Advertisement for orthosearch.org.uk
Results 1 - 20 of 395
Results per page:
Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_20 | Pages 12 - 12
12 Dec 2024
Langton D Bhalekar R Wells S Nargol M Natu S Nargol A Waller S Pabbruwe M Sidaginamale R
Full Access

Objectives

Several studies have reported elevated blood cobalt (Co) and chromium (Cr) concentrations in patients with total knee replacements (TKRs). Up to 44% of tissue samples taken from patients with failed TKRs exhibit histological evidence of metal sensitivity/ALVAL. In simulated conditions, metal particles contribute approximately 12% of total wear debris in TKR. We carried out this investigation to determine the source and quantity of metal release in TKRs.

Design and Methods

We analysed 225 explanted fixed-bearing TKRs (Attune, Genesis II, NexGen, PFC, and Vanguard) revised for any indication. These were analysed using peer-reviewed [coordinate measuring machine (CMM)] methodology to measure the volumetric wear of the polyethylene (PE) bearing surfaces and trays. The trays were analysed using 2D profilometry (surface roughness-Ra) and light microscopy. Histological and blood metal ion concentration analyses were performed in a sub-sample of patients.


Bone & Joint Open
Vol. 5, Issue 11 | Pages 971 - 976
5 Nov 2024
Baker G Hill J O'Neill F McChesney J Stevenson M Beverland D

Aims

In 2015, we published the results of our ceramic-on-metal (CoM) total hip arthroplasties (THAs) performed between October 2007 and July 2009 with a mean follow-up of 34 months (23 to 45) and a revision rate of 3.1%. The aim of this paper is to present the longer-term outcomes.

Methods

A total of 264 patients were reviewed at a mean of 5.8 years (4.6 to 7.2) and 10.1 years (9.2 to 10.6) to determine revision rate, pain, outcome scores, radiological analysis, and blood ion levels. Those who were unwilling or unable to travel were contacted by telephone.


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1050 - 1058
1 Oct 2024
Holleyman RJ Jameson SS Meek RMD Khanduja V Reed MR Judge A Board TN

Aims

This study evaluates the association between consultant and hospital volume and the risk of re-revision and 90-day mortality following first-time revision of primary hip arthroplasty for aseptic loosening.

Methods

We conducted a cohort study of first-time, single-stage revision hip arthroplasties (RHAs) performed for aseptic loosening and recorded in the National Joint Registry (NJR) data for England, Wales, Northern Ireland, and the Isle of Man between 2003 and 2019. Patient identifiers were used to link records to national mortality data, and to NJR data to identify subsequent re-revision procedures. Multivariable Cox proportional hazard models with restricted cubic splines were used to define associations between volume and outcome.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_16 | Pages 38 - 38
19 Aug 2024
Meek D
Full Access

In 1997 the Birmingham Hip Resurfacing was introduced to address the needs of young active patients. Alternative designs were introduced to try and improve wear performance. The aim of this study was a comparative cohort study of two types of metal-on-metal bearing to determine the mechanism of failure at 15 years. The study reviewed 91 Brimingham Hip Resurfacings (BHR) (Smith and Nephew) and 715 DUROM hip resurfacing (Zimmer) procedures in prior to 2009. Failure was defined as revision of either component for any reason. Kaplan-Meyer survivorship analysis performed. Routine follow-up with serum metal ion levels and radiographs. Mean follow-up was 17.9 years (range 15.2 – 25.1). The mean age at operation was 51.6 years (SD 8.6, range 20.7 to 70.2), including 299 women (37.1%). The Birmingham resurfacing demonstrated 92.3% survivorship at 15 years (SE 2.8, 95% CI 3.9 – 7.8) and 90.0% at latest follow-up (SE 3.5, 95% CI 4.9 to 9.4). By comparison, the DUROM survivorship at 15 years was 89.1% at 15 years (SE 1.2, 95% CI 2.0 to 2.5) and 87.4% (SE 1.3, 95% CI 2.5 to 2.3) at latest follow-up. There was no statistically significant difference in survivorship between groups (p= 0.32). Survival in male patients was 92.7% compared to 80.0% in females. The reported failures occurred from Adverse Reaction to Metal Debris (32 patients), periprosthetic femoral neck fracture (6) and aseptic loosening (41), PJI (12) and undiagnosed pain (6). The mean cobalt and chromium levels at last follow-up were 33.4 nmol/L and 36.5 nmol/L respectively. This study demonstrates two differently designed metal-on-metal hip resurfacing provided a durable alternative to total hip replacement, particularly in younger male patients with osteoarthritis. Differences in design did determine the reason for revision with acetabular fixation being one of the principal failure mechanisms for the DUROM compared to elevated ion levels


Bone & Joint Open
Vol. 5, Issue 6 | Pages 514 - 523
24 Jun 2024
Fishley W Nandra R Carluke I Partington PF Reed MR Kramer DJ Wilson MJ Hubble MJW Howell JR Whitehouse SL Petheram TG Kassam AM

Aims

In metal-on-metal (MoM) hip arthroplasties and resurfacings, mechanically induced corrosion can lead to elevated serum metal ions, a local inflammatory response, and formation of pseudotumours, ultimately requiring revision. The size and diametral clearance of anatomical (ADM) and modular (MDM) dual-mobility polyethylene bearings match those of Birmingham hip MoM components. If the acetabular component is satisfactorily positioned, well integrated into the bone, and has no surface damage, this presents the opportunity for revision with exchange of the metal head for ADM/MDM polyethylene bearings without removal of the acetabular component.

Methods

Between 2012 and 2020, across two centres, 94 patients underwent revision of Birmingham MoM hip arthroplasties or resurfacings. Mean age was 65.5 years (33 to 87). In 53 patients (56.4%), the acetabular component was retained and dual-mobility bearings were used (DM); in 41 (43.6%) the acetabulum was revised (AR). Patients underwent follow-up of minimum two-years (mean 4.6 (2.1 to 8.5) years).


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_12 | Pages 18 - 18
10 Jun 2024
Haston S Langton D Townshend D Bhalekar R Joyce T
Full Access

Despite advancements, revision rates following total ankle replacement (TAR) are high in comparison to other total joint replacements. This explant analysis study aimed to investigate whether there was appreciable metal particulate debris release from various contemporary TARs by describing patterns of material loss. Twenty-eight explanted TARs (9 designs: 3 fixed and 6 mobile bearing), revised for any reason, were studied. The articulating surfaces of the metal tibial and talar components as well as the polyethylene insert were assessed for damage features using light microscopy. Based on the results of the microscopic analysis, scanning electron microscopy with energy dispersive X-ray spectroscopy was performed to determine the composition of embedded debris identified, as well as non-contacting 3D profilometry. Pitting, indicative of material loss, was identified on the articulating surfaces of 54% of tibial components and 96% of talar components. Bearing constraint was not found to be a factor, with similar proportions of fixed and mobile bearing metal components showing pitting. More cobalt-chromium than titanium alloy tibial components exhibited pitting (63% versus 20%). Significantly higher average surface roughness (Sa) values were measured for pitted areas in comparison to unpitted areas of these metal components (p<0.05). Additionally, metallic embedded debris (cobalt-chromium likely due to pitting of the tibial and talar components or titanium likely from loss of their porous coatings) was identified in 18% of polyethylene inserts. The presence of hard 3. rd. body particles was also indicated by macroscopically visible sliding plane scratching, identified on 79% of talar components. This explant analysis study demonstrates that metal debris is released from the articulating surfaces and the coatings of various contemporary TARs, both fixed and mobile bearing. These findings suggest that metal debris release in TARs may be an under-recognised issue that should be considered in the study of painful or failed TAR moving forwards


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 540 - 547
1 Jun 2024
Nandra RS Elnahal WA Mayne A Brash L McBryde CW Treacy RBC

Aims. The Birmingham Hip Resurfacing (BHR) was introduced in 1997 to address the needs of young active patients using a historically proven large-diameter metal-on-metal (MoM) bearing. A single designer surgeon’s consecutive series of 130 patients (144 hips) was previously reported at five and ten years, reporting three and ten failures, respectively. The aim of this study was to extend the follow-up of this original cohort at 25 years. Methods. The study extends the reporting on the first consecutive 144 resurfacing procedures in 130 patients for all indications. All operations were undertaken between August 1997 and May 1998. The mean age at operation was 52.1 years (SD 9.93; 17 to 76), and included 37 female patients (28.5%). Failure was defined as revision of either component for any reason. Kaplan-Meier survival analysis was performed. Routine follow-up with serum metal ion levels, radiographs, and Oxford Hip Scores (OHSs) was undertaken. Results. Overall implant survival was 83.50% (95% confidence interval (CI) 0.79 to 0.90) at 25 years, and the number at risk was 79. Survival in male patients at 25 years was 89.5% (95% CI 0.83 to 0.96) compared to 66.9% for female patients (95% CI 0.51 to 0.83). Ten additional failures occurred in the period of ten to 25 years. These involved an adverse reaction to metal debris in four patients, a periprosthetic femoral neck fracture affecting five patients, and aseptic loosening in one patient. The median chromium levels were 49.50 nmol/l (interquartile range (IQR) 34 to 70), and the median cobalt serum levels were 42 nmol/l (IQR 24.50 to 71.25). The median OHS at last follow-up was 35 (IQR 10 to 48). During the 25-year study period, 29 patients died. Patient survival at 25 years was 75.10% (95% CI 0.67 to 0.83). Conclusion. This study demonstrates that MoM hip resurfacing using the BHR provides a durable alternative to total hip arthroplasty (THA), particularly in younger male patients with osteoarthritis wishing to maintain a high level of function. These results compare favourably to the best results for THAs. Cite this article: Bone Joint J 2024;106-B(6):540–547


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 555 - 564
1 Jun 2024
Leal J Holland CT Cochrane NH Seyler TM Jiranek WA Wellman SS Bolognesi MP Ryan SP

Aims

This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection.

Methods

A total of 1,171 total hip arthroplasty (THA) patients with MoM articulations from August 2000 to March 2014 were retrospectively identified. Of those, 328 patients underwent metal artefact reduction sequence MRI and had minimum two years’ clinical follow-up, and met our inclusion criteria. Data collected included demographic details, surgical indication, laterality, implants used, history of pseudotumour, and their corresponding preoperative ESR (mm/hr) and CRP (mg/dl) levels. Multivariate logistic regression modelling was used to evaluate PJI and history of pseudotumour, and receiver operating characteristic curves were created to assess the diagnostic capabilities of ESR and CRP to determine the presence of infection in patients undergoing revision surgery.


The Bone & Joint Journal
Vol. 106-B, Issue 5 Supple B | Pages 118 - 124
1 May 2024
Macheras GA Argyrou C Tzefronis D Milaras C Tsivelekas K Tsiamtsouris KG Kateros K Papadakis SA

Aims

Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI.

Methods

The study included 48 THAs in 48 patients with a clinical suspicion of PJI, but who did not meet European Bone and Joint Infection Society (EBJIS) PJI criteria preoperatively, out of 105 patients undergoing revision THA at our institution for possible PJI between November 2020 and December 2022. Intraoperatively, synovial fluid calprotectin was measured with LFI. Cases with calprotectin levels ≥ 50 mg/l were considered infected and treated with two-stage revision THA; in negative cases, one-stage revision was performed. At least five tissue cultures were obtained; the implants removed were sent for sonication.


The Bone & Joint Journal
Vol. 106-B, Issue 5 Supple B | Pages 32 - 39
1 May 2024
Briem T Stephan A Stadelmann VA Fischer MA Pfirrmann CWA Rüdiger HA Leunig M

Aims

The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI).

Methods

This single-centre study focused on a cohort of 24 patients with cam- or pincer-type FAI, full-thickness femoral or acetabular chondral lesions, or osteochondral lesions ≥ 2 cm2, who underwent surgical hip dislocation for FAI correction in combination with AMIC between March 2009 and February 2016. Baseline data were retrospectively obtained from patient files. Mid-term outcomes were prospectively collected at a follow-up in 2020: cartilage repair tissue quality was evaluated by MRI using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Patient-reported outcome measures (PROMs) included the Oxford Hip Score (OHS) and Core Outcome Measure Index (COMI). Clinical examination included range of motion, impingement tests, and pain.


The Bone & Joint Journal
Vol. 106-B, Issue 5 Supple B | Pages 47 - 53
1 May 2024
Jones SA Parker J Horner M

Aims

The aims of this study were to determine the success of a reconstruction algorithm used in major acetabular bone loss, and to further define the indications for custom-made implants in major acetabular bone loss.

Methods

We reviewed a consecutive series of Paprosky type III acetabular defects treated according to a reconstruction algorithm. IIIA defects were planned to use a superior augment and hemispherical acetabular component. IIIB defects were planned to receive either a hemispherical acetabular component plus augments, a cup-cage reconstruction, or a custom-made implant. We used national digital health records and registry reports to identify any reoperation or re-revision procedure and Oxford Hip Score (OHS) for patient-reported outcomes. Implant survival was determined via Kaplan-Meier analysis.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 149 - 156
4 Apr 2024
Rajamäki A Lehtovirta L Niemeläinen M Reito A Parkkinen J Peräniemi S Vepsäläinen J Eskelinen A

Aims. Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium. Methods. Periprosthetic metal concentrations in the synovia and histopathological samples were analyzed from 230 patients from our institution from October 2016 to December 2019. An ordinal regression model was calculated to investigate the effect of the accumulated metals on the histopathological reaction of the synovia. Results. Median metal concentrations were as follows: cobalt: 0.69 μg/g (interquartile range (IQR) 0.10 to 6.10); chromium: 1.1 μg/g (IQR 0.27 to 4.10); and titanium: 1.6 μg/g (IQR 0.90 to 4.07). Moderate ALVAL scores were found in 30% (n = 39) of the revised knees. There were ten patients with an ALVAL score of 6 or more who were revised for suspected periprosthetic joint infection (PJI), aseptic loosening, or osteolysis. R2 varied between 0.269 and 0.369 for the ordinal regression models. The most important variables were model type, indication for revision, and cobalt and chromium in the ordinal regression models. Conclusion. We found that metal particles released from the knee prosthesis can accumulate in the periprosthetic tissues. Several patients revised for suspected culture-negative PJI had features of an ALVAL reaction, which is a novel finding. Therefore, ALVAL-type reactions can also be found around knee prostheses, but they are mostly mild and less common than those found around metal-on-metal prostheses. Cite this article: Bone Joint Res 2024;13(4):149–156


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 312 - 318
1 Apr 2024
Sheth NP Jones SA Sanghavi SA Manktelow A

The advent of modular porous metal augments has ushered in a new form of treatment for acetabular bone loss. The function of an augment can be seen as reducing the size of a defect or reconstituting the anterosuperior/posteroinferior columns and/or allowing supplementary fixation. Depending on the function of the augment, the surgeon can decide on the sequence of introduction of the hemispherical shell, before or after the augment. Augments should always, however, be used with cement to form a unit with the acetabular component. Given their versatility, augments also allow the use of a hemispherical shell in a position that restores the centre of rotation and biomechanics of the hip. Progressive shedding or the appearance of metal debris is a particular finding with augments and, with other radiological signs of failure, should be recognized on serial radiographs. Mid- to long-term outcomes in studies reporting the use of augments with hemispherical shells in revision total hip arthroplasty have shown rates of survival of > 90%. However, a higher risk of failure has been reported when augments have been used for patients with chronic pelvic discontinuity. Cite this article: Bone Joint J 2024;106-B(4):312–318


The Bone & Joint Journal
Vol. 106-B, Issue 3 Supple A | Pages 31 - 37
1 Mar 2024
Bunyoz KI Tsikandylakis G Mortensen K Gromov K Mohaddes M Malchau H Troelsen A

Aims

In metal-on-polyethylene (MoP) total hip arthroplasty (THA), large metal femoral heads have been used to increase stability and reduce the risk of dislocation. The increased size of the femoral head can, however, lead to increased taper corrosion, with the release of metal ions and adverse reactions. The aim of this study was to investigate the relationship between the size of the femoral head and the levels of metal ions in the blood in these patients.

Methods

A total of 96 patients were enrolled at two centres and randomized to undergo MoP THA using either a 32 mm metal head or a femoral head of between 36 mm and 44 mm in size, being the largest possible to fit the thinnest available polyethylene insert. The levels of metal ions and patient-reported outcome measures (Oxford Hip Score, University of California, Los Angeles Activity Scale) were recorded at two and five years postoperatively.


The Bone & Joint Journal
Vol. 106-B, Issue 3 Supple A | Pages 89 - 96
1 Mar 2024
Heckmann ND Chung BC Liu KC Chen XT Lovro LR Kistler NM White E Christ AB Longjohn DB Oakes DA Lieberman JR

Aims

Modular dual-mobility (DM) articulations are increasingly used during total hip arthroplasty (THA). However, concerns remain regarding the metal liner modularity. This study aims to correlate metal artifact reduction sequence (MARS)-MRI abnormalities with serum metal ion levels in patients with DM articulations.

Methods

A total of 45 patients (50 hips) with a modular DM articulation were included with mean follow-up of 3.7 years (SD 1.2). Enrolled patients with an asymptomatic, primary THA and DM articulation with over two years’ follow-up underwent MARS-MRI. Each patient had serum cobalt, chromium, and titanium levels drawn. Patient satisfaction, Oxford Hip Score, and Forgotten Joint Score-12 (FJS-12) were collected. Each MARS-MRI was independently reviewed by fellowship-trained musculoskeletal radiologists blinded to serum ion levels.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_3 | Pages 11 - 11
23 Jan 2024
Raj S Magan A Jones SA
Full Access

Dual mobility (DM) is an established bearing option in Total Hip Arthroplasty (THA). The traditional mono-block DM designs have limited ability for additional fixation, whereas the modular DM designs allow additional screw fixation but limit internal diameter and have the potential to generate metal debris. We report the early results of a CoCrMo alloy mono-block implant manufactured by additive technology with a highly porous ingrowth surface to enhance primary fixation and osseointegration. Prospective follow-up of the Duplex. TM. implant first inserted in March 2016 enrolled into Beyond Compliance (BC). Primary outcome measure was all-cause revision and secondary outcomes dislocation, peri-prosthetic fracture (PPF) and Oxford Hip Score (OHS). Patients were risk stratified and all considered to be high risk for instability. Complications were identified via hospital records, clinical coding linkage using national database and via BC website. 159 implants in 154 patients with a mean age 74.0 years and a maximum F/U of 7 years. Survivorship for all-cause revision 99.4% (95% CI 96.2–99.8). One femoral only revision. Mean gain in OHS 27.4. Dislocation rate 0.6% with a single event. Patients with a cemented Polished taper stem (PTS) had a Type B PPF rate of 2.1% requiring revision/fixation. Compared to conventional THA this cohort was significantly older (74.0 vs 68.3 years), more co-morbidity (ASA 3 46.5% vs 14.4%) and more non-OA indications (32.4% vs 8.5%). Every patient had at least one risk factor for falling and >50% of cohort had 4 or more risk factors using NICE tool. We believe our results demonstrate that risk stratification successfully aids implant selection to prevent dislocation in high-risk patients. This novel design has provided excellent early results in a challenging cohort where individuals are very different to the “average” THA patient. NJR data on DM has reported an increase in revision for PPF. A “perfect storm” maybe created using DM in high-risk falls risk population. This re-enforces the need to consider all patient and implant factors when deciding bearing selection


Bone & Joint Open
Vol. 4, Issue 11 | Pages 853 - 858
10 Nov 2023
Subbiah Ponniah H Logishetty K Edwards TC Singer GC

Aims

Metal-on-metal hip resurfacing (MoM-HR) has seen decreased usage due to safety and longevity concerns. Joint registries have highlighted the risks in females, smaller hips, and hip dysplasia. This study aimed to identify if reported risk factors are linked to revision in a long-term follow-up of MoM-HR performed by a non-designer surgeon.

Methods

A retrospective review of consecutive MoM hip arthroplasties (MoM-HRAs) using Birmingham Hip Resurfacing was conducted. Data on procedure side, indication, implant sizes and orientation, highest blood cobalt and chromium ion concentrations, and all-cause revision were collected from local and UK National Joint Registry records.


The Bone & Joint Journal
Vol. 105-B, Issue 10 | Pages 1060 - 1069
1 Oct 2023
Holleyman RJ Jameson SS Reed M Meek RMD Khanduja V Hamer A Judge A Board T

Aims

This study describes the variation in the annual volumes of revision hip arthroplasty (RHA) undertaken by consultant surgeons nationally, and the rate of accrual of RHA and corresponding primary hip arthroplasty (PHA) volume for new consultants entering practice.

Methods

National Joint Registry (NJR) data for England, Wales, Northern Ireland, and the Isle of Man were received for 84,816 RHAs and 818,979 PHAs recorded between April 2011 and December 2019. RHA data comprised all revision procedures, including first-time revisions of PHA and any subsequent re-revisions recorded in public and private healthcare organizations. Annual procedure volumes undertaken by the responsible consultant surgeon in the 12 months prior to every index procedure were determined. We identified a cohort of ‘new’ HA consultants who commenced practice from 2012 and describe their rate of accrual of PHA and RHA experience.


The Bone & Joint Journal
Vol. 105-B, Issue 9 | Pages 946 - 952
1 Sep 2023
Dhawan R Young DA Van Eemeren A Shimmin A

Aims

The Birmingham Hip Resurfacing (BHR) arthroplasty has been used as a surgical treatment of coxarthrosis since 1997. We present 20-year results of 234 consecutive BHRs performed in our unit.

Methods

Between 1999 and 2001, there were 217 patients: 142 males (65.4%), mean age 52 years (18 to 68) who had 234 implants (17 bilateral). They had patient-reported outcome measures collected, imaging (radiograph and ultrasound), and serum metal ion assessment. Survivorship analysis was performed using Kaplan-Meier estimates. Revision for any cause was considered as an endpoint for the analysis.


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 775 - 782
1 Jul 2023
Koper MC Spek RWA Reijman M van Es EM Baart SJ Verhaar JAN Bos PK

Aims

The aims of this study were to determine if an increasing serum cobalt (Co) and/or chromium (Cr) concentration is correlated with a decreasing Harris Hip Score (HHS) and Hip disability and Osteoarthritis Outcome Score (HOOS) in patients who received the Articular Surface Replacement (ASR) hip resurfacing arthroplasty (HRA), and to evaluate the ten-year revision rate and show if sex, inclination angle, and Co level influenced the revision rate.

Methods

A total of 62 patients with an ASR-HRA were included and monitored yearly postoperatively. At follow-up, serum Co and Cr levels were measured and the HHS and the HOOS were scored. In addition, preoperative patient and implant variables and the need for revision surgery were recorded. We used a linear mixed model to relate the serum Co and Cr levels to different patient-reported outcome measures (PROMs). For the survival analyses we used the Kaplan-Meier and Cox regression model.