Treatment of Trochanteric Hip Fractures with Cephalomedullary Nails: Single Head Screw vs. Dual Integrated Compression Screw Systems.

Extracapsular hip fractures are very common in the elderly. They are mainly treated surgically with an intramedullary nail. Nowadays, both endomedullary hip nails with single cephalic screw systems and interlocking double screw systems are available on the market. The latter are supposed to increase rotational stability and therefore decrease the risk of collapse and cut-out. A retrospective cohort study was carried out, in which 387 patients with extracapsular hip fracture undergoing internal fixation with an intramedullary nail were included to study the occurrence of complications and reoperations. Of the 387 patients, 69% received a single head screw nail and 31% received a dual integrated compression screw nail. The median follow-up was 1.1 years, and in that time, a total of 17 reoperations were performed (4.2%; 2.1% for single head screw nails vs. 8.7% for double head screws). According to the multivariate logistic regression model adjusted for age, sex and basicervical fracture, the adjusted hazard risk of reoperation required was 3.6 times greater when using double interlocking screw systems (p = 0.017). A propensity scores analysis confirmed this finding. In conclusion, despite the potential benefits of using two interlocking head screw systems and the increased risk of reoperation in our single center, we encourage to other researchers to explore this question in a wider multicenter study.

Ethical Dilemmas with Regard to Elderly Patients with Hip Fracture: The Problem of Nonagenarians and Centenarians.

Hip fracture is the most feared complication of osteoporosis, producing up to 30% mortality at the first year. With the aging of society, it is increasingly common to deal with ethical dilemmas that involve decision making in the elderly patient with a hip fracture. The objectives of the present work are to describe the main bioethical dilemmas in this group of patients and their relationship with surgical delay. We conducted a retrospective descriptive study that studied an elderly population admitted to a University Hospital with a diagnosis of hip fracture. In total, 415 patients were analyzed. The majority received surgical treatment, a correct application of the principles of justice, non-maleficence and beneficence is verified, but a possible violation of the principle of autonomy is confirmed. Based on the results of this study, the elderly population may somehow lose their principle of autonomy when they enter a hospital due to a hip fracture. On the other hand, the so-called ageism due to ignorance can influence the surgical delay and therefore the mortality of these patients.

Organochlorine contaminants in Rio skate (Rioraja agassizii), an endangered batoid species, from southeastern coast of Brazil.

A global movement towards decreases in elasmobranch overfishing has been noted in the last decades. However, discussion concerning the effects of POP contamination on the health and survival of these organisms is still recent. These compounds can affect the immune and endocrine systems of both sharks and batoids, impairing reproduction and impacting species recruitment, acting synergistically alongside overfishing effects. In this context, this study investigated the concentration of organochlorine compounds in liver of 29 individuals of Rioraja agassizii, a commercially exploited skate classified as Vulnerable by IUCN and as Endangered in Brazil. Contaminant concentrations were higher in adults compared to juveniles. Distinct contamination profiles were observed, suggesting different groups within the investigated population and revealing contaminants as a potential tool to assess population ecology. PCB levels were considered a concern as they resemble concentrations in ecosystems from the northern hemisphere, where deleterious effects on elasmobranchs have been observed.

MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells.

BACKGROUND: The recurrent immunoglobulin translocation, t(4;14)(p16;q32) occurs in 15% of multiple myeloma patients and is associated with poor prognosis, through an unknown mechanism. The t(4;14) up-regulates fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain (MMSET) genes. The involvement of MMSET in the pathogenesis of t(4;14) multiple myeloma and the mechanism or genes deregulated by MMSET upregulation are still unclear. DESIGN AND METHODS: The expression of MMSET was analyzed using a novel antibody. The involvement of MMSET in t(4;14) myelomagenesis was assessed by small interfering RNA mediated knockdown combined with several biological assays. In addition, the differential gene expression of MMSET-induced knockdown was analyzed with expression microarrays. MMSET gene targets in primary patient material was analyzed by expression microarrays. RESULTS: We found that MMSET isoforms are expressed in multiple myeloma cell lines, being exclusively up-regulated in t(4;14)-positive cells. Suppression of MMSET expression affected cell proliferation by both decreasing cell viability and cell cycle progression of cells with the t(4;14) translocation. These findings were associated with reduced expression of genes involved in the regulation of cell cycle progression (e.g. CCND2, CCNG1, BRCA1, AURKA and CHEK1), apoptosis (CASP1, CASP4 and FOXO3A) and cell adhesion (ADAM9 and DSG2). Furthermore, we identified genes involved in the latter processes that were differentially expressed in t(4;14) multiple myeloma patient samples. CONCLUSIONS: In conclusion, dysregulation of MMSET affects the expression of several genes involved in the regulation of cell cycle progression, cell adhesion and survival.

Streptolysin-O reversible permeabilisation is an effective method to transfect siRNAs into myeloma cells.

RNA interference (RNAi) has been shown to be a valuable tool to specifically target gene expression in a number of organisms becoming an indispensable weapon in the arsenal in functional genomics. In this study, we demonstrate that streptolysin-O (SLO) reversible permeabilisation is an efficient method to deliver small interfering RNAs (siRNAs) to hard-to-transfect human myeloma cell lines. We used published, pre-validated siRNAs for ERK2 and non-silencing siRNA control. We transfected siRNAs into human myeloma cell lines using SLO reversible permeabilisation method. Flow cytometry and western blot analysis were performed to assess the effect of SLO on transfection efficiency and ERK2 knockdown. These experiments demonstrate that SLO reversible permeabilisation method is an efficient and easy-to-use method to deliver siRNAs into human myeloma cell lines. Optimised SLO permeabilisation method showed to transfect >80% of JIM-3, H929, RPMI8226 and U266 cells, with minimal effect on cell viability (<10%) and cell cycle. Equally important, SLO permeabilisation induced a substantial knockdown of ERK2 at the protein level. These studies demonstrate that reversible SLO permeabilisation can successfully be applied to hard-to-transfect human myeloma cell lines to effectively silence genes.

Locking versus non-locking one-third tubular plates for treating osteoporotic distal fibula fractures: a comparative study.

INTRODUCTION: Ankle fractures represent the third most common fracture in elderly patients, after hip and wrist fractures. Distal fibula fractures in this population are closely related to osteoporosis, which renders commonly used methods of internal fixation technically demanding and prone to failure. Currently there is a tendency to fix osteoporotic metaphyseal and epiphyseal fractures with locking plates. However, published accounts about the use of this technology in osteoporotic distal fibula fractures are scarce. In this study we compare the results of two groups of patients who underwent surgery for these types of fracture, one group received locking and the other non-locking screws, both using one-third tubular plates. METHODS: Sixty-two patients, aged over 64 years, underwent surgery for osteoporotic distal fibula fractures between 2011 and 2014. Forty-five of them were stabilized with a non-locking plate and the remaining 17 with a locking plate fixation. Follow-up was performed at 4, 8, 12, 26, and 52 weeks. Results were assessed according to the AOFAS Ankle-Hindfoot Score and radiological criteria for consolidation. RESULTS: Average time to union and AOFAS scores at 6 and 12 months were similar in both groups, including for the individual categories: function, pain, mobility, and alignment. Only time until partial weight bearing was significantly lower in the locking plate group (4.69 ± 2.63 vs 7.77 ± 4.30, p = 0.03). The most common complications were wound dehiscence and superficial infection (two cases of both). CONCLUSIONS: Both locking and conventional non-locking plates achieved similar treatment outcomes in this group of osteoporotic patients aged over 64. However, locking plates may offer more benefits in cases that have to take into account immobilization time and concomitant soft-tissue damage.

Transfection of siRNAs in multiple myeloma cell lines.

RNA interference (RNAi), a valuable tool to specifically silence gene expression, is becoming an indispensable weapon in the arsenal of functional genomics, target validation and gene-specific therapeutic research. We have shown that Streptolysin-O (SLO) reversible permeabilization is an efficient method to deliver small interfering RNAs (siRNAs) to hard-to-transfect human myeloma cell lines. In addition, we have shown that transfection of siRNAs, using the SLO reversible permeabilization, specifically and efficiently induces gene silencing in myeloma cell lines.

Homozygous deletion mapping in myeloma samples identifies genes and an expression signature relevant to pathogenesis and outcome.

PURPOSE: Myeloma is a clonal malignancy of plasma cells. Poor-prognosis risk is currently identified by clinical and cytogenetic features. However, these indicators do not capture all prognostic information. Gene expression analysis can be used to identify poor-prognosis patients and this can be improved by combination with information about DNA-level changes. EXPERIMENTAL DESIGN: Using single nucleotide polymorphism-based gene mapping in combination with global gene expression analysis, we have identified homozygous deletions in genes and networks that are relevant to myeloma pathogenesis and outcome. RESULTS: We identified 170 genes with homozygous deletions and corresponding loss of expression. Deletion within the "cell death" network was overrepresented and cases with these deletions had impaired overall survival. From further analysis of these events, we have generated an expression-based signature associated with shorter survival in 258 patients and confirmed this signature in data from two independent groups totaling 800 patients. We defined a gene expression signature of 97 cell death genes that reflects prognosis and confirmed this in two independent data sets. CONCLUSIONS: We developed a simple 6-gene expression signature from the 97-gene signature that can be used to identify poor-prognosis myeloma in the clinical environment. This signature could form the basis of future trials aimed at improving the outcome of poor-prognosis myeloma.