Midterm results of modular hinge total knee arthroplasty using cementless osseointegrating stems: low fixation associated complications and good functional outcome in primary and revision knee arthroplasty.

PURPOSE: This study aimed to investigate functional outcome and complications after primary and revision modular H-TKA using hybrid fixation with cementless stems. METHODS: Between 2015 and 2018, 48 patients with 50 implants were included after hybrid implantation of a single design H-TKA system using cementless osseointegrating stems and modular components. Complications and clinical outcome were analysed using Knee Society Score (KSS), the Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) and the Short-Form Health Survey 12 (SF-12) score. RESULTS: Indications for implantation were aseptic revision (n = 29, 58%), primary TKA (n = 19, 38%) and two-stage septic revisions (n = 2, 4%). Complications were reported in 26% (n = 12), whereas complications associated with hybrid fixation occurred in 5 (10%) cases, with 2 (4%) requiring revision surgery for aseptic loosening and 3 (6%) treated with an adapted postoperative protocol for perioperative fractures. Implant survivorship was 84% after a mean follow-up of 54 months. Postoperative KSS significantly improved from 51.50 (12-100) to 78.36 (41-99; p < 0.001). The mean WOMAC score was 19.26 (0-55), SF-12 PCS was 41.56 points (22.67-57.66) and SF-12 MCS was 49.21 points (23.87-63.21). CONCLUSION: Hybrid modular implantation in H-TKA provides satisfactory clinical and functional results in primary and revision TKA. Clinical outcomes significantly improve with reduced pain, increased mobility, and good-to-excellent functional scores after implantation. Whilst implant survival is comparable to previous studies and complications associated with hybrid fixation are low, general complication rates are comparably high.

The optimal diagnostic cut-off of WBC and PMN counts for joint aspiration in periprosthetic joint infection is 2479/µL and 67%, respectively: ICM criteria thresholds are too high.

BACKGROUND: Various organizations have published definitions for periprosthetic joint infection (PJI) with significant differences in the cut-offs of white blood cell (WBC) count and polymorphonuclear (PMN) leukocyte cells. Herein, we aim to analyze optimal cut-offs in patients which are planned to undergo a prosthesis revision and compare them with the actual published thresholds of the International Consensus Meeting (ICM) and European Bone and Joint Infection Society (EBJIS). METHODS: A test kit was compiled in a monocentric prospective study, according to the ICM criteria (2018) and 2021 EBJIS criteria. The kit was implemented using: blood samples (including leukocyte count and C-reactive protein); samples for examining the synovial fluid (WBC count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin ELISA laboratory test, and leukocyte-esterase test). The cut-offs for WBC and PMN counts were investigated using ROC analyses and Youden index. The ICM 2018 criteria were applied, using alpha-defensin in all cases. Patients which have to undergo a prosthesis revision were included, a pre-operative joint aspiration had been performed, and the patients had been followed up prospectively. RESULTS: 405 patients were examined with the compiled test kit; 100% had a complete dataset with respect to alpha-defensin; 383 patients, according to WBC count; and 256, according to PMN cell differentiation The cut-off of 2478.89 cells/µl in the WBC count (sensitivity: 87.70%; specificity: 88.10%) and the cut-off of 66.99% in PMN differentiation showed the best accuracy (sensitivity: 86.00%; specificity: 88.80%). Other published cut-offs for WBC were tested in this cohort and showed the following accuracy: 3000/µl (EBJIS/ICM; sensitivity: 82.10%; specificity: 91.00%), 2000/µl (sensitivity: 89.60%; specificity: 83.40%), and 1500/µl (sensitivity: 91.50%; specificity: 75.00%). The published cut-offs for PMN had the following accuracy in this cohort: 80% (ICM; sensitivity: 66.3%; specificity: 96.50%), 70% (sensitivity: 82.6%; specificity: 90%), and 65% (EBJIS, sensitivity: 86%; specificity: 88.8%). CONCLUSIONS: This study aims to improve current cut-offs for PMN- and WB-Count, even though PJI diagnosis is based on the combination of all defined tests. The optimal diagnostic cut-off of WBC and PMN counts was found to be 2479/µL and 67%, respectively, whereas ICM cut-offs in this cohort seem too high, as they provide high specificity but very low sensitivity. On the other hand, a cut-off for WBC count of 1500/µl alone would be very low, leading to low specificity and very high suspicion of PJI. The current consensus guidelines could be actualized considering these results to significantly improve the diagnostic quality. LEVEL OF EVIDENCE: II.

[Implementation of a standardized clinical test kit for diagnostics of periprosthetic infections in the clinical routine. German version]. / Implementierung eines standardisierten Test-Kits zur Diagnostik von periprothetischen Infektionen in der klinischen Routine.

BACKGROUND: The number of primary arthroplasties is increasing and the proportion of revision arthroplasties is becoming increasingly more important. The need for standardized and guideline-based diagnostics for the safe detection of a periprosthetic joint infection (PJI) is becoming apparent. In the past 10 years various organizations have published definitions and diagnostic guidelines. The implementation of an inhouse standard test kit could help to simplify the process and could improve the diagnostic quality. METHOD: In 2016 a test kit was compiled in a monocentric prospective study, taking the International Consensus Meeting (ICM) criteria 2014 and the Infectious Diseases Society of America (IDSA) criteria into account, which also fulfils the definitions of the ICM criteria 2018 and criteria of the European Bone and Joint Infection Society 2021. The test kit was implemented in the clinical setting of a special department for aseptic and septic revision arthroplasty. The usability and accuracy of the test kit were examined. RESULTS: The test kit was implemented using blood samples (leukocyte count; C­reactive protein, CRP), samples for examining the synovial fluid (white blood cell count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin enzyme-linked immunosorbent assay, ELISA, leukocyte esterase test strips) together with information and request forms. Between April 2016 and February 2020 a total of 405 patients were investigated. Within 3 calendar years, the use of the test kit increased from 59% initially to 86%, and finally to 96% of cases in the third calendar year. The leukocyte esterase test strip was reliable in only 72%, due to undifferentiated readability or blood contamination. The costs increased by the only commercially available alpha-defensin ELISA test by approx. 52€ per puncture. The best individual test showed a sensitivity/specificity of 92.8%/95.2% with alpha-defensin. It was calculated which combinations showed a similar test quality and different combinations, such as CRP+ cell count+ microbiology showed a sensitivity/specificity both of around 90%. Metallosis is a challenge for preoperative PJI diagnostics. DISCUSSION: In a prospective study it was shown, that the implementation of the standardized test kit lead to a guideline based PJI diagnostic in all cases and thus to a significantly increase of the diagnostic quality. There is currently no single test that reliably excludes or proves an infection. The alpha-defensin laboratory ELISA test showed the best test accuracy, whereby the consideration of test combinations is obligatory and at the same time safe.

Implementation of a standardized clinical test kit for diagnostics of periprosthetic infections in the clinical routine.

BACKGROUND: The number of primary arthroplasties is increasing and the proportion of revision arthroplasties is becoming increasingly more important. The need for standardized and guideline-based diagnostics for the safe detection of a periprosthetic joint infection (PJI) is becoming apparent. In the past 10 years various organizations have published definitions and diagnostic guidelines. The implementation of an inhouse standard test kit could help to simplify the process and could improve the diagnostic quality. METHOD: In 2016 a test kit was compiled in a monocentric prospective study, taking the International Consensus Meeting (ICM) criteria 2014 and the Infectious Diseases Society of America (IDSA) criteria into account, which also fulfils the definitions of the ICM criteria 2018 and criteria of the European Bone and Joint Infection Society 2021. The test kit was implemented in the clinical setting of a special department for aseptic and septic revision arthroplasty. The usability and accuracy of the test kit were examined. RESULTS: The test kit was implemented using blood samples (leukocyte count; C­reactive protein, CRP), samples for examining the synovial fluid (white blood cell count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin enzyme-linked immunosorbent assay, ELISA, leukocyte esterase test strips) together with information and request forms. Between April 2016 and February 2020 a total of 405 patients were investigated. Within 3 calendar years, the use of the test kit increased from 59% initially to 86%, and finally to 96% of cases in the third calendar year. The leukocyte esterase test strip was reliable in only 72%, due to undifferentiated readability or blood contamination. The costs increased by the only commercially available alpha-defensin ELISA test by approx. 52€ per puncture. The best individual test showed a sensitivity/specificity of 92.8%/95.2% with alpha-defensin. It was calculated which combinations showed a similar test quality and different combinations, such as CRP+ cell count+ microbiology showed a sensitivity/specificity both of around 90%. Metallosis is a challenge for preoperative PJI diagnostics. DISCUSSION: In a prospective study it was shown, that the implementation of the standardized test kit lead to a guideline based PJI diagnostic in all cases and thus to a significantly increase of the diagnostic quality. There is currently no single test that reliably excludes or proves an infection. The alpha-defensin laboratory ELISA test showed the best test accuracy, whereby the consideration of test combinations is obligatory and at the same time safe.

Modular knee arthrodesis secures limb, mobility, improves quality of life, and leads to high infection control in periprosthetic knee infection, when revision knee arthroplasty is not an option.

INTRODUCTION: This study compared the outcome of knee arthrodesis versus hinged total knee arthroplasty (TKA) in patients suffering from periprosthetic joint infection (PJI). METHODS: 104 patients with PJI were treated using a two-stage exchange of failed TKA. In case of non reconstructable bone loss or loss of extension mechanism, a modular intramedullary arthrodesis nail was used for reimplantation [Knee Arthrodesis Module (KAM); n = 52]. The control group was retrospectively matched treated using a hinged revision TKA [Rotating Hinge Knee (RHK); n = 52]. PJI remission rates, functional outcome (WOMAC; KSS) and quality of life (SF-12), as well as comorbidities and pain were evaluated. RESULTS: Mean age was 72.5 years. Charlson Comorbidity Index was higher in the KAM group (3.3 vs. 2.8). PJI remission rate was 89.4% (88.5% vs. 90.4%, respectively). In case of reinfection, implant retention was mostly possible in the RHK group (7.7%), whereas amputations were mostly performed in the KAM group (9.6%). Significant pain reduction (VAS 7.9-2.8) was achieved in both groups. Walking distance was significantly reduced in the KAM groups versus the RHK group (504 vs. 1064 m). WOMAC and KSS function scores were significantly reduced in the KAM group (25 vs. 40 and 35 vs. 64). Only moderate reduction in quality of life in the KAM group was observed (SF-12 physical: 34 vs. 40; SF-12 mental: 51 vs. 56) respectively. CONCLUSIONS: Arthrodesis using a modular intramedullary nail is an alternative for limb salvage, pain reduction, and preservation of quality of life and everyday mobility, when revision TKA is not an option. This study presents the largest number of case, comparing the outcome after performing an arthrodesis versus hinged TKA after septic failed TKA.

Salvage procedure for chronic periprosthetic knee infection: the application of DAIR results in better remission rates and infection-free survivorship when used with topical degradable calcium-based antibiotics.

PURPOSE: Debridement, systemic antibiotics and implant retention (DAIR) is very successful for early periprosthetic joint infection (PJI), but can fail in late-onset cases. We selected patients with PJI who were unsuitable for two-stage exchange total knee arthroplasty (TKA) and compared the outcomes of DAIR with or without degradable calcium-based antibiotics. METHODS: All patients fulfilled the criteria for late-onset PJI of TKA, as defined by an International Consensus Meeting in 2013, but were unsuitable for multistage procedures and TKA exchange due to operative risk. Fifty-six patients (mean age: 70.6 years, SD ± 10.8), in two historical collectives, were treated using a single-stage algorithm consisting of DAIR without antibiotics (control group, n = 33, 2012-2014), or by DAIR following the implantation of degradable antibiotics as indicated by an antibiogram (intervention group, n = 23, 2014-2017). OSTEOSET® (admixed vancomycin/tobramycin), and HERAFILL-gentamicin® were used as carrier systems. The primary endpoint was re-infection or surgical intervention after DAIR. RESULTS: There were no significant differences between the two groups in terms of mean age, Charlson comorbidity index or the rate of mixed infections. Overall, 65.2% of patients achieved remission in the intervention group compared with only 18.2% in the control group (p < 0.001); 50% of re-infections in the intervention group even occurred after 36 months. Kaplan-Meier analysis showed that, compared with controls, the intervention group experienced significantly longer 3-year infection-free survival. CONCLUSION: DAIR shows poor efficacy in difficult-to-treat cases, as demonstrated in our control group, which had a re-infection rate of 81.8%. In contrast, a DAIR group receiving topical calcium-based antibiotics showed significantly higher 3-year infection-free survival. Therefore, the combination of DAIR and degradable antibiogram-based local antibiotics is a reasonable salvage procedure for this body of patients. This is important as the number of severely sick patients who are too old for appropriate PJI treatment is estimated to increase significantly due to demographic change.

Structure and electrical properties of nanoparticulate tungsten oxide prepared by microwave plasma synthesis.

Nanoparticulate WO(3) films were prepared using microwave plasma synthesis and studied with respect to the electrical conductivity in dependence of ambient conditions. The WO(3) films with a monoclinic structure were made from cluster-assembled nanoparticles (diameter 3 nm) by means of dispersion and spin-coating. Above 100 °C a thermally activated decrease of the electrical resistance due to oxygen vacancy donors is found. A reversible increase of the electrical resistance R due to oxygen uptake is observed. The decrease of R in response to reducing H(2)S in the ppm range is studied in dependence of temperature and pre-annealing conditions.

Note: On the deconvolution of Kelvin probe force microscopy data.

In Kelvin probe force microscopy (KPFM) proper interpretation of the data is often difficult because the measured surface potential is affected by the interaction of the cantilever with the sample. In this work, the tip's interaction with a modeled surface potential distribution was simulated, leading to a calculated KPFM image. Although simplified, the calculation is capable of showing the influence of the cantilever in the correct qualitative manner, proven by a comparison with experimental data. Additionally, a deconvolution was performed on the simulated image, showing that for simple geometries revealing the "real" surface potential data is possible in principle.

Granzyme K: a novel mediator in acute airway inflammation.

BACKGROUND: Granzymes are a subfamily of serine proteases involved in the pathogenesis of many inflammatory disorders. In contrast with granzyme A and B, the role of granzyme K (GrK) in human lung diseases is unknown. Therefore, the release and expression of GrK in allergic asthma, chronic obstructive pulmonary disease (COPD) and bronchopneumonia were investigated. METHODS: Soluble GrK was quantified using an enzyme linked immunosorbent assay in the bronchoalveolar lavage fluid of patients with allergic asthma (before and after segmental allergen challenge), and in patients with mild COPD, pneumonia and in healthy controls. The molecular form of GrK was analysed by western blot. Flow cytometry was performed to determine the cellular expression of GrK. RESULTS: Compared with healthy controls, there were normal levels of soluble GrK in the bronchoalveolar lavage fluid of patients with COPD, and patients with allergic asthma before allergen challenge. In contrast, soluble GrK was strongly increased in the bronchoalveolar lavage fluid of patients with acute bronchopneumonia. In patients with allergic asthma, there was a significant increase in soluble GrK as well as in GrK expressing CD8(+) T cells in the bronchoalveolar lavage fluid 24 h and 72 h after allergen challenge. After allergen challenge, soluble GrK correlated with the percentage of GrK expressing CD8(+) T cells. Finally, it was shown that the endobronchial release of the CCR5 ligand CCL3 might be a mechanism for the recruitment of GrK(+)CD8(+) T cells after allergen challenge. CONCLUSION: These data provide the first evidence that expression of GrK is upregulated in acute airway inflammation, both in infectious and non-infectious diseases.

[Sexuality of suicidal elderly]. / Sexualität suizidaler Alterer.

Sexuality and suicidality in the elderly seem to underlie a taboo in science and in therapeutic practice. It is urgent to find an understanding about both aspects of human experience and behaviour by explorative studies. In a sample (N=67), the narratives of 56 persons (suicidal=43 and non-suicidal=23) on questions concerning their sexuality were transcribed and ideal types were developed with the systematic qualitative method of forming types by understanding. Four of these types consist of clearly more suicidal persons, in two the non-suicidals predominate, the rest is more heterogeneous in this aspect. Some of these types can be interpreted unequivocally. One type was surprisingly clearly suicidal dynamic, while others were a "female narcissistic" or a "male narcissistic" type. This explorative typology may help the interested therapist/counsellor as a landmark to relate to sexuality as an important aspect of life, even in old age, and to use the discussion of sexuality to improve the understanding of patients, especially in suicidal crisis.

Towards therapeutic applications of engineered zinc finger proteins.

It has long been the goal of molecular biologists to design DNA-binding proteins for the specific control of gene expression. The zinc finger design is ideally suited for such purposes, discriminating between closely related sequences both in vitro and in vivo. Whereas other DNA-binding proteins generally make use of the 2-fold symmetry of the double helix, zinc fingers do not and so can be linked linearly in tandem to recognize DNA sequences of different lengths, with high fidelity. This modular design offers a large number of combinatorial possibilities for the specific recognition of DNA. By fusing zinc finger peptides to repression or activation domains, genes can be selectively targeted and switched off and on. Several recent applications of such engineered zinc finger proteins (ZFPs) are described, including the activation of vascular endothelial growth factor (VEGF) in a human cell line and an animal model. Clinical trials have recently begun on using VEGF-activating ZFPs to treat human peripheral arterial disease, by stimulating vascular growth. Also in progress are pre-clinical studies using ZFPs to target the defective genes in two monogenic disorders, SCID and SCA. The aim is to replace them in each case by a correct copy from an extrachromosomal DNA donor by means of homologous recombination. Promising results are reported.

[Bavarian mammography screening: results of consistency tests in X-ray units over three months]. / Ergebnisse aus drei Monaten Konstanzprüfung an Röntgeneinrichtungen im Bayerischen Mammographie-Screening.

PURPOSE: To find out whether the quality requirements in daily, weekly or monthly tests of the "European protocol for the quality control of the physical and technical aspects of mammographic screening (EPQC)" can be maintained when screening the population of a large area. Furthermore, to check the specific tolerances of different test positions given by the EPQC for redundancy and statistical correlation. MATERIALS AND METHODS: Daily test images were obtained with an additional exposition of a sensitometric step wedge according DIN 6868 - 2. Weekly densitometry and visual inspection were performed at the University of Applied Sciences, Cologne. RESULTS: All units were able to maintain basic requirements on image quality as long as films of the same batch number were used. Some tolerance requirements of the EPQC are inconsistent and redundant. CONCLUSION: The occasionally considerable fluctuations of film processing require a daily check on the processing conditions. Daily test images of the units are only obligatory in the first 4 to 5 weeks of a new operation. All test results should be analyzed retrospectively in an independent test laboratory with emphasis on the statistical behavior of the unit. The tolerances prescribed by the EPQC are not always consistent and should be adapted to today's scientific standard when applied in mammography screening centers.

A rapid, generally applicable method to engineer zinc fingers illustrated by targeting the HIV-1 promoter.

DNA-binding domains with predetermined sequence specificity are engineered by selection of zinc finger modules using phage display, allowing the construction of customized transcription factors. Despite remarkable progress in this field, the available protein-engineering methods are deficient in many respects, thus hampering the applicability of the technique. Here we present a rapid and convenient method that can be used to design zinc finger proteins against a variety of DNA-binding sites. This is based on a pair of pre-made zinc finger phage-display libraries, which are used in parallel to select two DNA-binding domains each of which recognizes given 5 base pair sequences, and whose products are recombined to produce a single protein that recognizes a composite (9 base pair) site of predefined sequence. Engineering using this system can be completed in less than two weeks and yields proteins that bind sequence-specifically to DNA with Kd values in the nanomolar range. To illustrate the technique, we have selected seven different proteins to bind various regions of the human immunodeficiency virus 1 (HIV-1) promoter.

Design of polyzinc finger peptides with structured linkers.

Zinc finger domains are perhaps the most versatile of all known DNA binding domains. By fusing up to six zinc finger modules, which normally recognize up to 18 bp of DNA, designer transcription factors can be produced to target unique sequences within large genomes. However, not all continuous DNA sequences make good zinc finger binding sites. To avoid having to target unfavorable DNA sequences, we designed multizinc finger peptides with linkers capable of spanning long stretches of nonbound DNA. Two three-finger domains were fused by using either transcription factor IIIA for the Xenopus 5S RNA gene (TFIIIA) finger 4 or a non-sequence-specific zinc finger as a "structured" linker. Our gel-shift results demonstrate that these peptides are able to bind with picomolar affinities to target sequences containing 0--10 bp of nonbound DNA. Furthermore, these peptides display greater sequence selectivity and bind with higher affinity than similar six-finger peptides containing long, flexible linkers. These peptides are likely to be of use in understanding the behavior of polydactyl proteins in nature and in the targeting of human, animal, or plant genomes for numerous applications. We also suggest that in certain polydactyl peptides an individual finger can "flip" out of the major groove to allow its neighbors to bind shorter, nontarget DNA sequences.