Hyponatremia is common in older people, most often of multifactorial origin, and can be associated with poor clinical outcomes. The aim was to analyze the frequency of severe hyponatremia (sodium concentration below 125 mmol/L), risk factors and mortality association in hospitalized older patients. A retrospective study was performed in older patients (over 65 years) with hyponatremia, diagnosed at admission in an Internal Medicine Department during one year. A control group of 127 older patients without hyponatremia was considered. Statistical analysis of the data gathered was made with SPSS Statistics 20. The main results were: a group of 1060 patients with age superior to 65 years was identified (representing 72.26% of total admissions); incidence of hyponatremia in those patients was 27.55% and severe hyponatremia was 5.94%; diagnosis of hyponatremia was mentioned in the discharge note in 66.67% of cases; mortality was 27.0%, against 16.0% in the control group (p=0.057, Odds Ratio (OR)=1.940); drugs were a significant risk factor (p<0.001), specially thiazide diuretics (p=0.029, OR=2.774), angiotensin receptor blockers (ARB) (p=0.001, OR=4.097), proton-pump inhibitors (PPI) (p=0.007, OR=2.561) and spironolactone (p=0.011, OR=4.473); other relevant risk factors were: increased water intake (p=0.004), tube feeding (p<0.001), vomiting (p=0.032, OR=2.492), cirrhosis (p=0.008, OR=10.862) and hyperhidrosis (p=0.017, OR=2.542). We conclude that, although this group of patients had a high mortality, hyponatremia is often not investigated and not always mentioned as a diagnosis. Clinicians should have a clear appreciation of the roles that iatrogenic interventions and lapses in nutrition frequently play in upsetting the homeostatic balance in older patients.

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Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) share common features: elevated oxidative stress, DNA repair deficiency, and aberrant DNA methylation. We performed a hospital-based case-control study to evaluate the association in variants of genes involved in oxidative stress, folate metabolism, DNA repair, and DNA methylation with susceptibility and prognosis of these malignancies. To that end, 16 SNPs (one per gene: CAT, CYBA, DNMT1, DNMT3A, DNMT3B, GPX1, KEAP1, MPO, MTRR, NEIL1, NFE2F2, OGG1, SLC19A1, SOD1, SOD2, and XRCC1) were genotyped in 191 patients (101 MDS and 90 AML) and 261 controls. We also measured oxidative stress (reactive oxygen species/total antioxidant status ratio), DNA damage (8-hydroxy-2'-deoxyguanosine), and DNA methylation (5-methylcytosine) in 50 subjects (40 MDS and 10 controls). Results showed that five genes (GPX1, NEIL1, NFE2L2, OGG1, and SOD2) were associated with MDS, two (DNMT3B and SLC19A1) with AML, and two (CYBA and DNMT1) with both diseases. We observed a correlation of CYBA TT, GPX1 TT, and SOD2 CC genotypes with increased oxidative stress levels, as well as NEIL1 TT and OGG1 GG genotypes with higher DNA damage. The 5-methylcytosine levels were negatively associated with DNMT1 CC, DNMT3A CC, and MTRR AA genotypes, and positively with DNMT3B CC genotype. Furthermore, DNMT3A, MTRR, NEIL1, and OGG1 variants modulated AML transformation in MDS patients. Additionally, DNMT3A, OGG1, GPX1, and KEAP1 variants influenced survival of MDS and AML patients. Altogether, data suggest that genetic variability influence predisposition and prognosis of MDS and AML patients, as well AML transformation rate in MDS patients. © 2016 Wiley Periodicals, Inc.

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Background Vδ1+ T cells, a subset of γδ T cells, are responsible for innate‐like immune responses. Recently, an anti‐tumor function mediated by MHC‐unrestricted recognition of lipid and stress molecules, has also been described in these cells. This study aimed to quantify and phenotypically characterize circulating Vδ1+ T cells in B cell Chronic Lymphocytic Leukemia (CLL) and Monoclonal B cell lymphocytosis (MBL). Methods This study enrolled 58 individuals distributed in five groups: Binet B and C CLL (n = 9), Binet A CLL (n = 26), High count‐MBL (n = 10), Low count‐MBL (n = 5), and a control group (n = 8). The phenotypic characterization of Vδ1+ T cells, as well as the other T cell subpopulations (CD4+, CD8+, CD4+/CD8+, and Vδ1− γδT cells), were assessed by flow cytometry, evaluating the frequency of each subset expressing CD27, CD69, and cytoplasmic granzyme B. Results We observed an increasing percentage of Vδ1+ T cells belonging to CD27− compartment from controls to advanced stages of the disease, which was accompanied by an increasing percentage of these cells expressing granzyme B, a phenotypic pattern that was also observed in the other T cell subpopulations under study since earlier stages of the disease. Moreover, a striking expansion of Vδ1+ T cells in Binet B and C CLL was observed. Conclusions These experiment findings point to an expansion of CD27‐Vδ1+ T cells with a cytotoxic profile, from controls to advanced stages of the disease, which points to a role of Vδ1+ T cells in the host's anti‐tumor responses against clonal B‐cells in MBL and CLL. © 2018 Clinical Cytometry Society

Hepatosplenic T-cell lymphoma (HSTCL) is a rare, aggressive type of peripheral T-cell lymphoma that is characterised by extranodal disease, with infiltration and proliferation of malignant T-cells within the liver, spleen and bone marrow. The authors report the case of a young immunocompetent man, who was admitted to the hospital with a history of prolonged, unexplained fever, fatigue and weight loss. Initial blood work showed mild pancytopaenia and imaging studies revealed hepatosplenomegaly. The diagnosis was challenging, initially mimicking infectious disease, and it required an extensive investigation that ultimately revealed the characteristic clinical, histopathological and cytogenetic features of HSTCL. The clinical course was aggressive, and despite multiagent chemotherapy, the patient died 4 months after the diagnosis. This case highlights the difficulty of diagnosing HSTCL and the importance of considering it in a differential diagnosis of hepatosplenomegaly in young men who present with constitutional symptoms and no lymphadenopathy.

Rationale/aimDespite the increasing efficacy of recanalization therapies for acute ischemic stroke, a large number of patients are left with long-term functional impairment, devoid of efficacious treatments. CD34+ cells comprise a subset of bone marrow-derived mononuclear cells with the capacity to promote angiogenesis in ischemic lesions and have shown promising results in observational and in vitro studies. In this study, we aim to assess the efficacy of an autotransplant of CD34+ cells in acute ischemic stroke.Sample size estimates30 patients will be randomized for a power of 90% and alpha of 0.05 to detect a difference in 3 months infarct volume.Methods and designWe will screen 18–80 years old patients with acute ischemic stroke due to occlusion of a middle cerebral artery (MCA) for randomization. Persistent arterial occlusions, contra-indications to magnetic resonance imaging (MRI), premorbid dependency, or other severe diseases will be excluded. Treatment will involve bone marrow aspiration, selection of CD34+ cells, and their administration intra-arterially in the symptomatic MCA by angiography. Patients will be randomized for treatment at 7 (±2) days, 20 (±5 days) or sham procedure, 10 in each group.Study outcomesThe primary outcome will be infarct volume in MRI performed at 3 months. Secondary outcomes will include adverse events and multidimensional functional and neurological measures.Discussion/conclusionSTROKE34 is a PROBE design phase IIa clinical trial to assess the efficacy of intra-arterial administration of CD34+ cells 7 and 20 days after acute ischemic stroke.Trial registration (EU Clinical Trials Register)2017-002456-88.

Onze doentes evoluíram para leucemia aguda; estes têm, em média, eritropoietina sérica superior (p < 0,05). Adicionalmente, a eritropoietina sérica acima do limite superior da normalidade associa-se a menor sobrevivência (p = 0,0336). Após ajuste do modelo de regressão de Cox, o valor preditivo da eritropoietina para a sobrevivência global manteve-se (p < 0,001). Em análise multivariada, a eritropoietina sérica demonstrou ser um factor de prognóstico independente (p < 0,001). Discussão: A eritropoietina sérica é um factor preditivo de resposta à terapêutica com eritropoietina subcutânea, sendo que os doentes com síndrome mielodisplásica com valores mais elevados de eritropoietina apresentam uma pior resposta à administração de eritropoietina, mesmo com doses mais elevadas. A nossa amostra demonstra que a eritropoietina sérica apresenta também valor prognóstico, e em todos os subtipos de síndrome mielodisplásica. Além disso, isoladamente ou em associação com outros factores ou índices de prognóstico, poderá melhorar o valor prognóstico de índices como o International Prognostic Scoring System, uma vez que valores elevados de eritropoietina estão associados a progressão para leucemia aguda e, consequentemente, a menor sobrevivência. Conclusão: Os resultados sugerem que o aumento dos níveis séricos de eritropoietina ao diagnóstico pode constituir um factor de mau prognóstico em doentes com síndrome mielodisplásica, associando-se a maior risco de evolução para leucemia aguda e menor sobrevivência global. Palavras-chave: Eritropoietina; Prognóstico; Síndrome Mielodisplásica. ABSTRACT Introduction:This myelodysplastic syndromes are a heterogeneous entity characterized by dysplasia, hypercellular bone marrow, cytopenias and risk of transformation to acute leukaemia. Prognostic factors, such as bone marrow fibrosis, lactate dehydrogenase and β2-microglobulin elevation have been described, but treatment is mainly based in the International Prognostic Scoring System. Material and Methods:Our aim was to analyze serum´s erythropoietin at diagnosis in de novo myelodysplastic syndromes patients, through its impact in overall survival and possible implementation as prognostic marker. Clinical and laboratorial data from 102 patients with de novo myelodysplastic syndromes diagnosed between October/2009 and March/2014 were collected. Survival analysis was performed according to serum erythropoietin level stratification, using Kaplan-Meier methodology. Results: Our 102 patients had a median age of 74 years, with a male:female ratio of 0.8. Mean erythropoietin was significantly lower in refractory cytopenia with unilineage dysplasia patients in contrast with the higher values observed in 5q-syndrome (p < 0.05). Eleven patients progressed to acute leukaemia; these have higher mean erythropoietin values (p < 0.05). In addition, elevated serum erythropoietin was associated with lower survival rates (p = 0.0336). Predictive value of serum erythropoietin was maintained after Cox regression adjustment. In multivariate analysis, serum ery...