigorimeter for risk stratification and care planning in hospitalized older adults, particularly in settings where subtle neuromuscular deficits may influence outcomes.