| 1. |
- Bitar, C., et al.
(författare)
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11-Year outcomes in patients with metal-on-metal ASR hip arthroplasty
- 2022
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Ingår i: Journal of Orthopaedics. - : Elsevier BV. - 0972-978X .- 2589-9082. ; 32, s. 98-103
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Bitar, C., et al.
(författare)
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Living with a recalled implant: a qualitative study of patients' experiences with ASR hip resurfacing arthroplasty
- 2021
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Ingår i: Patient Safety in Surgery. - : Springer Science and Business Media LLC. - 1754-9493. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTotal hip arthroplasty is the traditional treatment for osteoarthritis in the hip joint. Hip resurfacing arthroplasty, with metal on metal bearing, is a modern concept initially developed mainly for young active people. The metal-on-metal hip arthroplasty implant, Articular Surface Replacement (ASR), was implanted in approximately 93,000 patients before it was recalled in 2010 due to a high complication rate. This study aimed to evaluate patients' own experiences living with an implant that they knew had a high complication rate and had been recalled from the market.MethodsA total of 14 patients, still living with the implant, of a cohort of 34 patients were available for follow-up. Qualitative semi-structured interviews were conducted with 14 patients where a majority actively sought for metal-on-metal hip resurfacing arthroplasty (HRA), and subsequently underwent HRA with an ASR prosthesis between 11/21/2006 and 09/28/2009. The responses were analyzed using content analysis described by Graneheim and Lundman to compress text and identify categories and subcategories.ResultsThe results showed that most patients had already decided that they wanted a metal-on-metal HRA implant before meeting the surgeon. They expressed that the implant made it possible to live an active life. A majority did not think about the fact that they had a hip implant, because they lacked subjective pain. Most of the patients were positive about the annual exams at the hospital and wanted them to continue. None of them felt that their trust towards the healthcare system had changed after the implant recall. They expressed a belief that they would need new surgery sooner than they first thought.ConclusionsDespite all the attention when the ASR prosthesis was recalled, patients with ASR-HRA did not report themselves negatively affected by the recall in this group of patients where a majority had actively sought for an HRA procedure. The healthcare system has an obligation to continue the annual exams, even if the implant provider does not continue reimbursement.
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| 3. |
- Bovinder Ylitalo, Erik, et al.
(författare)
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A novel DNA methylation signature is associated with androgen receptor activity and patient prognosis in bone metastatic prostate cancer
- 2021
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Ingår i: Clinical Epigenetics. - : BioMed Central. - 1868-7083 .- 1868-7075. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with metastatic prostate cancer (PC) are treated with androgen deprivation therapy (ADT) that initially reduces metastasis growth, but after some time lethal castration-resistant PC (CRPC) develops. A better understanding of the tumor biology in bone metastases is needed to guide further treatment developments. Subgroups of PC bone metastases based on transcriptome profiling have been previously identified by our research team, and specifically, heterogeneities related to androgen receptor (AR) activity have been described. Epigenetic alterations during PC progression remain elusive and this study aims to explore promoter gene methylation signatures in relation to gene expression and tumor AR activity.Materials and methods: Genome-wide promoter-associated CpG methylation signatures of a total of 94 tumor samples, including paired non-malignant and malignant primary tumor areas originating from radical prostatectomy samples (n = 12), and bone metastasis samples of separate patients with hormone-naive (n = 14), short-term castrated (n = 4) or CRPC (n = 52) disease were analyzed using the Infinium Methylation EPIC arrays, along with gene expression analysis by Illumina Bead Chip arrays (n = 90). AR activity was defined from expression levels of genes associated with canonical AR activity.Results: Integrated epigenome and transcriptome analysis identified pronounced hypermethylation in malignant compared to non-malignant areas of localized prostate tumors. Metastases showed an overall hypomethylation in relation to primary PC, including CpGs in the AR promoter accompanied with induction of AR mRNA levels. We identified a Methylation Classifier for Androgen receptor activity (MCA) signature, which separated metastases into two clusters (MCA positive/negative) related to tumor characteristics and patient prognosis. The MCA positive metastases showed low methylation levels of genes associated with canonical AR signaling and patients had a more favorable prognosis after ADT. In contrast, MCA negative patients had low AR activity associated with hypermethylation of AR-associated genes, and a worse prognosis after ADT.Conclusions: A promoter methylation signature classifies PC bone metastases into two groups and predicts tumor AR activity and patient prognosis after ADT. The explanation for the methylation diversities observed during PC progression and their biological and clinical relevance need further exploration.
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| 4. |
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| 6. |
- Bovinder Ylitalo, Erik, et al.
(författare)
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Subgroups of castration-resistant prostate cancer bone metastases defined through an inverse relationship between androgen receptor activity and immune response
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 71:5, s. 776-787
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Tidskriftsartikel (refereegranskat)abstract
- Background: Novel therapies for men with castration-resistant prostate cancer (CRPC) are needed, particularly for cancers not driven by androgen receptor (AR) activation. Objectives: To identify molecular subgroups of PC bone metastases of relevance for therapy.Design, setting, and participants: Fresh-frozen bone metastasis samples from men with CRPC (n = 40), treatment-naïve PC (n = 8), or other malignancies (n = 12) were characterized using whole-genome expression profiling, multivariate principal component analysis (PCA), and functional enrichment analysis. Expression profiles were verified by reverse transcription–polymerase chain reaction (RT-PCR) in an extended set of bone metastases (n = 77) and compared to levels in malignant and adjacent benign prostate tissue from patients with localized disease (n = 12). Selected proteins were evaluated using immunohistochemistry. A cohort of PC patients (n = 284) diagnosed at transurethral resection with long follow-up was used for prognostic evaluation.Results and limitations: The majority of CRPC bone metastases (80%) was defined as AR-driven based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1, HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were non–AR-driven. Functional enrichment analysis indicated high metabolic activity and low immune responses in AR-driven metastases. Accordingly, infiltration of CD3+ and CD68+ cells was lower in AR-driven than in non–AR-driven metastases, and tumor cell HLA class I ABC immunoreactivity was inversely correlated with nuclear AR immunoreactivity. RT-PCR analysis showed low MHC class I expression (HLA-A, TAP1, and PSMB9 mRNA) in PC bone metastases compared to benign and malignant prostate tissue and bone metastases of other origins. In primary PC, low HLA class I ABC immunoreactivity was associated with high Gleason score, bone metastasis, and short cancer-specific survival. Limitations include the limited number of patients studied and the single metastasis sample studied per patient.Conclusions: Most CRPC bone metastases show high AR and metabolic activities and low immune responses. A subgroup instead shows low AR and metabolic activities, but high immune responses. Targeted therapy for these groups should be explored. Patient summary: We studied heterogeneities at a molecular level in bone metastasis samples obtained from men with castration-resistant prostate cancer. We found differences of possible importance for therapy selection in individual patients.
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| 7. |
- Crnalic, Sead, et al.
(författare)
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Early diagnosis and treatment is crucial for neurological recovery after surgery for metastatic spinal cord compression in prostate cancer
- 2013
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Ingår i: Acta Oncologica. - London : Informa Healthcare. - 0284-186X .- 1651-226X. ; 52:4, s. 809-815
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Tidskriftsartikel (refereegranskat)abstract
- 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 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 centre (p=0.004). The rate of diagnosis with MRI increased through the week and peaked on Friday, with few patients being diagnosed during weekends. 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 of 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. Rising of awareness for the condition among patients at risk and among physicians is mandatory as well as improvement of local and regional guidelines for treatment.
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| 8. |
- Crnalic, Sead, 1960-
(författare)
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Metastatic spinal cord compression in prostate cancer : clinical and morphological studies
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Bone metastases occur in most patients with advanced hormone-refractory prostate cancer causing pain, pathologic fractures, and spinal cord compression. Few studies specifically address surgical treatment of metastatic spinal cord compression (MSCC) in prostate cancer. Criteria for identifying patients who may benefit from surgery are poorly defined. Most of the current knowledge regarding tumor biology in prostate cancer is based on studies of primary tumors or soft tissue metastases. The mechanisms regulating growth of bone metastases are not fully established. Aims: a) to evaluate outcome after surgery for MSCC in prostate cancer and to identify prognostic factors for survival and functional recovery; b) to evaluate current practice for referral of prostate cancer patients with MSCC; c) to analyze expression of androgen receptor (AR), cell proliferation, apoptosis, and prostate-specific antigen (PSA) in bone metastases with regard to survival after surgery for complications of bone metastases. Patients and Methods: We retrospectively evaluated the hospital records of 68 consecutive patients operated for metastatic spinal cord compression. Tumor tissue from bone metastases was obtained on spinal surgery (54 patients), fracture surgery (4 patients) and biopsy (2 patients), and analyzed by immunohistochemistry. Results: Study I: Mortality and complication rate after surgery was high. Patients with hormone-naïve disease and those with hormone-refractory disease with good performance status and without visceral metastases had more favorable survival. The ability to walk after surgery was related to better survival. Study II: A new score for prognosis of survival after surgery for spinal cord compression includes: hormone status of prostate cancer, Karnofsky performance status, evidence of visceral metastasis, and preoperative serum PSA. The score is simple, tumor specific, and easy to apply in clinical practice. Study III: Our results suggest that delays in diagnosis and treatment may have negative impact on functional outcome. Pretreatment ability to walk, hormone status of prostate cancer, and time from loss of ambulation influenced neurological recovery after surgery for spinal cord compression. Study IV: High nuclear AR immunostaining in bone metastases and high preoperative serum PSA were associated with a poor outcome after metastasis surgery in patients with hormone-refractory prostate cancer. Short-term effect of castration therapy disclosed that nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected. Conclusion: Prostate cancer patients with metastatic spinal cord compression represent a heterogeneous group. We identified prognostic factors for survival and functional outcome, which may help clinicians in making decisions about treatment. Our results also implicate the need for development of local and regional guidelines for treatment of patients with spinal cord compression, as well as the importance of information to patients at risk.
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| 9. |
- Crnalic, Sead
(författare)
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Metastatisk ryggmärgskompression får inte missas : ökad medvetenhet om tidiga symtom möjliggör snabb behandling
- 2014
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Ingår i: Läkartidningen. - Stockholm : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 111:7, s. 276-277
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Metastatisk ryggmärgskompression är ett akut tillstånd. Tidig diagnos och snabb behandling är avgörande för neurologisk restitution. Ökad medvetenhet om de tidiga symtomen vid tillståndet bland läkare, övrig sjukvårdspersonal och särskilt cancerpatienter är nödvändig för att öka möjligheten till tidig behandling. Regionala riktlinjer för handläggning av denna patientgrupp bör införas eller förbättras och – framför allt – efterlevas.
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