High Cefuroxime Concentrations and Long Elimination in an Orthopaedic Surgical Deadspace-A Microdialysis Porcine Study.

Deadspace is the tissue and bony defect in a surgical wound after closure. This space is presumably poorly perfused favouring bacterial proliferation and biofilm formation. In arthroplasty surgery, an obligate deadspace surrounding the prosthesis is introduced and deadspace management, in combination with obtaining therapeutic prophylactic antibiotic concentrations, is important for limiting the risk of acquiring a periprosthetic joint infection (PJI). This study aimed to investigate cefuroxime distribution to an orthopaedic surgical deadspace in comparison with plasma and bone concentrations during two dosing intervals (8 h × 2). In a setup imitating shoulder arthroplasty surgery, but without insertion of a prosthesis, microdialysis catheters were placed for cefuroxime sampling in a deadspace in the glenohumeral joint and in cancellous bone of the scapular neck in eighteen pigs. Blood samples were collected as a reference. Cefuroxime was administered according to weight (20 mg/kg). The primary endpoint was time above the cefuroxime minimal inhibitory concentration of the free fraction of cefuroxime for Staphylococcus aureus (fT > MIC (4 µg/mL)). During the two dosing intervals, mean fT > MIC (4 µg/mL) was significantly longer in deadspace (605 min) compared with plasma (284 min) and bone (334 min). For deadspace, the mean time to reach 4 µg/mL was prolonged from the first dosing interval (8 min) to the second dosing interval (21 min), while the peak drug concentration was lower and half-life was longer in the second dosing interval. In conclusion, weight-adjusted cefuroxime fT > MIC (4 µg/mL) and elimination from the deadspace was longer in comparison to plasma and bone. Our results suggest a deadspace consolidation and a longer diffusions distance, resulting in a low cefuroxime turn-over. Based on theoretical targets, cefuroxime appears to be an appropriate prophylactic drug for the prevention of PJI.

Early offset-increasing migration predicts later revision for humeral head resurfacing implants. A randomized controlled radiostereometry trial with 10-year clinical follow-up.

In a randomized controlled setting, medium-term implant migration and long-term clinical outcomes were compared for the Copeland and the Global C.A.P. humeral head resurfacing implants (HHRI). Thirty-two patients (mean age 63 years) were randomly allocated to a Copeland (n = 14) or Global C.A.P. (n = 18) HHRI. Patients were followed for 5 years with radiostereometry, Constant Shoulder Score, and the Western Ontario Osteoarthritis of the Shoulder Index (WOOS). WOOS and revision status were also obtained cross-sectionally at a mean 10-year follow-up. At the 5-year follow-up, total translation (TT) was 0.75 mm (95% confidence interval [CI]: 0.53-0.97) for the Copeland HHRIs and 1.15 mm (95% CI: 0.85-1.46) for the Global C.A.P. HHRIs (p = 0.04), but the clinical scores were similar at all follow-ups. The cumulative risks of revision at 5 and 10 years were 29% and 43% for Copeland and 35% and 41% for Global C.A.P HHRIs (p > 0.7). No implants were loose at revision, but HHRIs that were later revised followed an early offset-increasing migration pattern with medial translation and lift-off resulting in a mean 0.53 mm (95% CI: 0.18-0.88) higher TT at the 1-year follow-up compared to non-revised HHRIs. In conclusion, the Global C.A.P. HHRI had higher TT compared with the Copeland HHRI, but clinical scores and revision rates were similar. Nonetheless, revision rates were high and challenge the use of HHRIs. Interestingly, an early radiostereometry evaluated HHRI migration pattern with increased off-set predicted later implant revision.

Weight-based cefuroxime dosing provides comparable orthopedic target tissue concentrations between weight groups - a microdialysis porcine study.

Antibiotic prophylaxis is a key element in prevention of surgical site infections. For the majority of orthopedic procedures, antibiotic administration follows fixed dosing regimens irrespective of weight. However, this may result in insufficient antibiotic target tissue concentrations and higher risk of surgical site infections in obese individuals. The aim of this study was to investigate the effect of weight-based cefuroxime dosing on plasma and target tissue concentrations. Eighteen female pigs were allocated into three groups differentiated by weight: 53-57 kg, 73-77 kg, and 93-97 kg. Microdialysis catheters were placed for continuous sampling in bone, muscle, and subcutaneous tissue during an 8h sampling interval. Blood samples were collected as reference. Cefuroxime was administered intravenously as a bolus according to weight (20 mg/kg). The primary endpoint was the time above the cefuroxime minimal inhibitory concentration for Staphylococcus aureus (T > MIC (4 µg/mL)). Comparable target tissue T > MICs (4 µg/mL) were found between weight groups. Mean T > MIC ranged between 116-137 min for plasma, 118-154 min for bone, 109-146 min for the skeletal muscle, and 117-165 min for subcutaneous tissue across the groups. Weight-based cefuroxime (20 mg/kg) dosing approach provides comparable perioperative plasma and target tissue T > MIC (4 µg/mL) in animals between 50-100 kg body weight, and thus a comparable prophylaxis of surgical site infections.

Microdialysis for the Assessment of Intervertebral Disc and Vertebral Cancellous Bone Metabolism in a Large Porcine Model.

BACKGROUND/AIM: It remains challenging to evaluate the in vivo pathophysiological biochemical characteristics in spine tissue, due to lack of an applicable model and feasible methods. The aim of this study was to apply microdialysis for the assessment of basic metabolites from the C3-C4 intervertebral disc, C3 vertebral cancellous bone and subcutaneous adipose tissue in a large porcine model. MATERIALS AND METHODS: In 7 pigs, glucose, pyruvate, lactate and glycerol concentrations were evaluated in an 8-hour sampling period. RESULTS: The mean lactate/pyruvate (L/P) ratios for the intervertebral disc and vertebral cancellous bone were comparable and exceeded the ischemic cut-off value of 25 for the entire sampling interval. For subcutaneous adipose tissue, the L/P ratio was below the ischemic cut-off. CONCLUSION: This exploratory study confirms previous findings of ischemia in bone and the intervertebral disc. This encourages new microdialysis study designs in spine tissue employing large porcine models to create new knowledge and a greater understanding of the metabolism and pathogenesis in spine tissue.

Diagnostic accuracy of ultrasound-guided core biopsy of peripheral nerve sheath tumors.

PURPOSE: To retrospectively evaluate the diagnostic accuracy of and complications from ultrasound-guided core needle biopsy (UGCNB) of suspected peripheral nerve sheath tumors (PNSTs). METHODS: Patients undergoing UGCNB from January 2004 to December 2016, based on the suspicion of PNST, were included in the study. Age, gender, anatomical location, dates of relevant events, and histopathological reports of the UGCNB cores and the resected tumors were retrieved from the patients' medical records. RESULTS: A total of 154 UGCNBs were identified. One hundred and forty (90.9%) of these resulted in a conclusive histopathological report, while 14 were unsuited for histopathological analysis due to insufficient amount of tissue and/or nonrepresentative tissue. The overall diagnostic accuracy of UGCNB with respect to discriminate malignant from benign tumors was 99.3%, while correct specific UGCNB diagnoses were confirmed in 95.1% of the cases. Sensitivity and specificity were 90.9% (95% CI: 58.7-99.8%) and 100% (95% CI: 97.2-100%), respectively. The positive predictive value was 100%, and the negative predictive value was 99.2%. Except for one patient, who reported mild dysesthesia, which resolved 2 days after the UGCNB, no complications were reported. CONCLUSION: This study suggests that UGCNB is accurate and safe in patients suspected for PNST.

Simultaneous Retrodialysis by Drug for Cefuroxime Using Meropenem as an Internal Standard-A Microdialysis Validation Study.

Microdialysis is a valuable pharmacokinetic tool for obtaining samples of drug concentrations from tissues of interest. When an absolute tissue concentration is needed, a calibration of the microdialysis catheter is required. The use of an internal standard offers a number of advantages compared to standard calibration methods. However, meticulous validation both in vitro and in vivo is needed, as this method requires an internal standard with physiochemical similarities to the analyte of interest with no interference. A series of in vitro and in vivo setups were conducted to determine the relative recovery by gain and by loss for cefuroxime, with and without a constant meropenem concentration. The cefuroxime and meropenem concentrations were determined using ultra-HPLC. The main finding was that cefuroxime and meropenem relative recovery behaved similarly both in vitro and in vivo, signifying that meropenem is a representative internal standard for cefuroxime. Furthermore, cefuroxime relative recovery in vitro was not affected by either the cefuroxime concentration or the presence of meropenem, and the in vivo meropenem relative recovery was constant over 6 h.

Bone, subcutaneous tissue and plasma pharmacokinetics of cefuroxime in total knee replacement patients - a randomized controlled trial comparing continuous and short-term infusion.

Cefuroxime is widely used as antibiotic prophylaxis for orthopaedic procedures. We evaluated bone, subcutaneous tissue (SCT) and plasma pharmacokinetics of cefuroxime in male patients undergoing total knee replacement (TKR) after both traditional short-term infusion (STI) and continuous infusion (CI). Eighteen male patients undergoing TKR were randomly assigned to STI or CI of 1.5 g of cefuroxime. Measurements were obtained in plasma, SCT, cancellous and cortical bone every 30 min for 8 h following surgery. For sampling in solid tissues, microdialysis was applied. Population pharmacokinetic modelling was performed in order to estimate pharmacokinetic parameters, and to assess the probability of attaining cefuroxime concentrations above clinically relevant minimal inhibitory concentrations (MICs) for 65% and 90% of the 8 h dosing interval. Low SCT and cortical bone penetration were found in both the STI and the CI group, but the findings were only significant in the STI group. Irrespective of MIC, tissue and target, CI leads to improved probability of attaining relevant pharmacokinetic targets compared with STI. For the Staphylococcus aureus MIC breakpoint (4 µg/mL), STI leads to inadequate probability of target attainment. CI of 1.5 g of cefuroxime leads to improved probability of attaining relevant pharmacokinetic targets in male TKR patients compared with traditional STI. These findings suggest that application of CI may improve antibiotic prophylaxis for male TKR patients.

Vancomycin concentrations in the cervical spine after intravenous administration: results from an experimental pig study.

Background and purpose - Vancomycin may be an important drug for intravenous perioperative antimicrobial prophylaxis in spine surgery. We assessed single-dose vancomycin intervertebral disc, vertebral cancellous bone, and subcutaneous adipose tissue concentrations using microdialysis in a pig model. Material and methods - 8 female pigs received 1,000 mg of vancomycin intravenously as a single dose over 100 minutes. Microdialysis probes were placed in the C3-C4 intervertebral disc, C3 vertebral cancellous bone, and subcutaneous adipose tissue, and vancomycin concentrations were obtained over 8 hours. Venous blood samples were obtained as reference. Results - Ranging from 0.24 to 0.60, vancomycin tissue penetration, expressed as the ratio of tissue to plasma area under the concentration-time curve from 0 to the last measured value, was incomplete for all compartments. The lowest penetration was found in the intervertebral disc. The time to a mean clinically relevant minimal inhibitory concentration (MIC) of 4 µg/mL was 3, 17, 25, and 156 min for plasma, subcutaneous adipose tissue, vertebral cancellous bone, and the intervertebral disc, respectively. In contrast to the other compartments, a mean MIC of 8 µg/mL was not reached in the intervertebral disc. An approximately 3-times longer elimination rate was observed in the intervertebral disc in comparison with all the other compartments (p < 0.001), and the time to peak drug concentration was higher for all tissues compared with plasma Interpretation - Preoperative administration of 1,000 mg of vancomycin may provide adequate vancomycin tissue concentrations with a considerable delay, though tissue penetration was incomplete. However, in order also to achieve adequate intervertebral disc concentrations in all individuals and accommodating a potentially higher MIC target, supplemental application of vancomycin may be necessary.

Population Pharmacokinetics of Meropenem in Plasma and Subcutis from Patients on Extracorporeal Membrane Oxygenation Treatment.

The objectives of this study were to describe meropenem pharmacokinetics (PK) in plasma and/or subcutaneous adipose tissue (SCT) in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) treatment and to develop a population PK model to simulate alternative dosing regimens and modes of administration. We conducted a prospective observational study. Ten patients on ECMO treatment received meropenem (1 or 2 g) intravenously over 5 min every 8 h. Serial SCT concentrations were determined using microdialysis and compared with plasma concentrations. A population PK model of SCT and plasma data was developed using NONMEM. Time above clinical breakpoint MIC for Pseudomonas aeruginosa (8 mg/liter) was predicted for each patient. The following targets were evaluated: time for which the free (unbound) concentration is maintained above the MIC of at least 40% (40% fT>MIC), 100% fT>MIC, and 100% fT>4×MIC. For all dosing regimens simulated in both plasma and SCT, 40% fT>MIC was attained. However, prolonged meropenem infusion would be needed for 100% fT>MIC and 100% fT>4×MIC to be obtained. Meropenem plasma and SCT concentrations were associated with estimated creatinine clearance (eCLCr). Simulations showed that in patients with increased eCLCr, dose increment or continuous infusion may be needed to obtain therapeutic meropenem concentrations. In conclusion, our results show that using traditional targets of 40% fT>MIC for standard meropenem dosing of 1 g intravenously every 8 h is likely to provide sufficient meropenem concentration to treat the problematic pathogen P. aeruginosa for patients receiving ECMO treatment. However, for patients with an increased eCLCr, or if more aggressive targets, like 100% fT>MIC or 100% fT>4×MIC, are adopted, incremental dosing or continuous infusion may be needed.

Bone and subcutaneous adipose tissue pharmacokinetics of vancomycin in total knee replacement patients.

Background and purpose - The incidence of orthopedic methicillin-resistant Staphylococcus aureus (MRSA) infections is increasing. Vancomycin may therefore play an increasingly important role in orthopedic perioperative antimicrobial prophylaxis. Studies investigating perioperative bone and soft tissue concentrations of vancomycin are sparse and challenged by a lack of appropriate methods. We assessed single-dose plasma, subcutaneous adipose tissue (SCT) and bone concentrations of vancomycin using microdialysis in male patients undergoing total knee replacement. Methods - 1,000 mg of vancomycin was administered postoperatively intravenously over 100 minutes to 10 male patients undergoing primary total knee replacement. Vancomycin concentrations in plasma, SCT, cancellous, and cortical bone were measured over the following 8 hours. Microdialysis was applied for sampling in solid tissues. Results - For all solid tissues, tissue penetration of vancomycin was significantly impaired. The time to a mean clinically relevant minimal inhibitory concentration (MIC) of 2 mg/L was 3, 36, 27, and 110 min for plasma, SCT, cancellous, and cortical bone, respectively. As opposed to the other compartments, a mean MIC of 4 mg/L could not be reached in cortical bone. The area under the concentration-time curve from 0 to the last measured value and peak drug concentrations (Cmax) for SCT, cancellous, and cortical bone was lower than that of free plasma. The time to Cmax was higher for all tissues compared with free plasma. Interpretation - Postoperative penetration of vancomycin to bone and SCT was impaired and delayed in male patients undergoing total knee replacement surgery. Adequate perioperative vancomycin concentrations may not be reached using standard prophylactic dosage.

Single-dose bone pharmacokinetics of vancomycin in a porcine implant-associated osteomyelitis model.

The increasing incidence of orthopaedic methicillin-resistant Staphylococcus aureus (MRSA) infections represents a significant therapeutic challenge. Being effective against MRSA, the role of vancomycin may become more important in the orthopaedic setting in the years to come. Nonetheless, vancomycin bone and soft tissue penetration during infection remains unclear. In eight pigs, implant-associated osteomyelitis was induced on day 0, using a Staphylococcus aureus strain. Following administration of 1,000 mg of vancomycin on day 5, vancomycin concentrations were obtained with microdialysis for 8 h in the implant bone cavity, in cancellous bone adjacent to the implant cavity, in subcutaneous adipose tissue (SCT) adjacent to the implant cavity, and in healthy cancellous bone and healthy SCT in the contralateral leg. Venous blood samples were also obtained. The extent of infection and inflammation was evaluated by post-mortem computed tomography scans, C-reactive protein serum levels and cultures of blood and swabs. In relation to all the implant cavities, bone destruction was found. Ranging from 0.20 to 0.74, tissue penetration, expressed as the ratio of the area under the concentration-time curve from 0 to the last measured value, was incomplete for all compartments except for healthy SCT. The lowest penetration was found in the implant cavity. In conclusion, Staphylococcus aureus implant-associated osteomyelitis was found to reduce vancomycin bone penetration, especially in the implant cavity. These findings suggest that it may be unsafe to rely solely on vancomycin therapy when treating acute osteomyelitis. Particularly when metaphyseal cavities are present, surgical debridement seems necessary. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1093-1098, 2018.

Effects of Implant-Associated Osteomyelitis on Cefuroxime Bone Pharmacokinetics: Assessment in a Porcine Model.

BACKGROUND: The prolonged antibiotic therapy that is often needed for successful management of osteomyelitis may be related to incomplete penetration of antibiotics into the target site. The objective of this study was to assess the effects of implant-associated osteomyelitis on cefuroxime penetration into bone. METHODS: Implant-associated osteomyelitis using a Staphylococcus aureus strain was induced in the right tibia in ten pigs. After five days and following administration of 1500 mg of cefuroxime, measurements of cefuroxime were obtained using microdialysis for eight hours in the implant-related bone cavity, in the adjacent infected cancellous bone and infected subcutaneous tissue, and in healthy cancellous bone and subcutaneous tissue in the contralateral leg. Measurements of the corresponding free plasma concentrations were also obtained. The extent of the infection was assessed by postmortem computed tomography (CT) scans and cultures of blood, swabs, and bone specimens. RESULTS: Bone destruction was found in the implant cavities. No structural bone changes in the adjacent infected cancellous bone were visible on CT scans. S. aureus was grown on culture of specimens from all implant cavities and from eight of ten swabs and seven of ten bone samples from the infected bone. The areas under the concentration-time curves for the different tissues differed significantly, with the lowest area under the curve found in the implant cavity (analysis of variance; p < 0.001). Although not as notable as for the implant cavity, cefuroxime penetration into infected cancellous bone was incomplete but comparable with that in healthy bone. Despite poorer tissue penetration, slightly increased time with concentrations above the minimal inhibitory concentration (MIC) was achieved in the implant cavity up to MICs of 2 mg/L compared with the other tissues, but the time was shorter for higher MICs. CONCLUSIONS: Cefuroxime penetration into infected cancellous bone was incomplete but comparable with that in healthy bone. The destructive bone processes associated with acute osteomyelitis reduced cefuroxime penetration further. CLINICAL RELEVANCE: These findings support the general clinical perception that fast diagnosis and early initiation of antibiotics before the development of implant-associated cavities is important in nonsurgical management of acute osteomyelitis.

Pharmacokinetics of single-dose cefuroxime in porcine intervertebral disc and vertebral cancellous bone determined by microdialysis.

BACKGROUND: Pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates. Nevertheless, tissue pharmacokinetic studies of relevant antimicrobials in both prophylactic and therapeutic situations are still sparse. Previous approaches based on bone biopsy and discectomy exhibit important methodological limitations. PURPOSE: The objective of this study was to assess the C3-C4 intervertebral disc (IVD), C3 vertebral body cancellous bone, and subcutaneous adipose tissue (SCT) pharmacokinetics of cefuroxime by use of microdialysis in a large animal model. STUDY DESIGN: This was a single-dose, dense sampling large animal study of cefuroxime spine penetration. METHODS: Ten female pigs were assigned to receive 1,500 mg of cefuroxime intravenously over 15 minutes. Measurements of cefuroxime were obtained from plasma, SCT, vertebral cancellous bone, and IVD for 8 hours thereafter. Microdialysis was applied for sampling in solid tissues. RESULTS: For both IVD and vertebral cancellous bone, the area under the concentration curve from zero to the last measured value (AUC(0-last)) was significantly lower than that of free plasma. As estimated by the ratio of tissue AUC(0-last) to plasma AUC(0-last), tissue penetration (95% confidence interval) of cefuroxime was significantly incomplete for the IVD 0.78 (0.57; 0.99), whereas for vertebral cancellous bone 0.78 (0.51; 1.04) and SCT 0.94 (0.73; 1.15) it was not. The penetration of cefuroxime from plasma to the IVD was delayed, and the maximal concentration and the elimination of cefuroxime were also reduced compared with both SCT and vertebral cancellous bone. Because of this delay in elimination of cefuroxime, the time with concentrations above the minimal inhibitory concentration (T(>MIC)) was significantly longer in the IVD compared with the remaining compartments up to MICs of 6 µg/mL. CONCLUSIONS: Microdialysis was successfully applied for serial assessment of the concentration of cefuroxime in the IVD and the vertebral cancellous bone. Penetration of cefuroxime from plasma to IVD was found to be incomplete and delayed, but because of a prolonged elimination, superior T(>MIC) was found in the IVD up to MICs of 6 µg/mL.

Single-dose pharmacokinetics of vancomycin in porcine cancellous and cortical bone determined by microdialysis.

High treatment failure rates and the need for prolonged antimicrobial therapy for osteomyelitis and implant-associated infections suggest that antimicrobial bone penetration may be incomplete. Assessment of the bone pharmacokinetics of antimicrobials is challenged by a lack of validated methods. In this study, 1000 mg of vancomycin was administered as a single dose over 100 min to eight female pigs. Plasma, subcutaneous adipose tissue (SCAT) and bone pharmacokinetics were investigated over 12 h. Microdialysis was applied for collection of samples in bone and SCAT. The vancomycin concentration in microdialysates was determined using ultra-high performance liquid chromatography, whilst the free plasma concentration was determined using Cobas c501. The mean (95% CI) area under the concentration-time curve (AUC(0-last); minµg/mL) was 9375 (7445-11304), 9304 (7374-11233), 5998 (3955-8040) and 3451 (1522-5381) for plasma, SCAT, and cancellous and cortical bone, respectively (ANOVA P-value < 0.001). Both cortical and cancellous bone AUC0-last were lower than that of free plasma (P < 0.01). Peak drug concentrations (C(max)) in cortical and cancellous bone were also significantly lower than that of free plasma (P < 0.001). Moreover, both AUC(0-last) and C(max) were significantly lower in cortical bone than in cancellous bone (P < 0.025). Bone penetration of vancomycin was found to be incomplete and delayed. Significant differences in pharmacokinetics between cancellous and cortical bone suggest that bone may not be considered as one compartment. Future studies should focus on validating the applicability of microdialysis for assessment of antimicrobial bone pharmacokinetics.

Continuous versus short-term infusion of cefuroxime: assessment of concept based on plasma, subcutaneous tissue, and bone pharmacokinetics in an animal model.

The relatively short half-lives of most ß-lactams suggest that continuous infusion of these time-dependent antimicrobials may be favorable compared to short-term infusion. Nevertheless, only limited solid-tissue pharmacokinetic data are available to support this theory. In this study, we randomly assigned 12 pigs to receive cefuroxime as either a short-term or continuous infusion. Measurements of cefuroxime were obtained every 30 min in plasma, subcutaneous tissue, and bone. For the measurements in solid tissues, microdialysis was applied. A two-compartment population model was fitted separately to the drug concentration data for the different tissues using a nonlinear mixed-effects regression model. Estimates of the pharmacokinetic parameters and time with concentrations above the MIC were derived using Monte Carlo simulations. Except for subcutaneous tissue in the short-term infusion group, the tissue penetration was incomplete for all tissues. For short-term infusion, the tissue penetration ratios were 0.97 (95% confidence interval [CI], 0.67 to 1.39), 0.61 (95% CI, 0.51 to 0.73), and 0.45 (95% CI, 0.36 to 0.56) for subcutaneous tissue, cancellous bone, and cortical bone, respectively. For continuous infusion, they were 0.53 (95% CI, 0.33 to 0.84), 0.38 (95% CI, 0.23 to 0.57), and 0.27 (95% CI, 0.13 to 0.48) for the same tissues, respectively. The absolute areas under the concentration-time curve were also lower in the continuous infusion group. Nevertheless, a significantly longer time with concentrations above the MIC was found for continuous infusion up until MICs of 4, 2, 2, and 0.5 µg/ml for plasma and the same three tissues mentioned above, respectively. For drugs with a short half-life, like cefuroxime, continuous infusion seems to be favorable compared to short-term infusion; however, incomplete tissue penetration and high MIC strains may jeopardize the continuous infusion approach.

Pharmacokinetics of cefuroxime in porcine cortical and cancellous bone determined by microdialysis.

Traditionally, the pharmacokinetics of antimicrobials in bone have been investigated using bone biopsy specimens, but this approach suffers from considerable methodological limitations. Consequently, new methods are needed. The objectives of this study were to assess the feasibility of microdialysis (MD) for measuring cefuroxime in bone and to obtain pharmacokinetic profiles for the same drug in porcine cortical and cancellous bone. The measurements were conducted in bone wax sealed and unsealed drill holes in cortical bone and in drill holes in cancellous bone and in subcutaneous tissue. As a reference, the free and total plasma concentrations were also measured. The animals received a bolus of 1,500 mg cefuroxime over 30 min. No significant differences were found between the key pharmacokinetic parameters for sealed and unsealed drill holes in cortical bone. The mean ± standard error of the mean area under the concentration-time curve (AUC) values from 0 to 5 h were 6,013 ± 1,339, 3,222 ± 1086, 2,232 ± 635, and 952 ± 290 min · µg/ml for free plasma, subcutaneous tissue, cancellous bone, and cortical bone, respectively (P < 0.01, analysis of variance). The AUC for cortical bone was also significantly different from that for cancellous bone (P = 0.04). This heterogeneous tissue distribution was also reflected in other key pharmacokinetic parameters. This study validates MD as a suitable method for measuring cefuroxime in bone. Cefuroxime penetration was impaired for all tissues, and bone may not be considered one distinct compartment.

The value of routine flexible sigmoidoscopy within 48 hours after surgical repair of ruptured abdominal aortic aneurysms.

BACKGROUND: Left-sided colonic and rectal ischemia is commonly seen after surgery for ruptured abdominal aortic aneurysms (rAAAs) and is associated with increased mortality. Earlier studies have shown that flexible sigmoidoscopy (FS) may detect ischemia when performed postoperatively, and suggestions have been made that patients can be selected for FS based on clinical and biochemical parameters. We sought to perform FS in all patients surviving the first 24 hours after surgery for rAAA and to compare the findings of FS to clinical and biochemical parameters. METHODS: All patients undergoing emergency surgery for rAAA and surviving the first 24 hours underwent FS to assess any degree of ischemia. RESULTS: During the study period, 41 patients survived the first 24 hours after surgery. In 9 (22%) patients, some degree of colonic ischemia was found. Segmental necrosis was only shown in 5% at first FS. Patients with ischemia received more blood transfusions intraoperatively than those with normal findings at FS. They also had longer periods with mean blood pressure <60 mm Hg postoperatively, and lower arterial pH on the first postoperative day. Blood lactate levels did not differ between the groups. None of the parameters were sufficiently discriminative to be used for distinguishing between patients with and without ischemia. CONCLUSIONS: Severe colonic ischemia was less common than previously reported. All cases of colonic ischemia were identified by early FS, but none of the clinical and biochemical parameters were sufficiently reliable to distinguish between patients with and without ischemia. It is suggested that all patients initially surviving surgery for rAAA should be offered FS to screen for colonic ischemia.

Diagnostics of septic arthritis in the sternoclavicular region: 10 consecutive patients and literature review.

BACKGROUND: Septic arthritis in the sternoclavicular (SC) region is rare and may be difficult to diagnose clinically and radiologically. It mainly affects immunocompromised persons, and can clinically be misinterpreted as tumor and rheumatic disorders. Lacking radiological reference standard, a multimodality approach may contribute to a prolonged diagnostic process. PURPOSE: To describe the diagnostics of septic arthritis in the SC region. MATERIAL AND METHODS: Between 2001 and 2011 10 patients with Staphylococcus infection in the SC region were investigated in our institution. Clinical, biochemical, radiological, and microbiological findings were studied retrospectively; all CT and MR examinations were re-evaluated. RESULTS: Initial radiography in nine patients and ultrasonography in six patients were inconclusive resulting in supplementary MRI and/or CT. Five patients examined by MRI were immediately diagnosed with septic arthritis whereas CT in five patients led to the diagnosis in only one. Three were subsequently diagnosed by MRI, but delayed more than 2.5 weeks, and one was diagnosed by surgery. The median time to diagnosis was 1.5 weeks. The delay caused by imaging was 0 days to 11.5 weeks (median 0 days). By re-evaluation overlooked complications included mediastinitis in seven patients (three diffuse, four localized), and abscesses and pleuritis each in four patients. CONCLUSION: Awareness of infection in the SC region is important to avoid diagnostic delay. MRI is proposed as the initial imaging procedure.

[Rectal pain and tenesmi caused by a large appendix mucocele]. / Analsmerter og tenesmi udløst af stort appendixmukocele.

A 60 year-old man presented with rectal pain and tenesmi. On digital rectal examination a pelvic mass was detected. Computed tomography and MR scans showed a 14 × 5.5 × 5 cm large cystic process located in the right side of the pelvis with no clear indication of its origin. Explorative laparotomy revealed a large appendix mucocele based on a cystadenoma. The mucocele was resected in healthy tissue and without perforation. Needle aspiration or drainage should be avoided in cystic intraabdominal processes of unknown origin, and careful operative handling is imperative, because spillage of mucin may result in later development of pseudomyxoma peritonei. Careful digital rectal examination may detect important pelvic pathology.

[Can fish be dangerous for the heart? If so, a high content of methylmercury in certain fish species casts doubt on current food guidelines]. / Kan fisk vaere skadeligt for hjertet? Hvis ja, kan et højt indhold af methylkviksølv i visse fiskearter gøre gaengse kostanbefalinger problematiske.

Recent studies have shown an association between myocardial infarction and the intake of MeHg from fish in amounts near the current reference dose (RfD). Biochemical studies support the association. This article considers the results of recent epidemiological studies in relation to an evaluation of RfD and food guidelines. MeHg levels in certain Danish fish are close to harmful levels if the food guidelines are followed. Revised food guidelines should be based on assessments of the MeHg amount in each fish species.