The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: a systematic review and meta-analysis.

BACKGROUND: A variety of diagnostic imaging techniques is available for excluding or confirming chronic osteomyelitis. Until now, an evidence-based algorithmic model for choosing the most suitable imaging technique has been lacking. The objective of this study was to determine the accuracy of current imaging modalities in the diagnosis of chronic osteomyelitis. METHODS: A systematic review and meta-analysis of the literature was conducted with a comprehensive search of the MEDLINE, EMBASE, and Current Contents databases to identify clinical studies on chronic osteomyelitis that evaluated diagnostic imaging modalities. The value of each imaging technique was studied by determining its sensitivity and specificity compared with the results of histological analysis, findings on culture, and clinical follow-up of more than six months. RESULTS: A total of twenty-three clinical studies in which the accuracy was described for radiography (two studies), magnetic resonance imaging (five), computed tomography (one), bone scintigraphy (seven), leukocyte scintigraphy (thirteen), gallium scintigraphy (one), combined bone and leukocyte scintigraphy (six), combined bone and gallium scintigraphy (three), and fluorodeoxyglucose positron emission tomography (four) were included in the review. No meta-analysis was performed with respect to computed tomography, gallium scintigraphy, and radiography. Pooled sensitivity demonstrated that fluorodeoxyglucose positron emission tomography was the most sensitive technique, with a sensitivity of 96% (95% confidence interval, 88% to 99%) compared with 82% (95% confidence interval, 70% to 89%) for bone scintigraphy, 61% (95% confidence interval, 43% to 76%) for leukocyte scintigraphy, 78% (95% confidence interval, 72% to 83%) for combined bone and leukocyte scintigraphy, and 84% (95% confidence interval, 69% to 92%) for magnetic resonance imaging. Pooled specificity demonstrated that bone scintigraphy had the lowest specificity, with a specificity of 25% (95% confidence interval, 16% to 36%) compared with 60% (95% confidence interval, 38% to 78%) for magnetic resonance imaging, 77% (95% confidence interval, 63% to 87%) for leukocyte scintigraphy, 84% (95% confidence interval, 75% to 90%) for combined bone and leukocyte scintigraphy, and 91% (95% confidence interval, 81% to 95%) for fluorodeoxyglucose positron emission tomography. The sensitivity of leukocyte scintigraphy in detecting chronic osteomyelitis in the peripheral skeleton was 84% (95% confidence interval, 72% to 91%) compared with 21% (95% confidence interval, 11% to 38%) for its detection of chronic osteomyelitis in the axial skeleton. The specificity of leukocyte scintigraphy in the axial skeleton was 60% (95% confidence interval, 39% to 78%) compared with 80% (95% confidence interval, 61% to 91%) for the peripheral skeleton. CONCLUSIONS: Fluorodeoxyglucose positron emission tomography has the highest diagnostic accuracy for confirming or excluding the diagnosis of chronic osteomyelitis. Leukocyte scintigraphy has an appropriate diagnostic accuracy in the peripheral skeleton, but fluorodeoxyglucose positron emission tomography is superior for detecting chronic osteomyelitis in the axial skeleton.

Reliability of the clinical teaching effectiveness instrument.

INTRODUCTION: The Clinical Teaching Effectiveness Instrument (CTEI) was developed to evaluate the quality of the clinical teaching of educators. Its authors reported evidence supporting content and criterion validity and found favourable reliability findings. We tested the validity and reliability of this instrument in a European context and investigated its reliability as an instrument to evaluate the quality of clinical teaching at group level rather than at the level of the individual teacher. METHODS: Students participating in a surgical clerkship were asked to fill in a questionnaire reflecting a student-teacher encounter with a staff member or a resident. We calculated variance components using the urgenova program. For individual score interpretation of the quality of clinical teaching the standard error of estimate was calculated. For group interpretation we calculated the root mean square error. RESULTS: The results did not differ statistically between staff and residents. The average score was 3.42. The largest variance component was associated with rater variance. For individual score interpretation a reliability of > 0.80 was reached with 7 ratings or more. To reach reliable outcomes at group level, 15 educators or more were needed with a single rater per educator. DISCUSSION: The required sample size for appraisal of individual teaching is easily achievable. Reliable findings can also be obtained at group level with a feasible sample size. The results provide additional evidence of the reliability of the CTEI in undergraduate medical education in a European setting. The results also showed that the instrument can be used to measure the quality of teaching at group level.

Bone morphogenetic proteins. Development and clinical efficacy in the treatment of fractures and bone defects.

The discovery of bone morphogenetic proteins marks a major step forward in the understanding of bone physiology and in the development of advanced methods in skeletal surgery. The cornerstones for successful growth-factor therapy in skeletal surgery remain biomechanical stability and biological vitality of the bone providing an adequate environment for new bone formation. Knowledge of the biological characteristics, mechanisms of action, and methods of delivery of growth factors will become essential for skeletal surgeons. The current clinical application of bone morphogenetic proteins is safe and efficacious as a result of a well-regulated cascade of events leading to bone formation. Clinical trials have not yet determined whether different clinical indications each require a specific bone-tissue-engineering format or if a single pathway for stimulating bone-healing with growth factors is sufficient.

The impact of multifaceted educational structuring on learning effectiveness in a surgical clerkship.

INTRODUCTION: Various measures have been introduced to enhance learning experiences in clerkships, generally with limited success. This study evaluated the impact of a multifaceted approach on the effectiveness of learning in a surgical clerkship. In accordance with results obtained in continuing medical education, several interventions were introduced simultaneously. We compared students' evaluations of the traditional surgical clerkship with those of the restructured clerkship. METHODS: Two consecutive cohorts of students were asked to complete a questionnaire about the quality and quantity of their learning experiences. Cohort 1 (n = 28) undertook the traditional clerkship and cohort 2 (n = 72) the restructured clerkship. A Mann-Whitney test was used to compare outcomes between the 2 cohorts. RESULTS: There were few statistically significant differences between cohorts 1 and 2. Overall, quality indicators did not differ between the 2 cohorts. DISCUSSION: A short-term multifaceted intervention led to a slight increase in the performance of clinical skills and a slight decrease in time spent on activities of limited educational value. The intervention may have been too brief to produce substantial effects. Future interventions should also target teachers, including trainees, in order to assess their opinions and address their educational needs.

Primary immune response to keyhole limpet haemocyanin following trauma in relation to low plasma glutamine.

Severe trauma can lead to a compromised immune response, thereby increasing susceptibility to infections. Here we will study to what extent these early changes in the immune status upon trauma affect a primary immune response to keyhole limpet haemocyanin (KLH). Because glutamine is the preferred respiratory substrate for immune competent cells and known to be depleted after trauma, we studied the immune status and the primary sensitization in relation to the glutamine plasma concentration in a group of severe trauma patients [injury severity score (ISS) >17]. Trauma patients (n = 31) were sensitized with KLH within 12 h after trauma; plasma glutamine concentrations and immune parameters were determined, after which KLH-specific immune responsiveness was evaluated on days 9 and 14. Low plasma glutamine concentrations were found after trauma. Significantly elevated numbers of granulocytes and CD14-positive leucocytes were found, whereas the HLA-DR expression on CD14-positive cells was significantly lower in trauma patients than in healthy controls. Trauma did not change the in vitro proliferative capacity of lymphocytes when cultured with glutamine; however, when lymphocytes were cultured without glutamine, trauma resulted in lower proliferation than healthy controls. Phytohaemagglutinin-(PHA)-induced interferon (IFN)-gamma and interleukin (IL)-10 production was significantly lower after trauma, whereas IL-4 production was not affected. KLH sensitization following trauma resulted in poor skin test reactivity and low in vitro KLH-induced lymphocyte proliferation compared to controls. In contrast, the development of anti-KLH IgM, IgG, IgA, IgG1, IgG2, IgG3 and IgG4 production on days 9 and 14 following trauma was not different from that in healthy controls. Major trauma was associated with a reduced cell-mediated immune response, correlating with low plasma glutamine concentrations, while no effects of trauma were found on the development of a primary humoral immune response.

A qualitative study of constructive clinical learning experiences.

Little is known about the effectiveness of clinical education. A more educational structure is considered to be potentially beneficial. The following structured components were added to a surgical clerkship: logbooks, an observed student-patient encounter, individual appraisals, feedback on patient notes, and (case) presentations by students. The authors organized two focus-group sessions in which 19 students participated to explore their perceptions about effective clinical learning experiences and the newly introduced structured components. The analysis of the transcripts showed that observation and constructive feedback are key features of clinical training. The structured activities were appreciated and the results show the direction to be taken for further improvement. Learning experiences depended vastly on individual clinicians' educational qualities. Students experienced being on call, assisting in theatre and time for self-study as instructive elements. Recommended clerkship components are: active involvement of students, direct observation, selection of teachers, a positive learning environment and time for self-study.

Effect of recombinant human osteogenic protein-1 on the healing of a freshly closed diaphyseal fracture.

Osteogenic protein-1 (OP-1), or bone morphogenetic protein-7, is an osteoinductive morphogen that is involved in embryonic skeletogenesis and in bone repair. In bone defect models without spontaneous healing, local administration of recombinant human OP-1 (rhOP-1) induces complete healing. To investigate the ability of rhOP-1 to accelerate normal physiologic fracture healing, an experimental study was performed. In 40 adult female goats a closed tibial fracture was made, stabilized with an external fixator, and treated as follows: (1) no injection; (2) injection of 1 mg rhOP-1 dissolved in aqueous buffer; (3) injection of collagen matrix; and (4) injection of 1 mg rhOP-1 bound to collagen matrix. The test substances were injected in the fracture gap under fluoroscopic control. At 2 and 4 weeks, fracture healing was evaluated with radiographs, three-dimensional computed tomography (CT), dual-energy X-ray absorptiometry, biomechanical tests, and histology. At 2 weeks, callus diameter, callus volume, and bone mineral content at the fracture site were significantly increased in both rhOP-1 groups compared with the no-injection group. As signs of accelerated callus maturation, bending and torsional stiffness were higher and bony bridging of the fracture gap was observed more often in the group with rhOP-1 dissolved in aqueous buffer than in uninjected fractures. Treatment with rhOP-1 plus collagen matrix did not result in improved biomechanical properties or bony bridging of the fracture gap at 2 weeks. At 4 weeks there were no differences between groups, except for a larger callus volume in the rhOP-1 plus collagen matrix group compared with the control groups. All fractures showed an advanced stage of healing at 4 weeks. In conclusion, the healing of a closed fracture in a goat model can be accelerated by a single local administration of rhOP-1. The use of a carrier material does not seem to be crucial in this application of rhOP-1.

The assessment of cortical heat during intramedullary reaming of long bones.

BACKGROUND: This experimental study was designed to compare different in vitro methods of measuring the cortical temperature when reaming the medullary cavity. This was done to validate an approved mathematical model which can be used to determine the temperature gradient in cortical bone in the presence or absence of sensors. METHODS: Artificial bone was used with an intramedullary heat source instead of a reamer. Temperatures were measured with thermocouples placed radially and axially in the cortical wall. This method with these two measurement positions were compared and used to validate an approved mathematical model. This model was used to determine the temperature gradient in cortical bone in the absence of sensors. RESULTS: The measurement of the cortical temperature with the thermocouples in a radial position only reflects maximally 14% of the temperature of the reamer (calculated 55%). The measurement with the thermocouples in axial position reflects maximally 65% (calculated 70%) of the reamer temperature, which is similar to undisturbed bone. CONCLUSION: The measuring method with the thermocouples in a radial position cannot be recommended. It is likely that a much higher temperature is generated and conducted through reaming than has been assumed until now.

The reliability of plain radiography in experimental fracture healing.

OBJECTIVE: To investigate the reliability of radiographs in the evaluation of healing of closed fractures. DESIGN: A closed midshaft tibial fracture was created in 40 goats and stabilized with an external fixator. The animals were assigned to four groups: no injection, injection of 1 mg osteogenic protein-1 (OP-1), 1 mg OP-1 with collagenous carrier, or carrier alone. Radiographs were performed weekly until the animals were killed after 2 and 4 weeks. Healing was evaluated using radiographs, biomechanical testing, and histological examination. All radiographs were examined by two independent observers. Interobserver agreement was calculated and radiographic scores were compared with mechanical and histological scores using regression analysis. RESULTS: Regression analysis showed poor correlation between radiographic scores and biomechanical and histological data. Correlation coefficients varied between 0.39 and 0.63. Good agreement between the observers was seen in only three parameters: visibility of the fracture line, weightbearing ability, and a combined healing parameter. CONCLUSION: Plain radiography provides poor parameters for monitoring the fracture healing process.

Traumatic rupture of the thoracic aorta: time to diagnosis and treatment.

Survival of patients with traumatic rupture of the thoracic aorta (TRTA) depends on early surgical repair. Six cases of TRTA were treated at our institution in 7 years. Time to diagnosis was 1.5, 3, 4, 36, 91 and 140 hours (mean = 46 hours). Diagnosis was made by computed tomography in one and by angiography in five cases. Time from arrival to treatment was 3, 9, 5, 46, 117 and 152 hours (mean = 55 hours). All six patients were treated by clamp and suture technique, with a mean cross clamp time of 48 minutes. Significant delay in diagnosis and treatment occurred in three patients. The reasons for delay were unrecognized signs for TRTA on the initial chest X-ray, a false-negative result of transoesophageal echography and not considering the diagnosis of TRTA. The diagnosis of TRTA requires a high index of suspicion and should always be considered in victims of high impact trauma.

Biomechanical and histological aspects of fracture healing, stimulated with osteogenic protein-1.

Fracture healing could be stimulated with osteoinductive bone morphogenetic proteins (bmp's), such as osteogenic protein-1 (OP-1), but little is known about its effectiveness in stimulation of fracture healing. In this study, biomechanical and histological aspects of fracture healing after an injection of OP-1 in the fracture gap were investigated. In 40 goats, a closed fracture was created in the left tibia. The fractures were stabilized with an external fixator and the animals were assigned to four different groups: no injection, injection of 1 mg OP-1, injection of 1 mg OP-1 with collagenous carrier material, and injection of carrier material alone. Twenty-one animals were sacrificed after 2 weeks and 19 after 4 weeks. Biomechanical testing was perfomed on both explanted tibiae. Four longitudinal samples of the fracture were sawn, processed for histology, and examined by two observers. Biomechanical evaluation showed a higher stiffness and strength at 2 weeks after injection of OP-1. Histological evaluation showed normal fracture healing patterns in all animals without adverse effects of the given injections. These data show that fracture healing can be accelerated with a single injection of OP-1, eventually resulting in normally healed bone.

Reaming debris in osteotomized sheep tibiae.

BACKGROUND: Reamed nailing gives better fracture healing than unreamed nailing in operative treatment of fractures and nonunions. This study investigates the effect of isolated reaming debris on fracture healing in an animal model. METHODS: Thirty sheep were treated with an osteotomy of the tibia with 5-mm distraction. In one group, the osteotomy gap was left empty; in the second group, the gap was packed with reaming debris from the ipsilateral femur; and in the third group, the gap was packed with cancellous bone from the iliac crest. At follow-up, callus volume was measured on standard radiographs. RESULTS: After 3 weeks, callus volume from the reaming debris group as well as the iliac crest group had increased significantly compared with the empty group. CONCLUSION: This study shows that isolated reaming debris supports callus building as much as conventional bone grafting, which might explain why fractures heal with more callus formation when treated with reamed nailing compared with unreamed nailing.

How effective is a clerkship as a learning environment?

To assess the educational quality of a traditional clerkship, a questionnaire was administered to 28 students at the end of their 10-week surgical clerkship. The questionnaire contained 116 items on learning objectives, patient problems encountered by students, clinical skills performed, feedback received and amounts of time spent on various activities. The students indicated that they had adequate ability to correctly analyse and manage patient problems. However, the standard deviations and ranges show that individual students' exposure to various patient problems was insufficient. Students generally saw too few emergency patients. The frequencies of performance of diagnostic and therapeutic skills varied widely among students. Most of the feedback received by students was given by residents rather than faculty physicians. Students spent considerable time on activities of limited educational value. It appears that learning during a clerkship occurs rather haphazardly. There are indications that the 'educational exposure' varies substantially from student to student.

Destination of debris during intramedullary reaming. An experimental study on sheep femurs.

This study was designed to further explain the better fracture healing in fractures treated with a reamed nail. It investigates the location and quantity of the reaming debris in an ex vivo animal model to test the autograft theory. In 10 cadaveric sheep femurs, a 5-mm semicircular gap was created at the midshaft. The medullary cavity was opened and the reaming debris that dropped from the gap during reaming and the debris from the proximal opening were collected and weighed separately. The mean harvest of reaming debris at the gap was 0.99 g +/- 0.12 g (24%) and from the proximal opening at the medullary cavity 3.08 g +/- 0.31 g (76%) (total 4.07 +/- 0.34 g). This study proves that a significant amount of reaming debris collects at an artificial fracture gap during reaming of the medullary cavity. This finding supports the theory of bone autografting.

Evaluation of strength of healing fractures with dual energy Xray absorptiometry.

Dual energy xray absorptiometry was investigated as a method for evaluation of the strength of closed tibial fractures. In 40 goats, a closed midshaft fracture was created in the left tibia. The fractures were stabilized with an external fixator. After 2 weeks (n = 21) and after 4 weeks (n = 19), both tibias were explanted and, using dual energy xray absorptiometry, bone mineral density and bone mineral content were measured in a 1 cm region. With nondestructive bending tests, area ratio and stiffness index were determined and torsional strength and torsional stiffness were determined with a torsional test to failure. Linear regression analysis was used to calculate the squared correlation coefficients for the relations between dual energy xray absorptiometry and the outcome of the mechanical tests. The squared correlation coefficients for the relation between bone mineral density and torsional strength, torsional stiffness, and area ratio and stiffness index were 0.72, 0.76, 0.64, and 0.72, respectively. The squared correlation coefficients for the relation between bone mineral content and these mechanical parameters were 0.72, 0.77, 0.63, and 0.77, respectively. The results using dual energy xray absorptiometry indicate the strength of healing closed fractures. Additional research is required to investigate specific aspects of this technique.

Resorbable calcium phosphate particles as a carrier material for bone marrow in an ovine segmental defect.

Resorbable calcium phosphate ceramics are only osteoconductive; therefore, their combination with osteogenic substances may lead to stimulation of bone healing. In the present study this combination, using autologous bone marrow, was investigated. In 31 sheep, a 3-cm tibial segmental defect was created and stabilized with an intramedullary nail. The animals were divided into four groups: empty defects (group 1, n = 7), and defects filled with 10-mL dense resorbable calcium phosphate particles (group 2, n = 8), with 10-mL particles soaked in bone marrow (group 3, n = 8), or with 10-mL autologous bone (group 4, n = 8). On evaluation after 12 weeks, significantly higher values were seen in group 3 than in group 2 for callus volume (p = .016), bone mineral density ratio (p = .03), bone mineral content ratio (p = .04), torsional strength (p = .005), and torsional stiffness (p = .01). For all end points, the outcome of group 3 was lower than that of group 4. In the histology, there was direct contact between newly formed bone and remnants of the particles. There were no signs of inflammatory reactions. Although a stimulatory effect of bone marrow was seen, the combination of resorbable calcium phosphate particles with bone marrow does not provide an alternative for autologous bone grafting.

The effect of alendronate on bone mass after distal forearm fracture.

Fracture and immobilization of an extremity lead to bone loss at the fracture and at adjacent sites. We conducted a 1-year, single-center, prospective, randomized, double-blind study to determine whether bone loss would occur in the distal radius after a Colles' fracture and whether this loss could be prevented using an antiresorptive drug (alendronate). Thirty-seven women with a recent fracture of the distal forearm and low bone mineral density (BMD) of the lumbar spine were randomized to receive either 10 mg alendronate daily or placebo. BMD of both forearms was measured at baseline and after 3, 6, and 12 months. The results of four women who developed reflex sympathetic dystrophy were not included in the analysis. In the placebo group, there was a significant reduction at 3 months and 6 months in BMD of total radius (p < 0.01), one-third distal radius (p < 0.01), middistal radius (p < 0.05), and ultradistal radius (p < 0.01) on the fractured side. The loss in BMD at one-third distal radius remained significant at month 12 (p < or = 0.001). In the alendronate group BMD of total distal radius, one-third distal radius, and middistal radius at the fractured side remained unchanged. BMD of ultradistal radius increased significantly at months 3, 6, and 12, compared with baseline (p < 0.05). The difference between the two treatment groups was significant at 3 months and 6 months and borderline significant (p = 0.054) after 1 year in total distal radius. In ultradistal radius the differences were significant at all time points. We conclude that BMD of the distal radius of a recently fractured forearm decreases significantly in the 6 months after fracture and the resulting deficit remains evident at least 1 year after fracture. This bone loss can be prevented by alendronate.

New segmental long bone defect model in sheep: quantitative analysis of healing with dual energy x-ray absorptiometry.

An appropriate animal model is required for the study of treatments that enhance bone healing. A new segmental long bone defect model was developed for this purpose, and dual energy x-ray absorptiometry was used to quantify healing of this bone defect. In 15 sheep, a 3-cm segmental defect was created in the left tibia and fixed with an interlocking intramedullary nail. In seven animals, the defect was left empty for the assessment of the spontaneous healing response. In eight animals serving as a positive control, autologous bone grafting was performed. After 12 weeks, healing was evaluated with radiographs, a torsional test to failure, and dual energy x-ray absorptiometry. The mechanical test results were used for the assessment of unions and nonunions. Radiographic determination of nonunion was not reliably accomplished in this model. By means of dual energy x-ray absorptiometry, bone mineral density and content were measured in the middle of the defect. Bone mineral density was 91+/-7% (mean +/- SEM) and 72+/-6% that of the contralateral intact tibia in, respectively, the autologous bone-grafting and empty defect groups (p = 0.04). For bone mineral content, the values were, respectively, 117+/-18 and 82+/-9% (p = 0.07). Torsional strength and stiffness were also higher, although not significantly, in the group with autologous bone grafting than in that with the empty defect. Bone mineral density and content were closely related to the torsional properties (r2 ranged from 0.76 to 0.85, p < or = 0.0001). Because interlocking intramedullary nailing is a very common fixation method in patients, the newly developed segmental defect model has clinical relevance. The interlocking intramedullary nail provided adequate stability without implant failure. This model may be useful for the study of treatments that affect bone healing, and dual energy x-ray absorptiometry may be somewhat helpful in the analysis of healing of this bone defect.

Bone tissue response to biodegradable polymers used for intra medullary fracture fixation: a long-term in vivo study in sheep femora.

Since the degradability of the synthetic polymers used for fracture fixation is still unclear, a research project with biodegradable interlocking nails with a longterm implantation period has been started. In 21 female sheep a complete mid-shaft osteotomy of the left femur was performed to mimic a fracture of the femoral shaft. For the fixation, an intramedullary stainless-steel interlocking nail, a PLA rod or a PLA/PGA rod was used. After 30 months of implantation the histological results of these three materials were examined. In contrast to most reports the degradation rate of both polymers was much lower than the suggested ultimate period of two years. Even the tissue response was more pronounced than expected and this reaction can imply certain risks for repulsion. One can conclude that the volume quantity of polymeric implant in the bony tissue must be reduced if possible to avoid severe foreign body responses. The immunologic responses and the clinical consequences need more studies. The degradation behavior of the polymer is still not under control.