Docking site interventions following bone transport using external fixation: a systematic review of the literature.

PURPOSE: Although bone transport is a well-recognised technique to address segmental bone defects, optimal management of docking sites is not absolutely determined. Some surgeons routinely intervene in all cases, and others prefer to observe and intervene only if spontaneous union does not occur. Primary aim of the study was to compare rates of docking site union between patients who underwent routine docking site intervention and those who did not. METHODS: A systematic literature review using the keywords "bone transport", "docking", "tibia", and "femur" was performed in PubMed using PRISMA guidelines. Studies published in English from January 2000 to August 2022 were included and assessed independently by two reviewers. Pooled analysis was undertaken dividing patients into two groups: those managed by routine intervention and those initially observed. RESULTS: Twenty-three clinical studies met the eligibility criteria for pooled analysis, including 1153 patients, 407 in the routine intervention and 746 in the observed group. The rate of union after initial treatment was 90% in the routine intervention group and 66% in the observed group (p < 0.0001). Overall union rates at the end of treatment were similar at 99% in both groups. Patients in the observed group required an average of 2.2 procedures to achieve union overall compared with 3.8 in the routine intervention group. Time in frame was similar between groups. CONCLUSION: Based on the current literature, routine docking site interventions cannot be recommended, since this may lead to unnecessary interventions in two thirds of patients. Timely selective intervention in those at high risk or after a defined period of observation would appear to be a logical approach.

Predictors of psychological distress following major trauma.

AIM: The aim of this study was to identify variables that may predict later psychological distress in patients following admission to a Major Trauma Centre (MTC) and to determine whether a psychological screening tool, the Posttraumatic Adjustment Screen (PAS), administered on admission was able to contribute to this. METHODS: Patients referred to the MTC clinical psychology service completed the PAS during their inpatient stay over an eight-month period. Following discharge from hospital, patients were telephoned (1 month, 3 months and 6 months post injury) by a member of the clinical psychology team and asked two validated questionnaires; the Impact of Events Scale revised (IES-R) (measure of posttraumatic stress symptoms) and the CORE-10 (measure of global psychological distress). In addition, patients' data from the local Trauma Audit & Research Network (TARN) database was reviewed to identify information related to injury and other demographic data. Patients were divided into groups for comparison based upon their PAS scores using previously described severity cut offs for posttraumatic stress symptoms and depression. Receiver Operator Characteristic and Multiple Linear Regression analysis was used to examine for significant baseline predictors of psychological distress during follow up according to the IES and CORE-10 scores. RESULTS: One hundred and fourteen patients completed the PAS over the study period. Follow-up psychological data was available for 63 (56%) of patients. Except for the patient's home address, no baseline parameter examined in this study regarding patient demographics, injury or treatment was associated with reported psychological symptoms in the first six months post injury as measured by the IES-R or CORE-10 scores. Multiple linear regression analysis revealed that both PAS-P and PAS-D were significant predictor variables for patients reporting significant symptoms of posttraumatic stress and global psychological distress (according to IES-R and CORE-10 scores) in the first six months post injury. CONCLUSIONS: Psychological screening on admission may be helpful in identifying patients admitted to MTCs who are at risk at developing posttraumatic stress symptoms and psychological distress following major trauma.

A safe technique for insertion of heel wires for hindfoot external fixation frames: an anatomical study.

Aims: Anatomical atlases document classical safe corridors for the placement of transosseous fine wires through the calcaneum during circular frame external fixation. During this process, the posterior tibial neurovascular bundle (PTNVB) is placed at risk, though this has not been previously quantified. We describe a cadaveric study to investigate a safe technique for posterolateral to anteromedial fine wire insertion through the body of the calcaneum. Materials and Methods: A total of 20 embalmed cadaveric lower limbs were divided into two groups. Wires were inserted using two possible insertion points and at varying angles. In Group A, wires were inserted one-third along a line between the point of the heel and the tip of the lateral malleolus while in Group B, wires were inserted halfway along this line. Standard dissection techniques identified the structures at risk and the distance of wires from neurovascular structures was measured. The results from 19 limbs were subject to analysis. Results: In Group A, no wires pierced the PTNVB. Wires were inserted a median 22.3 mm (range 4.7 to 39.6) from the PTNVB; two wires (4%) passed within 5 mm. In Group B, 24 (46%) wires passed within 5 mm of the PTNVB, with 11 wires piercing it. The median distance of wires from the PTNVB was 5.5 mm (range 0 to 30). A Mann-Whitney U test showed that this was significantly closer than in Group A (Hodges-Lehmann shift, 14.06 mm; 95% confidence interval (CI) 10.52 to 16.88; p < 0.0001). In Group B, with an increased angle of insertion there was greater risk to the PTNVB (rs = -0.80; p < 0.01). Conclusion: Insertion of wires using an entry point one-third along a line from the point of the heel to the tip of the lateral malleolus (Group A) appears to be the safer technique. An insertion angle of up to 30° to the coronal plane can be used without significant risk to the PTNVB. Insertion of wires halfway along a line from the point of the heel to the tip of the lateral malleolus (Group B) carried a significantly higher risk of injury to neurovascular structures and, if necessary, an angle of insertion parallel to the coronal plane should be used. Cite this article: Bone Joint J 2018;100-B:1054-9.

Ionising radiation exposure in patients with circular frame treatment of distal tibial fractures.

Total radiation exposure accumulated during circular frame treatment of distal tibial fractures was quantified in 47 patients treated by a single surgeon from February 2007 until Oct 2010. The radiation exposures for all relevant radiology procedures for the distal tibial injury were included to estimate the radiation risk to the patient. The median time of treatment in the frame was 169 days (range 105-368 days). Patients underwent a median of 13 sets of plain radiographs; at least one intra operative exposure and 16 patients underwent CT scanning. The median total effective dose per patient from time of injury to discharge was 0.025mSv (interquartile range 0.013-0.162 and minimum to maximum 0.01-0.53). The only variable shown to be an independent predictor of cumulative radiation dose on multivariate analysis was the use of CT scanning. This was associated with a 13-fold increase in overall exposure. Radiation exposure during treatment of distal tibial fractures with a circular frame in this group was well within accepted safe limits. The fact that use of CT was the only significant predictor of overall exposure serves as a reminder to individually assess the risk and utility of radiological investigations on an individual basis. This is consistent with the UK legal requirements for justification of all X-ray imaging, as set out in the Ionising Radiation (Medical Exposure) Regulations 2000 [1].

Products of gamma-tocopherol reaction with NO2 and their formation in rat insulinoma (RINm5F) cells.

gamma-Tocopherol, commonly found in seed oils, is the major tocopherol in the U.S. diet, is superior to alpha-tocopherol in preventing neoplastic transformation, and demonstrates unique reactivity toward NO2. This article describes the products of reaction between gamma-tocopherol and low concentrations of gaseous nitrogen dioxide (NO2), as well as their endogenous formation in NO-producing RINm5F cells. gamma-Tocopherol in hexane reacts with NO2 to yield two products identified as 2,7,8-trimethyl-2(4,8,12-trimethyltridecyl)-5,6-chromaquinone++ +, "tocored," and 2,7,8 trimethyl-2(4,8,12-trimethyltridecyl) 5-nitro, 6-chromanol, "tocoyellow." Physical data for these two compounds and reaction characteristics are described. The formation of tocored is consistent with a proposed mechanism of gamma-tocopherol-mediated reduction of NO2 to NO involving initial reaction by NO2 at the C-5 position to form an intermediate nitrite ester tocopheryl radical, which then reacts internally to release NO and form 5,6 epoxy gamma-tocopherol. Tautomerization and further oxidation of the latter intermediate by NO2 yields tocored as the main product observed. The reaction of gamma-tocopherol with NO2 to form NO occurs independently of light, whereas alpha-tocopherol requires light to generate NO from NO2. gamma-Tocopherol and aminoguanidine, an NO synthase inhibitor, were superior to alpha-tocopherol in preventing RINm5F cell toxicity induced by Interleukin-1 beta (IL-1 beta). Both tocored and tocoyellow were observed to form in RINm5F cells loaded with gamma-tocopherol and producing NO constitutively, although a consistent increase in these products as a result of induced NO synthesis was not observed.

Seasonal variations in plasma micronutrients and antioxidants.

Plasma samples were collected at monthly intervals for a period of 1 year from a group of healthy nonsmoking men and women (n = 21) living in Honolulu, HI. Analysis of plasma cholesterol and triglyceride levels showed marked seasonal variations, with higher mean levels in winter months and lower values in the summer. Cholesterol and triglycerides were highly and inversely correlated with plasma levels of the provitamin A carotenoids. Mean beta- and alpha-carotene levels were highest in late summer and fall. Plasma retinol levels were significantly lower in the summer and higher in the winter. Variations (either between individuals or seasonally) in plasma retinol were unrelated to plasma provitamin A carotenoid levels. Plasma levels of alpha-tocopherol, gamma-tocopherol, beta-cryptoxanthin, and lutein were also higher in the winter and lower in the summer. Significant seasonal correlations, both positive and negative, with environmental variables, such as temperature, solar UV radiation, and rainfall, are noted for many of these plasma micronutrients. The number of samples required to accurately characterize long-term plasma levels for an individual generally ranged from 1 to 4. However, plasma retinol levels exhibited the highest ratio of intra- to interindividual variability, suggesting the need for multiple sampling (> 8 samples) for this micronutrient. Some of this variability for retinol was associated with seasonal changes. Assessment by a diet history of food and supplement intake of micronutrients and phytochemicals for 1 year showed good agreement with 1-year mean plasma levels for most carotenoids, vitamin C, and alpha-tocopherol. Retinol, gamma-tocopherol, cholesterol, and triglyceride levels in plasma were unrelated to estimates of dietary intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of micronutrients and antioxidants on lipid peroxidation in human plasma and in cell culture.

Plasma levels of triglycerides, retinol, cholesterol, lipid-phase antioxidants (alpha-, gamma-tocopherols, beta-carotene, alpha-carotene, lycopene, beta-cryptoxanthin and lutein/zeaxanthin), and thiobarbituric acid-reactive substances (TBA-RS), as an indicator of lipid peroxidation, were repeatedly determined in nine individuals over a 3-month period. Levels of TBA-RS were positively correlated with plasma triglycerides and gamma-tocopherol, and negatively correlated with plasma carotenoids. These results were consistent with in vitro cell culture studies which showed increased TBA-RS for cells supplemented with linolenic acid and decreased levels when treated with beta-carotene. We conclude that TBA-RS measurements in plasma accurately reflect the level of peroxidizable substrate as modified by the presence of a variety of dietary antioxidants, particularly carotenoids. Although the inter- and intra-individual variabilities for TBA-RS are comparable with the micronutrients and antioxidants measured in this study, high interassay variability and the strong association with the more commonly measured plasma triglycerides suggest the TBA-RS assay to be of limited use in epidemiologic studies. However, this assay does appear to be useful in cell culture studies where experimental conditions can be better controlled. Low ratios of inter- to intra-individual variability in some of the plasma micronutrient and lipid-phase antioxidants measured suggest that multiple samples may be required to characterize individuals in studies evaluating the relation between these plasma constituents and disease incidence.

Light-mediated conversion of nitrogen dioxide to nitric oxide by carotenoids.

Plants are more susceptible to the toxic effects of nitrogen dioxide when exposure takes place in the dark. Beta-carotene and other common carotenoids react with nitrogen dioxide in the dark to yield intermediate nitrosating agents consistent with the formation of nitrate esters. Simultaneous exposure of carotenoids to NO2 and light significantly reduced formation of nitrosating intermediates and resulted in the release of nitric oxide (NO) into the gas phase. Light-mediated reduction of NO2 to NO by carotenoids may be an important mechanism for preventing damage in plants exposed to NO2. The formation of nitrosating agents from the reaction of carotenoids with NO2 suggests that their ability to prevent nirosative damage associated with NO2 exposure in both plants and animals may be limited in the absence of light.

The 'Retro-Fibular Wire': an anatomical study describing a safe corridor for placement of fine wires in the distal tibia.

Anatomical atlases document safe corridors for placement of wires when using fine-wire circular external fixation. The furthest posterolateral corridor described in the distal tibia is through the fibula. This limits the crossing angle and stability of the frame. In this paper we describe a new, safe Retro-Fibular Wire corridor, which provides greater crossing angles and increased stability. In a cadaver study, 20 formalin-treated legs were divided into two groups. Wires were inserted into the distal quarter of the tibia using two possible corridors and standard techniques of dissection identified the distance of the wires from neurovascular structures. In both groups the posterior tibial neurovascular bundle was avoided. In group A the peroneal artery was at risk. In group B this injury was avoided. Comparison of the groups showed a significant difference (p < 0.001). We recommend the Retro-Fibular wire technique whereby wires are inserted into the tibia mid-way between the posteromedial border of the fibula and the tendo Achillis, at 30 degrees to 45 degrees to the sagittal plane, and introduced from a posterolateral to an anteromedial position. Subsequently, when using this technique in 30 patients, we have had no neurovascular complications or problems relating to tethering of the peroneal tendons.

Severe and multiple trauma in older patients; incidence and mortality.

OBJECTIVE: To examine the differences between severely injured older patients (aged over 65 years) compared with similarly injured younger adults in terms of incidence, inpatient mortality and factors predicting outcome. METHODS: Data prospectively entered into the Trauma Audit and Research Network (TARN) database from our level I trauma unit over a 5-year period were retrospectively examined, with 3172 patients included in the final analysis. RESULTS: Older patients accounted for 13.8% of those with severe injuries (Injury Severity Score 16 or more) and almost 2% of our trauma admissions overall. High energy injuries were responsible for the majority of these injuries though relatively minor trauma became increasingly important in older patients. Mortality rates in the older patients were more than twice those seen in the adult population (19% in the under 40's to almost 50% in the over 75's). Age, Injury Severity Score and Glasgow Coma Score continued to be predictive of mortality in older patients but other factors relevant in younger adults were not. CONCLUSIONS: Patients in the older group without physiological derangement on admission were still at a relatively high risk of inpatient mortality. This was in contrast to the younger patients, suggesting that it might be more difficult to predict which older patients might benefit from more aggressive monitoring or treatment. Despite increased mortality in older patients, significant survival rates were achieved even in the oldest. Active treatment should not be withdrawn on the basis of age alone.

Early experience with linezolid for infections in orthopaedics.

In infections following orthopaedic surgery, isolated staphylococci are reported to be methicillin resistant (MRSA) in up to 50% of cases. Linezolid, the first in a new class of antibiotics, has excellent efficacy against gram positive organisms that are resistant to other therapies and is 100% orally bioavailable. We report early results of its use for the treatment of resistant infections in orthopaedic practice. Infections were characterised according to the UK Nosocomial Infections National Surveillance Service classification of surgical infections as superficial, deep or organ/space. Osteomyelitis, joint sepsis and deep infection involving orthopaedic implants were included into the final category. Outcome was recorded as clinical, microbiological and blood parameter cure or fail. Over the 12-month study period, 54 patients received linezolid therapy, 41% of these had significant co-morbidity that might affect their ability to fight infection. Sixty-seven percent of infections were in association with implanted metal work. The majority of patients were treated with vancomycin for a short period before linezolid was used as oral 'switch' therapy for longer-term administration, allowing early discharge in all cases. MRSA was isolated in 87% of the patients treated. The mean length of linezolid therapy was 39 days (2-151). Clinical success was achieved in 90% of patients overall. Though there were no life-threatening complications, adverse event rates were significantly higher than those recorded in the literature, with 19% of patients needing to cease therapy. Linezolid offers an alternative to traditional treatments for resistant infections and can facilitate early discharge. Patients need to be monitored closely, particularly where long-term therapy is planned.

The safety and efficacy of linezolid in orthopaedic practice for the treatment of infection due to antibiotic-resistant organisms.

Linezolid is the first of a new class of antibacterial agents, the oxazolidinones. It is particularly effective against Gram-positive infections and little resistance has been reported, even amongst methicillin- and vancomycin-resistant bacteria. The compound's excellent oral bioavailability and reasonable safety profile, along with the increasing incidence of resistant infections, means that linezolid offers a valuable alternative to more traditional therapies such as vancomycin. Although no large randomised trials have been carried out in patients with orthopaedic infections such as osteomyelitis and septic arthritis, early results are encouraging. However, the apparent increase in observed adverse events, particularly bone marrow suppression, seen with prolonged administration, means that treatment of such patients must be undertaken with careful surveillance, at least until these complications are better understood.

Significance of circulatory clearance of tumour-localising IgG and F(ab')2 for potential therapy studied in a CEA-producing xenograft model.

The significance of circulatory clearance of tumour-localising IgG and F(ab')2 for potential cancer therapy has been studied in immunodeprived mice bearing a carcinoembryonic antigen (CEA)-producing colon tumour. Intact radiolabelled anti-CEA (1H12) exhibited a prolonged localisation in tumour up to 8 days with injected doses between 4 and 256 g. Increased dosage caused a rise in the absolute concentration in tumour which, for the highest dose, reached 5.1 micrograms/g at 3 days after injection. A concomitant increase in concentration of 1H12 in blood occurred, which with the highest dose, remained above that in the tumour up to 7 days after injection. With F(ab')2 fragments (prepared from anti-CEA, 1C12) increased doses up to 380 micrograms also resulted in an increased uptake in tumour reaching almost 3 micrograms/g for a 234-micrograms dose. Circulatory clearance of F(ab')2-1C12 was essentially complete by 2 days for all doses up to 234 micrograms. Differences in clearance between 1H12 and F(ab')2-1C12 were reflected in the tumour to blood ratios. For high doses of 1H12 this ratio did not exceed unity up to 8 days. With F(ab')2, however, the tumour to blood ratio remained unaffected by dosage after 2 days. Our data suggest that F(ab')2 fragments clear sufficiently quickly to allow compensation by dosage for their premature escape from tumour. Therapeutic administration of intact antibody, however, appears to be limited by a protracted excretory process.

Effect of dose escalation of a monoclonal anti-CEA IgG on tumour localisation and tissue distribution in nude mice xenografted with human colon carcinoma.

A monoclonal anti-CEA antibody (1H12) has been examined for the effect of dosage on tumour localisation in immunodeprived mice xenografted with human colon carcinoma. Increased doses produced a linear rise in the absolute concentration found in the tumour but this was found to depend on tumour size, with the smaller tumours (mean weight 44 mg) accumulating significantly more antibody compared to larger tumours (mean weight 146 mg). With the smallest tumour (18 mg), in which saturation was achieved, a 500 micrograms dose produced a concentration in tumour of 60 micrograms/g. In the larger tumours a dose of 256 micrograms produced a mean concentration of 5.2 micrograms/g. Prolonged retention of 1H12 by tumour up to 8 days, observed at doses of 4, 128 and 256 micrograms, indicated that the dynamics of localisation is unaffected by dosage. Increased doses of 125I-1H12 caused an increase in the levels of radioactivity associated with all normal tissues studied. Thus at 8 days after injection an increase from 4 to 128 micrograms produced 50% and 42% declines in the tumour to blood and liver ratios, respectively. Cumulative localisation of 1H12 in tumour, from 4 h to 8 days, relative to normal tissue clearance was diminished on increasing dosage. This study shows that attempted therapy with escalated amounts of intact antibody is likely to be limited by a protracted excretory process and measures aimed at accelerating circulatory clearance are necessary.

Comparative tumour localization of antibody fragments and intact IgG in nude mice bearing a CEA-producing human colon tumour xenograft.

The dynamics of distribution of radiolabelled F(ab')2 fragments of a monoclonal anti-CEA antibody have been studied in the nude mouse bearing a CEA-producing human colon carcinoma. Our results showed that the fragment was rapidly cleared from all normal organs reaching about 1% of that injected by 24 hr. Specific tumour localization occurred as early as 2 hr after injection and was complete by 4 hr. The amount of fragment localized in tumour was 4% of the injected dose, equivalent to that obtained with the intact antibody. Greatly improved tumour:normal tissue ratios were obtained with the fragment compared to intact IgG. However, the residence time of the fragment was much shorter (24 hr) than that of intact antibody (more than 3 days). Tumour localization indices suggested that fragments were superior to intact IgG at locating tumour specifically. The specificity indices based on lung, spleen and liver were much higher than those for intact antibody, reflecting the lack of Fc-receptor binding of fragments and their reduced excretion by these organs. The 'fragment index' enabled tumour:normal tissue ratios for the fragment and intact IgG to be compared. Together with the distribution study at different time points, this simplifies the task of defining a 'time window' in which tumour imaging and therapy might be optimal.

Mapping epitope characteristics on carcinoembryonic antigen.

A method of epitope analysis is described in which the binding of one monoclonal antibody (MAb) to radiolabeled carcinoembryonic antigen (CEA) competes with the subsequent binding of an immobilised second MAb. From the degree of blocking obtained, we have identified both structurally related and independent epitopes on CEA. Using this technique to study fifteen MAbs, we have been able to recognise at least 6 unrelated epitopes of the CEA glycoprotein. Further characterisation of these epitopes was accomplished by means of immunohistochemistry. Of the fifteen MAbs, 6 were specific for CEA and reacted with at least 3 unrelated regions of the glycoprotein. Of the remaining 9 MAbs, 2 cross-reacted with erythrocytes, 5 with components of liver and 7 with polymorphonuclear neutrophils. Cross-reactions with liver were varied showing differential antibody specificity for bile canaliculi, Kupffer cells and bile duct epithelium. A high degree of correlation between epitope relatedness and immunohistochemical specificity was found. Two CEA-specific and 4 cross-reactive MAbs were also shown to react with ion-sensitive sites on the CEA glycoprotein.

Dynamics of monoclonal antibody distribution and prolonged tumour localisation in nude mice bearing a human CEA-producing colon carcinoma xenograft.

A new monoclonal anti-CEA antibody (1H12) has been raised which has localising characteristics in a human colon tumour xenograft which could make it suitable for human immuno-radiotherapy. The amount of 1H12 localising in tumour reached about 5% of the injected dose by 7 hours. This rate appeared to be related to the concentration of 1H12 in the blood pool since non-excretory normal organs such as colon and stomach accumulated similar amounts up to 4 hours. Whereas 1H12 was lost from normal organs after 4 hours, the amount in the tumour continued to increase slightly reaching a maximum concentration of 6.5% of the injected dose by day 9. Prolonged retention of 1H12 in tumour enabled increasing tumour: normal tissue ratios to be attained during the residence time of the antibody thus providing scope for maximising the dose of radiation delivered to tumour cells. Preliminary dose escalation showed that up to 500 micrograms of 1H12 could be administered with increasing concentrations of antibody localising in tumour. Saturation of the tumour site was evident in only one mouse where 1.09 micrograms of 1H12 actually localised--equivalent to 60 micrograms per gram of tumour.

Citrullinemia: enzymatic evidence for genetic heterogeneity.

The specific activity of argininosuccinate synthetase (micromoles of 14CO2 per milligram of protein per hour) was 0.00104 and 0.00087 in fibroblasts derived from two patients with citrullinemia, and was undetectable in both fibroblasts and cultured lymphocytes from a third patient. In five obligate heterozygotes the specific activity in fibroblasts was 0.012-0.029 and in nine control subjects was 0.058 +/- 0.014 (0.030-0.076). In both control and patient cells, the maximum activity was obtained at pH 8.5 and there was no inhibition of normal argininosuccinate synthetase by any of the mutant cells.

Gamma-tocopherol detoxification of nitrogen dioxide: superiority to alpha-tocopherol.

In the vitamin E group, alpha-tocopherol is generally considered to be the most potent antioxidant with the highest vitamin bioactivity, yet gamma-tocopherol is produced in greater amounts by many plants and is the principal tocopherol in the United States diet. This report describes a fundamental difference in the chemical reactivities of alpha-tocopherol and gamma-tocopherol with nitrogen dioxide (NO2), which leads to the formation of a nitrosating agent from alpha-tocopherol, but not from gamma-tocopherol. Nitric oxide (NO) is a major product of the reaction of gamma-tocopherol with NO2, while alpha-tocopherol reacts with NO2 to form an intermediate tocopheroxide analogue. The biological significance of gamma-tocopherol is suggested by limited epidemiological data as well as the observation that it is a more potent inhibitor than alpha-tocopherol of neoplastic transformation during the postinitiation phase in 3-methylcholanthrene-treated C3H/10T1/2 murine fibroblasts. This latter property suggests the superiority of gamma-tocopherol in a mammalian biological assay and a role for endogenous NO production in promotion of neoplastic transformation.