Mutational Studies of Aldose Reductase to Trace a Transient Pocket Opening and to Explain Ligand Affinity Cliffs.

Human aldose reductase, a target for the development of inhibitors for preventing diabetic complications, displays a transient specificity pocket which opens upon binding with specific, potent inhibitors. We investigated the opening mechanism of this pocket by mutating leucine residues involved in the gate keeping mechanism to alanine. Two isostructural inhibitors distinguished only by a single nitro to carboxy group replacement, have a 1000-fold difference in their binding affinity to the wild type. This difference is reduced to 10-fold in the mutated variants as the nitro derivative loses in affinity but conserves binding to the open transient pocket. The affinity of the carboxylate analog is minimally altered but the analog binding preference changes from the closed to open state of the transient pocket. Differences in the solvation properties of ligands and the transient pocket as well as changes from induced fit to conformational selections provide an explanation for the altered behavior of the ligands with respect to their binding to the different variants.

Connection of a hip prosthesis and an intramedullary nail as a special solution in a subtrochanteric femoral fracture with fibrous dysplasia.

Treatment of fractures associated with fibrous dysplasia is difficult because of poor bone quality. In a brief report we present a case in which a hip prosthesis is connected with the distal part of a broken cannulated intramedullary femur nail. Postoperatively, the patient was mobilized with full weight bearing. Radiographs proved the correct position of the implant and a favorable clinical function could be achieved.

Effects of a WLAN-based real time location system on outpatient contentment in a Level I trauma center.

BACKGROUND: Pre-existing wireless local area network (WLAN) infrastructures enable the implementation of a real-time location system (RTLS) in the clinical setting. RTLS enable clinics to capture and process patient position data and link it with clinical data. The improvements in workflow and treatment brought about by RTLS may improve patient satisfaction. The aim of this study was to analyze the impact of a WLAN-based RTLS on outpatient satisfaction in our Level I trauma center. METHODS: This investigation was performed under different study arms (termed "phase"): In phase 0, patient satisfaction was determined (with a questionnaire) without RTLS implementation. In phase I, patient tracking with RTLS was performed, and satisfaction was determined (with a questionnaire); however, medical personnel did not utilize information gathered by RTLS. In phase II, patients were tracked by RTLS and satisfaction was determined (with a questionnaire); however, unlike phase I, the RTLS-acquired data was utilized by medical personnel. Information obtained from the questionnaire included: treatment rendered, subjective estimation of length of visit, subjective estimation of the most time-consuming portions of the clinic visit, subjective estimation of time of medical treatment, overall contentment, and contentment with wait time. In phase I and phase II, position data was automatically collected and analyzed. Statistical analyses were performed using Student's t-test and one-way Anova test. Significance level was set at 0.05. RESULTS AND DISCUSSION: In total, 1234 patients were included in our study (188 in phase 0, 540 in phase I, and 506 in phase II). Completed questionnaires were collected in 53% (654) of the patients. Statistically significant higher patient contentment and lower subjective wait times were noted in phase II patients as compared to phase I patients. However, no statistical differences in the questionnaire findings were noted between phase 0 and I patients. CONCLUSIONS: WLAN-based RTLS can help alleviate process inefficiencies associated with traditional clinic workflow methods, which can lead to improved patient satisfaction.

Improvement in the workflow efficiency of treating non-emergency outpatients by using a WLAN-based real-time location system in a level I trauma center.

BACKGROUND: Patient localization can improve workflow in outpatient settings, which might lead to lower costs. The existing wireless local area network (WLAN) architecture in many hospitals opens up the possibility of adopting real-time patient tracking systems for capturing and processing position data; once captured, these data can be linked with clinical patient data. OBJECTIVE: To analyze the effect of a WLAN-based real-time patient localization system for tracking outpatients in our level I trauma center. METHODS: Outpatients from April to August 2009 were included in the study, which was performed in two different stages. In phase I, patient tracking was performed with the real-time location system, but acquired data were not displayed to the personnel. In phase II tracking, the acquired data were automatically collected and displayed. Total treatment time was the primary outcome parameter. Statistical analysis was performed using multiple linear regression, with the significance level set at 0.05. Covariates included sex, age, type of encounter, prioritization, treatment team, number of residents, and radiographic imaging. RESULTS/DISCUSSION: 1045 patients were included in our study (540 in phase I and 505 in phase 2). An overall improvement of efficiency, as determined by a significantly decreased total treatment time (23.7%) from phase I to phase II, was noted. Additionally, significantly lower treatment times were noted for phase II patients even when other factors were considered (increased numbers of residents, the addition of imaging diagnostics, and comparison among various localization zones). CONCLUSIONS: WLAN-based real-time patient localization systems can reduce process inefficiencies associated with manual patient identification and tracking.

Two-stage multilevel en bloc spondylectomy with resection and replacement of the aorta.

OBJECTIVE: We report a case of multilevel spondylectomy in which resection and replacement of the adjacent aorta were done. Although spondylectomy is nowadays an established technique, no report on a combined aortic resection and replacement has been reported so far. METHODS: The case of a 43-year-old man with a primary chondrosarcoma of the thoracic spine is presented. The local pathology necessitated resection of the aorta. We did a two-stage procedure with resection and replacement of the aorta using a heart-lung machine followed by secondary tumor resection and spinal reconstruction. RESULTS: The procedure was successful. A tumor-free margin was achieved. The patient is free of disease 48 months after surgery. CONCLUSION: En bloc spondylectomy in combination with aortic resection is feasible and might expand the possibility of producing tumor-free margins in special situations.

Development of a WLAN-based real time localization system for patient tracking in a Level I Trauma center.

BACKGROUND: Patient tracking helps improve workflow, decrease wait times, optimize costs, and enhance medical treatment in the outpatient setting. In that regard, real-time patient tracking may serve as a potential way to perform efficient patient care. In recent years, the increasing popularity of wireless local area networks (WLANs) has led to a growing number of devices utilizing wireless fidelity (WiFi) networks. This application has been used in various industries to enhance management processes. In that regard, we believe that this technology may enhance patient tracking, as the existing WLAN architecture in many clinics may allow for real-time tracking of patients. However, current literature regarding the clinical applicability of these devices is sparse. The aim of this study is to analyze the developmental process and feasibility of our protytope model for real-time patient tracking, using WLAN in the outpatient setting of our Level I Trauma center. METHODS: We performed the study in various stages. First, we analyzed our current patient workflow, and then devised a study protocol and prototype model that implemented both this workflow schematic and our current technology infrastructure. Second, we implemented our prototype model to determine the accuracy, feasibility, and safety of data transmission in our clinical setting. The factors examined during prototype implementation included the accuracy of patient localization and the time spent by each patient in the various areas of our clinic (as determined by patient tracking). RESULTS: In our outpatient clinic, our prototype was capable of localizing and automating patient data with excellent accuracy and security. CONCLUSIONS: WLAN-based real-time patient localization systems can help overcome a number of common challenges and inefficiencies seen in the outpatient clinics. Real-time localization systems using WLAN technology performed adequately and safely in this pilot study. We believe that this will eventually lead to lower costs overall due to the improvements in efficiency. While the initial investment costs may be high, implemeting this system in a pre-existing WLAN and WiFi infrastructure should help minimize the start-up costs.

Navigated femoral shaft fracture treatment: current status.

Femoral malrotation is a common complication after internal fixation of a femoral shaft fracture. The only valid, objective monitoring method is computer tomography-assisted torsion measurement between the proximal and distal femur; unfortunately, this can only be carried out postoperatively. A difference of 15° compared to the contralateral femur is seen as an indication for revision. With the development of computer-assisted surgery, new possibilities for performing torsion control and correction intraoperatively has been introduced. These methods also allow for navigation-assisted definition of the optimal incision site, intramedullary access, femoral nail and interlocking. The main problem lies in the extra time of surgery, which is due to performing all the steps of the surgery navigated. The solution for this problem is "hybrid navigation", in which the surgeon can select the steps he needs from the navigation system, depending on his experience or surgical technique.

The aseptic femoral and tibial shaft non-union in healthy patients - an analysis of the health-related quality of life and the socioeconomic outcome.

UNLABELLED: Long bone non-unions may lead to recurrent surgical procedures and in-hospital stays. Thus, restrictions of the health-related quality of life and of socioeconomic parameters might be expected. Knowledge of the impact on several parameters of professional life is sparse. Therefore, we analyzed the outcome in patients following non-unions of the tibial and femoral shaft after fracture compared to patients with uneventful healing. MATERIAL AND METHODOLOGY: 51 patients following non-unions of the the femoral (FNU) or tibial shaft (TNU) were compared to 51 patients (groups FH and TH) with uneventful fracture healing. Physical and mental health was assessed using the Short-Form Health Survey (SF-12), Hospital Anxiety and Depression Scale (HADS) and the Impact of Event Scale (IES). We also analyzed employment status and the usage of medical aids. RESULTS: Scores of the SF-12 physical and psychological were lower in group TNU compared to group TH, the score of SF-12 physical but not psychological was significantly lower in group FNU compared to FH. Compared to uneventful healing, a significantly more frequent usage of medical aids was found in both non-union groups. A higher incidence of early retirement and unemployment was found in group FNU but not in group TNU. CONCLUSIONS: There is a profound influence on the quality of life following femoral or tibial non-unions after trauma. Compared to patients with uneventful fracture healing, patients with tibial and even more so femoral non-union show worse scores of the SF-12. Medical aids are frequently used following both, femoral and tibial non-unions. Not tibial, but femoral non-unions frequently lead to severe restrictions in professional life such as early retirement and unemployment.

Are polymorphisms of molecules involved in bone healing correlated to aseptic femoral and tibial shaft non-unions?

Fracture healing is a well-organized process between several molecules and mediators. As known from other diseases, genetic polymorphisms may exhibit different expression patterns in these mediators. Concerning fracture healing, this may lead to an extended healing process or non-union. We investigated the incidence of polymorphisms in patients with aseptic non-unions after femoral and tibial shaft fractures as compared to patients with uneventful healing. Exclusion criteria were smoking, diabetes, bilateral fractures, systemic corticoid therapy, and septic non-unions. Analysis of allele frequencies and genotype distribution of various mediators were carried out following PCR. Clinical parameters such as injury severity and in-hospital were analyzed. Fifty patients following non-union (group NU) were enrolled, the control group consisted of 44 patients (group H). A significant association of a PDGF haplotype and non-unions following fracture could be observed. There was a significantly increased in-hospital time and amount of surgical procedures in group NU. Polymorphisms within the PDGF gene seem to be a genetic risk factor for the development of non-unions of the lower extremity following fracture. The early identification of high risk patients could result in an adapted therapeutical strategy and might contribute to a significant decrease of posttraumatic non-unions.

Femoral malrotation after unreamed intramedullary nailing: an evaluation of influencing operative factors.

OBJECTIVE: The objective of this study was to determine which clinical factors influence the presence and extent of femoral malrotation during unreamed nail insertion performed without a fracture table. DESIGN: Retrospective chart review. SETTING: Academic trauma center. INTERVENTION: Patients were treated statically locked femoral nails inserted without reaming in either a retrograde or antegrade manner without the use of a fracture table between April 1, 2000, and December 31, 2005. All patients received postoperative computed tomography scans. Institutional radiographic threshold for revision surgery was 15° of either internal or external rotation. MAIN OUTCOME MEASUREMENTS: Postoperative computed tomography measurements of rotation were compared with the opposite side. Patients were grouped by 1) Orthopaedic Trauma Association fracture classification; 2) closed versus mini open reduction; 3) surgeon experience; 4) antegrade versus retrograde femoral nail; and 5) time of day surgery performed (day shift versus night shift). The following parameters were measured from the chart and x-ray: rotational malalignment, x-ray time, and duration of surgery. RESULTS: There were 82 femurs in 82 patients, 59 men and 23 women, with a mean age of 32 years (range, 17-83 years). Eighteen femurs (22%) showed a malrotation of greater than 15°. Seven were internally malrotated (mean, 23°; range 16°-32°), whereas 11 were externally malrotated (mean, 24.2°; range, 16°-39.7°). After clinical examination, only 11 of the 18 patients (61%) underwent revision surgery, six patients for external malrotation (mean, 27.47°; range, 21.9°-39.7°) and five for internal malrotation (mean, 23.6°; range, 16°-32°). Malrotation varied significantly with fracture severity with Type C averaging 19.4° (24 patients), Type B 9° (26 patients), and Type A 6.6° (32 patients). No difference was found between an open and closed technique nor the experience of surgeon or the type of implant. There was a significant difference depending on the time of surgery in which an average malrotation of 15.2° (14 patients) was found on the night shift and an average malrotation of 10.3° (68 patients) was found during the day. CONCLUSION: Rotational malalignment greater than 15° was found in 22% of femurs treated in this study. Fracture comminution and time of day the surgery was performed had the greatest effect on the severity of malrotation.

Mechanical stability analysis of reference clamp fixation in computer-assisted spine surgery.

BACKGROUND: Pedicle screw misplacement is a common complication, while 7% may result in neurological complications. Computer-assisted navigation improves the rate of ideally placed screws. Inappropriate reference marker attachment can cause major problems in the outcome and duration of surgery. OBJECTIVE: To improve fixation of reference bases by comparing different designs of spine clamps and measuring their stability against the relevant thoracic and lumbar anatomy. METHODS: Force needed to dislocate the clamp from the processus spinosus using defined fixation of 0.79, 0.90 and 1.02 Nm torque was evaluated. Force transmission from clamp to the processus spinosus was also examined. Artificial thoracic and lumbar vertebral bodies were used for attaching spine clamps of three different designs. An instrument transmitted linear force onto the reference clamp and recorded the force when dislocation occurred. Another device determined transmitted force for each clamp utilizing 0.79, 0.90, 1.02, 1.13 and 1.24 Nm torque. RESULTS: L-clamp had the most stable fixation in lumbar section for every torque and developed the greatest forces. These transmitted forces were similar to the less stable Y-design. I-design created the smallest forces and had the most stable fixation for thoracic spine. The Y- and the L-design caused a notably high number of fractures. CONCLUSION: Great force leads to great stability, but also creates more fractures, favoring the use of smaller forces. Specific anatomy adaptation is important. Different clamp designs create different forces, while still differing in stability depending on their application in the thoracic or the lumbar spine.

Femoral malrotation following intramedullary nailing in bilateral femoral shaft fractures.

INTRODUCTION: This study was designed to evaluate the incidence of femoral malrotation in bilateral femoral shaft fractures. MATERIALS AND METHODS: All closed bilateral femoral shaft fractures in patients aged 18 or over treated between April 2000 and December 2009 were included in the current study. All patients received a postoperative CT-scan to estimate femoral antetorsion and leg length. All bilateral fractures were treated with intramedullary nailing on a radiolucent table. Retrospectively, all patients were analyzed according to the following parameters: (1) femoral antetorsion of both limbs and antetorsion difference in degrees, (2) femoral length discrepancy (cm), (3) incidence of femoral malrotation >15°, (4) revision rate due to femoral malrotation. RESULTS: A total of 24 patients (11 [45.8%] female; 13 [52.8%] male) with bilateral femoral shaft fractures were included in this study of average age 38 years (median 38 years, range 18-74 years). Clinically relevant malrotation (greater than 15°) was found in 10 cases (41.2%), whereas in 4 cases (40%) a revision surgery was required. DISCUSSION: Bilateral femoral shaft fractures are associated with a high incidence of clinically relevant femoral malrotation over 15°. Measurement of intraoperative femoral antetorsion in bilateral femoral shaft fractures is quite difficult and currently only feasible postoperatively.

Influence of femoral malrotation on knee joint alignment and intra-articular contract pressures.

INTRODUCTION: The standard treatment of femoral diaphyseal fractures is intramedullary nailing. Torsion error remains a largely unsolved problem. We hypothesized that femoral malrotation would change the coronal alignment of the lower extremity and the center of force (COF) in the tibiofemoral joint as compared to the native state. METHOD: Ten cadaveric legs were used. Intraarticularly placed sensor foil was used to measure contact pressures for each condyle. The resultant pressure of this two-force measurement was calculated as the COF for the joint. Mechanical axis was defined by the navigation system. Two novel devices were used: (1) to simulate bodyweight with leg attachment and fixation to the anterior pelvis and (2) to fix the femur at various degrees of malrotation. A mid-diaphyseal osteotomy was performed and the distal fragment was rotated both internally and externally in 5° increments to a maximum of 25°. COF and axial alignment were assessed at each step with application of a half-bodyweight specific to each specimen. RESULTS: Internal rotation resulted in valgus deviation of the mechanical axis and a shift in COF towards the lateral condyle (P < 0.05). External rotation caused varus deviation and switched COF towards the medial condyle (P < 0.05). This study shows that femoral malrotation has a significant effect on mechanical axis alignment and force vectors within the knee. Correlation with clinical outcomes is necessary and further research into minimizing such errors of torsion is warranted. CONCLUSION: Torsion errors are not merely cosmetic issues, but may result in further morbidity, such as varus or valgus deformity and shifting of the COF, which may lead to joint arthrosis.

Reliability of computer-assisted surgery as an intraoperative ruler in navigated high tibial osteotomy.

BACKGROUND: Computer-assisted surgery (CAS) can act as an intraoperative ruler in high tibial osteotomy (HTO) to visualize continuously the leg during surgery. QUESTIONS: The aim of the study is to evaluate the accuracy of CAS with respect to preoperative planning and postoperative deviation from the planned leg axis in HTO. In addition, the influence of surgeon experience as well as operation time and perioperative complications are analyzed. METHODS: A prospective multicenter study case series with follow-up at 6 weeks was performed in six centers. Medial open-wedge HTO with Tomofix(®) was done using computer assisted navigation technique with the Brainlab VV Osteotomy 1.0 module. RESULTS: Fifty-one patients with medial gonarthritis were treated with navigated HTO. The follow-up rate was 98%. The majority of HTO-CAS patients fell within the tolerated limit of ±3° for leg axis deviation, however, seven patients were reported with deviations outside of this range: three patients had deviations of >3°-4.5° and four patients >4.5°, respectively. Eight intraoperative complications were documented, partially resulting from technical problems associated with the navigation system. During the 6-week follow-up period, three postoperative complications were experienced, all not associated with navigation technology. CONCLUSIONS: In about 85% of cases, a perfect result in terms of deviation of the planned mechanical leg axis could be achieved. Computer assistance in HTO proved to be a helpful tool regarding intraoperative control of leg axis. LEVEL OF EVIDENCE: Level I, High quality prospective study (all patients were enrolled at the same preoperative planning point with ≥80% follow-up of enrolled patients).

Navigated reconstruction of a tibial plateau compression fracture post-virtual reconstruction: a case report.

Post-traumatic arthrosis is a common problem following tibial plateau fractures. Computed tomography (CT) with 3D reconstruction is essential in facilitating accurate analysis of the fracture type and depth of compression, but is typically only available pre- or postoperatively. Special reconstruction software tools, based on 3D imaging, have been developed. Limiting factors include a lengthy preoperative planning phase. This study assessed a specific type of navigation software, which is currently in use in maxillofacial surgery, to establish whether it might play a critical role in orthopaedic procedures. We report the case of a 43 year old female who sustained an isolated tibial plateau compression fracture (Schatzker IIIa), and who was successfully treated with open reduction and internal fixation, with the aid of intraoperative 3D imaging and new software navigation tools. This case demonstrates a combined approach using a new software tool based on intraoperative fluoroscopy-3D imaging.

Navigated minimally invasive thoracolumbar pedicle screw placement with flat panel 3-D imaging. A feasibility study.

STUDY DESIGN: The current study involves a cadaveric specimen with navigated pedicle screw placement using conventional reference markers and isocentric 3D fluoroscopy and also minimally invasive reference marker use with a flat panel 3D scanner. OBJECTIVE: To test the feasibility of a novel minimally invasive reference marker system for navigated pedicle screw placement in combination the use of a new imaging modality i.e. flat panel 3D imaging. SUMMARY OF BACKGROUND DATA: A major limiting factor of navigated pedicle screw placement is the requirement for intraosseous fixation of reference markers. This usually necessitates an open approach to the spinous process. To address this issue, the current authors have developed a minimally-invasive fixation device for spinal reference marker fixation. METHODS: A fresh-frozen cadaver with no history of spinal injury or deformity was positioned prone on a radiolucent table. L3 and L4 vertebrae were randomly selected for conventional pedicle screw insertion while T5 and T6 were selected for the percutaneous technique. A flat detector 3D C-arm (Ziehm vision FD 3D; Ziehm, Nuremberg, Germany) was used to evaluate the position of the pedicle screws at the vertebral levels targeted in the study. RESULTS: All screws placed within the lumbar spine involved conventional reference markers. The average depth deviation was 0.73 mm and the average axis deviation was 1.67 mm. Within the thoracic spine, the minimally-invasive marker fixation devices were used. The average depth deviation was 0.85 mm and the average axis deviation was 1.75 mm. In both cases, the plan and navigation were performed satisfactorily. The Y-jaw clamp for minimally-invasive reference fixation seemed to provide stable and robust fixation of the markers, requiring only two small incisions. CONCLUSIONS: The minimally invasive reference marker system produced results which were comparable to the conventional intra-osseous markers while the flat detector-based navigation was shown to be easier to use and faster than isocentric Iso-3D technology.

Complete dislocation of the talus: a case report using intraoperative 3D fluoroscopy.

INTRODUCTION: In a complete dislocation of the talus, the talus is stripped of all its ligament connections in the triple articulated ankle joint. This case report describes the treatment and the 3-year follow-up of a complete dislocation of the talus with the use of intraoperative 3D imaging. PATIENTS AND METHODS: The 19-year-old patient was involved as a driver in a car accident. After the radiological diagnosis of a complete talus dislocation, an emergency operation was performed due to the critical soft tissue condition. The ISO-C3D fluoroscope from the company Siemens (Erlangen, Germany) was utilized for reduction control. RESULTS: Follow-up evaluations were completed three years after the treatment, the patient had no complaints. DISCUSSION: Since these types of serious injuries are always combined with severe soft tissue damage, the main goals of this treatment have to be debridement and minimized iatrogenic surgical damage. By using intraoperative 3D imaging, immediate reduction control is available, so that revision operations can be avoided. CONCLUSION: Complete dislocation of the talus is an extremely rare injury, which may cause serious complications. A fast and careful reduction, whether open or closed, should be the goal of treatment. Successful reduction can be determined intraoperatively with the use of 3D imaging.

A customized modular reference array clamp for navigated spine surgery.

INTRODUCTION: The current authors have developed a modular system of reference array fixation which is tailored specifically to the spinal level being operated upon. They believe that this system may further increase the precision and accuracy of pedicle screw placement. MATERIALS AND METHODS: Two formalin-fixed whole body cadavers were used for this study. For cervical spine evaluation of the reference clamp, four odontoid screws (two per cadaver) for C1/C2-fusion and four lateral mass screws (two per cadaver) were implanted. Following navigated screw placement with 2D and 3D fluoroscopic verification, insertion of two lateral mass screws was performed. In the same way, lumbar and thoracic pedicle screws were implanted. Two pedicle screws were placed at two levels of the lumbar and two levels of the thoracic areas giving an overall of 16 screws implanted (8 cervical, 4 thoracic, and 4 lumbar). Postoperative evaluation involved comparison of postoperative 3D scans and preoperative planning images. A simple classification system was used for evaluation of any deviation from the planned trajectory. RESULTS: All pedicle screw placements were performed as planned without any technical problems. The reference array clamps remained in position at all the spinal levels at which they were employed with no loosening or displacement and no secondary damage to any of the spinous processes. Manual manipulation was performed but no displacement or slippage was observed. Image artefacts caused by the reference clamp were not significant as to obscure the area of interest. Both imaging modalities (Iso-C 3D and Vario 3D) generated sufficiently precise 3D images. There was no substantial difference in quality when those two systems were compared. DISCUSSION: Insufficient fixation of the reference clamp can lead to failure and complications. To date, no reference clamp systems have been developed specifically for navigated spine surgery. CONCLUSIONS: Stable reference array fixation is a critical step in navigated surgery. To date, the same reference clamps have been applied to the spinal anatomy as have been developed originally for the appendicular skeleton. The current investigators have developed a novel modular clamp and have demonstrated its efficacy in a cadaveric model.