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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.

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.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.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.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.

Background Scapulothoracic orientation, especially scapular internal rotation (SIR) may influence range of motion in reverse total shoulder arthroplasty (RTSA) and is subjected to body posture. Clinical measurements of SIR rely on apical bony landmarks which are subjected to changes in scapulothoracic orientation, while radiographic measurements are often limited by the restricted field of view (FOV) in CT scans. Therefore, the goal of this study was (1) to determine whether the use of CT scans with a limited FOV to measure SIR is reliable and (2) if a clinical measurement could be a valuable alternative. Methods This anatomical study analyzed the whole-body CT-scans of 100 shoulders in 50 patients (32 male and 18 female) with a mean age of 61.2 ± 20.1 years (range 18; 91). (1) CT-scans were rendered into 3D models and SIR was determined as previously described. Results were compared to measurements taken in 2D CT-scans with a limited FOV. (2) Three apical bony landmarks were defined: (the angulus acromii (AA), the midpoint between the AA and the coracoid process tip (C) and the acromioclavicular (AC) joint. The scapular axis was determined connecting the trigonum scapulae with these landmarks and referenced to the glenoid center. The measurements were repeated with 0°, 10°, 20°, 30° and 40° anterior scapular tilt. Results Mean SIR was 44.8° ± 5.9° and 45.6° ± 6.6° in the 3D and 2D model, respectively (p

In severe cases of postoperative spinal implant infections (PSII) multiple revision surgeries may be needed. Little is known if changes in the microbiological spectrum and antibiotic resistance pattern occur between revision surgeries.Analysis of the microbiological spectrum and antibiotic resistance pattern in patients with multiple revision surgeries for the treatment of PSII STUDY DESIGN: Retrospective database analysis.Between 01/2011 and 12/2018, 103 patients underwent 248 revision surgeries for the treatment of PSII. Twenty patients (19.4%) who underwent multiple revision surgeries for PSII were included in this study.Microbiological spectrum, antibiotic resistance pattern.A retrospective analysis of a prospectively maintained single center spine infection database was performed with a minimum follow-up of 3 years. Overall, 20 patients (six male/14 female) underwent 82 revisions for PSII (median 3; range 2-12). There were 55 of 82 (67.1%) procedures with a positive microbiological result. Microbiological analysis was performed on tissue and implant sonication fluid. Changes in microbial spectrum and antibiotic resistance pattern between surgeries were evaluated using Chi-Square and Fisher's exact test.In total, 74 microorganisms (83.3% gram-positive; 10.8% gram-negative) were identified. The most common microorganisms were Staphylococcus epidermidis (18.9%) and Cutibacterium acnes (18.9%). All S. epidermidis identified were methicillin-resistant (MRSE). Overall, there were 15 of 55 (27.3%) polymicrobial infections. The microbiological spectrum changed in 57.1% (20/35) between the revision stages over the entire PSII period. In 42.9% (15/35) the microorganism persisted between the revision surgeries stages. Overall, changes of the antibiotic resistance pattern were seen in 17.4% (8/46) of the detected microorganisms, comparing index revision and all subsequent re-revisions. Moreover, higher resistance rates were found for moxifloxacin and for ciprofloxacin at first re-revision surgery compared with index PSII revision. Resistances against vancomycin increased from 4.5% (1/23) at index PSII revision to 7.7% (2/26) at first re-revision surgery.Changes of the microbiological spectrum and the resistance pattern can occur in patients with severe PSII who require multiple revision surgeries. It is important to consider these findings in the antimicrobial treatment of PSII. The microbiological analysis of intraoperative tissue samples should be performed at every revision procedure for PSII.

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.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.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.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.

Gadolinium-based contrast agents (GBCAs) are frequently used in patients undergoing magnetic resonance imaging. In GBCAs gadolinium (Gd) is present in a bound chelated form. Gadolinium is a rare-earth element, which is normally not present in human body. Though the blood elimination half-life of contrast agents is about 90 minutes, recent studies demonstrated that some tissues retain gadolinium, which might further pose a health threat due to toxic effects of free gadolinium. It is known that the bone tissue can serve as a gadolinium depot, but so far only bulk measurements were performed. Here we present a summary of experiments in which for the first time we mapped gadolinium in bone biopsy from a male patient with idiopathic osteoporosis (without indication of renal impairment), who received MRI 8 months prior to biopsy. In our studies performed by means of synchrotron radiation induced micro- and submicro-X-ray fluorescence spectroscopy (SR-XRF), gadolinium was detected in human cortical bone tissue. The distribution of gadolinium displays a specific accumulation pattern. Correlation of elemental maps obtained at ANKA synchrotron with qBEI images (quantitative backscattered electron imaging) allowed assignment of Gd structures to the histological bone structures. Follow-up beamtimes at ESRF and Diamond Light Source using submicro-SR-XRF allowed resolving thin Gd structures in cortical bone, as well as correlating them with calcium and zinc.

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.

Periprosthetic joint infection (PJI) is a serious complication of total hip arthroplasty. Staged revision surgery is considered effective in eradicating PJI. We aimed to determine the rate of infection resolution after each stage of staged revision surgery (first stage, repeat first stage, second stage, excision arthroplasty, and reimplantation) and to assess functional outcomes and the mortality rate at ten years in a consecutive series of 30 chronic PJI of total hip arthroplasties. Infection resolution was defined as no clinical nor laboratory evidence of infection at 24 months after the last surgery and after a minimum of 12 months following cessation of antimicrobial treatment. Four patients died within 24 months of their final surgery. Nineteen patients, 73% (worst-case analysis (wca) 63%), were infection free after 1 surgery; 22 patients, 85% (wca 73%), were infection free after 2 surgeries; and 26 patients, 100% (wca 87%), were infection free after three and four surgeries. The median Harris Hip Score was 41 prior to first revision surgery and improved to 74 at twelve months and 76 at ten years after the final surgery. Thirteen patients died at a mean of 64 months from first revision, giving a mortality rate of 43% at ten years, which is approximately 25% higher than that of an age-matched general population. The results show that with repeated aggressive surgical treatment, most PJIs of the hip are curable. Ten years after successful treatment of PJI, functional outcomes and pain are improved and maintained compared to before initial surgery, but this must be balanced against the high 10-year mortality. Level of evidence: cohort studies.

Resection arthroplasty can be performed as the first stage of a two-stage procedure in some patients with severe periprosthetic hip joint infections with poor bone stock. This retrospective study aimed to evaluate factors associated with the subsequent failure or success of these patients. Between 2011 and 2020, in 61 (26.4%) of 231 patients who underwent a two-stage protocol of periprosthetic hip joint infections, no spacer was used in the first stage. The minimum follow-up period was 12 months. Patient’s demographics and various infection risk factors were analyzed. In total, 37/61 (60.7%) patients underwent a successful reimplantation, and four patients died within the follow-up period. Patients within the failure group had a significantly higher Charlson comorbidity index (p = 0.002), number of operations prior to resection arthroplasty (p = 0.022) and were older (p = 0.018). Failure was also associated with the presence of a positive culture in the first- and second-stage procedures (p = 0.012). Additional risk factors were persistent high postoperative CRP values and the requirement of a negative-pressure wound therapy (p ≤ 0.05). In conclusion, multiple factors need to be evaluated when trying to predict the outcome of patients undergoing resection arthroplasty as the first stage of a two-stage procedure in patients with challenging periprosthetic hip joint infections.

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. 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. 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. 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.

The increasing incidence of antimicrobial resistance (AMR) is a major global challenge. Routine techniques for molecular AMR marker detection are largely based on low-plex PCR and detect dozens to hundreds of AMR markers. To allow for comprehensive and sensitive profiling of AMR markers, we developed a capture-based next generation sequencing (NGS) workflow featuring a novel AMR marker panel based on the curated AMR database ARESdb. Our primary objective was to compare the sensitivity of target enrichment-based AMR marker detection to metagenomics sequencing. Therefore, we determined the limit of detection (LOD) in synovial fluid and urine samples across four key pathogens. We further demonstrated proof-of-concept for AMR marker profiling from septic samples using a selection of urine samples with confirmed monoinfection. The results showed that the capture-based workflow is more sensitive and requires lower sequencing depth compared with metagenomics sequencing, allowing for comprehensive AMR marker detection with an LOD of 1000 CFU/mL. Combining the ARESdb AMR panel with 16S rRNA gene sequencing allowed for the culture-free detection of bacterial taxa and AMR markers directly from septic patient samples at an average sensitivity of 99%. Summarizing, the newly developed ARESdb AMR panel may serve as a valuable tool for comprehensive and sensitive AMR marker detection.

Autosomal Dominant Osteopetrosis type II (ADOII), also known as Albers-Schönberg disease, is caused by mutation of the CLCN7 chloride channel gene and is characterized by reduced bone resorption. Here we report on an individual with the classic features of ADOII, who had a history of fractures from childhood, displayed high bone mass and characteristic “sandwich vertebrae” on x-ray. Our genetic analyses showed no amino acid converting mutation in the patient’s DNA but we did find evidence of haploinsufficiency of CLCN7 mRNA. An iliac crest bone sample from the patient revealed bone tissue and material abnormalities relative to normal controls based on quantitative backscattered electron imaging and histomorphometric analyses. Additionally to lamellar bone, we observed significant amounts of woven bone and mineralised cartilage, as well as an increased frequency and thickness (up to 15 microns) of cement lines. Giant osteoclasts with numerous nuclei were present. The bone mineralisation density distribution (BMDD) of the entire bone area 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 the OLS shape which was unusually circular. 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.

Joint replacement surgeries are one of the most frequent medical interventions globally. Infections of prosthetic joints are a major health challenge and typically require prolonged or even indefinite antibiotic treatment. As multidrug-resistant pathogens continue to rise globally, novel diagnostics are critical to ensure appropriate treatment and help with prosthetic joint infections (PJI) management. To this end, recent studies have shown the potential of molecular methods such as next-generation sequencing to complement established phenotypic, culture-based methods. Together with advanced bioinformatics approaches, next-generation sequencing can provide comprehensive information on pathogen identity as well as antimicrobial susceptibility, potentially enabling rapid diagnosis and targeted therapy of PJIs. In this review, we summarize current developments in next generation sequencing based predictive antibiotic susceptibility testing and discuss potential and limitations for common PJI pathogens.

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 theCLCN7gene 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 inCLCN7but an apparent haploinsufficiency and suppression ofCLCN7mRNA levels in peripheral blood mononuclear cells. Next generation sequencing revealed low-frequency intronic homozygous variations inCLCN7, 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 impairCLCN7expression. 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 (CaMeanT-score + 10.1) and frequency of bone with highest mineral content (CaHighT-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 ofCLCN7mRNA 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.

The aim of this study was to evaluate the number of primary and revision total joint arthroplasties (TJA/rTJA) in 2020 compared to 2019. Specifically, the first and the second waves of the COVID-19 pandemic were evaluated as well as the pre-operative COVID-19 test. A cross-sectional single-center study of our prospectively maintained institutional arthroplasty registry was performed. The first COVID-19 wave and the second COVID-19 wave led to a socioeconomic lockdown in 2020. Performed surgeries, cause of revision, age, gender, and American Society of Anesthesiologists-level were analyzed. Preoperative COVID-19 testing was evaluated and nationwide COVID-19 data were compared to other countries. In 2020, there was a decrease by 16.2% in primary and revision TJAs of the hip and knee compared to 2019. We observed a reduction of 15.8% in primary TJAs and a reduction of 18.6% on rTJAs in 2020 compared to 2019. There is an incline in total hip arthroplasties (THAs) and a decline in total knee arthroplasties (TKAs) comparing 2019 to 2020. During the first wave, there was a reduction in performed primary TJAs of 86%. During the second wave, no changes were observed. This is the first study quantifying the impact of the COVID-19 pandemic on primary and revision TJAs regarding the first and second wave.

Hip dysplasia (DDH) as well as femoroacetabular impingement (FAI) are common causes of hip pain in young adults and lead to premature osteoarthritis (OA). However, not all patients with radiographic features of DDH or FAI develop symptoms and degenerative changes, which indicates that various factors play a role in the disease process. Here we use a diamond concept to illustrate anatomical factors that play a role in the pathomechanism of symptomatic DDH and FAI. This concept may help clinicians in the diagnosis of hip pain in young adults. For DDH, the following factors are included: (1) acetabular and (2) femoral morphology, (3) pelvic shape and geometry, (4) spinopelvic alignment and (5) soft tissue properties. For FAI, the following factors are included: (1) intraarticular acetabular and (2) intraarticular femoral morphology, (3) extraarticular pelvic and (4) extraarticular femoral morphology, (5) spinopelvic alignment and (6) soft tissue properties. Knowledge of these factors can help to identify an adequate treatment. Surgical treatment options include (1) extraarticular acetabular, (2) extraarticular femoral, (3) intraarticular acetabular and (4) intraarticular femoral procedures. Further research is warranted on the specific role and the interaction of the parameters presented in the diamond concept in the disease process of hip joint degeneration.

Objective The objective of the study was to specify the thickness of Zn and Pb accumulation within the tidemark (TM), a narrow structure between the non-calcified and the calcified articular cartilage. It is considered an active or resting calcification front. This banded structure of the cartilage-bone interface is known to undergo changes in osteoarthritis. Therefore, gaining knowledge about this structure is of interest. Methods Femoral head samples were collected from patients suffering from various bone diseases, 6 samples have been investigated. Thin bone slices (3 ​μm thick) were measured with high resolution synchrotron micro-X-ray fluorescence (SR micro-XRF) analysis using a beam with dimensions of 500 ​× ​800 ​nm2. The tidemark region was found in all analyzed samples. The Savitzky-Golay filter was used to smooth the measured imaging data and Kaplan-Meier estimation to gain reliable tidemarks medians for Pb and Zn. To our knowledge this was the first time that these methods have been applied to gain information on histological structures obtained by elemental imaging. Results The thickness of the Zn and Pb layer ranged from about 3 to 11 ​μm for Zn and 4–14.5 ​μm for Pb. Our Zn ratios (TM/matrix) were found to be 1.5-3-fold ratio between Zn tidemark values and in mineralized matrix and are similar in all samples. Conclusions The determined thickness of the layer is much smaller than found in previous measurements with the beam having 20 ​× ​14 ​μm2 size. The Zn ratios agree with our previous findings.

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.

Introduction Lesions of the lateral cutaneous femoral nerve are a reported complication of the direct anterior approach (DAA) for total hip arthroplasty (THA). Little is known about the incidence rates of this lesion. The goal of this study was to answer the following questions: (1) Is the true incidence rate of LFCN lesions after DAA THA known? (2) What are the reasons for the wide range of reported incidence rates in the literature? (3) Are surgeons increasingly aware of the significance of LFCN lesions? Methods A US Medical Library of Medicine database search was performed for DAA THA. In total, 1261 search results were screened for reported LFCN lesions. Results Forty-five studies were included reporting LFCN lesions rates of 0–83%. Subgroup analysis for studies with (group A, 6 studies, n = 1113 cases) and without (group B, 39 studies n = 16,741) primary focus on the LFCN lesions was performed. Incidence in group A ranged from 14.8–81% (mean 31%) and 0–83% (mean 3.8%) in group B. The difference between the groups was significant (p = 0.005). No uniform and time sensitive definition of postoperative LFCN lesions was found in the literature. An analysis of the publication year and the discovered incidence rate showed an increase of incidence rates [rs = 0.521 (p Conclusion Despite the absence of a uniform definition: LFCN lesions after DAA THA are a frequent and, in the past, often underestimated complication. Level of evidence IV; systematic review of level II to level IV studies.

Background: The clinical presentation, phenotypic characterization and natural history of fibrodysplasia ossificans progressiva (FOP) are diverse and the natural history of the disease is, to a certain extent, different from one patient to another. Methods: In a series of 11 patients (eight girls and three boys, aged 0 - 16 years), variable clinical presentations were the landmarks of these patients. At birth, all of our patients manifested short great toes in a valgus position. Marfan syndrome was the suggested diagnosis in three children aged 3 - 8 years and in two pre-adult patients. Clinical symptoms were torticollis, painful spine, and painful and marked limitation of the pelvic movements. Monophalangia associated with Marfanoid habitus was also a prevailing clinical presentation. Results: Our results were based upon the appearance of the earliest pathologic feature of FOP in correlation with the clinical presentation. In infants (0 - 1 year), three infants showed congenital hallux valgus and stiff spine. In the pediatric group (3 - 8 years), all children showed no mutation in the fibrillin-1 ( FBN1 ) gene. Their prime presentation was a progressive torticollis with simultaneous development of erythematous subfascial nodules, most commonly located on the posterior neck and back. In pre-adult group (10 - 16 years), four patients presented with monophalangia associated with painful movements because of the progressive heterotopic ossification of the spine and the weight bearing zones and marked elevation of alkaline phosphatase. Genetic confirmation has been performed in six patients who manifested the classical mutation of the ACVR1 gene. The rest of the patients were assessed via clinical and radiographic phenotypes. Conclusion: The early recognition of FOP can be performed by noticing the short halluces and thumbs at early infancy and later on the high alkaline phosphatase activity in areas of heterotopic ossification. Misconception of FOP is of common practice and eventually unnecessary diagnostic biopsies might deteriorate the progression of the condition. The detection of ACVR1 gene mutation was a confirmatory procedure. Interestingly, the timing of the onset and the location of progressive heterotopic ossifications were extremely variable and confusing among our group of patients. J Clin Med Res. 2016;8(3):246-253 doi: http://dx.doi.org/10.14740/jocmr2465w

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 (VDR&Delta, /&Delta, ) or wild-type mice were exposed to a rescue diet (RD) (baseline) and subsequently to a low calcium challenge diet (CD). Thereafter, VDR&Delta, mice received either the CD, a normal diet (ND), or the RD. At baseline, BMDD and OLS characteristics were similar in VDR&Delta, and wild-type mice. The CD induced large cortical pores, osteomalacia, and a reduced epiphyseal average degree of mineralization in the VDR&Delta, mice relative to the baseline (&minus, 9.5%, p &lt, 0.05 after two months and &minus, 10.3%, p &lt, 0.01 after five months of the CD). Switching VDR&Delta, 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 VDR&Delta, 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 VDR&Delta, mice attempt to correct a calcium challenge by enhanced osteoclastic resorption rather than by osteocytic osteolysis.

BackgroundNon-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.PurposeTo 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 MethodsTwelve 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.ResultsSubchondral 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).ConclusionSubchondral 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.

Background Advances in multimodal treatment have improved survival of patients with nonmetastatic osteosarcoma. At the same time, implant design has improved the outcomes of limb salvage with modular endoprostheses. However, little is known about sports activity in long-term survivors with osteosarcoma.

Rationale: Craniosynostosis is a disorder characterized by premature fusion of cranial sutures with subsequent development of abnormal craniofacial contour associated with variable skeletal and extra-skeletal abnormalities. In this family syndromic type of craniosynostosis was recognized and the etiology behind diverse forms of deformities have been diagnosed. Patient concerns: The negative impact of the disorder on the child and his family is enormous. Particularly when the diagnosis is late and little can be done. Though counselling the family through discussing the whole picture of the disorder might lessens their concern. Diagnoses: Diagnosis is the corner stone of management. In this paper we aimed to sensitize pediatricians, physicians, and orthopedic surgeons concerning the necessity to recognize syndromic associations early on. Interventions: Patients with syndromic craniosynostosis are usually associated with a complexity of malformation complex. Craniofacial surgery can be of remarkable help if the diagnosis is made early. It requires a series of corrections to avoid intellectual disability and other neurological deficits. The timing of interventions is strongly correlated on the timing of diagnosis. Outcomes: The earliest the diagnoses, the much better the outcomes are. And consequently avert the psychological and the financial cost on the patient and his family. Lessons: The golden principle of medicine should prevail in all medical disciplines, which states: The more you see, the more you know and conversely the more you know is the more you see.

We investigated the detailed anatomy of the gluteus maximus, gluteus medius and gluteus minimus and their neurovascular supply in 22 hips in 11 embalmed adult Caucasian human cadavers. This led to the development of a surgical technique for an extended posterior approach to the hip and pelvis that exposes the supra-acetabular ilium and preserves the glutei during revision hip surgery. Proximal to distal mobilisation of the gluteus medius from the posterior gluteal line permits exposure and mobilisation of the superior gluteal neurovascular bundle between the sciatic notch and the entrance to the gluteus medius, enabling a wider exposure of the supra-acetabular ilium. This technique was subsequently used in nine patients undergoing revision total hip replacement involving the reconstruction of nine Paprosky 3B acetabular defects, five of which had pelvic discontinuity. Intra-operative electromyography showed that the innervation of the gluteal muscles was not affected by surgery. Clinical follow-up demonstrated good hip abduction function in all patients. These results were compared with those of a matched cohort treated through a Kocher–Langenbeck approach. Our modified approach maximises the exposure of the ilium above the sciatic notch while protecting the gluteal muscles and their neurovascular bundle. Cite this article: Bone Joint J 2014;96-B:48–53.

Schnurri-3 (Shn3) is an essential regulator of postnatal skeletal remodeling. Shn3-deficient mice (Shn3-/-) have high bone mass; however, their bone mechanical and material properties have not been investigated to date. We performed three-point bending of femora, compression tests of L3 vertebrae. We also measured intrinsic material properties, including bone mineralization density distribution (BMDD) and osteocyte lacunae section (OLS) characteristics by quantitative backscatter electron imaging, as well as collagen cross-linking by Fourier transform infrared microspectroscopy of femora from Shn3-/- and WT mice at different ages (6 weeks, 4 months, and 18 months). Moreover, computer modeling was performed for the interpretation of the BMDD outcomes. Femora and L3 vertebrae from Shn3-/- aged 6 weeks revealed increased ultimate force (2.2- and 3.2-fold, p < .01, respectively). Mineralized bone volume at the distal femoral metaphysis was about twofold (at 6 weeks) to eightfold (at 4 and 18 months of age) in Shn3-/- (p < .001). Compared with WT, the average degree of trabecular bone mineralization was similar at 6 weeks, but increased at 4 and 18 months of age (+12.6% and +7.7%, p < .01, respectively) in Shn3-/-. The analysis of OLS characteristics revealed a higher OLS area for Shn3-/- versus WT at all ages (+16%, +23%, +21%, respectively, p < .01). The collagen cross-link ratio was similar between groups. We conclude that femora and vertebrae from Shn3-/- had higher ultimate force in mechanical testing. Computer modeling demonstrated that in cases of highly increased bone volume, the average degree of bone matrix mineralization can be higher than in WT bone, which was actually measured in the older Shn3-/- groups. The area of 2D osteocyte lacunae sections was also increased in Shn3-deficiency, which could only partly be explained by larger remnant areas of primary cortical bone. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Objective: To further investigate the underlying pathology of axial and appendicular skeletal abnormalities such as painful spine stiffness, gait abnormalities, early onset osteoarthritis and patellar instability in patients with Stickler syndrome type I. Radiographic and tomographic analyses were organized. Methods: From a series of Stickler syndrome patients followed from early life to late childhood. Ten patients (6 boys and four girls of different ethnic origins were consistent with the diagnosis of Stickler syndrome type I ). Phenotypic characterization was the baseline tool applied for all patients and genotypic correlation was performed on four families Results: A constellation of axial abnormalities namely; anterolateral ossification of the anterior longitudinal spinal ligament with subsequent fusion of two cervical vertebrae, early onset Forestier disease (progressive spinal hyperostosis with subsequent vertebral fusion on top of bridging osteophytes and “Bamboo-like spine” resembling ankylosing spondylitis) and severe premature spine degeneration were evident. Appendicular abnormalities in connection with generalized epiphyseal dysplasia were the underlying aetiology in patients with Intoeing gait and femoral anteversion, early onset severe osteoarthritis of the weight bearing joint. Remarkable trochleo-patellar dysplasia secondary to severe osteoarthritis causing effectively the development of patellar instability was additional pathology. Mutation of COL2A1 has been confirmed as the causative gene for Stickler syndrome type I Conclusion: We concluded that conventional radiographs and the molecular determination of a COL2A1 in patients with (Stickler syndrome type I) are insufficient tools to explain the reasons behind the tremendous magnitude of axial and appendicular skeletal abnormalities. We were able to modify the criteria of the clinical phenotype as designated by Rose et al in accordance with the novel axial and appendicular criteria as emerged from within our current study.

Introduction The goal of this in vitro validation study was to investigate the feasibility of biochemical MRI techniques, such as sodium imaging, T 2 mapping, fast imaging with steady state precession (FISP), and reversed FISP (PSIF), as potential markers for collagen, glycosaminoglycan and water content in the Achilles tendon. Materials and methods Five fresh cadaver ankles acquired from a local anatomy department were used in the study. To acquire a sodium signal from the Achilles tendon, a 3D-gradient-echo sequence, optimized for sodium imaging, was used with TE = 7.71 ms and TR = 17 ms. The T 2 relaxation times were obtained using a multi-echo, spin-echo technique with a repetition time (TR) of 1200 ms and six echo times. A 3D, partially balanced, steady-state gradient echo pulse sequence was used to acquire FISP and PSIF images, with TR/TE = 6.96/2.46 ms. MRI parameters were correlated with each other, as well as with histologically assessed glycosaminoglycan and water content in cadaver Achilles tendons. Results The highest relevant Pearson correlation coefficient was found between sodium SNR and glycosaminoglycan content ( r = 0.71, p = 0.007). Relatively high correlation was found between the PSIF signal and T 2 values ( r = 0.51, p = 0.036), and between the FISP signal and T 2 values ( r = 0.56, p = 0.047). Other correlations were found to be below the moderate level. Conclusion This study demonstrated the feasibility of progressive biochemical MRI methods for the imaging of the AT. A GAG-specific, contrast-free method (sodium imaging), as well as collagen- and water-sensitive methods ( T 2 mapping, FISP, PSIF), may be used in fast-relaxing tissues, such as tendons, in reasonable scan times.

Little is known about the tumor matrix mineralization of highly sclerotic osteosarcoma. We used quantitative backscattered electron imaging (qBEI) to determine the Bone mineralization density distribution (BMDD) of a highly sclerosing osteosarcoma of the proximal tibia as well as adjacent normal bone of a 10-year-old girl following chemotherapy according to the EURAMOS-1 protocol. Data were compared to recently published normative reference data for young individuals. Backscattered electron imaging of the tumor region revealed a dense accumulation of mineralized tumor bone matrix (up to 90% of the medullar space). The BMDD was shifted tremendously towards higher matrix mineralization (CaMean + 18.5%, CaPeak + 22.5%, CaHigh + 100 fold) compared to normal bone. Additionally the BMDD became much wider, indicating a higher heterogeneity in mineralization (CaWidth + 40%). In contrast to lamellar bone, which mineralizes via a mineralization front, the mineralization of the tumor matrix starts by randomly distributed spots of mineral clusters fusing together to a highly mineralized non-lamellar bone matrix. We also found an altered BMDD of the patient's normal bone when compared with the reference BMDD of young individuals. In conclusion this high radiodensity region of the sclerosing sarcoma is not only due to the high amount of tumor matrix but also to its high mineralization density. Chemotherapy may lead to altered matrix mineralization of normal bone due to suppression of bone turnover. The mechanism of matrix mineralization in a sclerosing osteosarcoma warrants further studies.

Abnormal tissue levels of certain trace elements such as zinc (Zn) were reported in various types of cancer. Little is known about the role of Zn in osteosarcoma. Using confocal synchrotron radiation micro X‐ray fluorescence analysis, we characterized the spatial distribution of Zn in high‐grade sclerosing osteosarcoma of nine patients (four women/five men; seven knee/one humerus/one femur) following chemotherapy and wide surgical resection. Levels were compared with adjacent normal tissue. Quantitative backscattered electron imaging as well as histological examinations was also performed. On average, the ratio of medians of Zn count rates (normalized to calcium) in mineralized tumor tissue was about six times higher than in normal tissue. There was no difference in Zn levels between tumor fraction areas with a low fraction and a high fraction of mineralized tissue, which were clearly depicted using quantitative backscattered electron imaging. Moreover, we found no correlation between the Zn values and the type of tumor regression according to the Salzer‐Kuntschik grading. The underlying mechanism of Zn accumulation remains unclear. Given the emerging data on the role of trace elements in other types of cancer, our novel results warrant further studies on the role of trace elements in bone cancer. Copyright © 2016 The Authors. X‐Ray Spectrometry published by John Wiley & Sons Ltd.

Background: We studied an unusual combination of severe short stature, mesomelia (Leri-Weill dyschondrosteosis syndrome), and multiple exostosis in several family subjects over three generations. The pattern of inheritance was compatible with autosomal dominant. Methods: Of 21 affected members over three generations, shortness of stature, associated with mesomelia resembling Leri-Weill dyschondrosteosis syndrome with no exostoses was evident in three family subjects. The rest of the family subjects manifested with normal height, and yet multiple exostoses. In this family, the skeletal manifestations were sufficiently variable for the presentation to be with either short stature or scoliosis, a Madelung’ deformity, or with severe hallux valgus associated with exostosis and with Leri-Weill dyschondrosteosis syndrome. Results: Subjects with structural chromosomal aberrations of the proband IV-7, who manifested with normal height but with multiple exostoses were excluded via 20 CAG-banded mitoses (there were no microdeletions or microduplication after performing Array-CGH-analysis). In addition, DNA examination for subject IV-8 (male cousin of the proband showed short stature and Leri-Weill dyschondrosteosis syndrome) revealed no evidence of SHOX deletions. Conclusion: We described a multigenerational non-consanguineous North African family , in which mesomelic dysplasia, whose clinical and radiological phenotypes resembled dyschondrosteosis, was a prominent feature in three family subjects. Multiple exostoses were evident in several other family subjects (most were with normal height). We would like to emphasize the variability in the phenotypic expression of multiple exostosis, especially the confusion that might arise when the condition appears both clinically and radiologically to be more complicated, and the overall picture might then be overlapped with one of the other bone dysplasias such as Leri-Weill dyschondrosteosis syndrome. J Clin Med Res. 2016;8(8):605-609 doi: http://dx.doi.org/10.14740/jocmr2593w