Resident training does not influence the complication risk in total knee and hip arthroplasty

Background and purpose - Gaining experience in the surgery room during residency is an important part of learning the skills needed to perform arthroplasties. However, in practice, patients are often not fully comfortable with trainee involvement in their own surgery. Therefore, we investigated complications, revision rates, mortality, and operative time of orthopedic surgeons and residents as primary surgeon performing total knee arthroplasties (TKAs) or total hip arthroplasties (THAs). Patients and methods - In this multi-center retrospective cohort study, 3,098 TKAs and 4,027 THAs performed between 2007 and 2013 were analyzed. Complications, revisions, mortality, and operative time were compared for patients operated on by the orthopedic surgeon or a resident as primary surgeon. An additional analysis was performed to determine whether the complication risk was affected by the postgraduate year of the resident. Results - Orthopedic complication rates were similar (TKA: orthopedic surgeon: 10%, resident: 11%; THA: 9% and 8%), revision rates (TKA: 3% and 2%, THA: 3% and 2%), or mortality rates (TKA: 0.1% and 0.3%, THA: 0.2% and 0.3%). For both procedures a higher non-orthopedic complication rate was found in the resident group (TKA: 8% and 10%; p = 0.03, THA: 8% and 10%; p = 0.01) and a slightly longer operative time (TKA: mean difference 9.0 minutes (8%); THA: 11.3 minutes (11%)). Interpretation - Complications, revisions, and mortality were similar in TKAs or THAs performed by the resident as primary surgeon compared with surgeries performed by an orthopedic surgeon. This data can be used in teaching hospitals and may help to reassure patients.Orthopaedics, Trauma Surgery and Rehabilitatio

External validation of twelve existing survival prediction models for patients with spinal metastases

BACKGROUND CONTEXT:Survival prediction models for patients with spinal metastases may inform patients and clinicians in shared decision-making. PURPOSE: To externally validate all existing survival prediction models for patients with spinal metastases. DESIGN: Prospective cohort study using retrospective data. PATIENT SAMPLE: 953 patients. OUTCOME MEASURES: Survival in months, area under the curve (AUC), and calibration intercept and slope. METHOD: This study included patients with spinal metastases referred to a single tertiary referral center between 2016 and 2021. Twelve models for predicting 3, 6, and 12-month survival were externally validated Bollen, Mizumoto, Modified Bauer, New England Spinal Metastasis Score, Original Bauer, Oswestry Spinal Risk Index (OSRI), PathFx, Revised Katagiri, Revised Tokuhashi, Skeletal Oncology Research Group Machine Learning Algorithm (SORG-MLA), Tomita, and Van der Linden. Discrimination was assessed using (AUC) and calibration using the intercept and slope. Calibration was considered appropriate if calibration measures were close to their ideal values with narrow confidence intervals. RESULTS:In total, 953 patients were included. Survival was 76.4% at 3 months (728/953), 62.2% at 6 months (593/953), and 50.3% at 12 months (479/953). Revised Katagiri yielded AUCs of 0.79 (95% CI, 0.76–0.82) to 0.81 (95% CI, 0.79–0.84), Bollen yielded AUCs of 0.76 (95% CI, 0.73–0.80) to 0.77 (95% CI, 0.75–0.80), and OSRI yielded AUCs of 0.75 (95% CI, 0.72–0.78) to 0.77 (95% CI, 0.74–0.79). The other 9 prediction models yielded AUCs ranging from 0.59 (95% CI, 0.55–0.63) to 0.76 (95% CI, 0.74–0.79). None of the twelve models yielded appropriate calibration. CONCLUSIONS: Twelve survival prediction models for patients with spinal metastases yielded poor to fair discrimination and poor calibration. Survival prediction models may inform decision-making in patients with spinal metastases, provided that recalibration using recent patient data is performed.</p

Long-term (> 10 years) clinical outcomes of instrumented posterolateral fusion for spondylolisthesis

PURPOSE: Despite the rapid increase in instrumented spinal fusions for a variety of indications, most studies focus on short-term fusion rates. Long-term clinical outcomes are still scarce and inconclusive. This study investigated clinical outcomes > 10 years after single-level instrumented posterolateral spinal fusion for lumbar degenerative or isthmic spondylolisthesis with neurological symptoms. METHODS: Cross-sectional long-term follow-up among the Dutch participants of an international multicenter randomized controlled trial comparing osteogenic protein-1 with autograft. Clinical outcomes were assessed using the Oswestry Disability Index (ODI), EQ-5D-3L and visual analogue scale (VAS) for leg and back pain, as well as questions on satisfaction with treatment and additional surgery. RESULTS: The follow-up rate was 73% (41 patients). At mean 11.8 (range 10.1-13.7) years after surgery, a non-significant deterioration of clinical outcomes compared to 1-year follow-up was observed. The mean ODI was 20 ± 19, mean EQ-5D-3L index score 0.784 ± 0.251 and mean VAS for leg and back pain, respectively, 34 ± 33 and 31 ± 28. Multiple regression showed that diagnosis (degenerative vs. isthmic spondylolisthesis), graft type (OP-1 vs. autograft) and 1-year fusion status (fusion vs. no fusion) were not predictive for the ODI at long-term follow-up (p = 0.389). Satisfaction with treatment was excellent and over 70% of the patients reported lasting improvement in back and/or leg pain. No revision surgeries for non-union were reported. CONCLUSION: This study showed favourable clinical outcomes > 10 years after instrumented posterolateral spinal fusion and supports spondylolisthesis with neurological symptoms as indication for fusion surgery

Neurologic Outcomes After Radiation Therapy for Severe Spinal Cord Compression in Multiple Myeloma: A Study of 162 Patients

BACKGROUND: Bone destruction is the most frequent disease-defining clinical feature of multiple myeloma (MM), resulting in skeletal-related events such as back pain, pathological fractures, or neurologic compromise including epidural spinal cord compression (ESCC). Up to 24% of patients with MM will be affected by ESCC. Radiation therapy has been proven to be highly effective in pain relief in patients with MM. However, a critical knowledge gap remains with regard to neurologic outcomes in patients with high-grade ESCC treated with radiation. METHODS: We retrospectively included 162 patients with MM and high-grade ESCC (grade 2 or 3) who underwent radiation therapy of the spine between January 2010 and July 2021. The primary outcome was the American Spinal Injury Association (ASIA) score after 12 to 24 months, or the last known ASIA score if the patient had had a repeat treatment or died. Multivariable logistic regression was used to assess factors associated with poor neurologic outcomes after radiation, defined as neurologic deterioration or lack of improvement. RESULTS: After radiation therapy, 34 patients (21%) had no improvement in their impaired neurologic function and 27 (17%) deteriorated neurologically. Thirty-six patients (22%) underwent either surgery or repeat irradiation after the initial radiation therapy. There were 100 patients who were neurologically intact at baseline (ASIA score of E), of whom 16 (16%) had neurologic deterioration. Four variables were independently associated with poor neurologic outcomes: baseline ASIA (odds ratio [OR] = 6.50; 95% confidence interval [CI] = 2.70 to 17.38; p < 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (OR = 6.19; 95% CI = 1.49 to 29.49; p = 0.015), number of levels affected by ESCC (OR = 4.02; 95% CI = 1.19 to 14.18; p = 0.026), and receiving steroids prior to radiation (OR = 4.42; 95% CI = 1.41 to 16.10; p = 0.015). CONCLUSIONS: Our study showed that 38% of patients deteriorated or did not improve neurologically after radiation therapy for high-grade ESCC. The results highlight the need for multidisciplinary input and efforts in the treatment of high-grade ESCC in patients with MM. Future studies will help to improve patient selection for specific and standardized treatments and to clearly delineate which patients are likely to benefit from radiation therapy. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence

Analysis of complications and revisions after spine surgery in 270 multiple myeloma patients with spinal involvement

BACKGROUND CONTEXT: Patients with multiple myeloma (MM) are at increased risk of infections and suffer from poor bone quality due to their disseminated malignant bone disease. Therefore, postoperative complications may occur following surgical treatment of MM lesions. PURPOSE: In this study, we aimed to determine the incidence of postoperative complications and retreatments after spinal surgery in MM patients. Additionally, we sought to identify risk factors associated with complications and retreatments. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: In total, 270 patients with MM who received surgical treatment for spinal involvement between 2008 and 2021 were included. OUTCOME MEASURES: The incidence of perioperative complications within 6 weeks and reoperations within 2.5 years and individual odds ratios for factors associated with these complications and reoperations. METHODS: Data were collected through manual chart review. Hosmer and Lemeshow's purposeful regression method was used to identify risk factors for complications and reoperations. RESULTS: The median age of our cohort was 65 years (SD = 10.8), and 58% were male (n = 57). Intraoperative complications were present in 24 patients (8.9%). The overall 6-week complication rate after surgery was 35% (n = 95). The following variables were independently associated with 6-week complications: higher Genant grading of a present vertebral fracture (OR 1.41; 95% CI 1.04-1.95; p = .031), receiving intramuscular or intravenous steroids within a week prior to surgery (OR 3.97; 95% CI 1.79-9.06; p = .001), decompression surgery without fusion (OR 6.53; 95% CI 1.30-36.86; p = .026), higher creatinine levels (OR 2.18; 95% CI 1.19-5.60; p = .014), and lower calcium levels (OR 0.58; 95% CI 0.37-0.88; p = .013). A secondary surgery was indicated for 53 patients (20%), of which 13 (4.8%) took place within two weeks after the initial surgery. We additionally discovered factors associated with retreatments, which are elucidated within the manuscript. CONCLUSION: The goal of surgical treatment for MM bone disease is to enhance patient quality of life and reduce symptom burden. However, postoperative complication rates remain relatively high after spine surgery in patients with MM, likely attributable to both inherent characteristics of the disease and patient comorbidities. The risk for complications and secondary surgeries should be explored and a multidisciplinary approach is crucial

Stereotactic Body radiotherapy and pedicLE screw fixatioN During one hospital visit for patients with symptomatic unstable spinal metastases: a randomized trial (BLEND RCT) using the Trials within Cohorts (TwiCs) design

BACKGROUND: Spinal metastases can lead to unremitting pain and neurological deficits, which substantially impair daily functioning and quality of life. Patients with unstable spinal metastases receive surgical stabilization followed by palliative radiotherapy as soon as wound healing allows. The time between surgery and radiotherapy delays improvement of mobility, radiotherapy-induced pain relief, local tumor control, and restart of systemic oncological therapy. Stereotactic body radiotherapy (SBRT) enables delivery of preoperative high-dose radiotherapy while dose-sparing the surgical field, allowing stabilizing surgery within only hours. Patients may experience earlier recovery of mobility, regression of pain, and return to systemic oncological therapy. The BLEND RCT evaluates the effectiveness of SBRT followed by surgery within 24 h for the treatment of symptomatic, unstable spinal metastases. METHODS: This phase III randomized controlled trial is embedded within the PRospective Evaluation of interventional StudiEs on boNe meTastases (PRESENT) cohort. Patients with symptomatic, unstable spinal metastases requiring stabilizing surgery and radiotherapy will be randomized (1:1). The intervention group (n = 50) will be offered same-day SBRT and surgery, which they can accept or refuse. According to the Trial within Cohorts (TwiCs) design, the control group (n = 50) will not be informed and receive standard treatment (surgery followed by conventional radiotherapy after 1-2 weeks when wound healing allows). Baseline characteristics and outcome measures will be captured within PRESENT. The primary outcome is physical functioning (EORTC-QLQ-C15-PAL) 4 weeks after start of treatment. Secondary endpoints include pain response, time until return to systemic oncological therapy, quality of life, local tumor control, and adverse events up to 3 months post-treatment. DISCUSSION: The BLEND RCT evaluates the effect of same-day SBRT and stabilizing surgery for the treatment of symptomatic, unstable spinal metastases compared with standard of care. We expect better functional outcomes, faster pain relief, and continuation of systemic oncological therapy. The TwiCs design enables efficient recruitment within an ongoing cohort, as well as prevention of disappointment bias and drop-out as control patients will not be informed about the trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05575323. Registered on October 11, 2022

Bone regeneration for spinal fusion - translational studies and the pathway to the patient

Aim of this thesis: The central aim of this thesis is to study the potential of several promising bone grafts substitutes in comparison to iliac crest autograft for spinal fusion. The emphasis will be on posterolateral fusion, since this is one of the most commonly performed techniques, but also one of the most challenging indications for bone grafts, due to the large distance that needs to bridged, limited contact surface and the unfavorable biomechanical environment. This thesis includes several preclinical and clinical studies including a randomized clinical trial. Outline: We started with critically investigating two assumptions that are generally made when discussing the use of autograft: 1) the morbidity of bone graft harvesting and 2) the relevance of viable cells within this graft. Although many severe and major complications are reported from harvesting bone from iliac crest, 6,7,11,12,62–64 the most common complication is enduring pain at the donor site. As mentioned before, the reported incidence of donor site pain varies between 6% to 39%. 10,12,13,15,17,18,63 The close proximity of the primary surgery to the iliac crest, however, could interfere with the reported incidence. In Chapter 2 the incidence of donor site pain was compared between patients who underwent fusion of different spinal levels to evaluate this effect and to determine the ‘true’ importance of donor site pain after posterior iliac crest bone harvesting. In Chapter 3 we investigate the relevance of viable osteogenic cells in autologous bone grafts. This is important as viable cells are a prominent difference between autologous bone graft and most conventional alternatives, which may be a reason for its superiority. On the other hand it is unlikely that these cells survive after transplantation. 65,66 The bone forming capacity between viable and devitalized autologous bone grafts was evaluated in a chamber model mounted on the transverse processes of a goat. In the continuing chapters several bone grafts or enhancers were compared to iliac crest autograft. In Chapter 4 the effect of adding platelet-leukocyte gel to three bone grafts (autologous bone graft, biphasic calcium phosphate and trabecular metal) was evaluated in the same transverse process cassette model that represents the initial phase of bone formation for spinal fusions. The next objective was to determine if a new putatively bioactive tricalcium phosphate was a suitable bone graft substitute for spinal fusions in a large animal model. It was compared to the currently most used grafts: iliac crest autograft and allograft. In Chapter 5 we present the results of an instrumented posterolateral fusion study in goats. The final part of this thesis focuses on bone morphogenetic proteins (BMPs). In Chapter 6 we describe how the sequential converging of the technologies of biochemistry, biomaterial science, imaging, and molecular biology finally resulted in the development of a new regenerative treatment (the use of BMPs) in orthopaedics. In contrast to the decades it took from the discovery of BMPs to becoming commercially available, these proteins are rapidly incorporated in the clinical routine with limited, if any, evidence for most indications. In this thesis, we conducted a European multi-center study comparing OP-1 (BMP-7) to iliac crest autograft in instrumented posterolateral fusions, which is one of the most applied indications of BMPs. We started with a pilot phase to obtain information on safety and feasibility of which the results are shown in Chapter 7. After this pilot, we continued the whole study that is presented in Chapter 8. During the course of this clinical study, the European Union adopted a new Clinical Trials Directive (2001/20/EC) as a framework for good management in trials of medicine. The goal of this directive was simplifying and harmonizing the administrative provisions governing clinical trials in EU countries. In Chapter 9, we discuss the practical consequences of this Clinical Trials Directive. Especially with respect to our situation during the conduction of a European multi-center study. We conclude this thesis with a general summery, which addresses the previously discussed items in Chapter 10, and finish with a general discussion and future perspectives in Chapter 1