Does virtual reality simulation have a role in training trauma and orthopaedic surgeons?

Aims: The aim of this study was to assess the current evidence relating to the benefits of virtual reality (VR) simulation in orthopaedic surgical training, and to identify areas of future research. Materials and Methods: A literature search using the MEDLINE, Embase, and Google Scholar databases was performed. The results' titles, abstracts, and references were examined for relevance. Results: A total of 31 articles published between 2004 and 2016 and relating to the objective validity and efficacy of specific virtual reality orthopaedic surgical simulators were identified. We found 18 studies demonstrating the construct validity of 16 different orthopaedic virtual reality simulators by comparing expert and novice performance. Eight studies have demonstrated skill acquisition on a simulator by showing improvements in performance with repeated use. A further five studies have demonstrated measurable improvements in operating theatre performance following a period of virtual reality simulator training. Conclusion: The demonstration of 'real-world' benefits from the use of VR simulation in knee and shoulder arthroscopy is promising. However, evidence supporting its utility in other forms of orthopaedic surgery is lacking. Further studies of validity and utility should be combined with robust analyses of the cost efficiency of validated simulators to justify the financial investment required for their use in orthopaedic training. Cite this article: Bone Joint J 2018;100-B:559-65.

Bisphosphonates and atypical subtrochanteric fractures of the femur.

OBJECTIVES: Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs. METHODS: We present an evaluation of current literature relating to the pathogenesis and treatment of AFFs in the context of bisphosphonate use. RESULTS: Six broad themes relating to the pathogenesis and management of bisphosphonate-related AFFs are presented. The key themes in fracture pathogenesis are: bone microdamage accumulation; altered bone mineralisation and altered collagen formation. The key themes in fracture management are: medical therapy and surgical therapy. In addition, primary prevention strategies for AFFs are discussed. CONCLUSIONS: This article presents current knowledge about the relationship between bisphosphonates and the development of AFFs, and highlights key areas for future research. In particular, studies aimed at identifying at-risk subpopulations and organising surveillance for those on long-term therapy will be crucial in both increasing our understanding of the condition, and improving population outcomes.Cite this article: N. Kharwadkar, B. Mayne, J. E. Lawrence, V. Khanduja. Bisphosphonates and atypical subtrochanteric fractures of the femur. Bone Joint Res 2017;6:144-153. DOI: 10.1302/2046-3758.63.BJR-2016-0125.R1.

Functional outcomes of conservatively managed acute ruptures of the Achilles tendon.

AIMS: This prospective cohort study aims to determine if the size of the tendon gap following acute rupture of the Achilles tendon shows an association with the functional outcome following non-operative treatment. PATIENTS AND METHODS: All patients presenting within two weeks of an acute unilateral rupture of the Achilles tendon between July 2012 and July 2015 were considered for the study. In total, 38 patients (nine female, 29 male, mean age 52 years; 29 to 78) completed the study. Dynamic ultrasound examination was performed to confirm the diagnosis and measure the gap between ruptured tendon ends. Outcome was assessed using dynamometric testing of plantarflexion and the Achilles tendon Total Rupture score (ATRS) six months after the completion of a rehabilitation programme. RESULTS: Patients with a gap ≥ 10 mm with the ankle in the neutral position had significantly greater peak torque deficit than those with gaps < 10 mm (mean 23.3%; 7% to 52% vs 14.3%; 0% to 47%, p = 0.023). However, there was no difference in ATRS between the two groups (mean score 87.2; 74 to 100 vs 87.4; 68 to 97, p = 0.467). There was no significant correlation between gap size and torque deficit (τ = 0.103), suggesting a non-linear relationship. There was also no significant correlation between ATRS and peak torque deficit (τ = -0.305). CONCLUSION: This is the first study to identify an association between tendon gap and functional outcome in acute rupture of the Achilles tendon. We have identified 10 mm as a gap size at which deficits in plantarflexion strength become significantly greater, however, the precise relationship between gap size and plantarflexion strength remains unclear. Large, multicentre studies will be needed to clarify this relationship and identify population subgroups in whom deficits in peak torque are reflected in patient-reported outcome measures. Cite this article: Bone Joint J 2017;99-B:87-93.

Data errors in the National Hip Fracture Database: a local validation study.

AIMS: We present an audit comparing our level I major trauma centre's data for a cohort of patients with hip fractures in the National Hip Fracture Database (NHFD) with locally held data on these patients. PATIENTS AND METHODS: A total of 2036 records for episodes between July 2009 and June 2014 were reviewed. RESULTS: The demographics of nine patients were recorded incorrectly. The rate of incorrect data in operation codes was most significant with overall accuracy of 0.637 (95% CI 0.615 to 0.658). The sensitivity of NHFD coding ranged from 0.250 to 1.000 and the specificity 0.879 to 0.999. The recording of cementation had a sensitivity of 0.932 and specificity of 0.713. The recording of total hip arthroplasty had a sensitivity of 0.739 and specificity of 0.983. The overall accuracy of mortality data was 0.942 (95% CI 0.931 to 0.952), with sensitivity of 0.967 and specificity of 0.419. CONCLUSION: This paper highlights the need for local audit of the integrity of data uploaded to the NHFD. Cite this article: Bone Joint J 2016;98-B:1406-9.

The complete nucleotide sequence of hydrangea ringspot virus. Brief report.

The complete nucleotide sequence of the genome of the potexvirus, hydrangea ringspot virus, has been determined. The sequence is 6,185 nt in length, excluding the poly (A) tail, and contains six ORFs coding for proteins of 156, 26, 12, 8, 24, and 16 kDa, respectively. ORF 6 is contained within ORF 5 and in this respect the virus is similar to the potexviruses CsCMV, NMV, and SMYEV. Phylogenetic analysis of the putative products of the ORFs and signature motifs contained within these products shows the virus to be most closely related to CsCMV. A similar analysis of data for the coat proteins of potexviruses did not support the previously reported serological relationships between HdRSV and other potexviruses. This is the first complete sequence published for the genome of a potexvirus infecting a dicotyledonous, temperate, deciduous woody species.

Lysogeny and lytic viral production during a bloom of the cyanobacterium Synechococcus spp.

Lytic viral production and lysogeny were investigated in cyanobacteria and heterotrophic bacteria during a bloom of Synechococcus spp. in a pristine fjord in British Columbia, Canada. Triplicate seawater samples were incubated with and without mitomycin C and the abundances of heterotrophic bacteria, cyanobacteria, total viruses and infectious cyanophage were followed over 24 h. Addition of mitomycin C led to increases in total viral abundance as well as the abundance of cyanophages infecting Synechococcus strain DC2. Given typical estimates of burst size, these increases were consistent with 80% of the heterotrophic bacteria and 0.6% of Synechococcus cells being inducible by the addition of mitomycin C. This is the highest percentage of lysogens reported for a natural microbial community and demonstrates induction in a marine Synechococcus population. It is likely that the cyanophage production following the addition of mitomycin C was much higher than that titered against a single strain of Synechococcus; hence this estimate is a minimum. In untreated seawater samples, lytic viral production was estimated to remove ca. 27% of the gross heterotrophic bacterial production, and a minimum of 1.0% of the gross cyanobacterial production. Our results demonstrate very high levels of lysogeny in the heterotrophic bacterial community, outside of an oligotrophic environment, and the presence of inducible lysogens in Synechococcus spp. during a naturally occurring bloom. These data emphasize the need for further examination of the factors influencing lytic and lysogenic viral infection in natural microbial communities.

Biological control of the phytoparasitic nematode Mesocriconema xenoplax on peach trees.

Seven fluorescent Pseudomonas spp. capable of inhibiting reproduction of Mesocriconema xenoplax have been isolated from soil sites that suppress both nematode multiplication and Peach Tree Short Life (PTSL). One of these seven strains, Pseudomonas sp. BG33R, inhibits M. xenoplax multiplication in vivo and egg hatch in vitro. Mesocriconema xenoplax populations on peach seedlings inoculated with BG33R and planted into soil-solarized field plots remained at or below the economic threshold for nematicide treatment in South Carolina for nearly 18 months. Soil solarization alone induced a shift toward a microbial community that was suppressive to nematode multiplication. Additionally, five Tn5 mutants of BG33R, lacking the ability to kill eggs, have been generated. The Tn5 insertion site in each mutant has been cloned and sequenced. DNA sequence analysis has revealed a high degree of homology to several genes of interest because of their potential involvement in the production of the egg-kill factor. These Tn5 egg-kill negative mutants also no longer produce protease or salicylic acid while producing nearly twice the amount of fluorescent siderophore as the wild type parent.

The effect of recombinant human tsh on the thyroid (123)i uptake in iodide treated normal subjects.

UNLABELLED: Radioactive iodine therapy is often successful in the treatment of toxic or non-toxic multinodular goiter. However, when the patient has been exposed to iodine in the form of medication or radiocontrast agents prior to therapy, the thyroid radioactive iodine is often too low for successful ablation. Recently, administration of 0.9 mg of recombinant human TSH (rhTSH) has been shown to nearly double the 24-hour thyroid radioactive iodine uptake (RAIU) in euthyroid men living in the United States. In addition, 0.01 to 0.03 mg rhTSH administered 24 hours prior to (131)I in patients with a history of non-toxic multinodular goiter residing in an area of modestly low iodine intake, has also been shown to increase the 24-hour thyroid radioactive iodine uptake. We now have determined whether rhTSH administration prior to (123)I would increase the low thyroid RAIU in subjects treated with sodium iodide. Nine euthyroid men were given 15 mg iodide daily for 7 days. There was a marked increase in serum TSH values 8 and 24 hours after rhTSH administration, which induced elevated serum T4 and T3 concentrations. A 16 hour thyroid RAIU was measured at baseline, after 5 days of iodide administration, and either 8 or 32 hours after intramuscular administration of rhTSH. Administration of rhTSH 8 hours before (123)I to 4 subjects increased the 16 hour thyroid RAIU by 62% above the low post iodide thyroid RAIU. Administration of rhTSH 32 hours before (123)I administration to 5 subjects increased the 16 hour thyroid RAIU by 97% above the low iodide induced RAIU. Thus, the overall increase in the thyroid RAIU was 88% in the 9 subjects. CONCLUSION: Recombinant TSH moderately increased the thyroid RAIU in subjects with depressed thyroid RAIU's during iodide administration and thus may be useful in preparing patients with non-toxic or toxic goiters and low thyroid RAIU's due to excess iodine for radioactive iodine treatment. Further studies to determine the optimal protocol to enhance the effect of rhTSH will be carried out.

The effect of droloxifene and estrogen on thyroid function in postmenopausal women.

Estrogen is known to increase serum T4-binding globulin (TBG) concentrations, thereby increasing serum total T4 concentrations. Serum free T4 concentrations, however, remain normal. Tamoxifen, a selective estrogen receptor modifier (SERM), also raises serum TBG concentrations, but whether newer SERMs with less stimulatory action on the endometrium do so is not known. We, therefore, compared the effect of droloxifene, a SERM, and conjugated equine estrogen on pituitary-thyroid function in normal postmenopausal women. Ten women were treated for 6 weeks with conjugated estrogen (Premarin), 0.625 mg/day, and droloxifene, 60 mg/day, in a double-blind crossover study with an intervening 4-week no-treatment period. We measured serum T4, T3, TBG, free T4 index, and TSH at baseline and at the end of each 6-week period. The baseline values were compared with the 6-week values using paired t tests. The mean (+/- SD) serum TBG concentrations increased significantly during both treatment periods (baseline, 1.5+/-0.4 mg/dL; conjugated estrogens, 2.7+/-0.6 mg/dL; droloxifene, 2.1+/-0.6 mg/dL; P < 0.001 and P = 0.001, respectively). There were no significant changes in the serum free T4 index. Serum T4 and T3 concentrations increased during both treatment periods, however, the increase was significant only for T4 during the conjugated estrogen treatment period. The serum TSH concentrations increased significantly during both treatment periods (18% during conjugated estrogen and 11% during droloxifene), and the values remained within the normal range in all women. Administration of both conjugated estrogen and droloxifene for 6 weeks increases serum TSH and TBG concentrations, but does not alter free T4 index values in postmenopausal women.

Postprandial lipemia in young men and women of contrasting training status.

This study compared the postprandial triacylglycerol (TAG) response to a high-fat meal in trained and untrained normolipidemic young adults after 2 days' abstinence from exercise. Fifty-three subjects (11 endurance-trained men, 9 endurance-trained women, 10 sprint/strength-trained men, 11 untrained men, 11 untrained women) consumed a meal (1.2 g fat, 1.1 g carbohydrate, 66 kJ per kg body mass) after a 12-h fast. Venous blood samples were obtained in the fasted state and at intervals until 6 h. Postprandial responses were the areas under the plasma or serum concentration-vs.-time curves. Neither fasting TAG concentrations nor the postprandial TAG response differed between trained and untrained subjects. The insulinemic response was 29% lower in endurance-trained men than in untrained men [mean difference -37.4 (95% confidence interval -62.9 to -22.9) microIU/ml x h, P = 0.01]. Responses of plasma glucose, serum insulin, and plasma nonesterified fatty acids were all lower for endurance-trained men than for untrained men. These findings suggest that, in young adults, no effect of training on postprandial lipemia can be detected after 60 h without exercise. The effect on postprandial insulinemia may persist for longer.

The effect of short-term low-dose perchlorate on various aspects of thyroid function.

Perchlorate (ClO4) salts are found in rocket fuel, fireworks, and fertilizer. Because of ground water contamination, ClO4 has recently been detected in large public water supplies in several states in the 4-18 microg/L (parts per billion [ppb]) range. The potential adverse effect of chronic low level ClO4 ingestion on thyroid function is of concern to the Environmental Protection Agency (EPA). The daily ingestion of ClO4 at these levels would be magnitudes below the therapeutic effect level of hundreds of milligrams of ClO4 used in treating hyperthyroidism. Studies were carried out in nine healthy male volunteers who had normal thyroid function and negative thyroid antibodies to determine whether the ingestion of 10 mg of ClO4 daily (approximately 300 times the estimated maximum amount of ClO4 consumed from the affected water supplies) would affect any aspect of thyroid function. They ingested 10 mg of ClO4 dissolved in a liter of spring water during waking hours for 14 days. Baseline serum thyrotropin (TSH), free thyroxine index (FTI), total triiodothyronine (TT3), 4-, 8-, and 24-hour thyroid 123I uptakes (RAIU), serum and 24-hour urine ClO4, 24-hour urine iodine, complete blood count (CBC), and chemistry profile were determined. All blood and urine tests were repeated on days 7 and 14 of ClO4 administration and thyroid RAIU on day 14 of ClO4 administration. All tests were repeated 14 days after ClO4 was discontinued. No effect of ClO4 on serum thyroid hormone or TSH concentrations, urinary iodine excretion, CBC, or blood chemistry was observed. Urine and serum ClO4 levels were appropriately elevated during the course of ClO4 ingestion in all subjects, demonstrating compliance. By day 14 of ClO4 administration, the 4-, 8-, and 24-hour thyroid RAIU values decreased in all nine subjects by a mean value of 38% from baseline and rebounded above baseline values by 25% at 14 days after ClO4 withdrawal (p < 0.01 analysis of variance (ANOVA) and Tukey). It is well known that the major effect of ClO4 on the thyroid is a decrease in the thyroid iodide trap by competitive inhibition of the sodium iodide symporter (NIS). The present study demonstrates the sensitivity of the thyroid iodide trap to ClO4 because a low dose of 10 mg daily significantly decreased the thyroid RAIU without affecting circulating thyroid hormone or TSH concentrations. It is possible, however, that the daily consumption of low levels of ClO4 in drinking water over a prolonged period of time could adversely affect thyroid function but no evidence of hypothyroidism was observed at 10 mg of ClO4 daily in this 2-week study. It is now of interest to determine a no effect level for ClO4 on the inhibition of the thyroid RAIU and to carry out a long-term ClO4 exposure study.

Cross-reactivity of an anti-okadaic acid antibody to dinophysistoxin-4 (DTX-4), dinophysistoxin-5 (DTX-5), and an okadaic acid diol ester.

The cross-reactivity of the 6/50 monoclonal anti-okadaic acid antibody (mAb) to the recently discovered diarrhetic shellfish poisoning (DSP) metabolites dinophysistoxin-4 (DTX-4), dinophysistoxin-5 (DTX-5), and an okadaic acid (OA) diol ester was determined using a competitive indirect enzyme-linked immunosorbent assay (ELISA). The reactivity of the antibody to these molecules was compared to that with OA; the 6/50 mAb recognized all of these DSP compounds with equal sensitivity within the working range of the antibody (10-100 nM for OA). This confirms the ability of the antibody to detect all DSP compounds when used in analyses including ELISA and immunocytochemistry.

Postprandial lipemia in endurance-trained people during a short interruption to training.

This study examined changes in postprandial lipemia in endurance-trained people during a short interruption to training. Nine men and one woman (ages 18-55 yr) undertook fat tolerance tests after 15 h, 60 h, and 6.5 days without exercise. The test meal (1.2 g fat, 1.1 g carbohydrate, 66 kJ/kg body mass) was consumed after a 12-h fast. Postprandial lipemia increased rapidly with detraining (area under plasma triacylglycerol vs. time curve: 8.42 +/- 1.40, 11. 35 +/- 1.38, and 11.97 mM x 6 h at 15 h, 60 h and 6.5 days, respectively). In the fasted state, plasma triacylglycerol concentration (0.85 +/- 0.15, 1.09 +/- 0.12, and 1.10 +/- 0.11 mM at 15 h, 60 h and 6.5 days, respectively) and the ratio of total cholesterol to high-density-lipoprotein cholesterol increased with detraining. Values were significantly higher at 60 h and 6.5 days than values at 15 h ( P < 0.05) for each of these three variables. The serum insulin response was higher ( P < 0.05) at 6.5 days than at 15 h (81.6 +/- 11.3, 87.6 +/- 11.4, and 94.5 +/- 9.4 microIU/ml x 6 h at 15 h, 60 h, and 6.5 days, respectively). Frequent exercise is needed to maintain a low level of postprandial lipemia and insulinemia in trained people.

AMPA-preferring receptors mediate excitatory synaptic inputs to retinal ganglion cells.

Pharmacological studies were performed to determine whether alpha-amino-3-hydroxy-5-methyl-4-isoazoleprionic acid (AMPA)- and/or kainate (KA)-preferring receptors mediate excitatory synaptic inputs to tiger salamander retinal ganglion cells. Excitatory postsynaptic currents (EPSCs), evoked either by light or by stimulating bipolar cells with puffs of K+, were measured using whole cell recording techniques in the tiger salamander retinal slice. The AMPA/KA component of the EPSCs was isolated by including antagonists of glycine-, gamma-aminobutyric acid (GABA)- and NMDA-receptors in the bath. The AMPA-preferring receptor antagonists, 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI-52466) and 1-(4-aminophenyl)-3-methylcarbamyl-4-methyl-7,8-methylenedioxy-3,4 - dihydro-5H-2,3-benzodiazepine (GYKI-53665), reduced light-evoked EPSCs and K+ puff-evoked EPSCs amplitudes in a concentration-dependent manner. The IC50 values for GYKI-52466 were 3.6 and 4.2 microM for the light- and puff-evoked responses, respectively. The more potent GYKI-53665 had IC50 values of 0.7 microM for both the light- and puff evoked responses. KA activates both KA- and AMPA-preferring receptors. KA-evoked currents were completely blocked by 10-40 microM GYKI-53665, indicating that little or no excitatory synaptic current was mediated by KA-preferring receptors. Concanavalin A, a compound that preferentially potentiates responses mediated by KA-preferring receptors, did not enhance either EPSCs or glutamate-evoked responses. By contrast, cyclothiazide, which selectively enhances AMPA-preferring receptor mediated responses, was found to enhance both EPSCs and glutamate-evoked currents. Our results indicate that the non-NMDA component of ganglion cell EPSCs is mediated by AMPA-preferring receptors and not significantly by KA-preferring receptors.

Desensitizing glutamate receptors shape excitatory synaptic inputs to tiger salamander retinal ganglion cells.

AMPA/kainate (KA) receptors mediate a component of ganglion cell excitatory postsynaptic currents (EPSCs). We investigated whether desensitization at these receptors contribute to the shape of transient EPSCs in ON-OFF ganglion cells. Whole-cell, voltage-clamp recordings were made from ganglion cells in the retinal slice or in isolation. EPSCs were evoked by either stimulating the slice with light or puffing K+ at the outer plexiform layer (OPL). The AMPA/KA receptor-mediated component of the EPSCs was isolated by including NMDA receptor antagonists in the bath. Strychnine and picrotoxin blocked inhibitory inputs. In isolated ganglion cells, cyclothiazide (10 microM), which blocks desensitization in non-NMDA receptors, enhanced both the amplitude and the duration of currents evoked by puffs of AMPA or glutamate. EPSCs evoked by K(+)-puffs in the OPL were also enhanced by cyclothiazide (30 microM). When AMPA/KA receptors were blocked with NBQX (10 microM), no enhancement of the EPSCs by cyclothiazide was observed, indicating that cyclothiazide did not act presynaptically. Cyclothiazide also enhanced the amplitude and duration of both the ON and OFF light-evoked (L-) EPSCs recorded in ON-OFF ganglion cells. Current-voltage relationships showed the enhancement was not voltage dependent. When control and enhanced responses where normalized, it was observed that the rate of desensitization of both the ON and OFF L-EPSCs was decreased by cyclothiazide. Cyclothiazide selectively enhanced the AMPA/KA receptor-mediated component of ganglion cells EPSCs, suggesting that desensitization of AMPA/KA receptors shape transient L-EPSCs.

Affinity chromatography to remove viruses during preparation of plasma derivatives.

The use of affinity chromatography methods to purify proteins from complex solutions is well established. The specific use of immuno-affinity chromatography, wherein antibody directed toward a target protein is utilized, has proven to be a particularly effective purification method. Application of immuno-affinity chromatography methods for the isolation of plasma derivatives has now been established and the purity of such products has been truly remarkable. Studies conducted by Baxter have compared the effect of immuno-affinity chromatography on the separation of plasma protein contaminants and model viruses from Factor VIII:C. The results of these studies have indicated that plasma protein contaminant (eg. fibrinogen) reduction during the process of Factor VIII:C immuno-affinity chromatography occurs more gradually than does virus reduction. By using residual plasma protein contamination in Factor VIII:C preparations, the general effectiveness of the immuno-affinity chromatography step in removing virus can be routinely evaluated. Determinations made by Baxter have indicated that greater than 4 logs of reduction in protein contamination is routinely achieved during Factor VIII:C immuno-affinity chromatography at manufacturing scale. Bench scale studies have confirmed this result as well as showing the reduction of model viruses. While the viral safety of plasma derivatives is dependent on the overall manufacturing process, it is clear that immuno-affinity chromatography offers a powerful means of reducing product contamination and enhancing safety.

Mid-facial sensation following craniofacial surgery.

During mid-face advancement and correction of orbital dystopia, the infraorbital nerves are always stretched and displaced by the orbital floor osteotomies and bone displacement, and are at risk of damage. We have found no published work that has investigated the function of the infraorbital nerves following elective craniofacial procedures. In this study the cheek sensation and tooth sensibility in 20 patients who have had either mid-face advancement or correction of orbital dystopia was assessed. The function of the infraorbital nerve is largely undisturbed by the osteotomies and bone displacement performed during these procedures. A small proportion of patients could not feel cold in their anterior maxillary teeth, suggesting that there is damage to the anterior superior alveolar nerve branch of the infraorbital nerve.

A comparison of calcium alginate and scarlet red dressings in the healing of split thickness skin graft donor sites.

Forty-six patients had split thickness skin grafts harvested from the upper inner thigh. Calcium alginate (Kaltostat) and scarlet red dressings were applied to each half of the wound. Dressings were changed after 10 days and healing of the donor site was assessed. Seventy-two per cent of wounds dressed with calcium alginate and 84% of wounds dressed with scarlet red were healed at 10 days. Scarlet red was shown to be significantly better than Kaltostat in the healing of split thickness skin graft donor sites when assessed at 10 days (p less than 0.04).