Characterization of comorbid factors in hip fracture related in-hospital mortality.

It is important to delineate factors which influence in-hospital mortality rates following a hip fracture. The current study aimed to identify the nature and frequency of comorbidities prevalent in this patient cohort. A retrospective chart review of cases of in-patient mortality following admission for a hip fracture was performed. These cases (n=127) were characterized for comorbidities, complications, medical status indicators, and other contributory factors. Cardiovascular 104 (81.9%), respiratory 66 (52.0%), genitourinary 41 (32.3%), psychiatric 41 (32.3%), vascular 40 (31.5%), and gastrointestinal 40 (31.5%), are the physiological systems, most commonly associated with comorbidity amongst hip fracture patients who succumb to in-hospital mortality. Renal failure, pneumonia, sepsis, myocardial infarction, congestive cardiac failure (CCF), respiratory failure, and Clostridium difficile infection are conditions which are associated with postoperative complications leading to in-patient mortality. Analysis of medical status indicators illustrated an inverse correlation between ASA scores and postoperative survival time, in this cohort-of hip fracture patients (R2 = 0.9485).

Assessment of the quality of care and financial impact of a virtual renal clinic compared with the traditional outpatient service model.

BACKGROUND: Patients with chronic kidney disease (CKD) have better outcomes when they have access to specialist nephrology services early in the course of their disease. However, up to 30% of patients with advanced kidney disease face late referral. Virtual clinics represent a potentially innovative mechanism for early assessment of high patient volumes efficiently and cost effectively while maintaining high standards of care. METHODS: A retrospective observational cohort study was completed over a 4-year period from April 2004 to March 2008 at a regional nephrology centre within Northern Ireland. All new patient attendances at the nephrology clinic were identified and those managed via the virtual renal clinic approach were included in this study. A cost comparison of this innovative modality was made with the traditional outpatient service model. RESULTS: There were 427 patients (51.3% female, 48.7% male) managed through the virtual renal clinic. Comorbidities included 180 patients (42.1%) with known CKD and 31 patients (7.3%) with newly identified kidney disease. A total of 118 patients (27.6%) had hypertension while 6 (1.4%) and 57 (13.3%) had type I and II diabetes mellitus (DM) respectively. Referral indications included 211 patients (49.4%) with abnormal renal biochemistry, 35 (8.2%) with proteinuria, 12 (2.8%) with haematuria and 87 patients (20.4%) with a combination of issues. A conservative treatment plan consisting of biochemical surveillance was appropriate for 246 patients (57.6%) while medication review was completed for 113 patients (26.5%) and surgical referral was indicated in 20 patients (4.7%). The virtual renal clinic provided a minimum cost saving of £111.56 per patient attendance compared with traditional outpatient care resulting in 23.3% of patient referrals being managed by the virtual clinic approach in 2009. CONCLUSION: Delayed referral to a renal specialist adversely affects patient outcomes. This study suggests that the implementation of a virtual renal clinic for non-complex renal pathologies can offer a cost-effective, rapid referral mechanism for patient assessment combined with readily available specialist advice.

CD8+ T cells specific for a single nonamer epitope of Listeria monocytogenes are protective in vivo.

Class I major histocompatibility complex (MHC)-restricted CD8+ T cells have been demonstrated to be effective mediators of both acquired and adoptive immunity to the intracellular bacterium Listeria monocytogenes. We have recently determined that L. monocytogenes-infected H-2d mice recognize a nonamer peptide, residues 91-99, of the secreted protein listeriolysin O (LLO), in a H-2Kd-restricted fashion. In this report we have generated CD8+ T cell lines with specificity for LLO 91-99 in the context of H-2Kd by in vitro stimulation with P815 (H-2d) cells transfected with LLO. These CD8+ lines have been generated from immune donors after sublethal infection with L. monocytogenes, or after in vivo immunization with syngeneic spleen cells coated with synthetic LLO 91-99 peptide. LLO-specific CD8+ T cells derived from either protocol were capable of significant protection against L. monocytogenes infection. The in vivo protection by these CD8+ T cell lines has been shown to be solely due to recognition of LLO 91-99 in the context of H-2Kd. These studies demonstrate that CD8+ T cell immunity to a single, naturally produced peptide epitope has the potential for significant protection in a bacterial infection. Thus, the allele-specific motif approach to epitope prediction has identified a naturally produced bacterial epitope with biological relevance.

Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma.

T cell memory depends on factors that regulate expansion and death of these cells after antigenic stimulation. Mice deficient in perforin and interferon-gamma (IFN-gamma) exhibited increased expansion, altered immunodominance, and decreased death of antigen-specific CD8+ T cells after infection with an attenuated strain of Listeria monocytogenes, which was cleared from these mice. Expansion of CD8+ T cells was controlled by perforin, whereas IFN-gamma regulated immunodominance and the death phase. Thus, perforin and IFN-gamma regulate distinct elements of CD8+ T cell homeostasis independently of their role as antimicrobial effector molecules.

Comparison of acetabular reamings during hip resurfacing versus uncemented total hip arthroplasty.

PURPOSE: To compare the quantity of bone removed from the acetabulum during resurfacing hip arthroplasty versus uncemented total hip arthroplasty (THA). METHODS: 62 consecutive patients with osteoarthritis of the hip were prospectively studied. 24 men and 7 women aged 40 to 86 (mean, 59) years underwent Birmingham hip resurfacing. 13 men and 18 women aged 34 to 88 (mean, 61) years underwent uncemented THA using the trident acetabular cup. Obese elderly women at risk of femoral neck fracture and patients with large subchondral pseudocysts or a history of avascular necrosis of the femoral head were assigned to uncemented THA. Acetabular reamings were collected; marginal osteophytes were not included. The reamings were dehydrated, defatted, and weighed. RESULTS: The mean weight of acetabular reamings was not significantly different between patients undergoing hip resurfacing and uncemented THA (p=0.57). CONCLUSION: In hip resurfacing, the use of an appropriately small femoral component avoids oversizing the acetabular component and removal of excessive bone stock.

Responses of CD8(+) T cells to intracellular bacteria.

Recent studies of CD8(+) T cell responses against intracellular bacteria have provided insights into the relevance of the exogenous and endogenous MHC class I presentation pathways during the priming and effector stages. The capacity of these organisms to deliver vaccine antigens, either as bacterial protein or as plasmid DNA expressed by host antigen-presenting cells, has been investigated. Ongoing studies of CD8(+) T cell effector functions suggest the existence of novel pathways of resistance to bacterial infection. These results, together with advances in our understanding of nonclassical MHC class I presentation, reveal the impact of pathogen biology on host immunity to infection.

Primary and secondary immune responses to Listeria monocytogenes.

Recent studies have revealed the complexity of cytokine and cellular interactions required for resistance to primary Listeria monocytogenes infection and have illustrated that resistance to secondary infection may occur through multiple pathways. Analyses of Listeria epitope generation and the specificity of protective CD8(+) T cells have suggested that future research should focus on secreted protein antigens in specific resistance to infection and have increased our understanding of Listeria antigens presented by MHC class l-b molecules.

Anti-platelet agents and surgical delay in elderly patients with hip fractures.

PURPOSE: To assess the risk of surgical delay in elderly hip fracture patients on anti-platelet agents. METHODS: Records of 180 patients aged over 65 years with either an intertrochanteric or femoral neck fracture were reviewed. The clopidogrel group included 10 patients on clopidogrel alone and 11 others on clopidogrel and aspirin, whereas the control group included 69 on aspirin alone and the remaining 90 not on any anti-coagulants. The 2 groups were compared with regard to time to surgery, preoperative American Society of Anesthesiologists (ASA) score, pre- and post-operative haemoglobin levels, in-patient complication rates, duration of hospital stay, and 30-day mortality. RESULTS: In the clopidogrel and control groups respectively, the mean times to surgery were 7.2 and 2.1 days (p=0.03, t-test), the mean preoperative ASA scores were 3.35 and 2.8 (p=0.29, t-test), the mean preoperative haemoglobin levels were 119 and 115 g/l (p=0.5, t-test), the mean postoperative haemoglobin levels were 98 and 96 g/l (p=0.68, t-test), the mean durations of hospital stay were 7.4 and 3.1 days (p=0.02, t-test). The 30-day mortalities were 6/21 (29%) and 6/159 (4%) [p=0.0003, Fisher's exact test]. CONCLUSION: Surgical delay in elderly patients on anti-platelet agents with hip fracture was associated with higher mortality. Despite the risk of increased blood loss, we suggest early surgery be carried out by an experienced surgeon to expedite the operating time. Pooled platelets should be given intravenously one to 2 hours preoperatively.

The cost and mortality of hip fractures in centenarians.

BACKGROUND: Centenarians are the fastest rising age group in Ireland. Hip fractures most commonly affect older adults and are associated with significant morbidity and mortality, as well as the financial cost of healthcare resources. Despite this, very little is known regarding hip fractures in centenarians. The aim of this study was to investigate our experience with hip fractures in this group and to record the cost of treating these fractures to identify both the social and economic impact these injuries impose on the health system. METHODS: The study was a retrospective data review at a major trauma centre. Nine proximal femoral fractures from June 2010-2016 were identified through a stepwise analysis of theatre data and patient notes. Time of death was recorded directly from patient records or by contacting the patient's general practitioner. With the assistance of the hospital finance department, individual inpatient costs were calculated using length of stay, theatre time and implant costs. RESULTS: Over the 7-year period we examined nine patients over 100 years of age were managed operatively for hip fractures with an average inpatient cost of €14,898. The mean age at the time of fracture was 101 years and 7 months. Eight of the patients were female and there was one male. Our inpatient, 30-day and 1-year mortality rate were 22, 22, and 71%. CONCLUSIONS: The 1-year mortality rate of any person aged 100 years or older is thought to be 67% for men and 59% for women. This suggests that the 1-year mortality rate of 71% in this current study is only slightly worse than the usual life expectancy of a person older than 100 years of age. Our data suggest that the extreme elderly should be offered operative management.

Hydrogen peroxide as an irrigation solution in arthroplasty - a potential contributing factor to the development of aseptic loosening.

The reason for revision of primary total hip arthroplasty is quoted as aseptic loosening in 60.6% of cases between 1979 and 2003 in the Swedish National Hip Arthroplasty Registry. Much research effort has been directed toward enhancing the bone-cement interface of total joint arthroplasties, in an attempt to reduce this complication. Haemostatic agents have been popularized as effective means of retarding the development of potentially harmful debris interposition adjacent to, and blood lamination patterns within, the methylmethacrylate. Such agents include hydrogen peroxide (H(2)O(2)), local freezing saline, saline at room temperature and adrenaline solution. One main concern with the use of hydrogen peroxide is whether it affects the material properties of bone cement such that in the long term it contributes to aseptic loosening. This would have enormous clinical consequences. Preliminary studies indicate that porosity increases and that the tensile strength and yield stresses are reduced by up to a factor of 10 by contaminating samples with increasing concentrations of hydrogen peroxide. We postulate that the current use of hydrogen peroxide as an irrigation solution in arthroplasty contributes to the development of aseptic loosening.

Effects of homoharringtonine on protein glycosylation in human bladder carcinoma cell T-24.

Rates of [3H]glucosamine and mannose incorporation into glycoproteins and dolichol-linked oligosaccharides in exponentially growing T-24 bladder cancer cells were examined after exposure to homoharringtonine (HHT). Two-h treatment of HHT (10 ng/ml) reduced [3H]glucosamine and mannose incorporation into the glycoproteins to 61% and 32% of controls. Concomitantly, respective sugar incorporation into dolichol-linked oligosaccharides was elevated 29% and 30% above control. The maximal inhibition of glycoprotein biosynthesis and stimulation of the lipid-linked oligosaccharides occurred within 2 to 4 h after exposure to 50 ng/ml of the drug. Prolonged drug exposure (greater than 8 h) resulted in generalized suppression of glycoprotein biosynthesis and lipid-linked oligosaccharide formation. The kinetic study indicated that the time course on reduction of glycoprotein biosynthesis and accumulation of dolichol-linked oligosaccharides paralleled the decline in protein synthesis. Further, the inhibition of glycoprotein synthesis and stimulation of dolichol-linked oligosaccharides were reversible 4 h after drug withdrawal. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiographic analysis of the [3H]mannose-labeled glycoprotein revealed no pronounced difference between HHT-treated and control cells. These data suggest that the inhibition of glycosylation results from combined decrease of acceptors for glycoprotein biosynthesis with a simultaneous accumulation of the dolichol-linked oligosaccharides. Collectively these data may account for many of the HHT-induced bioresponses.

In vitro effects of soy phytoestrogens on rat L6 skeletal muscle cells.

Soy isoflavones display estrogenic activity in humans and animals, and thus are referred to as phytoestrogens. This study was performed to observe the effects of the soy isoflavones genistein, daidzein, and glycitein on cell cultures of rat skeletal muscles. [3H]Thymidine incorporation was used to determine cell proliferation, while protein synthesis and degradation were determined by tracking radiolabeled leucine. For the proliferation studies, insulin, estradiol, genistein, daidzein, or glycitein was supplemented at 0, 0.04, 0.08, 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10, or 20 microM, respectively, or in combinations with final concentrations of 0, 0.1, 1, or 10 microM. Genistein reacted most similarly to estradiol, inhibiting proliferation at > or = 1 microM (P < .001). A combination of phytoestrogens resulted in significant inhibition of cell proliferation, but not to the extent observed with genistein alone. For the protein synthesis and degradation experiments, treatments of 0.1 microM dexamethasone or 1 microM concentrations of insulin, genistein, daidzein, or glycitein were used. Phytoestrogens did not inhibit or stimulate protein degradation or synthesis (P > .05). A one-tailed univariate analysis of variance revealed a trend (P < or = .1) in protein stimulation with genistein and glycitein treatments. These results suggest that the tyrosine kinase inhibiting activity of genistein may be affecting phosphorylation of the mitosis-promoting factor, preventing the advancement of the mitotic cell cycle. In addition, at higher total combined concentrations, daidzein and glycitein may be able to outcompete genistein for receptor sites. These results suggest that soy isoflavones in the diet may potentially modulate normal growth and development in humans and animals that ingest soy-based products.

Odontoid lateral mass asymmetry: do we over-investigate?

OBJECTIVES: This study aimed to evaluate the necessity for further radiological investigation in patients with suspected traumatic rotatory subluxation of the atlanto-axial complex on plain radiography following acute cervical trauma and outline guidelines for assessment of patients with atlanto-axial asymmetry on plain radiography. METHODS: A retrospective review of all patients who had undergone atlanto-axial CT scanning as a result of radiographic C1-C2 asymmetry following cervical spine trauma. The plain x ray and CT images were reviewed retrospectively and correlated with the clinical presentation and outcome. RESULTS AND CONCLUSION: Records of 29 patients (16 men, 13 women; age range 21-44 years) were reviewed. All patients were found to have atlanto-odontoid asymmetry on the initial plain x ray. CT images of none of the patients revealed rotatory subluxation. Ten patients (32%) were found to have congenital odontoid lateral mass asymmetry. All patients were treated conservatively without any further intervention. On review, in 19 patients the orientation of the x ray beam in combination with head rotation was found to be at fault. Approximately 1050 trauma cervical spine x rays were taken in the department where this study was conducted over the period 1999-2001. This study identified 10 patients out of a total of 29 as having congenital odontoid lateral mass asymmetry. This represents approximately 1% of the patients attending the emergency department. Thus congenital odontoid lateral mass asymmetry should be considered in the differential diagnosis following acute cervical trauma.

The need for multidisciplinary management of patients with upper thoracic spine fractures caused by high-velocity impact: a review of 32 surgically stabilised cases.

PURPOSE: To analyse the characteristics of patients who underwent surgery for fractures of the upper thoracic spine (T1-T6) in our institution. The thoracic spine is supported by the rib cage and associated ligaments; therefore, displacement and fracture of the upper thoracic spine in healthy young adults require a great force. The relatively narrow spinal canal around the spinal cord in this area could result in severe neurological deficit should fractures occur. METHODS: The treatment course of 32 patients (26 men and 6 women) who underwent surgery for fractures of the upper thoracic spine between February 1995 and March 2001 was retrospectively reviewed. Parameters of injuries and treatment methods were evaluated. RESULTS: Of the 32 patients, 29 were injured in traffic accidents (15 motorcycle and 14 vehicle), 2 in falls, and one by a heavy door falling on his back. 29 patients had spinal fractures at more than one level. 23 patients had complete, 7 had incomplete, and 2 had no neurological deficit. 30 patients required multiple modalities of radiological imaging (in addition to plain radiography) for diagnosis. 20 patients sustained other injuries apart from spinal fractures, 15 of them had associated chest injuries. CONCLUSION: High-velocity fractures of the upper thoracic spine are injuries with devastating consequences, and can result in severe neurological deficit and concomitant injuries. These patients are best treated by a multidisciplinary approach.

Primary total hip replacement--a survey of current practice and identifying changing trends.

Primary total hip replacement (THR) surgery is the most commonly performed and successful reconstructive procedure in orthopaedic surgery. We performed a survey of Irish Orthopaedic consultants to elucidate current practices of primary THR in elderly and young patients and identify changing trends. There was an 83% response rate. Most respondents use a cemented THR in elderly patients. 69% use a different THR in younger patients compared to older patients. 9% refer younger patients to hip replacement specialist consultant colleagues. 70% report changing to a new implant or new technique in younger patients and 45% use a hybrid THR, 15% an uncemented THR, 15% perform hip resurfacing and 47% use different bearing surfaces. Only 17% use the Charnley hip prosthesis in younger patients. Young and active patients will place high demands on a new THR and newer techniques, implants and bearing surfaces are being adopted in the hope of better outcomes.

Interleukin-1 beta stimulates interleukin-6 production in placental villous core mesenchymal cells.

Interleukin-6 (IL-6) is a pleiotropic mediator of immune function and a growth factor for a variety of hematopoietic cell types. Because IL-1 beta is known to induce IL-6 production in nonplacental mesenchymal cells and is locally produced by maternal decidua, this study was designed to determine whether IL-1 beta could regulate IL-6 production by second trimester placental villous core mesenchymal cells (VCMC) in vitro. VCMC were prepared for culture by enzymatic digestion of placentas (14-20 weeks gestation; n = 7). Immunohistochemistry performed on the confluent cells demonstrated that more than 95% of the cells had a fibroblast-like morphology and were vimentin positive, less than 5% were leukocyte common antigen (CA-45) positive, and no trophoblast contamination was demonstrated by the lack of cytokeratin staining. In dose-response experiments, a specific dose-response induction of IL-6 mRNA expression and IL-6-immunoreactive protein production by IL-1 beta was demonstrated; this was first seen at 100 pg/ml IL-1 beta [455 +/- 191 ng/ml (+/- SEM); controls, 42 +/- 16 ng/ml; P < 0.05]. In time-course studies, the addition of 10 ng/ml IL-1 beta significantly increased IL-6 production rates; this was first seen at 8 h of culture and increased in a linear fashion up to 48 h. At 48 h of culture, IL-6 levels were 17 times higher in treated VCMC (861 +/- 179 ng/ml) compared to those in nontreated VCMC (51 +/- 14 ng/ml). In summary, IL-1 beta stimulates VCMC IL-6 production in a specific dose- and time-dependent manner. From these results, we conclude that VCMC are an important source of IL-6 in second trimester placenta and that production of placental IL-6 be may regulated by decidual IL-1 beta.

Interleukin-1 beta stimulates colony-stimulating factor-1 production in placental villous core mesenchymal cells.

The human placenta is known to produce hematopoietic growth factors, including colony-stimulating factor-1 (CSF-1). We have previously demonstrated interleukin-1 beta (IL-1 beta) production by decidualized endometrium during pregnancy. Since IL-1 stimulates CSF-1 production in fibroblasts, endothelial cells, and bone marrow stromal cells, our present study was designed to determine whether IL-1 could also regulate CSF-1 production by placental villous core mesenchymal cells. Initial studies using enzymatic digestion separation of the trophoblast and villous core demonstrated that CSF-1 mRNA is mainly expressed in the placental villous core. Subsequently, long term monolayer cultures of villous core mesenchymal cells isolated from 9- to 16-week gestation placentas were established after enzymatic dissociation of intact placental villi to study the regulation of villous core cell CSF-1 production. The morphology of the cells and immunohistochemical staining for vimentin, cytokeratin, and CD45 antigen confirmed that cultured cells were more than 95% mesenchymal fibroblasts. Time-course experiments demonstrated a maximal increase in CSF-1 mRNA expression of approximately 6.0-fold over baseline levels 3 h after IL-1 beta treatment (10 ng/mL), whereas increased CSF-1 protein production was first detected in the culture medium 3 h after IL-1 beta treatment and rose progressively over 42 hours. Villous core mesenchymal cells incubated with 0-10 ng/mL IL-1 beta demonstrated a specific dose-response relationship for CSF-1 mRNA expression and protein production, first seen at 0.10 ng/mL and maximal with 10 ng/mL IL-1 beta. These results demonstrate that production of CSF-1 by placental villous core mesenchymal cells can be stimulated by IL-1 beta in vitro and suggest that decidual IL-1 may regulate placental CSF-1 production in vivo.

Detection and analysis of antigen-specific CD8+ T cells.

Based on recent advances in techniques that can detect and enumerate antigen-specific CD8+ T cells, it is evident that these cells can differentially regulate CD8+ T cell effector mechanisms at the single-cell level. Interplay between effector mechanisms that are employed by antigen-specific CD8+ T cells during the immune response in vivo can be addressed with different techniques that "count" cells either directly (T cell receptor (TCR) expression) or indirectly (antigen-specific cytokine production).

The effects of oral pentoxifylline on interleukin-2 toxicity in patients with metastatic renal cell carcinoma.

Interleukin-2 (IL-2) mediates the regression of metastatic renal cell carcinoma, but clinical application has been limited by associated toxicities. Preclinical studies show that pentoxifylline (PTXF), a methylxanthine derivative, inhibits IL-2 toxicity while preserving anti-tumour efficacy. This study was designed to determine whether oral PTXF would alter IL-2-induced toxicities. Patients with disseminated renal cell carcinoma were treated with continuous infusion of 18 x 10(6) IU/m2/24 h for 4 days followed by 3 days without treatment, for 4 consecutive weeks. After a 2-week interval, the 4-week treatment cycle was repeated. All patients concomitantly received oral PTXF (2000 mg/24 h) in five divided doses. Despite the co-administration of PTXF, all patients demonstrated a spectrum and severity of toxicities consistent with previous reports of continuous infusion of IL-2 alone. There was considerably more nausea and vomiting associated with the administration of PTXF which improved on withdrawal of PTXF. Oral PTXF in IL-2 therapy did not show any substantiated benefit. Indeed, patients suffered more severe nausea and vomiting than if they had received IL-2 alone, resulting in the early termination of the trial.

Intracellular staining for TNF and IFN-gamma detects different frequencies of antigen-specific CD8(+) T cells.

CD8(+) T lymphocytes are important mediators of adaptive immunity against certain viral, protozoan and bacterial pathogens. Activated CD8(+) T cells are able to induce cytolysis of infected cells (perforin and CD95-CD95L mediated pathways) and also elaborate cytokines, including IFN-gamma and TNF after appropriate MHC class I-peptide recognition. New technologies for the detection of antigen-specific CD8(+) T cells, including tetrameric MHC class I-peptide complexes, intracellular IFN-gamma staining and IFN-gamma ELISPOT analysis have revised our understanding of the magnitude of the CD8(+) T cell response to infection. Here, using intracellular cytokine staining, we compare detection of IFN-gamma and TNF in the analysis of pathogen-specific CD8(+) T cell lines and CD8(+) T cells after primary viral infection (LCMV) or secondary bacterial infection (Listeria monocytogenes). Under multiple conditions and with multiple epitopes, we find that staining for intracellular IFN-gamma consistently detects a higher frequency of antigen-specific CD8(+) T cells than detection of intracellular TNF. However, (a) intracellular staining for TNF can be used to detect antigen-specific CD8(+) T cell responses and (b) intracellular staining for cytokines is a useful approach for in vitro characterization of antigen-specific CD8(+) T cell lines.