Zirconium as a Promising Synovial Biomarker for Loose Cemented Knee Prosthesis.

BACKGROUND: Aseptic loosening is the most common mode of failure after total knee arthroplasty. Despite this, the diagnosis often remains challenging and mainly relies on imaging modalities. Until today, no biomarker exists to aid in diagnosing loosening of the implants. As zirconium (Zr) is often found in bone cement, where it serves as radiopacifier, this study aimed to establish Zr as a synovial biomarker for loosened cemented knee prostheses. METHODS: A total of 31 patients scheduled for revision of a cemented knee prostheses were included. In all patients, the initial used cement contained Zr. After arthrotomy, specimens of synovial fluid were taken and levels of Zr were measured by inductively coupled plasma mass spectrometry. Depending on the necessary amount of force for explantation, the implants were graded "loose" or "well-fixed". Preoperative radiographs were evaluated by 2 independent physicians. RESULTS: The concentration of Zr in the synovial fluid differed significantly (P < .001) between the "loose" (mean 170.9 µg/L, range 0 to 1941 µg/L) and the "well-fixed" (mean 0.6 µg/L, range 0 to 6 µg/L) implants. The receiver operating characteristic analysis revealed 0.25 µg/l as an optimal cutoff value leading to a sensitivity of 0.84, a specificity of 0.92, a positive predictive value of 0.94, and a negative predictive value of 0.79. There was no significant difference in the diagnostic performance compared to radiographs (P = .66). CONCLUSIONS: Zirconium proved to be a reliable novel synovial biomarker for diagnosing aseptic loosening of knee prothesis fixed with cement containing Zr. This biomarker should not be interpreted in isolation, but in combination with existing diagnostic tools.

Accuracy of Personalized Computed Tomographic 3D Templating for Acetabular Cup Placement in Revision Arthroplasty.

Background: Revision hip arthroplasty presents a surgical challenge, necessitating meticulous preoperative planning to avert complications like periprosthetic fractures and aseptic loosening. Historically, assessment of the accuracy of three-dimensional (3D) versus two-dimensional (2D) templating has focused exclusively on primary hip arthroplasty. Materials and Methods: In this retrospective study, we examined the accuracy of 3D templating for acetabular revision cups in 30 patients who underwent revision hip arthroplasty. Utilizing computed tomography scans of the patients' pelvis and 3D templates of the implants (Aesculap Plasmafit, B. Braun; Aesculap Plasmafit Revision, B. Braun; Avantage Acetabular System, Zimmerbiomet, EcoFit 2M, Implantcast; Tritanium Revision, Stryker), we performed 3D templating and positioned the acetabular cup implants accordingly. To evaluate accuracy, we compared the planned sizes of the acetabular cups in 2D and 3D with the sizes implanted during surgery. Results: An analysis was performed to examine potential influences on templating accuracy, specifically considering factors such as gender and body mass index (BMI). Significant statistical differences (p < 0.001) in the accuracy of size prediction were observed between 3D and 2D templating. Personalized 3D templating exhibited an accuracy rate of 66.7% for the correct prediction of the size of the acetabular cup, while 2D templating achieved an exact size prediction in only 26.7% of cases. There were no statistically significant differences between the 2D and 3D templating methods regarding gender or BMI. Conclusion: This study demonstrates that 3D templating improves the accuracy of predicting acetabular cup sizes in revision arthroplasty when compared to 2D templating. However, it should be noted that the predicted implant size generated through 3D templating tended to overestimate the implanted implant size by an average of 1.3 sizes.

Total Synthesis of Nosiheptide.

Total synthesis of the bismacrocyclic thiopeptide antibiotic nosiheptide was achieved through the assembly of a fully functionalized linear precursor followed by consecutive macrocyclizations. Key features are a critical macrothiolactonization and a mild deprotection strategy for the 3-hydroxypyridine core. The natural product was identical to isolated authentic material in terms of spectral data and antibiotic activity.

[Innovative image-based planning in musculoskeletal surgery]. / Innovative bildbasierte Operationsplanung in der muskuloskelettalen Chirurgie.

BACKGROUND: For the preparation of surgical procedures in orthopedics and trauma surgery, precise knowledge of imaging and the three-dimensional imagination of the surgeon are of outstanding importance. Image-based, preoperative two-dimensional planning is the gold standard in arthroplasty today. In complex cases, further imaging such as computed tomography (CT) or magnetic resonance imaging is also performed, generating a three-dimensional model of the body region and helping the surgeon in the planning of the surgical treatment. Four-dimensional, dynamic CT studies have also been reported and are available as a complementary tool. DIGITAL AIDS: Furthermore, digital aids should generate an improved representation of the pathology to be treated and optimize the surgeon's imagination. The finite element method allows patient-specific and implant-specific parameters to be taken into account in preoperative surgical planning. Intraoperatively, relevant information can be provided by augmented reality without significantly influencing the surgical workflow.

Comparison of the scientific performance in hip and knee arthroplasty between the leading continents.

Background: Scientific progress in the field of knee and hip arthroplasty has enabled the preservation of mobility and quality of life in the case of patients with many primary degenerative and (post-) traumatic joint diseases. This comparative study aims to investigate differences in scientific performance between the leading continents in the field of hip and knee arthroplasty. Methods: Using specific search terms all studies published by the scientific leading continents Europe, North America, Asia and Oceania listed in the Web of Science databases were included. All identified publications were analysed and comparative conclusions were drawn regarding the qualitative and quantitative scientific merit of each continent. Results: Europe, followed by North America, Asia, and Oceania, had the highest overall number of publications in the field of arthroplasty. Since 2000, there has been a strong increase in knee arthroplasty publication rate, particular pronounced in Asia. Studies performed and published in North America and those on knee arthroplasty received the highest number of fundings. Publications regarding hip arthroplasty achieved the highest average citation rate. In contradistinction to the others, in North America most funding was provided by private agencies. Conclusion: Although Europe showed the highest total number of publications, authors and institutions, arthroplasty research from North America received greater scientific attention and financial support. Measured by citations, publications on hip arthroplasty attained higher scientific interest and studies on knee arthroplasty received higher economic affection.

Optimal drilling at femoral head-neck junction for treatment of the femoral head necrosis: Experimental and numerical evaluation.

BACKGROUND: Advanced core decompression (ACD) is a relative new technique for treatment of early stages of avascular femoral head necrosis. Although it is a promising treatment option, there is a need to modify this technique for achieving higher hip survival rates. An idea was to combine this technique with the lightbulb procedure in order to get a complete removal of the necrosis. This study aimed at evaluating the fracture risk of the femora treated by the combined Lightbulb-ACD technique as the basis for clinical application. METHODS: Subject-specific models were generated from CT scan data of five intact femora. Several treated models were then created from each intact bone and simulated during normal walking activity. Biomechanical testing was additionally performed on 12 pairs of cadaver femora to confirm the simulation results. FINDINGS: The finite element results revealed that the risk factor of the treated models with a 8 mm-drill increased, but was not significantly greater than that of their corresponding intact models. However, for the femur treated with a 10 mm-drill, the risk factor increased significantly. Fracture always initiated on the femoral neck, i.e. it was either subcapital or transcervical fracture. Our biomechanical testing results correlated well with the simulation data which confirmed the usefulness and effectiveness of the bone models. INTERPRETATION: The combined Lightbulb-ACD technique using a 10 mm drill increased the fracture risk of femur postoperatively. A drill of up to 8 mm at the anterior head-neck junction did not however lead to the weakening of the femur so that full load bearing may be possible.

Indications and possible limitations using medio-plantar plate systems in tarsometatarsal 1 fusions - A cadaveric study.

BACKGROUND: The tarsometatarsal 1 arthrodesis is an adequate treatment for moderate to severe hallux valgus deformity and instability of the first ray. Plantar plating arthrodesis has been shown to provide better mechanical stability and fewer postoperative complications than screw fixation or medial plating. The medio-plantar plate is a new plate design for Lapidus arthrodesis. It could combine the biomechanical advantages of the plantar plate and the anatomical overview of a medial plate. However, the implanted material can cause irritation of the tibialis anterior, which in some cases may require removal of the material. The purpose of this study was to examine the possibility of tendon irritation following medio-plantar first tarsometatarsal joint arthrodesis using cadaveric specimens. METHODS: The study involved the simulated surgical procedure of medio-plantar plate arthrodesis on 30 lower extremities. After the plates were fixed, a thorough examination of the feet was conducted to assess any tendon irritation and to determine a recommendation for placement of the medio-plantar plate based on the Olewnik classification. RESULTS: Irritation of the tibialis anterior tendon components with the medio-plantar plate depends mainly on the anatomic norm variant, classified according to Olewnik et al. A medio-plantar plate is particularly recommended in TA tendon Olewnik type 3 and type 5. The positioning of a medio-plantar plate in Olewnik type 1 and type 2 tendons depends on the anatomic fit of the medio-plantar plate and the bony configuration of the TMT 1 joint. A large portion of the TA tendon must be detached, so a different plate design may be preferred in these patients. CONCLUSIONS: TMT 1 arthrodesis with medio-plantar plating of the first tarsometatarsal joint should be performed considering the anatomic TA tendon variations. LEVEL OF EVIDENCE: Level V, Expert Opinion includes Case Reports and Technique Tips.

Subgroup analysis of scientific performance in the field of arthroplasty.

Introduction: Arthroplasty is the final treatment option for maintaining mobility and quality of life in many primary degenerative and (post-) traumatic joint diseases. Identification of research output and potential deficits for specific subspecialties may be an important measure to achieve long-term improvement of patient care in this field. Methods: Using specific search terms and Boolean operators, all studies published since 1945 to the subgroups of arthroplasty listed in the Web of Science Core Collection were included. All identified publications were analysed according to bibliometric standards, and comparative conclusions were drawn regarding the scientific merit of each subgroup. Results: Most publications investigated the subgroups of septic surgery and materials followed by approach, navigation, aseptic loosening, robotic and enhanced recovery after surgery (ERAS). In the last 5 years, research in the fields of robotic and ERAS achieved the highest relative increase in publications In contrast, research on aseptic loosening has continued to lose interest over the last 5 years. Publications on robotics and materials received the most funding on average while those on aseptic loosening received the least. Most publications originated from USA, Germany, and England, except for research on ERAS in which Denmark stood out. Relatively, publications on aseptic loosening received the most citations, whereas the absolute scientific interest was highest for the topic infection. Discussion: In this bibliometric subgroup analysis, the primary scientific outputs focused on septic complications and materials research in the field of arthroplasty. With decreasing publication output and the least financial support, intensification of research on aseptic loosening is urgently recommended.

Comparison of the Accuracy of 2D and 3D Templating for Revision Total Hip Replacement.

INTRODUCTION: Revision hip arthroplasty is a challenging surgical procedure, especially in cases of advanced acetabular bone loss. Accurate preoperative planning can prevent complications such as periprosthetic fractures or aseptic loosening. To date, the accuracy of three-dimensional (3D) versus two-dimensional (2D) templating has been evaluated only in primary hip and knee arthroplasty. METHODS: We retrospectively investigated the accuracy of 3D personalized planning of reinforcement cages (Burch Schneider) in 27 patients who underwent revision hip arthroplasty. Personalized 3D modeling and positioning of the reinforcement cages were performed using computed tomography (CT) of the pelvis of each patient and 3D templates of the implant. To evaluate accuracy, the sizes of the reinforcement cages planned in 2D and 3D were compared with the sizes of the finally implanted cages. Factors that may potentially influence planning accuracy such as gender and body mass index (BMI) were analyzed. RESULTS: There was a significant difference (p = 0.003) in the accuracy of correct size prediction between personalized 3D templating and 2D templating. Personalized 3D templating predicted the exact size of the reinforcement cage in 96.3% of the patients, while the exact size was predicted in only 55.6% by 2D templating. Regarding gender and BMI, no statistically significant differences in planning accuracy either for 2D or 3D templating were observed. CONCLUSION: Personalized 3D planning of revision hip arthroplasty using Burch Schneider reinforcement cages leads to greater accuracy in the prediction of the required size of implants than conventional 2D templating.

Endoscopically Assisted Percutaneous Harvesting of the Flexor Hallucis Tendon in Zone 2: An Anatomical Study.

BACKGROUND: Flexor hallucis longus (FHL) transfer is a well-established method for treating chronic Achilles tendon ruptures and tendinopathy. Harvesting of the FHL tendon in zone 2 results in greater length but is also associated with an increased risk of injury to the medial plantar nerve and requires an additional plantar incision. Because of the anatomic proximity of the FHL tendon to the tibial neurovascular bundle in zone 2, the purpose of this study was to investigate the risk of vascular or nerve injury with arthroscopic assisted percutaneous tenotomy in zone 2 of the FHL tendon. METHODS: Endoscopically assisted percutaneous FHL transfer was performed on 10 right lower extremities from 10 cadaveric human specimens. The FHL tendon lengths and the relationship between FHL tendon and the tibial neurovascular bundle at zone 2 was analyzed. RESULTS: We observed a complete transection of the medial plantar nerve in 1 case (10%). The mean length of the FHL tendon was 54.7 ± 9.5 mm and the mean distance from the distal stump of the FHL tendon to local neurovascular structures was 1.3 ± 0.7 mm. CONCLUSION: There is a risk of neurovascular injury after endoscopic FHL tenotomy in zone 2. The tenotomy site is within 2 mm of the local neurovascular structures in the majority of cases. The additional length gained from this technique is unlikely to be required for the majority of FHL tendon transfer procedures. If additional length is needed, we would recommend the use of intraoperative ultrasonography or a mini-open approach to minimize injury risk. LEVEL OF EVIDENCE: Level V, expert opinion.

Access to skipped polyene macrolides through ring-closing metathesis: total synthesis of the RNA polymerase inhibitor ripostatin B.

Rip-Roaring! A convergent total synthesis of antibiotic ripostatin B was developed. A key step in the synthesis is a metathesis reaction allowing for a ring closure to the labile doubly skipped triene macrolide.

[The importance of removing osteonecrosis during treatment of femoral head osteonecrosis]. / Stellenwert der Ausräumung bei der Behandlung von Femurkopfosteonekrosen.

Atraumatic femoral head necrosis (aFHN) in adults is estimated to be the leading cause of approximately 10% of all hip prosthesis implantations. Due to the relatively frequent occurrence of aFHN at a young age, the possibility of a joint-preserving intervention should be examined. This includes the classic "core decompression" and modifications based on it. There are different data on the success rates of this method. Reasons for treatment failure could include a lack of clearance of the necrosis zone. The clearance of the necrosis zone is taken into account by alternative surgical procedures for the treatment of aFHN. These are the "trap-door procedure", the "light-bulb procedure" and "advanced core decompression". The current state of knowledge on these procedures is reviewed in this keynote article. It is shown that the extensive excision of femoral head necrosis is of particular importance. None of the procedures mentioned can currently be recommended in preference over the others.

Hip joint mechanics in patients with osteonecrosis of the femoral head following treatment by advanced core decompression.

BACKGROUND: Osteonecrosis of the femoral head is a serious disease which, if left untreated, leads to destruction of the affected hip joint. For treatment of early stages of this disease, core decompression is the most common procedure. This study investigated the influence of the necrotic lesion and core decompression on the stress pattern in the hip joint using finite element analysis. METHODS: Subject-specific models were generated from CT scan data of 5 intact hips. For each intact hip, twelve affected hip models were created by imposing a necrotic lesion in the femoral head, and four treated models were then created from four affected ones with central lesion, respectively. Treated models were created by supposing that the defect zone and the drill canal were filled with a bone substitute. Totally 105 hip models from three groups (intact, affected and treated) were simulated during normal walking activity. FINDINGS: Necrotic lesion modified the stress distribution within the femoral head. Peak stress increased significantly up to 186% in mean in hips with a large lesion indicating an increased risk of femoral head collapse. Additionally, the presence of a medium to large necrosis altered significantly stress values (P < 0.05) and pattern in the articular cartilage. Our study revealed that advanced core decompression can recover normal cartilage stress values and pattern in treated joint. INTERPRETATION: The presence of a large lesion increased the risk of femoral head collapse. Advanced core decompression with bone grafts can restore normal cartilage mechanics in hip postoperatively.

Early posttraumatic stress symptoms and levels of distress in trauma patients treated in the resuscitation room: an exploratory study.

BACKGROUND: The aim of the present study was to investigate the incidence of psychological distress and posttraumatic stress symptoms in trauma patients who have been recruited from the resuscitation room. Further, we wanted to explore risk factors for posttraumatic stress symptoms, taking different accident types into account. METHODS: Our sample consisted of 45 patients who have been treated in the resuscitation room and were interviewed within the first ten days after treatment. Type of accident, third party fault, previous mental health problems and pretraumatic stress were examined. Patients were interviewed with respect to their currently felt distress regarding the accident. Posttraumatic stress symptoms were measured with the German version of the Impact of Event Scale. Injury severity was assessed by means of the Injury Severity Score. RESULTS: Our exploratory and cross-sectional project reveals that more severe injuries were associated with higher distress. However, posttraumatic stress symptoms were predicted by high distress and being involved in a car accident, but not by injury severity. CONCLUSIONS: We identified two potential risk factors for the development of posttraumatic stress in trauma patients recruited from the resuscitation room: Being involved in a car accident and high distress. TRIAL REGISTRATION: The project has been registered at the Study Center of Mental Disorders (SPE) at the University Medical Center Mainz (No: 92072014 ).

Doppler sonography enhances rtPA-induced fibrinolysis in an in vitro clot model of spontaneous intracerebral hemorrhages.

BACKGROUND: Transcranial Doppler (TCD) was shown to enhance intravascular fibrinolysis by rtPA in ischemic stroke. Studies revealed that catheter-based administration of rtPA induces lysis of intracerebral hemorrhages (ICH). However, it is unknown whether TCD would be suitable to enhance rtPA-induced fibrinolysis in patients with ICH. The aim of this study was to assess the potential of TCD to enhance rtPA-induced fibrinolysis in an in vitro clot system. METHODS: Reproducible human blood clots of 25 ml were incubated in a water bath at 37°C during treatments. They were weighed before and after 6 different treatments: (I) control (incubation only), (II) rtPA only, (III) one Doppler probe, (IV) two Doppler probes placed vis-à-vis, (V) one probe and rtPA and (VI) two probes and rtPA. To quantify lysis of the blood clots and attenuation of the Doppler through a temporal squama acoustic peak rarefaction pressure (APRP) was measured in the field of the probes. Temperature was assessed to evaluate possible side effects. RESULTS: Clot weight was reduced in all groups. The control group had the highest relative end weight of 70.2%±7.2% compared to all other groups (p<0,0001). Most efficient lysis was achieved using (VI) 2 probes and rtPA 36.3%±4.4% compared to (II, III, IV) (p<0.0001; p = 0.0002; p = 0.048). APRP was above lysis threshold (535.5±7.2 kPa) using 2 probes even through the temporal squama (731.6±32.5 kPa) (p = 0.0043). There was a maximal temperature elevation of 0.17±0.07°C using both probes. CONCLUSIONS: TCD significantly enhances rtPA-induced lysis of blood clots, and the effect is amplified by using multiple probes. Our results indicate that bitemporal TCD insonation of hematomas could be a new and safe approach to enhance fibrinolysis of ICH´s treated with intralesional catheter and rtPA.

Correction: Combination of ultrasound and rtPA enhances fibrinolysis in an In Vitro clot system.

[This corrects the article DOI: 10.1371/journal.pone.0188131.].

Combination of ultrasound and rtPA enhances fibrinolysis in an In Vitro clot system.

BACKGROUND: Catheter-based lysis with recombinant tissue plasminogen activator (rtPA) is a well-established therapy for spontaneous intracerebral hemorrhage (ICH). The effectiveness of this therapy can be increased with ultrasound, but the optimal conditions are not yet clearly established. Using a novel in vitro system of blood clots previously developed by our group, we investigated various parameters of intralesional sonothrombolysis using an endosonography catheter in combination with rtPA. METHODS: Standardized human blood clots were equipped with a drainage catheter and weighed before and after 4 treatments: control (drainage only), rtPA only, ultrasound only and the combination of rtPA+ultrasound. The effectiveness of ultrasound was further analysed in terms of optimal frequency, duration and distance to the probe. Temperature and acoustic peak rarefaction pressure (APRP) were assessed to analyse potential adverse effects and quantify lysis. Histo-morphological analysis of the treated clots was performed by H&E staining and confocal laser scanning microscopy using fluorescent fibrinogen. RESULTS: The combined treatment rtPA+ultrasound achieved the highest lysis rates with a relative weight of 30.3%±5.5% (p≤0.0001) compared to all other groups. Similar results were observed when treating aged clots. Confocal fluorescent microscopy of the treated clots revealed a rarefied fibrin mesh without cavitations. No relevant temperature increase occurred (0.53±0.75°C). The optimal insonation treatment time was 1 hour. APRP measurements showed a lysis threshold of 515.5±113.4 kPa. Application of 10 MHz achieved optimal lysis and lysis radius, while simultaneously proving to be the best frequency for morphologic imaging of the clot and surrounding tissue. CONCLUSIONS: These promising data provide the basis for an individualized minimal invasive ICH therapy by rtPA and sonothrombolysis independent of ICH age.

Transforming terpene feedstock into polyketide architecture.

The Cu-catalyzed synthesis of skipped 1,4-dienes from allylic acetates and vinyl-Grignard reagents is key to bidirectional modifications of acyclic terpene acetates. As a result, trisubstituted double bond containing subunits can be readily transferred into complex polyketides from inexpensive bulk terpenes.

Transforming terpene-derived aldehydes into 1,2-epoxides via asymmetric α-chlorination: subsequent epoxide opening with carbon nucleophiles.

Merging Jørgensen's and MacMillan's organocatalytic aldehyde chlorinations enables the synthesis of chiral vinylcyclopropanes and (-)-cis-aerangis lactone via terpene-derived 1,2-epoxides.