Conservation of kinetic stability, but not the unfolding mechanism, between human transthyretin and a transthyretin-related enzyme.

Kinetic stability is thought to be an attribute of proteins that require a long lifetime, such as the transporter of thyroxine and holo retinol-binding protein or transthyretin (TTR) functioning in the bloodstream, cerebrospinal fluid, and vitreous humor. TTR evolved from ancestral enzymes known as TTR-related proteins (TRPs). Here, we develop a rate-expansion approach that allows unfolding rates to be measured directly at low denaturant concentration, revealing that kinetic stability exists in the Escherichia coli TRP (EcTRP), even though the enzyme structure is more energetically frustrated and has a more mutation-sensitive folding mechanism than human TTR. Thus, the ancient tetrameric enzyme may already have been poised to mutate into a kinetically stable human transporter. An extensive mutational study that exchanges residues at key sites within the TTR and EcTRP dimer-dimer interface shows that tyrosine 111, replaced by a threonine in TTR, is the gatekeeper of frustration in EcTRP because it is critical for function. Frustration, virtually absent in TTR, occurs at multiple sites in EcTRP and even cooperatively for certain pairs of mutations. We present evidence that evolution at the C terminus of TTR was a compensatory event to maintain the preexisting kinetic stability while reducing frustration and sensitivity to mutation. We propose an "overcompensation" pathway from EcTRPs to functional hybrids to modern TTRs that is consistent with the biophysics discussed here. An alternative plausible pathway is also presented.

[Cervical stenosis-Diagnostics and treatment of symptomatic spinal canal stenosis and neuroforaminal stenosis]. / Zervikale Stenose ­ Diagnostik und Therapie der symptomatischen Spinalkanalstenose und Neuroforamenstenose.

Cervical stenosis is a clinical picture that is regularly encountered by both hospital physicians and orthopedic surgeons in the daily clinical practice. While advanced cervical spinal canal stenosis may lead to myelopathic symptoms in cases of sufficient manifestation and spinal cord injury, neuroforaminal stenosis leads to radicular symptoms due to compression of the nerve roots. The clinical examination can provide initial clues as to the suspected cause of the patient's symptoms; however, reliable diagnostics are based only on sectional imaging of the cervical spine. Depending on the extent of the symptoms, the treatment options vary between nonsurgical treatment for moderate symptoms without neurological deficits and surgical decompression of the spinal cord or nerve roots. The surgical treatment can be performed from anterior or posterior depending on the findings. Surgery can lead to an improvement of the neurological symptoms; however, the primary aim of surgical treatment is to avoid deterioration of the neurological deficits.

Differences in the Synovial Fluid Proteome of Septic and Aseptic Implant Failure.

Implant loosening is a severe complication after total joint replacement. Here, differential diagnosis between septic and aseptic cases is crucial for further surgical treatment, but low-grade periprosthetic joint infections (PJIs) in particular remain a challenge. In this study, we analyzed the synovial fluid proteome of 21 patients undergoing revision surgery for septic (eight cases) or aseptic (thirteen cases) implant failure using LC-MS/MS to identify potential new biomarkers as future diagnostic tools. Staphylococci were found in four cases, Streptococci in two cases, Serratia marcescens and Cutibacterium acnes in one case. Proteomic analysis of the synovial fluid resulted in the identification of 515 different proteins based on at least two peptides. A statistical comparison revealed 37 differentially abundant proteins (p < 0.05), of which 17 proteins (46%) showed a higher abundance in the septic group. The proteins with the highest fold change included the known marker proteins c-reactive protein (7.57-fold) and the calprotectin components protein S100-A8 (4.41-fold) and protein S100-A9 (3.1-fold). However, the protein with the highest fold change was leucine-rich alpha-2-glycoprotein 1 (LRG1) (9.07-fold), a currently discussed new biomarker for inflammatory diseases. Elevated LRG1 levels could facilitate the diagnosis of PJI in the future, but their significance needs to be further investigated.

Surgical Site-Released Tissue Is Potent to Generate Bone onto TCP and PCL-TCP Scaffolds In Vitro.

There is evidence that surgical site tissue (SSRT) released during orthopedic surgery has a strong mesenchymal regenerative potential. Some data also suggest that this tissue may activate synthetic or natural bone substitute materials and can thus upgrade its osteopromoting properties. In this comparative in vitro study, we investigate the composition of SSRT during total hip replacement (n = 20) harvested using a surgical suction handle. In addition, the osteopromoting effect of the cells isolated from SSRT is elucidated when incubated with porous beta-tricalcium phosphate (ß-TCP) or 80% medical-grade poly-ε-caprolactone (PCL)/20% TCP composite material. We identified multiple growth factors and cytokines with significantly higher levels of PDGF and VEGF in SSRT compared to peripheral blood. The overall number of MSC was 0.09 ± 0.12‱ per gram of SSRT. A three-lineage specific differentiation was possible in all cases. PCL-TCP cultures showed a higher cell density and cell viability compared to TCP after 6 weeks in vitro. Moreover, PCL-TCP cultures showed a higher osteocalcin expression but no significant differences in osteopontin and collagen I synthesis. We could demonstrate the high regenerative potential from SSRT harvested under vacuum in a PMMA filter device. The in vitro data suggest advantages in cytocompatibility for the PCL-TCP composite compared to TCP alone.

1st EFORT European Consensus "Medical & Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices": Background, Delphi Methodology & Consensus process.

The objectives of the 1st EFORT European Consensus on 'Medical and Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices' were foremost to focus on patient safety by establishing performance requirements for medical devices. The 1st EFORT European Consensus applied an a priori-defined, modified Delphi methodology to produce unbiased, high-quality recommendation statements, confirmed by consensus voting of a European expert panel. Intended key outcomes are practical guidelines justified by the current stage of knowledge and based on a broad European Expert Consensus, to maintain innovation and optimisation of orthopaedic devices within the boundaries of MDR 2017/745. Twenty-one main research areas of relevance were defined relying on input from the EFORT IPSI WG1 'Introduction of Innovation' recommendations and a related survey. A modified Delphi approach with a preparatory literature review and work in small groups were used to prepare answers to the research questions in the form of 32 draft Consensus statements. A Consensus Conference in a hybrid format, on-site in the Carl Gustav Carus University of Dresden was organised to further refine the draft statements and define consensus within the complete group of participants by final voting, intended to further quantify expert opinion knowledge. The modified Delphi approach provides practical guidelines for hands-on orientation for orthopaedic surgeons, research institutes and laboratories, orthopaedic device manufacturers, patient representatives, Notified Bodies, National Institutes and authorities. For the first time, initiated by the EFORT IPSI (WG1 'Introduction of Innovation'), knowledge of all related stakeholders was combined in the 1st EFORT European Consensus to develop guidelines and result in a comprehensive set of recommendations.

Introduction of innovations in joint arthroplasty: Recommendations from the 'EFORT implant and patient safety initiative'.

With the implementation of the new MDR 2017/745 by the European Parliament, more robust clinical and pre-clinical data will be required due to a more stringent approval process. The EFORT Implant and Patient Safety Initiative WG1 'Introduction of Innovation', combined knowledge of orthopaedic surgeons, research institutes, orthopaedic device manufacturers, patient representatives and regulatory authorities to develop a comprehensive set of recommendations for the introduction of innovations in joint arthroplasty within the boundaries of MDR 2017/745. Recommendations have been developed to address key questions about pre-clinical and clinical requirements for the introduction of new implants and implant-related instrumentation with the participation of a steering group, invited by the EFORT Board in dialogue with representatives from European National Societies and Speciality Societies. Different degrees of novelty and innovation were described and agreed on in relation to when surgeons can start, using implants and implant-related instrumentation routinely. Before any clinical phase of a new implant, following the pre-market clinical investigation or the equivalent device PMCF pathway, it is a common understanding that all appropriate pre-clinical testing (regulatory mandatory and evident state of the art) - which has to be considered for a specific device - has been successfully completed. Once manufacturers receive the CE mark for a medical device, it can be used in patients routinely when a clinical investigation has been conducted to demonstrate the conformity of devices according to MDR Article 62 or full equivalence for the technical, biological and clinical characteristics has been demonstrated (MDR, Annex XIV, Part A, 3.) and a PMCF study has been initiated.

Acute traumatic patellar tendon rupture and simultaneous fracture of the tibial tubercle avulsion in a premature soccer player.

Bone-tendon junctions are prone for acute trauma due to its structural weakness, especially in premature males. For the lower limb, the most eminent area is the tibial tubercle apophysis. Osgood Schlatter disease (OSD) due to repetitive trauma or epiphyseal fractures due to one trauma is well described in literature and known in pediatric practice. Traumatic distal patella tendon ruptures on the other hand are a typical injury of the knee extensor mechanism of mature patients in the fourth decade. Here, the very rare condition of fracture of the tibial tubercle apophysis with simultaneous rupture of the distal patellar tendon of a 15 year old soccer player with previous history of OSD is presented including a review of the recent literature.

[Injuries in the First German Inline Skater Hockey League]. / Verletzungen in der 1. Inline-Skaterhockey-Bundesliga.

Inline skater hockey is a sport originating from ice hockey, which is practised in Germany by about 6000 athletes. There are some differences to ice hockey, which lead to a special risk profile of the athletes.All 315 active players of the First German Inline Skater Hockey League in the years 2018 and 2019 were contacted to participate in an online survey. The subjects of the study completed an anonymised 83-item multiple-choice questionnaire about injuries, training frequency, training content, and sports equipment. 178 athletes responded and 116 questionnaires could be analysed (100 men, 8 women, 8 without information/16 goalies, 55 forwards, 44 defenders).The overall injury incidence was 36.98 per 1000 hours. Minor injuries (wounds, bruises, and blunt muscle injuries) most frequently comprised leg injuries (9.4/1000 hours) and arm injuries (7.2/1000 hours). Relevant injuries (fractures, dislocations, and ligamentous injuries) were most common to the foot (2.4/1000 hours) (n=147) and to the head (1.9/1000 hours) (n=140) and knee (1.7/1000 hours) (n=126). Of 76 fractures, 48 (63.2%) resulted from direct or indirect body contact. Goalkeepers suffered more knee injuries compared with field players, while field players sustained more shoulder injuries. Head injuries (fractures, dental injuries, traumatic brain injuries) were significantly more frequent in players without face protection (3.0/1000h vs. 1.8/1000h). Players who did not perform additional fitness training had significantly more relevant injuries. In this group, knee injuries occurred more frequently as well (4.2/1000h vs. 1.3/1000h). The duration of stretching exercises showed a negative correlation with overall injury incidence (0 minutes: 53.5/1000 hours, 1-4 minutes: 55.8/1000 hours, 5-9 minutes: 23.5/1000 hours, ≥10 minutes: 21.5/1000 hours, p<0.05).In particular, mild injuries occurred with a highly significant reduction in frequency if the subjects performed stretching exercises. Inline skater hockey in the First German League is characterised by a high risk of injury, which can be compared with professional ice hockey. Serious injuries are mainly caused by physical contact. Relevant injuries are most common to the head and lower extremity. The implementation of fitness training had a positive influence on the frequency of injuries. In the context of further professionalisation of this sport, these findings can contribute to the prevention of injuries in inline skater hockey.

Accurate determination of hip implant wear, cup anteversion and inclination through AI automated 2D-3D registration.

The precise and accurate measurement of implant wear, acetabular cup anteversion and inclination from routine anterior-posterior radiographs still poses a challenge. Current approaches suffer from time-consuming procedures accompanied by low and observer-dependent accuracy and precision. We present and validate a novel, automated method for determining total hip arthroplasty parameters by comparing its accuracy and precision with methods in contemporary scientific literature. The algorithm uses CAD-model-based two dimensional-three dimensional (2D-3D)-registration supported by convolutional neural networks. Two in-vitro experimental set-ups were designed to validate the proposed 2D-3D-method. The set-ups provided 84 predefined wear values and 24 configurations of anteversion and inclination in 114 radiographs. Accuracy and precision were evaluated by systematically comparing the predefined ground truth and the automatically calculated values from in-vitro X-rays. In addition, an algorithm was developed and validated against physician's measurements on clinical X-rays to determine the inclination of the interteardrop (ITL) and biischial line (BL) to account for the individual patient's pelvic rotation in the frontal plane. Using X-rays from experimental set-ups, the determined mean error was 0.014 mm (standard deviation: 0.020 mm; root-mean-square-error: 0.024 mm) for wear in pelvic position, -0.01° (0.24°; 0.23°) for radiographic cup anteversion, and 0.11° (0.38°; 0.39°) for radiographic cup inclination. The inclination of ITL and BL was automatically determined in all clinical X-rays with excellent interclass correlation coefficients of 0.95 and 0.91, respectively. The presented algorithm allows the accurate and precise evaluation of total hip arthroplasty parameters without additional equipment. The method might help to investigate different implant designs, biomaterials, and surgical techniques with greater objectivity.

Do we still need to screen our patients?-Orthopaedic scoring based on motion tracking.

PURPOSE: Orthopaedic scores are essential for the clinical assessment of movement disorders but require an experienced clinician for the manual scoring. Wearable systems are taking root in the medical field and offer a possibility for the convenient collection of motion tracking data. The purpose of this work is to demonstrate the feasibility of automated orthopaedic scorings based on motion tracking data using the Harris Hip Score and the Knee Society Score as examples. METHODS: Seventy-eight patients received a clinical examination and an instrumental gait analysis after hip or knee arthroplasty. Seven hundred forty-four gait features were extracted from each patient's representative gait cycle. For each score, a hierarchical multiple regression analysis was conducted with a subsequent tenfold cross-validation. A data split of 70%/30% was applied for training/testing. RESULTS: Both scores can be reproduced with excellent coefficients of determination R2 for training, testing and cross-validation by applying regression models based on four to six features from instrumental gait analysis as well as the patient-reported parameter 'pain' as an offset factor. CONCLUSION: Computing established orthopaedic scores based on motion tracking data yields an automated evaluation of a joint function at the hip and knee which is suitable for direct clinical interpretation. In combination with novel technologies for wearable data collection, these computations can support healthcare staff with objective and telemedical applicable scorings for a large number of patients without the need for trained clinicians.

Characterising diflunisal as a transthyretin kinetic stabilizer at relevant concentrations in human plasma using subunit exchange.

Transthyretin (TTR) dissociation is the rate limiting step for both aggregation and subunit exchange. Kinetic stabilisers, small molecules that bind to the native tetrameric structure of TTR, slow TTR dissociation and inhibit aggregation. One such stabiliser is the non-steroidal anti-inflammatory drug (NSAID), diflunisal, which has been repurposed to treat TTR polyneuropathy. Previously, we compared the efficacy of diflunisal, tafamidis, tolcapone, and AG10 as kinetic stabilisers for transthyretin. However, we could not meaningfully compare diflunisal because we were unsure of its plasma concentration after long-term oral dosing. Herein, we report the diflunisal plasma concentrations measured by extraction, reversed phase HPLC separation, and fluorescence detection after long-term 250 mg BID oral dosing in two groups: a placebo-controlled diflunisal clinical trial group and an open-label Japanese polyneuropathy treatment cohort. The measured mean diflunisal plasma concentration from both groups was 282.2 µM ± 143.7 µM (mean ± standard deviation). Thus, quantification of TTR kinetic stabilisation using subunit exchange was carried out at 100, 200, 300, and 400 µM diflunisal concentrations, all observed in patients after 250 mg BID oral dosing. A 250 µM diflunisal plasma concentration reduced the wild-type TTR dissociation rate in plasma by 95%, which is sufficient to stop transthyretin aggregation, consistent with the clinical efficacy of diflunisal for ameliorating transthyretin polyneuropathy.

Cup positioning and its effect on polyethylene wear of vitamin E- and non-vitamin E-supplemented liners in total hip arthroplasty: radiographic outcome at 5-year follow-up.

BACKGROUND: Aseptic loosening remains a challenging problem after total hip arthroplasty. Accurate cup placement and supplementation of antioxidants in acetabular liners might reduce material failure rates. The aim of this study is to assess the effect of the cup position on the wear behaviour of UHMWPE-XE and UHMWPE-X liners in vivo using virtual radiographs. METHODS: We conducted a prospective, randomized, controlled, multicenter trial. Clinical data of 372 probands were analyzed. Anteroposterior pelvic X-rays of 324 patients immediately postoperatively and after 1 and 5 years were evaluated by the RayMatch® analysis software regarding cup position and wear behaviour. RESULTS: Mean cup anteversion was 20.3° (± 7.4) and inclination was 41.9° (± 7.0) postoperatively. 62.3% of all patients had an anteversion and inclination within the Lewinnek safe zone. Anterior and anterolateral approaches led to significantly higher cup anteversion compared to lateral approaches (27.3° ± 5.5; 20.9° ± 7.2; 17.5° ± 6.6; p < 0.001 and p = 0.001, respectively). Mean anteversion increased to 24.6° (± 8.0) after 1 year (p < 0.001). Only one revision occurred because of implant dislocation. Wear rates from UHMWPE-X and UHMWPE-XE did not differ significantly. Anteversion angles ≥ 25° correlated to increased polyethylene wear (23.7 µm/year ± 12.8 vs. 31.1 µm/year ± 22.8, p = 0.012) and this was amplified when inclination angles were ≥ 50° (23.6 µm/year ± 12.8 vs. 38.0 µm/year ± 22.7, p = 0.062). CONCLUSION: Anterior approaches lead to the highest inaccuracy of cup placement, but cup positioning outside the Lewinnek safe zone does not necessarily cause higher dislocation rates. Moreover, mean anteversion increased by approximately four degrees within the first year after operation, which is expected to be functional due to a regularization of pelvic tilt after intervention. Mid-term wear rates of UHMWPE-X and UHMWPE-XE liners are comparable, but steep cup positions lead to significantly increased polyethylene wear. In summary, a re-evaluation of target zones for intraoperative cup positioning might be considered. In the long-term reduced oxidative embrittlement could lead to superior wear behaviour of vitamin E-blended liners.

Measures of Knee Capability in Handball Players Differ by Age: A Cross Sectional Study.

The return to sport after knee injury is challenging. This is burdensome for sports with a high incidence of injuries, such as team handball. Various tests guide decision making, but often the athlete's preinjury performance of these measures remains unknown. Moreover, objective return-to-sport criteria of a matching population are missing. The purpose of this study was to evaluate objective measures of knee capability in handball depending on players' age. Two hundred sixty-one handball players performed a functional test battery designed to evaluate knee capability after an anterior cruciate ligament injury: two- and one-legged stability analysis, jumps, speed tests, and agility assessments. For age-specific evaluation, athletes were divided into three age groups (16-19; 20-29;≥30 years). Male players showed differences in two and one-legged jumping height (p<0.02) as well as power per body weight (p<0.01) between age groups. Young female players reached better results in two-and one-legged stability. Besides the quick feet test, results of females did not differ between age groups. Functional knee stability in healthy handball players is partly influenced by age, and females show better results in stability and male athletes in power measurements. This aspect should be considered for return to sports testing and underlines the importance of performance measures in athletic testing.

[Synthetic bone replacement substances]. / Synthetische Knochenersatzstoffe.

Bone substitute materials have been successfully used for bone defects in orthopedics and trauma surgery for a long time; however, there are cases, especially in bone defects with a critical size, in which the treatment is complicated. Nowadays, multiple bone substitute materials are available. Autologous cancellous bone grafts remain the gold standard among the bone replacement materials; however, donor site morbidity and the limited availability of autologous cancellous bone represent restrictions for autologous bone grafting. Allogeneic cancellous bone grafts have also been successfully for years in the treatment of bone defects; however, infection rates of more than 10% have been described for the use of allogeneic cancellous bone. By introducing synthetic bone substitutes further alternatives are currently available to the user for the individual treatment of bone defects. The aim of this study is to demonstrate the advantages and disadvantages of various synthetic bone substitute materials.

Influence of a Calcium Phosphate Coating (BONIT®) on the Proliferation and Differentiation Potential of Human Mesenchymal Stroma Cells in the Early Phase of Bone Healing.

When implanting osteosynthetic materials or orthopedic implants, the surface condition plays a decisive role for mid- to long-term osseointegration. BONIT®, an electrochemically produced calcium phosphate (CaP) coating, has been used in the surface refinement of implants since 1995. More than 3.5 million coated implants have been successfully placed so far. BONIT® has thus been able to demonstrate clinical success. However, due to its surface properties and solubility, and the resulting difficulty in culturing cells, there are no in vitro studies investigating its influence at the molecular level, particularly on bone metabolism. In a first step, the cells from a total of ten donors were seeded separately on four different surfaces: 1. a pure corundum-blasted titanium surface (CELLTex®, CT), 2. CT with additional BONIT® coating (CT + B), 3. a hydroxyapatite-blasted titanium surface (DUOTex®, DT), 4. DT with additional BONIT® coating (DT + B). In a second step, the cells were grown for 48 h. The proliferation behavior and differentiation potential of hMSCs were investigated at three consecutive time points (12 h, 24 h and 48 h) by quantifying the mRNA expression of ten important differentiation markers using quantitative real-time polymerase chain reaction (qRT-PCR). We were able to show that BONIT® has an influence on the early proliferation and differentiation behavior of hMSCs in patients of all age groups. The additional BONIT® coating on CELLTex® or DUOTex® led to a defined mRNA expression pattern for the investigated factors: a tendency towards a higher expression rate with coating present could be found for bone morphogenetic protein 2 (BMP2), osteopontin (OPN), osteocalcin (OC), receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). A similar or lower expression rate was detected for runt-related transcription factor 2 (RUNX2), alpha-1 type I collagen (COL1A1), alkaline phosphatase (AP), osteonectin (ON) and insulin-like growth factor I (IGF1). We have developed a new method that allows the cultivation of human mesenchymal stromal cells (hMSCs) on the soluble coating BONIT® for gene expression analysis. BONIT® has a significant influence on the proliferation and differentiation behavior of human mesenchymal stroma cells. This study describes a defined gene expression pattern of bone metabolism that may help to understand the influence of this CaP coating on the early phase of implant osseointegration.

SuperPath® vs. direct anterior approach : A retrospective comparison between two minimally invasive approaches in total hip arthroplasty.

OBJECTIVE: Minimally invasive approaches are subject to controversy in orthopedic surgery. The aim of the current study was to compare the radiographic parameters between two minimally invasive approaches in total hip arthroplasty. MATERIAL AND METHODS: Between January 2018 and February 2019, the radiographic parameters of 80 patients undergoing total hip arthroplasty via minimally invasive approaches (DAA: n = 40; SuperPath® SP: n = 40) have been measured. The radiographic analysis was performed with digital software tool mediCad® (HECTEC™ GmbH, Landshut, Germany). RESULTS: Patients treated with DAA showed significantly higher inclination (SP: 39.7°â€¯± 7.3° vs. DAA: 44.7°â€¯± 5.3°) and significantly lower cup anteversion values (SP: 31.2°â€¯± 7.9° vs. DAA: 27. 5°â€¯± 5.3°, p < 0.001) than patients undergoing THA via SP postoperatively. The horizontal femoral offset was neither preoperatively nor postoperatively higher in DAA than in SP cohort (preoperative: p = 0.71, postoperative: p = 0.25) (preoperative: SP:37.2 mm ± 7.3 vs. DAA 38.2 mm ± 7.5; postoperative: SP: 38.0 mm ± 7.2 vs. DAA: 40.5 mm ± 7.0). At both times, the acetabular offset was significantly higher in DAA cohort than in SP cohort (preoperative: SP: 32.9 mm ± 5.9 vs. DAA: 36.8 mm ± 4.9; postoperative: SP: 28.9 mm ± 4.2 vs. DAA: 33.4 mm ± 3.8) (preoperative: 0.001; postoperative: p < 0.001). The vertical height was preoperatively and postoperatively not significantly higher in SP cohort than in DAA cohort (preoperative: SP: 16.1 mm ± 4.1 vs. DAA: 15.5 mm ± 4.9; postoperative: SP: 16.6 mm ± 4.6 vs. DAA: 16.1 mm ± 4.6) (preoperative: p = 0.77; postoperative: p = 0.58). The preoperatively existing leg length discrepancy of the affected leg could be compensated via surgery without showing significant differences between the two cohorts (preoperative: SP: -3.2 mm ± 5.4 vs. DAA: 1.9 mm ± 4.9; postoperative: SP: 1.5 mm ± 5.4 vs. DAA: 4.8 mm ± 5.6) (preoperative: p = 0.34; postoperative: p = 0.09). CONCLUSION: The current study demonstrates suitable cup positioning and stem alignment in the coronal plane using minimal-invasive approaches DAA and Superpath®.

Metal Artefact Reduction Sequences (MARS) in Magnetic Resonance Imaging (MRI) after Total Hip Arthroplasty (THA) : A non-invasive approach for preoperative differentiation between periprosthetic joint infection (PJI) and aseptic complications?

BACKGROUND: In the past, radiographic imaging was of minor relevance in the diagnosis of periprosthetic joint infections (PJI). Since metal artefact reduction sequences (MARS) are available, magnetic resonance imaging (MRI) has become a promising diagnostic tool for the evaluation of hip arthroplasty implants. The purpose of the present study was to evaluate the efficacy of MARS-MRI in comparison to established diagnostic tools to distinguish between aseptic failure and PJI. METHODS: From July 2018 to September 2019, 33 patients classified as having an aseptic joint effusion were recruited into the study. The group included 22 women and 11 men with a mean age of 70.4 ± 13.7 (42-88) years. In the same period, 12 patients were classified as having a PJI. The group consisted of 9 women and 3 men with a mean age of 72.5 ± 10.6 (54-88) years. MARS-MRI was conducted using the optimized parameters at 1.5 T in a coronal and axial STIR (short-tau-inversion recovery), a non-fat-saturated T2 in coronal view and a non-fat-saturated T1 in transverse view in 45 patients with painful hip after total hip arthroplasty (THA). Normally distributed continuous data were shown as mean ± standard deviation (SD) and compared using student's t-test. Non-normally distributed continuous data were shown as mean and compared using the Mann-Whitney U test. RESULTS: Synovial layering and muscle edema were significant features of periprosthetic joint infection, with sensitivities of 100% and specifities of 63.0-75.0%. The combined specifity and sensitivity levels of synovial layering and muscular edema was 88.0% and 90.0%. Granulomatous synovitis was a significant feature for aseptic failure, with 90.0% sensitivity and 57.0% specifity. CONCLUSION: MARS-MRI is as suitable as standard diagnostic tools to distinguish between aseptic failure and PJI in patients with THA. Further studies with larger patient numbers have to prove whether MARS-MRI could be integral part of PJI diagnostic.

The Implant Proteome-The Right Surgical Glue to Fix Titanium Implants In Situ.

Titanium implants are frequently applied to the bone in orthopedic and trauma surgery. Although these biomaterials are characterized by excellent implant survivorship and clinical outcomes, there are almost no data available on the initial protein layer binding to the implant surface in situ. This study aims to investigate the composition of the initial protein layer on endoprosthetic surfaces as a key initiating step in osseointegration. In patients qualified for total hip arthroplasty, the implants are inserted into the femoral canal, fixed and subsequently explanted after 2 and 5 min. The proteins adsorbed to the surface (the implant proteome) are analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A statistical analysis of the proteins' alteration with longer incubation times reveals a slight change in their abundance according to the Vroman effect. The pathways involved in the extracellular matrix organization of bone, sterile inflammation and the beginning of an immunogenic response governed by neutrophils are significantly enriched based on the analysis of the implant proteome. Those are generally not changed with longer incubation times. In summary, proteins relevant for osseointegration are already adsorbed within 2 min in situ. A deeper understanding of the in situ protein-implant interactions in patients may contribute to optimizing implant surfaces in orthopedic and trauma surgery.

Diagnostic Accuracy of Synovial Neopterin, TNF-α and Presepsin in Periprosthetic Joint Infection: A Prospective Study.

BACKGROUND: Due to the lack of specificity of conventional diagnostic tools, the prediction of periprosthetic joint infections (PJI) remains challenging. The purpose of this study was to evaluate the accuracy of synovial fluid neopterin, presepsin, and TNF-α as diagnostic parameters and to compare it to the biomarkers recommended in the 2018 definition of periprosthetic hip and knee infection. METHODS: Between August 2018 and July 2019, a prospective cohort study was conducted in 80 patients with painful hip, shoulder, and knee arthroplasty. In addition to medical history, clinical and laboratory data were gathered. PJI was diagnosed based on the 2018 definition of periprosthetic hip and knee infection. Synovial joint fluid was analyzed for biomarker measurement using standard quantitative enzyme immunoassay kits. RESULTS: Fifty-three patients (66%) were classified as the aseptic group and twenty-seven patients (34%) as the PJI group. The mean levels of synovial fluid neopterin were significantly higher (p < 0.01) in the PJI group than those in the aseptic group (aseptic 8.3 ± 6.9 vs. PJI 20.9 ± 21.4 nmol/L). The average values of synovial fluid TNF-α and presepsin were not significantly higher in the PJI group than those in the aseptic group (presepsin: aseptic 0.13 ± 0.19 vs. PJI 0.11 ± 0.32 ng/mL, p = 0.08; TNF-α: aseptic 6.6 ± 7.3 vs. PJI 46.3 ± 123.2 pg/mL, p = 0.17). Synovial fluid neopterin was 59% specific and 74% sensitive with a cut-off value of 7.2 nmol/L. The sensitivity and specificity of synovial fluid TNF-α were 63 and 51% with a cut-off value of 3.9 pg/mL. Synovial fluid presepsin was 51% specific and 29% sensitive with a cut-off value above 0.06 ng/mL. CONCLUSION: Synovial fluid neopterin appears to a reliable diagnostic marker for detection of PJI. In contrast, synovial fluid TNF-α and presepsin are not suitable to exclude or diagnose PJI.

A Retrospective Single-Center Study of 23 Patients to Compare Gait Before and After Total Hip Arthroplasty Using the S-ROM Modular Hip System.

BACKGROUND This retrospective study used the Harris hip score (HHS) and range of motion (ROM) to compare gait before and after total hip arthroplasty using the modular S-ROM® hip prosthesis in 23 patients treated at a single center. MATERIAL AND METHODS For this study, 23 patients with severe hip deformity, who were treated with a total hip replacement using the S-ROM® modular hip system by DePuy® in the period from 2003 until 2008, underwent a 3-dimensional gait analysis before and after surgery. Values were compared with a validated data set of healthy subjects. Gait analysis took place using 8 infrared cameras (50 Hz), 2 force platforms of Advanced Medical Technology, Inc. (AMTI)®, and the Vicon® 512 system. The HHS and ROM of the hip joint were determined preoperatively and postoperatively. The follow-up period was 16.7±15.2 months. RESULTS A healthy gait pattern is characterized by an even stride length of both legs in relation to body height and relative symmetry of certain gait phases. These characteristics are influenced by the range of motion of the hip joint and by pelvic tilt. Symmetry could be achieved postoperatively in the stance phase and in the single-leg stance phase. However, the gait phases could not normalize. HHS and ROM improved postoperatively. CONCLUSIONS The findings from this retrospective study showed that ROM and HHS significantly improved following THA with the S-ROM® hip prosthesis, but that gait did not completely return to normal.