Assessing accuracy requirements in high tibial osteotomy: a theoretical, computer-based model using AP radiographs.

PURPOSE: High tibial osteotomy (HTO) is a recognised treatment for medial compartment knee arthritis and in recent years has regained popularity. Preoperative planning of wedge opening is based on standing AP radiographs, aiming to deliver the WBL to a desired point. Clinical results can be unpredictable, and this may be due to an inability to deliver the preoperative plan. This study explores the theoretical wedge opening accuracy required to deliver preoperative plans, based on clinical AP radiographs. METHODS: A theoretical 2-D model of osteotomy was developed to determine the degree of radiological wedge opening accuracy required to deliver the weight-bearing line to a preoperative target of 62-66 % of the width of the tibial plateau. RESULTS: This model suggests that, to deliver the weight-bearing line to the preoperative target on plane radiographs, the theoretical medial wedge must be opened to an accuracy of ±0.9 mm. CONCLUSION: Although this study only explores a model of wedge opening based on AP radiographs, with current surgical systems, it is unlikely that the surgeon can achieve this level of accuracy within a real-life surgical setting. Surgical accuracy in HTO is known to be important for both short- and long-term clinical outcomes. This study highlights the need for improved surgical accuracy aids and/or patient stratification to mitigate the effects of surgical errors. LEVEL OF EVIDENCE: II.

A survival analysis of 1084 knees of the Oxford unicompartmental knee arthroplasty: a comparison between consultant and trainee surgeons.

AIMS: The aim of this to study was to compare the previously unreported long-term survival outcome of the Oxford medial unicompartmental knee arthroplasty (UKA) performed by trainee surgeons and consultants. PATIENTS AND METHODS: We therefore identified a previously unreported cohort of 1084 knees in 947 patients who had a UKA inserted for anteromedial knee arthritis by consultants and surgeons in training, at a tertiary arthroplasty centre and performed survival analysis on the group with revision as the endpoint. RESULTS: The ten-year cumulative survival rate for revision or exchange of any part of the prosthetic components was 93.2% (95% confidence interval (CI) 86.1 to 100, number at risk 45). Consultant surgeons had a nine-year cumulative survival rate of 93.9% (95% CI 90.2 to 97.6, number at risk 16). Trainee surgeons had a cumulative nine-year survival rate of 93.0% (95% CI 90.3 to 95.7, number at risk 35). Although there was no differences in implant survival between consultants and trainees (p = 0.30), there was a difference in failure pattern whereby all re-operations performed for bearing dislocation (n = 7), occurred in the trainee group. This accounted for 0.6% of the entire cohort and 15% of the re-operations. CONCLUSION: This is the largest single series of the Oxford UKA ever reported and demonstrates that good results can be achieved by a heterogeneous group of surgeons, including trainees, if performed within a high-volume centre with considerable experience with the procedure. Cite this article: Bone Joint J 2016;(10 Suppl B):22-7.

A review of current surgical practice in the operative treatment of proximal humeral fractures: Does the PROFHER trial demonstrate a need for change?

OBJECTIVES: The PROximal Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial has recently demonstrated that surgery is non-superior to non-operative treatment in the management of displaced proximal humeral fractures. The objective of this study was to assess current surgical practice in the context of the PROFHER trial in terms of patient demographics, injury characteristics and the nature of the surgical treatment. METHODS: A total of ten consecutive patients undergoing surgery for the treatment of a proximal humeral fracture from each of 11 United Kingdom hospitals were retrospectively identified over a 15 month period between January 2014 and March 2015. Data gathered for the 110 patients included patient demographics, injury characteristics, mode of surgical fixation, the grade of operating surgeon and the cost of the surgical implants. RESULTS: A majority of the patients were female (66%, 73 of 110). The mean patient age was 62 years (range 18 to 89). A majority of patients met the inclusion criteria for the PROFHER trial (75%, 83 of 110). Plate fixation was the most common mode of surgery (68%, 75 patients), followed by intramedullary fixation (12%, 13 patients), reverse shoulder arthroplasty (10%, 11 patients) and hemiarthroplasty (7%, eight patients). The consultant was either the primary operating surgeon or supervising the operating surgeon in a large majority of cases (91%, 100 patients). Implant costs for plate fixation were significantly less than both hemiarthroplasty (p < 0.05) and reverse shoulder arthroplasty (p < 0.0001). Implant costs for intramedullary fixation were significantly less than plate fixation (p < 0.01), hemiarthroplasty (p < 0.0001) and reverse shoulder arthroplasty (p < 0.0001). CONCLUSIONS: Our study has shown that the majority of a representative sample of patients currently undergoing surgical treatment for a proximal humeral fracture in these United Kingdom centres met the inclusion criteria for the PROFHER trial and that a proportion of these patients may, therefore, have been effectively managed non-operatively.Cite this article: Mr B. J. F. Dean. A review of current surgical practice in the operative treatment of proximal humeral fractures: Does the PROFHER trial demonstrate a need for change? Bone Joint Res 2016;5:178-184. DOI: 10.1302/2046-3758.55.2000596.

A novel use of reticulated hyaluronic acid (Healaflow) for hypotony eyes in patients with uveitis.

Persistent ocular hypotony is a complex and ongoing challenge faced in ophthalmology. It can result in early ocular phthisis and associated visual decline, pain and deformity. We present the first case series, in which repeated intracameral injections of highly reticulated hyaluronic acid (Healaflow) have successfully prevented the complications of ocular hypotony in the long term. We believe it is a viable management option that can bring about a significant improvement to the quality of life in this subgroup of patients while avoiding frequent intervention.

The clinical symptom profile of early radiographic knee arthritis: a pain and function comparison with advanced disease.

PURPOSE: Early knee OA is a significant problem that can be disabling. The purpose of this study was to understand the symptomatic profile of patients with early knee OA when compared to those with end-stage knee OA. METHODS: A cross-sectional case control study design was used to compare those with early structural change to those with advanced structural change. In total, 100 consecutive patients with early radiographic knee OA presenting to the knee service outpatient clinic from December 2010 to August 2011 were prospectively identified on the basis of their radiographic changes. All met the symptomatic and radiological diagnostic criteria of early knee OA as defined by Luyten et al. They were compared with 200 knees with full thickness anteromedial knee OA and 200 knees with full thickness tricompartmental knee OA for their demographic, pain and functional profile. RESULTS: Patients with early knee OA were younger than those with full thickness disease. However, 78% of individual patients with early radiographic OA had pain and function scores equal to individual patients presenting for UKA, whilst 74% of individual patients with early radiographic OA had pain and function scores that are equal to or worse than individual patients presenting for TKA. CONCLUSIONS: Patients with early radiographic knee OA demonstrate considerable overlap in the severity of their symptoms with those demonstrating end-stage structural changes within the knee. Patients with early structural changes of arthritis should not be assumed by clinicians to have mild disease. In many cases, their symptoms are as bad as those with end-stage structural changes. This work will help clinicians to identify and categorise those with early arthritis and thereby assist in guiding appropriate treatments.

Indirect trauma causing dislocation of the crystalline lens--a case report.

PURPOSE: To report a case of indirect trauma causing dislocation of the crystalline lens in a patient with no underlying risk factors. METHODS: Case report. RESULTS: A 76-year-old woman fell injuring her right temple area. She complained of blurring of vision in her right eye. Her vision was reduced to 6/60. Ocular examination revealed right aphakia associated with complete posterior dislocation of the crystalline lens into the vitreous cavity. No predisposing factors as pigment dispersion or pseudoexfoliation material was found on gonioscopy. CONCLUSIONS: Dislocation of the crystalline lens has been reported following direct trauma. It is known to occur spontaneously in mature and hypermature cataracts and in cases of weak zonules. Our case shows that indirect trauma can cause complete dislocation of the crystalline lens in the absence of any predisposing factors.

Antibody and interleukin-12 treatment in murine models of encephalitogenic flavivirus (St. Louis encephalitis, tick-borne encephalitis) and alphavirus (Venezuelan equine encephalitis) infection.

Early and sustained treatment with interleukin-12 (IL-12) ameliorated disease in a mouse model of infection with the encephalitogenic flavivirus, St. Louis encephalitis virus (SLEV, Japanese encephalitis serogroup). However, this effect was not reproduced in murine infections with either the flavivirus tick-bore encephalitis virus (TBEV) or the alphavirus Venezuelan equine encephalitis virus (VEEV). IL-12 exacerbated TBEV disease when used in conjunction with monoclonal antibody (mAb), suggesting an enhancement of immunopathology, and was without clinical effects in VEEV infection. These data confirm the need to fully understand the pathogenesis of viral infection before cytokine intervention may be employed as a broad-spectrum antiviral therapy.

Cytotoxic T-cell activity is not detectable in Venezuelan equine encephalitis virus-infected mice.

Previously published research has established that the immune response to the Venezuelan equine encephalitis virus (VEEV) vaccine strain TC-83 is Th 1-mediated, with local activation of both CD4+ and CD8+ T cells. This suggests that cytotoxic lymphocytes CTL may play a role in protection against virulent VEEV. Studies involving a variety of immunisation schedules with either TC-83 or strain CAAR 508 (serogroup 5) of VEEV, and six different haplotypes of mice, failed to reveal functional CTL activity against VEEV-infected targets in secondary antigen-stimulated lymphocyte cultures from either the draining lymph nodes (LN) or spleen. Nor were VEEV-specific CTL detected after immunisation of mice (three haplotypes) with recombinant vaccinia viruses (VV) expressing either the non-structural (nsP1-4) or the structural (C-E3-E2-6K-E1) genes of TC-83. Reciprocal experiments in which mice were immunised with TC-83, and their lymphocytes tested against VV recombinant-infected targets also failed to detect CTL activity. These data suggest that VEEV infection of mice does not elicit detectable CTL activity, and that CTL are unlikely to play a role in protection against virulent VEEV.

Monoclonal antibody protects mice against infection and disease when given either before or up to 24 h after airborne challenge with virulent Venezuelan equine encephalitis virus.

Airborne infection with Venezuelan equine encephalitis virus (VEEV) is a significant hazard for laboratory workers, who may not be immunised against VEEV infection as there is no vaccine currently available suitable for human use. We describe a potential alternative strategy that could protect workers exposed to VEEV or similar viruses. VEEV-specific murine monoclonal antibodies (MAB), given by intraperitoneal (i.p.) injection to mice as a single dose of 100 microg, have a half-life of 6-10 days in serum and spread by transudation to respiratory secretions. Administration of MAB (approximately 4 mg/kg) to mice 24h before challenge with approximately 100LD50 of virulent VEEV protected up to 100% animals. The same dose of MAB delivered up to 24h after challenge protected approximately 50%. Two MAB that were synergistic in vitro in plaque reduction neutralisation tests were not synergistic in vivo in protection assays. An examination of virus multiplication, in the blood and internal organs (brain, spleen, lung) of MAB-treated mice infected by the airborne route with VEEV, suggested that therapeutic activity depended both upon the prevention of virus infection of the brain, and the rapid clearance of virus from the periphery. Antiviral therapy with VEEV-specific human or "humanised" MAB, providing that they are administered early, may offer an alternative means of specific medical intervention for those with a known exposure to VEEV.

Tick-borne encephalitis virus in northern Italy: molecular analysis, relationships with density and seasonal dynamics of Ixodes ricinus.

Ixodes ricinus ticks were collected from dragging vegetation and from shot roe deer in the province of Trento and Belluno in northern Italy. Ticks were pooled for analyses and from 1060 pools of ticks collected in the province of Belluno and 12390 tick samples collected in Trentino, four proved positive by immunofluorescence microscopy using a tick-borne encephalitis (TBE)-specific antiserum. The identity of the virus isolates was determined by RT-PCR cycle sequencing and they were all found to be closely similar (> 98% nucleotide identity) to typical western European TBE complex viruses as found in Austria. The isolates from Trentino differed from the Neudorfl strain of western European TBE virus at eight nucleotide positions but as these nucleotide substitutions were all synonymous, there were no amino acid changes. These results imply that the virus isolates in Trentino have changed slightly from the typical European strains isolated in nearby Austria. The abundance of questing ticks and ticks feeding on roe deer was greater in TBE positive hunting districts than in hunting districts where TBE complex viruses were only probable or believed to be absent. In TBE positive and probable districts synchrony in the seasonal dynamics of larvae and nymphs of L. ricinus was observed. This study provides evidence to suggest that roe deer may have an important role to play in the maintenance of tick density and in the persistence of TBE virus.

Role of small mammals in the persistence of Louping-ill virus: field survey and tick co-feeding studies.

Louping-ill (LI) is a tick-borne viral disease of red grouse, Lagopus lagopus scoticus Lath. (Tetraonidae: Galliformes), and sheep, Ovis aries L. (Bovidae: Artiodactyla), that causes economic loss to upland farms and sporting estates. Unvaccinated sheep, grouse and mountain hares, Lepus timidus L. (Leporidae: Lagomorpha), are known to transmit LI virus, whereas red deer, Cenrus elaphus L. (Cervidae: Artiodactyla), and rabbits, Oryctolagus cuniculus L. (Leporidae: Lagomorpha), do not. However, the role of small mammals is unknown. Here, we determine the role of small mammals, in particular field voles, Microtus agrestis L. (Muridae: Rodentia), in the persistence of LI virus on upland farms and sporting estates in Scotland, using field sampling and non-viraemic transmission trials. Small mammals were not abundant on the upland sites studied, few ticks were found per animal and none of the caught animals tested seropositive to LI virus. Laboratory trials provided no evidence that small mammals (field voles, bank voles, Clethrionomys glareolus L. (Muridae: Rodentia), and wood mice, Apodemus sylvaticus L. (Muridae: Rodentia), can transmit LI virus between cofeeding ticks and, in the field, LI virus was prevalent only in areas with known LI virus competent hosts (grouse, mountain hares or unvaccinated sheep) and absent elsewhere. In contrast to the case of tick-borne encephalitis (TBE) virus in Europe, it is concluded that small mammals seem to be relatively unimportant in LI virus persistence.

Divergent selection for heat loss in mice: I. Selection applied and direct response through fifteen generations.

Divergent selection for heat production/loss (kcal.kg-.75.d-1), measured in 9- to 11-wk-old male mice, was conducted for 15 generations. Heat loss was measured for 15 h on individual animals placed overnight in direct, gradient-layer calorimeters. Selection for high (MH) and low (ML) heat loss and unselected control (MC) occurred in each of three replicates for a total of nine unique lines. Repeatability of the heat loss measurement was .45 and the CV was 10.5%. Cumulative realized selection differentials, averaged for the three replicates, were 145.1 and -105.0 (kcal.kg-.75.d-1) and ranged from 136.9 to 149.2 and -17.1 to -101.3 for MH and ML selection, respectively. Cumulative standardized realized selection differentials, averaged for the three replicates, were 10.06 and -9.51 for MH and ML selection, respectively. Direct responses (kcal.kg-.75.d-1) in heat loss after 15 generations were 44.2 for MH and -27.4 for ML as deviations from MC. Asymmetry of response was evident (P = .03) by Generation 10. Realized heritability was .28 +/- .01 based on divergence of MH and ML selection. For selection for higher and lower heat loss, realized heritabilities were .31 +/- .01 and .26 +/- .01, respectively.

Divergent selection for heat loss in mice: II. Correlated responses in feed intake, body mass, body composition, and number born through fifteen generations.

Divergent selection for heat loss (kcal.kg-.75.d-1), measured in 9- to 11-wk-old male mice, was conducted for 15 generations. Selection for high (MH) and low (ML) heat loss and unselected control (MC) occurred in each of three replicates for a total of nine unique lines. Feed intake in males was measured during Generations 9 through 15. Body mass at commencement of mating in females and at time of measurement of heat loss in males was recorded. Body fat percentage at 12 wk for animals of Generations 6, 10, and 14 was predicted as a function of electrical conductivity and body mass. Litter size was recorded for all generations, and components of litter size were evaluated at Generation 11 in one replicate and Generation 12 in the other two replicates. Feed intake changed in the same direction as heat loss for the MH and ML selections; at Generation 15, the difference between MH and ML (P < .002) was 20.6% of the MC mean. Body mass did not change with selection for heat loss. Differences in body fat percentage were not significant in earlier generations, but at Generation 14, MH and ML were significantly (P < .01) different with MH mice having the lowest fat percentage; MC was intermediate. Selection had a significant (MH vs ML; P < .01) effect on litter size, causing an increase in MH and a decrease in ML. This difference was explained by a difference (P < .01) in ovulation rate. There was no asymmetry of response in feed intake, fatness, litter size, or number of ovulations.

Baculovirus-expressed nonstructural protein NS2 of bluetongue virus induces a cytotoxic T-cell response in mice which affords partial protection.

Virus-specific cytotoxic T lymphocytes were generated in two strains of mice (BALB/c and CBA/Ca) against baculovirus recombinant proteins (minor and nonstructural) derived from bluetongue virus serotype 10. Immunization of mice with recombinant baculovirus insect cell extracts expressing the nonstructural protein NS2 (Bac-NS2) conferred partial protection against infection with vaccinia virus expressing the NS2 protein. This protective immunity was mediated by CD8+ cells. In contrast, no protection was observed when mice were immunized with similarly expressed Bac-NS1 or -NS3 or the virion minor structural proteins (Bac-VP1, -VP4, or -VP6). Furthermore, the in vitro cytotoxicity activity of T cells derived from immunized animals did not correlate to the protective efficacy of baculovirus recombinant proteins. The implications of this work with regard to the design of noninfectious subunit vaccines are discussed.

Transmission of louping ill virus between infected and uninfected ticks co-feeding on mountain hares.

Most of the data on oral infection of ticks by louping ill virus have been obtained from experiments in which animals were infected by syringe inoculation with infectious material. Using infected ticks to mimic the natural situation, we have demonstrated that louping ill (LI) virus transmission can occur from infected to uninfected Ixodes ricinus feeding in close proximity on mountain hares (Lepus timidus). Under these conditions the hares developed either low or undetectable viraemias. Highest prevalence of LI virus infection was observed in recipient nymphs which had fed to repletion between days 3 and 7 post-attachment of virus-infected adults; following engorgement, 56% of nymphs acquired virus. These results demonstrate the efficient transmission of LI virus between co-feeding ticks on naive mountain hares. However, when ticks were allowed to co-feed on virus-immune hares a significant reduction in the frequency of infection was observed. Neither red deer (Cervus elaphus) nor New Zealand White rabbits supported transmission of LI virus. The significance of virus transmission between cofeeding ticks on LI virus epidemiology is discussed.

Definitive identification of louping ill virus by RT-PCR and sequencing in field populations of Ixodes ricinus on the Lochindorb estate.

Rapid and precise virus detection procedures are an important component of any epizootiological study. An automated one tube reverse transcriptase and nested primer polymerase chain reaction (RT-PCR) followed by nucleotide sequencing of the cDNA product, was used for the rapid detection and identification of louping ill (LI) virus in field caught Ixodes ricinus and compared with a classical isolation method i.e. infectivity in cell culture. The results establish the genetic identity of LI virus on the Lochindorb Estate. There was a high correlation between the results obtained by RT-PCR and infectivity assays. RT-PCR and sequencing proved to be a rapid and accurate system for identifying LI virus in field specimens. Development of this system should improve the capacity to undertake detailed epizootiological studies of LI virus.

Building the information infrastructure required for managed care.

PURPOSE: To describe the information used by health care purchasers, policymakers, and administrators when making the decisions required in a managed-care environment and what the profession must do to develop an information infrastructure to demonstrate its contribution to patient outcomes. SCOPE: Managed care has created a competitive environment for all health care organizations in which they must offer the best value for their dollar. The purchasing processes germane to managed care rely heavily on information for the selection of cost-effective providers and the provision of efficient care. Information used in these processes is derived from transaction systems that largely describe physician and other health care worker's services, but not nursing care. Data analysis by computers requires that data be obtained using a standardized language. Currently, nursing lacks a unified approach to the use of a standardized nursing language. CONCLUSIONS: Individual nurses, nurse managers, executives, and educators should strive to develop an information infrastructure that will overcome barriers. Nurses should both adopt a unified approach to a standardized language, and develop a nationwide information infrastructure that will demonstrate nursing's contribution to patient outcomes.

The non-structural proteins of bluetongue virus are a dominant source of cytotoxic T cell peptide determinants.

Virus-specific, CD8+ cytotoxic T lymphocytes (CTLs) were generated in two strains of mice (BALB/c, CBA/Ca) against bluetongue virus serotype 10 (BTV-10). Recombinant vaccinia viruses (VV) expressing the individual structural and non-structural proteins of BTV were used to infect syngeneic target cells. We found that in both BALB/c (H-2d) and CBA/Ca (H-2k) mice, polyclonal CTL populations recognized target cells expressing the non-structural proteins better than those expressing the structural proteins. CTLs generated against other BTV serotypes also predominantly recognized the non-structural proteins. However, the extent of cross-reactivity was dependent on the H-2 background of the animals immunized. No CTLs cross-reactive to the BTV-10 heterotype were demonstrated with the panel of molecularly cloned recombinants in the H-2d haplotype. The outer capsid proteins VP2 and VP5 which vary considerably between serotypes were not recognized by heterotypic CTLs. Using this murine model we have determined which BTV proteins are the major targets of the CTL response. The implications for the design and development of subunit vaccines are discussed.