The Treatment of Very Large Traumatic Bone Defects of the Tibia With a Polycaprolactone-Tricalcium Phosphate 3D-Printed Cage: A Review of Three Cases.

The need for an artificial scaffold in very large bone defects is clear, not only to limit the risk of graft harvesting but also to improve clinical success. The use of custom osteoconductive scaffolds made from biodegradable polyester and ceramics can be a valuable patient-friendly option, especially in case of a concomitant infection. Multiple types of scaffolds for the Masquelet procedure (MP) are available. However, these frequently demonstrate central graft involution when defects exceed a certain size and the complication rates remain high. This paper describes three infected tibial defect nonunions with a segmental defect over 10 centimeters long treated with a three-dimensional (3D)-printed polycaprolactone-tricalcium phosphate (PCL-TCP) cage in combination with biological adjuncts. Three male patients, between the ages of 37 and 47, were treated for an infected tibial defect nonunion after sustaining Gustilo grade 3 open fractures. All had a segmental midshaft bone defect of more than 10 centimeters (range 11-15cm). First-stage MPs consisted of extensive debridement, external fixation, and placement of anterior lateral thigh flaps. Positive cultures were obtained from all patients during this first stage, which were treated with specific systemic antibiotics for 12 weeks. The second-stage MP was carried out at least two months after the first stage. CT scans were obtained after the first stage to manufacture defect-specific cages. In the final procedure, a custom 3D-printed PCL-TCP cage (Osteopore, Singapore) was placed in the defect in combination with biological adjuncts (BMAC, RIA-derived autograft, iFactor, and BioActive Glass). Bridging of the defect, assessed at six months by CT, was achieved in all cases. SPECT scans six months post-operatively demonstrated active bone regeneration, also involving the central part of the scaffold. All three patients regained function and reported less pain with full weight bearing. This case report shows that 3D-printed PCL-TCP cages in combination with biological adjuncts are a novel addition to the surgical treatment of very large bone defects in (infected) post-traumatic nonunion of the tibia. This combination could overcome some of the current drawbacks in this challenging indication.

Patient reported and functional outcome measures after surgical salvage procedures for posttraumatic radiocarpal osteoarthritis - a systematic review.

BACKGROUND: Posttraumatic wrist osteoarthritis is an irreversible and often progressive condition. Many surgical treatments, used in (daily) practice, aim to relieve symptoms like pain and restore function. The aim of this systematic review is to assess the patient reported and functional outcomes of the most common surgical interventions in patients with posttraumatic wrist osteoarthritis. This overview can help clinicians select the best treatment and manage patient's expectations. METHODS: A literature search was performed in Pubmed, Embase and Cochrane for articles published between 1990 and November 2022 according to the PRISMA guidelines. The study protocol has been registered in the PROSPERO database (CRD42017080427). Studies that describe patient reported outcomes (pain and Disability of Arm, Shoulder and Hand (DASH) -score) and functional outcomes (range of motion (ROM) and grip strength) after surgical intervention with a minimal follow-up of 1 year were included. The identified surgical procedures included denervation, proximal row carpectomy, interpositional- and total arthroplasty, and midcarpal-, radiocarpal- and total arthrodesis. The pre-and postoperative outcomes were pooled and presented per salvage procedure. RESULTS: Data from 50 studies was included. Pain score improved after all surgeries except denervation. Flexion/extension decreased after radiocarpal arthrodesis, did not show significant changes after proximal row carpectomy, and improved for all other surgeries. DASH score improved after arthroplasty, proximal row carpectomy and midcarpal arthrodesis. Grip strength improved after interposition arthroplasty and partial arthrodesis. CONCLUSION: Evidence from this review did not support the indication for denervation in this particular patient population. In patients with SLAC/SNAC II, proximal row carpectomy might be favourable to a midcarpal arthrodesis solely based on better FE ROM of the radiocarpal joint after proximal row carpectomy. In terms of radiocarpal mobility, total wrist arthroplasty might be preferred to radiocarpal arthrodesis in patients with osteoarthritis after a distal radius fracture. More uniform measurements of outcomes would improve the understanding of the effect of surgical treatments of the posttraumatic osteoarthritic wrist.

Enhancing the Evaluation of Physical Function Following Orthopaedic Trauma Care: Comparison of PROMIS Computerized Adaptive Testing and Short Musculoskeletal Function Assessment.

OBJECTIVES: To compare measurement properties of Patient-Reported Outcomes Measurement Information System (PROMIS) (physical function [PF] and pain interference [PI]) computerized adaptive testing to traditional Short Musculoskeletal Function Assessment (SMFA) (dysfunction index [DI] and bother index [BI]). To explore factors associated with PROMIS scores. DESIGN: Cross-sectional study. SETTING: Level I Trauma Center. PATIENT SELECTION CRITERIA: Isolated upper/lower extremity fracture patients were recruited from the orthopaedic trauma outpatient clinic (October 1, 2021 to January 1, 2023). OUTCOME MEASURES: Correlations (Pearson), reliability (standard error [SE] [T score]), efficiency (amount of information per item [1 - SE2/Nitems]), and floor/ceiling effects were assessed. An r > 0.7 represented high correlation, and SE ≤ 2.2 represented sufficient reliability. Factors associated with worse PROMIS scores were also identified. RESULTS: In total, 202 patients completed PROMs at median 98 days follow-up. Correlations between PROMIS-PF and SMFA-DI, and PROMIS-PI and SMFA-BI were -0.84 and 0.65. Reliability was very high for both instruments (mean SE 2.0 [PROMIS-PF], SE 2.1 [PROMIS-PI], and SE 1.2 [SMFA-DI], SE 1.8 [SMFA-BI]). Relative efficiency for PROMIS-PF versus SMFA-DI, and PROMIS-PI versus SMFA-BI was 7.8 (SD 2.5) and 4.1 (SD 1.7), respectively. Neither PROMIS nor SMFA exhibited floor/ceiling effects. In the multivariable regression analyses, elevated levels of depression, among other factors, showed an (independent) association with worse PROMIS-PF and PROMIS-PI scores. CONCLUSIONS: PROMIS-PF and PROMIS-PI CATs showed a (high and moderate) correlation with SMFA and hence measure a comparable construct of physical function and discomfort. As computerized adaptive tests are much more efficient to administer, they present a compelling alternative to SMFA for evaluating impact of fracture treatment. The relation between symptoms of depression and PROMIS scores emphasizes the importance of psychosocial aspects of health in orthopaedic trauma patients. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

'Role Model Moments' and 'Troll Model Moments' in Surgical Residency: How Do They Influence Professional Identity Formation?

Introduction: Role models are powerful contributors to residents' professional identity formation (PIF) by exhibiting the values and attributes of the community. While substantial knowledge on different attributes of role models exists, little is known about their influence on residents' PIF. The aim of this study was to explore surgical residents' experiences with role models and to understand how these contribute to residents' PIF. Methods: Adopting a social constructivist paradigm, the authors used a grounded theory approach to develop an explanatory model for residents' experiences with role models regarding PIF. Fourteen surgical residents participated in individual interviews. The authors iteratively performed data collection and analysis, and applied constant comparison to identify relevant themes. Results: Role model behavior is highly situation dependent. Therefore, residents learn through specific 'role model moments'. These moments arise when residents (1) feel positive about a moment, e.g. "inspiration", (2) have a sense of involvement, and (3) identify with their role model. Negative role model moments ('troll model moments') are dominated by negative emotions and residents reject the modeled behavior. Residents learn through observation, reflection and adapting modeled behavior. As a result, residents negotiate their values, strengthen attributes, and learn to make choices on the individual path of becoming a surgeon. Discussion: The authors suggest a nuance in the discussion on role modelling: from 'learning from role models' to 'learning from role model moments'. It is expected that residents' PIF will benefit from this approach since contextual factors and individual needs are emphasized. Residents need to develop antennae for both role model moments and troll model moments and acquire the skills to learn from them. Role model moments and troll model moments are strong catalysts of PIF as residents follow in the footsteps of their role models, yet learn to go their own way.

Fracture haematoma proteomics.

Aims: The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. Methods: A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Results: The early fxH proteome was characterized by immunomodulatory and osteogenic proteins, and proteins involved in the coagulation cascade. Treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodelling. Conversely, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodelling, and proteins related to anti-inflammatory and osteogenic processes. Conclusion: The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regeneration, and gained insights into regulatory mechanisms of fracture healing after severe trauma.

Polytherapy versus monotherapy in the treatment of tibial non-unions: a retrospective study.

BACKGROUND: Treating tibial non-unions efficiently presents a challenge for orthopaedic trauma surgeons. The established gold standard involves implanting autologous bone graft with adequate fixation, but the addition of biologicals according to the so-called diamond concept has become increasingly popular in the treatment of non-unions. Previous studies have indicated that polytherapy, which involves implanting mesenchymal stem cells, bioactive factors and osteoconductive scaffolds, can improve bone healing. This study aims to evaluate the efficacy of polytherapy compared with monotherapy in treating tibial non-unions of varying severity. MATERIALS AND METHODS: Data from consecutive tibial non-unions treated between November 2014 and July 2023 were retrospectively analysed. The Non Union Scoring System (NUSS) score before non-union surgery, and the Radiographic Union Score for Tibial fractures (RUST), scored at 1, 3, 6, 9, 12 and 18 months post-surgery, were recorded. Initially, a comparison was made between the polytherapy and monotherapy groups. Subsequently, patients receiving additional surgical non-union treatment were documented, and the frequency of these treatments was tallied for a subsequent per-treatment analysis. RESULTS: A total of 34 patients were included and divided into a polytherapy group (n = 15) and a monotherapy group (n = 19). The polytherapy group demonstrated a higher NUSS score (44 (39, 52) versus 32 (29, 43), P = 0.019, z = -2.347) and a tendency towards a higher success rate (93% versus 68%, P = 0.104) compared with the monotherapy group. For the per-treatment analysis, 44 treatments were divided into the polytherapy per-treatment group (n = 20) and the monotherapy per-treatment group (n = 24). The polytherapy per-treatment group exhibited a higher NUSS score (48 (43, 60) versus 38 (30, 50), P = 0.030, z = -2.173) and a higher success rate (95% versus 58%, P = 0.006) than the monotherapy per-treatment group. Within the monotherapy per-treatment group, the NUSS score displayed excellent predictive performance (AUC = 0.9143). Setting the threshold value at 48, the sensitivity and specificity were 100.0% and 70.0%, respectively. CONCLUSIONS: Polytherapy is more effective than monotherapy for severe tibial non-unions, offering a higher success ratio. The NUSS score supports decision-making in treating tibial non-unions. LEVEL OF EVIDENCE: Level III.

Mass Spectrometry Reveals Molecular Effects of Citrulline Supplementation during Bone Fracture Healing in a Rat Model.

Bone fracture healing is a complex process in which specific molecular knowledge is still lacking. The citrulline-arginine-nitric oxide metabolism is one of the involved pathways, and its enrichment via citrulline supplementation can enhance fracture healing. This study investigated the molecular effects of citrulline supplementation during the different fracture healing phases in a rat model. Microcomputed tomography (µCT) was applied for the analysis of the fracture callus formation. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and liquid-chromatography tandem mass spectrometry (LC-MS/MS) were used for lipid and protein analyses, respectively. µCT analysis showed no significant differences in the fracture callus volume and volume fraction between the citrulline supplementation and control group. The observed lipid profiles for the citrulline supplementation and control group were distinct for the different fracture healing stages. The main contributing lipid classes were phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs). The changing effect of citrulline supplementation throughout fracture healing was indicated by changes in the differentially expressed proteins between the groups. Pathway analysis showed an enhancement of fracture healing in the citrulline supplementation group in comparison to the control group via improved angiogenesis and earlier formation of the soft and hard callus. This study showed the molecular effects on lipids, proteins, and pathways associated with citrulline supplementation during bone fracture healing, even though no effect was visible with µCT.

Is there a role for N1-N2 neutrophil phenotypes in bone regeneration? A systematic review.

PURPOSE: This review aims to provide an overview of the multiple functions of neutrophils, with the recognition of the inflammatory (N1) and regenerative (N2) phenotypes, in relation to fracture healing. METHODS: A literature search was performed using the PubMed database. The quality of the articles was evaluated using critical appraisal checklists. RESULTS: Thirty one studies were included in this review. These studies consistently support that neutrophils exert both beneficial and detrimental effects on bone regeneration, influenced by Tumor Necrosis Factor-α (TNF-α), Interleukin 8 (IL-8), mast cells, and macrophages. The N2 phenotype has recently emerged as one promoter of bone healing. The N1 phenotype has progressively been connected with inflammatory neutrophils during fracture healing. CONCLUSIONS: This review has pinpointed various aspects and mechanisms of neutrophil influence on bone healing. The recognition of N1 and N2 neutrophil phenotypes potentially shed new light on the dynamic shifts taking place within the Fracture Hematoma (FH).

Surgical suction filter-derived bone graft displays osteogenic miRNA and mRNA patterns.

PURPOSE: Recently, a surgical suction filter device was introduced which aims at generating a suction filter-derived bone grafting substitute (SF-BGS). The osteogenic capacity of this grafting material, however, is unclear. MicroRNAs (miRNAs) and osteogenic mRNAs may influence these processes. The aim of this study was therefore to investigate the quality of the SF-BGS by determining the expression of miRNAs and osteogenic mRNAs. METHODS: Samples were collected during non-union surgery. Upon exposure of the intramedullary canal, the surgical vacuum system was fitted with the suction filter device containing collagen complex and synthetic ß-TCP: (Ca3(PO4)2, granule size 5-8 mm, total volume 10 mL (Cerasorb Foam®, Curasan AG, Kleinostheim, Germany). As a control, venous blood was used as in current clinical practice. Samples were snap-frozen and mechanically disrupted. MiRNAs and mRNAs were isolated, transcribed, and pooled for qPCR analysis. Lastly, mRNA targets were determined through in silico target analyses. RESULTS: The study population consisted of seven patients with a posttraumatic long bone non-union (4♀; mean age 54 ± 16 years). From the array data, distinct differences in miRNA expression were found between the SF-BGS and control samples. Osteogenic marker genes were overall upregulated in the SF-BGS. Qiagen IPA software identified 1168 mRNA targets for 43 of the overall deregulated miRNAs. CONCLUSION: This study revealed distinctly deregulated and exclusively expressed osteogenic miRNAs in SF-BGS, as well as overall enhanced osteogenic marker gene expression, as compared to the venous blood control group. These expression profiles were not seen in control samples, indicating that the derived material displays an osteogenic profile. It may therefore be a promising tool to generate a BGS or graft extender when needed.

Are the non-weight bearing guidelines for the after treatment of calcaneal fractures still decisive? A Dutch survey among orthopaedic and trauma surgeons.

PURPOSE: The current rehabilitation for patients with surgically treated displaced intra-articular calcaneal fractures (DIACFs) consists of non-weightbearing for 8-12 weeks. The purpose of the present survey was to investigate the current pre-, peri- and post-operative practices among Dutch foot and ankle surgeons. Moreover, it aims to analyze whether surgeons comply to the Arbeitsgemeinschaft für Osteosynthesefragen (AO) guidelines and which decision criteria were used in the determination of the start of weightbearing. METHODS: A survey was distributed among Dutch trauma and orthopaedic surgeons to determine the most common practices in postoperative weightbearing in patients with DIACFs. RESULTS: 75 surgeons responded to the survey. 33% of the respondents adhered to the AO guidelines. 4% of the respondents strictly followed non-weightbearing guidelines, while 96% interpret the AO guidelines or their local protocol freely, in any frequency. When respondents tended to deviate from the AO guidelines or local protocol, a good patients' compliance to therapy was expected. 83% of the respondents started weightbearing on the fracture, based on reported patient complaints. 87% of the respondents did not see any relation between early weightbearing and the occurrence of complications, including loosening of osteosynthesis materials. CONCLUSION: This study demonstrates that there is limited consensus on the rehabilitation for DIACFs. Moreover, it shows that most surgeons are inclined to interpret the current (AO) guideline or their own local protocol freely. New guidelines, supported with well-founded literature, could help surgeons in a more appropriate daily practice in weightbearing for the rehabilitation of calcaneal fractures.

Effectiveness of permissive weight bearing in surgically treated trauma patients with peri- and intra-articular fractures of the lower extremities: a prospective comparative multicenter cohort study.

PURPOSE: The aim of the present study was to investigate the effectiveness of a novel approach involving permissive weight bearing (PWB) in surgically treated trauma patients with peri- and intra-articular fractures of the lower extremities. METHODS: Prospective comparative multicenter cohort study in one level 1 trauma center and five level 2 trauma centers. Surgically treated trauma patients with peri- and intra-articular fractures of the lower extremities were included. Permissive weight bearing (PWB) in comparison to restricted weight bearing (RWB) was assessed over a 26-week post-surgery follow-up period. Patients' self-perceived outcome levels regarding activities of daily living (ADL), quality of life (QoL), pain and weight bearing compliance were used. RESULTS: This study included 106 trauma patients (N = 53 in both the PWB and RWB groups). Significantly better ADL and QoL were found in the PWB group compared to the RWB group at 2-, 6-, 12- and 26-weeks post-surgery. There were no significant differences in postoperative complication rates between the PWB and RWB groups. CONCLUSION: PWB is effective and is associated with a significantly reduced time to full weight bearing, and a significantly better outcome regarding ADL and QoL compared to patients who followed RWB regimen. Moreover, no significant differences in complication rates were found between the PWB and RWB groups. LEVEL OF EVIDENCE: Level II. REGISTRATION: This study is registered in the Dutch Trial Register (NTR6077). Date of registration: 01-09-2016.

Cost-effectiveness analysis of the Geriatric Fracture Center (GFC) concept: a prospective multicentre cohort study.

INTRODUCTION: Geriatric Fracture Centers (GFCs) are dedicated treatment units where care is tailored towards elderly patients who have suffered fragility fractures. The primary objective of this economic analysis was to determine the cost-utility of GFCs compared with usual care centres. METHODS: The primary analysis was a cost-utility analysis that measured the cost per incremental quality-adjusted life-year gained from treatment of hip fracture in GFCs compared with treatment in usual care centres from the societal perspective over a 1-year time horizon. The secondary analysis was a cost-utility analysis from a societal perspective over a lifetime time horizon. We evaluated these outcomes using a cost-utility analysis using data from a large multicentre prospective cohort study comparing GFCs versus usual care centres that took place in Austria, Spain, the USA, the Netherlands, Thailand and Singapore. RESULTS: GFCs may be cost-effective in the long term, while providing a more comprehensive care plan. Patients in usual care centre group were slightly older and had fewer comorbidities. For the 1-year analysis, the costs per patient were slightly lower in the GFC group (-$646.42), while the quality-adjusted life-years were higher in the usual care centre group (+0.034). The incremental cost-effectiveness ratio was $18 863.34 (US$/quality-adjusted life-year). The lifetime horizon analysis found that the costs per patient were lower in the GFC group (-$7210.35), while the quality-adjusted life-years were higher in the usual care centre group (+0.02). The incremental cost-effectiveness ratio was $320 678.77 (US$/quality-adjusted life-year). CONCLUSIONS: This analysis found that GFCs were associated with lower costs compared with usual care centres. The cost-savings were greater when the lifetime time horizon was considered. This comprehensive cost-effectiveness analysis, using data from an international prospective cohort study, found that GFC may be cost-effective in the long term, while providing a more comprehensive care plan. A greater number of major adverse events were reported at GFC, nevertheless a lower mortality rate associated with these adverse events at GFC. Due to the minor utility benefits, which may be a result of greater adverse event detection within the GFC group and much greater costs of usual care centres, the GFC may be cost-effective due to the large cost-savings it demonstrated over the lifetime time horizon, while potentially identifying and treating adverse events more effectively. These findings suggest that the GFC may be a cost-effective option over the lifetime of a geriatric patient with hip fracture, although future research is needed to further validate these findings. LEVEL OF EVIDENCE: Economic, level 2. TRIAL REGISTRATION NUMBER: NCT02297581.

Trabecular, but not cortical, bone tissue protein synthesis rates are lower in the femoral head when compared to the proximal femur following an intracapsular hip fracture.

BACKGROUND: All musculoskeletal tissues are in a constant state of turnover, with a dynamic equilibrium between tissue protein synthesis and breakdown rates. The synthesis of protein allows musculoskeletal tissues to heal following injury. Yet, impaired tissue healing is observed following certain injuries, such as geriatric hip fractures. It is assumed that the regenerative properties of femoral head bone tissue are compromised following an intracapsular hip fracture and therefore hip replacement surgery is normally performed. However, the actual impact on in vivo bone protein synthesis rates has never been determined. DESIGN: In the present study, 10 patients (age: 79 ± 10 y, BMI: 24 ± 4 kg/m2) with an acute (<24 h) intracapsular hip fracture received a primed continuous intravenous infusion of L-[ring-13C6]-phenylalanine before and throughout their hip replacement surgery. Trabecular and cortical bone tissue from both the femoral head and proximal femur were sampled during surgery to assess protein synthesis rates of affected (femoral head) and unaffected (proximal femur) bone tissue, respectively. In addition, tissue samples of gluteus maximus muscle, synovium, ligamentum teres, and femoral head cartilage were collected. Tissue-specific protein synthesis rates were assessed by measuring L-[ring-13C6]-phenylalanine incorporation in tissue protein. RESULTS: Femoral head trabecular bone protein synthesis rates (0.056 [0.024-0.086] %/h) were lower when compared to proximal femur trabecular bone protein synthesis rates (0.081 [0.056-0.118] %/h; P = 0.043). Cortical bone protein synthesis rates did not differ between the femoral head and proximal femur (0.041 [0.021-0.078] and 0.045 [0.028-0.073] %/h, respectively; P > 0.05). Skeletal muscle, synovium, ligamentum teres, and femoral head cartilage protein synthesis rates averaged 0.080 [0.048-0.089], 0.093 [0.051-0.130], 0.121 [0.110-0.167], and 0.023 [0.015-0.039] %/h, respectively. CONCLUSION: In contrast to the general assumption that the femoral head is avital after an intracapsular displaced hip fracture in the elderly, our data show that bone protein synthesis is still ongoing in femoral head bone tissue during the early stages following an intracapsular hip fracture in older patients. Nonetheless, trabecular bone protein synthesis rates are lower in the femoral head when compared to the proximal femur in older patients following an acute intracapsular hip fracture. Trial register no: NL9036.

Serum metabolomics analysis for quantification of muscle loss in critically ill patients: An explorative study.

BACKGROUND: During Intensive Care Unit (ICU) admission, patients demonstrate up to 15% muscle loss per week, contributing to neuromuscular weakness, complicating recovery and delaying return to daily life. Biomarkers for muscle loss could aid in early detection of patients at risk and help guide resources to mitigate muscle loss, e.g. physical therapy and protein supplementation. AIMS: To explore serum biomarkers for muscle mass and muscle loss in ICU patients using a metabolomics approach. METHODS: Mechanically ventilated patients with an unplanned ICU admission between June and December 2021 were prospectively studied. The cross-sectional area of the rectus femoris muscle was assessed using ultrasound (RFcsa) and 188 serum metabolites were assessed using the Biocrates™ AbsoluteIDQ p180 kit for targeted metabolomics. Patients were eligible for analysis when a serum sample drawn within 5 days of ICU admission and at least 1 RFcsa were available. In patients with sequential RFcsa measurements, muscle loss was defined as the negative slope of the regression line fitted to the RFcsa measurements per patient in the first 10 days of ICU admission. Correlations between baseline metabolite concentrations and baseline muscle mass, as well as between baseline metabolite concentrations and muscle loss were assessed using Pearson's test for correlations. To correct for multiple testing, the Benjamini-Hochberg procedure was used. RESULTS: Seventeen patients were eligible for analysis. Mean age was 62 (SD ± 9) years and the cohort was predominantly male (76%). Four metabolites correlated with baseline muscle mass: creatinine (R = 0.5, p = 0.041), glycerophospholipid PC_ae_C30_0 (R = 0.5, p = 0.034) and two acylcarnitines: C14_2 (R = 0.5, p = 0.042) and C10_2 (R = 0.5, p = 0.049). For muscle loss, significant associations were found for histidine (R = -0.8, p = 0.002) and three glycerophospholipids; PC_aa_C40_2 (R = 0.7, p = 0.015), PC_ae_C40_1 (R = 0.6, p = 0.032) and PC_aa_C42_1 (R = 0.6, p = 0.037). After correction for multiple testing, no significant associations remained. CONCLUSIONS: This exploratory analysis found certain metabolites to be associated with muscle mass and muscle loss. Future research, specifically addressing these metabolites is necessary to confirm or refute an association with muscle loss and determine their role as potential muscle loss marker.

The contribution of lower-mineralized tissue to the healing of distal radius fractures assessed using HR-pQCT.

High-resolution peripheral quantitative CT (HR-pQCT) enables quantitative assessment of distal radius fracture healing. In previous studies, lower-mineralized tissue formation was observed on HR-pQCT scans, starting early during healing, but the contribution of this tissue to the stiffness of distal radius fractures is unknown. Therefore, the aim of this study was to investigate the contribution of lower-mineralized tissue to the stiffness of fractured distal radii during the first twelve weeks of healing. We did so by combining the results from two series of micro-finite element (µFE-) models obtained using different density thresholds for bone segmentation. Forty-five postmenopausal women with a conservatively-treated distal radius fracture had HR-pQCT scans of their fractured radius at baseline (BL; 1-2 weeks post-fracture), 3-4 weeks, 6-8 weeks, and 12 weeks post-fracture. Compression stiffness (S) was computed using two series of µFE-models from the scans: one series (Msingle) included only higher-mineralized tissue (>320 mg HA/cm3), and one series (Mdual) differentiated between lower-mineralized tissue (200-320 mg HA/cm3) and higher-mineralized tissue. µFE-elements were assigned a Young's Modulus of 10 GPa (higher-mineralized tissue) or 5 GPa (lower-mineralized tissue), and an axial compression test to 1 % strain was simulated. The contribution of the lower-mineralized tissue to S was quantified as the ratio Sdual/Ssingle. Changes during healing were quantified using linear mixed effects models and expressed as estimated marginal means (EMMs) with 95 %-confidence intervals (95 %-CI). Median time to cast removal was 5.0 (IQR: 1.1) weeks. Sdual and Ssingle gradually increased during healing to a significantly higher value than BL at 12 weeks post-fracture (both p < 0.0001). In contrast, Sdual/Ssingle was significantly higher than BL at 3-4 weeks post-fracture (p = 0.0010), remained significantly higher at 6-8 weeks post-fracture (p < 0.0001), and then decreased to BL-values at the 12-week visit. EMMs ranged between 1.05 (95 %-CI: 1.04-1.06) and 1.08 (95 %-CI: 1.07-1.10). To conclude, combining stiffness results from two series of µFE-models obtained using single- and dual-threshold segmentation enables quantification of the contribution of lower-mineralized tissue to the stiffness of distal radius fractures during healing. This contribution is minor but changes significantly around the time of cast removal. Its course and timing during healing may be clinically relevant. Quantification of the contribution of lower-mineralized tissue to stiffness gives a more complete impression of strength recovery post-fracture than the evaluation of stiffness using a single series of µFE-models.

Alignment of CCI total ankle replacements in relation to midterm functional outcome and complication incidence.

BACKGROUND: Total ankle arthroplasty is increasingly used as a treatment for end stage ankle arthropathy. The aim of this study was to report the mid-term clinical function and survival results of Ceramic Coated Implant (CCI) ankle replacements and assess the association between the alignment of the CCI total ankle replacements and early functional outcome and complication incidence. METHODS: Data of 61 patients, who received 65 CCI implants between 2010 and 2016, were obtained from a prospectively documented database. Mean follow-up time was 85.2 months (range 27-99 months). Clinical function was assessed with AOFAS questionnaire and passive range of motion (ROM). Survival analysis and elaborate radiographic analysis was performed. Furthermore, complications and reoperations were recorded for all patients. RESULTS: Progression in ROM was most seen in the first 10 months from 21.8 degrees of passive range of motion preoperative to 27.6 degrees postoperative (p < 0.001), while the mean AOFAS gradually increased during follow-up postoperative from a mean of 40.9 points preoperative to an average of 82.5 but shows a small decline towards the end of follow-up (p < 0.001). During follow-up we recorded 8 failures (12.3%) resulting in a Kaplan-Meier survival analysis of 87.7% with a median follow-up of 85.2 months. CONCLUSION: We observed excellent clinical results and survival after TAA with the CCI implant with only a low mid-term complication rate. LEVEL OF EVIDENCE: Level III, prospective cohort study.

The effect of perturbation-based balance training on balance control and fear of falling in older adults: a single-blind randomised controlled trial.

BACKGROUND: Perturbation-based balance training (PBT) is an emerging intervention shown to improve balance recovery responses and reduce falls in everyday life in older adults. However, perturbation interventions were heterogeneous in nature and need improvement. This study aims to investigate the effects of a PBT protocol that was designed to address previously identified challenges of PBT, in addition to usual care, on balance control and fear of falling in older adults at increased risk of falling. METHODS: Community-dwelling older adults (age ≥ 65 years) who visited the hospital outpatient clinic due to a fall incident were included. Participants received PBT in addition to usual care (referral to a physiotherapist) versus usual care alone. PBT consisted of three 30-minute sessions in three weeks. Unilateral treadmill belt accelerations and decelerations and platform perturbations (shifts and tilts) were applied during standing and walking on the Computer Assisted Rehabilitation Environment (CAREN, Motek Medical BV). This dual-belt treadmill embedded in a motion platform with 6 degrees of freedom is surrounded by a 180° screen on which virtual reality environments are projected. Duration and contents of the training were standardised, while training progression was individualised. Fear of falling (FES-I) and balance control (Mini-BESTest) were assessed at baseline and one week post-intervention. Primary analysis compared changes in outcome measures between groups using Mann-Whitney U tests. RESULTS: Eighty-two participants were included (PBT group n = 39), with a median age of 73 years (IQR 8 years). Median Mini-BESTest scores did not clinically relevantly improve and were not significantly different between groups post-intervention (p = 0.87). FES-I scores did not change in either group. CONCLUSIONS: Participation in a PBT program including multiple perturbation types and directions did not lead to different effects than usual care on clinical measures of balance control or fear of falling in community-dwelling older adults with a recent history of falls. More research is needed to explore how to modulate PBT training dose, and which clinical outcomes are most suitable to measure training effects on balance control. TRIAL REGISTRATION: Nederlands Trial Register NL7680. Registered 17-04-2019 - retrospectively registered. https://www.trialregister.nl/trial/7680 .

The influence of inter-hospital transfers on mortality in severely injured patients.

PURPOSE: The importance of treating severely injured patients in higher-level trauma centers is undisputable. However, it is uncertain whether severely injured patients that were initially transported to a lower-level trauma center (i.e., undertriage) benefit from being transferred to a higher-level trauma center. METHODS: This observational study included all severely injured patients (i.e., Injury Severity Score ≥ 16) that were initially transported to a lower-level trauma center within eight ambulance regions. The exposure of interest was whether a patient was transferred to a higher-level trauma center. Primary outcomes were 24-h and 30-day mortality. Generalized linear models including inverse probability weights for several potential confounders were constructed to evaluate the association between transfer status and mortality. RESULTS: We included 165,404 trauma patients that were transported with high priority to a trauma center, of which 3932 patients were severely injured. 1065 (27.1%) patients were transported to a lower-level trauma center of which 322 (30.2%) were transferred to a higher-level trauma center. Transferring undertriaged patients to a higher-level trauma center was significantly associated with reduced 24-h (relative risk [RR] 0.26, 95%-CI 0.10-0.68) and 30-day mortality (RR 0.65, 0.46-0.92). Similar results were observed in patients with critical injuries (24-h: RR 0.35, 0.16-0.77; 30-day: RR 0.55, 0.37-0.80) and patients with traumatic brain injury (24-h: RR 0.31, 0.11-0.83; 30-day: RR 0.66, 0.46-0.96). CONCLUSIONS: A minority of the undertriaged patients are transferred to a higher-level trauma center. An inter-hospital transfer appears to be safe and may improve the survival of severely injured patients initially transported to a lower-level trauma center.

What Is the Diagnostic Performance of Conventional Radiographs and Clinical Reassessment Compared With HR-pQCT Scaphoid Fracture Diagnosis?

BACKGROUND: Conventional radiographs and clinical reassessment are considered guides in managing clinically suspected scaphoid fractures. This is a unique study as it assessed the value of conventional radiographs and clinical reassessment in a cohort of patients, all of whom underwent additional imaging, regardless of the outcome of conventional radiographs and clinical reassessment. QUESTIONS/PURPOSES: (1) What is the diagnostic performance of conventional radiographs in patients with a clinically suspected scaphoid fracture compared with high-resolution peripheral quantitative CT (HR-pQCT)? (2) What is the diagnostic performance of clinical reassessment in patients with a clinically suspected scaphoid fracture compared with HR-pQCT? (3) What is the diagnostic performance of conventional radiographs and clinical reassessment combined compared with HR-pQCT? METHODS: Between December 2017 and October 2018, 162 patients with a clinically suspected scaphoid fracture presented to the emergency department (ED). Forty-six patients were excluded and another 25 were not willing or able to participate, which resulted in 91 included patients. All patients underwent conventional radiography in the ED and clinical reassessment 7 to 14 days later, together with CT and HR-pQCT. The diagnostic performance characteristics and accuracy of conventional radiographs and clinical reassessment were compared with those of HR-pQCT for the diagnosis of fractures since this was proven to be superior to CT scaphoid fracture detection. The cohort included 45 men and 46 women with a median (IQR) age of 52 years (29 to 67). Twenty-four patients with a median age of 44 years (35 to 65) were diagnosed with a scaphoid fracture on HR-pQCT. RESULTS: When compared with HR-pQCT, conventional radiographs alone had a sensitivity of 67% (95% CI 45% to 84%), specificity of 85% (95% CI 74% to 93%), positive predictive value (PPV) of 62% (95% CI 46% to 75%), negative predictive value (NPV) of 88% (95% CI 80% to 93%), and a positive and negative likelihood ratio (LR) of 4.5 (95% CI 2.4 to 8.5) and 0.4 (95% CI 0.2 to 0.7), respectively. Compared with HR-pQCT, clinical reassessment alone resulted in a sensitivity of 58% (95% CI 37% to 78%), specificity of 42% (95% CI 30% to 54%), PPV of 26% (95% CI 19% to 35%), NPV of 74% (95% CI 62% to 83%), as well as a positive and negative LR of 1.0 (95% CI 0.7 to 1.5) and 1.0 (95% CI 0.6 to 1.7), respectively. Combining clinical examination with conventional radiography produced a sensitivity of 50% (95% CI 29% to 71%), specificity of 91% (95% CI 82% to 97%), PPV of 67% (95% CI 46% to 83%), NPV of 84% (95% CI 77% to 88%), as well as a positive and negative LR of 5.6 (95% CI 2.4 to 13.2) and 0.6 (95% CI 0.4 to 0.8), respectively. CONCLUSION: The accuracy of conventional radiographs (80% compared with HR-pQCT) and clinical reassessment (46% compared with HR-pQCT) indicate that the value of clinical reassessment is limited in diagnosing scaphoid fractures and cannot be considered directive in managing scaphoid fractures. The combination of conventional radiographs and clinical reassessment does not increase the accuracy of these diagnostic tests compared with the accuracy of conventional radiographs alone and is therefore also limited in diagnosing scaphoid fractures. LEVEL OF EVIDENCE: Level II, diagnostic study.

Arginine Availability in Reamed Intramedullary Aspirate as Predictor of Outcome in Nonunion Healing.

Fracture healing and nonunion development are influenced by a range of biological factors. Adequate amino acid concentrations, especially arginine, are known to be important during normal bone healing. We hypothesize that bone arginine availability in autologous bone marrow grafting, when using the reamer-irrigator-aspirator (RIA) procedure, is a marker of bone healing capacity in patients treated for nonunion. Seventeen patients treated for atrophic long bone nonunion by autologous bone grafting by the RIA procedure were included and divided into two groups, successful treatment of nonunion and unsuccessful, and were compared with control patients after normal fracture healing. Reamed bone marrow aspirate from a site distant to the nonunion was obtained and the amino acids and enzymes relevant to arginine metabolism were measured. Arginine and ornithine concentrations were higher in patients with successful bone healing after RIA in comparison with unsuccessful healing. Ornithine concentrations and arginase-1 expression were lower in all nonunion patients compared to control patients, while citrulline concentrations were increased. Nitric oxide synthase 2 (Nos2) expression was significantly increased in all RIA-treated patients, and higher in patients with a successful outcome when compared with an unsuccessful outcome. The results indicate an influence of the arginine-nitric oxide metabolism in collected bone marrow, on the outcome of nonunion treatment, with indications for a prolonged inflammatory response in patients with unsuccessful bone grafting therapy. The determination of arginine concentrations and Nos2 expression could be used as a predictor for the successful treatment of autologous bone grafting in nonunion treatment.