Radiographic assessment of distal femur cemented stems in tumor endoprostheses.

BACKGROUND: Distal femoral endoprosthesis (DFE) has become the optimal method of reconstruction in the skeletally mature patients treated for malignant bone tumor. Albeit literature has reported wide range of aseptic loosening in cemented components (6-32%), few authors showed that cement was not detrimental to long-term success of primary distal femoral implants possibly relating to cementing technique. METHODS: A series of consecutive of DFE (MRS and GMRS, Styker Orthopaedics, Mahwah, NJ) was retrospectively reviewed for evidence of loosening on plain radiographs. All prostheses had the standard straight 127-mm stem and a cemented polyethylene tibial component. Cementing technique involved reaming line to line to the selected stem size and cementing without pressurization. Radiographs were assessed by two independent blinded reviewers and scored for radiolucent zones (>1 mm) and graded as not loose, possibly, probable and definite loose. Furthermore, the final reamer/stem diameters, length of resection, tumor type, adjuvant treatment modalities, bushing exchange/revision surgery and infection rate were recorded. RESULTS: There were 70 patients and none were lost to follow-up. The average radiographic follow-up was 7.2 years (58% had f/u >5 years). Examiner A found 89% of femoral components to be "Not Loose" and 11% (n = 6) "Possibly Loose". Examiner B found 96% of femoral components to be "Not Loose" and 4% (n = 2) to be "Possibly Loose". No components scored as probably or definitely loose. Two DFE stems were reported as "Possibly Loose" by both reviewers. No femoral stem required revisions for either loosening, femur fracture or metal failure. Although infection was frequent, there was no septic loosening. CONCLUSION: Despite our study limitations, no radiographic evidence of loosening was found. Cementing distal femur prosthesis with a tight canal fit and with a thin and inconsistent cement mantle appears to be a viable option at short and medium term.

Using a family history questionnaire to identify adult patients with increased genetic risk for sarcoma.

BACKGROUND: Sarcomas in adults can be associated with hereditary cancer syndromes characterized by early-onset predisposition to numerous types of cancer. Because of variability in familial presentation and the largely unexplained genetic basis of sarcomas, ascertainment of patients for whom a genetics evaluation is most indicated poses challenges. We assessed the utility of a Sarcoma Clinic Genetic Screening (scgs) questionnaire in facilitating that task. METHODS: Between 2008 and 2012, 169 patients (median age: 53 years; range: 17-88 years) completed a self-administered scgs questionnaire. A retrospective chart review was completed for all respondents, and descriptive statistics were reported. Probands were divided into two groups depending on whether they did or did not report a family history of Li-Fraumeni syndrome-type cancers. RESULTS: A family history of cancer (as far as 3rd-degree relatives) was reported in 113 of 163 sarcoma patients (69%). Eeles Li-Fraumeni-like (lfl) criteria were fulfilled in 46 probands (28%), Chompret lfl in 21 (13%), Birch lfl in 8 (5%), and classic Li-Fraumeni in none. In the 10 probands tested for TP53 mutations, 1 pathogenic mutation was found. Further investigation of selected families led to the discovery of germline mutations in MLH1, MSH2, and APC genes in 3 individuals. CONCLUSIONS: The scgs questionnaire was useful for ascertaining probands with sarcoma who could benefit from a genetic assessment. The tool allowed us to identify high-risk families fitting the criteria for lfl and, surprisingly, other hereditary cancer syndromes. Similar questionnaires could be used in other cancer-specific clinics to increase awareness of the genetic component of these cancers.

Hyperthermic isolated limb perfusion for extremity soft tissue sarcomas: systematic review of clinical efficacy and quality assessment of reported trials.

BACKGROUND AND OBJECTIVES: Extremity soft tissue sarcomas (STS) are managed with radiotherapy and limb-sparing surgery however aggressive or recurrent cases require amputation. Hyperthermic isolated limb perfusion (HILP) has been proposed as an alternative. Our aim was to systematically review phase II HILP trials, assess tumor response, limb salvage (LS), and quality of scientific publications on this technique. METHODS: We conducted a literature search of electronic databases (MEDLINE, EMBASE, Scopus, Cochrane Library) and clinical trial registries for phase II HILP trials on non-resectable extremity STS. Outcomes of interest were complete response (CR), partial response (PR), and LS rates. Quality of published trials was assessed using a quality checklist. RESULTS: Of 518 patients across 12 studies, 408 had some response (CR or PR), and 428 had the limb spared. Median CR, PR, and LS rates were 31%, 53.5%, and 82.5%, respectively. Median Wieberdink loco-regional toxicity rates were 3.8%, 45.5%, 17%, 1%, and 0% for levels 1-5, respectively. No trial fulfilled either all ideal or essential quality criteria. Seven trials did not include statistical methodology. CONCLUSION: HILP seems effective in treating advanced extremity STS. However, poor publication quality hinders results validity. Technical and methodological standardization, well-designed, multi-institutional trials are warranted.

Big and little forms of osteoclast activating factor.

We have further characterized osteoclast activating factor (OAF) using a bioassay for bone resorption which utilizes the release of previously incorporated (45)Ca from fetal rat long bones in organ culture. When supernatant media from activated leukocyte cultures were concentrated on Amicon PM10 membranes (assigned molecular weight cutoff 10,000 daltons) and chromatographed on Sephadex G-50 columns, the bone-resorbing activity eluted between the molecular weight markers chymotrypsinogen (25,000 daltons) and cytochrome c (12,500 daltons). This peak of biological activity has been called big OAF. When filtrates from the PM10 membranes were concentrated on Amicon UM2 membranes (assigned molecular weight cutoff 1,000 daltons) and chromatographed on Sephadex G-50 columns, some of the biological activity eluted between the molecular weight markers chymotrypsinogen and cytochrome c (big OAF), but there was a separate peak of biological activity which eluted with [(3)H]proline (140 daltons). This second peak has been called little OAF. Little OAF was eluted from Bio-Gel P6 columns between the molecular weight markers calcitonin (approximately 3,500 daltons) and vitamin B(12) (1,330 daltons), but was retained by Spectrapor dialysis tubing (nominal molecular weight cutoff 3,500 daltons). Big OAF was converted to little OAF by equilibration in 1 M NaCl or 2 M urea. Little OAF was self-associated back to big OAF by equilibration in buffers of low ionic strength (Tris-HCl 10-50 mM). Little OAF was extracted into the organic phase in ethyl acetate after acidification of the sample to pH 3.5. The biological activity remained in the aqueous phase after ethyl acetate extraction at pH 7.5-8.4. Little OAF has been purified more than 6,000-fold compared with the original material so that bone-resorbing activity is maximal in a sample with a protein concentration of 80 ng/ml.

The inter-rater reliability of the diagnosis of surgical site infection in the context of a clinical trial.

OBJECTIVES: The diagnosis of surgical site infection following endoprosthetic reconstruction for bone tumours is frequently a subjective diagnosis. Large clinical trials use blinded Central Adjudication Committees (CACs) to minimise the variability and bias associated with assessing a clinical outcome. The aim of this study was to determine the level of inter-rater and intra-rater agreement in the diagnosis of surgical site infection in the context of a clinical trial. MATERIALS AND METHODS: The Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial CAC adjudicated 29 non-PARITY cases of lower extremity endoprosthetic reconstruction. The CAC members classified each case according to the Centers for Disease Control (CDC) criteria for surgical site infection (superficial, deep, or organ space). Combinatorial analysis was used to calculate the smallest CAC panel size required to maximise agreement. A final meeting was held to establish a consensus. RESULTS: Full or near consensus was reached in 20 of the 29 cases. The Fleiss kappa value was calculated as 0.44 (95% confidence interval (CI) 0.35 to 0.53), or moderate agreement. The greatest statistical agreement was observed in the outcome of no infection, 0.61 (95% CI 0.49 to 0.72, substantial agreement). Panelists reached a full consensus in 12 of 29 cases and near consensus in five of 29 cases when CDC criteria were used (superficial, deep or organ space). A stable maximum Fleiss kappa of 0.46 (95% CI 0.50 to 0.35) at CAC sizes greater than three members was obtained. CONCLUSIONS: There is substantial agreement among the members of the PARITY CAC regarding the presence or absence of surgical site infection. Agreement on the level of infection, however, is more challenging. Additional clinical information routinely collected by the prospective PARITY trial may improve the discriminatory capacity of the CAC in the parent study for the diagnosis of infection.Cite this article: J. Nuttall, N. Evaniew, P. Thornley, A. Griffin, B. Deheshi, T. O'Shea, J. Wunder, P. Ferguson, R. L. Randall, R. Turcotte, P. Schneider, P. McKay, M. Bhandari, M. Ghert. The inter-rater reliability of the diagnosis of surgical site infection in the context of a clinical trial. Bone Joint Res 2016;5:347-352. DOI: 10.1302/2046-3758.58.BJR-2016-0036.R1.

Function and health status outcomes in a randomized trial comparing preoperative and postoperative radiotherapy in extremity soft tissue sarcoma.

PURPOSE: Morbidity associated with wound complications may translate into disability and quality-of-life disadvantages for patients treated with radiotherapy (RT) for soft tissue sarcoma (STS) of the extremities. Functional outcome and health status of extremity STS patients randomized in a phase III trial comparing preoperative versus postoperative RT is described. PATIENTS AND METHODS: One hundred ninety patients with extremity STS were randomized after stratification by tumor size dichotomized at 10 cm. Function and quality of life were measured by the Musculoskeletal Tumor Society Rating Scale (MSTS), the Toronto Extremity Salvage Score (TESS), and the Short Form-36 (SF-36) at randomization, 6 weeks, and 3, 6, 12, and 24 months after surgery. RESULTS: One hundred eighty-five patients had function data. Patients treated with postoperative RT had better function with higher MSTS (25.8 v 21.3, P <.01), TESS (69.8 v 60.6, P =.01), and SF-36 bodily pain (67.7 v 58.5, P =.03) scores at 6 weeks after surgery. There were no differences at later time points. Scores on the physical function, role-physical, and general health subscales of the SF-36 were significantly lower than Canadian normative data at all time points. After treatment arm was controlled for, MSTS change scores were predicted by a lower-extremity tumor, a large resection specimen, and motor nerve sacrifice; TESS change scores were predicted by lower-extremity tumor and prior incomplete excision. When wound complication was included in the model, patients with complications had lower MSTS and TESS scores in the first 2 years after treatment. CONCLUSION: The timing of RT has minimal impact on the function of STS patients in the first year after surgery. Tumor characteristics and wound complications have a detrimental effect on patient function.

Cellular target of in vitro-induced suppressor cells derived from the spleen of Mycobacterium lepraemurium-infected mice and role of IFN-gamma in their development.

Unfractionated spleen cells from C3H mice infected a few weeks before with Mycobacterium lepraemurium developed a suppressor activity after overnight culture. This requires contact of plastic adherent cells with nonadherent cells distinct from T, B, or natural killer cells. The present study demonstrates that anti-interferon-gamma (IFN-gamma) monoclonal antibody and indomethacin totally abrogate the expression, although not the induction, of this activity. Furthermore, culture-induced suppressor cells selectively inhibit T lymphocyte proliferation, probably by altering the generation of interleukin-2 (IL-2) responsiveness through reduction of the affinity and density of high-affinity IL-2 receptors on activated cells. These and other previously determined properties of culture-induced suppressor cells, similar to those of adherent suppressor cells detected in freshly harvested spleen cells at a later stage of M. lepraemurium infection, suggest a common precursor. If so, the present observations should help in defining a strategy to prevent the impairment of cell-mediated immunity in infected mice.

The effect of acetylsalicylic acid on TSH and PRL secretion after TRH stimulation in the human.

In order to study the effect of prostaglandins on TSH release in the human, Acetylsalicylic Acid was given to 9 normal subjects at doses necessary to obtain a salicylate level of 20 mg/dl. TRH, 400 mug was injected prior to and after the medication. Thyroid hormone parameters were measured at time 0, and TSH and PRL at time 10, 20, 30, 45 minutes after the injection. The free fraction of thyroid hormones remained constant during treatment but a significant decrease of TSH concentration (30%) was noted after TRH injection on Acetylsalicylic Acid treatment whereas no changes were noted for PRL. As noted in the animal, this study indicates that in the human, prostaglandins potentiate the effect of TRH on TSH liberation by the pituitary where it has no effect on PRL.

Pathogenesis of hypercalcemia in lymphosarcoma cell leukemia. Role of an osteoclast activating factor-like substance and a mechanism of action for glucocorticoid therapy.

The pathogenesis of hypercalcemia and mode of action of glucocorticoid therapy was examined in a patient with lymphosarcoma cell leukemia. Circulating neoplastic cells were cultured in vitro and secreted a bone-resorbing factor. The bone-resorbing factor was partially purified with the use of a bioassay for bone resorption, and was found to be chromatographically and pharmacologically similar to osteoclast activiating factor (OAF), which is produced by normal mitogen-activated peripheral blood lymphocytes. Other factors which stimulate bone resorption, such as parathyroid hormone, prostaglandins and the vitamin D metabolites, were excluded by criteria which included dose-response curves, radioimmunoassays, extraction in organic solvents and failure of glucocorticoids to inhibit bone-resorbing activity. The patient's hypercalcemia responded rapidly to prednisone therapy. The effects of the bone-resorbing factor secreted by the neoplastic cells on bone cultures to which cortisol was added were examined. Cortisol inhibited bone resorption directly at low doses (10(-8) M), which suggests that prednisone may have lowered the serum calcium in this patient by direct inhibition of bone resorption.

Chondroblastoma.

Chondroblastoma of the bone is a benign tumor that has well-characterized radiographic and histologic features. It tends to affect the epiphyseal ends of long bones in men during the second and third decades of life. The tumor is located more frequently at other sites in older patients. The treatment of choice is complete curettage with bone grafting, which in our series provided local control in 82% of patients at 2 years' follow-up. Recurrent tumors usually can be treated in the same manner.

Effects of physical conditioning on endogenous nitric oxide output during exercise.

Nitric oxide (NO) has been detected in the expiratory air of normal animals and human subjects. Recent experiments revealed that expiratory NO production rises during exercise and correlates well with O2 consumption (VO2) and heart rate. Whether physical conditioning influences expiratory NO output production remains unclear. In this study, NO concentration in expired gas was measured in 18 healthy male volunteers subdivided into three groups (sedentary, intermediate, and athletic) on the basis of the subjects' state of physical conditioning. Measurements were taken at rest and during two steady-state exercise bouts on a bicycle ergometer designed to elicit VO2 of 1 and 2 l/min with the athletes performing an additional bout at VO2 of 4 l/min. In the sedentary and intermediate groups, expired NO concentrations declined significantly with increasing VO2. In contrast, expired NO levels declined only slightly with increasing VO2 in the athletes. At a VO2 of 2 l/min, expired NO concentrations were significantly higher in the athletes compared with values in the other groups. When correlated with minute ventilation (VE), expired NO concentrations declined linearly with the increase in VE in sedentary and intermediate groups but not in the athletes. Only the athletes had a significant linear increase in NO output (expired NO x VE) with increasing VO2 (P < 0.001). These results support the notion that physical conditioning increases expiratory NO output during exercise. We speculate that the rise in expiratory NO output in the athletes might be due to increased vascular and/or epithelial production of NO. Enhanced vascular NO production may be the result of increased shear stress and/or upregulation of endothelial NO synthase gene expression.

Exercise-induced cardiac hypertrophy. Fact or fallacy?

After a century of research reports, the notion of exercise-induced cardiac hypertrophy is still an expected adaptation to regular exercise training. Experimental evidence reported both in animals and in humans over the past 3 decades suggests, however, that this conclusion may not be totally warranted. Data from 20 years of echocardiographic investigations of athletes and nonathletes indicate that differences in cardiac dimensions are not very large. Cross-sectional comparisons of over 1000 athletes and roughly 800 control individuals indicate an average difference of 1.6 mm in left ventricular (LV) wall thickness and of 5.3 mm in end-diastolic diameter. Differences reported after training programmes lasting 4 to 52 weeks are even smaller, with average increases of 0.3 mm in LV wall thickness and only 2.1mm in end-diastolic diameter. This article reviews data from animal and human studies concerning cardiac morphology and exercise training to show that the traditional interpretation of the literature has failed to take into account several methodological considerations or factors that may act as confounders in the interpretation of data. Results from animal studies indicate that the observation of cardiac hypertrophy is equivocal at best. In many reports the reported changes in heart size are not significant, and in instances where significant changes are reported these may be seen to be confounded by a number of factors. For example, in rats the reported training-induced hypertrophy may be related to gender differences in the responsiveness of cardiac dimensions or body and/or organ growth rather than to true heart hypertrophy. Furthermore, the interpretation of results from training studies in rats has often been based on the assumption that the metabolic, haemodynamic and thermoregulatory requirements of swimming and running exercise in rats are similar, which may in fact not be the case. In addition, the use of the heart weight/body weight ratio as an index of cardiac hypertrophy, although widespread in animal studies, is open to criticism owing to failure to control for concurrent changes in body weight. Several methodological considerations and factors confounding the outcome of exercise training in humans have also been omitted when interpreting echocardiographic cross-sectional and longitudinal findings. For example, in adult echocardiography the practical resolution of the echocardiographic technique amounts to roughly 2.2mm. It follows, therefore, that unless differences of changes in cardiac dimensions exceed the limit of resolution they are meaningless although statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)

Unstable intertrochanteric fracture of the femur. A prospective randomised study comparing anatomical reduction and medial displacement osteotomy.

We conducted a prospective randomised trial to compare the results of anatomical reduction and medial displacement osteotomy in 127 consecutive patients with unstable intertrochanteric fractures, of whom 109 completed the study. After an average follow-up of 11 months, we found no significant differences in walking ability, social status or failure of fixation in the two groups. Postoperative complication rates and the early mortality rate were not significantly different, but operating time and blood loss were significantly higher in the osteotomy group. With the use of modern sliding hip screws, medial displacement osteotomy is rarely indicated for unstable intertrochanteric fractures.

Partial characterization of suppressor factors in spleen cell culture supernatants of Mycobacterium lepraemurium-infected mice.

Suppressor factors (SF) were released into the culture supernatant when spleen cells from M. lepraemurium-infected C57BL/6 mice were incubated at 37 degrees C in the absence of any inducing agents. Some of the SF appeared to be specific in that they inhibited the blastogenic response to mycobacterial antigens by opposition to the others which inhibited the blastogenic responses to PHA, Con A and LPS. All SF seemed to be produced in a cyclic manner. In mice infected 9 weeks earlier, the release of "specific" SF occurred early (4-8 h) during the incubation period whereas, the nonspecific SF were released later on (12-32 h). Adoptive transfers of SF-containing culture supernatants depressed the expression of DTH to M.1m antigens but not its induction.

Thermal hazard assessment of AN and AN-based explosives.

Ammonium nitrate (AN) is an essential ingredient in most fertilizers. It is also widely used in the commercial explosives industry. In this latter application, it is mostly mixed with fuel oil to form the most popular commercial explosive: ANFO. In both the fertilizer and the explosive industry, aqueous AN solutions (ANS) of various concentrations are processed. These solutions also form the basis of ammonium nitrate emulsion explosives (also called ammonium nitrate emulsions or ANE), which are produced either in bulk or in packaged form. For all these AN-based products, quantities of the order of 20,000kg are being manufactured, transported, stored, and processed at elevated temperatures and/or elevated pressures. Correspondingly, major accidents involving overheating of large quantities of these products have happened in several of these operations. In comparison, convenient laboratory quantities to investigate thermal decomposition properties are generally less than 1kg. As a result, in order to provide information applicable to real-life situations, any laboratory study must use techniques that minimize heat losses from the samples to their environment. In the present study, two laboratory-scale calorimeters providing an adiabatic environment were used: an accelerating rate calorimeter (ARC) and an adiabatic Dewar calorimeter (ADC). Experiments were performed on pure AN, ANFO, various ANS systems, and typical bulk and packaged ANE systems. The effects of sample mass, atmosphere, and formulation on the resulting onset temperatures were studied. A comparison of the results from the two techniques is provided and a proposed method to extrapolate these results to large-scale inventories is examined.

An on-site test battery to evaluate giant slalom skiing performance.

The purpose of this study was to determine if an on-site test battery would distinguish among three levels of giant slalom skiing ability. The test battery consisted of a 20-m shuttle run test, Wingate 60s cycling test, hexagonal obstacle test, high box test, double leg jumping test and vertical jump test. These tests were selected since previous studies have identified aerobic endurance, anaerobic endurance, power and agility as important components for Alpine skiers. Both construct validity and criterion related validity of the test battery were examined using data from 11 club skiers, 14 divisional level skiers, and 9 provincial level skiers. To establish construct validity, univariate F tests examined differences among the three levels of skiers. Significant (P less than 0.05) differences were found between the club skiers and the better skiers (divisional and provincial level) for the following test variables: peak power, mean power, and post-exercise lactate for a 60s Wingate cycle ergometer test, high box test, hexagonal obstacle test, double leg jumping test, and shuttle run test. Criterion related validity was established since there were significant correlations between giant slalom performance time and the hexagonal obstacle test (r = 0.82), high box test (r = -0.80), and double leg jumping (r = -0.86). These data illustrate that an on-site test battery can be used to distinguish among giant slalom Alpine skiers.

Fire and explosion hazards related to the industrial use of potassium and sodium methoxides.

Sodium and potassium methoxides are used as an intermediary for a variety of products in several industrial applications. For example, current production of so called "1G-biodiesel" relies on processing a catalytic reaction called "transesterification". This reaction transforms lipid resources from biomass materials into fatty acid methyl and ethyl esters. 1-G biodiesel processes imply the use of methanol, caustic potash (KOH), and caustic soda (NaOH) for which the hazards are well characterized. The more recent introduction of the direct catalysts CH3OK and CH3ONa may potentially introduce new process hazards. From an examination of existing MSDSs concerning these products, it appears that no consensus currently exists on their intrinsic hazardous properties. Recently, l'Institut National de l'Environnement Industriel et des Risques (France) and the Canadian Explosives Research Laboratory (Canada) have embarked upon a joint effort to better characterize the thermal hazards associated with these catalysts. This work employs the more conventional tests for water reactivity as an ignition source, fire and dust explosion hazards, using isothermal nano-calorimetry, isothermal basket tests, the Fire Propagation Apparatus and a standard 20 L sphere, respectively. It was found that these chemicals can become self-reactive close to room temperature under specific conditions and can generate explosible dusts.