Non-invasive sampling of tumor-derived genetic material in circulation through liquid biopsy may be very beneficial for an accurate diagnosis and evaluation of response to treatment in patients with malignant and benign soft tissue tumors. We previously showed that tumor-derived genomic aberrations can be detected in plasma of patients with leiomyosarcoma (LMS) and leiomyoma (LM). In LMS patients, we also showed that the levels of circulating tumor DNA (ctDNA) correspond with response to treatment. We developed an approach tailored to genomic profile of LMS (characterized by intermediate levels of point mutations and copy number alterations, CNAs). Based on TCGA data, we designed a panel of 89 most frequently mutated genes in LMS, which we profiled in plasma DNA by deep sequencing. In parallel, plasma samples were analyzed by shallow whole genome sequencing for detection of CNAs. With this approach, we detected ctDNA in 71% (20/28) of samples from 6/7 patients with advanced disease with >98% specificity. The combination approach for orthogonal profiling of point mutations and CNAs proved to increase the sensitivity of ctDNA detection. Currently, we seek to further improve the sensitivity of ctDNA detection by refining our capture panel and tracking LMS-specific DNA methylation markers in circulation, in addition to point mutations and CNAs. The ultimate goals of our ctDNA studies are 1) to develop a highly sensitive assay for evaluation of response to therapy and long-term surveillance for patients with LMS, and 2) to develop a blood-based test for accurate pre-operative distinction between LMS and LM. To identify LMS-specific DNA methylation markers, we analyzed a test cohort of 76 LM, 35 uterine LMS and 31 extra-uterine LMS by Illumina Infinium EPIC arrays. We identified differentially methylated CpGs between LM and uterine LMS, and between LM and all LMS using a newly developed custom pipeline in R. The results of this analysis are currently being validated in a new dataset of 41 LM and 153 LMS generated by our group. Recently published (PMID: 34301934) genomic data from new 53 LMS samples are used to refine the panel of the most frequently mutated genes that we identified previously in the LMS TCGA data. Our preliminary analysis of test cohort revealed >270 differentially methylated CpGs between LM and uterine LMS, and >1000 differentially methylated CpGs between LM and all LMS. The preliminary analysis of genomic data shows that the initial panel of 89 frequently mutated genes could be substantially narrowed down to cover only selected tumor suppressor genes. Once validated, these results will be used to refine the ctDNA assay for LMS and LM. Our results point to multiple epigenetic markers that could be used for ctDNA profiling, in addition to point mutations or CNAs. Further validation will allow us to select the most reliable LMS- and LM-specific DNA methylation markers and the most frequently mutated regions across independent datasets, and these markers will be incorporated into our new ctDNA test for a concurrent detection of point mutations, CNAs and DNA methylation markers in circulation.
Reverse total shoulder arthroplasty (RTSA) is rapidly being adopted as the standard procedure for a growing number of shoulder arthropathies. Though short-term outcomes are promising, mid- and long-term follow-ups present a number of complications – among them, humeral stem and glenosphere component loosening. Though not the primary complication, previously reported aseptic loosening required revision in 100% of cases. As the number of patients undergoing RTSA increases, especially in the younger population, it is important for surgeons to identify and utilize prostheses with stable long-term fixation. It has previously been shown in the hip and knee literature that implant migration in the first two years following surgery is predictive of later failure due to loosening in the 5=10-year postoperative window. The purpose of this study is to, for the first time, evaluate the pattern and total magnitude of implant migration in reverse shoulder arthroplasty using the gold standard imaging technique radiostereometric analysis (RSA). Forty patients were prospectively randomized to receive either a cemented or press-fit humeral stem, and a glenosphere secured to the glenoid with either autologous bone graft or 3D printed porous titanium for primary reverse total shoulder arthroplasty. Following surgery, participants are imaged using RSA, a calibrated, stereo x-ray technique. Radiographs are acquired at 6 weeks (baseline), 3 months, 6 months, 1 year, and 2 years. Migration of the humeral stem and glenosphere at each time point is compared to baseline. Migration of the prostheses is independently compared between humeral stem fixation groups and glenosphere fixation groups using a two-way repeated measures ANOVA with Tukey's test for multiple comparisons.Introduction
Methods
Reverse total shoulder arthroplasty (RTSA) is a semi-constrained joint replacement with an articulating cobalt-chromium glenosphere and ultra-high molecular weight polyethylene (PE). Because of its limited load bearing, surgeons and implant manufacturers have not elicited the use of highly cross-linked PE in the shoulder, and to date have not considered excessive PE wear in the reverse shoulder a primary concern. As the number of shoulder procedures is expected to grow exponentially in the next decade, however, it is important to evaluate how new designs and bearing materials interact and to have an understanding of what is normal in well-functioning joint replacements. Currently, no in vivo investigation into RTSA PE wear has been conducted, with limited retrieval and simulation studies. In vitro and in silico studies demonstrate a large range in expected wear rates, from 14.3 mm3/million cycles (MC) to 126 mm3/MC, with no obvious relationship between wear rate and polyethylene diameter. The purpose of this study is to evaluate, for the first time, both volumetric and linear wear rates in reverse shoulder patients, with a minimum six-year follow-up using stereo radiographic techniques. To date, seven patients with a self-reported well-functioning Aequalis Reversed II (Wright Medical Group, Edina, MN, USA) RTSA implant system have been imaged (mean years from surgery = 7.0, range = 6.2 to 9). Using stereo radiographs, patients were imaged at the extents of their range of motion in internal and external rotation, lateral abduction, forward flexion, and with their arm at the side. Multiple arm positions were used to account for the multiple wear vectors associated with activities of daily living and the shoulder's six degrees of motion. Using proprietary software, the position and orientation of the polyethylene and glenosphere components were identified and their transformation matrices recorded. These transformation matrices were then applied to the CAD models of each component, respectively, and the apparent intersection of the glenosphere into the PE recorded. Using previously validated in-house software, volumetric and maximum linear wear depth measurements were obtained. Linear regression was used to identify wear rates.Introduction
Methods
Total shoulder arthroplasty is the fastest growing joint replacement in recent years, with projected compound annual growth rates of 10% for 2016 through 2021 – higher than those of both the hip and knee combined. Reverse total shoulder arthroplasty (RTSA) has gained particular interest as a solution for patients with irreparable massive rotator cuff tears and failed conventional shoulder replacement, for whom no satisfactory intervention previously existed. As the number of indications for RTSA continues to grow, so do implant designs, configurations, and fixation techniques. It has previously been shown that continuous implant migration within the first two years postoperatively is predictive of later loosening and failure in the hip and knee, with aseptic loosening of implant components a guaranteed cause for revision in the reverse shoulder. By identifying implants with a tendency to migrate, they can be eliminated from clinical practice prior to widespread use. The purpose of this study is to, for the first time, evaluate the pattern and magnitude of implant component migration in RTSA using the gold standard imaging technique radiostereometric analysis (RSA). Forty patients were prospectively randomized to receive either a cemented or press-fit humeral stem, and a glenosphere secured to the glenoid with either autologous bone graft or 3D printed porous titanium (Aequalis Ascend Flex, Wright Medical Group, Memphis, TN, USA) for primary reverse total shoulder arthroplasty. Following surgery, partients are imaged using RSA, a calibrated, stereo x-ray technique, at 6 weeks (baseline), 3 months, 6 months, 1 year, and 2 years. Migration of the humeral stem and glenosphere at each time point is compared to baseline. Preliminary results are presented, with 15 patients having reached the 6-month time point by presentation.Introduction
Methods
There is a theoretical advantage for immediate postoperative start of rifampicin after debridement, antibiotics and implant retention (DAIR). Anti-biofilm treatment may be mostly needed during the first postoperative days in order to prevent new biofilm formation. However, there are concerns with regard to development of rifampicin resistance if rifampicin is started too early. Rifampicin monotherapy will rapidly result in rifampicin resistance, but this may not occur when prescribed as part of combination antimicrobial therapy and after thorough surgical debridement. We hypothesized that in this setting the probability of development of rifampicin resistance is very low. We evaluated the frequency of development of rifampicin resistance in patients with acute staphylococcal PJI who were treated with DAIR followed by immediate postoperative start of rifampicin in combination with a betalactam or glycopeptide. During 2003–2014, all patients with an acute staphylococcal PJI were treated with five days of high-dose rifampicin (600mg bid) in combination with at least 6 weeks of betalactam or glycopeptide antibiotics, both started immediately postoperative after DAIR. Clinical outcome and development of rifampicin resistance in patients who failed were monitored. Susceptibility testing for rifampicin was performed by Vitek 2 (Biomerieux). Until 2014, Clinical and Laboratory Standards Institute (CLSI) criteria for rifampicin resistance were applied (S ≤ 1), from 2014 EUCAST criteria (S ≤ 0.06) were applied.Aim
Method
Early discharge of patients after joint arthroplasty leaves patients responsible for monitoring their postoperative wound by themselves. This might result in a delayed presentation of postoperative complications. The use of a mobile woundcare app by patients after arthroplasty might result in (1) earlier report of complications, (2) an increase in patient satisfaction and (3) insight in the incidence and duration of postoperative wound leakage. Therefore, the ease of use and perceived usefulness of using a postoperative mobile woundcare app in patients after joint arthroplasty was investigated. A cohort study was conducted in 2017 in 2 Dutch Hospitals. Eligible cases were all consecutive patients that received an arthroplasty and who owned a smartphone. During the first 30 postoperative days, patients filled in daily reviews of their wound and took a photo of the wound. Based on the review, an underlying algorithm calculated daily a score that prompted a mobile alert if needed, which advised patients to contact the hospital. Patients filled in a form on day 30 and day 90 in order to document occurrence of any postoperative wound complication. On day 15 and 30, patients were requested to fill in a questionnaire evaluating the perceived usefulness and the ease of use of the App.Aim
Method
The goal of the study was to perform quality control with a commercially available navigation system when introducing PST technique at our academic department. The learning curve was assessed by the Cumulative Sum (CUSUM) test. We hypothesized that the PST process for TKA was immediately under control after its introduction when analyzed with the CUSUM technique. The first 50 TKAs implanted with the use of PST at an academic department were scheduled to enter in a prospective, observational study. All TKAs were implanted by an experienced, high volume senior consultant with high experience in knee navigation. PSTs were carefully positioned over the bone and articular surfaces to the best fit position, without any navigated information. Then the 3D femoral and tibia PSTs positioning were recorded. The surgical procedure was then completed following the routine navigated procedure with standard navigated templates. To assess the 3D positioning of each template individually and of both templates together as a surrogate of the final TKA positioning, one point was given for each item inside the target, giving a maximal femur and tibia scores of 4 points, and a maximal knee score of 8 points, when all items were fulfilled. Following dataset was used for CUSUM chart plotting: allowable slack = 0.5SD, acceptable limit score = 6 points for knee score and 2 points for femur and tibia scores. For each measurement Mx, two CUSUMs (upper and lower CUSUMs) were calculated. These sums were plotted against the rank of the observation i. A trend in the process results in a change in the slope of the CUSUM, whereas the values are expected to fluctuate around a horizontal line if the process is in control. The process was considered out of control if upper CUSUM or lower CUSUM is outside the acceptable deviation interval.INTRODUCTION
MATERIAL AND METHODS
The patient-specific templates (PST) for total knee arthroplasty (TKA) have been developed to improve accuracy of implantation, decrease operating time and decrease costs. There remains controversy about the accuracy of PST in comparison with either navigated or conventional instruments. Furthermore, the learning curve after introducing PST has not been well defined. The goal of the present study was to perform quality control with a commercially available navigation system and the CUCUM test when introducing PST technique at our academic department. The first 50 TKAs implanted with the use of PST at an academic department were scheduled to enter in a prospective, observational study. PSTs were designed to obtain a neutral coronal alignment. All TKAs were implanted by an experienced, high volume senior consultant with high experience in knee navigation. PSTs were carefully positioned over the bone and articular surfaces to the best fit position, without any navigated information. Then the 3D femoral and tibia PSTs positioning were recorded by the navigation system. The difference between expected and achieved position was calculated, and an accuracy score was calculated and plotted according to the rank of observation into a CUSUM test.INTRODUCTION
MATERIAL AND METHODS
An appropriate positioning of a total knee replacement (TKR) is a prerequisite for a good functional outcome and a prolonged survival. Navigation systems may facilitate this proper positioning. Patient specific templates have been developed to achieve at least the same accuracy than conventional instruments at a lower cost. We hypothesised that there was no learning curve at our academic department when using patient specific templates for TKR instead of the routinely used navigation system. The first 20 patients operated on for TKR at our academic department using a patient specific template entered the study. All patients had a pre-operative CT-scan planning with a dedicated software. The patient specific templates were positioned on the bone according to the best fit technique. The position of the templates was controlled at each step of the procedure by the navigation system, and eventually corrected to achieve the expected goal. The discrepancy between the initial and the final positioning was recorded. The paired difference between each set of measurement was analysed with appropriate statistical tests at a 0.05 level of significance.Introduction
Material
High-dose antibiotic-loaded acrylic cement (ALAC) is used for managing periprosthetic joint infections (PJIs). The marked increase in resistant high-virulence bacteria is drawing the attention of physicians towards alternative antimicrobial formulations to the routinely used antibiotics. To date, few studies simultaneously investigated the elution properties of a broad range of antibiotics. The aim of thepresent All the ALAC samples showed a burst release of antibiotics in the first hour, progressively decreasing overtime, and elution curves strictly adhered to a non-linear regression analysis formula. Among aminoglycosides, commonly addressed as the most appropriate antibiotics to be loaded into the bone cement, the highest elution rate was that of tobramycin. Among the glycopeptides, commonly used to treat PJIs because of the prevalence of aminoglycoside resistance, vancomycin showed better elution in comparison with teicoplanin. Clindamycin, that can be associated with aminoglycosides to prepare ALACsshowed the highest absolute and relative elutions among all the tested formulations. A noticeable elution was also detected for colistin, an antibiotic of last resort for treating multi-drug resistant bacteria. The current study demonstrates theoretical advantages in the preparation of ALAC for some antibiotics notroutinely used in the clinical setting for PJIs. The use of these antibiotics based on the infecting bacteria sensitivity may represent an useful option for physicians to eradicate PJIs.
With the increase in the average age of the population, the incidence of symptomatic rotator cuff tears will also increase. Combined with more access to information via the internet etc., the patient population is more informed of the treatment modalities available and is expecting good reproducible results of their surgeries. 288 of 426 consecutive open rotator cuff repairs (2010–2012) were examined at 6 month follow up and evaluated for ranges of motion, the integrity of the deltoid and specifically the sonographic integrity of the cuff. All procedures were done in the same manner by the same surgeon (TdB). At the 6 months follow-up all had a sonar of the repaired cuff. As a second part of the study 319 of 462 consecutive cuff repair patients were phoned and evaluated by means of the ASES score insofar satisfaction with their shoulder as well as functional outcome are concerned.Background:
Study:
The objective of this study was to determine the tensile strength of the different components of the rotator cuff tendons and their relationship to rotator cuff tears. The tests were done on a newly designed and built test-bench that performed the tests at a consistent rupture speed. The tests were done on four fresh frozen cadaver shoulders. The capsular and tendinous layers of the rotator cuff were divided leaving them only attached on the humeral side. Separate tensile tests were done on these tendons, after they were divided into 10 mm wide strips before testing. The tendon thickness was also measured.Purpose:
Method:
To determine the insertion of the different layers of the rotator cuff and apply it to rotator cuff tears. Anatomical insertion of the rotator cuff holds the key to a proper anatomical repair. A study of the rotator cuff insertion was done in conjunction with MSc student department Anatomy. The rotator cuff consists of a capsular and tendinous layer. They have different mechanical properties. The capsular layer inserts ± 3 mm more medially on the tuberosity and the tendinous layer more laterally. It was shown that the superficial layer extends beyond the greater tuberosity and connects the supra-spinatus tendon to the sub-scapularis tendon via the bicepital groove. This connection was called the “rotator hood”. The “rotator hood” has a mechanically advantageous insertion, is a strong structure with a compressive force on the proximal humerus.Purpose:
Method:
Segmental excision of long-bone sarcomas can require complex reconstruction, often resulting in the use of prosthetic replacements at a young age. The use of vascularised free fibula grafting (VFFG) is well established as a reconstruction modality in sarcoma surgery. To analyse the experience of two European sarcoma centres and their use of vascularised free fibula grafting as a primary and revision procedure in limb salvage for diaphyseal long-bone defects in sarcoma surgery. A retrospective analysis was carried out of 70 consecutive patients undergoing VFFG between 1996 and 2009 under the Oxford Sarcoma Service (Nuffield Orthopaedic Centre) and the Dutch Orthopaedic Tumour Society (Leiden University Hospital). Clinical and radiological assessments were made and functional outcome scores collected.Aims
Methods
Many studies have looked at the effects of titanium tibial baseplates compared to cobalt chrome baseplates on backside wear. However, the surface finish of the materials is usually different (polished/unpolished) [1,2]. Backside wear may be a function not only of tray material but also of the locking mechanism. The purpose of this study was to evaluate the wear performance of conventional polyethylene inserts when mated with titanium tibial trays or cobalt chrome tibial trays that both have non-polished topside surfaces. Three titanium (Ti) trays were used along with three cobalt chrome (CoCr) trays. The Ti trays underwent Type II anodization prior to testing. All trays were Triathlon® design (Stryker Orthopaedics, Mahwah, NJ). Tibial inserts were manufactured from GUR 1020 conventional polyethylene then vacuum/flush packaged and sterilized in nitrogen (30 kGy). Appropriate sized CoCr femoral components articulated against the tibial inserts (Triathlon®, Stryker Orthopaedics, Mahwah, NJ). Surface roughness of the tibial trays was taken prior to testing using white light interferometry (Zygo Corp, Middlefield, CT). A 6-station knee simulator (MTS, Eden Prairie, MN) was used for testing. Two phases were conducted. The first phase used a normal walking profile, as dictated by ISO 14243-3 [3]. The second phase used waveforms created specifically for stair climbing kinematics. Testing was conducted at a frequency of 1 Hz for 2 million cycles for each test with a lubricant of Alpha Calf Fraction serum (Hyclone Labs, Logan, UT) diluted to 50% with a pH-balanced 20-mMole solution of deionized water and EDTA (protein level = 20 g/l) [4]. The serum solution was replaced and inserts were weighed for gravimetric wear at least every 0.5 million cycles. Standard test protocols were used for cleaning, weighing and assessing the wear loss of the tibial inserts [5]. Soak control specimens were used to correct for fluid absorption with weight loss data converted to volumetric data (by material density). Statistical analysis was performed using the Student's t-test (p<0.05).INTRODUCTION
MATERIALS AND METHODS
