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01 februari 2023, Item does not contain fulltext, PURPOSE: This study aims to investigate the symmetry of the left and right tibial plateau in young healthy individuals to determine whether left-right mirroring can be reliably used to optimize preoperative 3D virtual planning for patients with tibial plateau fractures. METHODS: One hundred healthy subjects, without previous knee surgery, severe knee trauma, or signs of osteoarthritis were included for a previous dynamic imaging study of the knee. The subjects underwent a CT scan, scanning the left and right knee with a slice thickness of 0.8 mm. 3D surface models of the femur, patella, and tibia were created using a convolutional neural network. The 3D models of the left and right tibias were exported to MATLAB © and the tibias were mirrored. The mirrored tibias were superimposed on the contralateral tibia using a coherent point drift surface matching algorithm. Correspondence points on both surfaces were established, the mean root squared distance was calculated and visualized in a boxplot and heatmaps. RESULTS: The overall mean difference between correspondence points on the left and right tibial plateau is 0.6276 ± 0.0343 mm. The greatest differences between correspondence points were seen around two specific surfaces on the outside of the tibial plateau; where the distal tibia was cut 15 mm below the tibial plateau and around the tibiofibular joint. CONCLUSIONS: The differences between the left and right tibial plateau are small and therefore, we can be confident that the mirrored contralateral, unfractured, tibial plateau can be used as a template for 3D virtual preoperative planning for young patients without previous damage to the knee.

Item does not contain fulltext, Background: Three-Dimensional Virtual Planning (3DVP) has been proven to be effective for limiting intra-articular screw penetration and improving the quality of reduction for numerous fractures. However, the value of 3DVP for patients with tibial plateau fractures has yet to be determined. Purposes: The research question of this study is: Can Computed Tomography Micromotion Analysis (CTMA) provide a reliable quantification of the difference between 3DVP and the postoperative reduction on CT for tibial plateau fractures? Methods: Nine consecutive adult patients who received surgical treatment for a tibial plateau fracture and received pre- and postoperative CT scans were included from a level I trauma center in the Netherlands. The preoperative CT scans of the patients were uploaded in a 3DVP software. In this software, fracture fragments were reduced and the reduction was saved as a 3D file (STL). The quality of the reduction from the 3DVP software was compared with the postoperative results using CT Micromotion Analysis (CTMA). In this analysis, the translation of the largest intra-articular fragment was calculated by aligning the postoperative CT with the 3DVP. Coordinates and measurement points were defined in the X, Y, and Z axes. The combined values of X and Y were used to define the intra-articular gap. The Z-axis was defined as the line from cranial to caudal and was used to define intra-articular step-off. Results: The intra-articular step-off was 2.4 mm (Range 0.5-4.6). Moreover, the mean translation of the X-axis and Y-axis, which was defined as the intra-articular gap, was 4.2 mm (Range 0.6-10.7). Conclusions: 3DVP provides excellent insight into the fracture and its fragments. Utilizing the largest intra-articular fragment, it is feasible to quantify the difference between 3DVP and a postoperative CT using CTMA. A prospective study to further analyze the use of 3DVP in terms of intra-articular reduction and surgical and patient-related outcomes has been

01 juni 2023, Item does not contain fulltext, PURPOSE: Isolated acetabular fractures can occur as a result of a high energy impact on the hip joint. Surgery is required for most patients with an isolated acetabular fracture in order to alleviate pain, restore joint stability, and regain hip function. This study was conducted in order to examine the course of hip function in patients after surgical treatment of an isolated traumatic acetabular fracture. MATERIALS AND METHODS: This prospective series of consecutive cases included patients who underwent surgery for treatment of an isolated acetabular fracture in a European level one trauma center between 2016 and 2020. Patients with relevant concomitant injuries were excluded. Scoring of hip function was performed by a trauma surgeon using the Modified Merle d'Aubigné and Postel score at six-week, 12-week, six-month, and one-year follow-up. Scores between 3-11 indicate poor, 12-14 fair, 15-17 good, and 18 excellent hip function. RESULTS: Data on 46 patients were included. The mean score for hip function was 10 (95% confidence interval [CI] 7.09-12.91) at six-week follow-up (23 patients), 13.75 (95% CI 10.74-16.76) at 12-week follow-up (28 patients), 16 (95% CI 13.40-18.60) at six-month follow-up (25 patients), and 15.50 (95% CI 10.55-20.45) at one-year follow-up (17 patients). After one-year follow-up, the scores reflected an excellent outcome in 11 patients, good in five patients, and poor in one patient. CONCLUSION: This study reports on the course of hip function in patients who have undergone surgical treatment for isolated acetabular fractures. Restoration of excellent hip function takes six months.

01 februari 2023, Item does not contain fulltext, PURPOSE: This study aims to investigate the symmetry of the left and right tibial plateau in young healthy individuals to determine whether left-right mirroring can be reliably used to optimize preoperative 3D virtual planning for patients with tibial plateau fractures. METHODS: One hundred healthy subjects, without previous knee surgery, severe knee trauma, or signs of osteoarthritis were included for a previous dynamic imaging study of the knee. The subjects underwent a CT scan, scanning the left and right knee with a slice thickness of 0.8 mm. 3D surface models of the femur, patella, and tibia were created using a convolutional neural network. The 3D models of the left and right tibias were exported to MATLAB © and the tibias were mirrored. The mirrored tibias were superimposed on the contralateral tibia using a coherent point drift surface matching algorithm. Correspondence points on both surfaces were established, the mean root squared distance was calculated and visualized in a boxplot and heatmaps. RESULTS: The overall mean difference between correspondence points on the left and right tibial plateau is 0.6276 ± 0.0343 mm. The greatest differences between correspondence points were seen around two specific surfaces on the outside of the tibial plateau; where the distal tibia was cut 15 mm below the tibial plateau and around the tibiofibular joint. CONCLUSIONS: The differences between the left and right tibial plateau are small and therefore, we can be confident that the mirrored contralateral, unfractured, tibial plateau can be used as a template for 3D virtual preoperative planning for young patients without previous damage to the knee.

Contains fulltext : 296164.pdf (Publisher’s version ) (Open Access), AIMS: The aim of this study was to investigate the association between fracture displacement and survivorship of the native hip joint without conversion to a total hip arthroplasty (THA), and to determine predictors for conversion to THA in patients treated nonoperatively for acetabular fractures. METHODS: A multicentre cross-sectional study was performed in 170 patients who were treated nonoperatively for an acetabular fracture in three level 1 trauma centres. Using the post-injury diagnostic CT scan, the maximum gap and step-off values in the weightbearing dome were digitally measured by two trauma surgeons. Native hip survival was reported using Kaplan-Meier curves. Predictors for conversion to THA were determined using Cox regression analysis. RESULTS: Of 170 patients, 22 (13%) subsequently received a THA. Native hip survival in patients with a step-off ≤ 2 mm, > 2 to 4 mm, or > 4 mm differed at five-year follow-up (respectively: 94% vs 70% vs 74%). Native hip survival in patients with a gap ≤ 2 mm, > 2 to 4 mm, or > 4 mm differed at five-year follow-up (respectively: 100% vs 84% vs 78%). Step-off displacement > 2 mm (> 2 to 4 mm hazard ratio (HR) 4.9, > 4 mm HR 5.6) and age > 60 years (HR 2.9) were independent predictors for conversion to THA at follow-up. CONCLUSION: Patients with minimally displaced acetabular fractures who opt for nonoperative fracture treatment may be informed that fracture displacement (e.g. gap and step-off) up to 2 mm, as measured on CT images, results in limited risk on conversion to THA. Step-off ≥ 2 mm and age > 60 years are predictors for conversion to THA and can be helpful in the shared decision-making process.

Item does not contain fulltext, The distal radius fracture is a common fracture with a prevalence of 17% on the emergency departments. The conservative treatment of distal radius fractures usually consists of three to six weeks of plaster immobilization. Several studies show that one week of plaster immobilization is safe for non- or minimally displaced distal radius fractures that do not need reduction. A shorter period of immobilization may lead to a better functional outcome, faster reintegration and participation in daily activities. Due to upcoming innovations such as three-dimensional printed splints for distal radius fractures, a patient specific splint can be produced which may offer more comfort. Furthermore, these three-dimensional printed splints are expected to be more environmental friendly in comparison with traditional plaster casts.

Background: The COVID-19 pandemic might affect mental health. Data from population-representative panel surveys with multiple waves including pre-COVID data investigating risk and protective factors are still rare. Methods: In a stratified random sample of the German household population (n=6,684), we conducted survey-weighted multiple linear regressions to determine the association of various psychological risk and protective factors assessed between 2015 and 2020 with changes in psychological distress (PD; measured via PHQ-4) from pre-pandemic (average of 2016 and 2019) to peri-pandemic (both 2020 and 2021) time points. Control analyses on PD change between two pre-pandemic time points (2016 and 2019) were conducted. Regularized regressions were computed to inform on which factors were statistically most influential in the multicollinear setting. Results: PHQ-4 scores in 2020 (M=2.45) and 2021 (M=2.21) were elevated compared to 2019 (M=1.79). Several risk factors (catastrophizing, neuroticism, asking for instrumental support) and protective factors (perceived stress recovery, positive reappraisal, optimism) were identified for the peri-pandemic outcomes. Control analyses revealed that in pre-pandemic times, neuroticism and optimism were predominantly related to PD changes. Regularized regression mostly confirmed the results and highlighted perceived stress recovery as most consistent influential protective factor across peri-pandemic outcomes. Conclusions: We identified several psychological risk and protective factors related to PD outcomes during the COVID-19 pandemic. Comparison to pre-pandemic data stress the relevance of longitudinal assessments to potentially reconcile contradictory findings. Implications and suggestions for targeted prevention and intervention programs during highly stressful times such as pandemics are discussed.

Background: Recent trauma guidelines recommend non-operative management for grade III splenic injury without contrast extravasation on computed tomography. Nevertheless, such recommendations rely on low-quality evidence, and practice variation characterizes clinical management for this type of injury. We aimed to identify the role of eleven selected clinical factors influencing the management of grade III splenic injury without contrast extravasation by expert consensus and a modified Delphi approach. Methods: A questionnaire was developed with the endorsement of the World Society of Emergency Surgery (WSES). This was delivered and answered live by acute care surgeons attending the 6th WSES congress in Nijmegen in 2019. A dedicated mobile phone application was utilized to collect the answers. All answers were evaluated for areas of discrepancy with an 80% threshold for consensus between respondents. Results: Three factors generated discrepancy in opinion for managing this pattern of injury: the patients' injury severity, the presence of a bleeding diathesis, and an associated intra-abdominal injury. Agreement was obtained for the other eight factors. Conclusion: Researchers should focus their efforts on the identified area of discrepancy. Clinicians should use additional care in the presence of the three factors for which discordant opinions were found.

Contains fulltext : 248974.pdf (Publisher’s version ) (Open Access)

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Contains fulltext : 248778.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, Currently, steel implants are used for osteosynthesis of (comminuted) fractures and intra-articular bone defects. These osteosyntheses can sometimes be complicated procedures and can have several drawbacks including stress shielding of the bone. A bone glue might be a safe and effective alternative to current materials. Despite numerous animal studies on bone adhesives, no such material is clinically applied yet. We have conducted a systematic review to summarize the evidence in experimental animal models used in research on bone adhesive materials for trauma and orthopedic surgery. Additionally, we analysed the efficacy of the different bone adhesives for different experimental designs. A heterogeneity in experimental parameters including animal species, defect types, and control measurements resulted in a wide variety in experimental models. In addition, no standard outcome measurements could be identified. Meta-analysis on bone regeneration between adhesive treatment and nonadhesive treatment showed a high heterogeneity and no statistically significant overall effect (M: -0.71, 95% confidence interval [CI]: -1.63-0.21, p = 0.13). Besides, currently there is not enough evidence to draw conclusions based on the effectiveness of the individual types of adhesives or experimental models. A positive statistically significant effect was found for the adhesive treatment in comparison with conventional osteosynthesis materials (M: 2.49, 95% CI: 1.20-3.79, p = 0.0002). To enhance progression in bone adhesive research and provide valuable evidence for clinical application, more standard experimental parameters and a higher reporting quality in animal studies are needed. Statement of Clinical Significance: Current materials restoring anatomical alignments of bones have several drawbacks. A (biodegradable) adhesive for fixating bone defects can be a treatment breakthrough. Although numerous bone adhesives have been researched, most seemed to fail at the preclinical stage. An

Background: The COVID-19 pandemic might affect mental health. Data from population-representative panel surveys with multiple waves including pre-COVID data investigating risk and protective factors are still rare. Methods: In a stratified random sample of the German household population (n=6,684), we conducted survey-weighted multiple linear regressions to determine the association of various psychological risk and protective factors assessed between 2015 and 2020 with changes in psychological distress (PD; measured via PHQ-4) from pre-pandemic (average of 2016 and 2019) to peri-pandemic (both 2020 and 2021) time points. Control analyses on PD change between two pre-pandemic time points (2016 and 2019) were conducted. Regularized regressions were computed to inform on which factors were statistically most influential in the multicollinear setting. Results: PHQ-4 scores in 2020 (M=2.45) and 2021 (M=2.21) were elevated compared to 2019 (M=1.79). Several risk factors (catastrophizing, neuroticism, asking for instrumental support) and protective factors (perceived stress recovery, positive reappraisal, optimism) were identified for the peri-pandemic outcomes. Control analyses revealed that in pre-pandemic times, neuroticism and optimism were predominantly related to PD changes. Regularized regression mostly confirmed the results and highlighted perceived stress recovery as most consistent influential protective factor across peri-pandemic outcomes. Conclusions: We identified several psychological risk and protective factors related to PD outcomes during the COVID-19 pandemic. Comparison to pre-pandemic data stress the relevance of longitudinal assessments to potentially reconcile contradictory findings. Implications and suggestions for targeted prevention and intervention programs during highly stressful times such as pandemics are discussed.

Contains fulltext : 250473.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 284085.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 284415.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 250067.pdf (Publisher’s version ) (Open Access), Currently, steel implants are used for osteosynthesis of (comminuted) fractures and intra-articular bone defects. These osteosyntheses can sometimes be complicated procedures and can have several drawbacks including stress shielding of the bone. A bone glue might be a safe and effective alternative to current materials. Despite numerous animal studies on bone adhesives, no such material is clinically applied yet. We have conducted a systematic review to summarize the evidence in experimental animal models used in research on bone adhesive materials for trauma and orthopedic surgery. Additionally, we analysed the efficacy of the different bone adhesives for different experimental designs. A heterogeneity in experimental parameters including animal species, defect types, and control measurements resulted in a wide variety in experimental models. In addition, no standard outcome measurements could be identified. Meta-analysis on bone regeneration between adhesive treatment and nonadhesive treatment showed a high heterogeneity and no statistically significant overall effect (M: -0.71, 95% confidence interval [CI]: -1.63-0.21, p = 0.13). Besides, currently there is not enough evidence to draw conclusions based on the effectiveness of the individual types of adhesives or experimental models. A positive statistically significant effect was found for the adhesive treatment in comparison with conventional osteosynthesis materials (M: 2.49, 95% CI: 1.20-3.79, p = 0.0002). To enhance progression in bone adhesive research and provide valuable evidence for clinical application, more standard experimental parameters and a higher reporting quality in animal studies are needed. Statement of Clinical Significance: Current materials restoring anatomical alignments of bones have several drawbacks. A (biodegradable) adhesive for fixating bone defects can be a treatment breakthrough. Although numerous bone adhesives have been researched, most seemed to fail at the preclinical stage. An

Contains fulltext : 284415.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 250067.pdf (Publisher’s version ) (Open Access), Currently, steel implants are used for osteosynthesis of (comminuted) fractures and intra-articular bone defects. These osteosyntheses can sometimes be complicated procedures and can have several drawbacks including stress shielding of the bone. A bone glue might be a safe and effective alternative to current materials. Despite numerous animal studies on bone adhesives, no such material is clinically applied yet. We have conducted a systematic review to summarize the evidence in experimental animal models used in research on bone adhesive materials for trauma and orthopedic surgery. Additionally, we analysed the efficacy of the different bone adhesives for different experimental designs. A heterogeneity in experimental parameters including animal species, defect types, and control measurements resulted in a wide variety in experimental models. In addition, no standard outcome measurements could be identified. Meta-analysis on bone regeneration between adhesive treatment and nonadhesive treatment showed a high heterogeneity and no statistically significant overall effect (M: -0.71, 95% confidence interval [CI]: -1.63-0.21, p = 0.13). Besides, currently there is not enough evidence to draw conclusions based on the effectiveness of the individual types of adhesives or experimental models. A positive statistically significant effect was found for the adhesive treatment in comparison with conventional osteosynthesis materials (M: 2.49, 95% CI: 1.20-3.79, p = 0.0002). To enhance progression in bone adhesive research and provide valuable evidence for clinical application, more standard experimental parameters and a higher reporting quality in animal studies are needed. Statement of Clinical Significance: Current materials restoring anatomical alignments of bones have several drawbacks. A (biodegradable) adhesive for fixating bone defects can be a treatment breakthrough. Although numerous bone adhesives have been researched, most seemed to fail at the preclinical stage. An

Contains fulltext : 284085.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 244087.pdf (Publisher’s version ) (Open Access), It has recently been shown that acute stress affects the allocation of neural resources between large-scale brain networks, and the balance between the executive control network and the salience network in particular. Maladaptation of this dynamic resource reallocation process is thought to play a major role in stress-related psychopathology, suggesting that stress resilience may be determined by the retained ability to adaptively reallocate neural resources between these two networks. Actively training this ability could hence be a potentially promising way to increase resilience in individuals at risk for developing stress-related symptomatology. Using real-time functional Magnetic Resonance Imaging, the current study investigated whether individuals can learn to self-regulate stress-related large-scale network balance. Participants were engaged in a bidirectional and implicit real-time fMRI neurofeedback paradigm in which they were intermittently provided with a visual representation of the difference signal between the average activation of the salience and executive control networks, and tasked with attempting to self-regulate this signal. Our results show that, given feedback about their performance over three training sessions, participants were able to (1) learn strategies to differentially control the balance between SN and ECN activation on demand, as well as (2) successfully transfer this newly learned skill to a situation where they (a) did not receive any feedback anymore, and (b) were exposed to an acute stressor in form of the prospect of a mild electric stimulation. The current study hence constitutes an important first successful demonstration of neurofeedback training based on stress-related large-scale network balance - a novel approach that has the potential to train control over the central response to stressors in real-life and could build the foundation for future clinical interventions that aim at increasing resilience.

Contains fulltext : 242453.pdf (Publisher’s version ) (Open Access), The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods. https://www.trialregister.nl/trial/7955

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Contains fulltext : 226480.pdf (publisher's version ) (Open Access), BACKGROUND: Recent trauma guidelines recommend non-operative management for grade III splenic injury without contrast extravasation on computed tomography. Nevertheless, such recommendations rely on low-quality evidence, and practice variation characterizes clinical management for this type of injury. We aimed to identify the role of eleven selected clinical factors influencing the management of grade III splenic injury without contrast extravasation by expert consensus and a modified Delphi approach. METHODS: A questionnaire was developed with the endorsement of the World Society of Emergency Surgery (WSES). This was delivered and answered live by acute care surgeons attending the 6(th) WSES congress in Nijmegen in 2019. A dedicated mobile phone application was utilized to collect the answers. All answers were evaluated for areas of discrepancy with an 80% threshold for consensus between respondents. RESULTS: Three factors generated discrepancy in opinion for managing this pattern of injury: the patients' injury severity, the presence of a bleeding diathesis, and an associated intra-abdominal injury. Agreement was obtained for the other eight factors. CONCLUSION: Researchers should focus their efforts on the identified area of discrepancy. Clinicians should use additional care in the presence of the three factors for which discordant opinions were found.

Contains fulltext : 226480.pdf (publisher's version ) (Open Access), BACKGROUND: Recent trauma guidelines recommend non-operative management for grade III splenic injury without contrast extravasation on computed tomography. Nevertheless, such recommendations rely on low-quality evidence, and practice variation characterizes clinical management for this type of injury. We aimed to identify the role of eleven selected clinical factors influencing the management of grade III splenic injury without contrast extravasation by expert consensus and a modified Delphi approach. METHODS: A questionnaire was developed with the endorsement of the World Society of Emergency Surgery (WSES). This was delivered and answered live by acute care surgeons attending the 6(th) WSES congress in Nijmegen in 2019. A dedicated mobile phone application was utilized to collect the answers. All answers were evaluated for areas of discrepancy with an 80% threshold for consensus between respondents. RESULTS: Three factors generated discrepancy in opinion for managing this pattern of injury: the patients' injury severity, the presence of a bleeding diathesis, and an associated intra-abdominal injury. Agreement was obtained for the other eight factors. CONCLUSION: Researchers should focus their efforts on the identified area of discrepancy. Clinicians should use additional care in the presence of the three factors for which discordant opinions were found.

Contains fulltext : 226480.pdf (publisher's version ) (Open Access), BACKGROUND: Recent trauma guidelines recommend non-operative management for grade III splenic injury without contrast extravasation on computed tomography. Nevertheless, such recommendations rely on low-quality evidence, and practice variation characterizes clinical management for this type of injury. We aimed to identify the role of eleven selected clinical factors influencing the management of grade III splenic injury without contrast extravasation by expert consensus and a modified Delphi approach. METHODS: A questionnaire was developed with the endorsement of the World Society of Emergency Surgery (WSES). This was delivered and answered live by acute care surgeons attending the 6(th) WSES congress in Nijmegen in 2019. A dedicated mobile phone application was utilized to collect the answers. All answers were evaluated for areas of discrepancy with an 80% threshold for consensus between respondents. RESULTS: Three factors generated discrepancy in opinion for managing this pattern of injury: the patients' injury severity, the presence of a bleeding diathesis, and an associated intra-abdominal injury. Agreement was obtained for the other eight factors. CONCLUSION: Researchers should focus their efforts on the identified area of discrepancy. Clinicians should use additional care in the presence of the three factors for which discordant opinions were found.

Item does not contain fulltext, AIMS: This study was conducted to determine long-term (5-10 years) health-related quality of life (HRQOL) and ceiling effects in patients with a pelvic ring fracture. PATIENTS AND METHODS: We identified all patients with pelvic ring fractures after high-energy trauma admitted at two level 1 trauma centres in the Netherlands from 2006 to 2011. Patients were asked to complete the Majeed Pelvic Score (MPS), EuroQol-5D (EQ-5D) and Short Musculoskeletal Function Assessment (SMFA) questionnaires. HRQOL analysis used a multiple linear regression model. RESULTS: In total, 136 patients returned the questionnaires. The median follow-up period was 8.7 years. The mean MPS and EQ-5D-VAS scores were 85.1 and 74, respectively. The mean EQ-5D index scores were 0.87, 0.81 and 0.82 in Tile B, A and C patients, respectively. The mean SMFA index was 24. A ceiling effect was observed for 1/3 of the patients. After multiple linear regression analysis, no differences were identified among the various fracture types for each questionnaire, with the exception of 2 subscales of the MPS. CONCLUSION: Patients who suffer pelvic ring fractures generally have good HRQOL outcomes after 5-10 years. No significant differences were found among different fracture types. Long-term follow-up of patients with Tile C fractures is warranted.

Contains fulltext : 208790.pdf (publisher's version ) (Closed access), BACKGROUND: Many muscular dystrophies currently remain untreatable. Recently, dietary ribitol has been suggested as a treatment for cytidine diphosphate (CDP)-l-ribitol pyrophosphorylase A (CRPPA, ISPD), fukutin (FKTN), and fukutin-related protein (FKRP) myopathy, by raising CDP-ribitol concentrations. Thus, to facilitate fast diagnosis, treatment development, and treatment monitoring, sensitive detection of CDP-ribitol is required. METHODS: An LC-MS method was optimized for CDP-ribitol in human and mice cells and tissues. RESULTS: CDP-ribitol, the product of CRPPA, was detected in all major human and mouse tissues. Moreover, CDP-ribitol concentrations were reduced in fibroblasts and skeletal muscle biopsies from patients with CRPPA myopathy, showing that CDP-ribitol could serve as a diagnostic marker to identify patients with CRPPA with severe Walker-Warburg syndrome and mild limb-girdle muscular dystrophy (LGMD) phenotypes. A screen for potentially therapeutic monosaccharides revealed that ribose, in addition to ribitol, restored CDP-ribitol concentrations and the associated O-glycosylation defect of alpha-dystroglycan. As the effect occurred in a mutation-dependent manner, we established a CDP-ribitol blood test to facilitate diagnosis and predict individualized treatment response. Ex vivo incubation of blood cells with ribose or ribitol restored CDP-ribitol concentrations in a patient with CRPPA LGMD. CONCLUSIONS: Sensitive detection of CDP-ribitol with LC-MS allows fast diagnosis of patients with severe and mild CRPPA myopathy. Ribose offers a readily testable dietary therapy for CRPPA myopathy, with possible applicability for patients with FKRP and FKTN myopathy. Evaluation of CDP-ribitol in blood is a promising tool for the evaluation and monitoring of dietary therapies for CRPPA myopathy in a patient-specific manner.

Contains fulltext : 219098.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 206906.pdf (publisher's version ) (Closed access)

Radboud University, 18 april 2019, Promotores : Edwards, M.J.R., Goslings, J.C. Co-promotores : Biert, J., Lansink, K.W.W, Contains fulltext : 201887.pdf (publisher's version ) (Open Access)

Contains fulltext : 198259pos.pdf (postprint version ) (Open Access)

Item does not contain fulltext, AIMS: This study was conducted to determine long-term (5-10 years) health-related quality of life (HRQOL) and ceiling effects in patients with a pelvic ring fracture. PATIENTS AND METHODS: We identified all patients with pelvic ring fractures after high-energy trauma admitted at two level 1 trauma centres in the Netherlands from 2006 to 2011. Patients were asked to complete the Majeed Pelvic Score (MPS), EuroQol-5D (EQ-5D) and Short Musculoskeletal Function Assessment (SMFA) questionnaires. HRQOL analysis used a multiple linear regression model. RESULTS: In total, 136 patients returned the questionnaires. The median follow-up period was 8.7 years. The mean MPS and EQ-5D-VAS scores were 85.1 and 74, respectively. The mean EQ-5D index scores were 0.87, 0.81 and 0.82 in Tile B, A and C patients, respectively. The mean SMFA index was 24. A ceiling effect was observed for 1/3 of the patients. After multiple linear regression analysis, no differences were identified among the various fracture types for each questionnaire, with the exception of 2 subscales of the MPS. CONCLUSION: Patients who suffer pelvic ring fractures generally have good HRQOL outcomes after 5-10 years. No significant differences were found among different fracture types. Long-term follow-up of patients with Tile C fractures is warranted.

Contains fulltext : 208790.pdf (publisher's version ) (Closed access), BACKGROUND: Many muscular dystrophies currently remain untreatable. Recently, dietary ribitol has been suggested as a treatment for cytidine diphosphate (CDP)-l-ribitol pyrophosphorylase A (CRPPA, ISPD), fukutin (FKTN), and fukutin-related protein (FKRP) myopathy, by raising CDP-ribitol concentrations. Thus, to facilitate fast diagnosis, treatment development, and treatment monitoring, sensitive detection of CDP-ribitol is required. METHODS: An LC-MS method was optimized for CDP-ribitol in human and mice cells and tissues. RESULTS: CDP-ribitol, the product of CRPPA, was detected in all major human and mouse tissues. Moreover, CDP-ribitol concentrations were reduced in fibroblasts and skeletal muscle biopsies from patients with CRPPA myopathy, showing that CDP-ribitol could serve as a diagnostic marker to identify patients with CRPPA with severe Walker-Warburg syndrome and mild limb-girdle muscular dystrophy (LGMD) phenotypes. A screen for potentially therapeutic monosaccharides revealed that ribose, in addition to ribitol, restored CDP-ribitol concentrations and the associated O-glycosylation defect of alpha-dystroglycan. As the effect occurred in a mutation-dependent manner, we established a CDP-ribitol blood test to facilitate diagnosis and predict individualized treatment response. Ex vivo incubation of blood cells with ribose or ribitol restored CDP-ribitol concentrations in a patient with CRPPA LGMD. CONCLUSIONS: Sensitive detection of CDP-ribitol with LC-MS allows fast diagnosis of patients with severe and mild CRPPA myopathy. Ribose offers a readily testable dietary therapy for CRPPA myopathy, with possible applicability for patients with FKRP and FKTN myopathy. Evaluation of CDP-ribitol in blood is a promising tool for the evaluation and monitoring of dietary therapies for CRPPA myopathy in a patient-specific manner.

Contains fulltext : 219098.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 206906.pdf (publisher's version ) (Closed access)

Radboud University, 18 april 2019, Promotores : Edwards, M.J.R., Goslings, J.C. Co-promotores : Biert, J., Lansink, K.W.W, Contains fulltext : 201887.pdf (publisher's version ) (Open Access)

Radboud University, 18 april 2019, Promotores : Edwards, M.J.R., Goslings, J.C. Co-promotores : Biert, J., Lansink, K.W.W, Contains fulltext : 201887.pdf (publisher's version ) (Open Access)

Contains fulltext : 219098.pdf (Publisher’s version ) (Closed access)

Item does not contain fulltext, AIMS: This study was conducted to determine long-term (5-10 years) health-related quality of life (HRQOL) and ceiling effects in patients with a pelvic ring fracture. PATIENTS AND METHODS: We identified all patients with pelvic ring fractures after high-energy trauma admitted at two level 1 trauma centres in the Netherlands from 2006 to 2011. Patients were asked to complete the Majeed Pelvic Score (MPS), EuroQol-5D (EQ-5D) and Short Musculoskeletal Function Assessment (SMFA) questionnaires. HRQOL analysis used a multiple linear regression model. RESULTS: In total, 136 patients returned the questionnaires. The median follow-up period was 8.7 years. The mean MPS and EQ-5D-VAS scores were 85.1 and 74, respectively. The mean EQ-5D index scores were 0.87, 0.81 and 0.82 in Tile B, A and C patients, respectively. The mean SMFA index was 24. A ceiling effect was observed for 1/3 of the patients. After multiple linear regression analysis, no differences were identified among the various fracture types for each questionnaire, with the exception of 2 subscales of the MPS. CONCLUSION: Patients who suffer pelvic ring fractures generally have good HRQOL outcomes after 5-10 years. No significant differences were found among different fracture types. Long-term follow-up of patients with Tile C fractures is warranted.