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Okan W Bastian,1 Anne Kuijer,1 Leo Koenderman,2 Rebecca K Stellato,3 Wouter W van Solinge,4 Luke PH Leenen,1 Taco J Blokhuis1 1Department of Traumatology, 2Department of Respiratory Medicine, 3Department of Biostatistics and Research Support, Julius Center, 4Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands Abstract: Animal studies have shown that the systemic inflammatory response to major injury impairs bone regeneration. It remains unclear whether the systemic immune response contributes to impairment of fracture healing in multitrauma patients. It is well known that systemic inflammatory changes after major trauma affect leukocyte kinetics. We therefore retrospectively compared the cellular composition of peripheral blood during the first 2 weeks after injury between multitrauma patients with normal (n=48) and impaired (n=32) fracture healing of the tibia. The peripheral blood-count curves of leukocytes, neutrophils, monocytes, and thrombocytes differed significantly between patients with normal and impaired fracture healing during the first 2 weeks after trauma (P-values were 0.0122, 0.0083, 0.0204, and

Introduction: The diagnosis of low-grade infection in post-traumatic long bone non-unions poses challenges due to the absence of clinical signs. This study aimed to review the available literature on the diagnostic accuracy of imaging techniques for low-grade infections and assess the diagnostic accuracy of 18 F-FDG PET-CT scans for low-grade infection in post-traumatic long bone non-unions., Methods: A mini-review was conducted using Pubmed in March 2024. A retrospective study was conducted including adult patients with a long bone non-union, suspected of infection. All patients underwent 18 F-FDG PET-CT scans as the index test before surgical intervention, with peri‑operative cultures obtained during surgery serving as the reference standard. Quantitative analyses were performed on the standardized uptake value (SUV) measurements obtained from the 18 F-FDG PET-CT scans. Diagnostic accuracy measures including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the discriminatory ability of SUV measurements., Results: Literature suggests that 18 F-FDG PET-CT is the most accurate imaging technique to detect low-grade infections. The study included a total of 51 18 F-FDG PET-CT scans and cultures from 50 patients with long bone non-unions. The diagnostic accuracy was found to be 0.67 (95 % CI 0.44-0.87). The PPV and NPV were calculated as 0.79 (95 % CI 0.53-1.00) and 0.52 (95 % CI 0.30-0.73), respectively. Quantitative analyses of SUV measurements demonstrated a low level of accuracy, with all area under the curve (AUC) values < 0.75 and ROC curves showing a trajectory fairly parallel to the diagonal line., Conclusion and Discussion: The findings of this study indicate that in post-traumatic long bone non-unions, where a low-grade fracture-related infection (FRI) is suspected, the 18 F-FDG PET-CT has a performance that is advantageous over other imaging techniques. A careful interpretation of the scan results is warranted, possibly including the quantitative analysis on tracer uptake as an adjunct. Nevertheless, the diagnostic accuracy in this condition is not as good as in early-onset FRI cases, and this should be taken into account when treating these challenging cases., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

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., Competing Interests: F. Hildebrand reports grants and consulting fees from Medudy and Stryker, unrelated to this study, and also participates in a Data Safety Monitoring Board or Advisory Board for the German Research Council, as well as a leadership or fiduciary role in the European Society of Trauma and Emergency Surgery and German Society of Orthopedics and Trauma Surgery. M. Huber-Lang is a board member and past President of the European Shock Society, President-elect of the International Federation of Shock Societies and President of the German Trauma Foundation. M. van Griensven reports royalties from Elsevier, participation on a Data Safety Monitoring Board or Advisory Board in CDT Manchester Sheffield and CIBER-BBN (Spain), reviewer grants from the European Union, NWO, and Springer Nature, all of which are unrelated to this study. M. van Griensven is also unpaid president of the basic research section of the German Society for Orthopaedics and Trauma Surgery. The authors declare that the research was conducted in the absence of any commercial, financial, or other relationships that could be construed as a potential conflict of interest., (© 2024 Groven et al.)

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., (© 2024. The Author(s).)

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)., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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 β-TCP: (Ca 3 (PO 4 ) 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., (© 2023. The Author(s).)

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/m 2 ) with an acute (<24 h) intracapsular hip fracture received a primed continuous intravenous infusion of L-[ring- 13 C 6 ]-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- 13 C 6 ]-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., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors. The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Two trauma treatment principles are Early Total Care (ETC), and Damage Control Orthopedics (DCO). Cellular mechanisms that underlie the connection between treatment type, its systemic effects, and tissue regeneration are not fully known. Therefore, this study aimed to: 1) profile microRNA (miRNA) expression in plasma derived Extracellular Vesicles (EVs) from a porcine multiple trauma model at different timepoints, comparing two surgical treatments; and 2) determine and validate the miRNA's messengerRNA (mRNA) targets., Methods: The porcine multiple trauma model consisted of blunt chest trauma, liver laceration, bilateral femur fractures, and controlled haemorrhagic shock. Two treatment groups were defined, ETC (n=8), and DCO (n=8). Animals were monitored under Intensive Care Unit-standards, blood was sampled at 1.5, 2.5, 24, and 72 hours after trauma, and EVs were harvested from plasma. MiRNAs were analysed using quantitative Polymerase Chain Reaction arrays. MRNA targets were identified in silico and validated in vivo in lung and liver tissue., Results: The arrays showed distinct treatment specific miRNA expression patterns throughout all timepoints, and miRNAs related to the multiple trauma and its individual injuries. EV-packed miRNA expression in the ETC group was more pro-inflammatory, indicating potentially decreased tissue regenerative capacities in the acute post-traumatic phase. In silico target prediction revealed several overlapping mRNA targets among the identified miRNAs, related to inflammation, (pulmonary) fibrosis, and Wnt-signalling. These were, among others, A Disintegrin and Metalloproteinase domain-containing protein 10, Collagen Type 1 Alpha 1 Chain, Catenin Beta Interacting Protein 1, and Signal Transducers and Activators of Transcription 3. Validation of these mRNA targets in the lung showed significant, treatment specific deregulations which matched the expression of their upstream miRNAs. No significant mRNA deregulations were observed in the liver., Discussion: This study showed treatment specific, EV-packed miRNA expression patterns after trauma that correlated with mRNA expressions in the lungs, target organs over distance. A systemic response to the increased surgical trauma in the ETC group was identified, with various miRNAs associated with injuries from the trauma model, and involved in (systemic) inflammation, tissue regeneration. EV-transported miRNAs demonstrated a clear role in multiple trauma, warranting further research into tissue-tissue talk and therapeutic applications of EVs after trauma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Groven, Greven, Mert, Horst, Zhao, Blokhuis, Huber-Lang, Hildebrand and van Griensven.)

The ability to manage the myriad of musculoskeletal conditions successfully requires multiple years of training. Access to and completion of orthopaedic surgical training entails an often grueling, highly regulated path to certification to practice. Although the world is more connected than ever, the question is whether the local certification criteria for medical specialists leads to a generic residency program and a similar training in all countries. This report from eight nations on five continents details the distinctive features of that training, including the number of positions available, the examinations required, the gender distribution of residents, and available possibilities once the residence period is complete. This analysis shows a wide variation in the orthopaedic trauma training program worldwide, with emphasis on different skills per country., Competing Interests: Declaration of Competing Interest The other authors and I have no pecuniary or other personal interest, direct or indirect, in any matter that raises or may raise a conflict with this paper., (Copyright © 2023. Published by Elsevier Ltd.)

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 (RF csa ) 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 RF csa were available. In patients with sequential RF csa measurements, muscle loss was defined as the negative slope of the regression line fitted to the RF csa 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&#95;ae&#95;C30&#95;0 (R = 0.5, p = 0.034) and two acylcarnitines: C14&#95;2 (R = 0.5, p = 0.042) and C10&#95;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&#95;aa&#95;C40&#95;2 (R = 0.7, p = 0.015), PC&#95;ae&#95;C40&#95;1 (R = 0.6, p = 0.032) and PC&#95;aa&#95;C42&#95;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., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Fracture non-unions have a detrimental effect on patients due to reduced mobility and severe pain. Current literature on the quality of life in non-unions is limited, hence the purpose of this study, to quantify the health-related quality of life (HRQoL) among patients with post-traumatic long bone non-unions. It was hypothesized that the HRQoL of these patients is lower than the Dutch population standard as well as for multiple chronic diseases and musculoskeletal disorders., Patients and Methods: From January 2020 to December 2021, this study included consecutive patients who were referred to a multidisciplinary (trauma, orthopedic and plastic surgery), non-union clinic at the Maastricht UMC+. All non-unions were evaluated using the Non-Union Scoring System (NUSS) questionnaire. Patient reported HRQoL outcomes were acquired using the EQ-5D-5L questionnaire and the Lower Extremity Functional Scale (LEFS)., Results: 50 patients were included, 18 females and 32 males, with a mean age of 55 years (± 15.5 SD). Eighteen patients presented with an open fracture, nine non-unions were infected and 39 patients had a lower extremity non-union. The mean NUSS score was 39.61 (± 14.6 SD). The mean EQ-5D-5L index score was 0.490 (± 0.261 SD), where patients experienced most problems with mobility. The mean EQ-5D-5L VAS was 61.4 (± 19.6 SD). The patients had a mean LEFS score of 28.7 (± 16.4 SD). The health-related quality of life was well below the age-corrected normative score of the Dutch population (EQ-5D-5L 0.857(p < 0.001); LEFS 77(p < 0.001)). This cohort's HRQoL was significantly lower than the HRQoL of multiple chronic and musculoskeletal disorders, including different forms of cancer and osteoarthritis., Conclusions: This study has quantified the detrimental effect of post-traumatic long bone non-unions on patient's health-related quality of life, being significantly lower than the HRQoL of the Dutch population as well as for multiple chronic and musculoskeletal medical conditions. This cohort demonstrates a patient population in need of more specialized care with a low health-related quality of life., Competing Interests: Declaration of Competing Interest The authors declare that they have not received any funding and that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Innovative techniques can help overcome the limitations of the human body. Operating on very small structures requires adequate vision of the surgical field and precise movements of sophisticated instruments. Both the human eye and hand are limited when performing microsurgery. Conventional microsurgery uses operation microscopes to enhance the visualization of very small structures. Evolving technology of high-definition 3D cameras provides the opportunity to replace conventional operation microscopes, thereby improving ergonomics for surgeons. This leaves the human hand as a limiting factor in microsurgery. A dedicated robot for microsurgery has been developed to overcome this limitation and enhance the precision and stability of the surgeons' hands. We present the first-in-human case in reconstructive microsurgery where both technologies are integrated using a dedicated microsurgical robot in combination with a 4K 3D exoscope.

Background: The presence of six or more rib fractures or a displaced rib fracture due to cardiopulmonary resuscitation (CPR) has been associated with longer hospital and intensive care unit (ICU) length of stay (LOS). Evidence on the effect of surgical stabilization of rib fractures (SSRF) following CPR is limited. This study aimed to evaluate outcomes after SSRF versus nonoperative management in patients with multiple rib fractures after CPR., Methods: An international, retrospective study was performed in patients who underwent SSRF or nonoperative management for multiple rib fractures following CPR between January 1, 2012, and July 31, 2020. Patients who underwent SSRF were matched to nonoperative controls by cardiac arrest location and cause, rib fracture pattern, and age. The primary outcome was ICU LOS., Results: Thirty-nine operatively treated patient were matched to 66 nonoperatively managed controls with comparable CPR-related characteristics. Patients who underwent SSRF more often had displaced rib fractures (n = 28 [72%] vs. n = 31 [47%]; p = 0.015) and a higher median number of displaced ribs (2 [P 25 -P 75 , 0-3] vs. 0 [P 25 -P 75 , 0-3]; p = 0.014). Surgical stabilization of rib fractures was performed at a median of 5 days (P 25 -P 75 , 3-8 days) after CPR. In the nonoperative group, a rib fixation specialist was consulted in 14 patients (21%). The ICU LOS was longer in the SSRF group (13 days [P 25 -P 75 , 9-23 days] vs. 9 days [P 25 -P 75 , 5-15 days]; p = 0.004). Mechanical ventilator-free days, hospital LOS, thoracic complications, and mortality were similar., Conclusion: Despite matching, those who underwent SSRF over nonoperative management for multiple rib fractures following CPR had more severe consequential chest wall injury and a longer ICU LOS. A benefit of SSRF on in-hospital outcomes could not be demonstrated. A low consultation rate for rib fixation in the nonoperative group indicates that the consideration to perform SSRF in this population might be associated with other nonradiographic or injury-related variables., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Sarcopenia is a muscle disease that involves loss of muscle strength and physical function and is associated with adverse health effects. Even though sarcopenia has attracted increasing attention in the literature, many research findings have not yet been translated into clinical practice. In this article, we aim to validate a deep learning neural network for automated segmentation of L3 CT slices and aim to explore the potential for clinical utilization of such a tool for clinical practice., Materials and Methods: A deep learning neural network was trained on a multi-centre collection of 3413 abdominal cancer surgery subjects to automatically segment muscle, subcutaneous and visceral adipose tissue at the L3 lumbar vertebral level. 536 Polytrauma subjects were used as an independent test set to show generalizability. The Dice Similarity Coefficient was calculated to validate the geometric similarity. Quantitative agreement was quantified using Bland-Altman's Limits of Agreement interval and Lin's Concordance Correlation Coefficient. To determine the potential clinical usability, randomly selected segmentation images were presented to a panel of experienced clinicians to rate on a Likert scale., Results: Deep learning results gave excellent agreement versus a human expert operator for all of the body composition indices, with Concordance Correlation Coefficient for skeletal muscle index of 0.92, Skeletal muscle radiation attenuation 0.94, Visceral Adipose Tissue index 0.99 and Subcutaneous Adipose Tissue Index 0.99. Triple-blinded visual assessment of segmentation by clinicians correlated only to the Dice coefficient, but had no association to quantitative body composition metrics which were accurate irrespective of clinicians' visual rating., Conclusion: A deep learning method for automatic segmentation of truncal muscle, visceral and subcutaneous adipose tissue on individual L3 CT slices has been independently validated against expert human-generated results for an enlarged polytrauma registry dataset. Time efficiency, consistency and high accuracy relative to human experts suggest that quantitative body composition analysis with deep learning should is a promising tool for clinical application in a hospital setting., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses r interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aim: Sarcopenia is defined as a loss of muscle mass and function, which can be caused by normal ageing or factors such as physical inactivity. Severe health consequences caused by sarcopenia highlight the need for early identification. Computed Tomography (CT) imaging, often mentioned as the gold standard due to its accuracy, is costly and not routinely performed in daily clinical care. Ultrasound of the rectus femoris, however, is low in costs and easily accessible. The aim is to present the current and most recent literature regarding the diagnostic value of ultrasound measurements of the rectus femoris for the diagnosis of sarcopenia in adults., Methods: The databases PubMed and Web of Science were used to search for studies comparing ultrasound of the rectus femoris with a reference test to diagnose sarcopenia in adults. The quality of the final eligible studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies, version 2, tool (QUADAS-2)., Results: Six studies were included in this systematic review. The muscle thickness and cross-sectional area of the rectus femoris were assessed and compared with the reference tests CT, Dual-Energy X-ray Absorptiometry (DXA), and Bioelectrical Impedance Analysis (BIA). Half of the studies had a low risk of bias on all QUADAS-2 domains. Three studies reported statistical significant outcomes and diagnostic values ranging from 60 to 81% sensitivity and 51 to 94% specificity., Conclusions: Ultrasound of the rectus femoris muscle to diagnose sarcopenia has been shown to be a promising method in multiple clinical populations. However, there were some limitations such as a high methodological heterogeneity. Future research should develop standardized protocols and determine clear cut-off values to allow for a better implementation of ultrasound in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Immediately after a fracture occurs, a fracture hematoma (fxH) is formed. This fxH plays an important role in fracture healing and, under normal circumstances, aids in generating an environment in which a wide variety of cells orchestrate processes involved in fracture healing. MicroRNAs (miRNAs) may influence these processes. The aim of this study was therefore to determine the miRNA expression signature of human fxH in normal fracture healing and examine the potential influence of clinical parameters on these expression levels., Methods: fxH was harvested from 61 patients (mean age 52 ± 19; 32 ♀ ) during fracture surgery. miRNAs were isolated, transcribed and pooled for qPCR array analysis and validation. Qiagen fibrosis- and inflammation qPCR arrays were used based on an extensive literature study related to fracture healing and osteogenesis. Additionally, miRNA targets were determined., Results: From the array data, a selection of the twenty most regulated miRNAs, 10 up- and 10 down regulated, was validated in the study population. The expression levels of seven out of these twenty miRNAs were correlated to several clinical parameters. The time interval between trauma and surgery showed to influence the expression of three miRNAs, three other miRNAs were expressed in a patient age dependent manner and one miRNA was associated with the severity of trauma., Conclusion: This study portrayed the role and importance of miRNAs in human fxH, linked to key processes in fracture healing. Seven miRNAs showed to be involved in multiple processes that are important in the fracture healing cascade, such as angiogenesis, mineralisation and cellular differentiation. In silico target analysis revealed 260 mRNA targets for 14 out of the 20 validated miRNAs., The Translational Potential of This Article: These data broaden our view on the potential diagnostic and therapeutic implications of miRNAs in fracture healing., Competing Interests: There are no conflicts of interest to declare., (© 2022 The Authors.)

Background & Aims: Sarcopenia is a muscle disorder associated with loss of muscle mass, strength and function. Early screening, diagnosis and treatment may improve outcome in different disease conditions. A wide variety of tools for estimation of muscle mass is available and each tool has specific technical requirements. However, different investigational settings and lack of homogeneity of populations influence the definition of gold standards, proving it difficult to systematically adopt these tools. Recently, the European Working Group on Sarcopenia in Older People (EWGSOP) published a revised recommendation (EWGSOP-2) and algorithm for using tools for screening and diagnosing sarcopenia. However, agreement of the EWGSOP2 criteria with other classifications is poor and although an overview of available tools is valuable, for the purpose of clinical decision-making the reverse is useful; a given scenario asks for the most suitable tools., Results: Tools were identified for screening, diagnostics and longitudinal monitoring of muscle mass. For each of these clinical scenarios the most appropriate tools were listed and for each technique their usability is specified based on sensitivity and specificity. Based on this information a specific recommendation is made for each clinical scenario., Conclusion: This narrative review provides an overview of currently available tools and future developments for different clinical scenarios such as screening, diagnosis and longitudinal monitoring of alterations in muscle status. It supports clinical decision-making in choosing the right tools for muscle mass quantification depending on the need within a given clinical scenario as well as the local availability and expertise., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Complex regional pain syndrome type I (CRPS) is a symptom-based diagnosis of which the reported incidence varies widely. In daily practice, there appears to be a decrease in incidence of CRPS after a distal radius fracture and in general., Questions/purposes: The aim of this study was to assess the trend in the incidence of CRPS after a distal radius fracture and in general in the Netherlands from 2014 to 2018., Methods: The incidence of CRPS after a distal radius fracture was calculated by dividing the number of confirmed cases of CRPS after distal radius fracture by the total number of patients diagnosed with a distal radius fracture. Medical records of these patients were reviewed. Hospital-based data were used to establish a trend in incidence of CRPS in general. A Dutch national database was used to measure the trend in the incidence of CRPS in the Netherlands by calculating annual incidence rates: the number of new CRPS cases, collected from the national database, divided by the Dutch mid-year population., Results: The incidence of CRPS after distal radius fracture over the whole study period was 0.36%. Hospital data showed an absolute decrease in CRPS cases from 520 in 2014 to 223 in 2018. National data confirmed this with a decrease in annual incidence from 23.2 (95% CI: 22.5-23.9) per 100,000 person years in 2014 to 16.1 (95% CI: 15.5-16.7) per 100,000 person years in 2018., Conclusion: A decreasing trend of CRPS is shown in this study. We hypothesize this to be the result of the changing approach towards CRPS and fracture management, with more focus on prevention and the psychological aspects of disproportionate posttraumatic pain., Level of Evidence: level 3 (retrospective cohort study)., Competing Interests: Conflict of interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The British Pain Society 2021.)

Background: Fracture healing is a complex process, involving cell-cell interactions, various cytokines, and growth factors. Although fracture treatment improved over the last decades, a substantial part of all fractures shows delayed or absent healing. The fracture hematoma (fxh) is known to have a relevant role in this process, while the exact mechanisms by which it influences fracture healing are poorly understood. To improve strategies in fracture treatment, regulatory pathways in fracture healing need to be investigated. Lipids are important molecules in cellular signaling, inflammation, and metabolism, as well as key structural components of the cell. Analysis of the lipid spectrum in fxh may therefore reflect important events during the early healing phase. This study aims to develop a protocol for the determination of lipid signals over time, and the identification of lipids that contribute to these signals, with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in fxh in healthy fracture healing. Methods: Twelve fxh samples (6 porcine; 6 human) were surgically removed, snap frozen, sectioned, washed, and analyzed using MALDI-MSI in positive and negative ion mode at different time points after fracture (porcine: 72 h; human samples: range 1-19 days). A tissue preparation protocol for lipid analysis in fxh has been developed with both porcine and human fxh. Data were analyzed through principal component- and linear discriminant analyses. Results: A protocol for the preparation of fxh sections was developed and optimized. Although hematoma is a heterogeneous tissue, the intra-variability within fxh was smaller than the inter-variability between fxh. Distinctive m/ z values were detected that contributed to the separation of three different fxh age groups: early (1-3 days), middle (6-10 days), and late (12-19 days). Identification of the distinctive m/ z values provided a panel of specific lipids that showed a time dependent expression within fxh. Conclusion: This study shows that MALDI-MSI is a suitable analytical tool for lipid analysis in fxh and that lipid patterns within fxh are time-dependent. These lipid patterns within fxh may serve as a future diagnostic tool. These findings warrant further research into fxh analysis using MALDI-MSI and its possible clinical implications in fracture treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Groven, Nauta, Gruisen, Claes, Greven, van Griensven, Poeze, Heeren, Porta Siegel, Cillero-Pastor and Blokhuis.)

Fracture healing is a complex, dynamic process that is directed by cellular communication and requires multiple cell types, such as osteoblasts, osteoclasts, and immune cells. Physiological fracture healing can be divided into several phases that consist of different processes, such as angiogenesis, osteogenesis, and bone resorption/remodelling. This is needed to guarantee proper bone regeneration after fracture. Communication and molecular regulation between different cell types and within cells is therefore key in successfully orchestrating these processes to ensure adequate bone healing. Among others, microRNAs (miRNAs) play an important role in cellular communication. microRNAs are small, non-coding RNA molecules of ~22 nucleotides long that can greatly influence gene expression by post-transcriptional regulation. Over the course of the past decade, more insights have been gained in the field of miRNAs and their role in cellular signalling in both inter- and intracellular pathways. The interplay between miRNAs and their mRNA targets, and the effect thereof on different processes and aspects within fracture healing, have shown to be interesting research topics with possible future diagnostic and therapeutic potential. Considering bone regeneration, research moreover focusses on specific microRNAs and their involvement in individual pathways. However, it is required to combine these data to gain more understanding on the effects of miRNAs in the dynamic process of fracture healing, and to enhance their translational application in research, as well as in the clinic. Therefore, this review aims to provide an integrative overview on miRNAs in fracture healing, related to several key aspects in the fracture healing cascade. A special focus will be put on hypoxia, angiogenesis, bone resorption, osteoclastogenesis, mineralization, osteogenesis, osteoblastogenesis, osteocytogenesis, and chondrogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Groven, van Koll, Poeze, Blokhuis and van Griensven.)

Microwave-based sensing for tissue analysis is recently gaining interest due to advantages such as non-ionizing radiation and non-invasiveness. We have developed a set of transmission sensors for microwave-based real-time sensing to quantify muscle mass and quality. In connection, we verified the sensors by 3D simulations, tested them in a laboratory on a homogeneous three-layer tissue model, and collected pilot clinical data in 20 patients and 25 healthy volunteers. This report focuses on initial sensor designs for the Muscle Analyzer System (MAS), their simulation, laboratory trials and clinical trials followed by developing three new sensors and their performance comparison. In the clinical studies, correlation studies were done to compare MAS performance with other clinical standards, specifically the skeletal muscle index, for muscle mass quantification. The results showed limited signal penetration depth for the Split Ring Resonator (SRR) sensor. New sensors were designed incorporating Substrate Integrated Waveguides (SIW) and a bandstop filter to overcome this problem. The sensors were validated through 3D simulations in which they showed increased penetration depth through tissue when compared to the SRR. The second-generation sensors offer higher penetration depth which will improve clinical data collection and validation. The bandstop filter is fabricated and studied in a group of volunteers, showing more reliable data that warrants further continuation of this development.

Introduction: Treatment of infected non-unions of the tibia is a challenging problem. The cornerstones of optimal infected non-union treatment consist of extensive debridement, fracture fixation, antimicrobial therapy and creation of an optimal local biological bone healing environment. The combination of S53P4 bioactive glass (BAG), as osteostimulative antibacterial bone graft substitute, and bone marrow aspirate concentrate (BMAC) for the implantation of mesenchymal stem cells and growth factors might be a promising combination. In this paper, preliminary results of a new treatment algorithm for infected non-unions of the tibia is presented., Methods: In this retrospective case series patients with infected non-unions of the tibia are treated according to a new treatment algorithm. Patients are treated with extensive debridement surgery, replacement of the osteosynthesis and implantation of S53P4 BAG and BMAC in a one-stage or two-stage procedure based on non-union severity. Subsequently patients are treated with culture based antibiotic therapy and followed until union and infection eradication., Results: Five patients with an infected non-union were treated, mean age was 55, average NUSS-score was 44 and the average segmental bone defect was 4.6cm. One patient was treated in a one-stage procedure and four patients in a two-stage induced membrane-, or "Masquelet"-procedure. On average, 23 ml S53P4 BAG and 6.2 ml BMAC was implanted. The mean follow-up period was 13.6 months and at the end of follow-up all patients had clinical consolidation with an average RUST-score of 7.8 and complete eradication of infection., Discussion: These early data on the combined implantation of S53P4 BAG and BMAC in treatment of infected non-unions shows promising results. These fracture healing results and eradication rates resulted in promising functional recovery of the patients. To substantiate these results, larger and higher quality studies should be performed., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Ltd.)

Manual segmentation of muscle and adipose compartments from computed tomography (CT) axial images is a potential bottleneck in early rapid detection and quantification of sarcopenia. A prototype deep learning neural network was trained on a multi-center collection of 3413 abdominal cancer surgery subjects to automatically segment truncal muscle, subcutaneous adipose tissue and visceral adipose tissue at the L3 lumbar vertebral level. Segmentations were externally tested on 233 polytrauma subjects. Although after severe trauma abdominal CT scans are quickly and robustly delivered, with often motion or scatter artefacts, incomplete vertebral bodies or arms that influence image quality, the concordance was generally very good for the body composition indices of Skeletal Muscle Radiation Attenuation (SMRA) (Concordance Correlation Coefficient (CCC) = 0.92), Visceral Adipose Tissue index (VATI) (CCC = 0.99) and Subcutaneous Adipose Tissue Index (SATI) (CCC = 0.99). In conclusion, this article showed an automated and accurate segmentation system to segment the cross-sectional muscle and adipose area L3 lumbar spine level on abdominal CT. Future perspectives will include fine-tuning the algorithm and minimizing the outliers.

Background: Ambulant biofeedback devices can be used to provide real-time feedback for trauma patients on weight-bearing regimes. The devices also enable prescribing clinicians to monitor and train patients' level of weight-bearing. However, there is limited evidence regarding the feasibility of use of such devices in controlling weight-bearing, and their full potential remains to be elucidated., Objective: To investigate the feasibility of using ambulant biofeedback training devices to improve compliance with weight-bearing regimes in trauma patients with lower extremity fractures., Methods: A literature review of the feasibility and clinical validity of ambulant biofeedback devices., Results: Three clinically validated biofeedback devices were found feasible for use in monitoring the compliance of patients who have lower extremity fractures with different weight-bearing regimes., Conclusion: Further information about the feasibility and clinical validity of biofeedback training devices is nee-ded in order to optimize weight-bearing instructions for patients.

Sarcopenia is related to adverse outcomes in various populations. However, little is known about the prevalence of sarcopenia in polytrauma patients. Identifying the number of patients at risk of adverse outcome will increase awareness to prevent further loss of muscle mass. We utilized data from a regional prospective trauma registry of all polytrauma patients presented between 2015 and 2019 at a single level-I trauma center. Subjects were screened for availability of computed tomography (CT)-abdomen and height in order to calculate skeletal mass index, which was used to estimate sarcopenia. Additional parameters regarding clinical outcome were assessed. Univariate analysis was performed to identify parameters related adverse outcome and, if identified, entered in a multivariate regression analysis. Prevalence of sarcopenia was 33.5% in the total population but was even higher in older age groups (range 60-79 years), reaching 82 % in patients over 80 years old. Sarcopenia was related to 30-day or in-hospital mortality ( p = 0.032), as well as age ( p < 0.0001), injury severity score ( p = 0.026), and Charlson comorbidity index ( p = 0.001). Log rank analysis identified sarcopenia as an independent predictor of 30-day mortality ( p = 0.032). In conclusion, we observed a high prevalence of sarcopenia among polytrauma patients, further increasing in older patients. In addition, sarcopenia was identified as a predictor for 30-day mortality, underlining the clinical significance of identification of low muscle mass on a CT scan that is already routinely obtained in most trauma patients.

Background: Adverse events are common in high-risk surgical patients, but early detection is difficult. Recent innovations have resulted in wireless and 'wearable' sensors, which may capture patient deterioration at an early stage, but little is known regarding their ability to timely detect events. The objective of this study is to describe the ability of currently available wireless sensors to detect adverse events in high-risk patients., Methods: A descriptive analysis was performed of all vital signs trend data obtained during an observational comparison study of wearable sensors for vital signs monitoring in high-risk surgical patients during the initial days of recovery at a surgical step-down unit (SDU) and subsequent traumatology or surgical oncology ward. Heart rate (HR), respiratory rate (RR) and oxygen saturation (SpO 2 ) were continuously recorded. Vital sign trend patterns of patients that developed adverse events were described and compared to vital sign recordings of patients without occurrence of adverse events. Two wearable patch sensors were used (SensiumVitals and HealthPatch), a bed-based mattress sensor (EarlySense) and a patient-worn monitor (Masimo Radius-7)., Results: Twenty adverse events occurred in 11 of the 31 patients included. Atrial fibrillation (AF) was most common (20%). The onset of AF was recognizable as a sudden increase in HR in all recordings, and all patients with new-onset AF after esophagectomy developed other postoperative complications. Patients who developed respiratory insufficiency showed an increase in RR and a decrease in SpO 2 , but an increase in HR was not always visible. In patients without adverse events, temporary periods of high HR and RR are observed as well, but these were transient and less frequent., Conclusions: Current systems for remote wireless patient monitoring on the ward are capable of detecting abnormalities in vital sign patterns in patients who develop adverse events. Remote patient monitoring may have potential to improve patient safety by generating early warnings for deterioration to nursing staff., Competing Interests: Declaration of Competing interest MJMB is part-time employee of Luscii Healthtech BV (Health ICT company, Amsterdam, The Netherlands)., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Vital signs are usually recorded once every 8 h in patients at the hospital ward. Early signs of deterioration may therefore be missed. Wireless sensors have been developed that may capture patient deterioration earlier. The objective of this study was to determine whether two wearable patch sensors (SensiumVitals [Sensium Healthcare Ltd., United Kingdom] and HealthPatch [VitalConnect, USA]), a bed-based system (EarlySense [EarlySense Ltd., Israel]), and a patient-worn monitor (Masimo Radius-7 [Masimo Corporation, USA]) can reliably measure heart rate (HR) and respiratory rate (RR) continuously in patients recovering from major surgery., Methods: In an observational method comparison study, HR and RR of high-risk surgical patients admitted to a step-down unit were simultaneously recorded with the devices under test and compared with an intensive care unit-grade monitoring system (XPREZZON [Spacelabs Healthcare, USA]) until transition to the ward. Outcome measures were 95% limits of agreement and bias. Clarke Error Grid analysis was performed to assess the ability to assist with correct treatment decisions. In addition, data loss and duration of data gaps were analyzed., Results: Twenty-five high-risk surgical patients were included. More than 700 h of data were available for analysis. For HR, bias and limits of agreement were 1.0 (-6.3, 8.4), 1.3 (-0.5, 3.3), -1.4 (-5.1, 2.3), and -0.4 (-4.0, 3.1) for SensiumVitals, HealthPatch, EarlySense, and Masimo, respectively. For RR, these values were -0.8 (-7.4, 5.6), 0.4 (-3.9, 4.7), and 0.2 (-4.7, 4.4) respectively. HealthPatch overestimated RR, with a bias of 4.4 (limits: -4.4 to 13.3) breaths/minute. Data loss from wireless transmission varied from 13% (83 of 633 h) to 34% (122 of 360 h) for RR and 6% (47 of 727 h) to 27% (182 of 664 h) for HR., Conclusions: All sensors were highly accurate for HR. For RR, the EarlySense, SensiumVitals sensor, and Masimo Radius-7 were reasonably accurate for RR. The accuracy for RR of the HealthPatch sensor was outside acceptable limits. Trend monitoring with wearable sensors could be valuable to timely detect patient deterioration.

Background: Multiple rib fractures are common injuries in both the young and elderly. Rib fractures account for 10% of all trauma admissions and are seen in up to 39% of patients after thoracic trauma. With morbidity and mortality rates increasing with the number of rib fractures as well as poor quality of life at long-term follow-up, multiple rib fractures pose a serious health hazard. Operative fixation of flail chest is beneficial over nonoperative treatment regarding, among others, pneumonia and both intensive care unit (ICU) and hospital length of stay. With no high-quality evidence on the effects of multiple simple rib fracture treatment, the optimal treatment modality remains unknown. This study sets out to investigate outcome of operative fixation versus nonoperative treatment of multiple simple rib fractures., Methods: The proposed study is a multicenter randomized controlled trial. Patients will be eligible if they have three or more multiple simple rib fractures of which at least one is dislocated over one shaft width or with unbearable pain (visual analog scale (VAS) or numeric rating scale (NRS) > 6). Patients in the intervention group will be treated with open reduction and internal fixation. Pre- and postoperative care equals treatment in the control group. The control group will receive nonoperative treatment, consisting of pain management, bronchodilator inhalers, oxygen support or mechanical ventilation if needed, and pulmonary physical therapy. The primary outcome measure will be occurrence of pneumonia within 30 days after trauma. Secondary outcome measures are the need and duration of mechanical ventilation, thoracic pain and analgesics use, (recovery of) pulmonary function, hospital and ICU length of stay, thoracic injury-related and surgery-related complications and mortality, secondary interventions, quality of life, and cost-effectiveness comprising health care consumption and productivity loss. Follow-up visits will be standardized and daily during hospital admission, at 14 days and 1, 3, 6, and 12 months., Discussion: With favorable results in flail chest patients, operative treatment may also be beneficial in patients with multiple simple rib fractures. The FixCon trial will be the first study to compare clinical, functional, and economic outcome between operative fixation and nonoperative treatment for multiple simple rib fractures., Trial Registration: www.trialregister.nl, NTR7248. Registered May 31, 2018., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: The incidence of hip fractures is increasing. Elderly patients with a hip fracture frequently present with comorbidities, which are associated with higher mortality rates. Clinical studies regarding long-term functional outcome and mortality in hip fractures are rare. The aim of this study was to analyse the functional outcome and the mortality rate after a follow-up of 5 years in elderly patients with a hip fracture., Materials and Methods: This combined retrospective and cross-sectional study included patients aged 65 years or older with a low energy hip fracture who underwent surgery in the Maastricht University Medical Center+, the Netherlands. Data such as demographics and mortality rates were retrospectively collected and functional outcome (i.e. mobility, pain, housing conditions and quality of life) was assessed by a questionnaire., Results: Two hundred and sixteen patients were included in this study (mean age 82.2, SD ± 7.5). No significant differences were found in pain before hip fracture and after 1-year and 5-year follow-ups. Long-term functional outcome deteriorated after a hip fracture, with a significant increase in the use of walking aids (p < 0.001), a significant decrease of patients living in a private home (p < 0.001), and a low physical quality of life (SF-12 PCS = 27.1). The mortality incidences after 30-day, 1-year and 5-year follow-ups were 7.9%, 37.0% and 69.4%, respectively., Conclusion: Long-term functional outcome in elderly patients with hip fractures significantly deteriorated, with an increased dependency for mobility and housing conditions and a decreased physical quality of life. In addition, hip fractures are associated with high mortality rates at the 5-year follow-up., Level of Evidence: Level III, a retrospective cohort study.

Older people with hip fractures are often malnourished at the time of fracture, which can have substantial influence on mortality and clinical outcomes, as well as functional outcome and quality of life. A close relationship between protein intake and muscle maintenance has been demonstrated. Skeletal muscle weakness is an independent risk factor for falls and fall-related injuries in the elderly and is an independent marker of prognosis. However, the effect of perioperative nutritional interventions on outcomes in elderly hip-fracture patients remains controversial. In this narrative review, an overview is presented of the existing literature on nutritional status and sarcopenia in elderly hip-fracture patients, clinical outcomes, and the effects of nutritional intervention on outcome and rehabilitation in this patient group., (© The Author(s) 2019. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The Non-Union Scoring System (NUSS) aims to classify non-unions according to their severity and relate them to four treatment categories. The main purpose of this study was to evaluate the reliability of the NUSS. In addition we assessed its clinical validity., Methods: Forty-four Patients with a tibia non-union between 2005 and 2015 were included in this study. Data from all included patients were scored independently by three observers according to the NUSS criteria. The interobserver agreement was evaluated using the intraclass correlation coefficient (ICC). The interobserver agreement of the Weber-Cech system was assessed using Fleiss' kappa. Finally, the clinical validity of the NUSS was analysed by comparing outcomes of the actual treatment groups to the proposed treatment groups following from the NUSS scores., Results: Forty-four patients were included. The comparison of NUSS scores between observers showed substantial agreement [ICC; 0.78 (0.67-0.86)]. The comparison of the Weber-Cech classification between observers showed only fair agreement [Fleiss κ; 0.30 (0.17-0.42)]. The χ 2 test for the treatment groups according to the NUSS and the treatments at index procedure showed an independent relation (χ 2  = 5.794, 6 degrees of freedom, p: 0.447). In contrast, the proposed treatment strategy corresponds well to the definitive treatment (χ 2  = 29.963, 9 degrees of freedom, p < 0.001)., Conclusion: We conclude that the NUSS is both a reliable and valid system to classify non-unions.

Background: Nonoperative management for blunt splenic injury is the preferred treatment. To improve the outcome of selective nonoperative therapy, the current challenge is to identify factors that predict failure. Little is known about the impact of concomitant injury on outcome. Our study has two goals. First, to determine whether concomitant injury affects the safety of selective nonoperative treatment. Secondly we aimed to identify factors that can predict failure., Methods: From our prospective trauma registry we selected all nonoperatively treated adult patients with blunt splenic trauma admitted between 01.01.2000 and 12.21.2013. All concurrent injuries with an AIS ≥ 2 were scored. We grouped and compared patients sustaining solitary splenic injuries and patients with concomitant injuries. To identify specific factors that predict failure we used a multivariable regression analysis., Results: A total of 79 patients were included. Failure of nonoperative therapy ( n  = 11) and complications only occurred in patients sustaining concomitant injury. Furthermore, ICU-stay as well as hospitalization time were significantly prolonged in the presence of associated injury (4 versus 13 days, p  < 0.05). Mortality was not seen. Multivariable analysis revealed the presence of a femur fracture and higher age as predictors of failure., Conclusions: Nonoperative management for hemodynamically normal patients with blunt splenic injury is feasible and safe, even in the presence of concurrent (non-hollow organ) injuries or a contrast blush on CT. However, associated injuries are related to prolonged intensive care unit- and hospital stay, complications, and failure of nonoperative management. Specifically, higher age and the presence of a femur fracture are predictors of failure., Competing Interests: We obtained ethical approval from the local Medical Ethical Committee (University Hospital Utrecht). General consent was obtained according to the institutional guidelines.General consent was obtained according to the institutional guidelines.The authors’ declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: The relation between timing of weight bearing after a fracture and the healing outcome is yet to be established, thereby limiting the implementation of a possibly beneficial effect for our patients. The current study was undertaken to determine the effect of timing of weight bearing after a surgically treated tibial shaft fracture., Materials and Methods: Surgically treated diaphyseal tibial fractures were retrospectively studied between 2007 and 2015. The timing of initial weight bearing (IWB) was analysed as a predictor for impaired healing in a multivariate regression., Results: Totally, 166 diaphyseal tibial fractures were included, 86 cases with impaired healing and 80 with normal healing. The mean age was 38.7 years (range 16-89). The mean time until IWB was significantly shorter in the normal fracture healing group (2.6 vs 7.4 weeks, p < 0.001). Correlation analysis yielded four possible confounders: infection requiring surgical intervention, fracture type, fasciotomy and open fractures. Logistic regression identified IWB as an independent predictor for impaired healing with an odds ratio of 1.13 per week delay (95% CI 1.03-1.25)., Conclusions: Delay in initial weight bearing is independently associated with impaired fracture healing in surgically treated tibial shaft fractures. Unlike other factors such as fracture type or soft tissue condition, early resumption of weight bearing can be influenced by the treating physician and this factor therefore has a direct clinical relevance. This study indicates that early resumption of weight bearing should be the treatment goal in fracture fixation., Level of Evidence: 3b.

In this paper, we investigate the use of fat tissue as a communication channel between in-body, implanted devices at R-band frequencies (1.7⁻2.6 GHz). The proposed fat channel is based on an anatomical model of the human body. We propose a novel probe that is optimized to efficiently radiate the R-band frequencies into the fat tissue. We use our probe to evaluate the path loss of the fat channel by studying the channel transmission coefficient over the R-band frequencies. We conduct extensive simulation studies and validate our results by experimentation on phantom and ex-vivo porcine tissue, with good agreement between simulations and experiments. We demonstrate a performance comparison between the fat channel and similar waveguide structures. Our characterization of the fat channel reveals propagation path loss of ∼0.7 dB and ∼1.9 dB per cm for phantom and ex-vivo porcine tissue, respectively. These results demonstrate that fat tissue can be used as a communication channel for high data rate intra-body networks.

A controlled local inflammatory response is essential for adequate fracture healing. However, the current literature suggests that local and systemic hyper-inflammatory conditions after major trauma induce increased influx of neutrophils into the fracture hematoma (FH) and impair bone regeneration. Inhibiting neutrophil chemotaxis towards the FH without compromising the hosts' defense may therefore be a target of future therapies that prevent impairment of fracture healing after major trauma. We investigated whether chemotaxis of neutrophils towards the FH could be studied in vitro. Moreover, we determined whether chemotaxis of neutrophils towards the FH was mediated by the CXCR1, CXCR2, FPR, and C5aR receptors. Human FHs were isolated during an open reduction internal fixation (ORIF) procedure within 3 days after trauma and spun down to obtain the fracture hematoma serum. Neutrophil migration towards the FH was studied using Ibidi™ Chemotaxis 3D μ-Slides and image analysis of individual neutrophil tracks was performed. Our study showed that the human FH induces significant neutrophil chemotaxis, which was not affected by blocking CXCR1 and CXCR2. In contrast, neutrophil chemotaxis towards the FH was significantly inhibited by chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS), which blocks FPR and C5aR. Blocking only C5aR with CHIPSΔ1F also significantly inhibited neutrophil chemotaxis towards the FH. Our finding that neutrophil chemotaxis towards the human FH can be blocked in vitro using CHIPS may aid the development of therapies that prevent impairment of fracture healing after major trauma.

Although controlled local inflammation is essential for adequate bone regeneration, several studies have shown that hyper-inflammatory conditions after major trauma are associated with impaired fracture healing. These hyper-inflammatory conditions include the trauma-induced systemic inflammatory response to major injury, open fractures, and significant injury to the surrounding soft tissues. The current literature suggests that increased or prolonged influx of neutrophils into the fracture hematoma may mediate impairment of bone regeneration after hyper-inflammatory conditions. The underlying mechanism remains unclear. We hypothesize that high neutrophil numbers inhibit synthesis of mineralized extracellular matrix (ECM) by bone marrow stromal cells (BMSCs). We therefore studied the effect of increasing concentrations of neutrophils on ECM synthesis by human BMSCs in vitro . Moreover, we determined how high neutrophil concentrations affect BMSC cell counts, as well as BMSC osteogenic activity determined by alkaline phosphatase (ALP) expression and ALP activity. Co-culture of BMSCs with neutrophils induced a 52% decrease in BMSC cell count ( p  < 0.01), a 64% decrease in the percentage of ALP+ cells ( p  < 0.001), a 28% decrease in total ALP activity ( p  < 0.01), and a significant decrease in the amount of mineralized ECM [38% decrease after 4 weeks ( p  < 0.05)]. Co-cultures with peripheral blood mononuclear cells and neutrophils within transwells did not induce a significant decrease in ALP activity. In conclusion, our data shows that a decreased amount of mineralized ECM became synthesized by BMSCs, when they were co-cultured with high neutrophil concentrations. Moreover, high neutrophil concentrations induced a decrease in BMSC cell counts and decreased ALP activity. Clarifying the underlying mechanism may contribute to development of therapies that augment bone regeneration or prevent impaired fracture healing after hyper-inflammatory conditions.

Background: Proximal femur fractures are a common injury after low energy trauma in the elderly. Most rehabilitation programs are based on restoring mobility and early resumption of weight-bearing. However, therapy compliance is low in patients following lower extremity fractures. Moreover, little is known about the relevance of gait parameters and how to steer the rehabilitation after proximal femur fractures in the elderly. Therefore, the aim of this prospective, randomized controlled trial is to gain insight in gait parameters and evaluate if real-time visual biofeedback can improve therapy compliance after proximal femur fractures in the elderly., Methods: This is a two-arm, parallel-design, prospective, randomized controlled trial. Inclusion criteria are age ≥ 60 years, a proximal femur fracture following low energy trauma, and unrestricted-weight bearing. Exclusion criteria are cognitive impairment and limited mobility before trauma. Participants are randomized into either the control group, which receives care as usual, or the intervention group, which receives real-time visual biofeedback about weight-bearing during gait in addition to care as usual. Spatiotemporal gait parameters will be measured in 94 participants per group during a 30-m walk with an ambulatory biofeedback system (SensiStep). The progress of rehabilitation will be evaluated by the primary outcome parameters maximum peak load and step duration in relation to the discharge date. Secondary outcome parameters include other spatiotemporal gait parameters in relation to discharge date. Furthermore, the gait parameters will be related to three validated clinical tests: Elderly Mobility Scale; Functional Ambulation Categories; and Visual Analogue Scale. The primary hypothesis is that participants in the intervention group will show improved and faster rehabilitation compared to the control group., Discussion: The first aim of this multicenter trial is to investigate the normal gait patterns after proximal femur fractures in the elderly. The use of biofeedback systems during rehabilitation after proximal femur fractures in the elderly is promising; therefore, the second aim is to investigate the effect of real-time visual biofeedback on gait after proximal femur fractures in the elderly. This could lead to improved outcome. In addition, analysis of the population may indicate characteristics of subgroups that benefit from feedback, making a differentiated approach in rehabilitation strategy possible., Trial Registration: TrialRegister.nl, NTR6794 . Registered on 31 October 2017.

Background: Previous studies have shown limited therapy compliance in weight-bearing in patients following total hip arthroplasty., Research Question: The purpose of this pilot RCT is to determine the immediate and late effect of real-time, visual biofeedback on weight-bearing during rehabilitation after THA in elderly., Methods: 24 participants who underwent THA were randomized to either the control or the intervention group. The intervention group received real-time, visual biofeedback on weight-bearing during training with the physical therapist during hospitalization and at twelve weeks follow up., Results: Without biofeedback, therapy compliance was limited. Significant improvement in peak load was found in the intervention group in the early postoperative phase. In contrast to the control group, the peak load at twelve weeks was significantly higher in the intervention group compared to the pre-operative peak load, indicating a lasting effect of early biofeedback. Other gait parameters were not significantly different in the early postoperative phase. In the intervention group a longer walking distance was observed and the use of walking aids was reduced at twelve weeks., Significance: Biofeedback systems could be promising to improve outcomes and reduce costs in future rehabilitation programs after THA., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Objectives: Intermittent vital signs measurements are the current standard on hospital wards, typically recorded once every 8 hours. Early signs of deterioration may therefore be missed. Recent innovations have resulted in 'wearable' sensors, which may capture patient deterioration at an earlier stage. The objective of this study was to determine whether a wireless 'patch' sensor is able to reliably measure respiratory and heart rate continuously in high-risk surgical patients. The secondary objective was to explore the potential of the wireless sensor to serve as a safety monitor., Design: In an observational methods comparisons study, patients were measured with both the wireless sensor and bedside routine standard for at least 24 hours., Setting: University teaching hospital, single centre., Participants: Twenty-five postoperative surgical patients admitted to a step-down unit., Outcome Measures: Primary outcome measures were limits of agreement and bias of heart rate and respiratory rate. Secondary outcome measures were sensor reliability, defined as time until first occurrence of data loss., Results: 1568 hours of vital signs data were analysed. Bias and 95% limits of agreement for heart rate were -1.1 (-8.8 to 6.5) beats per minute. For respiration rate, bias was -2.3 breaths per minute with wide limits of agreement (-15.8 to 11.2 breaths per minute). Median filtering over a 15 min period improved limits of agreement of both respiration and heart rate. 63% of the measurements were performed without data loss greater than 2 min. Overall data loss was limited (6% of time)., Conclusions: The wireless sensor is capable of accurately measuring heart rate, but accuracy for respiratory rate was outside acceptable limits. Remote monitoring has the potential to contribute to early recognition of physiological decline in high-risk patients. Future studies should focus on the ability to detect patient deterioration on low care environments and at home after discharge., Competing Interests: Competing interests: At the time of the study, MJMB was part-time employee of FocusCura (Health IT company, Driebergen-Zeist, The Netherlands) and DAJD is founder and CEO of FocusCura. No funding from FocusCura was obtained. To ensure independent analysis, the wearable sensor (HealthPatch MD) was purchased from VitalConnect, the manufacturer of the HealthPatch MD. VitalConnect neither had insight nor influence on the analysis of the data or drafting of the manuscript., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

In recent research, microwave sensors have been used to follow up the recovery of lower extremity trauma patients. This is done mainly by monitoring the changes of dielectric properties of lower limb tissues such as skin, fat, muscle, and bone. As part of the characterization of the microwave sensor, it is crucial to assess the signal penetration in in vivo tissues. This work presents a new approach for investigating the penetration depth of planar microwave sensors based on the Split-Ring Resonator in the in vivo context of the femoral area. This approach is based on the optimization of a 3D simulation model using the platform of CST Microwave Studio and consisting of a sensor of the considered type and a multilayered material representing the femoral area. The geometry of the layered material is built based on information from ultrasound images and includes mainly the thicknesses of skin, fat, and muscle tissues. The optimization target is the measured S 11 parameters at the sensor connector and the fitting parameters are the permittivity of each layer of the material. Four positions in the femoral area (two at distal and two at thigh) in four volunteers are considered for the in vivo study. The penetration depths are finally calculated with the help of the electric field distribution in simulations of the optimized model for each one of the 16 considered positions. The numerical results show that positions at the thigh contribute the highest penetration values of up to 17.5 mm. This finding has a high significance in planning in vitro penetration depth measurements and other tests that are going to be performed in the future., Competing Interests: The authors declare no conflict of interest.

Background: The standard aftercare treatment in surgically treated trauma patients with fractures around or in a joint, known as (peri)- or intra-articular fractures of the lower extremities, is either non-weight bearing or partial weight bearing. We have developed an early permissive weight bearing post-surgery rehabilitation protocol in surgically treated patients with fractures of the lower extremities. In this proposal we want to compare our early permissive weight bearing protocol to the existing current non-weight bearing guidelines in a prospective comparative cohort study., Methods/design: The study is a prospective multicenter comparative cohort study in which two rehabilitation aftercare treatments will be contrasted, i.e. permissive weight bearing and non-weight bearing according to the AO-guideline. The study population consists of patients with a surgically treated fracture of the pelvis/acetabulum or a surgically treated (peri)- or intra-articular fracture of the lower extremities. The inclusion period is 12 months. The duration of follow up is 6 months, with measurements taken at baseline, 2,6,12 and 26 weeks post-surgery., Primary Outcome Measure: ADL with Lower Extremity Functional Scale. Outcome variables for compliance, as measured with an insole pressure measurement system, encompass peak load and step duration., Discussion: This study will investigate the (cost-) effectiveness of a permissive weight bearing aftercare protocol. The results will provide evidence whether a permissive weight bearing protocol is more effective than the current non-weight bearing protocol., Trial Registration: The study is registered in the Dutch Trial Register ( NTR6077 ). Date of registration: 01-09-2016.

Background: Individuals with lower extremity fractures are often instructed on how much weight to bear on the affected extremity. Previous studies have shown limited therapy compliance in weight bearing during rehabilitation. In this study we investigated the effect of real-time visual biofeedback on weight bearing in individuals with lower extremity fractures in two conditions: full weight bearing and touch-down weight bearing., Methods: 11 participants with full weight bearing and 12 participants with touch-down weight bearing after lower extremity fractures have been measured with an ambulatory biofeedback system. The participants first walked 15m and the biofeedback system was only used to register the weight bearing. The same protocol was then repeated with real-time visual feedback during weight bearing. The participants could thereby adapt their loading to the desired level and improve therapy compliance., Results: In participants with full weight bearing, real-time visual biofeedback resulted in a significant increase in loading from 50.9±7.51% bodyweight (BW) without feedback to 63.2±6.74%BW with feedback (P=0.0016). In participants with touch-down weight bearing, the exerted lower extremity load decreased from 16.7±9.77kg without feedback to 10.27±4.56kg with feedback (P=0.0718). More important, the variance between individual steps significantly decreased after feedback (P=0.018)., Conclusions: Ambulatory monitoring weight bearing after lower extremity fractures showed that therapy compliance is low, both in full and touch-down weight bearing. Real-time visual biofeedback resulted in significantly higher peak loads in full weight bearing and increased accuracy of individual steps in touch-down weight bearing. Real-time visual biofeedback therefore results in improved therapy compliance after lower extremity fractures., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Selective non-operative management (NOM) for the treatment of blunt splenic trauma is safe. Currently, the feasibility of selective NOM for penetrating splenic injury (PSI) is unclear. Unfortunately, little is known about the success rate of spleen-preserving surgical procedures. The aim of this study was to investigate the outcome of selective NOM for penetrating splenic injuries., Methods: A dual-centre study is performed in two level-one trauma centres. All identified patients treated for PSI were identified. Patients were grouped based on the treatment they received. Group one consisted of splenectomised patients, the second group included patients treated by a spleen-preserving surgical intervention, and group three included those patients who were treated by NOM., Results: A total of 118 patients with a median age of 27 and a median ISS of 25 (interquartile range (IQR) 16-34) were included. Ninety-six patients required operative intervention, of whom 45 underwent a total splenectomy and 51 underwent spleen-preserving surgical procedures. Furthermore, 22 patients (12 stab wounds and 10 gunshot wounds) were treated by NOM. There were several anticipated significant differences in the baseline encountered. The median hospitalization time was 8 (5-12) days, with no significant differences between the groups. The splenectomy group had significantly more intensive care unit (ICU) days (2(0-6) vs. 0(0-1)) and ventilation days (1(0-3) vs. 0(0-0)) compared to the NOM group. Mortality was only noted in the splenectomy group., Conclusions: Spleen-preserving surgical therapy for PSI is a feasible treatment modality and is not associated with increased mortality. Moreover, a select group of patients can be treated without any surgical intervention at all.

Fat embolism is common in patients with major fractures, but leads to devastating consequences, named fat embolism syndrome (FES) in some. Despite advances in treatment strategies regarding the timing of definitive fixation of major fractures, FES still occurs in patients. In this overview, current literature is reviewed and optimal treatment strategies for patients with multiple traumatic injuries, including major fractures, are discussed. Considering the multifactorial etiology of FES, including mechanical and biochemical pathways, FES cannot be prevented in all patients. However, screening for symptoms of FES should be standard in the pre-operative work-up of these patients, prior to definitive fixation of major fractures., (Copyright © 2017. Published by Elsevier Ltd.)

Although bone defects after trauma appear in different locations and forms, many clinicians have adopted a single strategy to deal with any defect. In this overview, a distinction is made between metaphyseal, or cancellous defects, and diaphyseal, or cortical defects. The treatment goals and background of these two types of defects are discussed in order to describe the difference in strategy and hence the difference in treatment method., (Copyright © 2017. Published by Elsevier Ltd.)

The human body can act as a medium for the transmission of electromagnetic waves in the wireless body sensor networks context. However, there are transmission losses in biological tissues due to the presence of water and salts. This Letter focuses on lateral intra-body microwave communication through different biological tissue layers and demonstrates the effect of the tissue thicknesses by comparing signal coupling in the channel. For this work, the authors utilise the R-band frequencies since it overlaps the industrial, scientific and medical radio (ISM) band. The channel model in human tissues is proposed based on electromagnetic simulations, validated using equivalent phantom and ex-vivo measurements. The phantom and ex-vivo measurements are compared with simulation modelling. The results show that electromagnetic communication is feasible in the adipose tissue layer with a low attenuation of ∼2 dB per 20 mm for phantom measurements and 4 dB per 20 mm for ex-vivo measurements at 2 GHz. Since the dielectric losses of human adipose tissues are almost half of ex-vivo tissue, an attenuation of around 3 dB per 20 mm is expected. The results show that human adipose tissue can be used as an intra-body communication channel.