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result(s) for
"Blokhuis, Taco J"
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Proinflammatory Mediators Enhance the Osteogenesis of Human Mesenchymal Stem Cells after Lineage Commitment
by
Croes, Michiel
,
Dhert, Wouter J. A.
,
Alblas, Jacqueline
in
Alkaline phosphatase
,
Alkaline Phosphatase - metabolism
,
Biocompatibility
2015
Several inflammatory processes underlie excessive bone formation, including chronic inflammation of the spine, acute infections, or periarticular ossifications after trauma. This suggests that local factors in these conditions have osteogenic properties. Mesenchymal stem cells (MSCs) and their differentiated progeny contribute to bone healing by synthesizing extracellular matrix and inducing mineralization. Due to the variation in experimental designs used in vitro, there is controversy about the osteogenic potential of proinflammatory factors on MSCs. Our goal was to determine the specific conditions allowing the pro-osteogenic effects of distinct inflammatory stimuli. Human bone marrow MSCs were exposed to tumor necrosis factor alpha (TNF-α) and lipopolysaccharide (LPS). Cells were cultured in growth medium or osteogenic differentiation medium. Alternatively, bone morphogenetic protein 2 (BMP-2) was used as osteogenic supplement to simulate the conditions in vivo. Alkaline phosphatase activity and calcium deposition were indicators of osteogenicity. To elucidate lineage commitment-dependent effects, MSCs were pre-differentiated prior treatment. Our results show that TNF-α and LPS do not affect the expression of osteogenic markers by MSCs in the absence of an osteogenic supplement. In osteogenic differentiation medium or together with BMP-2 however, these mediators highly stimulated their alkaline phosphatase activity and subsequent matrix mineralization. In pre-osteoblasts, matrix mineralization was significantly increased by these mediators, but irrespective of the culture conditions. Our study shows that inflammatory factors potently enhance the osteogenic capacity of MSCs. These properties may be harnessed in bone regenerative strategies. Importantly, the commitment of MSCs to the osteogenic lineage greatly enhances their responsiveness to inflammatory signals.
Journal Article
Early Postoperative Gait Analysis in Elderly Patients Following Hip Fracture Surgery
2025
Hip fractures in elderly patients significantly reduce independence and quality of life. Early postoperative gait performance remains poorly understood, particularly regarding differences between surgical treatments, such as proximal femur nailing and hemiarthroplasty. Identifying gait alterations early in rehabilitation could optimize clinical interventions. This prospective observational cohort study included 40 elderly patients hospitalized after acute hip fracture surgery. Relative peak force and step duration were assessed using the ambulant pressure biofeedback system during postoperative mobilization. Additionally, three-dimensional gait analysis evaluated spatiotemporal parameters and sagittal plane kinematics of the hip, knee, and ankle. Results demonstrated significant improvements in median peak force (45.32% to 70.00%, (p < 0.001)) and median step duration (2.96 s to 137 s, (p < 0.001)) at the end of the hospitalization period. No significant differences in step duration and peak force were observed between the different surgical procedures, proximal femur nail, and hemiarthroplasty. Three-dimensional gait analysis showed significantly reduced hip extension during terminal stance in the operated leg compared to the healthy leg. These findings highlight the utility of biofeedback systems for monitoring early rehabilitation progress and emphasize the importance of 3D gait analysis in identifying early postoperative gait deficits. Targeted interventions during hospitalization could enhance functional recovery and improve patient outcomes.
Journal Article
Subcutaneous Adipose Tissue Radiation Attenuation Is Associated With Increased 1‐Year Mortality in Polytrauma Patients
2025
Background Polytrauma patients with an Injury Severity Score (ISS) ≥ 16 have a high mortality rate. Early identification of patients at risk of mortality is key. Different risk stratification models are available; however, body composition on third lumbar computed tomography (L3 CT) is not routinely used. The aim of this study is to determine the effect of CT body composition on 1‐year mortality in adult polytrauma patients. Methods Body composition analysis (L3 CT) was performed on 593 adult polytrauma patients. The associations with 1‐year mortality were assessed using uni‐ and multivariable logistic regression analysis. As a sensitivity analysis, 1‐year mortality was analysed using Kaplan–Meier survival curves, log‐rank tests and Cox regression. Results The study population was predominantly male (69.5%), with a mean age of 55 (±20) years and an average BMI of 25.34 kg/m2 (±4.07). Comorbidities were present in 327 (55.4%) patients, with an average Charlson Comorbidity Index (CCI) of 2.07 points (±2.1). The mean ISS score was 27.59 (±11.06); 323 (54.5%) patients had an ISS ≥ 25 points. Age, CCI, ISS, skeletal muscle index and skeletal muscle radiation attenuation (OR 1.053, 5.713, 3.711, 0. 563 and 0.533, respectively; p < 0.001), subcutaneous adipose tissue radiation attenuation (SATRA OR 1.253, p = 0.028) and visceral adipose tissue index (OR 1.242, p = 0.038) were significantly associated with 1‐year mortality. In multivariable logistic regression, age, ISS and SATRA remained statistically significantly associated with 1‐year mortality (OR 1.062, p < 0.001; OR 4.761, p < 0.001; OR 1.396, p = 0.009). Conclusions This study demonstrated that subcutaneous adipose tissue radiation attenuation on emergency trauma CT scans is significantly associated with 1‐year mortality in adult polytrauma patients. Additionally, we found a significant effect of age and ISS on 1‐year mortality. Incorporating body composition analysis could lead to a better selection of patients at risk for 1‐year mortality and aid in treatment decision‐making.
Journal Article
Reliability of wireless monitoring using a wearable patch sensor in high-risk surgical patients at a step-down unit in the Netherlands: a clinical validation study
2018
Background and objectivesIntermittent 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.DesignIn an observational methods comparisons study, patients were measured with both the wireless sensor and bedside routine standard for at least 24 hours.SettingUniversity teaching hospital, single centre.ParticipantsTwenty-five postoperative surgical patients admitted to a step-down unit.Outcome measuresPrimary 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.Results1568 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).ConclusionsThe 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.
Journal Article
Deep Learning Automated Segmentation for Muscle and Adipose Tissue from Abdominal Computed Tomography in Polytrauma Patients
by
Ten Bosch, Jan A.
,
Brecheisen, Ralph
,
Sánchez-González, Patricia
in
Abdomen
,
Adipose Tissue - diagnostic imaging
,
Algorithms
2021
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.
Journal Article
Characterization of the Fat Channel for Intra-Body Communication at R-Band Frequencies
2018
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.
Journal Article
Neutrophils Inhibit Synthesis of Mineralized Extracellular Matrix by Human Bone Marrow-Derived Stromal Cells In Vitro
by
Croes, Michiel
,
Leenen, Luke P. H.
,
Alblas, Jacqueline
in
Alkaline phosphatase
,
Antigens
,
Antigens, Surface - metabolism
2018
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
. 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 (
< 0.01), a 64% decrease in the percentage of ALP+ cells (
< 0.001), a 28% decrease in total ALP activity (
< 0.01), and a significant decrease in the amount of mineralized ECM [38% decrease after 4 weeks (
< 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.
Journal Article
MAS: Standalone Microwave Resonator to Assess Muscle Quality
by
Ten Bosch, Jan A.
,
Mattsson, Viktor
,
Vesseur, Maud A. M.
in
bandstop filter
,
Breast cancer
,
Costs
2021
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.
Journal Article
Polytherapy versus monotherapy in the treatment of tibial non-unions: a retrospective study
by
Qiu, Shan Shan
,
van Griensven, Martijn
,
Blokhuis, Taco J
in
Bone grafts
,
Bone healing
,
Decision making
2024
BackgroundTreating 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 methodsData 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.ResultsA 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.ConclusionsPolytherapy 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 evidenceLevel III.
Journal Article
Early fixation versus conservative therapy of multiple, simple rib fractures (FixCon): protocol for a multicenter randomized controlled trial
by
Pull ter Gunne, Albert F.
,
Wijffels, Mathieu M. E.
,
Van Montfort, Gust
in
Aged
,
Clinical trials
,
Conservative Treatment - standards
2019
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.
Journal Article