AZU1: a new promising marker for infection in orthopedic and trauma patients?

Early and reliable detection of infection is vital for successful treatment. Serum markers such as C-reactive protein (CRP) and procalcitonin (PCT) are known to increase with a time lag. Azurocidin 1 (AZU1) has emerged as a promising marker for septic patients, but its diagnostic value in orthopedic and trauma patients remains unexplored. Between July 2020 and August 2023, all patients necessitating inpatient treatment for periprosthetic joint infection (PJI), peri-implant infection (II), soft tissue infection, chronic osteomyelitis, septic arthrodesis, bone non-union with and without infection were enrolled. Patients undergoing elective total joint arthroplasty (TJA) served as the control group. Blood samples were collected and analyzed for CRP, white blood cell count (WBC), PCT, and AZU1. Based on the inclusion and exclusion criteria 222 patients were included in the study (trauma = 38, soft tissue infection = 75, TJA = 33, PJI/II = 39, others = 37). While sensitivity and specificity were comparably high for AZU1 (0.734/0.833), CRP and PCT had higher specificity (0.542/1 and 0.431/1, respectively), and WBC a slightly higher sensitivity (0.814/0.455) for septic conditions. Taken together, the area under the curve (AUC) showed the highest accuracy for AZU1 (0.790), followed by CRP (0.776), WBC (0.641), and PCT (0.656). The Youden-Index was 0.57 for AZU1, 0.54 for CRP, 0.27 for WBC, and 0.43 for PCT. Elevated AZU1 levels effectively distinguished patients with a healthy condition from those suffering from infection. However, there is evidence suggesting that trauma may influence the release of AZU1. Additional research is needed to validate the diagnostic value of this new biomarker and further explore its potential clinical applications.

Leukocyte esterase and alpha-defensin in periprosthetic joint infection: predictive quality and correlation in a prospective study.

PURPOSE: Periprosthetic joint infection (PJI) is a rare but serious complication of total joint arthroplasty (TJA). An accurate diagnosis of PJI preoperatively does not exist. Alpha-defensin (AD) is a proven and common indicator. The diagnostic marker of leukocyte esterase (LE) promises some advantages: feasibility, availability, and fast result reporting. The aim of this study was the evaluation of the predictive quality and correlation between both diagnostic tools in the diagnosis of PJI. METHODS: A prospective study was conducted between April 2018 and August 2022. All patients with suspicion of PJI on hip and knee joint were included and underwent a routine and standardized joint punction. For laboratory diagnostics of AD, the synovial liquid was analyzed by ELISA. The sample was additionally applied to a LE test strip (Combur 10 Test, Roche Diagnostics, Mannheim, Germany). RESULTS: A total of 249 patients were examined (mean age 67.12 ± 11.89; gender distribution man/woman 139 (55.8%)/110(44.2%), hip/knee 71(28.5%)/178 (71.5%). According to EBJIS criteria, PJI was diagnosed in 54 (21.7%) patients. AD showed excellent results with an AUC of 0.930 (sensitivity/specificity 0.870/0.990). LE yielded very good results with an AUC of 0.820 (sensitivity/specificity 0.722/0.918). Both parameters showed a strong positive correlation. CONCLUSION: LE is a rapidly available alternative in PJI diagnostics. The simultaneous determination of both markers may enhance diagnostic reliability. A routine usage may shorten the time from diagnosis to treatment of PJI.

CCR4 Blockade Diminishes Intratumoral Macrophage Recruitment and Augments Survival of Syngeneic Pancreatic Cancer-Bearing Mice.

Pancreatic cancer is known for its tumor microenvironment (TME), which is rich in stromal and immune cells supporting cancer growth and therapy resistance. In particular, tumor-associated macrophages (TAMs) are known for their angiogenesis- and metastasis-promoting properties, which lead to the failure of conventional therapies for pancreatic cancer. Hence, treatment options targeting TAMs are needed. The C-C chemokine receptor type 4 (CCR4) is critical for immune cell recruitment into the TME, and in this paper we explore the effects of its genetic or immunotherapeutic blockade in pancreatic-cancer-bearing mice. Murine PDA6606 pancreatic cancer cells and murine peritoneal macrophages were used for in vitro migration assays. In vivo, a syngeneic, orthotropic pancreatic cancer model was established. Tumor growth and survival were monitored under prophylactic and therapeutic application of a CCR4 antagonist (AF-399/420/18025) in wildtype (CCR4wt) and CCR4-knockout (CCR4-/-) mice. Immune infiltration was monitored in tumor tissue sections and via flow cytometry of lysed tumors. PDA6606 cells induced less migration in CCR4-/- than in CCR4wt macrophages in vitro. Pancreatic TAM infiltration was higher, and survival was reduced in CCR4wt mice compared to CCR4-/- mice. Antagonizing CCR4 in wildtype mice revealed similar results as in CCR4-/- mice without antagonization. Prophylactic CCR4 antagonist application in wildtype mice was more efficient than therapeutic antagonization. CCR4 seems to be critically involved in TAM generation and tumor progression in pancreatic cancer. CCR4 blockade may help prolong the relapse-free period after curative surgery in pancreatic cancer and improve prognosis.

Computer-Based Mechanobiological Fracture Healing Model Predicts Non-Union of Surgically Treated Diaphyseal Femur Fractures.

As non-unions are still common, a predictive assessment of healing complications could enable immediate intervention before negative impacts for the patient occur. The aim of this pilot study was to predict consolidation with the help of a numerical simulation model. A total of 32 simulations of patients with closed diaphyseal femoral shaft fractures treated by intramedullary nailing (PFNA long, FRN, LFN, and DePuy Synthes) were performed by creating 3D volume models based on biplanar postoperative radiographs. An established fracture healing model, which describes the changes in tissue distribution at the fracture site, was used to predict the individual healing process based on the surgical treatment performed and full weight bearing. The assumed consolidation as well as the bridging dates were retrospectively correlated with the clinical and radiological healing processes. The simulation correctly predicted 23 uncomplicated healing fractures. Three patients showed healing potential according to the simulation, but clinically turned out to be non-unions. Four out of six non-unions were correctly detected as non-unions by the simulation, and two simulations were wrongfully diagnosed as non-unions. Further adjustments of the simulation algorithm for human fracture healing and a larger cohort are necessary. However, these first results show a promising approach towards an individualized prognosis of fracture healing based on biomechanical factors.

The modified 5-item frailty index determines the length of hospital stay and accompanies with mortality rate in patients with bone and implant-associated infections after trauma and orthopedic surgery.

BACKGROUND: Bone and implant-associated infections are severe complications after trauma and orthopedic surgery. The modified 5-item frailty index (mFI-5) is an easily applicable score to predict adverse outcome after surgery. The current literature regarding mFI-5 is focused on a period of 30-days postoperative. PURPOSE: This study aims to assess the impact of frailty in orthopedic trauma patients with bone and implant-associated infections. mFI-5 was calculated from a database, which prospectively collects data about factors potentially correlated with peri- and postoperative complications since 2014. METHODS: In a level I trauma center a total of 345 patients with surgical site infections were enrolled in this study. Hereof, patients with fracture-related infections after osteosynthesis, periprosthetic joint infections of the hip and knee and post-operative osteomyelitis were included. Extensive medical baseline examination was performed in 2013/14, a three-year follow-up was organized as a telephone interview. The mFI-5 score was calculated based on the 5 factor-principle as established by Subramaniam. The nutritional status was assessed using the Nutritional Risk Screening (NRS-2002). RESULTS: 130 patients were included, whereof seven had died, resulting in 123 patients. A grouping of our patients was performed in mFI-5 = 0 (n = 46; 36,4%), mFI-5 = 1 (n = 41; 33,3%) or mFI-5 ≥ 2 (n = 36; 29,3%). Sex distribution showed 69,1% male and 30,9% female patients. Frailty did neither impact on the re-admission (p = 0,433) nor the reoperation (p = 0,327) rate in our cohort. The mortality risk nearly doubled (1,7 times) in frail patients, but did not reach significance. In hospital stay was prolonged due to frailty (12,1 ± 11,8; p = 0,004) compared to those with a mFI-5 = 0 (5,9 ± 5,1) or mFI-5 = 1 (6,9 ± 5,9). Frailty goes along with a risk of malnutrition and increases with age. CONCLUSION: The modified 5-item frailty index is not a suitable screening tool for predicting revision rate, re-admission rate, and mortality in our orthopedic trauma patient population with bone and implant-associated infections. Nevertheless, frailty is associated with an increased risk of malnutrition and increases with age.

[E-learning via webinars in orthopedics and trauma surgery : Increase in supply and demand during the COVID-19 pandemic]. / E-Learning per Webinar in der Orthopädie und Unfallchirurgie : Intensiviertes Angebot und gesteigerte Nachfrage in der COVID-19-Pandemie.

BACKGROUND: Contact teaching was prohibited by nationwide lockdowns during the COVID-19 pandemic. The scientific literature contains no concrete figures concerning e­learning via webinars in the subject of orthopedics and trauma surgery in the context of the COVID-19 pandemic. OBJECTIVE: This research study was established to collect facts and figures about webinars as a representative part of e­learning in the subject of orthopedics and trauma surgery in the context of the COVID-19 pandemic. MATERIAL AND METHODS: German-speaking non-commercial and edited webinars, produced by suppliers from Germany were identified using common search engines. Structured interviews with questionnaires about provider, format, and number of participants in the webinars over time, were offered to the operating companies. RESULTS: The study included four suppliers of webinars (AO Online Campus, BVOU Study Club, OU TO GO and WebDGU). There was approval of all operating companies to participate in the interviews and to disclose facts and figures about their webinars. All suppliers showed an increased supply and demand for webinars during the COVID-19 pandemic. DISCUSSION: OU TO GO and BVOU Study Club already offered webinars prior to the COVID-19 pandemic. AO online Campus was designed in addition to the existing portfolio. The supply of WebDGU was newly established. Limitations of this study are the exclusion of commercial suppliers, non-German operating companies and all other types of e­learning except webinars. The increased supply and demand for webinars during the COVID-19 pandemic gives hope for further improvement of e­learning in the subject of orthopedics and trauma surgery.

Evaluation of modified and newly applied patella height indices in primary total knee arthroplasty.

OBJECTIVE: The aim of this radiological study was to compare several relevant modified and newly applied patella height indices (PHI) in navigated primary total knee arthroplasty (TKA) to determine intra- and interobserver reliability in order to give a recommendation for clinical application in measuring patella height (PH) in primary TKA. MATERIALS AND METHODS: A retrospective data analysis assessing different PHI (modified Insall-Salvati index (mISI), Caton-Deschamps index (mCDI), Blackburne-Peel index (mBPI), Plateau-Patella Angle (mPPA); Miura-Kawaramura index (MKI), Knee-Triangular index (KTI)) on lateral knee radiographs was performed by two blinded observers using the same software three months pre- and postoperatively. Concordance correlation coefficient and Pearson's correlation respectively were determined for intra- and interobserver rating as well as a categorization according to Landis and Koch and Cohen. RESULTS: A total of 337/291 patients of a 5-year period could be analyzed pre-/postoperatively. Excellent postoperative interrater results according to the categorization of Landis and Koch were achieved for the mBPI (Pearson 0.98) > mPPA (0.90) > KTI (0.86), good results for the MKI (0.79) and the mCDI (0.69), and moderate results for the mISI (0.52) with a predominantly strong Cohen correlation in almost all cases. Preoperatively, the mBPI and the KTI were the best interrated PHI. No PH changes could be found postoperatively for the mISI, KTI, MKI, and mPPA. CONCLUSION: The mBPI, the mPPA, and the KTI can be recommended for PH assessment in TKA. The mPPA might be the easiest one to use in a daily clinical set-up.

Deep Learning in the Detection of Rare Fractures - Development of a "Deep Learning Convolutional Network" Model for Detecting Acetabular Fractures. / Deep Learning in der Erkennung seltener Frakturen ­ Entwicklung eines "Deep Convolutional Neural Network" (DCNN) am Beispiel der Azetabulumfraktur.

BACKGROUND: Fracture detection by artificial intelligence and especially Deep Convolutional Neural Networks (DCNN) is a topic of growing interest in current orthopaedic and radiological research. As learning a DCNN usually needs a large amount of training data, mostly frequent fractures as well as conventional X-ray are used. Therefore, less common fractures like acetabular fractures (AF) are underrepresented in the literature. The aim of this pilot study was to establish a DCNN for detection of AF using computer tomography (CT) scans. METHODS: Patients with an acetabular fracture were identified from the monocentric consecutive pelvic injury registry at the BG Trauma Center XXX from 01/2003 - 12/2019. All patients with unilateral AF and CT scans available in DICOM-format were included for further processing. All datasets were automatically anonymised and digitally post-processed. Extraction of the relevant region of interests was performed and the technique of data augmentation (DA) was implemented to artificially increase the number of training samples. A DCNN based on Med3D was used for autonomous fracture detection, using global average pooling (GAP) to reduce overfitting. RESULTS: From a total of 2,340 patients with a pelvic fracture, 654 patients suffered from an AF. After screening and post-processing of the datasets, a total of 159 datasets were enrolled for training of the algorithm. A random assignment into training datasets (80%) and test datasets (20%) was performed. The technique of bone area extraction, DA and GAP increased the accuracy of fracture detection from 58.8% (native DCNN) up to an accuracy of 82.8% despite the low number of datasets. CONCLUSION: The accuracy of fracture detection of our trained DCNN is comparable to published values despite the low number of training datasets. The techniques of bone extraction, DA and GAP are useful for increasing the detection rates of rare fractures by a DCNN. Based on the used DCNN in combination with the described techniques from this pilot study, the possibility of an automatic fracture classification of AF is under investigation in a multicentre study.

Automated Artificial Intelligence-Based Assessment of Lower Limb Alignment Validated on Weight-Bearing Pre- and Postoperative Full-Leg Radiographs.

The assessment of the knee alignment using standing weight-bearing full-leg radiographs (FLR) is a standardized method. Determining the load-bearing axis of the leg requires time-consuming manual measurements. The aim of this study is to develop and validate a novel algorithm based on artificial intelligence (AI) for the automated assessment of lower limb alignment. In the first stage, a customized mask-RCNN model was trained to automatically detect and segment anatomical structures and implants in FLR. In the second stage, four region-specific neural network models (adaptations of UNet) were trained to automatically place anatomical landmarks. In the final stage, this information was used to automatically determine five key lower limb alignment angles. For the validation dataset, weight-bearing, antero-posterior FLR were captured preoperatively and 3 months postoperatively. Preoperative images were measured by the operating orthopedic surgeon and an independent physician. Postoperative images were measured by the second rater only. The final validation dataset consisted of 95 preoperative and 105 postoperative FLR. The detection rate for the different angles ranged between 92.4% and 98.9%. Human vs. human inter-(ICCs: 0.85−0.99) and intra-rater (ICCs: 0.95−1.0) reliability analysis achieved significant agreement. The ICC-values of human vs. AI inter-rater reliability analysis ranged between 0.8 and 1.0 preoperatively and between 0.83 and 0.99 postoperatively (all p < 0.001). An independent and external validation of the proposed algorithm on pre- and postoperative FLR, with excellent reliability for human measurements, could be demonstrated. Hence, the algorithm might allow for the objective and time saving analysis of large datasets and support physicians in daily routine.

Patella-height analysis and correlation with clinical outcome after primary total knee arthroplasty.

BACKGROUND: It is the aim of this study to conceptualize a scheme for patellar-height analysis suitable for knees without and with implanted endoprosthesis. Furthermore, patellar-height and change of patellar-height by total-knee-arthroplasty (TKA) should be studied and correlated with clinical outcomes. We hypothesize that not only True-Patella-Infera (TPI) but also Pseudo-Patella-Infera (PPI) might be correlated with elevated anterior-knee-pain and reduced range-of-motion. METHODS: Several patellar-height indices were measured by three independent raters in two passes. Indices were analyzed and intra- and interobserver agreements were determined. For radiographic and clinical evaluation of 92 knee arthroplasties, the Insall-Salvati Index (ISI) and the Caton-Deschamps Index (CDI) were used to determine patellar-height and especially the amounts of TPI and PPI. Patellar-height was correlated with clinical outcome parameters: pain, ROM, Oxford Knee Score, Knee Society Score, Kujala Score, SF-36, Tegner and Lysholm. RESULTS: All used patellar-height indices demonstrated good intra- and interobserver agreement. Low preoperative ROM was correlated with low postoperative ROM after primary TKA. Postoperatively, 2.2% of the patients had a TPI and 9.8% had a PPI. Patella infera was not correlated with reduced subjective or objective clinical outcome parameters. CONCLUSIONS: Preoperative ROM is a good predictor of postoperative ROM after primary TKA. Patellar-height analysis can be sufficiently performed using the ISI and the CDI, respectively the derived CDI (dCDI) in cases with implanted endoprosthesis. As an alternative to the CDI/dCDI, the BPI/mBPI can be used. There seems to be a certain threshold of acceptable patellar-height reduction, in which clinical outcome is not deteriorated.

Reliability of a Caton-Deschamps-derived patella height index for knee arthroplasty.

PURPOSE: The original Caton-Deschamps index (oCDI) detects functional patella height. It cannot be used in knees with an implanted endoprosthesis. The "modified Caton-Deschamps index" (mCDI) for knee arthroplasty can miss pseudo-patella-infera (PPI), which is common after TKA. A derivate of the oCDI could be a simple analogue to the index published in 1982 using a modified tibial reference point at the anterior proximal point of the inlay, which can indirectly be located on the lateral knee radiograph. It was the aim of this study to determine the intra- and inter-rater agreement of a derived Caton-Deschamps index (dCDI) for knee arthroplasty. We hypothesized that the derived Caton-Deschamps index (dCDI) is a reliable radiological measure for patella height in knee arthroplasty. METHODS: Several patella height indices were measured by three independent raters in two passes. The second pass was performed after 6 weeks in random order. Intra- and inter-observer agreements were determined and analyzed using the intraclass correlation coefficient (ICC). For radiographic evaluation, digital lateral radiographs of 150 knees before and after primary TKA were used. RESULTS: We found high interrater reliability for all analyzed indices. We found the highest agreements for the ISI preop (ICC = 0.914) and postop (ICC = 0.920), respectively. We also found very good intra-rater reliability for the CDI (ICCpreop = 0.954), dCDI (ICCpostop = 0.945), ISI (ICCpreop = 0.960; ICCpostop=0.940) and BPI (ICCpreop = 0.969; ICCpostop = 0.955). Fourteen cases (9.3%) with insignificant PPI were found. CONCLUSION: The derived Caton-Deschamps index (dCDI) can easily be used in knee arthroplasty and demonstrated high intra- and interrater agreement, which was similar to other commonly used and established patella height indices.

[Potential of digitalization in undergraduate and postgraduate medical education and training in orthopedics and trauma surgery]. / Potenzial der Digitalisierung in Aus­, Fort- und Weiterbildung in Orthopädie und Unfallchirurgie.

INTRODUCTION: In its digital agenda the German Federal Government pursues the ambitious objective to facilitate digital competence and perform research into digital learning and teaching processes. Considerable investments are to be concentrated into the future viability of education, academic research and digitalization. As far as academic teaching and further education are concerned, not only in the field of orthopedics and trauma surgery, three aspects can be identified: digital organization, digital competence and digital tools. DIGITAL APPLICATIONS: New formats, such as the elective subject digital health of the Charité in Berlin, enable digital competences to be mediated in a multimodal and interdisciplinary way. With the help of a newly developed app the University of Essen provides teachers and students with mobile and flexible access to information on lectures in terms of content and organization. Especially because of transparency, high legal compliance and predictability, the digital logbook for the resident training program promises a real innovation for trainees in the further training reformation. Augmented and virtual reality play a crucial role in the imparting of practical skills and interconnect high-tech with classical craftsmanship. Digital training course formats have significantly gained in importance and are meanwhile well-established tools for efficient advanced medical training. OUTLOOK: If orthopedic and trauma surgeons take an active role in the process of digitalization of teaching, they can take part in decisions, adequately prepare the colleagues of tomorrow, optimize patient care, encourage innovations and altogether improve the discipline even more.

Closed Suction Drainage after Primary Total Knee Arthroplasty: A Prospective Randomized Trial.

The discussion as to whether or not to use closed suction drainage (CSD) after total knee arthroplasty (TKA) is still ongoing. A multitude of surgical techniques makes comparison between studies difficult. The aim of the present study was to investigate the benefit of CSD versus nondrainage following primary TKA when operating after exsanguination (by means of a rubber Esmarch bandage) with a tourniquet and without any form of hemostasis. A prospective randomized trial was performed with a homogeneous sample of 36 patients with strict inclusion and exclusion criteria. Patients were evaluated preoperatively, on a daily basis during their hospital stay, and at 6 weeks, 3 months, 6 months, and 1 year postoperatively. The use of CSD led to a significantly stronger drop in hemoglobin levels by approximately 1 g/dL (p = 0.012). Knee circumference, wound secretion, wound healing, and postoperative range of motion did not show significant differences. All discharge criteria were met in both groups by day 9. Interestingly, patients without CSD reported higher pain levels during the entire postoperative inpatient stay and also at the 6-week follow-up (p = 0.012). These differences could not be observed in longer follow-up. The use of CSD after primary TKA in this study did not lead to indispensable advantages but did lead to increased postoperative blood loss. When evaluating the advantages and disadvantages of the use of CSD after TKA from the data in the literature, special attention must be paid to the operating technique, as it has a strong impact on the results obtained.