Endurance Behavior of Cemented Tibial Tray Fixation Under Anterior Shear and Internal-External Torsional Shear Testing: A New Methodological Approach.

BACKGROUND: Early total knee arthroplasty failures continue to surface in the literature. Cementation technique and implant design are two of the most important scenarios that can affect implant survivorship. Our objectives were to develop a more suitable preclinical test to evaluate the endurance of the implant-cement-bone interface under anterior shear and internal-external (I/E) torsional shear testing condition in a biomechanical sawbones. METHODS: Implants tested included the AS VEGA System PS and the AS Columbus CR/PS (Aesculap AG, Germany), with zirconium nitride (ZrN) coating. Tibial implants were evaluated under anterior shear and I/E torsional shear conditions with 6 samples in 4 test groups. For the evaluation of the I/E torsional shear endurance behavior, a test setup was created allowing for clinically relevant I/E rotation with simultaneous high axial/tibio-femoral load. The test was performed with an I/E displacement of ±17.2°, for 1 million cycles with an axial preload of 3,000 N. RESULTS: After the anterior shear test an implant-cement-bone fixation strength for the AS VEGA System tibial tray of 2,674 ± 754 N and for the AS Columbus CR/PS tibial tray of 2,177 ± 429 N was determined (P = .191). After I/E rotational shear testing an implant-cement-bone fixation strength for the AS VEGA System PS tray of 2,561 ± 519 N and for the AS Columbus CR/PS tray of 2,824 ± 515 N was resulted (P = .39). CONCLUSION: Both methods had varying degrees of failure modes from debonding to failure of the sawbones foam. These two intense biomechanical loading tests are more strenuous and more representative of clinical activity.

Recent advances of Cas12a applications in bacteria.

Clustered regularly interspaced short palindromic repeats (CRISPR)-mediated genome engineering and related technologies have revolutionized biotechnology over the last decade by enhancing the efficiency of sophisticated biological systems. Cas12a (Cpf1) is an RNA-guided endonuclease associated to the CRISPR adaptive immune system found in many prokaryotes. Contrary to its more prominent counterpart Cas9, Cas12a recognizes A/T rich DNA sequences and is able to process its corresponding guide RNA directly, rendering it a versatile tool for multiplex genome editing efforts and other applications in biotechnology. While Cas12a has been extensively used in eukaryotic cell systems, microbial applications are still limited. In this review, we highlight the mechanistic and functional differences between Cas12a and Cas9 and focus on recent advances of applications using Cas12a in bacterial hosts. Furthermore, we discuss advantages as well as current challenges and give a future outlook for this promising alternative CRISPR-Cas system for bacterial genome editing and beyond. KEY POINTS: • Cas12a is a powerful tool for genome engineering and transcriptional perturbation • Cas12a causes less toxic side effects in bacteria than Cas9 • Self-processing of crRNA arrays facilitates multiplexing approaches.

Correlation between different instrumentation variants and the degree of destabilization in treating cervical spondylotic spinal canal stenosis by unilateral hemilaminectomy with bilateral decompression: a biomechanical investigation.

PURPOSE: Unilateral hemilaminectomy with bilateral decompression (BDZ) was proposed as an alternative decompressive procedure in cervical spondylotic myelopathy (CSM). Despite promising clinical results, the destabilizing effect is yet unknown. We therefore performed a biomechanical study to investigate whether lateral mass screw fixation should follow BDZ. METHODS: Six human C2-C7 cervical specimens were tested under various conditions: native, unilateral hemilaminectomy with bilateral decompression without/with fixation (BDZ/BDF), unilateral hemilaminectomy with bilateral decompression and unilateral foraminotomy without/with fixation (UFZ/UFF), unilateral hemilaminectomy with bilateral decompression and bilateral foraminotomy without/with fixation (BFZ/BFF), and laminectomy without/with fixation (LAZ/LAF). Instrumention was applied from C3-C6. For each condition, the three-dimensional kinematics of the cervical specimen were measured in three main loading directions with an ultrasonic motion analysis system. ANOVA was used to determine differences between the specific segment conditions to assess the parameter's range of motion (ROM) and neutral zone (NZ). RESULTS: For flexion-extension, lateral bending and axial rotation, ROM of BDZ, UFZ, BFZ and LAZ remained at the level of the native condition (p > 0.74), whereas fixation reduced ROM significantly (p < 0.01). Between BDF, UFF, BFF and LAF, no significant differences in reduction in ROM were seen (p > 0.49). Results for NZ were equivalent to ROM in flexion-extension and lateral bending. For axial rotation, NZ remained almost constant on the native level for all tested conditions. CONCLUSION: Bilateral decompression via a hemilaminectomy, even if combined with foraminotomy, could be a less invasive treatment option for multilevel CSM in patients with lordotic cervical alignment and absence of segmental instability.

Engineering of the 2,3-butanediol pathway of Paenibacillus polymyxa DSM 365.

Paenibacillus polymyxa is a Gram-positive, non-pathogenic soil bacterium that has been extensively investigated for the production of R-,R-2,3-butanediol in exceptionally high enantiomeric purity. Rational metabolic engineering efforts to increase productivity and product titers were restricted due to limited genetic accessibility of the organism up to now. By use of CRISPR-Cas9 mediated genome editing, six metabolic mutant variants were generated and compared in batch fermentations for the first time. Downstream processing was facilitated by completely eliminating exopolysaccharide formation through the combined knockout of the sacB gene and the clu1 region, encoding for the underlying enzymatic machinery of levan and paenan synthesis. Spore formation was inhibited by deletion of spoIIE, thereby disrupting the sporulation cascade of P. polymyxa. Optimization of the carbon flux towards 2,3-butanediol was achieved by deletion of the lactate dehydrogenase ldh1 and decoupling of the butanediol dehydrogenase from its natural regulation via constitutive episomal expression. The improved strain showed 45 % increased productivity, reaching a final concentration of 43.8 g L-1 butanediol. A yield of 0.43 g g-1 glucose was achieved, accounting for 86 % of the theoretical maximum.

Tibial Implant Fixation Behavior in Total Knee Arthroplasty: A Study With Five Different Bone Cements.

BACKGROUND: The objectives of this study are to (1) evaluate if there is a potential difference in cemented implant fixation strength between tibial components made out of cobalt-chromium (CrCoMo) and of a ceramic zirconium nitride (ZrN) multilayer coating and to (2) test their behavior with 5 different bone cements in a standardized in vitro model for testing of the implant-cement-bone interface conditions. We also analyzed (3) whether initial fixation strength is a function of timing of the cement apposition and component implantation by an early, mid-term, and late usage within the cement-specific processing window. METHODS: An in vitro study using a synthetic polyurethane foam model was performed to investigate the implant fixation strength after cementation of tibial components by a push-out test. A total of 20 groups (n = 5 each) was used: Vega PS CrCoMo tibia and Vega PS ZrN tibia with the bone cements BonOs R, SmartSet HV, Cobalt HV, Palacos R, and Surgical Simplex P, respectively, using mid-term cement apposition. Three different cement apposition times-early, mid-term, and late usage-were tested with a total of 12 groups (n = 5 each) with the bone cements BonOs R and SmartSet HV. RESULTS: There was no significant difference in implant-cement-bone fixation strength between CrCoMo and ZrN multilayer-coated Vega tibial trays tested with 5 different commonly used bone cements. CONCLUSION: Apposition of bone cements and tibial tray implantation in the early to mid of the cement-specific processing window is beneficial in regard to interface fixation in TKA.

Evaluation of impingement behaviour in lumbar spinal disc arthroplasty.

INTRODUCTION: The objective of our in vitro study was to introduce a test method to evaluate impingement in lumbar spinal disc arthroplasty in terms of wear, contact pattern, metal ion concentration and particle release. MATERIAL AND METHOD: Impingement wear simulation was performed on a 6-station spinal wear simulator (Endolab, Germany) on a lumbar spinal disc system (activ L Aesculap AG, Germany) using four different protocols specific to impingement in flexion, in extension, in lateral bending and in combined flexion bending. Impingement contact stress is intentionally created by applying an angular displacement of +2° in addition to the intended range of motion in the impingement direction, whereas a bending moment of 8 Nm remains constant during the impingement phase (plateau). RESULTS: An average volumetric wear rate of 0.67 mm(3)/million cycles was measured by impingement under flexion, of 0.21 mm(3)/million cycles under extension, of 0.06 mm(3)/million cycles under lateral bending and of 1.44 mm(3)/million cycles under combined flexion bending. The particle size distribution of the cobalt-chromium wear particles released by impingement in flexion (anterior), extension (posterior), lateral bending (lateral) and combined flexion bending (antero-lateral) revealed that most of the detected cobalt-chromium particles were in a size range between 0.2 and 2 µm. CONCLUSION: The impingement wear simulation introduced here proved to be suitable to predict in vivo impingement behaviour in regard to contact pattern seen on retrieved devices of the activ L lumbar disc arthroplasty design in a pre-clinical test.

Patterns of childhood abuse and neglect as predictors of treatment outcome in inpatient psychotherapy: a typological approach.

BACKGROUND: Childhood maltreatment is associated with the development and maintenance of mental disorders. The purpose of this naturalistic study was (a) to identify different patterns of childhood maltreatment, (b) to examine how these patterns are linked to the severity of mental disorders and (c) whether they are predictive of treatment outcome. METHODS: 742 adult patients of a university hospital for psychotherapy and psychosomatics were assessed at intake and discharge by standardized questionnaires assessing depression (Beck Depression Inventory, BDI) and general mental distress (Symptom Check List-90-R, SCL-90-R). Traumatic childhood experience (using the Childhood Trauma Questionnaire, CTQ) and ICD-10 diagnoses were assessed at intake. RESULTS: The patients could be allocated to three different patterns of early childhood trauma experience: mild traumatization, multiple traumatization without sexual abuse and multiple traumatization with sexual abuse. The three patterns showed highly significant differences in BDI, General Severity Index (GSI) and in the number of comorbidity at intake. For both BDI and GSI a general decrease in depression and general mental distress from intake to discharge could be shown. The three patterns differed in BDI and GSI at intake and discharge, indicating lowest values for mild traumatization and highest values for multiple traumatization with sexual abuse. Patients with multiple traumatization with sexual abuse showed the least favourable outcome. CONCLUSION: The results provide evidence that the severity of childhood traumatization is linked to the severity of mental disorders and also to the treatment outcome in inpatient psychotherapy. In the study, three different patterns of childhood traumatization (mild traumatization, multiple traumatization without sexual abuse, multiple traumatization with sexual abuse) showed differences in the severity of mental disorder and in the course of treatment within the same therapy setting.

Response to chemotherapy, reexposure to crizotinib and treatment with a novel ALK inhibitor in a patient with acquired crizotinib resistance.

The treatment of advanced non-small cell lung cancer (NSCLC) has dramatically changed over the last decade. It has developed from an unspecific approach based on platinum doublet chemotherapy to a personalized, molecularly targeted therapy. Crizotinib is a new tyrosine kinase inhibitor approved for the treatment of NSCLC with gene rearrangement of EML4 and ALK. Despite good initial responses, patients treated with crizotinib relapse after an average of 10 months. In this case report, we present a patient with acquired crizotinib resistance whose adenocarcinoma responded to a second course of crizotinib following a drug holiday and chemotherapy with pemetrexed. This is the second case report to suggest that retreatment with crizotinib is an option for patients with initial benefit from ALK inhibition.

The effect of design parameters of interspinous implants on kinematics and load bearing: an in vitro study.

INTRODUCTION: A number of concepts with controversy approaches are currently discussed for interspinous stabilization (IPS). However, comparative biomechanical studies among the different systems are rare. Nevertheless, it remains unclear which biomechanical characteristics are influenced by different design features of these implants, such as implant stiffness or an additional tension band. Therefore, the aim of the present study was to compare different interspinous implants to investigate the biomechanical impact of IPS implant design on intersegmental kinematics, such as range of motion, neutral zone, center of rotation (COR), as well as load transfer like intradiscal pressure (IDP), to gain additional experience for clinical indications and limitations. MATERIAL AND METHOD: Twelve human lumbar spine specimens were tested in a spine loading apparatus. In vitro flexibility testing was performed by applying pure bending moments of 7.5 Nm without and with additional preload of 400 N in the three principal motion planes. Four interspinous implants, Coflex "COF" (Paradigm Spine, Germany), Wallis "WAL" (Abbott Laboratories, France), DIAM "DIA" (Sofamor Danek, France) and InterActiv (Aesculap AG, Germany) with two treatment options (without dorsal tensioning "IAO" and with dorsal tensioning "IAM") were consecutively tested in comparison to the native situation "NAT" and to a defect situation "DEF" of the functional spinal unit. The tested IPS devices are comprised of a compression stiffness range of 133 to 1,674 N/mm and a tensile stiffness range of 0-39 N/mm. Range of motion, neutral zone, center of rotation and intradiscal pressure were analyzed for all instrumentation steps and load cases. CONCLUSION: For the IPS, we found a correlation between compression stiffness and stabilization in extension. Here, the system with the lowest stiffness, DIA, displayed nearly no stabilization of the treated segment, whereas the system with the highest stiffness, WAL and COF, was most pronounced. This applies also for the correlation between device stiffness and IDP. In flexion only the degree of stabilization is in correlation with the tensile stiffness, whereas the IDP stays constant and is not affected by the different tensile stiffness. IPS is not able to stabilize in the frontal and transversal plane. Furthermore IPS does not substantially alter the location of the COR.

Strains on the human femur after revision total knee arthroplasty: An in vitro study using digital image correlation.

Pain at the tip of the stem of a knee prosthesis (End-of-Stem Pain) is a common problem in revision total knee arthroplasty (TKA). It may be caused by a problematic interaction between stem and bone, but the exact biomechanical correlate is still unknown. On top of this, there is no biomechanical study investigating End-of-Stem Pain at the distal femur using human specimens. Aim of this study was to find out whether the implantation of a revision total knee implant leads to high femoral surface strains at the tip of the stem, which the authors expect to be the biomechanical correlate of End-of-Stem Pain. We implanted 16 rotating hinge knee implants into 16 fresh-frozen human femora using the hybrid fixation technique and comparing two reaming protocols. Afterwards, surface strains on these femora were measured under dynamic load in two different load scenarios (climbing stairs and chair rising) using digital image correlation (DIC) and fracture patterns after overcritical load were analysed. Peak surface strains were found at the tip of the stem in several measurements in both load scenarios. There were no significant differences between the two compared groups (different trial sizes) regarding surface strains and fracture patterns. We conclude that implantation of a long intramedullary stem in revision TKA can lead to high surface strains at the tip of the stem that may be the correlate of femoral End-of-Stem Pain. This finding might allow for a targeted development of future stem designs that can lead to lower surface strains and therefore might reduce End-of-Stem Pain. Digital Image Correlation proved valid for the measurement of surface strains and can be used in the future to test new stem designs in vitro.

The influence of third-body particles on wear rate in unicondylar knee arthroplasty: a wear simulator study with bone and cement debris.

The reduced intraoperative visibility of minimally invasive implanted unicondylar knee arthroplasty makes it difficult to remove bone and cement debris, which have been reported on the surface of damaged and retrieved bearings. Therefore, the aim of this study was to analyze the influence of bone and cement particles on the wear rate of unicompartmental knee prostheses in vitro. Fixed bearing unicompartmental knee prostheses were tested using a knee-wear-simulator according to the ISO standard 14243-1:2002(E) for 5.0 million cycles. Afterwards bone debris (particle size 671 ± 262 µm) were added to the test fluid in a concentration of 5 g/l for 1.5 million cycles, followed by 1.5 million cycles blended with cement debris (particle size 644 ± 186 µm) in the same concentration. Wear rate, knee-kinematics and wear-pattern were analyzed. The wear rate reached 12.5 ± 1.0 mm³/million cycles in the running-in and decreased during the steady state phase to 4.4 ± 0.91 mm³/million cycles. Bone particles resulted in a wear rate of 3.0 ± 1.27 mm³/million cycles with no influence on the wear rate compared to the steady state phase. Cement particles, however, lead to a significantly higher wear rate (25.0 ± 16.93 mm³/million cycles) compared to the steady state phase. The careful removal of extruded cement debris during implantation may help in reducing wear rate. Bone debris are suggested to have less critical influence on the prostheses wear rate.

Biomechanical comparison of different rod-to-rod connectors to a conventional titanium- and cobalt chromium posterior spinal fixation system.

Introduction: Several types of rod-to-rod connectors are available for the extension of spinal fixation systems. However, scientific literature regarding the mechanical performance of different rod-to-rod connector systems is lacking. Research question: The goal of this study was to evaluate the mechanical characteristics of axial and lateral rod connectors in comparison to a conventional pedicle screw rod (titanium and cobalt chromium) construct. Material and method: Six types of instrumentations were investigated in a standardized test model to quantify the mechanical differences: 1: titanium rod; 2: titanium rod with axial connector; 3: titanium rod with lateral connector; 4: cobalt chromium rod; 5: cobalt chromium rod with axial connector; 6: cobalt chromium rod with lateral connector. All groups were tested in static compression, static torsion and dynamic compression and statistically compared regarding failure load and stiffness. Results: In static compression loading, the use of connectors increased the construct stiffness, but unaffected the yield load. The use of a cobalt chromium rod significantly increased by approximately 40% the yield load and stiffness in comparison to the titanium rod configurations. Under dynamic compression, a similar or higher fatigue strength for all tested groups in comparison to the titanium rod configuration was evaluated, with the exception of titanium rod with axial connector. Conclusion: Biomechanically, using rod connectors is a secure way for the extension of a construct and is mechanically equal to a conventional screw rod construct. However, in clinical use, attention should be paid regarding placement of the connectors at high loaded areas.

Rheological characterization of artificial paenan compositions produced by Paenibacillus polymyxa DSM 365.

Microbial exopolysaccharides offer a sustainable alternative to petroleum-based rheological modifiers. Recent studies revealed that the heteroexopolysaccharide produced by Paenibacillus polymyxa is composed of three distinct biopolymers, referred to as paenan I, II and III. Using CRISPR-Cas9 mediated knock-out variants of glycosyltransferases, defined polysaccharide compositions were produced and rheologically characterized in detail. The high viscosity and gel-like character of the wildtype polymer is proposed to originate from the non-covalent interaction between a pyruvate residue of paenan I and the glucuronic acid found in the backbone of paenan III. Paenan II conveys thermostable properties to the exopolysaccharide mixture. In contrast to the wildtype polymer mixture, knock-out variants demonstrated significantly altered rheological behavior. Using the rheological characterization performed in this study, tailor-made paenan variants and mixtures can be generated to be utilized in a wide range of applications including thickening agents, coatings, or high-value biomedical materials.

Computer-based analysis of different component positions and insert thicknesses on tibio-femoral and patello-femoral joint dynamics after cruciate-retaining total knee replacement.

BACKGROUND: Positioning of the implant components and tibial insert thickness constitute critical aspects of total knee replacement (TKR) that influence the postoperative knee joint dynamics. This study aimed to investigate the impact of implant component positioning (anterior-posterior and medio-lateral shift) and varying tibial insert thickness on the tibio-femoral (TF) and patello-femoral (PF) joint kinematics and contact forces after cruciate-retaining (CR)-TKR. METHOD: A validated musculoskeletal multibody simulation (MMBS) model with a fixed-bearing CR-TKR during a squat motion up to 90° knee flexion was deployed to calculate PF and TF joint dynamics for varied implant component positions and tibial insert thicknesses. Evaluation was performed consecutively by comparing the respective knee joint parameters (e.g. contact force, quadriceps muscle force, joint kinematics) to a reference implant position. RESULTS: The PF contact forces were mostly affected by the anterior-posterior as well as medio-lateral positioning of the femoral component (by 3 mm anterior up to 31 % and by 6 mm lateral up to 14 %). TF contact forces were considerably altered by tibial insert thickness (24 % in case of + 4 mm increase) and by the anterior-posterior position of the femoral component (by 3 mm posterior up to 16 %). Concerning PF kinematics, a medialised femoral component by 6 mm increased the lateral patellar tilt by more than 5°. CONCLUSIONS: Our results indicate that regarding PF kinematics and contact forces the positioning of the femoral component was more critical than the tibial component. The positioning of the femoral component in anterior-posterior direction on and PF contact force was evident. Orthopaedic surgeons should strictly monitor the anterior-posterior as well as the medio-lateral position of the femoral component and the insert thickness.

CRISPR-Cas9 driven structural elucidation of the heteroexopolysaccharides from Paenibacillus polymyxa DSM 365.

Paenibacillus polymyxa is a Gram-positive soil bacterium known for producing a wide range of exopolysaccharides. However, due to the biopolymer's complexity, structural elucidation has so far been inconclusive. Combinatorial knock-outs of glycosyltransferases were generated in order to separate distinct polysaccharides produced by P. polymyxa. Using a complementary analytical approach consisting of carbohydrate fingerprints, sequence analysis, methylation analysis as well as NMR spectroscopy, the structure of the repeating units of two additional heteroexopolysaccharides termed paenan I and paenan III were elucidated. Results for paenan I identified a trisaccharide backbone consisting of 1➔4-ß-d-Glc, 1➔4-ß-d-Man and a 1,3,4-branching ß-d-Gal residue with a sidechain comprising of a terminal ß-d-Gal3,4-Pyr and 1➔3-ß-d-Glc. For paenan III, results indicated a backbone consisting of 1➔3-ß-d-Glc, 1,3,4-linked α-d-Man and 1,3,4-linked α-d-GlcA. NMR analysis indicated monomeric ß-d-Glc and α-d-Man sidechains for the branching Man and GlcA residues respectively.

Blood component use and associated costs after standard dose chemotherapy--a prospective analysis of routine hospital care in lymphoproliferative disorders and NSCLC in Germany.

PURPOSE: The purpose of this study was to describe blood component (BC) use and respective cost after standard dose chemotherapy (CT) in routine hospital care. METHODS: Analysis of data from a prospective, multicenter, longitudinal, observational study on lymphoproliferative disorder (LPD) and non-small cell lung cancer (NSCLC) patients undergoing first or second line standard dose (immuno-)CT. Data were collected from patient interviews and pre-planned chart reviews. Costs of BC are presented from provider perspective. RESULTS: One hundred eighty patients (n = 85 NSCLC, n = 95 LPD) receiving 189 CT lines/633 CT cycles) were evaluable (mean ± SD age, 59 ± 13.2 years, 68% stage III/IV, 14% Eastern Cooperative Oncology Group ≥ 2). During 11% of cycles, BC were transfused to 27% of patients (n = 49; n = 22 NSCLC, n = 27 LPD). Of 310 transfused units (TU), 68% were red blood cells (RBC). Mean number of TU per cycle with transfusion was 3.3 ± 2.9 (median = 2, range = 2-17) for RBC, 4.8 ± 6.8 (median = 2, range = 1-23) for platelets (PLT) and 12.8 ± 14.6 (median = 8, range = 2-33) for fresh frozen plasma (FFP). Fifteen per cent of RBC units, 60% of PLT units and 92% of FFP in this study were transfused in cycles with sepsis. Mean BC cost per CT line were euro 602 ± 1,458 (median = 135, range = 135-9,385; NSCLC: euro 292 ± 376, median = 135, range = 135-2,124; LPD: euro 1,010 ± 2,137, median = 212, range = 135-9,385, p = 0.2137). For 55% of transfused RBC units, haemoglobin levels on the day of transfusion were 8.0-8.9 g/dl, for 38% <8 g/dl and for 7% ≥ 9 g/dl. Seventy-five per cent of PLT units were transfused at a PLT count <11,000/µl and 21% at 20,000-11,000/µl. CONCLUSIONS: The results reflect the diversity of BC use after standard dose CT. High transfusion need is associated with infectious complications, i.e. sepsis emphasising the need for adequate prophylaxis and further knowledge of baseline risk factors.

Structural elucidation of the fucose containing polysaccharide of Paenibacillus polymyxa DSM 365.

Paenibacillus polymyxa is an avid producer of exopolysaccharides of industrial interest. However, due to the complexity of the polymer composition, structural elucidation of the polysaccharide remained unfeasible for a long time. By using a CRISPR-Cas9 mediated knock-out strategy, all single glycosyltransferases as well as the Wzy polymerases were individually deleted in the corresponding gene cluster for the first time. Thereby, it was observed that the main polymer fraction was completely suppressed (or deleted) and a pure minor fucose containing polysaccharide could be isolated, which was named paenan II. Applying this combinatorial approach, the monosaccharide composition, sequence and linkage pattern of this novel polymer was determined via HPLC-MS, GC-MS and NMR. Furthermore, we demonstrated that the knock-out of the glycosyltransferases PepQ, PepT, PepU and PepV as well as of the Wzy polymerase PepG led to the absence of paenan II, attributing those enzymes to the assembly of the repeating unit.

Biomechanical Effects of Stemmed Total Knee Arthroplasty on the Human Femur: A CT-Data Based Study.

End-of-stem pain of the femur is a common problem in revision total knee arthroplasty (TKA). It may be caused by a problematic interaction between stem and bone, but the exact biomechanical correlate is still unknown. The aim of this prospective study was to find out how the stem is positioned in the medullary canal, how the femoral geometry changes due to implantation, and whether the results are influenced by the diameter of the trial. We implanted 16 rotating hinge knee implants into 16 fresh-frozen human femora using the hybrid fixation technique and comparing two reaming protocols. We created 3-dimensional models of the specimens before and after implantation using CT-scans and calculated the differences. The main contact between stem and bone was found at the proximal 30 mm of the stem, especially anterior. We observed two different contact patterns of stem and bone. The cortical thickness was reduced especially at the anterior tip of the stem with a maximum reduction of 1405 ± 501 µm in the standard group and 980 ± 447 µm in the small_trial group, which is a relative reduction of 34 ± 14% (standard group) and 26 ± 14% (small_trial group). The bone experienced a deformation to posterior and lateral. We conclude that the tip of the stem is an important biomechanical region. Different contact patterns between stem and bone as well as the reduction in cortical thickness at the tip of the stem may play a role in the development of end-of-stem pain.

Management of febrile neutropenia--a German prospective hospital cost analysis in lymphoproliferative disorders, non-small cell lung cancer, and primary breast cancer.

BACKGROUND: Febrile neutropenia/leukopenia (FN/FL) is the most frequent dose-limiting toxicity of myelosuppressive chemotherapy, but German data on economic consequences are limited. PATIENTS AND METHODS: A prospective, multicentre, longitudinal, observational study was carried out to evaluate the occurrence of FN/FL and its impact on health resource utilization and costs in non-small cell lung cancer (NSCLC), lymphoproliferative disorder (LPD), and primary breast cancer (PBC) patients. Costs are presented from a hospital perspective. RESULTS: A total of 325 consecutive patients (47% LPD, 37% NSCLC, 16% PBC; 46% women; 38% age = 65 years) with 68 FN/FL episodes were evaluated. FN/FL occurred in 22% of the LPD patients, 8% of the NSCLC patients, and 27% of the PBC patients. 55 FN/FL episodes were associated with at least 1 hospital stay (LPD n = 34, NSCLC n = 10, PBC n = 11). Mean (median) cost per FN/FL episode requiring hospital care amounted to € 3,950 (€ 2,355) and varied between € 4,808 (€ 3,056) for LPD, € 3,627 (€ 2,255) for NSCLC, and € 1,827 (€ 1,969) for PBC patients. 12 FN/FL episodes (LPD n = 9, NSCLC n = 3) accounted for 60% of the total expenses. Main cost drivers were hospitalization and drugs (60 and 19% of the total costs). CONCLUSIONS: FN/FL treatment has economic relevance for hospitals. Costs vary between tumour types, being significantly higher for LPD compared to PBC patients. The impact of clinical characteristics on asymmetrically distributed costs needs further evaluation.