Adiponectin and resistin in acute and chronic graft-vs-host disease patients undergoing allogeneic hematopoietic stem cell transplantation

Aim To investigate the association of adiponectin and resistin levels in patients undergoing hematopoietic stem cell transplantation (HSCT) with the clinical outcome, including the occurrence of acute and chronic graft-vs-host disease (GVHD), non-relapse mortality, and overall survival. Methods We prospectively collected serum samples from 40 patients undergoing either autologous (n = 12; 10 male) or allogeneic (n = 28; 11 male) HSCT for up to 12 months post HSCT and determined adiponectin and resistin serum concentrations using enzyme-linked immunosorbent assay. Results There were no significant differences in adiponectin levels (18.5 vs 9.3 μg/mL, P = 0.071) and adiponectin/ BMI ratio (0.82 vs 0.39, P = 0.068) between patients with acute GVHD grades 2-4 and autologous controls. However, resistin values were significantly lower in patients with acute GVHD grades 2-4 than in autologous controls (4.6 vs 7.3 ng/mL, P = 0.030). Adiponectin levels were higher in patients with chronic GVHD (n = 17) than in autologous controls (13.5 vs 7.6 μg/mL, P = 0.051), but the difference was not significant. Adiponectin/BMI ratio was significantly higher in patients with chronic GVHD than in autologous controls (0.59 vs 0.25, P = 0.006). Patients dying from relapse also had significantly lower adiponectin levels (8.2 μg/mL) and adiponectin/BMI ratio (0.3) on admission than surviving allogeneic (15.8 μg/mL, P = 0.030 and 0.7, P = 0.004) and surviving autologous patients (19.2 μg/mL, P = 0.031 and 0.7, P = 0.021). Conclusion Adiponectin and resistin levels were altered in patients with acute and chronic GVHD compared to autologous controls and were associated with overall survival and relapse mortality in patients undergoing allogeneic HSCT

Behavior profiles in children with functional urinary incontinence before and after incontinence treatment

OBJECTIVE. The purpose of this work was to analyze prospectively the prevalence of behavioral disorders in children with urinary incontinence because of nonneuropathic bladder-sphincter dysfunction before and after treatment for incontinence. METHODS. A total of 202 children with nonneuropathic bladder-sphincter dysfunction were enrolled in the European Bladder Dysfunction Study, in branches for urge syndrome (branch 1) and dysfunctional voiding (branch 2); 188 filled out Achenbach's Child Behavior Checklist before treatment and 111 after treatment. Child Behavior Checklist scales for total behavior problems were used along with subscales for externalizing problems and internalizing problems. RESULTS. After European Bladder Dysfunction Study treatment, the total behavior problem score dropped from 19% to 11%, the same prevalence as in the normative population; in branch 1 the score dropped from 14% to 13%, and in branch 2 it dropped from 23% to 8%. The prevalence of externalizing problems dropped too, from 12% to 8%: in branch 1 it was unchanged at 10%, and in branch 2 it dropped from 14% to 7%. The decrease in prevalence of internalizing problems after treatment, from 16% to 14%, was not significant. CONCLUSION. More behavioral problems were found in dysfunctional voiding than in urge syndrome, but none of the abnormal scores related to the outcome of European Bladder Dysfunction Study treatment for incontinence. With such treatment, both the total behavior problem score and the score for externalizing problems returned to normal, but the score for internalizing problems did not change. The drops in prevalence are statistically significant only in dysfunctional voiding

Pharmacological interventions to reduce violence in patients with schizophrenia in forensic psychiatry.

Abstract Background The purpose was to systematically investigate which pharmacological strategies are effective to reduce the risk of violence among patients with Schizophrenia Spectrum Disorders (SSD) in forensic settings. Methods For this systematic review six electronic data bases were searched. Two researchers independently screened the 6,003 abstracts resulting in 143 potential papers. These were then analyzed in detail by two independent researchers. Of these, 133 were excluded for various reasons leaving 10 articles in the present review. Results Of the 10 articles included, five were merely observational, and three were pre-post studies without controls. One study applied a matched case-control design and one was a non-randomized controlled trial. Clozapine was investigated most frequently, followed by olanzapine and risperidone. Often, outcome measures were specific to the study and sample sizes were small. Frequently, relevant methodological information was missing. Due to heterogeneous study designs and outcomes meta-analytic methods could not be applied. Conclusion Due to substantial methodological limitations it is difficult to draw any firm conclusions about the most effective pharmacological strategies to reduce the risk of violence in patents with SSD in forensic psychiatry settings. Studies applying more rigorous methods regarding case-definition, outcome measures, sample sizes, and study designs are urgently needed

Glioblastomas with primitive neuronal component harbor a distinct methylation and copy‑number profle with inactivation of TP53, PTEN, and RB1

Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.publishedVersio

Monocyte-mediated T-cell suppression and augmented monocyte tryptophan catabolism after human hematopoietic stem-cell transplantation

T-cell dysfunction after human hematopoietic stem-cell transplantation (HSCT) is generally attributed to intrinsic T-cell defects. Here we show that the characteristic impaired proliferative responses to polyclonal stimulation of post-HSCT peripheral blood mononuclear cells (PB-MCs) were markedly (4-fold) improved by T-cell enrichment. Conversely, addback of post-HSCT monocytes to these enriched T cells dampened their proliferative responses, suggesting that post-HSCT monocytes effectively mediate T-cell suppression. As a mechanism possibly contributing to monocyte-mediated T-cell suppression, we investigated monocyte tryptophan catabolism by indoleamine 2,3-dioxygenase into kynurenine, which has been implicated in regulating T-cell responses. Compared with controls, all post-HSCT monocyte-containing cell cultures (total PBMCs, monocytes, and monocyte/T-cell cocultures), but not monocyte-depleted populations, secreted elevated amounts of kynurenine. Blockade of tryptophan catabolism improved the proliferative responses. The slightly increased kynurenine release and substantial release of neopterin by unstimulated post-HSCT monocytes suggests that they were in a state of continuous activation. Superimposed on this state, stimulation of these cells caused a striking, additional increase (10-fold) in kynurenine release, and they triggered marked apoptosis of autologous post-HSCT T cells. We conclude that the amplified kynurenine release by post-HSCT monocytes, particularly induced upon stimulation, may underlie their suppressor activity, which in turn may contribute to the depressed T-cell immune responses after HSCT