To systematically review the effect of core stability exercises in addition to usual care physiotherapy on patient outcomes after stroke.
Cumulative Index to Nursing and Allied Health, MEDLINE, ...Physiotherapy Evidence Database (PEDro), PubMed, and EMBASE were searched to November 2018.
Eleven randomized controlled trials that compared usual care physiotherapy with usual care physiotherapy with additional core stability exercises in people with stroke were included. The initial search yielded 1876 studies.
Two independent reviewers applied inclusion and exclusion criteria and extracted data on methodological quality using the PEDro scale, participant characteristics, intervention details, outcome measures, and results.
Postintervention means and SDs were pooled to calculate either the standardized mean difference (SMD) or the mean difference (MD) and 95% CIs using a random-effects model and inverse variance methods. There was moderate quality evidence to suggest the addition of core stability exercises to usual care physiotherapy improved trunk control (SMD, 0.94; 95% CI, 0.44-1.44; I
=69%), functional dynamic balance (SMD, 1.23; 95% CI, 0.5-1.97; I
=71%), and walking speed (MD, 0.27m/s; 95% CI, 0.01-0.52; I
=40%) in people with acute and chronic stroke. No significant effect was found when assessing functional ambulation categories or the timed Up and Go test, and mixed results were found for global functioning.
The addition of core stability exercises to usual care physiotherapy after stroke may lead to improved trunk control and dynamic balance. Therefore, core stability exercises should be included in rehabilitation if improvements in these domains will help clients achieve their goals. Future trials should consider incorporating outcomes of body kinematics during functional tasks to assess movement quality and assess participation outcomes.
Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)–like and unfavorable activated B-cell (ABC)–like subtypes based on gene expression ...signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). We show that MYC/BCL2 protein coexpression occurred significantly more commonly in the ABC subtype. Patients with the ABC or GCB subtype of DLBCL had similar prognoses with MYC/BCL2 coexpression and without MYC/BCL2 coexpression. Consistent with the notion that the prognostic difference between the 2 subtypes is attributable to MYC/BCL2 coexpression, there is no difference in gene expression signatures between the 2 subtypes in the absence of MYC/BCL2 coexpression. DLBCL with MYC/BCL2 coexpression demonstrated a signature of marked downregulation of genes encoding extracellular matrix proteins, those involving matrix deposition/remodeling and cell adhesion, and upregulation of proliferation-associated genes. We conclude that MYC/BCL2 coexpression in DLBCL is associated with an aggressive clinical course, is more common in the ABC subtype, and contributes to the overall inferior prognosis of patients with ABC-DLBCL. In conclusion, the data suggest that MYC/BCL2 coexpression, rather than cell-of-origin classification, is a better predictor of prognosis in patients with DLBCL treated with R-CHOP.
•DLBCL patients with MYC/BCL2 coexpression demonstrate inferior prognosis and high-risk gene expression signatures.
Cohesin complex members have recently been identified as putative tumor suppressors in hematologic and epithelial malignancies. The cohesin complex guides chromosome segregation; however, cohesin ...mutant leukemias do not show genomic instability. We hypothesized that reduced cohesin function alters chromatin structure and disrupts cis-regulatory architecture of hematopoietic progenitors. We investigated the consequences of Smc3 deletion in normal and malignant hematopoiesis. Biallelic Smc3 loss induced bone marrow aplasia with premature sister chromatid separation and revealed an absolute requirement for cohesin in hematopoietic stem cell (HSC) function. In contrast, Smc3 haploinsufficiency increased self-renewal in vitro and in vivo, including competitive transplantation. Smc3 haploinsufficiency reduced coordinated transcriptional output, including reduced expression of transcription factors and other genes associated with lineage commitment. Smc3 haploinsufficiency cooperated with Flt3-ITD to induce acute leukemia in vivo, with potentiated Stat5 signaling and altered nucleolar topology. These data establish a dose dependency for cohesin in regulating chromatin structure and HSC function.
Per the revised fourth edition World Health Organization classification of acute myeloid leukemia, pure erythroid leukemia is now the sole type of acute erythroid leukemia. The diagnosis of this rare ...entity is often challenging and the cytologic overlap with non-neoplastic (eg, megaloblastic anemia) and neoplastic entities (eg, other types of acute leukemia and non-hematopoietic malignancies) warrants a significant degree of clinical, laboratory, immunophenotypic, and genetic investigation. Given the limited number of reports of this rare and diagnostically challenging entity, we report detailed clinicopathologic characteristics from 15 patients, the largest series thus far, of primary de novo pure erythroid leukemia to provide further diagnostic insights into this entity and reveal strategies for making the diagnosis. We found that de novo pure erythroid leukemia is a disease of adults (median age 68 years), exhibits a striking male predominance, is universally associated with an abnormal karyotype and has an exceedingly poor overall median survival of 1.4 months. Given the general inability of immunophenotypic markers to discriminate neoplastic from non-neoplastic erythroid proliferations, key features identified in this study to help establish the diagnosis of pure erythroid leukemia and exclude mimickers include circulating pronormoblasts, clear-cut dysplasia in erythroid, granulocytic, and/or megakaryocytic lineage, utilization of a broad immunophenotypic panel, TP53 immunohistochemical positivity, and identification of a complex, often highly complex, karyotype. Given the gravity of a diagnosis of de novo pure erythroid leukemia, it should be rendered with utmost confidence.
BAFF and APRIL are innate immune mediators that trigger immunoglobulin G (IgG) and IgA class-switch recombination (CSR) in B cells by engaging the receptor TACI. The mechanism that underlies CSR ...signaling by TACI remains unknown. Here we found that the cytoplasmic domain of TACI encompasses a conserved motif that bound MyD88, an adaptor that activates transcription factor NF-kappaB signaling pathways via a Toll-interleukin 1 (IL-1) receptor (TIR) domain. TACI lacks a TIR domain, yet triggered CSR via the DNA-editing enzyme AID by activating NF-kappaB through a Toll-like receptor (TLR)-like MyD88-IRAK1-IRAK4-TRAF6-TAK1 pathway. TACI-induced CSR was impaired in mice and humans lacking MyD88 or the kinase IRAK4, which indicates that MyD88 controls a B cell-intrinsic, TIR-independent, TACI-dependent pathway for immunoglobulin diversification.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. ...We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its clinical and biologic significance in 773 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 231 patients treated with CHOP. We found that CD37 loss (CD37−) in ∼60% of DLBCL patients showed significantly decreased survival after R-CHOP treatment, independent of the International Prognostic Index (IPI), germinal center B-cell–like (GCB)/activated B-cell–like (ABC) cell of origin, nodal/extranodal primary origin, and the prognostic factors associated with CD37−, including TP53 mutation, NF-κBhigh, Mychigh, phosphorylated STAT3high, survivinhigh, p63−, and BCL6 translocation. CD37 positivity predicted superior survival, abolishing the prognostic impact of high IPI and above biomarkers in GCB-DLBCL but not in ABC-DLBCL. Combining risk scores for CD37− status and ABC cell of origin with the IPI, defined as molecularly adjusted IPI for R-CHOP (M-IPI-R), or IPI plus immunohistochemistry (IHC; IPI+IHC) for CD37, Myc, and Bcl-2, significantly improved risk prediction over IPI alone. Gene expression profiling suggested that decreased CD20 and increased PD-1 levels in CD37− DLBCL, ICOSLG upregulation in CD37+ GCB-DLBCL, and CD37 functions during R-CHOP treatment underlie the pivotal role of CD37 status in clinical outcomes. In conclusion, CD37 is a critical determinant of R-CHOP outcome in DLBCL especially in GCB-DLBCL, representing its importance for optimal rituximab action and sustained immune responses. The combined molecular and clinical prognostic indices, M-IPI-R and IPI+IHC, have remarkable predictive values in R-CHOP–treated DLBCL.
•CD37 positivity predicts significantly better survival for DLBCL, and is superior to other prognostic factors in GCB-DLBCL.•CD37 loss is an important risk factor for R-CHOP resistance in both GCB- and ABC-DLBCL.
PTEN loss has been associated with poorer prognosis in many solid tumors. However, such investigation in lymphomas is limited. In this study, PTEN cytoplasmic and nuclear expression, PTEN gene ...deletion, and PTEN mutations were evaluated in two independent cohorts of diffuse large B-cell lymphoma (DLBCL). Cytoplasmic PTEN expression was found in approximately 67% of total 747 DLBCL cases, more frequently in the activated B-cell–like subtype. Nuclear PTEN expression was less frequent and at lower levels, which significantly correlated with higher PTEN mRNA expression. Remarkably, loss of PTEN protein expression was associated with poorer survival only in DLBCL with AKT hyperactivation. In contrast, high PTEN expression was associated with Myc expression and poorer survival in cases without abnormal AKT activation. Genetic and epigenetic mechanisms for loss of PTEN expression were investigated. PTEN deletions (mostly heterozygous) were detected in 11.3% of DLBCL, and showed opposite prognostic effects in patients with AKT hyperactivation and in MYC rearranged DLBCL patients. PTEN mutations, detected in 10.6% of patients, were associated with upregulation of genes involved in central nervous system function, metabolism, and AKT/mTOR signaling regulation. Loss of PTEN cytoplasmic expression was also associated with TP53 mutations, higher PTEN-targeting microRNA expression, and lower PD-L1 expression. Remarkably, low PTEN mRNA expression was associated with down-regulation of a group of genes involved in immune responses and B-cell development/differentiation, and poorer survival in DLBCL independent of AKT activation. Collectively, multi-levels of PTEN abnormalities and dysregulation may play important roles in PTEN expression and loss, and that loss of PTEN tumor-suppressor function contributes to the poor survival of DLBCL patients with AKT hyperactivation.
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