Immunophenotypic characterization of myelomonocytic cells in patients with myelodysplastic syndrome

Summary. Infections, an important determinating factor in the clinical course of myelodysplastic syndromes (MDS), result in activation of myelomonocytic cells. In this study we demonstrate activation-associated immunophenotypic changes of cell surface antigens on monocytes and granulocytes observed in two groups of MDS patients, one with low and another one with high clinical risk, and compared them to healthy individuals. Significantly changed expression of the complement receptors 1 (CD35) and 3 (CD11b), the Fcγ receptor I (CD64), the leucocyte-homing receptor (CD44) and the activation associated membrane proteins CD67 and M5 were found on monocytes and/or granulocytes of MDS patients. In low-risk MDS patients we observed activation-associated phenotypic changes only in monocytes, whereas in high-risk MDS patients, both monocytes and granulocytes showed such changes. Additionally, we performed respiratory burst experiments and observed an impaired response of monocytes and granulocytes derived from MDS patients. Despite the fact that all patients were free of infection by clinical criteria, cell surface phenotyping as well as the reduced respiratory burst capacity of myelomonocytic cells suggests in vivo preactivation of these cells.     

Do cognitive interventions for preschoolers improve executive functions and reduce ADHD and externalizing symptoms? A meta-analysis of randomized controlled trials

Many interventions targeting executive function (EF) development in the preschool period, where malleability might be particularly high, have been created and evaluated. We conducted a meta-analysis of randomized controlled trials (RCTs) on the effects of these interventions on (a) EFs in preschool children from the general population as well as preschool children with (symptoms of) attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), and (b) ADHD and ODD symptoms in preschool children with ADHD/ODD (symptoms). Literature search yielded 35 RCTs. Risk of bias of the individual studies was assessed. A random-effects model was used. Moderator effects were tested using mixed model analyses. The overall effects on EFs were: d = 0.46 (95% CI 0.30–0.61) for working memory (WM), d = 0.30 (95% CI 0.21–0.38) for inhibitory control (IC), d = 0.33 (95% CI − 0.04 to 0.71) for reward-related IC, and d = 0.47 (95% CI 0.28–0.66) for flexibility. In children with ADHD/ODD, mean effects were d = 0.64 (95% CI 0.31–0.96) for WM and d = 0.46 (95% CI 0.07–0.84) for IC. Studies on reward-related IC and FL were lacking. Effects on ODD and ADHD symptoms were d = 0.40 (95% CI − 0.23 to 1.03) and d = 0.28 (95% CI − 0.08 to 0.64), respectively. Interventions targeting multiple EFs and using interpersonal cognitive scaffolding approaches showed large and statistically significant effects on ADHD and ODD symptoms. In preschool children of the general population and in those with ADHD/ODD (symptoms), interventions led to an improvement of EF performance. In children with ADHD and ODD, cognitive scaffolding interventions were most effective in terms of reducing ADHD and ODD symptoms. However, more well-controlled studies need to be conducted before any firm conclusions can be drawn.

     

Comparing the effect of positioning on cerebral autoregulation during radical prostatectomy: a prospective observational study

Journal of Clinical Monitoring and Computing - Surgery in the prolonged extreme Trendelenburg position may lead to elevated intracranial pressure and compromise cerebral hemodynamic regulation. We...     

Expression patterns and prognostic role of transketolase-like 1 in muscle-invasive bladder cancer

Purpose

The pentose phosphate pathway (PPP) has been shown to play an important role in the metabolism of cancer cells. The transketolase-like 1 gene (TKTL1) encodes an enzyme representing an essential component of this pathway. Its expression has been demonstrated to correlate with stage and outcome in various tumors. The aim of the present study was to assess expression patterns and the prognostic role of TKTL1 in muscle-invasive bladder cancer (MIBC).

Patients and methods

The expression of TKTL1 was assessed in a tissue microarray consisting of histopathologically benign and malign tissue of 112 patients who underwent radical cystectomy due to MIBC. Cytoplasmatic and nuclear expression were assessed by immunohistochemistry and compared separately with clinicopathologic parameters and outcome.

Results

Cytoplasmatic expression of TKTL1 was exclusively present in tumor tissue. In contrast, the proportion of nuclei positive for TKTL1 was higher in histopathologically benign tissue compared with malign tissue. No correlation was observed between cytoplasmatic or nuclear TKTL1 expression and tumor stage, grade or the presence of metastases. Patients with lymph node involvement showed a decreased frequency of cytoplasmatic expression compared with node-negative patients (p = 0.01). However, no further correlation was observed between the expression of TKTL1 and clinical outcome of patients.

Conclusions

The present study shows that the cytoplasmatic expression of TKTL1 is specific for MIBC tissue compared with histopathologically benign urothelium. This specific expression is present in a subgroup of MIBC potentially identifying patients with activated PPP suitable for a targeted inhibition of sugar metabolism. In contrast to other malignancies, TKTL1 shows no prognostic significance in MIBC.