The accuracy of digital templating in cementless total hip arthroplasty in dysplastic hips.

BACKGROUND: Total hip arthroplasty (THA) for developmental dysplasia of the hip (DDH) is a complex procedure due to associated anatomical abnormalities. We studied the extent to which preoperative digital templating is reliable when performing cementless THA in patients with DDH. METHODS: We templated and compared the pre- and postoperative sizes of the acetabular and femoral components and the center of rotation (COR), and analysed the postoperative cup coverage, leg length discrepancy (LLD), and stem alignment in 50 patients (56 hips) with DDH treated with THA. RESULTS: The implant size exactly matched the template size in 42.9% of cases for the acetabular component and in 38.2% of cases for the femoral component, whereas the templated ±1 size was used in 80.4 and 81.8% of cases for the acetabular and femoral components, respectively. There were no statistically significant differences between templated and used component sizes among different DDH severity levels (acetabular cup: p = 0.30 under the Crowe classification and p = 0.94 under the Hartofilakidis classification; femoral stem: p = 0.98 and p = 0.74, respectively). There were no statistically significant differences between the planned and postoperative COR (p = 0.14 horizontally and p = 0.52 vertically). The median postoperative LLD was 7 (range 0-37) mm. CONCLUSION: Digital preoperative templating is reliable in the planning of cementless THA in patients with DDH.

Uncemented or cemented femoral components work equally well in total knee arthroplasty.

PURPOSE: To study the pattern of migration and clinical results up to 10 years of uncemented versus cemented fixation of the femoral component in total knee arthroplasty. METHODS: Randomized controlled trial was conducted of 41 patients (23 women, 18 men) under the age of 60 years using radiostereometric analysis. RESULTS: About two-thirds of the cemented implants and half of the uncemented implants stabilized between 2 and 10 years, while the remainder displayed a small annual increase of maximum total point motion of 0.09-0.10 mm/year. At 10 years there were no statistically significant differences in migration or clinical results between the groups. CONCLUSION: Uncemented fixation with titanium fiber mesh coating of the femoral component in total knee arthroplasty works equally as well as cemented fixation up to 10 years. An annual migration of 0.1 mm seems compatible with excellent long-term performance. LEVEL OF EVIDENCE: I.

Uncemented cups with and without screw holes in primary THA: a Swedish Hip Arthroplasty Register study with 22,725 hips.

Background and purpose - Uncemented cups in total hip arthroplasty (THA) are often augmented with additional screws to enhance their primary stability. We investigated whether there is a difference in the risk for revision between cups with screw holes and cups without screw holes. Patients and methods - We analyzed the risk for cup revision of uncemented cups registered in the Swedish Hip Arthroplasty Register (SHAR) between 2000 and 2017 with respe ct to the presence of screw holes. Only patients with primary osteoarthritis (OA) were included. 22,725 cups, including 12,354 without screw holes and 10,371 with screw holes, were evaluated. Revision rates at 2 and 10 years after the primary operation were analyzed. Results - At a median follow-up time of 3.4 years (0-18), 459 cup revisions were reported. The main reasons for cup revision during the whole observation time were infection, 52% of all cup revisions, and dislocation, 26% of all cup revisions. The survival rate with cup revision due to aseptic loosening as endpoint was 99.9% (95% CI 99.8-99.9) at 2 years for both cups with and cups without screw holes, and the survival rates at 10 years were 99.5% (CI 99.3-99.7) and 99.1% (CI 98.6-99.5), respectively. Cups without screw holes showed a decreased risk of revision due to any reason at both 2 years (adjusted hazard ratio [HR] 0.6, CI 0.5-0.8) and 10 years (HR 0.7, CI 0.5-0.9). Interpretation - We found a very low revision rate for aseptic loosening with modern, uncemented cup designs. Cups with screw holes had an increased risk of revision due to any reason in patients with primary OA.

Uncemented monoblock trabecular metal posterior stabilized high-flex total knee arthroplasty: similar pattern of migration to the cruciate-retaining design - a prospective radiostereometric analysis (RSA) and clinical evaluation of 40 patients (49 knees) 60 years or younger with 9 years' follow-up.

Background and purpose - Uncemented monoblock cruciate retaining (CR) trabecular metal (TM) tibial components in total knee arthroplasty (TKA) work well in the long-term perspective in patients ≤ 60 years. Younger persons expect nearly normal knee flexion after TKA, but CR implants generally achieve less knee flexion compared with posterior stabilized (PS) implants. Cemented PS implants have higher revision rate than CR implants. Can an uncemented monoblock PS TM implant be used safely in younger patients? Patients and methods - 40 patients (49 knees) age ≤ 60 years with primary (20 knees) or posttraumatic osteoarthritis (OA) were operated with a high-flex TKA using an uncemented monoblock PS TM tibial component. Knees were evaluated with radiostereometric analysis (RSA) a mean 3 days (1-5) postoperatively, and thereafter at 6 weeks, 3 months, 1, 2, 5, and 9 years. Clinical outcome was measured with patient-related outcome measures (PROMs). Results - The implants showed a pattern of migration with initial large migration followed by early stabilization lasting up to 9 years, a pattern known to be compatible with good long-term results. Clinical and radiological outcome was excellent with 38 of the 40 patients being satisfied or very satisfied with the procedure and bone apposition to the entire implant surface in 46 of 49 knees. Mean knee flexion was 130°. 1 knee was revised at 3 months due to medial tibial condyle collapse. Interpretation - The uncemented monoblock PS TM implant works well in younger persons operated with TKA due to primary or secondary OA.

Bone Cell Activity in Clinical Prostate Cancer Bone Metastasis and Its Inverse Relation to Tumor Cell Androgen Receptor Activity.

Advanced prostate cancer frequently metastasizes to bone and induces a mixed osteoblastic/osteolytic bone response. Standard treatment for metastatic prostate cancer is androgen-deprivation therapy (ADT) that also affects bone biology. Treatment options for patients relapsing after ADT are limited, particularly in cases where castration-resistance does not depend on androgen receptor (AR) activity. Patients with non-AR driven metastases may, however, benefit from therapies targeting the tumor microenvironment. Therefore, the current study specifically investigated bone cell activity in clinical bone metastases in relation to tumor cell AR activity, in order to gain novel insight into biological heterogeneities of possible importance for patient stratification into bone-targeting therapies. Metastasis tissue obtained from treatment-naïve (n = 11) and castration-resistant (n = 28) patients was characterized using whole-genome expression analysis followed by multivariate modeling, functional enrichment analysis, and histological evaluation. Bone cell activity was analyzed by measuring expression levels of predefined marker genes representing osteoclasts (ACP5, CTSK, MMP9), osteoblasts (ALPL, BGLAP, RUNX2) and osteocytes (SOST). Principal component analysis indicated a positive correlation between osteoblast and osteoclast activity and a high variability in bone cell activity between different metastases. Immunohistochemistry verified a positive correlation between runt-related transcription factor 2 (RUNX2) positive osteoblasts and tartrate-resistant acid phosphatase (TRAP, encoded by ACP5) positive osteoclasts lining the metastatic bone surface. No difference in bone cell activity was seen between treatment-naïve and castration-resistant patients. Importantly, bone cell activity was inversely correlated to tumor cell AR activity (measured as AR, FOXA1, HOXB13, KLK2, KLK3, NKX3-1, STEAP2, and TMPRSS2 expression) and to patient serum prostate-specific antigen (PSA) levels. Functional enrichment analysis indicated high bone morphogenetic protein (BMP) signaling in metastases with high bone cell activity and low tumor cell AR activity. This was confirmed by BMP4 immunoreactivity in tumor cells of metastases with ongoing bone formation, as determined by histological evaluation of van Gieson-stained sections. In conclusion, the inverse relation observed between bone cell activity and tumor cell AR activity in prostate cancer bone metastasis may be of importance for patient response to AR and/or bone targeting therapies, but needs to be evaluated in clinical settings in relation to serum markers for bone remodeling, radiography and patient response to therapy. The importance of BMP signaling in the development of sclerotic metastasis lesions deserves further exploration.

High levels of the AR-V7 Splice Variant and Co-Amplification of the Golgi Protein Coding YIPF6 in AR Amplified Prostate Cancer Bone Metastases.

BACKGROUND: The relation between androgen receptor (AR) gene amplification and other mechanisms behind castration-resistant prostate cancer (CRPC), such as expression of constitutively active AR variants and steroid-converting enzymes has been poorly examined. Specific aim was to examine AR amplification in PC bone metastases and to explore molecular and functional consequences of this, with the long-term goal of identifying novel molecular targets for treatment. METHODS: Gene amplification was assessed by fluorescence in situ hybridization in cryo-sections of clinical PC bone metastases (n = 40) and by PCR-based copy number variation analysis. Whole genome mRNA expression was analyzed using H12 Illumina Beadchip arrays and specific transcript levels were quantified by qRT-PCR. Protein localization was analyzed using immunohistochemistry and confocal microscopy. The YIPF6 mRNA expression was transiently knocked down and stably overexpressed in the 22Rv1 cell line as representative for CRPC, and effects on cell proliferation, colony formation, migration, and invasion were determined in vitro. Extracellular vesicles (EVs) were isolated from cell cultures using size-exclusion chromatography and enumerated by nanoparticle tracking analysis. Protein content was identified by LC-MS/MS analysis. Blood coagulation was measured as activated partial thromboplastin time (APTT). Functional enrichment analysis was performed using the MetaCore software. RESULTS: AR amplification was detected in 16 (53%) of the bone metastases examined from CRPC patients (n = 30), and in none from the untreated patients (n = 10). Metastases with AR amplification showed high AR and AR-V7 mRNA levels, increased nuclear AR immunostaining, and co-amplification of genes such as YIPF6 in the AR proximity at Xq12. The YIPF6 protein was localized to the Golgi apparatus. YIPF6 overexpression in 22Rv1 cells resulted in reduced cell proliferation and colony formation, and in enhanced EV secretion. EVs from YIPF6 overproducing 22Rv1 cells were enriched for proteins involved in blood coagulation and, accordingly, decreased the APTT in a dose-dependent fashion. CONCLUSIONS: AR amplified CRPC bone metastases show high AR-V7 expression that probably gives resistance to AR-targeting drugs. Co-amplification of the Golgi protein coding YIPF6 gene with the AR may enhance the secretion of pro-coagulative EVs from cancer cells and thereby stimulate tumor progression and increase the coagulopathy risk in CRPC patients. Prostate 77: 625-638, 2017. © 2017 Wiley Periodicals, Inc.

Metastatic spinal cord compression as the first sign of malignancy.

Background and purpose - Metastatic spinal cord compression (MSCC) as the initial manifestation of malignancy (IMM) limits the time for diagnostic workup; most often, treatment is required before the final primary tumor diagnosis. We evaluated neurological outcome, complications, survival, and the manner of diagnosing the primary tumor in patients who were operated for MSCC as the IMM. Patients and methods - Records of 69 consecutive patients (51 men) who underwent surgery for MSCC as the IMM were reviewed. The patients had no history of cancer when they presented with pain (n = 2) and/or neurological symptoms (n = 67). Results - The primary tumor was identified in 59 patients. In 10 patients, no specific diagnosis could be established, and they were therefore defined as having cancer of unknown primary tumor (CUP). At the end of the study, 16 patients were still alive (median follow-up 2.5 years). The overall survival time was 20 months. Patients with CUP had the shortest survival (3.5 months) whereas patients with prostate cancer (6 years) and myeloma (5 years) had the longest survival. 20 of the 39 patients who were non-ambulatory preoperatively regained walking ability, and 29 of the 30 ambulatory patients preoperatively retained their walking ability 1 month postoperatively. 15 of the 69 patients suffered from a total of 20 complications within 1 month postoperatively. Interpretation - Postoperative survival with MSCC as the IMM depends on the type of primary tumor. Surgery in these patients maintains and improves ambulatory function.

Stability of Uncemented Cups - Long-Term Effect of Screws, Pegs and HA Coating: A 14-Year RSA Follow-Up of Total Hip Arthroplasty.

Screws, pegs and hydroxyapatite-coating are used to enhance the primary stability of uncemented cups. We present a 14-year follow-up of 48 hips randomized to four groups: press-fit only, press-fit plus screws, press-fit plus pegs and hydroxyapatite-coated cups. Radiostereometric migration measurements showed equally good stability regardless cup augmentation. The mean wear rate was high, 0.21 mm/year, with no differences between the groups. Seven hips had radiographical osteolysis but only in hips with augmented cups. Cups without screw-holes compared with cups with screw-holes resulted in better clinical outcome at the 14-year follow-up. Thus, augmentation of uncemented cups with screws, pegs, or hydroxyapatite did not appear to improve the long-term stability compared with press-fit only.

Association between changes in global femoral offset after total hip arthroplasty and function, quality of life, and abductor muscle strength. A prospective cohort study of 222 patients.

BACKGROUND AND PURPOSE: There is no consensus on the association between global femoral offset (FO) and outcome after total hip arthroplasty (THA). We assessed the association between FO and patients' reported hip function, quality of life, and abductor muscle strength. PATIENTS AND METHODS: We included 250 patients with unilateral hip osteoarthritis who underwent a THA. Before the operation, the patient's reported hip function was evaluated with the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and quality of life was evaluated with EQ-5D. At 1-year follow-up, the same scores and also hip abductor muscle strength were measured. 222 patients were available for follow-up. These patients were divided into 3 groups according to the postoperative global FO of the operated hip compared to the contralateral hip, as measured on plain radiographs: the decreased FO group (more than 5 mm reduction), the restored FO group (within 5 mm restoration), and the increased FO group (more than 5 mm increment). RESULTS: All 3 groups improved (p < 0.001). The crude results showed that the decreased FO group had a worse WOMAC index, less abductor muscle strength, and more use of walking aids. When we adjusted these results with possible confounding factors, only global FO reduction was statistically significantly associated with reduced abductor muscle strength. The incidence of residual hip pain and analgesics use was similar in the 3 groups. INTERPRETATION: A reduction in global FO of more than 5 mm after THA appears to have a negative association with abductor muscle strength of the operated hip, and should therefore be avoided.

The Influence of Leg Length Discrepancy after Total Hip Arthroplasty on Function and Quality of Life: A Prospective Cohort Study.

We investigated whether patients with lengthening (> 9 mm), restoration (between 9 mm lengthening and 5 mm shortening) or shortening (> 5 mm) of the operated leg after total hip arthroplasty (THA) had different function (WOMAC score), quality of life (EQ-5D), residual hip pain, use of shoe lift and walking aid and leg length discrepancy (LLD) awareness, 12-15 months postoperatively. All patients had a significant postoperative improvement in WOMAC and EQ-5D regardless the LLD. However, the lengthening group showed less improvement in WOMAC, more use of shoe lift, residual hip pain and LLD awareness compared with the other two groups. No differences in EQ-5D were found. In spite of the improvement in function and quality of life, lengthening had adverse effects and should therefore be avoided.

Uncemented trabecular metal high-flex posterior-stabilized monoblock total knee arthroplasty in patients aged 60 years or younger.

BACKGROUND: Uncemented trabecular metal (TM) monoblock tibial components in total knee arthroplasty (TKA) have shown excellent clinical results for up to 10 years. However, these studies were performed in highly specialized units, with few surgeons and often excluding knees with secondary osteoarthritis (OA), severe malalignments and previous surgery. The purpose of this study was to investigate implant survivorship and clinical and radiological outcome of the uncemented TM high-flex posterior stabilized (PS) monoblock tibial component in routine clinical practice. METHODS: A retrospective study of 339 knees (282 patients) operated with the implant in routine clinical practice at two hospitals on patients aged 60 years or younger between 2007 and 2015. The operations were performed by 12 surgeons and there were no specific contraindications for use of the implant. Follow up ended in 2020. The status of the implant of deceased patients at death and those not attending follow up was checked with the Swedish Knee Arthroplasty Register. Clinical follow up consisted of clinical investigation, PROMs, and knee X-ray. RESULTS: Follow up was mean (range) 8.5 (5-13.8) years, and the 8-year survival rate was 0.98 (standard error 0.007). Five patients five knees) were deceased, five knees were revised (none due to aseptic loosening), and 16 patients did not attend the clinical follow up. Forty-four percent of the knees had secondary OA and 45% had had previous operations. 93% were satisfied or very satisfied with the operation and forgotten joint score (FJS) was median (interquartile range) 81 (44-94). Radiographic analysis revealed bone in close contact with the tibial tray and pegs in most cases, and in only 2% of the knees were potential radiolucent lines found. CONCLUSION: The results indicate that this uncemented implant performs excellently in routine clinical practice and also in younger patients with secondary OA or previous knee operations.

Early diagnosis and treatment is crucial for neurological recovery after surgery for metastatic spinal cord compression in prostate cancer.

BACKGROUND: Spinal cord compression is an oncological and surgical emergency. Delays in referral and diagnosis may influence functional outcome. It is therefore important to identify patients who will regain or maintain the ability to walk after surgery. The aim of the present study was to examine current practice for referral and diagnosis of prostate cancer patients with spinal cord compression and to identify prognostic factors for neurological outcome after surgery. PATIENTS AND METHODS: The study includes 68 consecutive patients with prostate cancer who underwent surgery due to neurological compromise. Intervals from onset of neurological symptoms to referral, diagnosis, and treatment were analyzed in relation to functional outcome. The prognostic significance of preoperative clinical parameters on gait function one month after surgery was evaluated. RESULTS: Patients who were referred from local hospitals had longer delay to surgery than those who directly presented to the cancer center (p = 0.004). The rate of diagnosis with MRI increased through the week and peaked on Friday, with few patients being diagnosed during weekends. The ability to walk before surgery, hormone-naive prostate cancer, and/or shorter time from loss of ambulation were associated with more favorable neurological outcome. In patients with hormone-refractory disease who were unable to walk before surgery regaining ambulation was associated with: duration of paresis < 48 hours (p = 0.005), good preoperative performance status (p = 0.04), preoperative PSA serum level < 200 ng/ml (p = 0.03), and surgery with posterior decompression and stabilization (p = 0.03). CONCLUSION: Early diagnosis and rapid treatment of spinal cord compression in prostate cancer patients is crucial for neurological recovery. Raising awareness of the condition among patients at risk and among physicians is of outmost importance as well as improving local and regional guidelines for treatment.

A Novel Radiographic Pattern Related to Poor Prognosis in Patients with Prostate Cancer with Metastatic Spinal Cord Compression.

Background: Prostate cancer spinal bone metastases can have a radiographic profile that mimics multiple myeloma. Objective: To analyse the presence and prognostic value of myeloma-like prostate cancer bone metastases and its relation to known clinical, molecular, and morphological prognostic markers. Design setting and participants: A cohort of 110 patients with prostate cancer who underwent surgery for metastatic spinal cord compression (MSCC) was analysed. Spinal bone metastases were classified as myeloma like (n = 20) or non-myeloma like (n = 90) based on magnetic resonance imaging prior to surgery. An immunohistochemical analysis of metastasis samples was performed to assess tumour cell proliferation (percentage of Ki67-positive cells) and the expression levels of prostate-specific antigen (PSA) and androgen receptor (AR). The metastasis subtypes MetA, MetB, and MetC were determined from transcriptomic profiling. Outcome measurements and statistical analysis: Survival curves were compared with the log-rank test. Univariate and multivariate Cox proportional hazard models were used to assess the effects of prognostic variables. Groups were compared using the Mann-Whitney U test for continuous variables and the chi-square test for categorical variables. Results and limitations: Patients with the myeloma-like metastatic pattern had median survival after surgery for MSCC of 1.7 (range 0.1-33) mo, while the median survival period of those with the non-myeloma-like pattern was 13 (range 0-140) mo (p < 0.001). The myeloma-like appearance had an independent prognostic value for the risk of death after MSCC surgery (adjusted hazard ratio 2.4, p = 0.012). Postoperative neurological function was significantly reduced in the myeloma-like group. No association was found between the myeloma-like pattern and morphological markers of known relevance for this patient group: the transcriptomic subtypes MetA, MetB, and MetC; tumour cell proliferation; and AR and PSA expression. Conclusions: A myeloma-like metastatic pattern identifies an important subtype of metastatic prostate cancer associated with poor survival and neurological outcomes after surgery for MSCC. Patient summary: This study describes a novel radiographic pattern of prostate cancer bone metastases and its relation to poor patient prognosis.

Investigating microRNA Profiles in Prostate Cancer Bone Metastases and Functional Effects of microRNA-23c and microRNA-4328.

MicroRNAs (miRNAs) are aberrantly expressed in prostate cancer (PC), but comprehensive knowledge about their levels and function in metastatic PC is lacking. Here, we explored the differential expression of miRNA profiles during PC progression to bone metastasis, and further focused on the downregulation of miRNA-23c and -4328 and their impact on PC growth in experimental models. Using microarray screening, the levels of 1510 miRNAs were compared between bone metastases (n = 14), localized PC (n = 7) and benign prostate tissue (n = 7). Differentially expressed miRNAs (n = 4 increased and n = 75 decreased, p < 0.05) were identified, of which miRNA-1, -23c, -143-3p, -143-5p, -145-3p, -205-5p, -221-3p, -222-3p and -4328 showed consistent downregulation during disease progression (benign > localized PC > bone metastases). The downregulation of miRNA-23c and -4328 was confirmed by reverse transcription and quantitative polymerase chain reaction analysis of 67 metastasis, 12 localized PC and 12 benign prostate tissue samples. The stable overexpression of miRNA-23c and -4328 in the 22Rv1 and PC-3 cell lines resulted in reduced PC cell growth in vitro, and in the secretion of high levels of miRNA-23c (but not -4328) in extracellular vesicles. However, no tumor suppressive effects were observed from miRNA-23c overexpression in PC-3 cells subcutaneously grown in mice. In conclusion, bone metastases display a profound reduction of miRNA levels compared to localized PC and benign disease. The downregulation of those miRNAs, including miRNA-23c and -4328, may lead to a loss of tumor suppressive effects and provide biomarker and therapeutic possibilities that deserve to be further explored.

Outcome after surgery for metastatic spinal cord compression in 54 patients with prostate cancer.

BACKGROUND AND PURPOSE: The criteria for selecting patients who may benefit from surgery of spinal cord compression in metastatic prostate cancer are poorly defined. We therefore studied patients operated for metastatic spinal cord compression in order to evaluate outcome of surgery and to find predictors of survival. PATIENTS AND METHODS: We reviewed the records of 54 consecutive patients with metastatic prostate cancer who were operated for spinal cord compression at Umeå University Hospital. The indication for surgery was neurological deficit due to spinal cord compression. 41 patients had hormone-refractory cancer and 13 patients had previously untreated, hormone-naïve prostate cancer. 29 patients were operated with posterior decompression only, and in 25 patients posterior decompression and stabilization was performed. RESULTS: Preoperatively, 6/54 of patients were able to walk. 1 month after surgery, 33 patients were walking, 15 were non-ambulatory, and 6 had died. Mortality rate was 11% at 1 month, 41% at 6 months, and 59% at 1 year. In the hormone-naïve group, 8/13 patients were still alive with a median postoperative follow-up of 26 months. In the hormone-refractory group, median survival was 5 months. Patients with hormone-refractory disease and Karnofsky performance status (KPS) of ≤ 60% had median survival of 2.5 months, whereas those with KPS of 70% and KPS of ≥ 80% had a median survival of 7 months and 18 months, respectively (p < 0.001). Visceral metastases were present in 12/41 patients with hormone-refractory tumor at the time of spinal surgery, and their median survival was 4 months-as compared to 10 months in patients without visceral metastases (p = 0.003). Complications within 30 days of surgery occurred in 19/54 patients. INTERPRETATION: Our results indicate that patients with hormone-naive disease, and those with hormone-refractory disease with good performance status and lacking visceral metastases, may be helped by surgery for metastatic spinal cord compression.

11-Year outcomes in patients with metal-on-metal ASR hip arthroplasty.

Background: We analysed the long-term revision rate, clinical outcomes and metal ion concentrations in blood over time in patients who had undergone metal-on-metal Articular Surface Replacement (ASR) hip arthroplasty. Methods: A total of 38 patients (43 hips) were included: 24 patients (28 hips) underwent large-head total hip arthroplasty (XL THA), and 14 patients (15 hips) underwent hip resurfacing arthroplasty (HRA). The median follow-up time was 11 (range 7-12) years. Results: None of 15 HRA implants were revised. Nine of 28 XL THA implants (32%) in 8 patients were revised. The Co ion levels significantly increased in the XL THA group (p=0.009) over a median time period of 84 (25-97) months. Conclusion: The levels of Co ions in blood were higher in the patients who had undergone XL THA and increased significantly over time.

Evaluation of a new cemented highly cross-linked all-polyethylene cup: a prospective and randomised study assessing wear and fixation characteristics using radiostereometric analysis.

BACKGROUND AND PURPOSE: The aim of this prospective, randomised and controlled study was to evaluate the wear and fixation properties of a new cemented highly cross-linked all-polyethylene (HXLPE) cup in comparison with a conventional cemented ultra-high molecular weight polyethylene (ConvPE) cup using radiostereometric analysis (RSA). PATIENTS AND METHODS: A total of 58 patients (58 hips) with primary osteoarthritis (OA) were enrolled in a randomised controlled trial to receive either a ConvPE cup (control) or HXLPE cup (intervention) with identical geometry. The subjects were randomised in a 1:1 ratio. The primary endpoint was proximal wear measured as femoral head penetration into the cup, secondary outcomes were 3D-wear and annual proximal wear from 1 to 5 years. Cup fixation was measured as movement of the cup in relation to the acetabular bone with proximal migration being the primary outcome measure, 3D-migration and change in inclination as secondary outcomes. The patients were followed for 5 years with RSA performed postoperatively, at 3, 12, 24, and 60 months. RESULTS: The HXLPE displayed a lower median proximal femoral head penetration compared to ConvPE, with a median difference at 2 years of -0.07 mm (95% CI, -0.10 to -0.04 mm), and -0.19 mm (95% CI, -0.27 to -0.15 mm) at 5 years. Annual proximal wear between 1 and 5 years was 0.03 mm/year for HXLPE and 0.06 mm/year for ConvPE (mean difference 0.05 mm, [95% CI, 0.03-0.07 mm]). Proximal migration, 3D migration and change in inclination was numerically slightly higher for HXLPE, albeit not statistically significant. CONCLUSIONS: Compared to ConvPE, the HXLPE cup displayed significantly lower polyethylene wear. Cup migration was not statistically significant different. CLINICALTRIALS.GOV IDENTIFIER: NCT04322799.

Peri-implant femoral fractures in hip fracture patients treated with osteosynthesis: a retrospective cohort study of 1965 patients.

BACKGROUND AND PURPOSE: There are few studies on incidence rates, treatment and outcomes for peri-implant femoral fractures (PIFF) in the proximity of osteosynthesis. The purpose of this study was to investigate the incidence of PIFF following osteosynthesis of proximal femoral fractures. PATIENTS AND METHODS: This retrospective cohort study comprised a consecutive series of hip fracture patients aged 50 years or older and operated with osteosynthesis between 2003 and 2015. Patients were followed-up until 2018, removal of implants or death, for a mean of 4 years (range 0-15). Data on age, sex, housing, hip complications, and reoperations were recorded. The risk of PIFFs was assessed using Cox proportional hazards regression analysis. In patients with two fractures during the study period, only the first fracture was included. RESULTS: A total of 1965 osteosynthesis procedures were performed, of which 382 were cephalomedullary nails (CMN), 933 sliding hip devices (SHD) and 650 pins. Mean age was 80 years (range 50-104), 65% of patients were women. A total of 41 PIFFs occurred during the study period. The cumulative incidence of peri-implant fractures was 0.8% for CMN, 2.7% (HR 2.995% CI, 0.87-9.6, p = 0.08) for SHD and 2.0% (HR 2.3 95% CI, 0.6-8.1, p = 0.2) for pins. PIFFs occurred after a mean of 27 months (range 0-143). The 1-year mortality was 34% following PIFF. The majority was treated surgically (66%, 27/41) and the reoperation rate was 15% (4/27). CONCLUSION: In this retrospective cohort study, in contrast to previous reports, we found a tendency to a higher cumulative incidence of PIFFs for SHD compared to modern CMN. Our results show cumulative incidences of PIFFs comparable to those described for periprosthetic femur fractures after hip arthroplasty for femoral neck fracture.

Epithelial and Stromal Characteristics of Primary Tumors Predict the Bone Metastatic Subtype of Prostate Cancer and Patient Survival after Androgen-Deprivation Therapy.

Prostate cancer (PC) bone metastases can be divided into transcriptomic subtypes, by us termed MetA-C. The MetB subtype, constituting about 20% of the cases, is characterized by high cell cycle activity, low androgen receptor (AR) activity, and a limited response to standard androgen deprivation therapy (ADT). Complementary treatments should preferably be introduced early on if the risk of developing metastases of the MetB subtype is predicted to behigh. In this study, we therefore examined if the bone metastatic subtype and patient outcome after ADT could be predicted by immunohistochemical analysis of epithelial and stromal cell markers in primary tumor biopsies obtained at diagnosis (n = 98). In this advanced patient group, primary tumor International Society of Urological Pathology (ISUP) grade was not associated with outcome or metastasis subtype. In contrast, high tumor cell Ki67 labeling (proliferation) in combination with low tumor cell immunoreactivity for PSA, and a low fraction of AR positive stroma cells in the primary tumors were prognostic for poor survival after ADT. Accordingly, the same tissue markers were associated with developing metastases enriched for the aggressive MetB subtype. The development of the contrasting MetA subtype, showing the best response to ADT, could be predicted by the opposite staining pattern. We conclude that outcome after ADT and metastasis subtype can, at least to some extent, be predicted by analysis of primary tumor characteristics, such as tumor cell proliferation and PSA expression, and AR expression in stromal cells.

Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C.

To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n = 17), short-term castrated (n = 21), or castration-resistant (n = 65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples were also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism, and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen receptor-targeting treatments.