Do surgical site complications after ankle fracture surgery reduce with Aquacel Extra Ag®? / ¿Disminuyen las complicaciones cutáneas tras la cirugía de fracturas de tobillo con el uso de Aquacel Extra Ag®?

INTRODUCTION: Ankle fractures account for up to 10% of total fractures. Most of them require surgical fixation, which involves an important risk of wound complications. The aim of this study was to determine whether a silver-impregnated occlusive surgical dressing (Aquacel Ag Extra®) was effective in reducing the rates of wound complications after ankle fracture open reduction and internal fixation compared to standard sterile dressing. METHODS: We prospectively reviewed 233 patients who underwent ankle fracture open reduction and internal fixation. Surgeons switched from using a standard dressing to an Aquacel Ag Extra® from July 2017 to February 2018, without other major changes in perioperative management. We compared skin complications between both groups after 3 months' follow-up. RESULTS: The statistical analysis showed that there is no difference in the prevalence of skin complications between both groups. CONCLUSIONS: The theoretical advantages of silver impregnated dressings need further prospective randomized controlled studies to assess the appropriate indications for their use in orthopaedic surgery.

A novel short-term plasticity of intrinsic excitability in the hippocampal CA1 pyramidal cells.

Changes in neuronal activity often trigger compensatory mechanisms aimed at regulating network activity homeostatically. Here we have identified and characterized a novel form of compensatory short-term plasticity of membrane excitability, which develops early after the eye-opening period in rats (P16-19 days) but not before that developmental stage (P9-12 days old). Holding the membrane potential of CA1 neurons right below the firing threshold from 15 s to several minutes induced a potentiation of the repolarizing phase of the action potentials that contributed to a decrease in the firing rate of CA1 pyramidal neurons in vitro. Furthermore, the mechanism for inducing this plasticity required the action of intracellular Ca(2+) entering through T-type Ca(2+) channels. This increase in Ca(2+) subsequently activated the Ca(2+) sensor K(+) channel interacting protein 3, which led to the increase of an A-type K(+) current. These results suggest that Ca(2+) modulation of somatic A-current represents a new form of homeostatic regulation that provides CA1 pyramidal neurons with the ability to preserve their firing abilities in response to membrane potential variations on a scale from tens of seconds to several minutes.

Intrinsic excitability is altered by hypothyroidism in the developing hippocampal CA1 pyramidal cells.

Thyroid hormone plays an essential role in brain development, so its deficiency during a critical developmental period has been associated with profound neurological deficits, including irreversible mental retardation. Despite the importance of the disorder, the cellular mechanisms underlying these deficits remain largely unexplored. The aim of this study was to examine the effects of the absence of thyroid hormone on the postnatal development of membrane excitability of CA1 hippocampal pyramidal cells. Current clamp recordings in the whole cell patch clamp configuration showed that the action potential of cells from hypothyroid animals presented shorter width, slower depolarization, and faster repolarization rates compared with controls both in early postnatal and pre-weanling ages. Additionally, thyroid hormone deficiency reduced the intrinsic membrane excitability as measured by the reduced number of evoked action potentials for a given depolarizing slope and by the more depolarized firing threshold observed in hypothyroid animals. Then we analyzed the fast-repolarizing A- and D-type potassium currents, as they constitute one of the major factors underlying intrinsic membrane excitability. Hypothyroid rats showed increased A-current density and a reduced isolated I(D)-like current, accompanied by parallel changes in the expression of the channels responsible for these currents in the CA1 region: Kv4.2, Kv4.3, and Kv1.2. Therefore, we suggest that the increased A-current density, subsequent to an increment in its channel expression, together with the decrease of Na(+)-currents, might help explain the functional alterations in the neuronal discharge, in the firing threshold, and in the action potential repolarization of hypothyroid pyramidal neurons.

Involvement of RhoH GTPase in the development of B-cell chronic lymphocytic leukemia.

RhoH is a hematopoietic-specific, GTPase-deficient member of the Rho GTPase family that functions as a regulator of thymocyte development and T-cell receptor signaling by facilitating localization of zeta-chain-associated protein kinase 70 (ZAP70) to the immunological synapse. Here we investigated the function of RhoH in the B-cell lineage. B-cell receptor (BCR) signaling was intact in Rhoh(-/-) mice. Because RhoH interacts with ZAP70, which is a prognostic factor in B-cell chronic lymphocytic leukemia (CLL), we analyzed the mRNA levels of RhoH in primary human CLL cells and showed a 2.3-fold higher RhoH expression compared with normal B cells. RhoH expression in CLL positively correlated with the protein levels of ZAP70. Deletion of Rhoh in a murine model of CLL (Emu-TCL1(Tg) mice) significantly delayed the accumulation of CD5(+)IgM(+) leukemic cells in peripheral blood and the leukemic burden in the peritoneal cavity, bone marrow and spleen of Rhoh(-/-) mice compared with their Rhoh(+/+) counterparts. Phosphorylation of AKT and ERK in response to BCR stimulation was notably decreased in Emu-TCL1(Tg);Rhoh(-/-) splenocytes. These data suggest that RhoH has a function in the progression of CLL in a murine model and show RhoH expression is altered in human primary CLL samples.

BCL6 represses NFkappaB activity in diffuse large B-cell lymphomas.

BCL6 is a transcriptional repressor whose deregulated expression plays a key role in diffuse large B-cell lymphomas (DLBCLs). BCL6 expression characterizes one of the two main subtypes (GC type) of DLBCL, while the other (ABC type) is recognized by increased NFkappaB activation. The mechanistic basis of this distinction remains unclear and the BCL6 targets have been only partially explored. Here we describe how NFkappaB activity is increased after BCL6 silencing by shRNA in DLBCL cells, leading us to propose that BCL6 represses NFkappaB activity. We also demonstrate that this repression is brought about by a mechanism involving protein-protein interaction between BCL6 and NFkappaB members, both in vitro and in vivo. Analysis of a series of DLBCLs shows a negative correlation between the expression of NFkappaB target genes and BCL6. This combined approach using silenced cells and a series of human DLBCL samples leads us to a better understanding of the role of BCL6 as an NFkappaB regulator in B-cells.

Lymphoma microenvironment: culprit or innocent?

Studies are revealing that lymphoid neoplasms are characterized by well-defined chromosome translocations and by the accumulation of subsequent molecular alterations involving mainly the cell cycle and/or apoptotic pathways. However, survival of B and T tumor cells is also dependent on the interactions with the accompanying cells that comprise the lymphoma microenvironment. Although non-tumor cells can contribute both positive and negative signals to the lymphoma cells, in this review we present compelling evidence of the essential influence of the tumor microenvironment on the initiation and progression of specific lymphoma types, highlighting some new therapeutic approaches that target the lymphoma microenvironment.

Hodgkin's lymphoma cells express alternatively spliced forms of HDM2 with multiple effects on cell cycle control.

The HDM2 oncoprotein is a cellular inhibitor of p53 and is frequently deregulated in human cancer. However, the HDM2 gene encodes alternatively spliced variants whose functional significance is poorly understood. We had previously reported the detection of alternative HDM2 forms in Hodgkin's lymphoma (HL)-derived cell lines. Here, we have cloned several of these transcripts, including the previously described HDM2-A, -B and -C (which encode the COOH terminus of HDM2), and two novel variants (HDM2-HL1 and -HL2) containing a complete p53 interaction domain. Real-time PCR assays demonstrated that HDM2-A and -B were selectively expressed by HL cell lines and primary tumors, compared with their non-neoplastic counterparts. In transient transfection experiments, alternatively spliced HDM2 isoforms were partially or totally localized within the cytoplasm. HDM2-HL2 was able to inhibit transactivation of a p53-inducible reporter construct and induced a partial relocalization of p53 to the cytoplasm. Expression of HDM2-A and -B caused the activation of p53/p21 and induced growth arrest in primary cells, but also increased the expression levels of cyclins D1 and E. Other possible genes regulated by HDM2-A and -B were identified using cDNA microarray technology. These results imply that HDM2 isoforms may have multiple effects on cell cycle control, and provide insight into the mechanisms through which these molecules contribute to tumorigenesis.

Overall survival in aggressive B-cell lymphomas is dependent on the accumulation of alterations in p53, p16, and p27.

Different studies have already shown that the isolated inactivation of p21, p16, or p27 cyclin-dependent kinase inhibitors (CKIs) is associated with increased growth fraction, tumor progression, or decreased overall survival in cases of non-Hodgkin's lymphoma. In this study we linked molecular study of the p53 and p16 genes with immunohistochemical analysis of p27 expression in a group of aggressive B-cell lymphomas [large B-cell lymphomas (LBCLs) and Burkitt's lymphomas]. This was done to analyze the relationship between p53 and p16 silencing, p27 anomalous overexpression, and clinical follow-up, testing the hypothesis that the accumulation of CKI alterations could confer to the tumors a higher aggressivity. In a group of 62 patients, p53 inactivation as a result of mutation was observed in 11 cases (18%) and p16 silencing was seen in 27 cases (43.5%) as a result of methylation (20 of 62), 9p21 deletion (7 of 44), or p16 mutation (2 of 62). The simultaneous inactivation of p53 and p16 was detected exclusively in five LBCL cases. Anomalous expression of p27, which has been proven to be associated with the absence of p27/CDK2 complexes and the formation of p27/cyclin D3 complexes where p27 is inactivated, was detected in 19 of 61 cases (31%). Cases characterized by p27 anomalous expression display concurrent inactivation of p21 (provided by p53 mutations) and/or p16 CKIs in 11 of 14 LBCL cases (P = 0.040). When the relationship between the association of inactivated CKIs and overall survival was considered, a significant relationship was found between a lower overall survival probability and an increased number of inactivated CKIs in LBCL cases, with the worst prognosis for the cases displaying concurrent p53, p16, and p27 alterations. This proves that simultaneous inactivation of different tumor suppressor pathways does indeed take place, and that tumor aggressiveness takes advantage of this CKI-concerted silencing. In this same series of data, Burkitt's lymphoma patients seem to behave in a different way than LBCLs, with p53 and p16 alteration being mutually exclusive and the association with p27 anomalous expression not being clinically significant. These facts seem to support that the additive effect of the inactivation of different CKIs could be dependent of the histological type.