Accuracy of cup placement compared with preoperative surgeon targets in primary total hip arthroplasty using standard instrumentation and techniques: a global, multicenter study.

BACKGROUND: Acetabular cup positioning in total hip arthroplasty (THA) is closely related to outcomes. The literature has suggested cup parameters defined by the Lewinnek safe zone; however, the validity of such measures is in question. Several studies have raised concerns about the benefits of using the Lewinnek safe zone as a predictor of success. In this study we elected to use prospective surgeon targets as the basis for comparison to see how successful surgeons are positioning their cup using standard instruments and techniques. METHODS: A prospective, global, multicenter study was conducted. Cup positioning success was defined as a composite endpoint. Both cup inclination and version needed to be within 10° of the surgeon target to be considered a success. Radiographic analysis was conducted by a third-party reviewer. RESULTS: In 170 subjects, inclination, target versus actual, was 44.8° [standard deviation (SD 0.9°)] and 43.1° (SD 7.6°), respectively (p = 0.0029). Inclination was considered successful in 84.1% of cases. Mean version, target versus actual, was 19.4° (SD 3.9°) and 27.2° (SD 5.6°), respectively (p < 0.0001). Version was considered successful in 63.4% of cases, and combined position (inclination and version) was considered successful in 53.1%. CONCLUSION: This study shows that with traditional methods of placing the cup intraoperatively, surgeons are only accurate 53.1% of the time compared with a predicted preoperative plan. This study suggests that the inconsistency in cup positioning based on the surgeon's planned target is potentially another important variable to consider while using a mechanical guide or in freehand techniques for cup placement in THA. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, NCT03189303.

Use of thioglycolate broth as a pre-analytic transport medium in the diagnosis of prosthetic joint infection.

OBJECTIVES: This study aimed to investigate whether adding tissue samples directly into thioglycolate (TG) broth yielded a greater number of anaerobic organisms than freshly sampled tissue in suspected hip and knee prosthetic joint infections (PJIs). PATIENTS AND METHODS: Between January 2017 and December 2020, a total of 90 patients (46 males, 44 females; median age: 71.7 years; range, 50.8 and 87.8 years) who underwent revision hip or knee arthroplasty were included. Intraoperative samples were taken, with five placed in TG broth and five in standard containers (PC) with subsequent aerobic and anaerobic culturing conducted. Demographic and baseline data of the patients were recorded. The primary outcome was positive bacterial growth from a PJI specimen inoculated directly into TG broth at the time of collection or standard PJI specimen processing. Secondary outcomes investigated were the presence of Cutibacterium acnes (C. acnes) and the curative success of revision procedure. RESULTS: A total of 900 samples (450 PC and 450 TG) were taken from 90 revision arthroplasty patients (47 knees and 43 hips). There was no statistically significant difference in the number of positive bacterial growth samples between TG broth and standard processing (p=0.742). This was consistent with subgroup analysis analyzing C. acnes (p=0.666). CONCLUSION: In hip and knee arthroplasty, there is no benefit in substituting or adding TG broth as a culture medium to better identify both general bacterial species and C. acnes infections specifically. However, the use of TG may be useful in confirming a true positive result for infection.

Surgical Technique of the 3-Dimensional-printed Personalized Hip Implant for the Treatment of Canine Hip Dysplasia.

Hip dysplasia causes major disability in dogs. Treatment options are limited to palliative treatment (e.g., pain relief, physical exercise, lifestyle changes, and weight control) or invasive surgeries such as pelvic osteotomies and total hip arthroplasty. Hence, a strong unmet need exists for an effective and dog-friendly solution that enhances the quality of life of man's best friend. We fill this treatment gap by offering a minimally traumatic and extraarticular, dog-specific, 3-dimensional-printed, hip implant (3DHIP) that restores hip joint stability. The surgical treatment using a 3DHIP implant is less invasive than osteotomies and can be performed bilaterally in one surgical session. The 3DHIP implant extends the dorsal acetabular rim of the dysplastic hip joint thereby increasing coverage of the femoral head and inhibiting joint subluxation with fast recovery. Sufficient access to the dorsal acetabular rim and ventral border of the iliac body together with optimal fitting and fixation of the implant are key steps for a successful 3DHIP implantation and imply the need for a specific approach. The present article aims to showcase this innovative surgical technique with tips and tricks as a surgical manual for implantation of the 3DHIP implant in dogs affected by hip dysplasia.

Elevated cobalt levels in metal-on-polyethylene knee megaprostheses: a prospective 1-year cohort study of 56 patients with hip and knee megaprostheses.

BACKGROUND AND PURPOSE: Concerns have emerged regarding elevated levels of cobalt and chromium in patients with metal-on-metal megaprostheses. This prospective study aims to identify systemic cobalt and chromium levels in metal-on-polyethylene knee and hip megaprostheses and their associations with other factors. METHODS: 56 patients underwent knee or hip megaprosthesis surgery at 2 sarcoma centers. Serum cobalt and chromium levels were measured preoperatively and thrice within the first year using inductively coupled plasma mass spectrometry. RESULTS: A statistically significant difference in serum cobalt levels (1.4 ppb; 95% confidence interval [CI] 0.0-3.3) was observed 1 year after knee megaprosthesis surgery compared with preoperative levels. In contrast no difference in chromium levels was observed after 1 year compared with preoperative levels (0.05 ppb; CI 0.0-0.8). An association between younger age, higher eGFR, and increased cobalt levels was observed. No significant correlations were found between ion levels and resection length or the number of modular connections. CONCLUSION: We found elevated serum ion levels in metal-on-polyethylene knee megaprostheses in contrast to metal-on-polyethylene hip megaprostheses. Furthermore, a positive correlation between cobalt and chromium levels, and between cobalt and eGFR was identified, along with a negative correlation between cobalt and age. This study highlights the importance of monitoring systemic cobalt and chromium levels in patients with megaprostheses.

Small design modifications can improve the primary stability of a fully coated tapered wedge hip stem.

Increasing the stem size during surgery is associated with a higher incidence of intraoperative periprosthetic fractures in cementless total hip arthroplasty with fully coated tapered wedge stems, especially in femurs of Dorr type A. If in contrast a stem is implanted and sufficient primary stability is not achieved, such preventing successful osseointegration due to increased micromotions, it may also fail, especially if the stem is undersized. Stem loosening or periprosthetic fractures due to stem subsidence can be the consequence. The adaptation of an established stem design to femurs of Dorr type A by design modifications, which increase the stem width proximally combined with a smaller stem tip and an overall shorter stem, might reduce the risk of distal locking of a proximally inadequately fixed stem and provide increased stability. The aim of this study was to investigate whether such a modified stem design provides improved primary stability without increasing the periprosthetic fracture risk compared to the established stem design. The established (Corail, DePuy Synthes, Warsaw, IN, US) and modified stem designs (Emphasys, DePuy Synthes, Warsaw, IN, US) were implanted in cadaveric femur pairs (n = 6 pairs) using the respective instruments. Broaching and implantation forces were recorded and the contact areas between the prepared cavity and the stem determined. Implanted stems were subjected to two different cyclic loading conditions according to ISO 7206-4 using a material testing machine (1 Hz, 600 cycles @ 80 to 800 N, 600 cycles @ 80 to 1600 N). Translational and rotational relative motions between stem and femur were recorded using digital image correlation. Broaching and implantation forces for the modified stem were up to 40% higher (p = 0.024), achieving a 23% larger contact area between stem and bone (R2 = 0.694, p = 0.039) resulting in a four times lower subsidence during loading (p = 0.028). The slight design modifications showed the desired effect in this in-vitro study resulting in a higher primary stability suggesting a reduced risk of loosening. The higher forces required during the preparation of the cavity with the new broaches and during implantation of the stem could bare an increased risk for intraoperative periprosthetic fractures, which did not occur in this study.

Sex-based differences in neck selectivity in total hip arthroplasty using a modular femoral neck system.

BACKGROUND: Dislocation is a major complication of total hip arthroplasty (THA). The modular femoral neck system provides practical advantages by allowing adjustment of neck version and length in the presence of intraoperative instability. Anatomical studies have identified morphological differences in the hip joint between men and women. Despite sex-based differences in hip morphology, it remains unclear whether such differences affect neck selectivity in THA using a modular neck system and whether this approach achieves anatomical reconstruction, thereby reducing complications such as dislocation. This study aimed to investigate gender differences in neck selectivity in THA with the modular neck system and assess the clinical impact of the modular neck system. METHODS: A total of 163 THAs using a modular neck system were included in this study. Data on the type of modular neck and intraoperative range of motion (ROM) were retrieved from patient records. Pre- and post-operative leg length differences (LLD) were examined as part of the radiographic assessment. Dislocation was investigated as a postoperative complication. RESULTS: Neck selectivity did not significantly differ between men and women. The comparison of pre- and post-operative LLD revealed a tendency for varus necks to improve LLD more than version-controlled necks. Furthermore, no significant correlation was found between intraoperative ROM and neck selectivity, or postoperative dislocation and neck selectivity. CONCLUSIONS: This study on THA with a modular neck system provided valuable insights into sex-based differences in neck selectivity and highlighted the potential benefits of the modular neck system in addressing LLD and preventing postoperative dislocation.

The influence of surgical technique guidance and surgeon's experience on the femoral head assembly in total hip arthroplasty.

INTRODUCTION: The importance of the assembly procedure on the taper connection strength is evident. However, existent surgical technique guides frequently lack comprehensive and precise instructions in this regard. The aim of our experimental study was to evaluate the influence of the surgical technique guide on the femoral head assembly procedure in surgeons with differing levels of experience in total hip arthroplasty. MATERIALS AND METHODS: Twenty-eight participants, divided into four groups based on their lifetime experience in total hip arthroplasty, conducted a femoral head assembly procedure in a simulated intraoperative environment before and after reviewing the surgical technique guide. Demographic information and the number of hammer blows were documented. Hammer velocity and impaction angle were recorded using an optical motion capturing system, while the impaction force was measured using a dynamic force sensor within the impactor. RESULTS: We observed a high variation in the number of hammer blows, maximum force, and impaction angle. Overall, the number of hammer blows decreased significantly from 3 to 2.2 after reviewing the surgical technique guide. The only significant intragroup difference in the number of hammer blows was observed in the group with no prior experience in total hip arthroplasty. No correlation was found between individual factors (age, weight, height) or experience and the measured parameters (velocity, maximum force and angle). CONCLUSIONS: The present study demonstrated a high variation in the parameters of the femoral head assembly procedure. Consideration of the surgical technique guide was found to be a limited factor among participants with varying levels of experience in total hip arthroplasty. These findings underline the importance of sufficient preoperative training, to standardize the assembly procedure, including impaction force, angle, and use of instruments.

Equivalent revision rates and patient reported outcomes with routine use of a short (125mm) cemented stem for total hip arthroplasty compared to a standard length (150mm) cemented stem. A two surgeon series of 1335 patients.

BACKGROUND: Routine total hip arthroplasty (THA) using a short cemented stem as compared with a standard length cemented stem may have benefits in terms of stress distribution, bone preservation, stem subsidence and ease of revision surgery. Two senior arthroplasty surgeons transitioned their routine femoral implant from a standard 150 mm Exeter V40 cemented stem to a short 125 mm Exeter V40 cemented stem for all patients over the course of several years. We analysed revision rates, adjusted survival, and PROMS scores for patients who received a standard stem and a short stem in routine THA. METHODS: All THAs performed by the two surgeons between January 2011 and December 2021 were included. All procedures were performed using either a 150 mm or 125 mm Exeter V40 stem. Demographic data, acetabular implant type, and outcome data including implant survival, reason for revision, and post-operative Oxford Hip Scores were obtained from the New Zealand Joint Registry (NZJR), and detailed survival analyses were performed. Primary outcome was revision for any reason. Reason for revision, including femoral or acetabular failure, and time to revision were also recorded. RESULTS: 1335 THAs were included. 516 using the 150 mm stem and 819 using the 125 mm stem. There were 4055.5 and 3227.8 component years analysed in the standard stem and short stem groups respectively due to a longer mean follow up in the 150 mm group. Patient reported outcomes were comparable across all groups. Revision rates were comparable between the standard 150 mm stem (0.44 revisions/100 component years) and the short 125 mm stem (0.56 revisions/100 component years) with no statistically significant difference found (p = 0.240). CONCLUSION: Routine use of a short 125 mm stem had no statistically significant impact on revision rate or PROMS scores when compared to a standard 150 mm stem. There may be benefits to routine use of a short cemented femoral implant.

Risk factors for femoral stem fracture following total hip arthroplasty: a systematic review and meta analysis.

BACKGROUND: Femoral stem fracture following total hip arthroplasty (THA) is an infrequent but nevertheless devastating complication, with an increasing worldwide prevalence as demand for primary THA continues to increase. The aim of this study was to perform a systematic review and meta-analysis of risk factors for femoral stem fracture to help identify at risk patients. METHODS: A systematic search was conducted on EMBASE, MEDLINE and AMED to identify relevant studies. Data regarding study design, source, population, intervention, and outcomes was collated. Data extraction was performed on a custom form generated using Cochrane recommended methodology and analysis of risk factors performed including odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 15 studies reporting a total of 402 stem fractures in 49 723 THAs were identified. The median time from index procedure to stem fracture was 68 months (IQR 42.5-118) whilst mean age at index surgery was 61.8 years (SD 6.9). Male gender (OR = 3.27, 95% CI = 2.59-4.13, p < 0.001), patient weight above 80 kg (OR = 3.55, 95% CI = 2.88-4.37, p < 0.001), age under 63 years (OR = 1.22, 95% CI = 1.01-1.49, p < 0.001), varus stem alignment (OR = 5.77, 95% CI = 3.83-8.7, p < 0.001), use of modular implants (OR = 1.95, 95% CI = 1.56-2.44, p < 0.01) and undergoing revision arthroplasty (OR = 3.33, 95% CI = 2.70-4.1, p < 0.001) were significant risk factors for prosthetic stem fracture. A risk window of 15 years post-surgery was identified. CONCLUSIONS: This review concludes that patient weight, younger age, male sex, varus stem alignment, revision arthroplasty and use of modular stems are significant risk factors for femoral stem fracture. Modifying these risk factors where possible may help reduce incidence of femoral stem fracture in at risk patients.

Is AI 3D-printed PSI an accurate option for patients with developmental dysplasia of the hip undergoing THA?

BACKGROUND: In traditional surgical procedures, significant discrepancies are often observed between the pre-planned templated implant sizes and the actual sizes used, particularly in patients with congenital hip dysplasia. These discrepancies arise not only in preoperative planning but also in the precision of implant placement, especially concerning the acetabular component. Our study aims to enhance the accuracy of implant placement during Total Hip Arthroplasty (THA) by integrating AI-enhanced preoperative planning with Patient-Specific Instrumentation (PSI). We also seek to assess the accuracy and clinical outcomes of the AI-PSI (AIPSI) group in comparison to a manual control group. METHODS: This study included 60 patients diagnosed with congenital hip dysplasia, randomly assigned to either the AIPSI or manual group, with 30 patients in each. No significant demographic differences between were noted the two groups. A direct anterior surgical approach was employed. Postoperative assessments included X-rays and CT scans to measure parameters such as the acetabular cup anteversion angle, acetabular cup inclination angle, femoral stem anteversion angle, femoral offset, and leg length discrepancy. Functional scores were recorded at 3 days, 1 week, 4 weeks, and 12 weeks post-surgery. Data analysis was conducted using SPSS version 22.0, with the significance level was set at α = 0.05. RESULTS AND CONCLUSION: The AIPSI group demonstrated greater prosthesis placement accuracy. With the aid of PSI, AI-planned THA surgery provides surgeons with enhanced precision in prosthesis positioning. This approach potentially offers greater insights and guidelines for managing more complex anatomical variations or cases.

Accuracy of portable navigation during THA in patients with severe developmental dysplasia of hip.

INTRODUCTION: Correct cup placement in total hip arthroplasty (THA) for patients with developmental dysplasia of the hip (DDH) is considerably difficult. This study aimed to analyze the orientation accuracy of cup insertion during THA using a portable navigation system in patients with DDH. MATERIALS AND METHODS: In this retrospective cohort study, we analyzed data from 64 patients who underwent THA using infrared stereo camera-matching portable navigation. Patients underwent THA via the anterolateral approach in the lateral decubitus position. Navigation records for intraoperative cup angles, postoperative cup angles measured on computed tomography (CT) images, and cup angle measurement differences were measured and compared between patients with non-DDH/mild DDH and severe DDH. Furthermore, the predictive factors for outliers of accurate acetabular cup placement were analyzed. RESULTS: The average measurement absolute abduction differences (postoperative CT-navigation record) were 3.9 ± 3.5° (severe DDH) and 3.3 ± 2.6° (non-DDH/ mild DDH), and the anteversion differences were 4.7 ± 3.4° (severe DDH) and 2.3 ± 2.1° (non-DDH/ mild DDH). The anteversion difference was different between the two groups. Multivariate analysis showed that the navigation difference (absolute difference in anteversion between postoperative CT and navigation records of > 5°) was significantly associated with severe DDH (odds ratio [OR]: 3.3; p = 0.049, 95% confidence interval [CI]: 1.0-11.1) and posterior pelvic tilt (OR: 1.1; p = 0.042, 95% CI: 1.0-1.27). CONCLUSIONS: In patients with severe DDH, it is important to pay close attention during THA using portable navigation. However, the average difference was < 5º even in patients with severe DDH, and the accuracy may be acceptable in a clinical setting when the cost is considered.

Design and In Vitro Validation of an Orthopaedic Drill Guide for Femoral Stem Revision in Total Hip Arthroplasty.

OBJECTIVE: Cemented total hip arthroplasty (THA) demonstrates superior survival rates compared to uncemented procedures. Nevertheless, most younger patients opt for uncemented THA, as removing well-fixed bone cement in the femur during revisions is complex, particularly the distal cement plug. This removal procedure often increases the risk of femoral fracture or perforation, haemorrhage and weakening bone due to poor drill control and positioning. Aim of this study was to design a novel drill guide to improve drill positioning. METHODS AND PROCEDURES: A novel orthopaedic drill guide was developed, featuring a compliant centralizer activated by a drill guide actuator. Bone models were prepared to assess centralizing performance. Three conditions were tested: drilling without guidance, guided drilling with centralizer activation held, and guided drilling with centralizer activation released. Deviations from the bone centre were measured at the entry and exit point of the drill. RESULTS: In the centralizing performance test, the drill guide significantly reduced drill hole deviations in both entry and exit points compared to the control ([Formula: see text]). The absolute deviation on the exit side of the cement plug was 10.59mm (SD 1.56) for the 'No drill guide' condition, 3.02mm (SD 2.09) for 'Drill guide - hold' and 2.12mm (SD 1.71) for 'Drill guide - release'. The compliant drill guide centralizer significantly lowered the risk of cortical bone perforation during intramedullary canal drilling in the bone models due to better control of the cement drill position. Clinical and Translational Impact Statement: The drill guide potentially reduces perioperative risks in cemented femoral stem revision. Future research should identify optimal scenarios for its application.

15-year survivorship of a unique dual-modular femoral stem in primary hip arthroplasty.

BACKGROUND: Hip offset, version, and length are interdependent femoral variables which determine stability and leg length. Balancing these competing variables remains a core challenge in hip arthroplasty. The potential benefits of modular femoral stems have been overshadowed by higher rates of failure. The objective of this study was to assess the survivorship of a unique dual-modular femoral stem at an average 15-year follow-up period. METHODS: The records of all patients with osteoarthritis who underwent primary total hip arthroplasty with this device between 2004-2009 were reviewed. There were no exclusions for BMI or other factors. We examined the data with Kaplan-Meier survival analysis. The primary endpoint for survival was mechanical failure of the modular neck-body junction. RESULTS: The survivorship of this device in 172 subjects was 100% with none experiencing mechanical failure of the modular junction at an average of 15 years. 60 patients died of causes unrelated to their THA and 9 patients were lost to follow-up. There were three early (≤ 12 months) dislocations (1.7%), and seven total dislocations (4.1%). 16 patients underwent reoperations during the follow-up period, none for any complication of the modular junction. Radiographic results showed well-fixed femoral stems in all cases. There were no leg length discrepancies of greater than 10 mm, and 85% were within 5 mm. CONCLUSION: There were no mechanical failures of the modular junction in any of the subjects over the average 15-year period, demonstrating that this dual-modular design is not associated with increased failure rates. We achieved a 1.7% early dislocation rate and a 4.1% total dislocation rate without any clinically significant leg length discrepancies.

Revision ratio after Femoral Neck System implantation for hip fracture treatment: a retrospective cohort analysis.

The aim of the study is to determine the revision ratio after implantation of the femoral neck system (FNS) for the treatment of femoral neck fractures. A retrospective single center cohort analysis with a total of 71 patients who underwent the implantation of the FNS between December 2019 and December 2021, was performed. 31 males and 40 females were included. There was no exclusion based on BMI, ASA score, Garden classification or Pauwels classification. Primary outcome was the revision rate after FNS implantation. Secondary outcomes comprise the reason for revision surgery as well as the time toward revision surgery and the 30-day mortality. The revision ratio was 11 out of 71 patients (15.5%) with an average time to revision surgery of 10 months. Most common reason for revision was avascular necrosis (AVN) in 45.5%. Other reasons for revision surgery were implant failure due to a secondary fall on to the hip with the FNS implant in place, cut-out, cut-through and malunion in respectively 27.3%, 9%, 9% and 9% of the revision patients. The one- hole plate was used in 72% of the patients. Mean follow-up was 18.07 months (range 6-30 months). Full weight bearing instruction was given to 85.9% of the patients. Partial weight bearing in 14.1% of the patients. In conclusion, the FNS has similar revision ratio when used for femoral neck fractures compared to cannulated screw fixation in literature. The predominant reason for revision is AVN and implant failure with no difference between the use of the one- or-two-hole plate in this study.

Excellent survival of two anatomically adapted hydroxyapatite coated cementless Total Hip Arthroplasties. A mean follow-up of 11.3 years.

There are many different types of cementless anatomically adapted Total Hip Arthroplasties (THAs) on the market, the Anatomic Benoist Gerard (ABG) I and II are such types of cementless THAs. In this retrospective single-centre study we evaluated the overall survival with revision for any reason and aseptic loosening as endpoint at more than 11 years follow-up. Between 2000 and 2004, 244 cementless THAs were performed in 230 patients in a primary care hospital. At a mean of 11.3 years follow-up (range 9.8 - 12.8 years) clinical examination, plain radiography and Patient Reported Outcome Measures (PROMs) were obtained and analysed. The PROMs consisted of the Oxford Hip Score (OHS) and the Western Ontario and McMaster University Index (WOMAC). At a mean of 11.3 years follow-up 32 patients (13.1%) had died of unrelated causes. Of the remaining cohort all 198 patients (212 THAs) have been reached for evaluation. There were no patients considered as lost to follow-up. At a mean of 11.3 years 11 patients (11 THAs) have had a revision of either the femoral implant or acetabular component resulting in an overall survival of 95.5%. There was no statistically significant difference (p=0.564) in survival between the ABG I and II THAs. Radiographic there were no changes between the ABG I and II last follow up. The ABG II performed statistically significant better in PROMs. We concluded that both anatomically adapted hydroxyapatite coated cementless THAs show excellent survival at more than 11 years follow-up.

Clinical, functional and radiographic long-term follow-up (7-12 years) of Birmingham Hip Resurfacing, including metal ions evaluation: a single surgeon series.

Hip resurfacing arthroplasty (HRA) has been advocated as an attractive therapy for a younger, more demanding patient population with debilitating hip osteoarthritis. Controversies surrounding metal-on-metal (MoM) hip resurfacing have, however, led to a significant decline in the popularity of the HRA. Despite this, substantial evidence supports the use of specific implants in a selected group of patients. This is a continued retrospective analysis of a single surgeon series of the Birmingham Hip Resurfacing (BHR). Initial medium-term analysis was done in 2011 and published by Van der Bracht et al.13. This analysis includes a long-term follow-up of 7 to 12 years, including functional scoring (HHS, HOOS and UCLA activity score), metal ion evaluation and survival analysis. Failure was defined as revision for any cause. A total of 267 resurfacing procedures with the BHR were included in 247 patients. We had a mean follow-up of 8.3 years. Overall survival at ten years was 94.8%(97.2% for males and 90.1% for females). There was a statistically significant increase in mean HHS score at follow-up (56.03 - IQR 47-65 to 96.07 - IQR 96-100). Elevated metal ions were correlated with a statistically significant increase in the probability of complications. This cohort study further proved that hip resurfacing arthroplasty with the Birmingham Hip Resurfacing implant provides a good alternative to conventional total hip arthroplasty in young patients. There was a significant increase in functional scores at follow-up. There is further evidence of less favorable outcomes in female patients.