Penetration of linezolid into synovial fluid and muscle tissue after elective arthroscopy.

Objectives: Penetration of antibiotics into synovial fluid is crucial to combat septic arthritis efficiently. Since linezolid may be used for treatment of septic arthritis when methicillin-resistant bacterial strains are suspected, we investigated its target-site concentrations in synovial fluid. Patients and methods: Ten patients undergoing elective knee arthroscopy were included in this study. Subjects received a single dose of 600 mg of linezolid intravenously and linezolid concentrations were measured in plasma and by using microdialysis in muscle tissue and synovial fluid. Pharmacokinetic/pharmacodynamic calculations to predict bacterial killing ability were performed using CLSI breakpoints and MIC90 for clinical isolates. Results: All 10 subjects tolerated linezolid well. As indicated by AUCtissue/AUCfree plasma ratios of 0.76 ±âŸ0.34 (synovial fluid) and 0.98 ±âŸ0.62 (muscle tissue) linezolid penetrated well into the knee gap and tissue. In synovial fluid AUC0-24/MIC ratios for bacteria with an MIC of 1, 2 and 4 mg/L were 86.8 ±âŸ47.0, 43.4 ±âŸ23.5 and 21.7 ±âŸ11.8, respectively. Conclusions: Linezolid may be used to treat septic arthritis caused by bacterial strains with an MIC ≤1 mg/L. Assuming a pharmacokinetic/pharmacodynamic target of > 50 for AUC0-24/MIC, when treating strains with an MIC >1 mg/L treatment surveillance is warranted. However, pharmacokinetic/pharmacodynamic targets for tissue are poorly understood and clinical data are needed to verify our assumptions.

Pharmacokinetics of Cefuroxime in Synovial Fluid.

Cefuroxime is frequently used as preoperative antibiotic prophylaxis and may be used for the treatment of septic arthritis. A prerequisite for successful treatment of septic arthritis is the ability of an antibiotic agent to penetrate into the target site. Therefore, the concentration of cefuroxime in synovial fluid was evaluated. Ten patients who underwent elective knee arthroscopy were included in this study. Patients were treated with a single dose of 1,500 mg cefuroxime intravenously, and subsequently, the concentrations in plasma, the interstitial fluid of muscle tissue, and synovial fluid were measured by using microdialysis. Pharmacokinetic/pharmacodynamic calculations to predict bacterial killing were performed using the epidemiologically defined MIC90 for clinical isolates and CLSI breakpoints. Cefuroxime penetrated excellently into muscle tissue (ratio of the area under the concentration-time curve [AUC] for muscle tissue/AUC for free plasma, 1.79) and synovial fluid (ratio of the AUC for synovial fluid/AUC for free plasma, 1.94). The cefuroxime concentration was greater than the MIC90 for Staphylococcus aureus and S. epidermidis strains (≤2 mg/liter) over the complete dosing interval (the percentage of the dosing interval during which the free cefuroxime concentration exceeded the MIC for the pathogen [fTMIC]). CLSI defines staphylococci with MICs of ≤8 mg/liter to be susceptible to cefuroxime. For staphylococci with MICs of ≤8 mg/liter, the fTMIC in plasma was 52.5%, while the fTMIC in muscle tissue and synovial fluid was 93.6% and 96.3%, respectively. Cefuroxime may be used to treat septic arthritis caused by susceptible bacterial strains (MIC ≤ 8 mg/liter). The activity of cefuroxime in septic arthritis might be underestimated when relying exclusively on plasma concentrations.

Secondary femur shaft fracture following treatment with cephalomedullary nail: a retrospective single-center experience.

AIM: Secondary femur fracture subsequent to treatment of trochanteric fractures with cephalomedullary nailing (i.e., a periprosthetic fracture related to the cephalomedullary nail) is a rare but very severe complication. As such, the aim of this study was to assess the impact of revision surgery and general state of health on mortality and functional outcomes in patients suffering femur fractures following treatment with cephalomedullary nails. MATERIALS AND METHODS: Between 2000 and 2015, 3549 patients presenting with OTA/AO 31A1-3 femur fractures were admitted to our department and subsequently treated with either a Gamma® Nail or PFNA®. Out of this sample population, 42 patients suffered 43 secondary femur shaft fractures (1.2%). The mean follow-up time was 26 ± 9.7 months. Fractures were classified according to the AO classification and the modified Vancouver classification. Treatment options included ORIF, removing the cephalomedullary nail and fixation with a long nail with or without cerclage wires. General health status was defined according to the ASA Score. Mortality, pre- and postoperative mobility, hospital stay and complications were assessed retrospectively. RESULTS: A total of 14.3% patients died within 90 days following surgery. At least 16.6% patients died due to medical complications strongly related to the surgery. The average time to secondary fracture following initial surgery for trochanteric fracture was 122.7 ± 32 weeks. The most common fracture types were AO 32A1 (53.5%) and AO 32B1 (23.3), as well as Vancouver C and B1. A time-to-secondary-fracture of less than or longer than 6 months following surgery for trochanteric fracture and ASA Score all had no significant influence on mortality, complications, duration of surgery and postoperative mobility. CONCLUSION: Femoral shaft facture subsequent to fixation of trochanteric fracture with cephalomedullary nails is a severe complication. It leads to prolonged hospital stays and delayed recovery. Postoperative hospital stay mortality rates may be as high as 16.6%.

Does an additional antirotation U-Blade (RC) lag screw improve treatment of AO/OTA 31 A1-3 fractures with gamma 3 nail?

INTRODUCTION: Poor bone quality and unstable fractures increase the cut-out rate in implants with gliding lag screws. The U-Blade (RC) lag screw for the Gamma3® nail was introduced to provide monoaxial rotational stability of the femoral head and neck fragment. The purpose of this study was to evaluate whether the use of the U-Blade (RC) lag screw is associated with reduced cut-out in patients with OTA/AO 31A1-3 fractures. MATERIAL & METHODS: Between 2009 and 2014, 751 patients with OTA/AO 31A1-3 fractures were treated with a Gamma3® nail at our institution. Out of this sample 199 patients were treated with U-blade (RC) lag screws. A total of 135 patients (117 female, 18 male) with standard lag screw (treatment group A) were matched equally regarding age (±4 years) sex, fracture type and location to 135 patients with U-blade (RC) lag screw (treatment group B). Within a mean follow up of 9.2 months (range 6-18 months) we assessed the cut-out rate, the calTAD, lag screw migration, the Parker's mobility score and the Parker's ratio at postoperatively, six and 12 months following surgery. Furthermore we recorded all complications, ASA-Score, hospital stay and duration of surgery retrospectively. RESULTS: The most common fracture among group B with a cut-out of the lag screw were AO/OTA 2.3 and 3.2 fractures whereas in group A cut-out was most commonly seen in AO/OTA 2.1, 2.2 and 2.3 fractures, there was no significant reduction of the cut-out rate in group B 2.2% (n=3) compared to group A 3.7% (n=5). The duration of surgery was significantly shorter in group A (p<0.05). There was no significant difference in lag screw placement, the Parker's ratio and mobilization. CONCLUSION: In our study the U-Blade (RC) lag screw did not reduce the cut-out in treatment of OTA/AO 31A1-3 fractures at all. Considering the longer duration of surgery and the higher costs of the U-Blade (RC) lag screw, our results do not justify its use. However, further prospective randomized studies will be necessary.

Preliminary findings on biomarker levels from extracerebral sources in patients undergoing trauma surgery: Potential implications for TBI outcome studies.

BACKGROUND: Despite several experimental studies on the role of S100B and NSE in fractures, no studies on the influence of surgery on the biomarker serum levels have been performed yet. METHODS: The serum levels of S100B and NSE were analysed in patients with fractures that were located in the spine (group 1, n = 35) or in the lower extremity (group 2, n = 32) pre- and post-operatively. RESULTS: The mean S100B serum level showed a significant increase (p = 0.04) post-surgery in the patients of group 1. In patients undergoing acute surgery (< 24 hours) the mean S100B serum level was 0.23 ± 0.22 µg L(-1) pre-operatively and 1.24 ± 1.38 µg L(-1) post-operatively. Likewise, the mean S100B serum level significantly increased in group 2 after surgery (p < 0.0001). In this group patients undergoing acute surgery showed a mean S100B serum level of 0.23 ± 0.14 µg L(-1) and 1.11 ± 0.73 µg L(-1) pre- and post-operatively. CONCLUSION: This study demonstrates significant alterations of the biomarker S100B serum levels in patients undergoing surgery. Higher S100B serum levels were found within 24 hours and might be related to the acute fracture. The NSE serum levels were unchanged and this biomarker may offer the probability to serve as a future outcome predictor in studies with patients with traumatic brain injury and additional extracerebral injuries.

Third degree open fractures and traumatic sub-/total amputations of the upper extremity: Outcome and relevance of the Mangled Extremity Severity Score.

INTRODUCTION: Third degree open fractures and traumatic sub-/total amputations of the upper extremity represent severe injuries and are associated with a high rate of functional impairment of the affected extremity. More than 20 years ago, the Mangled Extremity Severity Score (MESS) was introduced to predict amputation following severe lower extremity trauma. However, there have been few studies evaluating MESS in connection with the mangled upper limb. MATERIAL AND METHODS: A retrospective medical chart review was performed of all patients diagnosed with the aforementioned fractures of the upper extremity treated at the Department of trauma surgery (level I trauma center) and the Clinical division of plastic and reconstructive surgery at the general hospital of Vienna between 1994 and 2014. RESULTS: Fifty-four out of 606 patients (9%) suffered from a total of 61 third degree open fractures or traumatic sub-/total amputations of the upper extremity (Gustilo-Anderson, type IIIA, n=30; Gustilo-Anderson, type IIIB, n=15; Gustilo-Anderson, type IIIC, n=9; traumatic sub-/total amputations, n=7). Thirty-seven out of 54 patients (69%) suffered fractures of the forearm, 10/54 (19%) patients of the humerus and 7/54 (13%) patients of the forearm and the humerus. The median MESS and Injury Severity Score (ISS) for all patients was 5 (range: 3-10) and 9 (range: 4-50), respectively. Seventeen out of 54 patients (31%) were diagnosed with a MESS≥7. Twenty-one out of 54 patients (39%) suffered severe vascular injuries and 22/54 (41%) patients suffered injuries of neural structures. Throughout the therapy process, 6/54 (11%) patients died. Definite limb salvage was achieved in 45 (94%) of the 48 survivors, of whom 9/45 (20%) subjects had a MESS≥7. DISCUSSION: It became apparent that definite limb salvage could be achieved in the mangled upper extremity regardless of MESS. It should be noted that in the current study, limb functionality was not assessed. However, without a standardized scoring system, there might be significant risk of salving dysfunctional upper limbs. LEVEL OF EVIDENCE: IV: retrospective or historical series.

The influence of non-osteogenic factors on the expression of M-CSF and VEGF during fracture healing.

INTRODUCTION: Macrophage colony stimulating factor (M-CSF) as well as vascular endothelial growth factor (VEGF) play an important role in bone homeostasis and in the process of fracture healing. To date, limited data regarding the influence of age, gender, diabetes, smoking, and alcohol consumption on the systemic expression of M-CSF and VEGF after long bone fracture exist. METHODS: From a total of 113 patients with long bone fractures 51 patients met inclusion criteria and were finally enrolled in this study. Patient's serum was collected over a period of 6 months following a standardised time schedule. M-CSF and VEGF serum concentrations were measured. Patient's history with special focus on cigarette smoking, diabetes mellitus, and regular alcohol intake was recorded. All patients were followed up clinically and radiologically for at least 24 weeks after trauma. A total of 22 male and 29 female patients formed the study population. RESULTS: The present results show significantly elevated mean overall M-CSF serum concentration in women, older patients as well as in non-smoking individuals. The mean overall VEGF serum concentration was significantly higher in women, older patients, and diabetic individuals as well as in non-smokers. Statistically significant differences were not observed at any time point regarding alcohol consumption. CONCLUSION: These results suggest that age, gender, diabetes mellitus and cigarette smoking significantly influence the expression of M-CSF and VEGF after fracture of long bones in human. Of note, diabetic patients showed significantly elevated overall VEGF levels when compared to non-diabetic patients. Therefore, further studies with larger patient cohorts are needed to better understand the influence of these endogenous and exogenous factors on the expression of the osteogenic during human fracture healing.

Analysis of factors predicting success and failure of treatment after type B periprosthetic humeral fractures: a case series study.

PURPOSE: The purpose of this study was to investigate which factors predict the failure and success of treatment of periprosthetic type B humeral fractures that have occurred traumatically. METHODS: The institutional admission database and the trauma registry were retrospectively reviewed. A total of 8 patients suffering from periprosthetic humeral fractures were included. The time span was 10 years (2000-2010). RESULTS: The average age at the time of the fracture was 77 years. Surgery was performed at an average of 5.6 days after injury. In three patients with a well-fixed and one with an unstable humeral component, open reduction and internal fixation with the use of a plate and screws was performed. Two patients with a Delta prosthesis had an unstable humeral component. A proximal humeral resection and an implantation of an HMRS prosthesis was performed in one patient. The other patient received a Delta revision stem prosthesis, cable and plate fixation. Two patients were treated conservatively. CONCLUSIONS: Early surgical treatment with angular stable implants in fractures with a stable stem and replacement with a revision long-stem component in fractures with a loose prosthesis is recommended. Special attention should be paid to bone quality and anatomical proximity to the radial nerve. Conservative treatment of type B fractures is not sufficient to achieve union, especially in short oblique or transverse fractures.

Growth factor release in extra- and intramedullary osteosynthesis following tibial fracture.

INTRODUCTION: Recent studies indicate alterations of local and systemic growth factor level during fracture healing. As a result, osteogenic and angiogenic growth factors allow us to monitor fracture healing on a molecular level. We hypothesised that closed intramedullary (IM) reaming and nail fixation, in contrast to open reduction and internal plate fixation (ORIF), could exert an effect on the cellular elements present in the intramedullary canal, leading to increased release of mediators. The purpose of the study was to investigate whether different osteosynthesis techniques influence the released quantity of cytokines. PATIENTS AND METHODS: A total of 34 patients with tibia fractures treated with IM fixation and 19 patients treated with ORIF were included in the study. In addition to clinical and radiological examination, serum concentrations of transforming growth factor beta 1(TGF-ß1), macrophage-colony stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF), were analysed at 1, 2, 4, 6, 8, 12, and 24 weeks after surgery. RESULTS: Expression of TGF-ß1 and M-CSF was increased during the first 2 weeks of fracture healing in patients treated with the IM fixation technique compared with those treated by ORIF. After 24 weeks, M-CSF levels in patients with IM fixation were clearly higher. Conversely, VEGF levels were higher during the first 2 weeks of fracture healing in patients treated by ORIF compared with IM fixation. However, these results were not significant. CONCLUSION: Our results show that 1 week after surgery neither reamed IM fixation nor ORIF of the tibia could increase the expression of VEGF, M-CSF and TGF-ß1 in its favour.

Intramedullary osteosynthesis for fracture associated with osteogenesis imperfecta.

Our aim was to analyse the complications associated with intramedullary stabilisation of the bone fractures which are a common complication of osteogenesis imperfecta. A total of 12 fractures among six individuals with osteogenesis imperfecta were treated by intramedullary stabilisation. The mean age of the patients (three male and three female) was 19.4 years, range 7-42 years. The most common fracture site was the femoral midshaft (seven fractures). After implant removal, one new fracture and one re-fracture occurred. Operative stabilisation of fractures is a safe treatment option for osteogenesis imperfecta.

Monitoring C2 level predicts exposure in maintenance lung transplant patients receiving the microemulsion formulation of cyclosporine (Neoral).

BACKGROUND: Dosing of the microemulsion formulation of cyclosporine (Neoral) is conventionally based on trough levels (C(0)). However, experience in renal transplantation has shown that cyclosporine exposure during the absorption phase (AUC(0-4)) is critical for optimizing immunosuppression, and that cyclosporine (CsA) concentration at 2 hours post-dose (C(2)) shows the closest correlation with AUC(0-4). This study evaluated whether C(2) values correlate more closely with AUC(0-4) than C(0) in lung transplant patients. METHODS: Pharmacokinetic data were collected prospectively from 20 clinically stable adult lung allograft recipients receiving CsA, mycophenolate mofetil and steroids. Indications for transplantation were emphysema (n = 15), idiopathic fibrosis (n = 2), primary pulmonary hypertension (n = 1), cystic fibrosis (n = 1) and lymphangioleiomyomatosis LAM (n = 1). Blood samples were collected at 0, 1, 2, 3 and 4 hours after administration of CsA, and then AUC(0-4) was calculated. The Correlation between cyclosporine concentration at each time-point and AUC(0-4) was also calculated. RESULTS: C(2) showed the closest correlation with AUC(0-4) (r(2) = 0.85). C(0) had the poorest correlation of all time-points (r(2) = 0.64). Two patients with radiologic signs of gastroparesis had no peak cyclosporine levels at all and were excluded from the correlation analysis. Mean AUC(0-4) was 3,700 ng . h/ml during Year 1 post-transplant, 2,400 ng . h/ml during Years 1 to 3, and 1,500 ng . h/ml thereafter. Mean C(2) values were 1.2 microg/ml during Year 1, 0.8 microg/ml during Years 1 to 3, and 0.5 microg/ml thereafter. CONCLUSIONS: C(2) is the single time-point that correlates most closely with AUC(0-4) in lung transplant recipients without gastroparesis. It remains to be demonstrated whether monitoring CsA based on C(2) levels results in a lower incidence of rejection without additional toxicity.

Electroencephalography in primary diagnosis of mild head trauma.

OBJECTIVE: the aim of this study was to compare the clinical examination and EEG examination regarding their relevance in diagnosing cerebral function changes in early head trauma. METHODS: ninety four male patients who suffered from mild head trauma (GCS 13-15) were assigned into two groups. The first group fulfilled at least one sign of cerebral concussion (amnesia, anisocoria, changes of vigilance or vegetative symptoms such as vomiting), the second group did not. EEG examination was performed in both groups. RESULTS: in the first group, more pathologic EEG records were found. These findings showed a statistical significance (p = 0.019). The concussion group showed more focal changes (p = 0.283) and specific changes (p = 0.317), but they were statistically not significant. CONCLUSION: EEG can be used for detecting pathologic unspecific alterations with a high accuracy, but is not useful in specifying the findings for an exact diagnosis.

[Bronchial anastomoses after lung transplantation: results with single running suture technique]. / Bronchialanastomosen nach Lungentransplantation: Ergebnisse mit fortlaufender Naht.

BACKGROUND: The standard technique for the bronchial anastomosis in LTX is a running suture on the membranous and single stitches on the cartilaginous portion of the bronchus. The aim of this retrospective study was to compare the results of this technique to the new single running suture technique. METHODS: Between January and December 1998, 56 consecutive single (n = 17) and bilateral (n = 39) lung transplants in 52 patients were performed. Eighty-three bronchial anastomoses were retrospectively analyzed and evaluated by separating into two groups: group 1 (24 patients, 39 anastomoses) with standard technique and group 2 (24 patients, 44 anastomoses) with single running suture. The two groups were comparable with regard to age, primary diagnosis, intraoperative use of extracorporeal circulation, ischemia time, duration of mechanical ventilation, ICU and number of acute rejections/100 days. Bronchial healing was assessed with bronchoscopic follow-up (5-16 months). RESULTS: Primary excellent airway healing was observed in 36 anastomoses (92%) in group 1 and in 41 (93%) in group 2. In 2 anastomoses in group 1 (5%) and in 2 anastomoses in group 2 (4.6%) necrosis less than 5 mm was observed. In one anastomosis in group 1 (2.7%) a 10-mm bronchial necrosis with partial occlusion of the bronchial lumen by necrotic tissue necessitated temporary intraluminal stenting. In one anastomosis in group 2 (2.3%) malacia of the bronchus intermedius occurred. CONCLUSION: The single running suture technique for bronchial anastomosis is a safe technique providing the same results as the established technique and we advocate its use for bronchial anastomosis.