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

GliMR: Cross-Border Collaborations to Promote Advanced MRI Biomarkers for Glioma

Purpose: There is an annual incidence of 50,000 glioma cases in Europe. The optimal treatment strategy is highly personalised, depending on tumour type, grade, spatial localization, and the degree of tissue infiltration. In research settings, advanced magnetic resonance imaging (MRI) has shown great promise as a tool to inform personalised treatment decisions. However, the use of advanced MRI in clinical practice rem

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

Extension type fracture of the ankylotic thoracic spine with gross displacement causing esophageal rupture

Purpose: This study aimed at discussing the relevance of the type B3 fracture of the new AOSpine classification. Methods: Hyperextension fractures of the spine are rare in the general population, but common in the ankylotic spine. We present a case of a severe spinal fracture with concomitant esophageal rupture, which was diagnosed early and could be treated during the initial trauma care. Results: The spinal column was stabilized using a percutaneous technique after which the perforated esophagus was sutured through a thoracotomy. The spinal injury was classified a type B3 fracture using the new AOSpine classification. Conclusion: The B3 typification raised a lot of discussion during the development of the new classification system and may be controversial. This case, however, nicely illustrates the relevance of an intact posterior hinge as compared to C-type injuries where complete dissociation is present with inherent spinal cord damage

Exploratory meta-analysis on dose-related efficacy and morbidity of bone morphogenetic protein in spinal arthrodesis surgery

Bone morphogenetic protein (BMP) is frequently used for spinal arthrodesis procedures in an "off-label" fashion. Whereas complications related to BMP usage are well recognized, the role of dosage is less clear. The objective of this meta-analysis was to assess dose-dependent effectiveness (i.e., bone fusion) and morbidity of BMP used in common spinal arthrodesis procedures. A quantitative exploratory meta-analysis was conducted on studies reporting fusion and complication rates following anterior cervical discectomy and fusion (ACDF), posterior cervical fusion (PCF), anterior lumbar interbody fusion (ALIF), transforaminal lumbar interbody fusion (TLIF), posterior lumbar interbody fusion (PLIF), and posterolateral lumbar fusion (PLF) supplemented with BMP. A literature search was performed to identify studies on BMP in spinal fusion procedures reporting fusion and/or complication rates. From the included studies, a database for each spinal fusion procedure, including patient demographic information, dose of BMP per level, and data regarding fusion rate and complication rates, was created. The incidence of fusion and complication rates was calculated and analyzed as a function of BMP dose. The methodological quality of all included studies was assessed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Data were analyzed using a random-effects model. Event rates are shown as percentages, with a 95% CI. Forty-eight articles met the inclusion criteria: ACDF (n = 7), PCF (n = 6), ALIF (n = 9), TLIF/PLIF (n = 17), and PLF (n = 9), resulting in a total of 5890 patients. In ACDF, the lowest BMP concentration analyzed (0.2-0.6 mg/level) resulted in a fusion rate similar to the highest dose (1.1-2.1 mg/level), while permitting complication rates comparable to ACDF performed without BMP. The addition of BMP to multilevel constructs significantly (p < 0.001) increased the fusion rate (98.4% [CI 95.4%-99.4%]) versus the control group fusion rate (85.8% [CI 77.4%-91.4%]). Studies on PCF were of poor quality and suggest that BMP doses of ≤ 2.1 mg/level resulted in similar fusion rates as higher doses. Use of BMP in ALIF increased fusion rates from 79.1% (CI 57.6%-91.3%) in the control cohort to 96.9% (CI 92.3%-98.8%) in the BMP-treated group (p < 0.01). The rate of complications showed a positive correlation with the BMP dose used. Use of BMP in TLIF had only a minimal impact on fusion rates (95.0% [CI 92.8%-96.5%] vs 93.0% [CI 78.1%-98.0%] in control patients). In PLF, use of ≥ 8.5 mg BMP per level led to a significant increase of fusion rate (95.2%; CI 90.1%-97.8%) compared with the control group (75.3%; CI 64.1%-84.0%, p < 0.001). BMP did not alter the rate of complications when used in PLF. The BMP doses used for various spinal arthrodesis procedures differed greatly between studies. This study provides BMP dosing recommendations for the most common spine procedures

Comparing autograft, allograft, and tricalcium phosphate ceramic in a goat instrumented posterolateral fusion model

The most common application of bone grafts is spinal fusion surgery, in which the use of iliac crest autograft is the gold standard. Harvesting of autograft, however, requires an extra surgical procedure, which is associated with additional morbidity. Allograft is the well-known alternative, but it is generally considered less effective in posterior fusions. Therefore, the need for an effective alternative remains. Recently, it was shown that ceramics can be endowed with biologically instructive properties by changing the basic parameters of the material. In this study, we compared a novel tricalcium phosphate ceramic (TCP) to iliac crest autograft and allograft, in instrumented posterolateral fusions in a goat model. A total of nine goats were included, who underwent a two-level lumbar fusion. Each side of the spine was randomized into one type of graft: iliac crest autograft; fresh-frozen allograft; TCP alone; or TCP combined with local autograft (50:50). The fusion rates after 16 weeks were comparable between the groups (autograft 3/8, allograft 4/8, TCP 4/8, and TCP/local autograft 5/8). Calculation of the fusion volume on computed tomography images, showed significantly greater volume in the control groups (autograft 7.8 mL and allograft 8.9 mL) compared with the groups with TCP (TCP 6.1 mL and TCP/local autograft 6.0 mL). No adverse tissue response was seen on histological analysis and TCP was almost completely resorbed. The results demonstrate that TCP is capable of achieving fusion at a similar rate to iliac crest autograft in posterolateral fusions, while almost completely resorbing within 16 weeks. Despite the lower fusion volume, the TCP is a promising alternative circumventing the disadvantages of autograft and allograft

Natural Antibodies Against Bone Morphogenic Proteins and Interferons in Healthy Donors and in Patients with Infections Linked to Type-1 Cytokine Responses

In patients receiving recombinant therapeutic proteins, the production of antibodies against the therapeutics is a rising problem. The antibodies can neutralize and interfere with the efficacy and safety of drugs and even cause severe side effects if they cross-react against the natural, endogenous protein. Various factors have been identified to influence the immunogenic potential of recombinant human therapeutics, including several patients' characteristics. In recent years, so-called naturally occurring antibodies against cytokines and growth factors have been detected in naive patients before start of treatment with recombinant human therapeutics. The role of naturally occurring antibodies is not well understood and their influence on production of anti-drug antibodies is not known. One might speculate that the presence of naturally occurring antibodies increases the likelihood of eliciting anti-drug antibodies once treatment with the corresponding recombinant therapeutic protein is started. We screened serum samples from 410 healthy controls and patients for auto-antibodies against bone morphogenetic proteins (BMPs) 2 and 7 and interferon (IFN)-alpha, -beta, and -gamma in a new 3-step approach: rough initial screening, followed by competition and protein A/G depletion. Naturally occurring antibodies against these proteins were detected in 2% to 4% of the tested sera. Individuals who are 65 years or older had a slightly higher occurrence of naturally occurring antibodies. Auto-antibodies against BMP-7 and IFN-alpha were mainly comprised of IgM isotypes, and natural antibodies against BMP-2, IFN-beta, and -gamma were mainly IgG. To ensure assay specificity, assays were also used to detect antibodies against BMP-7 in patients being treated with rhBMP-7 before and after surgical procedure. Fifty percent of the treated patients had persistent anti-BMP-7 antibodies over time. The 3-step approach provides an attractive tool to identify naturally occurring antibodies in naive patients