Lower limb reconstruction in tumor patients using modular silver-coated megaprostheses with regard to perimegaprosthetic joint infection: a case series, including 100 patients and review of the literature.

PURPOSE AND OBJECTIVE: Bone resection regarding adequate surgical margins is the treatment of choice for malignant bone tumors. In the case of metastasis-related complications, so-called skeletal-related events, it is highly important to achieve pain relief and a stable joint situation to re-mobilize the patients immediately following surgery. To bridge the often large osseous defect zones after tumor resection, both cemented and uncemented modular endoprosthetic systems are widely used. Patients undergoing tumor-related endoprosthetic orthopedic surgery are facing high risk for developing a periprosthetic joint infection (PJI). The immunocompromised condition due to anti-neoplastic treatment and long operation time with large exposure of tissue contributes to a high risk of infection. METHODS: The authors present a case series of 100 patients (31% primary bone tumor and 69% metastasis-related surgery) undergoing tumor-related lower limb salvage surgery with special regard to periprosthetic joint infection and the management of this "difficult to treat" situation. Furthermore, a review of the current literature regarding infection following bone tumor resection and endoprosthetic reconstruction is performed and discussed. RESULTS: The median follow-up was 24 months (range 12-108 months). Ten patients (10%) suffered from a periprosthetic joint infection. We recorded six acute infections (type I) <4 weeks after surgery, one infection >4 weeks after surgery (type II), and three late infections (type III). According to the definition of Laffer et al., three of our patients (30%) are probably free of infection, one patient died of PJI-associated sepsis, and five patients were free of infection, but without restoration of the affected joint. CONCLUSION: In conclusion, our own results show that perimegaprosthetic joint infection among silver-coated implants, in patients undergoing tumor-related surgery of the lower limb, is lower compared to non-silver-coated implants. Due to heterogeneity of patients and potential treatment options, the treatment regime should be tailored for the patients' individual situation.

[The Role of a Modular Universal Tumour and Revision System (MUTARS®) in Lower Limb Endoprosthetic Revision Surgery - Outcome Analysis of 25 Patients]. / Tumorprothesen in der endoprothetischen Revisionschirurgie der unteren Extremität ­ Ergebnisse von 25 Patienten nach Versorgung mit einem modularen Tumor- und Revisionssystem (MUTARS®).

Introduction/Background: With extended life expectancy, the number of primary joint arthroplasties has also increased. Revision surgery is also more often necessary, due to aseptic or septic loosening of the prosthesis or periprosthetic fracture. Large bone defects often occur in these patients and several non-modular, conventional implants are available to handle this difficult situation. Custom made implants offer an individually designed and defect-adapted shape with perfect covering of the lesion, but may delay the operation. The Modular Universal Tumor And Revision System (MUTARS®) offers the possibility to vary the length and angle of the femoral neck and the antetorsion angle. Thus, it permits intraoperative adaption to the individual patient's defect. The aim of our study is to present clinical, functional results and the rate of complications in a cohort of patients undergoing revision surgery for failed endoprosthetic replacement or failed trauma surgery, using the Modular Universal Tumor And Revision System with short-to midterm follow-up. Patients and Methods: Between August 2005 and September 2014, 25 patients (17 female, 8 male) with an average age of 72 years (min. 56, max. 92 years) were included in a retrospective study using the MUTARS® system. The patients underwent surgical revision of osseous defects that were not susceptible to conventional care. The mean follow-up was 16 months (min. 12, max. 72 months). The indications which led to revision surgery were as follows: loosened metal-on-metal prosthesis with an acetabular defect caused by a metal-induced granuloma (n = 1), pseudoarthrosis after implantation of femur nail (n = 2), cut-out of a femur nail (n = 1), aseptic loosening of an implanted endoprosthesis (n = 4), septic loosening of an implanted endoprosthesis (n = 1), periprosthetic fracture (n = 6) and periprosthetic infection after two stage revision surgery (infection consolidated Girdlestone situation) (n = 10). All patients were followed up at regular intervals, both clinically and radiologically. Apart from comorbidities, clinical and functional parameters were measured, including the Harris Hip Score. An outcome analysis was also performed with respect to peri- and postoperative complications. Serial plain X-rays were followed-up. Results: In all patients, stable reconstruction without the use of an allograft was possible. In total, 23 patients underwent surgery by using a proximal femur prosthesis; three patients also received a custom made acetabular component. One patient was treated by using a distal femur and one patient was treated by implantation of a total femur prosthesis. The average length of hospital stay was 25 days (min.11, max. 47 days). The Harris Hip Score improved from 28 points preoperatively to 81 points after surgery.In total we recorded 24 % of complications after surgery. Two patients suffered recurrent periprosthetic infection and the prosthesis had to be revised in a further two stage exchange; one patient had a tractus gap and was revised by surgery. Two patients suffered periprosthetic fracture due to trauma and the patient with the total femur prosthesis suffered recurrent periprosthetic infection of the silver - coated mega-prosthesis and committed suicide triggered by an episode of major depression. Conclusion: Because of its modular nature, the Modular Tumor And Revision System (MUTARS®) can be used for highly variable intraoperative defect adaption. Good clinical and functional results were achieved in patients with excessive bone defects. However, the high rate of infection, even with silver coated mega-implants, is still a problem and should be studied further.

[Cardiomyopathy during clozapine therapy]. / Cardiomyopathie tijdens clozapinegebruik.

A 45-year-old woman of Moroccan origin developed a dilated cardiomyopathy during clozapine treatment for a psychosis that did not respond to conventional antipsychotics. The onset of her illness was acute with chest pain. She subsequently developed shortness of breath and oedema of the face and legs. The cardiomyopathy appeared to be partially reversible after the clozapine was halted. Cardiomyopathy during the use of clozapine is rarely described in the literature, although myocarditis is a known complication. The cause of cardiomyopathy during the use of clozapine is not known. Myocarditis might evolve into cardiomyopathy. There are indications that myocarditis is caused by an allergic reaction to clozapine. It is advised that clozapine treatment should only be initiated under the close supervision of a psychiatrist, and that during the use of clozapine one should be alert to the risk of cardiac complications.

Assessment of mycobacterial viability by RNA amplification.

We investigated whether the presence of intact RNA is a valuable indicator of viability of mycobacteria with Mycobacterium smegmatis. M. smegmatis was exposed to various concentrations of rifampin and ofloxacin suspended in broth for different periods of time. The NASBA nucleic acid amplification system was used because of its rapid, sensitive, and specific detection of 16S rRNA. During drug exposure, the viability of the mycobacteria, expressed by the number of CFU, was compared with the presence of 16S rRNA as determined by NASBA and with the presence of DNA coding for 16S rRNA as determined by PCR. Both NASBA and PCR were shown to have a detection limit of approximately 5 x 10(2) CFU/ml. The intensity of the NASBA signal corresponded well with the number of CFU, and the lack of NASBA signal coincided with a loss of viability, which was reached after 3 days of exposure to bactericidal concentrations of both drugs. The presence of mycobacterial DNA, as determined by the intensity of the PCR signal, and the viability of M. smegmatis were not related, but an increase in the number of cells and intensity of PCR signal correlated well. Bacterial viability may thus be assessed by a rapid, sensitive, and specific, and semiquantitative technique by using NASBA. This system of viability testing provides the potential for rapid evaluation of drug susceptibility testing.

Nucleic acid sequence-based amplification (NASBA) for the identification of mycobacteria.

Nucleic acid sequence-based amplification (NASBA), an isothermal amplification technique for nucleic acids (NA), was investigated for the species-specific identification of mycobacteria. A set of primers was selected from a highly conserved region of the 16S rRNA sequence of mycobacteria sandwiching a variable sequence to perform amplification of mycobacterial RNA. Species-specific probes for the M. tuberculosis complex, M. avium-paratuberculosis, M. intracellulare and M. leprae were hybridized in-solution with the amplified nucleic acids of 10 pathogenic mycobacteria and 11 closely related bacteria, as well as with human-derived NA in an enzyme-linked gel assay (ELGA). Each probe was shown to hybridize specifically to the amplified single-stranded RNA of the corresponding species. Thirty-two clinical isolates of M. tuberculosis strains from different parts of the world were correctly identified by NASBA using the M. tuberculosis-complex-specific probe. In combination with the ELGA, NASBA could identify mycobacteria rapidly, i.e. in less than 6 h. The relative simplicity and rapidity of this technique makes it an attractive tool for species-specific identification of mycobacteria.

Retrieval of analytical data and substance identification in systematic toxicological analysis by the mean list length approach.

Chromatographic techniques are basic tools in systematic toxicological analysis. Extensive data bases with retention parameters of known drugs to aid in the identification of substances found are available or in preparation. For a search in such a data base the computer is indispenable. The commonly used window search has some disadvantages which can be overcome by a search based on the statistical concept, the mean list length. The latter retrieval system gives for each candidate in the identification process a probability value. It is shown that these probability values are highly influenced by the reproducibility of the retention parameters of the analytical systems used. Explanations for these phenomena are given.

System evaluation and substance identification in systematic toxicological analysis by the mean list length approach.

In systematic toxicological analyses (STA), analytical methods are needed with a high Identification Power. The mean list length (MLL) approach, which is an improved and extended version of the Identification Power concept, provides an objective tool for the evaluation and optimum choice of analytical methods for STA. The MLL approach is elucidated and applied to the screening for basic drugs by thin layer chromatography (TLC) and gas-liquid chromatography (GLC). Its usefulness for TLC and GLC systems for the identification of these basic drugs has been evaluated for both single systems and combinations of systems. The MLL approach is also substance directed and can be applied to computerized data searches and substance identification. The method is applicable for single analytical systems and combinations of systems. Mixtures of substances can also be handled.

Optimization of thin layer chromatography for toxicological screening: applicability of shorter development distances.

Over the years, numerous TLC systems have been developed, each of them having their special advantages. Yet little or no attention has been paid to the time-factor needed to obtain sufficiently reliable Rf-values, combined with satisfactory resolution. As speed remains an important factor in toxicology, the applicability of shorter development distances have been investigated, resulting in a considerable gain in time as the development times increase exponentially with developing distance. In this paper, the effects of shorter development distances on resolution, spot size, reproducibility of Rf-values, and sensitivity of detection are described.