LUMiC Endoprosthetic Reconstruction of Periacetabular Tumor Defects: A Multicenter Follow-up Study.

BACKGROUND: We previously reported promising early results for periacetabular tumor reconstructions using the LUMiC prosthesis. The current study evaluates mid-term complications, revision rates, cumulative incidence of implant revision, and risk factors for complications in a multicenter cohort. METHODS: We assessed patients in whom a tumor defect after type P1b+2, P2, P2+3, or P1b+2+3 internal hemipelvectomy was reconstructed with a LUMiC prosthesis during the period of 2008 to 2022. Complications were reported according to the Henderson classification. Competing risks models were used to estimate the cumulative incidence of implant revision for mechanical and nonmechanical reasons, and reoperations for any complication. Cox models were used to study the effect of risk factors on dislocation and infection. RESULTS: One hundred and sixty-six patients (median follow-up, 4.2 years [interquartile range, 2.6 to 7.6 years]) were included. A total of 114 (69%) were treated for a primary malignant tumor, 46 (28%) for metastatic carcinoma, 5 (3%) for a benign aggressive lesion, and 1 (1%) for another reason. One hundred and sixty-five reoperations were performed in 82 (49%) of the patients; 104 (63%) of the reoperations were within 6 months. Thirty-two (19%) of 166 implants were revised: 13 (8%) for mechanical reasons, mainly dislocation (n = 5, 3%), and 19 (11%) for nonmechanical reasons, mainly periprosthetic joint infection (PJI) (n = 15, 9%). The cumulative incidences of revision for mechanical reasons and PJI (Henderson 1 to 4) at 2, 5, and 10 years were 11% (95% confidence interval [CI], 7% to 17%), 18% (12% to 25%), and 24% (16% to 33%), respectively. Previous surgery at the same site was associated with an increased dislocation risk (cause-specific hazard ratio [HRCS], 3.0 [95% CI, 1.5 to 6.4]; p < 0.01), and resections involving the P3 region were associated with an increased infection risk (HRCS, 2.5 [95% CI, 1.4 to 4.7]; p < 0.01). CONCLUSIONS: Despite a substantial reoperation risk, the LUMiC prosthesis demonstrated its durability in the mid-term, with a low mechanical revision rate and most patients retaining their primary implant. Most complications occur in the first postoperative months. Patients with previous surgery at the same site had an increased dislocation risk and might benefit from more conservative rehabilitation and aftercare. Measures should be aimed at reducing the PJI risk, especially in resections involving the P3 region. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Virtual biomechanical assessment of porous tantalum and custom triflange components in the treatment of patients with acetabular defects and pelvic discontinuity.

Aims: The aim of this study was to compare the biomechanical models of two frequently used techniques for reconstructing severe acetabular defects with pelvic discontinuity in revision total hip arthroplasty (THA) - the Trabecular Metal Acetabular Revision System (TMARS) and custom triflange acetabular components (CTACs) - using virtual modelling. Methods: Pre- and postoperative CT scans from ten patients who underwent revision with the TMARS for a Paprosky IIIB acetabular defect with pelvic discontinuity were retrospectively collated. Computer models of a CTAC implant were designed from the preoperative CT scans of these patients. Computer models of the TMARS reconstruction were segmented from postoperative CT scans using a semi-automated method. The amount of bone removed, the implant-bone apposition that was achieved, and the restoration of the centre of rotation of the hip were compared between all the actual TMARS and the virtual CTAC implants. Results: The median amount of bone removed for TMARS reconstructions was significantly greater than for CTAC implants (9.07 cm3 (interquartile range (IQR) 5.86 to 21.42) vs 1.16 cm3 (IQR 0.42 to 3.53) (p = 0.004). There was no significant difference between the median overall implant-bone apposition between TMARS reconstructions and CTAC implants (54.8 cm2 (IQR 28.2 to 82.3) vs 56.6 cm2 (IQR 40.6 to 69.7) (p = 0.683). However, there was significantly more implant-bone apposition within the residual acetabulum (45.2 cm2 (IQR 28.2 to 72.4) vs 25.5 cm2 (IQR 12.8 to 44.1) (p = 0.001) and conversely significantly less apposition with the outer cortex of the pelvis for TMARS implants compared with CTAC reconstructions (0 cm2 (IQR 0 to 13.1) vs 23.2 cm2 (IQR 16.4 to 30.6) (p = 0.009). The mean centre of rotation of the hip of TMARS reconstructions differed by a mean of 11.1 mm (3 to 28) compared with CTAC implants. Conclusion: In using TMARS, more bone is removed, thus achieving more implant-bone apposition within the residual acetabular bone. In CTAC implants, the amount of bone removed is minimal, while the implant-bone apposition is more evenly distributed between the residual acetabulum and the outer cortex of the pelvis. The differences suggest that these implants used to treat pelvic discontinuity might achieve short- and long-term stability through different biomechanical mechanisms.

High accuracy of positioning custom triflange acetabular components in tumour and total hip arthroplasty revision surgery.

Aims: Custom triflange acetabular components (CTACs) play an important role in reconstructive orthopaedic surgery, particularly in revision total hip arthroplasty (rTHA) and pelvic tumour resection procedures. Accurate CTAC positioning is essential to successful surgical outcomes. While prior studies have explored CTAC positioning in rTHA, research focusing on tumour cases and implant flange positioning precision remains limited. Additionally, the impact of intraoperative navigation on positioning accuracy warrants further investigation. This study assesses CTAC positioning accuracy in tumour resection and rTHA cases, focusing on the differences between preoperative planning and postoperative implant positions. Methods: A multicentre observational cohort study in Australia between February 2017 and March 2021 included consecutive patients undergoing acetabular reconstruction with CTACs in rTHA (Paprosky 3A/3B defects) or tumour resection (including Enneking P2 peri-acetabular area). Of 103 eligible patients (104 hips), 34 patients (35 hips) were analyzed. Results: CTAC positioning was generally accurate, with minor deviations in cup inclination (mean 2.7°; SD 2.84°), anteversion (mean 3.6°; SD 5.04°), and rotation (mean 2.1°; SD 2.47°). Deviation of the hip centre of rotation (COR) showed a mean vector length of 5.9 mm (SD 7.24). Flange positions showed small deviations, with the ischial flange exhibiting the largest deviation (mean vector length of 7.0 mm; SD 8.65). Overall, 83% of the implants were accurately positioned, with 17% exceeding malpositioning thresholds. CTACs used in tumour resections exhibited higher positioning accuracy than rTHA cases, with significant differences in inclination (1.5° for tumour vs 3.4° for rTHA) and rotation (1.3° for tumour vs 2.4° for rTHA). The use of intraoperative navigation appeared to enhance positioning accuracy, but this did not reach statistical significance. Conclusion: This study demonstrates favourable CTAC positioning accuracy, with potential for improved accuracy through intraoperative navigation. Further research is needed to understand the implications of positioning accuracy on implant performance and long-term survival.

Mechanical stress and inflammation have opposite effects on Wnt signaling in human chondrocytes.

Dysregulation of Wingless and Int-1 (Wnt) signaling has been strongly associated with development and progression of osteoarthritis (OA). Here, we set out to investigate the independent effects of either mechanical stress (MS) or inflammation on Wnt signaling in human neocartilage pellets, and to relate this Wnt signaling to OA pathophysiology. OA synovium-conditioned media (OAS-CM) was collected after incubating synovium from human end-stage OA joints for 24 h in medium. Cytokine levels in the OAS-CM were determined with a multiplex immunoassay (Luminex). Human neocartilage pellets were exposed to 20% MS, 2% OAS-CM or 1 ng/mL Interleukin-1ß (IL-1ß). Effects on expression levels of Wnt signaling members were determined by reverse transcription-quantitative polymerase chain reaction. Additionally, the expression of these members in articular cartilage from human OA joints was analyzed in association with joint space narrowing (JSN) and osteophyte scores. Protein levels of IL-1ß, IL-6, IL-8, IL-10, tumor necrosis factor α, and granulocyte-macrophage colony-stimulating factor positively correlated with each other. MS increased noncanonical WNT5A and FOS expression. In contrast, these genes were downregulated upon stimulation with OAS-CM or IL-1ß. Furthermore, Wnt inhibitors DKK1 and FRZB decreased in response to OAS-CM or IL-1ß exposure. Finally, expression of WNT5A in OA articular cartilage was associated with increased JSN scores, but not osteophyte scores. Our results demonstrate that MS and inflammatory stimuli have opposite effects on canonical and noncanonical Wnt signaling in human neocartilage. Considering the extent to which MS and inflammation contribute to OA in individual patients, we hypothesize that targeting specific Wnt pathways offers a more effective, individualized approach.

An open comminuted tibia fracture including a 5 cm tibial bone defect in a child: Successful management using a locking compression plate.

Traumatic bone defects (TBDs), although rare in children, are severe injuries that often represents a challenge for both orthopaedic and trauma surgeons. We present a case of a 6-year-old girl who sustained an open (Gustilo-Anderson type II) comminuted tibia fracture including a ± 5.0 cm distal tibial TBD following a road traffic accident. Open reduction and internal fixation with a 3.5 Locking Compression Plate (LCP) without additional bone grafting was performed, followed by cast immobilization for four months. One and a half years after reconstruction, the patient regained pain-free activity including full-range of motion of her leg and radiographs showed good tibial and fibular alignment, the presence of fracture consolidation and sufficient filling of the TBD. This case report aims to show first evidence of the safety and efficacy of single LCP plating followed by cast immobilization applied in a paediatric patient with a large tibial TBD.

Custom triflange acetabular components for large acetabular defect reconstruction in revision total hip arthroplasty: a systematic review and meta-analysis on 1218 patients.

Purpose: This is a systematic review and meta(regression) analysis to assess the performance of custom triflange acetabular components (CTAC) in total hip arthroplasty (THA) revision surgery. Implant-related complications, failure rate, functional outcomes and implant and surgical technique-related predictors for outcome were assessed. Methods: This systematic review was performed according to PRISMA guidelines and registered with PROSPERO (2020 CRD42020209700). PubMed, Embase, Web of Science, COCHRANE Library and Emcare were searched. Studies on Paprosky type 3A and 3B or AAOS type 3 and 4 acetabular defects with a minimum follow-up of 12 months and cohorts > 10 patients were included. Results: Thirty-three studies were eligible for inclusion (n = 1235 hips, 1218 patients). The methodological quality of the studies was moderate (AQUILA: 7.4/11 points). Considerable heterogeneity was observed in terms of complications, re-operations and implant failure reporting. The total incidence of implant-related complications was 24%. The incidence of re-operation for any reason was 15%, and the implant failure rate was 12% at a mean of 46.9 months and the post-operative Harris Hip Score improved by a mean of 40 points. Several predictors for outcome were found, such as implant generation, follow-up length and study start date. Conclusions: The use of CTAC in revision THA has satisfactory complication and implant failure rates. The CTAC technique improves post-operative clinical outcomes and the meta-regression analysis showed that there is a clear association between improvements in the CTAC performance and the evolvement of this technique over time.

Osteomyelitis caused by Streptococcus intermedius in immunocompetent adults - a case report and systematic literature review.

Hematogenous osteomyelitis caused by Streptococcus intermedius is rare, particularly in immunocompetent adults. The aim of this paper is to provide an overview of the clinical presentation, prognosis as well as treatment of this disease, with the focus on immunocompetent adults. Six medical literature libraries were searched to identify studies reporting on Streptococcus intermedius induced hematogenous osteomyelitis in immunocompetent adults. In addition, we presented a case of a 44-year-old man from our institution that is illustrative for this disease. Four case reports describing four patients were identified by this systematic literature review. Hence, the data of five patients (including our case) were assessed. The most common presenting symptom was localised pain, followed by fever. Portal entries were found in two patients (general periodontitis and necrotic dentition). The localisations of osteomyelitis were diverse: femoral (two patients), lumbar spine (two patients), and the iliac bone (one patient). Treatment strategies varied strongly, but antibiotics (penicillins) were administered in each case, and two patients underwent surgical debridement. Follow-up ranged from 2 weeks to more than 6 months; one patient died from septic shock. Only a very limited number of immunocompetent adults with Streptococcus intermedius induced hematogenous osteomyelitis have been described. Based on the available data, we summarised the clinical presentation, prognosis as well as treatment of hematogenous osteomyelitis caused by Streptococcus intermedius in this patient population.

Custom designed and 3D-printed titanium pelvic implants for acetabular reconstruction after tumour resection.

BACKGROUND: Reconstructive procedure following resection of large pelvic tumours around the hip joint remains a complex challenge. METHODS: This study presents a retrospective case series of patients presenting with benign or malignant pelvic tumour for which an internal hemipelvectomy including the hip joint and subsequent reconstruction with a custom designed 3-dimensional printed titanium pelvic implant (3DPPI) has been performed between August 2013 and January 2018. RESULTS: 15 consecutive patients with a median age of 33.9 years (IQR 26.4-72.2) and a median BMI of 20.7 kg/m2 (IQR 19.0-33.3) were reviewed after median follow-up of 33.8 months (IQR 24.0-78.1). The majority of patients presented with a malignant tumour as their principal diagnosis (n = 13, 86.7%). The median surgical time was 5.5 hours (IQR 4.5-8.5) and median peri-operative blood loss was 5000 ml (IQR 2000-10000). The median MSTS score at follow-up was 63.3% (IQR 51.7-86.7%). The median NRS in rest was 0.0 (IQR 0.0-5.0), the median NRS during activity was 2.0 (IQR 0.5-7.0) and the median HOOS-PS was 76.6% (IQR 67.9-91.0). 4 patients had implant-specific complications (n = 4, 26.6%); 1 hip dislocation (Henderson type 1a), 3 structural complications (type 3a), 1 deep infection (type 4a) and 1 local tumour recurrence (type 5b). At follow-up, 4 out of 15 implants were classified as a failure, resulting in an implant survival rate of 73.3%. CONCLUSIONS: Acceptable peri-operative outcomes, functional results, complication rates and short-term implant survival can be achieved in a cohort of complex patients undergoing 3DPPI reconstruction after hemipelvectomy including the acetabulum.

Systemic Metal Ion Concentrations in Patients With Hip and Knee Megaprostheses: A Prospective Cohort Study.

Background: Local tissue and serum metal ions have been shown to be elevated in some metal-on-metal and metal-on-polyethylene joint replacements. Local elevations have been linked to adverse local tissue reactions in some patients, and systemic elevation has been less commonly implicated cardiac and neurologic issues. Using a prospective study design, we aimed to identify the changes in serum metal ion levels after hip or knee megaprosthesis reconstruction. Furthermore, we will evaluate the occurrence of adverse effects and complications, possibly linked to metal ion elevation. Methods: Fourteen consecutive patients receiving a Modular Universal Tumor Revision System megaprosthesis were enrolled. Blood samples were collected preoperatively and postoperatively to determine the serum ion concentrations of aluminum, chromium, cobalt, and silver. To evaluate the safety of the megaprostheses and the subsequently possible related (elevated) serum metal ion concentrations, all adverse effects and complications were registered until last outpatient clinic visit at the time of this study. Results: Compared to the preoperative median serum concentrations, the postoperative median serum concentrations of chromium, silver, and cobalt increased 11-fold, 62-fold, and 64-fold, respectively. The median serum concentration of aluminum increased with 16%. Elevations were primarily noted in patients with knee prostheses. Eight patients had no adverse effects or complications during the period between preoperative and postoperative blood sampling. One adverse effect directly related to the serum metal ion concentrations, namely argyria, was observed. Conclusions: This study documents significantly elevated concentrations of the metal ions, but only one adverse effect directly related to the metal ion concentrations was observed. Future studies are needed to further assess the impact of elevated metal ion levels after megaprostheses, specifically knee implants, which are metal-on-metal.

Inhibiting thyroid activation in aged human explants prevents mechanical induced detrimental signalling by mitigating metabolic processes.

OBJECTIVES: To investigate whether the deiodinase inhibitor iopanoic acid (IOP) has chondroprotective properties, a mechanical stress induced model of human aged explants was used to test both repeated dosing and slow release of IOP. METHODS: Human osteochondral explants subjected to injurious mechanical stress (65%MS) were treated with IOP or IOP encapsulated in poly lactic-co-glycolic acid-polyethylene glycol nanoparticles (NP-IOP). Changes to cartilage integrity and signalling were determined by Mankin scoring of histology, sulphated glycosaminoglycan (sGAG) release and expression levels of catabolic, anabolic and hypertrophic markers. Subsequently, on a subgroup of samples, RNA sequencing was performed on 65%MS (n = 14) and 65%MS+IOP (n = 7) treated cartilage to identify IOP's mode of action. RESULTS: Damage from injurious mechanical stress was confirmed by increased cartilage surface damage in the Mankin score, increased sGAG release, and consistent upregulation of catabolic markers and downregulation of anabolic markers. IOP and, though less effective, NP-IOP treatment, reduced MMP13 and increased COL2A1 expression. In line with this, IOP and NP-IOP reduced cartilage surface damage induced by 65%MS, while only IOP reduced sGAG release from explants subjected to 65%MS. Lastly, differential expression analysis identified 12 genes in IOP's mode of action to be mainly involved in reducing metabolic processes (INSIG1, DHCR7, FADS1 and ACAT2) and proliferation and differentiation (CTGF, BMP5 and FOXM1). CONCLUSION: Treatment with the deiodinase inhibitor IOP reduced detrimental changes of injurious mechanical stress. In addition, we identified that its mode of action was likely on metabolic processes, cell proliferation and differentiation.

Long non-coding RNA expression profiling of subchondral bone reveals AC005165.1 modifying FRZB expression during osteoarthritis.

OBJECTIVE: To gain insight in the expression profile of long non-coding RNAs (lncRNAs) in OA subchondral bone. METHODS: RNA sequencing data of macroscopically preserved and lesioned OA subchondral bone of patients that underwent joint replacement surgery due to OA (N = 22 pairs; 5 hips, 17 knees, Research osteoArthrits Articular Tissue (RAAK study) was run through an in-house pipeline to detect expression of lncRNAs. Differential expression analysis between preserved and lesioned bone was performed. Spearman correlations were calculated between differentially expressed lncRNAs and differentially expressed mRNAs identified previously in the same samples. Primary osteogenic cells were transfected with locked nucleic acid (LNA) GapmeRs targeting AC005165.1 lncRNA, to functionally investigate its potential mRNA targets. RESULTS: In total, 2816 lncRNAs were well-expressed in subchondral bone and we identified 233 lncRNAs exclusively expressed in knee and 307 lncRNAs exclusively in hip. Differential expression analysis, using all samples (N = 22 pairs; 5 hips, 17 knees), resulted in 21 differentially expressed lncRNAs [false discovery rate (FDR) < 0.05, fold change (FC) range 1.19-7.39], including long intergenic non-protein coding RNA (LINC) 1411 (LINC01411, FC = 7.39, FDR = 2.20 × 10-8), AC005165.1 (FC = 0.44, FDR = 2.37 × 10-6) and empty spiracles homeobox 2 opposite strand RNA (EMX2OS, FC = 0.41, FDR = 7.64 × 10-3). Among the differentially expressed lncRNAs, five were also differentially expressed in articular cartilage, including AC005165.1, showing similar direction of effect. Downregulation of AC005165.1 in primary osteogenic cells resulted in consistent downregulation of highly correlated frizzled related protein (FRZB). CONCLUSION: The current study identified a novel lncRNA, AC005165.1, being dysregulated in OA articular cartilage and subchondral bone. Downregulation of AC005165.1 caused a decreased expression of OA risk gene FRZB, an important member of the wnt pathway, suggesting that AC005165.1 could be an attractive potential therapeutic target with effects in articular cartilage and subchondral bone.

Early Failure of a Carbon-Fiber-Reinforced Polyetheretherketone Distal Femur Plate: A Case Report.

CASE: In this case, we report on a carbon-fiber-reinforced polyetheretherketone plate failure 4 months after implantation, radiation therapy, chemotherapy, and protective weight-bearing in a 75-year-old woman who sustained a nontraumatic pathological distal femur fracture due to lymphoma. CONCLUSION: Although carbon-fiber composite implants are regularly used and, to date, there have been no reports of early clinical failures, the longevity of the implant's structural integrity after high-dose radiation and/or chemotherapy treatment has not been fully explored. Therefore, we deem it too early to conclude that carbon-fiber-reinforced polyetheretherketone implants are superior to conventional implants in treating (pathological) fractures.

Elucidating Epigenetic Regulation by Identifying Functional cis-Acting Long Noncoding RNAs and Their Targets in Osteoarthritic Articular Cartilage.

OBJECTIVE: To identify robustly differentially expressed long noncoding RNAs (lncRNAs) with osteoarthritis (OA) pathophysiology in cartilage and to explore potential target messenger RNA (mRNA) by establishing coexpression networks, followed by functional validation. METHODS: RNA sequencing was performed on macroscopically lesioned and preserved OA cartilage from patients who underwent joint replacement surgery due to OA (n = 98). Differential expression analysis was performed on lncRNAs that were annotated in GENCODE and Ensembl databases. To identify potential interactions, correlations were calculated between the identified differentially expressed lncRNAs and the previously reported differentially expressed protein-coding genes in the same samples. Modulation of chondrocyte lncRNA expression was achieved using locked nucleic acid GapmeRs. RESULTS: By applying our in-house pipeline, we identified 5,053 lncRNAs that were robustly expressed, of which 191 were significantly differentially expressed (according to false discovery rate) between lesioned and preserved OA cartilage. Upon integrating mRNA sequencing data, we showed that intergenic and antisense differentially expressed lncRNAs demonstrate high, positive correlations with their respective flanking sense genes. To functionally validate this observation, we selected P3H2-AS1, which was down-regulated in primary chondrocytes, resulting in the down-regulation of P3H2 gene expression levels. As such, we can confirm that P3H2-AS1 regulates its sense gene P3H2. CONCLUSION: By applying an improved detection strategy, robustly differentially expressed lncRNAs in OA cartilage were detected. Integration of these lncRNAs with differential mRNA expression levels in the same samples provided insight into their regulatory networks. Our data indicates that intergenic and antisense lncRNAs play an important role in regulating the pathophysiology of OA.