Surgical management of 144 diffuse-type TGCT patients in a single institution: A 20-year cohort study.

BACKGROUND AND OBJECTIVES: Surgery is the mainstay of treatment for tenosynovial giant cell tumors (TGCTs). However, achieving a cure through surgery alone remains challenging, especially for the diffuse-type (D-TGCT). METHODS: Our goal was to describe the surgical management of patients with D-TGCT related to large joints, treated between 2000 and 2020. We analyzed the effect of (in)complete resections and the presence of postoperative tumor (POT) on magnetic resonance imaging (MRI) on radiological and clinical outcomes. RESULTS: A total of 144 patients underwent open surgery for D-TGCT, of which 58 (40%) had treatment before. The median follow-up was 65 months. One hundred twenty-five patients underwent isolated open surgeries, in which 25 (20%) patients' D-TGCT was intentionally removed incompletely. POT presence on the first postoperative MRI was observed in 64%. Both incomplete resections and POT presence were associated with higher rates of radiological progression (73% vs. 44%; Kaplan-Meier [KM] analysis p = 0.021) and 59% versus 7%; KM analysis p < 0.001), respectively. Furthermore, patients with POT presence clinically worsened more often than patients without having POT (49% vs. 24%; KM analysis p = 0.003). CONCLUSIONS: D-TGCT is often resected incompletely and tumor presence is commonly observed on the first postoperative MRI, resulting in worse radiological and clinical outcomes. Therefore, surgeons should try to remove D-TGCT in toto and consider other multimodal therapeutic strategies.

Meniscal allograft transplantation in The Netherlands: long-term survival, patient-reported outcomes, and their association with preoperative complaints and interventions.

PURPOSE: Evaluation of survival of meniscal allograft transplantation (MAT) and postoperative patient-reported outcome (PRO), and their association with prior interventions of the knee. METHODS: A prospective consecutive study of 109 consecutive patients who had an arthroscopic meniscal allograft transplantation (MAT) between 1999 and 2017 by a single surgeon. Patients were assessed with KOOS scores, preoperative and after a minimal follow-up of 2 years. Furthermore, two anchor questions (whether expectations were met and overall satisfaction, on a five-point Likert scale) were asked. Additionally, prior interventions to MAT were evaluated. RESULTS: Prior to MAT, patients had undergone an average of 2.8 (range 1-14) of surgical procedures of the knee. Overall, mean allograft survival was 16.1 years (95% CI 14.8-17.5 years). Higher age at surgery was associated with lower MAT survival: hazard ratio for MAT failure was 1.19 per year increase (95% CI 1.04 to 1.36, p = 0.009). At 4.5 years (IQR, 2-9) of follow-up, all KOOS score were still improved compared to baseline. Age below 35 years, simultaneous anterior cruciate ligament reconstruction and number of knee surgeries before MAT were associated with lower KOOS scores. Overall patient expectations and overall satisfaction after MAT were not associated with preoperative patient characteristics nor with the number or kind of preoperative interventions. CONCLUSION: Meniscal allograft transplantation has a good overall survival with a clinically relevant improvement. Both meniscal allograft survival and PRO were associated with age. PRO was lower in patients younger than 35 years at time of MAT and meniscal allograft survival was worse in patients older than 50 years. PRO was associated with preoperative patient characteristics and number of surgical procedures prior to MAT. All patients reported improved postoperative satisfaction and met expectations after MAT, both independent of the preoperative history of knee interventions. LEVEL OF EVIDENCE: Level III. Trial registration Medical ethical review board (METC) number: 17-104 (7 August 2017). Dutch Trial Register (NTR) number: NTR6630 (4 July 2017).

Dosing and treatment duration of suppressive antimicrobial therapy in orthopedic implant infections: a cohort study.

Introduction: Limited data inform about the optimal dosing and duration of suppressive antimicrobial therapy (SAT) for orthopedic implant infection (OII). We aimed to compare the effectiveness of low-dosage with standard-dosage SAT and evaluate the safety of stopping SAT. Methods: All patients with OII treated with SAT from 2011 to 2022 were retrospectively included. Data were extracted from electronic patient files. Low-dosage SAT was defined as antimicrobial therapy dosed lower than the standard dosage recommended for OII. The association of dosing strategy and other factors with failure-free survival were assessed by Kaplan-Meier and Cox proportional hazard models. Results: One-hundred-and-eight patients were included. The median follow-up time after SAT initiation was 21 months (interquartile range (IQR) 10-42 months). SAT was successful in 74 patients (69 %). Low-dosage SAT ( n = 82 ) was not associated with failure in univariate (hazard ratio (HR) 1.23, 95 % confidence interval (CI) 0.53-2.83) and multivariate analyses (HR 1.24, 95 % CI 0.54-2.90). In 25 patients (23 %), SAT was stopped after a median treatment duration of 26 months. In this group, one patient (4 %) developed a relapse. Conclusions: In this study, low-dosage SAT was as effective as standard dosage SAT. Moreover, stopping SAT after 2 to 3 years may be justified in patients with a good clinical course. These findings warrant further research on optimal dosing and duration of SAT and on the durability of in vivo biofilms.

Multimodal profiling of chordoma immunity reveals distinct immune contextures.

BACKGROUND: Chordomas are rare cancers from the axial skeleton which present a challenging clinical management with limited treatment options due to their anatomical location. In recent years, a few clinical trials demonstrated that chordomas can respond to immunotherapy. However, an in-depth portrayal of chordoma immunity and its association with clinical parameters is still lacking. METHODS: We present a comprehensive characterization of immunological features of 76 chordomas through application of a multimodal approach. Transcriptomic profiling of 20 chordomas was performed to inform on the activity of immune-related genes through the immunologic constant of rejection (ICR) signature. Multidimensional immunophenotyping through imaging mass cytometry was applied to provide insights in the different immune contextures of 32 chordomas. T cell infiltration was further evaluated in all 76 patients by means of multispectral immunofluorescence and then associated with clinical parameters through univariate and multivariate Cox proportional hazard models as well as Kaplan-Meier estimates. Moreover, distinct expression patterns of human leukocyte antigen (HLA) class I were assessed by immunohistochemical staining in all 76 patients. Finally, clonal enrichment of the T cell receptor (TCR) was sought through profiling of the variable region of TCRB locus of 24 patients. RESULTS: Chordomas generally presented an immune "hot" microenvironment in comparison to other sarcomas, as indicated by the ICR transcriptional signature. We identified two distinct groups of chordomas based on T cell infiltration which were independent from clinical parameters. The highly infiltrated group was further characterized by high dendritic cell infiltration and the presence of multicellular immune aggregates in tumors, whereas low T cell infiltration was associated with lower overall cell densities of immune and stromal cells. Interestingly, patients with higher T cell infiltration displayed a more pronounced clonal enrichment of the TCR repertoire compared with those with low T cell counts. Furthermore, we observed that the majority of chordomas maintained HLA class I expression. CONCLUSION: Our findings shed light on the natural immunity against chordomas through the identification of distinct immune contextures. Understanding their immune landscape could guide the development and application of immunotherapies in a tailored manner, ultimately leading to an improved clinical outcome for patients with chordoma.

Wound drainage after arthroplasty and prediction of acute prosthetic joint infection: prospective data from a multicentre cohort study using a telemonitoring app.

Background: Differentiation between uncomplicated and complicated postoperative wound drainage after arthroplasty is crucial to prevent unnecessary reoperation. Prospective data about the duration and amount of postoperative wound drainage in patients with and without prosthetic joint infection (PJI) are currently absent. Methods: A multicentre cohort study was conducted to assess the duration and amount of wound drainage in patients after arthroplasty. During 30 postoperative days after arthroplasty, patients recorded their wound status in a previously developed wound care app and graded the amount of wound drainage on a 5-point scale. Data about PJI in the follow-up period were extracted from the patient files. Results: Of the 1019 included patients, 16 patients (1.6 %) developed a PJI. Minor wound drainage decreased from the first to the fourth postoperative week from 50 % to 3 %. Both moderate to severe wound drainage in the third week and newly developed wound drainage in the second week after a week without drainage were strongly associated with PJI (odds ratio (OR) 103.23, 95 % confidence interval (CI) 26.08 to 408.57, OR 80.71, 95 % CI 9.12 to 714.52, respectively). The positive predictive value (PPV) for PJI was 83 % for moderate to heavy wound drainage in the third week. Conclusion: Moderate to heavy wound drainage and persistent wound drainage were strongly associated with PJI. The PPV of wound drainage for PJI was high for moderate to heavy drainage in the third week but was low for drainage in the first week. Therefore, additional parameters are needed to guide the decision to reoperate on patients for suspected acute PJI.

Aggressive unifocal bone Langerhans cell histiocytosis with soft tissue extension both responsive to radiotherapy: a case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare haematological neoplasm characterized by the accumulation of CD1a+, CD207/Langerin+ histiocytes within inflammatory lesions. LCH can involve any organ, but osteolytic bone lesions are most often encountered. Unifocal bone lesions may regress spontaneously after a thick needle biopsy has been taken. CASE PRESENTATION: In this case report, we describe the initial presentation of a single BRAFV600E mutated osteolytic LCH lesion in the left proximal humerus of a 46-year-old previously healthy woman. Despite multiple surgical interventions, she unexpectedly experienced progressive disease manifestation with significant soft tissue extension to the surrounding musculature, subcutis and epidermis. Because the disease manifestation remained loco-regional, radiotherapy (RT) (total dose of 20 Gy in 10 fractions) was initiated. CONCLUSION: The patient achieved a complete remission without any side effects. This case highlights that RT is a rational and relative mild local treatment option for patients with aggressive LCH affecting the bone and surrounding soft tissue.

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.

A human in vitro 3D neo-cartilage model to explore the response of OA risk genes to hyper-physiological mechanical stress.

Objective: Due to the complexity and heterogeneity of osteoarthritis (OA) pathophysiology, studying the interaction between intrinsic molecular changes in chondrocytes after hyper-physiological mechanical stress (MS) and aberrant signalling of OA risk genes remains a challenge. In this study we set out to set up an in vitro 3D neo cartilage pellet model that enables us to explore the responses of OA risk genes to hyper-physiological MS. Design: Human primary chondrocyte neo-cartilage pellets were exposed for 2 days to 2 â€‹× â€‹10 â€‹min of hyper-physiological dynamic MS attained by a 20% strain and a frequency of 5 â€‹Hz. In order to assess cartilage damage, sulphated glycosaminoglycan (sGAG) content in the neo-cartilage was quantified using Alcian blue staining and a dimethyl methylene blue (DMMB) assay, while cleavage of aggrecan was visualized by immunohistochemical staining of aggrecan neo-epitope NITEGE. In addition, changes in expression levels of catabolic, anabolic and hypertrophic genes, and of three OA risk genes; IL11, MGP and TGFA were determined. Results: Hyper-physiological MS induced cartilage damage, as reflected by decreased sGAG content. mRNA levels of aggrecanase ADAMTS5 were increased, while hypertrophic gene RUNX2 was downregulated. MS increased expression of pro-apoptotic marker NOXA. Furthermore, 20% MS led to increased expression of all three OA risk genes IL11, MGP and TGFA. Conclusions: We established a human in vitro model in which hyper-physiological MS induced cartilage damage and catabolic signalling. Next, we demonstrated its usage to study OA risk genes and their response to the mechanical aspects of OA pathophysiology.

Effectiveness of Different Antimicrobial Strategies for Staphylococcal Prosthetic Joint Infection: Results From a Large Prospective Registry-Based Cohort Study.

Background: Treatment of staphylococcal prosthetic joint infection (PJI) usually consists of surgical debridement and prolonged rifampicin combination therapy. Tailored antimicrobial treatment alternatives are needed due to frequent side effects and drug-drug interactions with rifampicin combination therapy. We aimed to assess the effectiveness of several alternative antibiotic strategies in patients with staphylococcal PJI. Methods: In this prospective, multicenter registry-based study, all consecutive patients with a staphylococcal PJI, treated with debridement, antibiotics and implant retention (DAIR) or 1-stage revision surgery between January 1, 2015 and November 3, 2020, were included. Patients were treated with a long-term rifampicin combination strategy (in 2 centers) or a short-term rifampicin combination strategy (in 3 centers). Antimicrobial treatment strategies in these centers were defined before the start of the registry. Patients were stratified in different groups, depending on the used antimicrobial strategy. Cox proportional hazards models were used to compare outcome between the groups. Results: Two hundred patients were included and stratified in 1 long-term rifampicin group (traditional rifampicin combination therapy) or 1 of 3 short-term rifampicin groups (clindamycin or flucloxacillin or vancomycin monotherapy, including rifampicin for only 5 postoperative days). Adjusted hazard ratios (aHRs) for failure in patients treated with short-term rifampicin and either flucloxacillin or clindamycin were almost equal to patients treated with long-term rifampicin combination therapy (aHR = 1.21; 95% confidence interval, .34-4.40). Conclusions: A short-term rifampicin strategy with either clindamycin or flucloxacillin and only 5 days of rifampicin was found to be as effective as traditional long-term rifampicin combination therapy. A randomized controlled trial is needed to further address efficacy and safety of alternative treatment strategies for staphylococcal PJI.

Elucidating mechano-pathology of osteoarthritis: transcriptome-wide differences in mechanically stressed aged human cartilage explants.

BACKGROUND: Failing of intrinsic chondrocyte repair after mechanical stress is known as one of the most important initiators of osteoarthritis. Nonetheless, insight into these early mechano-pathophysiological processes in age-related human articular cartilage is still lacking. Such insights are needed to advance clinical development. To highlight important molecular processes of osteoarthritis mechano-pathology, the transcriptome-wide changes following injurious mechanical stress on human aged osteochondral explants were characterized. METHODS: Following mechanical stress at a strain of 65% (65%MS) on human osteochondral explants (n65%MS = 14 versus ncontrol = 14), RNA sequencing was performed. Differential expression analysis between control and 65%MS was performed to determine mechanical stress-specific changes. Enrichment for pathways and protein-protein interactions was analyzed with Enrichr and STRING. RESULTS: We identified 156 genes significantly differentially expressed between control and 65%MS human osteochondral explants. Of note, IGFBP5 (FC = 6.01; FDR = 7.81 × 10-3) and MMP13 (FC = 5.19; FDR = 4.84 × 10-2) were the highest upregulated genes, while IGFBP6 (FC = 0.19; FDR = 3.07 × 10-4) was the most downregulated gene. Protein-protein interactions were significantly higher than expected by chance (P = 1.44 × 10-15 with connections between 116 out of 156 genes). Pathway analysis showed, among others, enrichment for cellular senescence, insulin-like growth factor (IGF) I and II binding, and focal adhesion. CONCLUSIONS: Our results faithfully represent transcriptomic wide consequences of mechanical stress in human aged articular cartilage with MMP13, IGF binding proteins, and cellular senescence as the most notable results. Acquired knowledge on the as such identified initial, osteoarthritis-related, detrimental responses of chondrocytes may eventually contribute to the development of effective disease-modifying osteoarthritis treatments.

SAAP-148 Eradicates MRSA Persisters Within Mature Biofilm Models Simulating Prosthetic Joint Infection.

Prosthetic joint infection (PJI) is a severe complication of arthroplasty. Due to biofilm and persister formation current treatment strategies often fail. Therefore, innovative anti-biofilm and anti-persister agents are urgently needed. Antimicrobial peptides with their broad antibacterial activities may be such candidates. An in vitro model simulating PJI comprising of rifampicin/ciprofloxacin-exposed, mature methicillin-resistant Staphylococcus aureus (MRSA) biofilms on polystyrene plates, titanium/aluminium/niobium disks, and prosthetic joint liners were developed. Bacteria obtained from and residing within these biofilms were exposed to SAAP-148, acyldepsipeptide-4, LL-37, and pexiganan. Microcalorimetry was used to monitor the heat flow by the bacteria in these models. Daily exposure of mature biofilms to rifampicin/ciprofloxacin for 3 days resulted in a 4-log reduction of MRSA. Prolonged antibiotic exposure did not further reduce bacterial counts. Microcalorimetry confirmed the low metabolic activity of these persisters. SAAP-148 and pexiganan, but not LL-37, eliminated the persisters while ADEP4 reduced the number of persisters. SAAP-148 further eradicated persisters within antibiotics-exposed, mature biofilms on the various surfaces. To conclude, antibiotic-exposed, mature MRSA biofilms on various surfaces have been developed as in vitro models for PJI. SAAP-148 is highly effective against persisters obtained from the biofilms as well as within these models. Antibiotics-exposed, mature biofilms on relevant surfaces can be instrumental in the search for novel treatment strategies to combat biofilm-associated infections.

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.

Talar beak-induced intermittent ischemia of the foot.

A 44-year-old man presented with symptoms of intermittent ischemia of the right foot. Computed tomography scanning of the right foot revealed a talar beak that had a close anatomic relation with the dorsalis pedis artery. Duplex ultrasound performed during a symptomatic episode confirmed ischemia induced by severe vasospasm of the dorsalis pedis artery that normalized 30 minutes later. The talar beak was removed by open surgery that resulted in complete resolution of the patient's symptoms. A talar beak should be considered in intermittent ischemic complaints of the foot in patients without atherosclerosis.

The Occurrence of Meniscal and Chondral Injury in Two-Stage Revision Anterior Cruciate Ligament Reconstruction: A Consecutive Case Series.

Two-stage revision anterior cruciate ligament (ACL) reconstruction is an effective way to revise suboptimal tunnel-placement allowing for proper graft fixation. However, prolonged increased laxity of the knee may increase the risk of meniscal or chondral injury. It was hypothesized that no additional meniscal or chondral lesions occur in between the two stages of the two-stage revision ACL reconstruction. In this retrospective study, 42 patients undergoing a two-stage revision ACL reconstruction were included. Surgical notes for both stages were screened for meniscal and chondral status, interventions to any concurrent injury, surgery dates, along with basic patient characteristics. In 4 of the 42 patients, a new meniscal tear occurred in between the two stages, of which three required partial meniscectomy during the second stage of the ACL revision. One patient experienced a new small degenerative tear that did not require intervention. Two out of the four menisci that were repaired during the first stage had failed and required partial meniscectomy. No significant difference was found in the time between the two stages with respect to the occurrence of meniscal tears. No significant differences in chondral status were found. In conclusion, approximately 10% of patients developed a new meniscal tear and no difference in macroscopic chondral injury was observed between the first and second stages.

[Prosthetic joint infection]. / Geïnfecteerde gewrichtsprothese.

Prosthetic joint infection A prosthetic joint infection (PJI) is a serious complication that can lead to lengthy hospitalization, significant limitations in mobility, and a reduced quality of life. For acute PJI, the aim is to cure the infection whilst retaining the prosthesis; this can be achieved by means of thorough surgical debridement, cleaning of the artificial material, replacement of exchangeable prosthesis parts and adjuvant antibiotic therapy. In cases of chronic PJI, the prosthetic joint needs to be replaced. For patients in whom surgery is not feasible, or who refuse surgical intervention, chronic suppressive antibiotic therapy can be applied if the infection persists. In order to increase the likelihood of a favourable outcome, it is important to take a multidisciplinary approach.

Two-year follow-up of bone mineral density changes in the knee after meniscal allograft transplantation: Results of an explorative study.

BACKGROUND: The potential chondroprotective effect of meniscal allograft transplantation (MAT) is unclear. Subchondral bone mineral density (BMD) and subchondral bone remodeling play important roles in osteoarthritis development. Evaluation of subchondral BMD after MAT might give more insight into the potential chondroprotective effect. The purpose of this study was to determine early BMD changes in the knee after MAT. METHODS: Twenty-six consecutive patients underwent MAT during 2010-2013. The BMD was measured using dual-energy x-ray absorptiometry (DXA) scan preoperatively, and six months, one and two years postoperatively. Bone mineral density was measured in six regions of interest (ROIs) in the tibia and femur (medial, central, lateral) in both treated and healthy contralateral knees. RESULTS: The BMD levels of MAT knees did not significantly change during two years of follow-up in almost all ROIs. Bone mineral density was significant higher in nearly all ROIs in MAT knees at almost all follow-ups compared to healthy contralateral knees. In the healthy contralateral knees, BMD slightly, but not statistically, decreased in the first postoperative year, where it normalized to baseline values at two-year follow-up. The BMD levels in all ROIs did not significantly differ between the patients with or without chondropathy at baseline and two-year follow-up. CONCLUSION: Based on the findings, MAT did not show a significant influence on BMD in the first two postoperative years. Longer follow-up is necessary to prove the potential chondroprotective effect of MAT using BMD measurements.

Translation and Validation of the Dutch Western Ontario Meniscal Evaluation Tool.

The aim of this study was to translate the Western Ontario Meniscal Evaluation Tool (WOMET) into Dutch, to evaluate the content validity, construct validity, reliability, and responsiveness, and to determine the minimal important change (MIC) of the Dutch version. The WOMET was translated into Dutch according to a standardized forward-backward translation protocol. A total of 86 patients (51 males, 35 females, median age 52 years [interquartile range, 43-60 years]) with isolated meniscal pathology were included. The WOMET was completed three times; at baseline, around 2 weeks, and after 3 months from the baseline. Knee injury and osteoarthritis outcome score, International Knee Documentation Committee subjective knee form, short-form 36, and an anchor question were also answered. There were good results for content validity (floor and ceiling effects [< 15%]), construct validity (79% of the predefined hypotheses were confirmed), internal consistency (Cronbach α = 0.87, 0.79, and 0.86 for each subscale score), test-retest reliability (intraclass correlation coefficient = 0.78 for total WOMET score), and responsiveness (79% of the predefined hypotheses were confirmed). The smallest detectable change and MIC for the Dutch WOMET are 20.5 and 14.7, respectively. The Dutch version of the WOMET is valid and reliable for assessing health-related quality of life in patients with meniscal pathology.