Ceramic Heads With 12/14 Titanium Sleeves Used on Manufacturer-Non-Compatible Retained Femoral Components Do Not Lead to Implant Failure in Revision Hip Arthroplasty.

BACKGROUND: Ceramic femoral heads with titanium sleeves are commonly used in revision total hip arthroplasty (rTHA). Companies advise against combination with a retained femoral component from another manufacturer. However, no data are available. The aim of this study was to evaluate and compare the implant failure and revision rates of ceramic heads with a 12/14 titanium sleeve used on manufacturer-compatible versus non-compatible retained femoral components. METHODS: A retrospective single-center cohort analysis was performed using a prospectively maintained institutional arthroplasty registry. We identified 439 patients who received a titanium 12/14 ceramic head during rTHA between January 1st, 2007 and December 31st, 2022. There were 229 manufacturer-compatible and 210 manufacturer-non-compatible retained femoral stems, according to the company's official product compatibility list. Implant failure and re-revision rates were evaluated. RESULTS: After a median follow-up of 6.6 years (IQR (Interquartile-range): 4.5 to 9.3), there was no significant difference (P = 0.770) in the re-revision rate between the manufacturer-compatible group (17.0%) and the non-compatible group (18.1%). Revision-free survival after rTHA was 81.2% in the manufacturer-compatible group and 78.9% in the manufacturer-non-compatible group after 15 years (P = 0.653). Most re-revisions occurred in the first year after rTHA, with 29 of 229 (12.7%) in the manufacturer-compatible group and 24 of 210 (11.4%) in the manufacturer-non-compatible group (P = 0.705). We observed only one implant failure in the manufacturer-non-compatible group, but this was not related to a mismatch problem. CONCLUSION: Although legal uncertainties remain, this study showed no increased risk of implant failure or revision rates when a ceramic femoral head with a 12/14 titanium sleeve was used on a non-compatible femoral stem from a manufacturer.

The Value of Preoperative Ultrasound-Determined Fluid Film and Joint Aspiration in Revision Hip Arthroplasty.

BACKGROUND: Data regarding the diagnostic value of ultrasound (US)-determined fluid film and joint aspiration prior to revision total hip arthroplasty for suspected periprosthetic joint infections (PJIs) are limited. This study aimed to analyze the value of US-determined fluid film, characterized the preoperative and intraoperative microbiological spectrum and resistance patterns, and compared the concordance between preoperative synovial fluid and intraoperative culture results. METHODS: We analyzed 366 US examinations from 324 patients prior to revision total hip arthroplasty. Selected cases were grouped into clearly infected, noninfected, and inconclusive cohorts, according to the International Consensus Meeting 2018 Criteria. For US-determined fluid film <1 mm, no aspiration was performed based on our institutional protocol. Patients were grouped into no aspiration (144 of 366; [39.3%]), dry tap (21 of 366; [5.7%]), and a successful tap (201 of 366; [54.9%]). The microbiological spectrum and antibiograms were compared between preoperative and intraoperative results. RESULTS: The absence of US-determined fluid film showed no correlation with the presence of a hip PJI. Overall, 31.9% cases of the no-aspiration group had a PJI. In total, 13.5% discrepancies were found between successful taps and intraoperative cultures. The most prevalent microorganisms in preoperative synovial fluid were Staphylococcus epidermidis and Staphylococcus aureus (20.8%), while intraoperatively S. epidermidis (26.3%) and Cutibacterium acnes (14.5%) were leading. Additional microorganisms were identified in 32.5% of intraoperative cultures. There were no differences between resistance patterns of preoperative and intraoperative concordant microorganisms. CONCLUSIONS: Absence of US-determined fluid film cannot rule out the presence of a hip PJI. Combined microbiological results from hip US aspirations and subsequent surgical procedures are crucial to design an effective treatment for suspected hip PJI.

High Demand for Psychological Support in Patients Who Have Periprosthetic Hip and Knee Joint Infections: An Analysis of 13,976 Patients.

BACKGROUND: There is only sparse knowledge on the psychological burden of patients who have periprosthetic joint infections. The aim of our study was to assess the need for psychological support following total joint arthroplasty of the hip and knee. A special focus was set on patients who had aseptic and septic complications. METHODS: A total of 13,976 patients who underwent total hip (n = 6,926) or total knee arthroplasty (n = 7,050) between January 1, 2012 and December 31, 2019 at a single institution were retrospectively evaluated for the postoperative need for a psychological consultation. Data were collected on age, sex, type of surgery, and indications for revision procedures. The need for a psychological consultation was assessed during the daily postoperative visits, which were further coordinated by 2 institutional psychologists. RESULTS: The average age was 68 years (range, 12 to 100), and there were 63.5% women. The overall rate of psychological consultations was 1.7%. Patients who had a septic indication for revision surgery had an 18.7-fold higher rate of postoperative psychological consultations compared to patients following primary surgery and a 5.4-fold higher rate compared to patients who had an aseptic indication. In detail, this rate was 1.0% in the primary subgroup, compared to 7.7% following revision arthroplasty (P < .001). In the revision subgroup, the rate was 17.9% for septic and 3.3% for aseptic revision arthroplasty cases (P < .001). Postoperative psychological consultations were twice as frequent in women (2.1%) compared to men (1.0%), P < .001. CONCLUSIONS: The present study raises awareness of the markedly high psychological burden in revision arthroplasty cases, in the view of the high estimated number of unknown cases. There is a significant correlation between periprosthetic joint infectionsand the postoperative need for a psychological consultation, with women being at an even higher risk. Health care providers should aim at offering psychological support for patients who have a septic complication, with affected patients being at risk for psychological stress. LEVEL OF EVIDENCE: IV.

Fully automated assessment of the knee alignment on long leg radiographs following corrective knee osteotomies in patients with valgus or varus deformities.

INTRODUCTION: The assessment of the knee alignment on long leg radiographs (LLR) postoperative to corrective knee osteotomies (CKOs) is highly dependent on the reader's expertise. Artificial Intelligence (AI) algorithms may help automate and standardise this process. The study aimed to analyse the reliability of an AI-algorithm for the evaluation of LLRs following CKOs. MATERIALS AND METHODS: In this study, we analysed a validation cohort of 110 postoperative LLRs from 102 patients. All patients underwent CKO, including distal femoral (DFO), high tibial (HTO) and bilevel osteotomies. The agreement between manual measurements and the AI-algorithm was assessed for the mechanical axis deviation (MAD), hip knee ankle angle (HKA), anatomical-mechanical-axis-angle (AMA), joint line convergence angle (JLCA), mechanical lateral proximal femur angle (mLPFA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibia angle (mMPTA) and mechanical lateral distal tibia angle (mLDTA), using the intra-class-correlation (ICC) coefficient between the readers, each reader and the AI and the mean of the manual reads and the AI-algorithm and Bland-Altman Plots between the manual reads and the AI software for the MAD, HKA, mLDFA and mMPTA. RESULTS: In the validation cohort, the AI software showed excellent agreement with the manual reads (ICC: 0.81-0.99). The agreement between the readers (Inter-rater) showed excellent correlations (ICC: 0.95-0. The mean difference in the DFO group for the MAD, HKA, mLDFA and mMPTA were 0.50 mm, - 0.12°, 0.55° and 0.15°. In the HTO group the mean difference for the MAD, HKA, mLDFA and mMPTA were 0.36 mm, - 0.17°, 0.57° and 0.08°, respectively. Reliable outputs were generated in 95.4% of the validation cohort. CONCLUSION:  he application of AI-algorithms for the assessment of lower limb alignment on LLRs following CKOs shows reliable and accurate results. LEVEL OF EVIDENCE: Diagnostic Level III.

Alpha-defensin as a diagnostic tool in revision total knee arthroplasties with unexpected positive intraoperative cultures and unexpected culture negative intraoperative cultures.

PURPOSE: Unexpected-positive-intraoperative-cultures (UPIC) are common in presumed aseptic revision-total-knee-arthroplasties (rTKA). However, the clinical significance is not entirely clear. In contrast, in some presumably septic rTKA, identification of an underlying pathogen was not possible, so-called unexpected-negative-intraoperative-cultures (UNIC). The purpose of this study was to evaluate the potential use of synovial alpha-defensin (AD) levels in these patients. METHODS: Synovial AD levels from 143 rTKAs were evaluated retrospectively from our prospectively maintained institutional periprostetic joint infection (PJI) biobank and database. The 2018-International Consensus Meeting (ICM) criteria was used to define the study groups. Samples from UPICs with a minimum of one positive intraoperative culture (ICM 2- ≥ 6) (n = 20) and UNIC's (ICM ≥ 6) (n = 14) were compared to 34 septic culture-positive samples (ICM ≥ 6) and 75 aseptic culture-negative (ICM 0-1). Moreover, AD-lateral-flow-assay (ADLF) and an enzyme-linked-immunosorbent-assay (ELISA) in detecting the presence of AD in native and centrifuged synovial fluid specimens was performed. Concentration of AD determined by ELISA and ADLF methods, as well as microbiological, and histopathological results, serum and synovial parameters along with demographic factors were analysed. RESULTS: AD was positive in 31/34 (91.2%) samples from the septic culture-positive group and in 14/14 (100%) samples in the UNIC group. All UPIC samples showed a negative AD result. Positive AD samples were highly associated with culture positive and histopathological results (p < 0.001). No high-virulent microorganisms (0/20) were present in the UPIC group, compared to infected-group (19/34; 55.9%). High virulent microorganisms showed a positive AD result in 89.5% (17/19) of the cases. Methicillin resistant Staphylococcus epidermis (MRSE) infections had significantly higher AD levels than with methicillin susceptible S. epidermdis (MSSE) (p = 0.003). ELISA and ADLF tests were positive with centrifuged (8/8) and native (8/8) synovial fluid. CONCLUSION: AD showed a solid diagnostic performance in infected and non-infected revisions, and it provided an additional value in the diagnosis of UPIC and UNIC associated to rTKAs. Pathogen virulence as well as antibiotic resistance pattern may have an effect on AD levels. Centrifugation of synovial fluid had no influence on ADLF results.

Gender-specific distribution of knee morphology according to CPAK and functional phenotype classification: analysis of 8739 osteoarthritic knees prior to total knee arthroplasty using artificial intelligence.

PURPOSE: Osteoarthritis of the knee is commonly associated with malalignment of the lower limb. Recent classifications, as the Coronal Plane Alignment of the Knee (CPAK) and Functional Phenotype classification, describe the bony knee morphology in addition to the overall limb alignment. Data on distribution of these classifications is not sufficient in large populations. The aim of this study was to analyse the preoperative knee morphology with regard to the aforementioned classifications in long leg radiographs prior to total knee arthroplasty surgery using Artificial Intelligence. METHODS: The cohort comprised 8739 preoperative long leg radiographs of 7456 patients of all total knee arthroplasty surgeries between 2009 and 2021 from our institutional database. The automated measurements were performed with the validated Artificial Intelligence software LAMA (ImageBiopsy Lab, Vienna) and included standardized axes and angles [hip-knee-ankle angle (HKA), mechanical lateral distal femur angle (mLDFA), mechanical medial proximal tibia angle (mMPTA), mechanical axis deviation (MAD), anatomic mechanic axis deviation (AMA) and joint line convergence angle (JLCA)]. CPAK and functional phenotype classifications were performed and all measurements were analysed for gender, age, and body mass index (BMI) within these subgroups. RESULTS: Varus alignment was more common in men (m: 2008, 68.5%; f: 2953, 50.8%) while neutral (m: 578, 19.7%; f: 1357, 23.4%) and valgus (m: 345, 11.8%; f: 1498, 25.8%) alignment was more common in women. The most common morphotypes according to CPAK classification were CPAK Type I (2454; 28.1%), Type II (2383; 27.3%), and Type III (1830; 20.9%). An apex proximal joint line (CPAK Type VII, VIII and IX) was only found in 1.3% of all cases (n = 121). In men, CPAK Type I (1136; 38.8%) and CPAK Type II (799; 27.3%) were the most common types and women were spread more equally between CPAK Type I (1318; 22.7%), Type II (1584; 27.3%) and Type III (1494; 25.7%) (p < 0.001). The most common combination of femur and tibia types was NEUmLDFA0°,NEUmMPTA0° (m: 514, 17.5%; f: 1004, 17.3%), but men showed femoral varus more often. Patients with a higher BMI showed a significantly lower age at surgery (R2 = 0.09, p < 0.001). There were significant differences between men and women for all radiographic parameters (p < 0.001). CONCLUSION: Distribution in knee morphology with gender-specific differences highlights the wide range in osteoarthritic knees, characterized by CPAK and phenotype classification and may influence future surgical planning. LEVEL OF EVIDENCE: Level III.

Can an artificial intelligence powered software reliably assess pelvic radiographs?

PURPOSE: Despite advances of three-dimensional imaging pelvic radiographs remain the cornerstone in the evaluation of the hip joint. However, large inter- and intra-rater variabilities were reported due to subjective landmark setting. Artificial intelligence (AI)-powered software applications could improve the reproducibility of pelvic radiograph evaluation by providing standardized measurements. The aim of this study was to evaluate the reliability and agreement of a newly developed AI algorithm for the evaluation of pelvic radiographs. METHODS: Three-hundred pelvic radiographs from 280 patients with different degrees of acetabular coverage and osteoarthritis (Tönnis Grade 0 to 3) were evaluated. Reliability and agreement between manual measurements and the outputs of the AI software were assessed for the lateral-center-edge (LCE) angle, neck-shaft angle, sharp angle, acetabular index, as well as the femoral head extrusion index. RESULTS: The AI software provided reliable results in 94.3% (283/300). The ICC values ranged between 0.73 for the Acetabular Index to 0.80 for the LCE Angle. Agreement between readers and AI outputs, given by the standard error of measurement (SEM), was good for hips with normal coverage (LCE-SEM: 3.4°) and no osteoarthritis (LCE-SEM: 3.3°) and worse for hips with undercoverage (LCE-SEM: 5.2°) or severe osteoarthritis (LCE-SEM: 5.1°). CONCLUSION: AI-powered applications are a reliable alternative to manual evaluation of pelvic radiographs. While being accurate for patients with normal acetabular coverage and mild signs of osteoarthritis, it needs improvement in the evaluation of patients with hip dysplasia and severe osteoarthritis.

Clinical impact of microbiological results in two-stage revision arthroplasty with spacer exchange.

INTRODUCTION: Patients who require a spacer exchange as part of a two-stage procedure for the treatment of periprosthetic hip and knee joint infections (PJI) have high failure rates. Little is known about the clinical impact of microbiological results and changes in the microbiological spectrum and resistance pattern in these patients. MATERIAL AND METHODS: Between 01/2011 and 12/2019, 312 patients underwent a total of 327 two-stage revision arthroplasties at our institution. A spacer exchange was required in 52/312 (16.7%) patients (27 knee/25 hip). Microbiological results, antibiotic resistance patterns, patient's host factors as well as re-revision and re-infection rates at a median follow-up of 47.8 months (range 12.2-116.7 months) were analyzed. A propensity score (PS)-matched analysis of patients who underwent spacer exchange and patients treated with standard two-stage procedure was performed. RESULTS: We found a high number of microbiological spectrum changes in patients with multiple culture positive procedures between explantations and spacer exchanges (10/12 [83.3%]), spacer exchanges and reimplantations (3/4 [75%]) as well as between reimplantations and subsequent re-revision surgeries (5/6 [83.3%]). In 9/52 (17.3%) patients, same microorganisms were detected repeatedly in two different procedures. We observed changes in the antibiotic resistance patterns in 6/9 (66.7%) of these patients. High re-infection rates were found in patients with culture positive reimplantations (10/12 [83.3%]), and low re-infection rates were found in patients with culture negative reimplantations (2/40 [5%]; p < 0.001). Between patients with and without spacer exchange, no differences were found in the re-revision rates (13/52 [25%] with vs. 13/52 [25%] without; p = 1.00) as well as re-infection rates (12/52 [23.1%] with vs. 8/52 [15.4%] without; p = 0.32). CONCLUSIONS: Changes in microbiological spectrum and antibiotic resistance patterns between stages are common in patients who require a spacer exchange. If eradication of the microorganism at reimplantation can be accomplished, comparable re-revision rates to standard two-stage procedures can be achieved.

Changes in microbiological spectrum and antibiotic susceptibility in two-stage exchange for periprosthetic shoulder infections.

BACKGROUND: Periprosthetic joint infections (PJI) are a major concern in shoulder arthroplasty, which in some cases require two-stage exchange. While it was shown that low-virulence bacteria are the most isolated pathogens in shoulder PJI, little is known about changes in microbiological spectrum and resistance patterns during two-stage revision. METHODS: This retrospective study included all patients (n = 25) who received a two-stage revision from January 2011 to December 2020 for shoulder PJI in one institution. Microbiological spectrum, antimicrobial resistance patterns, and re-revision rates of culture positive first- and second-stage procedures were analyzed. The mean follow-up time was 29.7 months (range 8; 115 months). At final follow-up, subjective shoulder value (SSV) and visual analog scale (VAS) score for pain and satisfaction with the surgery were assessed. RESULTS: In 25 patients, a total of 54 2-stage exchange procedures were performed and positive cultures were obtained in 36 of these surgeries (66.7%). A total of 7 out of 25 patients (28.0%) showed a positive microbiological culture at first and second stages. In those patients, the mean time between first and second stages was 30.9 weeks (range 6; 70). Three out of those seven patients (42.9%) had a polymicrobial spectrum with one microorganism persistent at stage two, including Cutibacterium acnes (n = 1) and Staphylococcus epidermidis (MRSE) (n = 2). In all these cases, antimicrobial resistance patterns changed. All cultures with monomicrobial spectrum (n = 4) at first stage showed a changed spectrum. Patients with positive first- and second-stage revisions showed a mean SSV of 49.3% ± 23.5 versus 52.9% ± 29.5 in single positive patients (p = 0.76). Re-revision was performed in five cases, two of those in patients with positive first- and second-stage cultures. CONCLUSION: There is a high rate of changes in microbiological spectrum and resistance patterns between culture positive first- and second-stage procedures as well as subsequent re-revisions. Intraoperative samples during reimplantation should be taken and resistance reconsidered in case of re-revision.

Dalbavancin in Gram-positive periprosthetic joint infections.

OBJECTIVES: The unique properties of dalbavancin (DAL) emphasize the need to explore its clinical benefits to treat periprosthetic joint infections (PJIs). The present study aimed to compare the treatment outcome of dalbavancin with Standard of Care (SoC) in hip and knee PJIs. METHODS: Eighty-nine patients were selected for each group of this study based on our prospectively maintained PJI database. A 1:1 propensity score-matching was performed between patients who received at least two doses of dalbavancin and those who received SoC. Patients were matched based on demographics, joint, patient risk factors, Musculoskeletal Infection Society (MSIS) criteria, surgical management and type of infection. Treatment outcome was evaluated considering re-infection and re-revision rates, safety and tolerability of dalbavancin after a minimum of 1 year follow-up. RESULTS: Infection eradication was achieved in 69 (77.5%) and 66 (74.2%) patients of the DAL and SoC groups, respectively. Thirteen (14.6%) patients in the DAL group and 12 (13.5%) patients in the SoC group had an infection-related re-revision. The most prevalent microorganisms among the two groups were Staphylococcus epidermidis (32.3%), Staphylococcus aureus (13.8%) and Cutibacterium spp. (11.3%). There were significantly less Gram-positive bacteria (P = 0.03) detected in patients who received dalbavancin (17.4%) treatment compared with those treated with SoC (48.0%) in culture-positive re-revisions. CONCLUSIONS: Dalbavancin treatment for Gram-positive PJIs resulted in a similar outcome to SoC, with excellent safety and low rate of adverse effects. Dalbavancin seems to be a promising antimicrobial against PJIs by reducing the risk of Gram-positive re-infections and allowing a less frequent dosage with potential outpatient IV treatment.

A Mild Case of Autosomal Recessive Osteopetrosis Masquerading as the Dominant Form Involving Homozygous Deep Intronic Variations in the CLCN7 Gene.

Osteopetrosis is a heterogeneous group of rare hereditary diseases characterized by increased bone mass of poor quality. Autosomal-dominant osteopetrosis type II (ADOII) is most often caused by mutation of the CLCN7 gene leading to impaired bone resorption. Autosomal recessive osteopetrosis (ARO) is a more severe form and is frequently accompanied by additional morbidities. We report an adult male presenting with classical clinical and radiological features of ADOII. Genetic analyses showed no amino-acid-converting mutation in CLCN7 but an apparent haploinsufficiency and suppression of CLCN7 mRNA levels in peripheral blood mononuclear cells. Next generation sequencing revealed low-frequency intronic homozygous variations in CLCN7, suggesting recessive inheritance. In silico analysis of an intronic duplication c.595-120_595-86dup revealed additional binding sites for Serine- and Arginine-rich Splicing Factors (SRSF), which is predicted to impair CLCN7 expression. Quantitative backscattered electron imaging and histomorphometric analyses revealed bone tissue and material abnormalities. Giant osteoclasts were present and additionally to lamellar bone, and abundant woven bone and mineralized cartilage were observed, together with increased frequency and thickness of cement lines. Bone mineralization density distribution (BMDD) analysis revealed markedly increased average mineral content of the dense bone (CaMean T-score + 10.1) and frequency of bone with highest mineral content (CaHigh T-score + 19.6), suggesting continued mineral accumulation and lack of bone remodelling. Osteocyte lacunae sections (OLS) characteristics were unremarkable except for an unusually circular shape. Together, our findings suggest that the reduced expression of CLCN7 mRNA in osteoclasts, and possibly also osteocytes, causes poorly remodelled bone with abnormal bone matrix with high mineral content. This together with the lack of adequate bone repair mechanisms makes the material brittle and prone to fracture. While the skeletal phenotype and medical history were suggestive of ADOII, genetic analysis revealed that this is a possible mild case of ARO due to deep intronic mutation.

Differential microbiological spectrum and resistance pattern in periprosthetic hip joint infections: a matched-cohort analysis comparing direct anterior versus lateral approach.

BACKGROUND: In recent years, total hip arthroplasty via the direct anterior approach (DAA) has become more common. Little is known on the influence of the surgical approach on the microbiological spectrum and resistance pattern in periprosthetic hip joint infections. The aim of the present study was to evaluate the microbiological spectrum and resistance pattern in periprosthetic hip joint infections comparing the direct anterior versus lateral approach in a matched-cohort analysis at a single institution. METHODS: Patients who underwent revision hip arthroplasty due to PJI following primary total hip arthroplasty with culture positive microbiology were analyzed. In all study patients, both the primary surgery and the revisions surgery were performed at the same institution. Only patients in whom primary surgery was performed via a direct anterior or lateral approach were included (n = 87). A matched cohort analysis was performed to compare the microbiological spectrum and resistance pattern in PJI following direct anterior (n = 36) versus lateral (n = 36) primary THA. RESULTS: We identified both a significantly different microbiological spectrum and resistance pattern in PJI comparing direct anterior versus lateral approach THA. Cutibacterium avidum was obtained more frequently in the anterior subgroup (22.2% vs. 2.8%, p = 0.028). In the subgroup of infections with Staphylococcus aureus (n = 12), methicillin resistance was detected in 3/5 cases in the direct anterior group versus 0/7 cases in the lateral group (p = 0.045). Overall, Staphylococcus epidermidis was the most common causative microorganism in both groups (direct anterior: 36.1%; lateral: 27.8%, p = 0.448). CONCLUSION: The present study indicates a potential influence of the localization of the skin incision in THA on the microbiological spectrum and resistance pattern in PJI. Cutibacterium avidum seemed to be a more common causative microorganism in PJI in patients who underwent direct anterior compared to lateral approach THA.

Fully automated deep learning for knee alignment assessment in lower extremity radiographs: a cross-sectional diagnostic study.

OBJECTIVES: Accurate assessment of knee alignment and leg length discrepancy is currently measured manually from standing long-leg radiographs (LLR), a process that is both time consuming and poorly reproducible. The aim was to assess the performance of a commercial available AI software by comparing its outputs with manually performed measurements. MATERIALS AND METHODS: The AI was trained on over 15,000 radiographs to measure various clinical angles and lengths from LLRs. We performed a retrospective single-center analysis on 295 LLRs obtained between 2015 and 2020 from male and female patients over 18 years. AI and expert measurements were performed independently. Kellgren-Lawrence score and reading time were assessed. All measurements were compared and non-inferiority, mean-absolute-deviation (sMAD), and intra-class-correlation (ICC) were calculated. RESULTS: A total of 295 LLRs from 284 patients (mean age, 65 years (18; 90); 97 (34.2%) men) were analyzed. The AI model produces outputs on 98.0% of the LLRs. Manually annotations were considered as 100% accurate. For each measurement, its divergence was calculated, resulting in an overall accuracy of 89.2% when comparing the AI outputs to the manually measured. AI vs. mean observer revealed an sMAD between 0.39 and 2.19° for angles and 1.45-5.00 mm for lengths. AI showed good reliability in all lengths and angles (ICC ≥ 0.87). Non-inferiority comparing AI to the mean observer revealed an equivalence-index (γ) between 0.54 and 3.03° for angles and - 0.70-1.95 mm for lengths. On average, AI was 130 s faster than clinicians. CONCLUSION: Automated measurements of knee alignment and length measurements produced with an AI tool result in reproducible, accurate measures with a time savings compared to manually acquired measurements.

Artificial intelligence enables reliable and standardized measurements of implant alignment in long leg radiographs with total knee arthroplasties.

PURPOSE: The purpose of this study was to evaluate the reliability of a newly developed AI-algorithm for the evaluation of long leg radiographs (LLR) after total knee arthroplasties (TKA). METHODS: In the validation cohort 200 calibrated LLRs of eight different common unconstrained and constrained knee systems were analysed. Accuracy and reproducibility of the AI-algorithm were compared to manual reads regarding the hip-knee-ankle (HKA) as well as femoral (FCA) and tibial component (TCA) angles. In the evaluation cohort all institutional LLRs with TKAs in 2018 (n = 1312) were evaluated to assess the algorithms' ability of handling large data sets. Intraclass correlation (ICC) coefficient and mean absolute deviation (sMAD) were calculated to assess conformity between the AI software and manual reads. RESULTS: Validation cohort: The AI-software was reproducible on 96% and reliable on 92.1% of LLRs with an output and showed excellent reliability in all measured angles (ICC > 0.97) compared to manual measurements. Excellent results were found for primary unconstrained TKAs. In constrained TKAs landmark setting on the femoral and tibial component failed in 12.5% of LLRs (n = 9). Evaluation cohort: Mean measurements for all postoperative TKAs (n = 1240) were 0.2° varus ± 2.5° (HKA), 89.3° ± 1.9° (FCA), and 89.1° ± 1.6° (TCA). Mean measurements on preoperative revision TKAs (n = 74) were 1.6 varus ± 6.4° (HKA), 90.5° ± 3.1° (FCA), and 88.9° ± 4.1° (TCA). CONCLUSIONS: AI-powered applications are reliable for automated analysis of lower limb alignment on LLRs with TKAs. They are capable of handling large data sets and could, therefore, lead to more standardized and efficient postoperative quality controls. LEVEL OF EVIDENCE: Diagnostic Level III.

A MicroRNA Next-Generation-Sequencing Discovery Assay (miND) for Genome-Scale Analysis and Absolute Quantitation of Circulating MicroRNA Biomarkers.

The plasma levels of tissue-specific microRNAs can be used as diagnostic, disease severity and prognostic biomarkers for chronic and acute diseases and drug-induced injury. Thereby, the combination of diverse microRNAs into biomarker signatures using multivariate statistics seems especially powerful from the perspective of tissue and condition specific microRNA shedding into the plasma. Although next-generation sequencing (NGS) technology enables one to analyse circulating microRNAs on a genome-scale level, it suffers from potential biases (e.g., adapter ligation bias) and lacks absolute transcript quantitation as well as tailor-made quality controls. In order to develop a robust NGS discovery assay for genome-scale quantitation of circulating microRNAs, we first evaluated the sensitivity, repeatability and ligation bias of four commercially available small RNA library preparation protocols. The protocol from RealSeq Biosciences was selected based on its performance and usability and coupled with a novel panel of exogenous small RNA spike-in controls to enable quality control and absolute quantitation, thus ensuring comparability of data across independent NGS experiments. The established microRNA Next-Generation-Sequencing Discovery Assay (miND) was validated for its relative accuracy, precision, analytical measurement range and sequencing bias and was considered fit-for-purpose for microRNA biomarker discovery. Summarized, all these criteria were met, and thus, our analytical platform is considered fit-for-purpose for microRNA biomarker discovery from biofluids in the setting of any diagnostic, prognostic or patient stratification need. The established miND assay was tested on serum, cerebrospinal fluid (CSF), synovial fluid (SF) and extracellular vesicles (EV) extracted from cell culture medium of primary cells and proved its potential to be used across different sample types.

Analysis of Culture Positive First and Second Stage Procedures in Periprosthetic Knee and Hip Joint Infections.

BACKGROUND: A positive microbiological result at reimplantation may lead to a failed 2-stage revision arthroplasty in the treatment of periprosthetic joint infections. Little is known about changes in microbiological spectrum and resistance pattern between culture positive first and second stage procedures in revision knee and hip arthroplasty. METHODS: Between January 2011 and December 2019, we performed 327 two-stage revision arthroplasties on 312 patients. There were 37 of 312 (11.9%) patients (20 hips/17 knees) who had a positive microbiological culture during the first and second stage procedure. We analyzed the microbiological spectrum, antimicrobial resistance pattern, and clinical outcome of culture positive first and second stage procedures as well as subsequent re-revisions. RESULTS: Re-revision was necessary in 40.5% (15/37) of patients with culture positive first and second stage procedure at a median follow-up of 3.5 years. We found microbiological changes in 83.8% (31/37) of patients between the first and second stage and in 88.9% (8/9) between the second stage and subsequent culture positive re-revision. Polymicrobial infections were found in 21.6% (8/37) of first and in 16.2% (6/37) of second stage procedures. In 27% (10/37) of patients, microorganisms persisted between the first and second stage procedure. The antimicrobial resistance pattern changed in 60% of persistent microorganisms between the first and second stage procedure. CONCLUSION: Changes in microbiological spectrum and resistance pattern are common between culture positive first and second stage procedures as well as subsequent re-revisions. This has to be considered in the antimicrobial treatment of periprosthetic joint infections.

No Role of Osteocytic Osteolysis in the Development and Recovery of the Bone Phenotype Induced by Severe Secondary Hyperparathyroidism in Vitamin D Receptor Deficient Mice.

Osteocytic osteolysis/perilacunar remodeling is thought to contribute to the maintenance of mineral homeostasis. Here, we utilized a reversible, adult-onset model of secondary hyperparathyroidism to study femoral bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) based on quantitative backscattered electron imaging. Male mice with a non-functioning vitamin D receptor (VDRΔ/Δ) or wild-type mice were exposed to a rescue diet (RD) (baseline) and subsequently to a low calcium challenge diet (CD). Thereafter, VDRΔ/Δ mice received either the CD, a normal diet (ND), or the RD. At baseline, BMDD and OLS characteristics were similar in VDRΔ/Δ and wild-type mice. The CD induced large cortical pores, osteomalacia, and a reduced epiphyseal average degree of mineralization in the VDRΔ/Δ mice relative to the baseline (-9.5%, p < 0.05 after two months and -10.3%, p < 0.01 after five months of the CD). Switching VDRΔ/Δ mice on the CD back to the RD fully restored BMDD to baseline values. However, OLS remained unchanged in all groups of mice, independent of diet. We conclude that adult VDRΔ/Δ animals on an RD lack any skeletal abnormalities, suggesting that VDR signaling is dispensable for normal bone mineralization as long as mineral homeostasis is normal. Our findings also indicate that VDRΔ/Δ mice attempt to correct a calcium challenge by enhanced osteoclastic resorption rather than by osteocytic osteolysis.

The role of the subchondral layer in osteonecrosis of the femoral head: analysis based on HR-QCT in comparison to MRI findings.

BACKGROUND: Non-traumatic avascular osteonecrosis of the femoral head (ONFH) is a severe disease causing destruction of the hip joint, often necessitating total hip arthroplasty (THA) even in young patients. Magnetic resonance imaging (MRI) is commonly used for diagnosis of ONFH, but provides limited insight into the subchondral bone microstructure. PURPOSE: To analyze routine MRI findings in comparison to high-resolution quantitative computed tomography (HR-QCT) with a special focus on the subchondral layer and to estimate the importance of differences determining the indication for THA. MATERIAL AND METHODS: Twelve patients with ONFH were included before THA. Preoperative MRI and HR-QCT of the retrieved femoral heads were aligned using a registration algorithm. Pathological findings and trabecular bone parameters in matched areas were analyzed by two readers. McNemar, marginal homogeneity test, and Pearson's correlation coefficient were used for comparison. RESULTS: Subchondral delamination was found in nine cases on HR-QCT, but missed or underestimated in all but one case on MRI ( P = 0.016). Chondral discontinuity was found in all cases on HR-QCT and in two cases on MRI ( P = 0.016). Areas of complete bone resorption on HR-QCT were linked to high signal intensity on 3D gradient-echo MRI sequences with water-selective excitation, while there was no correlation between trabecular bone parameters and MRI signal intensities in other areas ( P = 0.304). CONCLUSION: Subchondral delamination, subchondral resorption, and chondral discontinuity are found frequently in advanced stages of ONFH. These lesions tend to be underestimated on conventional MRI. Our results support the importance of CT imaging in the evaluation of ONFH.