Synthesis and preclinical evaluation of novel 18F-vancomycin-based tracers for the detection of bacterial infections using positron emission tomography.

INTRODUCTION: Bacterial infections are a major problem in medicine, and the rapid and accurate detection of such infections is essential for optimal patient outcome. Bacterial infections can be diagnosed by nuclear imaging, but most currently available modalities are unable to discriminate infection from sterile inflammation. Bacteria-targeted positron emission tomography (PET) tracers have the potential to overcome this hurdle. In the present study, we compared three 18F-labelled PET tracers based on the clinically applied antibiotic vancomycin for targeted imaging of Gram-positive bacteria. METHODS: [18F]FB-NHS and [18F]BODIPY-FL-NHS were conjugated to vancomycin. The resulting conjugates, together with our previously developed [18F]PQ-VE1-vancomycin, were tested for stability, lipophilicity, selective binding to Gram-positive bacteria, antimicrobial activity and biodistribution. For the first time, the pharmacokinetic properties of all three tracers were compared in healthy animals to identify potential binding sites. RESULTS: [18F]FB-vancomycin, [18F]BODIPY-FL-vancomycin, and [18F]PQ-VE1-vancomycin were successfully synthesized with radiochemical yields of 11.7%, 2.6%, and 0.8%, respectively. [18F]FB-vancomycin exhibited poor in vitro and in vivo stability and, accordingly, no bacterial binding. In contrast, [18F]BODIPY-FL-vancomycin and [18F]PQ-VE1-vancomycin showed strong and specific binding to Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), which was outcompeted by unlabeled vancomycin only at concentrations exceeding clinically relevant vancomycin blood levels. Biodistribution showed renal clearance of [18F]PQ-VE1-vancomycin and [18F]BODIPY-FL-vancomycin with low non-specific accumulation in muscles, fat and bones. CONCLUSION: Here we present the synthesis and first evaluation of the vancomycin-based PET tracers [18F]BODIPY-FL-vancomycin and [18F]PQ-VE1-vancomycin for image-guided detection of Gram-positive bacteria. Our study paves the way towards real-time bacteria-targeted diagnosis of soft tissue and implant-associated infections that are oftentimes caused by Gram-positive bacteria, even after prophylactic treatment with vancomycin.

A recalibrated prediction model can identify level-1 trauma patients at risk of nosocomial pneumonia.

INTRODUCTION: Nosocomial pneumonia has poor prognosis in hospitalized trauma patients. Croce et al. published a model to predict post-traumatic ventilator-associated pneumonia, which achieved high discrimination and reasonable sensitivity. We aimed to externally validate Croce's model to predict nosocomial pneumonia in patients admitted to a Dutch level-1 trauma center. MATERIALS AND METHODS: This retrospective study included all trauma patients (≥ 16y) admitted for > 24 h to our level-1 trauma center in 2017. Exclusion criteria were pneumonia or antibiotic treatment upon hospital admission, treatment elsewhere > 24 h, or death < 48 h. Croce's model used eight clinical variables-on trauma severity and treatment, available in the emergency department-to predict nosocomial pneumonia risk. The model's predictive performance was assessed through discrimination and calibration before and after re-estimating the model's coefficients. In sensitivity analysis, the model was updated using Ridge regression. RESULTS: 809 Patients were included (median age 51y, 67% male, 97% blunt trauma), of whom 86 (11%) developed nosocomial pneumonia. Pneumonia patients were older, more severely injured, and underwent more emergent interventions. Croce's model showed good discrimination (AUC 0.83, 95% CI 0.79-0.87), yet predicted probabilities were too low (mean predicted risk 6.4%), and calibration was suboptimal (calibration slope 0.63). After full model recalibration, discrimination (AUC 0.84, 95% CI 0.80-0.88) and calibration improved. Adding age to the model increased the AUC to 0.87 (95% CI 0.84-0.91). Prediction parameters were similar after the models were updated using Ridge regression. CONCLUSION: The externally validated and intercept-recalibrated models show good discrimination and have the potential to predict nosocomial pneumonia. At this time, clinicians could apply these models to identify high-risk patients, increase patient monitoring, and initiate preventative measures. Recalibration of Croce's model improved the predictive performance (discrimination and calibration). The recalibrated model provides a further basis for nosocomial pneumonia prediction in level-1 trauma patients. Several models are accessible via an online tool. LEVEL OF EVIDENCE: Level III, Prognostic/Epidemiological Study.

Long-term physical functioning and quality of life after pelvic ring injuries.

BACKGROUND: Pelvic ring injuries are serious injuries, often associated with substantial morbidity and mortality rates. The long-term consequences of these injuries might affect the patients' personal life. Our aim was to assess the long-term effects of pelvic ring injuries on physical functioning and quality of life (QoL) using validated patient-reported outcome measures (PROMs) and comparing these results to normative data from the general population. PATIENTS AND METHODS: A retrospective cohort study was conducted on adults treated for pelvic ring injuries between 2007 and 2016. Demographics, fracture type, injury mechanism, treatment and complications were recorded. PROMs questionnaires concerning physical functioning (SMFA) and quality of life (EQ-5D) were used. Patients were divided according to their age (18-30, 31-64, 65 and older) and fracture type (Tile/AO type A, B or C). Differences in SMFA and EQ-5D scores of the operatively and non-operatively treated patients and between the study population and general population were analyzed. RESULTS: A total of 413 patients were identified of which 279 were eligible for follow-up. One-hundred and ninety-two (69%) patients responded with a mean follow-up of 4.4 years. Patients reported a median score of 13.9 on the SMFA function index, 16.7 on the bother index, 12.5 on the lower extremity, 18.8 on the activities of daily living and 23.4 on the emotion subscale. A median EQ-5D score of 0.8 was reported. There was no difference in physical functioning and QoL between operatively and non-operatively treated patients. Comparison of these results to normative data of the general population revealed a significant (P < 0.05) decrease in physical functioning and QoL in patients with all types of pelvic ring injuries. CONCLUSION: Long-term physical functioning and QoL in patients who had sustained a pelvic ring injury seems fair, although significantly decreased in comparison with their peers from the general population.

What can they expect? Decreased quality of life and increased postoperative complication rate in patients with a fracture-related infection.

BACKGROUND: By gaining insight into the Quality of Life (QoL) status and occurrence of complications, critical facets in the care for patients with Fracture-Related Infection (FRI) can be mitigated and measures can be taken to improve their outcome. Therefore, the aims of this study were to 1) determine the QoL in FRI patients in comparison to non-FRI patients and 2) describe the occurrence of other complications in both FRI and non-FRI patients. METHODS: An ambidirectional cohort study was conducted in a level 1 trauma centre between January 1st 2016 and November 1st 2021. All patients who underwent surgical stabilisation of an isolated long bone fracture were eligible for inclusion. To avoid confounding, only patients with an Injury Severity Score (ISS) <16 were included. Data regarding patient demographics, fracture characteristics, treatment, follow-up and complications were collected of both non-FRI and FRI patients. QoL was assessed through the use of five-level EuroQol five-dimension (EQ-5D-5L) questionnaires twelve months post-injury. RESULTS: A total of 134 patients were included in this study, of whom 38 (28%) FRI patients and 96 (72%) non-FRI patients. In comparison to non-FRI patients, FRI patients scored significantly worse on the QoL assessment regarding the index value (p = 0.012) and the domains mobility (p<0.001), usual activities (p = 0.010) and pain/discomfort (p = 0.009). Other postoperative complications were more often reported (p<0.001) in FRI patients (66%, n = 25/38) compared to non-FRI patients (27%, n = 26/96). During the median follow-up of 14.5 months (interquartile range (IQR) 9.5-26.5), 25 FRI patients developed a total of 49 distinctive complications besides FRI. The complications nonunion (18%, n = 9/49), infection other than FRI (e.g. line infection, urinary tract infection, pneumonia) (18%, n = 9/49) and implant failure (14%, n = 7/49) were the most frequently described in the FRI group. CONCLUSION: Patients who suffered from an FRI have a decreased QoL in comparison to those without an FRI. Moreover, patients with an FRI have a higher rate of additional complications. These findings can help in patient counselling regarding the potential physical and mental consequences of having a complicated course of recovery due to an infection.

Semi-automated finite element analyses of surgically treated acetabular fractures to investigate the biomechanical behaviour of patient-specific compared to conventional implants.

BACKGROUND: In acetabular fracture surgery, understanding the biomechanical behaviour of fractures and implants is beneficial for clinical decision-making about implant selection and postoperative (early) weightbearing protocols. This study outlines a novel approach for creating finite element models (FEA) from actual clinical cases. Our objectives were to (1) create a detailed semi-automatic three-dimensional FEA of a patient with a transverse posterior wall acetabular fracture and (2) biomechanically compare patient-specific implants with manually bent off-the-shelf implants. METHODS: A computational study was performed in which we developed three finite element models. The models were derived from clinical imaging data of a 20-year-old male with a transverse posterior wall acetabular fracture treated with a patient-specific implant. This implant was designed to fit the patient's anatomy and fracture configuration, allowing for optimal placement and predetermined screw trajectories. The three FEA models included an intact hemipelvis for baseline comparison, one with a fracture fixated with a patient-specific implant, and another with a conventional implant. Two loading conditions were investigated: standing up and peak walking forces. Von Mises stress and displacement patterns in bone, implants and screws were analysed to assess the biomechanical behaviour of fracture fixation with either a patient-specific versus a conventional implant. RESULTS: The finite element models demonstrated that for a transverse posterior wall type fracture, a patient-specific implant resulted in lower peak stresses in the bone (30 MPa and 56 MPa) in standing-up and peak walking scenario, respectively, compared to the conventional implant model (46 MPa and 90 MPa). The results suggested that patient-specific implant could safely withstand standing-up and walking after surgery, with maximum von Mises stresses in the implant of 156 MPa and 371 MPa, respectively. The results from the conventional implant indicate a likelihood of implant failure, with von Mises stresses in the implant (499 MPa and 1000 MPa) exceeding the yield stress of stainless steel. CONCLUSION: This study presents a workflow for conducting finite element analysis of real clinical cases in acetabular fracture surgery. This concept of personalized biomechanical fracture and implant assessment can eventually be applied in clinical settings to guide implant selection, compare conventional implants with innovative patient-specific ones, optimizing implant designs (including shape, size, materials, screw positions), and determine whether immediate full weight-bearing can be safely permitted.

Costs of fracture-related infection: the impact on direct hospital costs and healthcare utilisation.

PURPOSE: Fracture-Related Infection (FRI) is associated with high medical costs and prolonged healthcare utilization. However, limited data is available on the financial impact. The purpose of this study was to investigate the impact of FRI on direct hospital costs and healthcare utilization. METHODS: This was a retrospective cohort study in a level-1 trauma centre in the Netherlands. Patients ≥ 18 years, after open reduction and internal fixation of a long bone fracture between January 1st 2016 and November 1st 2021, were included. Exclusion criteria were Injury Severity Score (ISS) ≥ 16, indefinable data on costs or incomplete follow-up. Hospital costs related to fracture treatment were individually calculated based on procedure codes raised with a fixed percentage of overhead expenses, in line with hospital billing policies. RESULTS: In total, 246 patients were included with a median follow-up of 1 year (IQR 0.6-1.8). A total of 45 patients developed FRI, of whom 15 patients had an FRI recurrence. Compared to non-FRI patients, median hospital costs from an FRI patient without and with recurrence, were respectively three (3.1) and seven (7.6) times higher. Compared to non-FRI patients, increased costs in patients with FRI or recurrent FRI are due to respectively a fivefold or even tenfold prolonged length-of-stay, two or seven additional infection-related surgeries, and 21 or 55 days of intravenous antibiotic treatment. CONCLUSION: Direct healthcare costs of patients with single occurrence of FRI after long bone fracture treatment are three times higher compared to non-FRI patients. In case of FRI-recurrence, the differences in costs might even increase to sevenfold. To put this in perspective, cost of severely injured trauma patients were recently established at approximately 25.000 euros. Compared to non-FRI patients, increased costs in patients with FRI or recurrent FRI are due to respectively a fivefold or even tenfold prolonged length-of-stay, two or seven additional infection-related surgeries and 21 or 55 days of intravenous antibiotic treatment. Not only from patient perspective but also from a financial aspect, it is important to focus on prevention of (recurrent) FRI.

Prevalence of Rotational Malalignment After Infrapatellar Versus Suprapatellar Intramedullary Nailing of Tibial Shaft Fractures.

Background: Up to 30% of patients with a tibial shaft fracture sustain iatrogenic rotational malalignment (RM) after infrapatellar (IP) nailing. Although IP nailing remains the management of choice for most patients, suprapatellar (SP) nailing has been gaining popularity. It is currently unknown whether SP nailing can provide superior outcomes with regard to tibial RM. The aim of this study was to compare the differences in the prevalence of RM following IP versus SP nailing. Methods: This retrospective study included 253 patients with a unilateral, closed tibial shaft fracture treated with either an IP or SP approach between January 2009 and April 2023 in a Level-I trauma center. All patients underwent a postoperative, protocolized, bilateral computed tomography (CT) scan for RM assessment. Results: RM was observed in 30% and 33% of patients treated with IP and SP nailing, respectively. These results indicate no significant difference (p = 0.639) in the prevalence of RM between approaches. Furthermore, there were no significant differences in the distribution (p = 0.553) and direction of RM (p = 0.771) between the 2 approaches. With the IP and SP approaches, nailing of left-sided tibial shaft fractures resulted in predominantly internal RM (85% and 73%, respectively), while nailing of right-sided tibial shaft fractures resulted in predominantly external RM (90% and 80%, respectively). The intraobserver reliability for the CT measurements was 0.95. Conclusions: The prevalence of RM was not influenced by the entry point of tibial nailing (i.e., IP versus SP). Hence, the choice of surgical approach should rely on factors other than the risk of RM. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Outcome and risk factors for recurrence of early onset fracture-related infections treated with debridement, antibiotics and implant retention: Results of a large retrospective multicentre cohort study.

INTRODUCTION: Early Fracture-Related Infections (FRIs) are a common entity in hospitals treating trauma patients and are often treated with a Debridement, Antibiotics and Implant Retention (DAIR) procedure. Aims of this study were to 1) evaluate the recurrence rate after DAIR procedures for early onset FRI, 2) establish the number of surgical procedures to gain control of the initial infection and 3) identify independent predictors for recurrence in this cohort. METHODS: A retrospective multicentre cohort study was conducted in two level 1 trauma centres. Consecutive patients who underwent a DAIR procedure between January 1st 2015 and July 1st 2020 for confirmed FRI with an onset of <6 weeks after the latest osseous operation were included. Recorded data included patient demographics, treatment characteristics and follow-up. Univariate and multivariate logistic regression analyses were performed to assess predictors for recurrent FRI. RESULTS: A total of 141 patients with early FRI were included in this study with a median age of 54.0 years (interquartile range (IQR) 34.5-64.0). The recurrence rate of FRI was 13% (n = 19) at one year follow-up and 18% (n = 25) at 23.1 months (IQR 15.3-36.4) follow-up. Infection control was achieved in 94% (n = 127/135) of cases. In total, 73 patients (52%) underwent at least two surgical procedures to treat the ongoing initial episode of FRI, of whom 54 patients (74%) required two to three procedures and 17 patients (23%) four to five procedures. Predictors for recurrent FRI were use of an intramedullary nail during index operation (odds ratio (OR) 4.0 (95% confidence interval (CI) 1.1-13.8)), need for additional surgical procedures to treat ongoing infection during the treatment period following the first presentation of early FRI (OR 1.9 (95% CI 1.1-3.5)) and a decreased Injury Severity Score (ISS) (inverted OR 1.1 (95% CI 1.0-1.1)). CONCLUSION: The recurrence rate after treatment of early onset FRI in patients treated with a DAIR procedure was 18% at 23.1 months follow-up. At least two surgical procedures to gain control of the initial infection were needed in 52% of patients. Independent predictors for recurrent FRI were the use of an intramedullary nail during index operation, need for additional surgical procedures and a decreased ISS.

What is the long-term clinical outcome after fragility fractures of the pelvis? - A CT-based cross-sectional study.

BACKGROUND: Recently, Rommens and Hoffman introduced a CT-based classification system for fragility fractures of the pelvis (FFP). Although fracture characteristics have been described, the relationship with clinical outcome is lacking. The purpose of this study was to get insight into the type of treatment and subsequent clinical outcome after all types of FFP. METHODS: A cross-sectional cohort study was performed including all elderly patients (≥ 65 years) with a CT-diagnosed FFP, between 2007-2019 in two level 1 trauma centers. Data regarding treatment, mortality and clinical outcome was gathered from the electronic patient files. Patients were asked to complete patient-reported outcome measures (PROMs) regarding physical functioning (SMFA) and quality of life (EQ-5D). Additionally, a standardized multidisciplinary treatment algorithm was constructed. RESULTS: A total of 187 patients were diagnosed with an FFP of whom 117 patients were available for follow-up analysis and 58 patients responded. FFP type I was most common (60%), followed by type II (27%), type III (8%) and type IV (5%). Almost all injuries were treated non-operatively (98%). Mobility at six weeks ranged from 50% (type III) to 80% type II). Mortality at 1 year was respectively 16% (type I and II), 47% (type III) and 13% (type IV). Physical functioning (SMFA function index) ranged from 62 (type III and IV) to 69 (type II) and was significantly decreased (P=<0.001) compared to the age-matched general population. Quality of life was also significantly decreased, ranging from 0.26 (type III) to 0.69 (type IV). CONCLUSIONS: FFP type I and II are most common. Treatment is mainly non-operative, resulting in good mobility after six weeks, especially for patients with FFP type I and II. Mortality rates at one year were substantial in all patients. Physical functioning and quality of life was about 20-30% decreased compared to the general population.

Trauma mechanism and patient reported outcome in tibial plateau fractures with posterior involvement.

INTRODUCTION: Posterior tibial plateau fractures (PTPF) have a high impact on functional outcome and the optimal treatment strategy is not well established. The goal of this study was to assess the relationship between trauma mechanism, fracture morphology and functional outcome in a large multicenter cohort and define possible strategies to improve the outcome. METHODS: An international retrospective cohort study was conducted in five level-1 trauma centers. All consecutive operatively treated PTPF were evaluated. Preoperative imaging was reviewed to determine the trauma mechanism. Patient reported outcome was scored using the Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS: A total of 145 tibial plateau fractures with posterior involvement were selected with a median follow-up of 32.2 months (IQR 24.1-43.2). Nine patients (6%) sustained an isolated posterior fracture. Seventy-two patients (49%) sustained a two-column fracture and three-column fractures were diagnosed in 64 (44%) patients. Varus trauma was associated with poorer outcome on the 'symptoms' (p = 0.004) and 'pain' subscales (p = 0.039). Delayed-staged surgery was associated with worse outcome scores for all subscales except 'pain'. In total, 27 patients (18%) were treated with posterior plate osteosynthesis without any significant difference in outcome. CONCLUSIONS: Fracture morphology, varus trauma mechanism and delayed-staged surgery (i.e. extensive soft-tissue injury) were identified as important prognostic factors on postoperative outcome in PTPF. In order to assess possible improvement of outcome, future studies with routine preoperative MRI to assess associated ligamentous injury in tibial plateau fractures (especially for varus trauma) are needed.

Machine learning based natural language processing of radiology reports in orthopaedic trauma.

OBJECTIVES: To compare different Machine Learning (ML) Natural Language Processing (NLP) methods to classify radiology reports in orthopaedic trauma for the presence of injuries. Assessing NLP performance is a prerequisite for downstream tasks and therefore of importance from a clinical perspective (avoiding missed injuries, quality check, insight in diagnostic yield) as well as from a research perspective (identification of patient cohorts, annotation of radiographs). METHODS: Datasets of Dutch radiology reports of injured extremities (n = 2469, 33% fractures) and chest radiographs (n = 799, 20% pneumothorax) were collected in two different hospitals and labeled by radiologists and trauma surgeons for the presence or absence of injuries. NLP classification was applied and optimized by testing different preprocessing steps and different classifiers (Rule-based, ML, and Bidirectional Encoder Representations from Transformers (BERT)). Performance was assessed by F1-score, AUC, sensitivity, specificity and accuracy. RESULTS: The deep learning based BERT model outperforms all other classification methods which were assessed. The model achieved an F1-score of (95 ± 2)% and accuracy of (96 ± 1)% on a dataset of simple reports (n= 2469), and an F1 of (83 ± 7)% with accuracy (93 ± 2)% on a dataset of complex reports (n= 799). CONCLUSION: BERT NLP outperforms traditional ML and rule-base classifiers when applied to Dutch radiology reports in orthopaedic trauma.

The accuracy of gap and step-off measurements in acetabular fracture treatment.

The assessment of gaps and steps in acetabular fractures is challenging. Data from various imaging techniques to enable accurate quantification of acetabular fracture displacement are limited. The aim of this study was to assess the accuracy of pelvic radiographs, intraoperative fluoroscopy, and computed tomography (CT) in detecting gaps and step-offs in acetabular fractures. Sixty patients, surgically treated for acetabular fractures, were included. Five observers (5400 measurements) measured the gaps and step-offs on radiographs and CT scans. Intraoperative fluoroscopy images were reassessed for the presence of gaps and/or step-offs. Preoperatively, 25% of the gaps and 40% of the step-offs were undetected on radiographs compared to CT. Postoperatively, 52% of the gaps and 80% of the step-offs were missed on radiographs compared to CT. Radiograph analysis led to a significantly smaller gap and step-off compared to the CT measurements, an underestimation by a factor of two. Approximately 70% of the residual gaps and step-offs was not detected using intraoperative fluoroscopy. Gaps and step-offs that exceed the critical cut-off indicating worse prognosis often remained undetected on radiographs compared to CT scans. Less-experienced observers tend to overestimate gaps and step-offs compared to the more-experienced observers. In acetabular fracture treatment, gaps and step-offs were often undetected and underestimated on radiographs and intraoperative fluoroscopy in comparison with CT scans. This means that CT is superior to radiographs in detecting acetabular fracture displacement, which is clinically relevant for patient counselling regarding treatment decisions and prognosis.

Plate vs. nail for extra-articular distal tibia fractures: How should we personalize surgical treatment? A meta-analysis of 1332 patients.

BACKGROUND: Treatment for distal diaphyseal or metaphyseal tibia fractures is challenging and the optimal surgical strategy remains a matter of debate. The purpose of this study was to compare plate fixation with nailing in terms of operation time, non-union, time-to-union, mal-union, infection, subsequent re-interventions and functional outcomes (quality of life scores, knee- and ankle scores). METHODS: A search was performed in PubMed/Embase/CINAHL/CENTRAL for all study designs comparing plate fixation with intramedullary nailing (IMN). Data were pooled using RevMan and presented as odds ratios (OR), risk difference (RD), weighted mean difference (WMD) or weighted standardized mean difference (WSMD) with a 95% confidence interval (95%CI). All analyzes were stratified for study design. RESULTS: A total of 15 studies with 1332 patients were analyzed, including ten RCTs (n = 873) and five observational studies (n = 459). IMN leads to a shorter time-to-union (WMD: 0.4 months, 95%CI 0.1 - 0.7), shorter time-to-full-weightbearing (WMD: 0.6 months, 95%CI 0.4 - 0.8) and shorter operation duration (WMD: 15.5 min, 95%CI 9.3 - 21.7). Plating leads to a lower risk for mal-union (RD: -10%, OR: 0.4, 95%CI 0.3 - 0.6), but higher risk for infection (RD: 8%, OR: 2.4, 95%CI 1.5 - 3.8). No differences were detected with regard to non-union (RD: 1%, OR: 0.7, 95%CI 0.3 - 1.7), subsequent re-interventions (RD: 4%, OR: 1.3, 95%CI 0.8 - 1.9) and functional outcomes (WSMD: -0.4, 95%CI -0.9 - 0.1). The effect estimates of RCTs and observational studies were equal for all outcomes except for time to union and mal-union. CONCLUSION: Satisfactory results can be obtained with both plate fixation and nailing for distal extra-articular tibia fractures. However, nailing is associated with higher rates of mal-union and anterior knee pain while plate fixation results in an increased risk of infection. This study provides a guideline towards a personalized approach and facilitates shared decision-making in surgical treatment of distal extra-articular tibia fractures. The definitive treatment should be case-based and aligned to patient-specific needs in order to minimize the risk of complications.

Introduction of a three-dimensional computed tomography measurement method for acetabular fractures.

INTRODUCTION: Acetabular fractures consist of complex fracture patterns whereby bone fragments are displaced in different directions. Two-dimensional computed tomography (2DCT) gap and step-off measurements tend to underestimate the multidirectional features of these fractures. The aim was to develop a three-dimensional computed tomography (3DCT) measurement method for acetabular fractures and validate whether this method will provide an observer independent fracture characterization. MATERIALS AND METHODS: Sixty patients, operated for an acetabular fracture between 2007 and 2018, were included. The displacement was measured on the pre- and postoperative CT scans. Pre- and postoperative CT-based 3D models were made for each patient. Multiple 3D measurements, namely the 3D step-off, gap and the total gap area were introduced to quantify the preoperative and postoperative displacement. The Wilcoxon signed rank analysis was used to compare the 2DCT and 3DCT measurements. RESULTS: The preoperative displacement was significantly underestimated by 2DCT measurements in comparison with 3DCT measurements (2D vs. 3D; step-off 8 vs. 16 mm with P < 0.001; gap 19 vs. 21 mm with P = 0.001). The same applies to the postoperative residual displacement (2D vs. 3D; step-off 0 vs. 6 mm; gap 3 vs. 8 mm; P < 0.001). The total gap area, defined as the surface area between all fracture lines in the 3D model, was measured for each patient, resulting in a median value of 722 mm2 preoperatively and 168 mm2 postoperatively, with excellent inter- and intra-rater reliability. CONCLUSION: 2DCT measurements tend to underestimate the initial and residual displacement in complex acetabular fractures. A 3DCT analysis of these injuries was developed to overcome this and should be used in addition to the Judet/Letournel and AO/OTA classification systems, in order to provide an observer independent quantifiable fracture description and accurate assessment of the fracture reduction.

Quantitative 3D measurements of tibial plateau fractures.

Fracture gap and step-off measurements on 2DCT-slices probably underestimate the complex multi-directional features of tibial plateau fractures. Our aim was to develop a quantitative 3D-CT (Q3DCT) fracture analysis of these injuries. CT-based 3D models were created for 10 patients with a tibial plateau fracture. Several 3D measures (gap area, articular surface involvement, 3D displacement) were developed and tested. Gaps and step-offs were measured in 2D and 3D. All measurements were repeated by six observers and the reproducibility was determined by intra-class correlation coefficients. Q3DCT measurements demonstrated a median gap of 5.3 mm, step-off of 5.2 mm, gap area of 235 mm2, articular surface involvement of 33% and 3D displacement of 6.1 mm. The inter-rater reliability was higher in the Q3DCT than in the 2DCT measurements for both the gap (0.96 vs. 0.81) and step-off (0.63 vs. 0.32). Q3DCT measurements showed excellent reliability (ICC of 0.94 for gap area, 1 for articular surface involvement and 0.99 for 3D displacement). Q3DCT fracture analysis of tibial plateau fractures is feasible and shows excellent reliability. 3D measurements could be used together with the current classification systems to quantify the true extent of these complex multi-directional fractures in a standardized way.

Diagnostic accuracy of serum inflammatory markers in late fracture-related infection: a systematic review and meta-analysis.

AIMS: To assess the diagnostic value of C-reactive protein (CRP), leucocyte count (LC), and erythrocyte sedimentation rate (ESR) in late fracture-related infection (FRI). MATERIALS AND METHODS: PubMed, Embase, and Cochrane databases were searched focusing on the diagnostic value of CRP, LC, and ESR in late FRI. Sensitivity and specificity combinations were extracted for each marker. Average estimates were obtained using bivariate mixed effects models. RESULTS: A total of 8284 articles were identified but only six were suitable for inclusion. Sensitivity of CRP ranged from 60.0% to 100.0% and specificity from 34.3% to 85.7% in all publications considered. Five articles were pooled for meta-analysis, showing a sensitivity and specificity of 77.0% and 67.9%, respectively. For LC, this was 22.9% to 72.6%, and 73.5% to 85.7%, respectively, in five articles. Four articles were pooled for meta-analysis, resulting in a 51.7% sensitivity and 67.1% specificity. For ESR, sensitivity and specificity ranged from 37.1% to 100.0% and 59.0% to 85.0%, respectively, in five articles. Three articles were pooled in meta-analysis, showing a 45.1% sensitivity and 79.3% specificity. Four articles analyzed the value of combined inflammatory markers, reporting an increased diagnostic accuracy. These results could not be pooled due to heterogeneity. CONCLUSION: The serum inflammatory markers CRP, LC, and ESR are insufficiently accurate to diagnose late FRI, but they may be used as a suggestive sign in its diagnosis.

High diagnostic accuracy of white blood cell scintigraphy for fracture related infections: Results of a large retrospective single-center study.

INTRODUCTION: White blood cell (WBC) scintigraphy for diagnosing fracture-related infections (FRIs) has only been investigated in small patient series. Aims of this study were (1) to establish the accuracy of WBC scintigraphy for diagnosing FRIs, and (2) to investigate whether the duration of the time interval between surgery and WBC scintigraphy influences its accuracy. PATIENTS AND METHODS: 192 consecutive WBC scintigraphies with 99mTc-HMPAO-labelled autologous leucocytes performed for suspected peripheral FRI were included. The golden standard was based on the outcome of microbiological investigation in case of surgery, or - when these were not available - on clinical follow-up of at least six months. The discriminative ability of the imaging modalities was quantified by several measures of diagnostic accuracy. A multivariable logistic regression analysis was performed to identify predictive variables of a false-positive or false-negative WBC scintigraphy test result. RESULTS: WBC scintigraphy had a sensitivity of 0.79, a specificity of 0.97, a positive predicting value of 0.91, a negative predicting value of 0.93 and a diagnostic accuracy of 0.92 for detecting an FRI in the peripheral skeleton. The duration of the interval between surgery and the WBC scintigraphy did not influence its diagnostic accuracy; neither did concomitant use of antibiotics or NSAIDs. There were 11 patients with a false-negative (FN) WBC scintigraphy, the majority of these patients (n = 9, 82%) suffered from an infected nonunion. Four patients had a false-positive (FP) WBC scintigraphy. CONCLUSIONS: WBC scintigraphy showed a high diagnostic accuracy (0.92) for detecting FRIs in the peripheral skeleton. Duration of the time interval between surgery for the initial injury and the WBC did not influence the results which indicate that WBC scintigraphy is accurate shortly after surgery.

The design, production and clinical application of 3D patient-specific implants with drilling guides for acetabular surgery.

An innovative procedure for the development of 3D patient-specific implants with drilling guides for acetabular fracture surgery is presented. By using CT data and 3D surgical planning software, a virtual model of the fractured pelvis was created. During this process the fracture was virtually reduced. Based on the reduced fracture model, patient-specific titanium plates including polyamide drilling guides were designed, 3D printed and milled for intra-operative use. One of the advantages of this procedure is that the personalised plates could be tailored to both the shape of the pelvis and the type of fracture. The optimal screw directions and sizes were predetermined in the 3D model. The virtual plan was translated towards the surgical procedure by using the surgical guides and patient-specific osteosynthesis. Besides the description of the newly developed multi-disciplinary workflow, a clinical case example is presented to demonstrate that this technique is feasible and promising for the operative treatment of complex acetabular fractures.

[The anatomy lesson of Dr Nicolaes Tulp by Rembrandt (1632) and the findings during dissection of the forearm of a cadaver: anatomical discrepancies]. / De anatomische les van dr. Nicolaes Tulp door Rembrandt (1632) en de bevindingen bij de dissectie van de onderarm van een kadaver: anatomische discrepanties.

OBJECTIVE: To compare The anatomy lesson of Dr Nicolaes Tulp by Rembrandt (1632) with the findings during dissection of the forearm of a cadaver. DESIGN: Descriptive. METHOD: The left forearm of a 41-year-old white male cadaver was dissected, photographs being taken at every stage of dissection. The anatomical structures in the original painting and during dissection were described and compared. At dissection, several structures were displaced in an attempt to reproduce the anatomical structures as shown in the painting. RESULTS: Dissection revealed four anatomical differences in comparison with Rembrandt's painting: (a) the muscle belly seen at the proximal ulnar side of the forearm in the painting was not seen on dissection; section of the insertion of the M. flexor carpi radialis and transposition of this muscle to the location of the muscle belly created the possibility of lifting up the M. flexor digitorum superficialis and reproducing the muscle belly; (b) in the painting, Tulp lifted only the M. flexor digitorum superficialis, but the amount of muscle tissue found in the forceps was increased in the painting compared with the dissection; (c) the positions of the bellies of the M. flexor digitorum superficialis to the index finger and 5th digit and to the 3rd and 4th digits were found to be reversed; (d) the longitudinal white structure situated in the ulnar part of the 5th digit in the painting was not found on dissection. This may have been an anatomical variant of the ulnar nerve. CONCLUSION: The anatomical characteristics of the painting could not be reproduced by dissection of the forearm of a cadaver.

Bidloo's and De Lairesse's early illustrations of the anatomy of the arm (1690): a successful collaboration between a prominent physician and a talented artist.

Govard Bidloo (1649-1713) was trained as a surgeon at the Amsterdam Guild of Surgeons, and later in his career, he became a professor of anatomy in The Hague and Leiden. At the end of the 17th century, he performed dissections on the corpses of executed criminals to teach and study anatomy. Based on his findings, he published a magnificent anatomical atlas in 1690, entitled Ontleding des Menschelijken Lichaams (Dissection of the Human Body). The talented painter Gerard De Lairesse, a pupil of Rembrandt, made the drawings of the anatomical dissections for the atlas in close collaboration with the dissector. The drawings of Bidloo and De Lairesse represent, in a unique and artistic way, an early series of anatomical preparations of the arm and hand from more than 300 years ago.