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.

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.

A novel mode of arbovirus transmission involving a nonviremic host.

In nature, infected and uninfected arthropod vectors often feed together on an animal. In mimicking this scenario in the laboratory, uninfected vectors were found to acquire virus while cofeeding on the same host as infected vectors. However, the vertebrate host on which they fed did not develop detectable levels of virus in its blood. These observations were made with Thogoto virus, an influenza-like virus of medical and veterinary significance. Rhipicephalus appendiculatus ticks were used as the vector and guinea pigs as the vertebrate host. The results demonstrate that a vertebrate that is apparently refractory to infection by an arthropod-borne virus can still play an important role in the epidemiology of the virus, and they suggest a novel mode of arthropod-borne virus transmission.

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.

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.

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.

The effect of virus-immune hosts on Thogoto virus infection of the tick, Rhipicephalus appendiculatus.

Thogoto (THO) virus infections of Rhipicephalus appendiculatus ticks were examined using tick hosts immune to the virus. In the first set of experiments, ticks were infected by feeding on viraemic hamsters. Inter-stadial infection of THO virus was not affected when ticks ingested a virus-immune bloodmeal but there was an effect on persistence of the virus. The incidence of intra-stadial infection was reduced by at least 40% when nymphs partially fed on viraemic hamsters and completed their bloodmeal on a virus-immune guinea pig. When the reverse situation was examined--feeding on a virus-immune host and then a viraemic host--no difference was observed in the number of ticks infected. In the second set of experiments, uninfected ticks acquired virus by co-feeding with infected ticks on apparently non-viraemic guinea pigs. Non-viraemic transmission of the viruses was inhibited when the guinea pigs were immune to either the Sicilian (SiAr 126) or prototype (IIA) isolates of THO virus. The laboratory data indicate that virus-immune hosts may have a significant effect on the role played by ticks in the epidemiology of tick-borne viruses.

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.

A comparative study of the infection thresholds of Thogoto virus in Rhipicephalus appendiculatus and Amblyomma variegatum.

Infection thresholds of Thogoto virus in 2 ixodid tick species, Rhipicephalus appendiculatus and Amblyomma variegatum, were compared. Thogoto virus has been isolated from naturally infected R. appendiculatus and A. variegatum in Central Africa, where both commonly parasitize the same hosts. No significant difference was found between the infection thresholds of Thogoto virus in the 2 species. The percentage of nymphs of both species infected by feeding on viremic hamsters was directly correlated with the time between host inoculation and tick engorgement. The blood titers in infected hamsters increased each day during the 3-4 day viremia until the hamsters died. The percentage of nymphs infected correlated with the viremic titer on the final day of engorgement (the time of maximum blood uptake). The 5% infection threshold for nymphs of R. appendiculatus and A. variegatum was estimated as 10(2.8) and 10(2.7) plaque forming units (PFU)/ml viremia, respectively. The prevalence of infection approached 100% for blood titers greater than 10(6.3) PFU/ml and greater than 10(7) PFU/ml, respectively. The apparent bloodmeal size of the 2 species differed by 8-fold and suggested that, in terms of the number of PFU ingested, R. appendiculatus was more susceptible than A. variegatum to per os infection by Thogoto virus.

Experimental studies on the transmission cycle of Thogoto virus, a candidate orthomyxovirus, in Rhipicephalus appendiculatus.

Thogoto (THO) virus, a candidate orthomyxovirus, replicated in and was transmitted by larvae, nymphs, and adults of the brown ear tick, Rhipicephalus appendiculatus. Larvae fed on viremic hamsters (10(7-8) PFU/ml blood) acquired an average of 10(2.5) PFU per tick. Following engorgement the titer dropped to 10(1.9) PFU on day 2 but increased by day 6 to 10(3.3) PFU. Virus survived transstadially in these ticks as demonstrated by the fact that, on day 10, newly moulted nymphs contained, on average, 10(3.5) PFU/tick. When 10 such infected nymphs were placed on a hamster a fatal infection of the animal developed involving a viremia of 10(6.7) PFU/ml blood. Another group of 6 infected nymphs did not elicit a detectable viremia in a hamster, or cause death. However the animal seroconverted to THO, virus indicating that virus transmission had occurred. Following acquisition of THO virus at the larval stage, virus was detected in adult ticks 138 days later. Uninfected nymphs fed on viremic hamsters acquired an average of 10(4) PFU/nymph. No virus was detected in the nymphs 4 days post-engorgement. Virus was, however, recovered by 6 days post-engorgement (10(4.7) PFU/nymph). Virus persisted transstadially as shown by the presence of an average of 10(3.4) PFU in newly moulted adults. Three groups of these infected adults (5-6 ticks/group) induced viremia in hamsters with blood titers of the order 10(2.8-3.5) PFU/ml. Virus persisted in engorged adults for up to 66 days following nymphal engorgement.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of mice and cell cultures for the isolation of tick-borne viruses.

Three methods of isolating viruses from 10 tick pools were compared; none of the methods produced all 13 of the viruses isolated (7 viruses of the bunyaviridae and 6 orbiviruses). Inoculation of homogenised ticks into various cell lines was the most successful, yielding 11 virus isolations. Only 2 tick homogenates induced overt signs of infection following intra-cerebral inoculation of 2-day-old mice. However, when inoculated mouse brain was passaged in various cell lines, 8 of 12 isolations were made. The rates of success of the 3 methods of virus isolation appeared to vary according to the type and titre of the virus in the tick pool.

Non-viraemic transmission of Thogoto virus: influence of time and distance.

Previous studies have demonstrated that Thogoto virus is transmitted from infected to uninfected ticks when co-feeding on uninfected guinea-pigs, even though the guinea-pigs do not develop detectable viraemia. The dynamics of this 'non-viraemic transmission' were investigated. The percentage of nymphs (recipients) that acquired virus increased from zero, when co-feeding with infected adults (donors) for 3 d, to 80% for a co-feeding period of 5 d. No statistically significant difference was detected when infected donors and uninfected recipients were separated physically up to a maximum distance of approximately 160 mm. These results indicate that the temporal, but not the spatial, relationship affects the number of recipient ticks that become infected.

Non-viraemic transmission of Thogoto virus: vector efficiency of Rhipicephalus appendiculatus and Amblyomma variegatum.

Previous studies have demonstrated that Thogoto virus is transmitted from infected to uninfected ticks when co-feeding on uninfected guinea-pigs, even though the guinea-pigs do not develop a detectable viraemia. Furthermore, tick to tick transmission is potentiated by factors associated with the salivary glands of ticks (saliva activated transmission). The vector efficiency of 2 ixodid tick species, Rhipicephalus appendiculatus and Amblyomma variegatum, for Thogoto virus was assessed using this model. The number of uninfected recipient ticks that acquired Thogoto virus when co-feeding with virus-infected ticks (donors) on uninfected guinea-pigs was determined. When nymphs of either tick species were employed as donors, there was no significant difference in the number of infected recipient nymphs. In contrast, a significant difference in the vector efficiency of adults ticks was observed: 77.0% of recipient ticks which co-fed with R. appendiculatus donor adults acquired Thogoto virus compared to 44.7% of recipient ticks which co-fed with A. variegatum donors. No significant difference in susceptibility to Thogoto virus infection was observed between recipient ticks of the 2 species. Thus, adults of R. appendiculatus are more efficient than A. variegatum in mediating non-viraemic transmission.

Adaptations of arboviruses to ticks.

Arboviruses differ from other viruses in their need to replicate in both vertebrate and invertebrate hosts. The invertebrate is a blood-sucking arthropod that is competent to transmit the virus between susceptible animals. Arboviruses transmitted by ticks must adapt to the peculiar physiological and behavioral characteristics of ticks, particularly with regard to blood feeding, bloodmeal digestion, and molting. Virus imbibed with the blood meal first infects cells of the midgut wall. During this phase the virus must contend with the heterophagic bloodmeal digestion of ticks (an intracellular process occurring within midgut cells) and overcome the as yet undefined "gut barrier" to infection. Genetic and molecular data for a number of tick-borne viruses indicate ways in which such viruses may have adapted to infecting ticks, but far more information is needed. After infection of midgut cells, tick-borne viruses pass to the salivary glands for transmission during the next blood-feeding episode. To do this, the virus must survive molting by establishing an infection in at least one cell type that does not undergo histolysis. Different tick-borne viruses have different strategies for surviving the molting period, targeting a variety of tick tissues. The infection can then persist for the life span of the tick with little evidence of any detrimental effects on the tick. Transmission to a vertebrate host during feeding most probably occurs via saliva that contains virus secreted from infected salivary gland cells. The virus then enters the skin site of feeding, which has been profoundly modified by the pharmacological effects of tick saliva. At least three tick-borne viruses exploit such tick-induced host changes. This phenomenon (saliva-activated transmission) is believed to underlie "nonviremic transmission," whereby a virus is transmitted from an infected to an uninfected cofeeding tick through a host that has an undetectable or very low viremia. Thus tick-borne viruses that have adapted to the feeding characteristics of their tick vectors may not need to induce a virulent infection (with high viremia) in their natural vertebrate hosts. Efficient transmission of tick-borne viruses between cofeeding ticks may be a means of amplifying virus infection prevalence in F1 generations infected by transovarial transmission.

Efficient transmission of tick-borne encephalitis virus between cofeeding ticks.

Most of the data on oral infections of ticks with tick-borne encephalitis virus have been derived from experiments using animals infected by syringe inoculation. To mimic the natural conditions of virus transmission, tick-borne encephalitis virus-infected Ixodes ricinus (Linnaeus) or Rhipicephalus appendiculatus Neumann adults (donors) were cofed with uninfected nymphs (recipients) of either tick species on uninfected guinea pigs. Two tick-retaining cells were attached to each guinea pig: cell 1 contained uninfected nymphs and virus-infected adults, and cell 2 contained uninfected nymphs. Following engorgement, 55% of I. ricinus nymphs and 65% of R. appendiculatus nymphs were shown to have acquired the virus while cofeeding with I. ricinus donor ticks. Similarly, 66% of R. appendiculatus recipient nymphs that cofed with R. appendiculatus virus-infected adults were infected. Some of the guinea pigs on which the ticks cofed were apparently nonviremic. The results indicate that efficient transmission of tick-borne encephalitis virus can occur between cofeeding ticks even when the host on which they feed does not develop a detectable viremia.

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.

Genetic variation in liver mass, body mass, and liver:body mass in mice.

Genetic variation for liver mass (LM), body mass (BM), and liver:body mass (LM/BM) was examined for outbred populations of laboratory mice. Liver mass and body mass data were collected on 170 pureline sires at 12 wk of age, representing four outbred stocks of laboratory mice; 523 of their male and female two-way-cross progeny at 9 or 12 wk; and 214 four-way-cross offspring at 12, 14, or 16 wk. Genetic differences for LM, BM, and LM/BM were found among the base sire lines and between two-way crosses. Heritabilities and genetic correlations for LM, BM, LM/BM, and LM/MBM (MBM = BM.75) were estimated using offspring-sire regression within and across characteristics. Estimates of heritabilities and genetic correlations were also derived from full-sib covariances in the two-way-cross generation. Heritability estimates pooled over all analyses were .53, .54, .36, and .40 for LM, BM, LM/BM, and LM/MBM, respectively. Body mass was highly genetically correlated (.87) with LM and lowly correlated with LM/BM. Previous research has indicated possible positive relationships between LM/BM and maintenance energy requirements in mature, nonlactating, nonpregnant animals. A selection index was developed for increasing BM but restricting genetic change in LM to zero. Selection using this index would be 40% as efficient in increasing BM as selection on BM alone but may hold maintenance energy requirements at a stable level.

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.