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Neuromusculoskeletal models can be used to evaluate aberrant muscle function in cerebral palsy (CP), for example by estimating muscle and joint contact forces during gait. However, to be accurate, models should include representative musculotendon parameters. We aimed to estimate personalised parameters that capture the mechanical behaviour of the plantarflexors in children with CP and typically developing (TD) children. Ankle angle (using motion capture), torque (using a load-cell), and medial gastrocnemius fascicle lengths (using ultrasound) were measured during slow passive ankle dorsiflexion rotation for thirteen children with spastic CP and thirteen TD children. Per subject, the measured rotation was input to a scaled OpenSim model to simulate the torque and fascicle length output. Musculotendon model parameters were personalised by the best match between simulated and experimental torque–angle and fascicle length-angle curves according to a least-squares fit. Personalised tendon slack lengths were significantly longer and optimal fibre lengths significantly shorter in CP than model defaults and than in TD. Personalised tendon compliance was substantially higher in both groups compared to the model default. The presented method to personalise musculotendon parameters will likely yield more accurate simulations of subject-specific muscle mechanics, to help us understand the effects of altered musculotendon properties in CP.

BACKGROUND: Developmental Dysplasia of the Hip (DDH) is one of the most common pediatric orthopedic disorders, affecting 1-3% of all newborns. The optimal treatment of centered DDH is currently under debate. This randomized controlled trial aims to study the (cost-)effectiveness of active monitoring versus abduction treatment for infants with centered DDH. METHODS: This is a multicenter, parallel-group, open-label, non-inferiority randomized controlled trial studying the (cost-)effectiveness of active monitoring versus abduction treatment for infants with centered DDH in fourteen hospitals in the Netherlands. In total, 800 infants with centered DDH (Graf IIa-/IIb/IIc), aged 10-16 weeks, will be randomly allocated to the active monitoring or abduction treatment group. Infants will be followed up until the age of 24 months. The primary outcome is the rate of normal hips, defined as an acetabular index lower than 25 degrees on an antero-posterior radiograph, at the age of 12 months. Secondary outcomes are the rate of normal hips at the age of 24 months, complications, time to hip normalization, the relation between baseline patient characteristics and the rate of normal hips, compliance, costs, cost-effectiveness, budget impact, health-related quality of life (HRQoL) of the infant, HRQoL of the parents/caregivers, and parent/caregiver satisfaction with the treatment protocol. DISCUSSION: The outcomes of this randomized controlled trial will contribute to improving current care-as-usual for infants with centered DDH. TRIAL REGISTRATION: Dutch Trial Register, NL9714, registered September 6, 2021. https://clinicaltrialregister.nl/en/trial/29596.

Background: Only a few papers are published on the safety and effectiveness of acute burn care in low-income countries. A cohort study was therefore carried out to determine such outcomes.Methods: The study was conducted in a rural Tanzanian hospital in 2017–2018. All patients admitted with burns were eligible. Complications were scored during admission as an indication for safety. Survivors of severe burn injuries were evaluated for time of reepithelialization, graft take, disability (WHODAS2.0) and quality of life (EQ5D-3L) up to 3 months post-injury, as an indication of effectiveness.Results: Patients presented on average at 5 days after injury (SD 11, median 1, IQR 0–4). Three patients died at admission. The remaining 79 were included in the cohort. Their median age was 3 years (IQR 2–9, range 0.5–49), mean TBSA burned 12% (SD10%) and mortality rate 11.4%. No surgery-related mortality or life-threatening complications were observed. Skin grafting was performed on 29 patients at a delayed stage (median 23 days, IQR 15–47). Complications of skin grafts included partial (25% of procedures) and complete graft necrosis (8% of procedures). The mean time to reepithelialization was 52 (SD 42) days after admission. Disability and quality of life improved from admission to 3 months after injury (pConclusion: In this resource-limited setting patients presented after a delay and with multiple complications. The mortality during the first two weeks after admission was high. Surgery was found to be safe and effective. A significant improvement in disability and quality of life was observed.

Bone defects caused by systemic or local factors cannot heal spontaneously. The repair of critical-sized bone defects in clinical practice remains challenging due to limited clinically available bone-defect filling material. To stimulate bone regeneration and resolve this clinical challenge, bone tissue engineering approaches have been developed during the past decades. Osteocytes have multiple functions in bone tissue. They can sense fluid shear stress as a result of mechanical loading, translating the mechanical stress into the production of biochemical signaling molecules. These effective biomolecules further regulate bone resorption and bone formation. Thus, it may well be that osteocytes not only regulate bone turnover but are also able to enhance osteogenesis of stem cells, suggesting a novel yet unrecognized role of osteocytes in governing bone tissue regeneration. In Chapter 2, we reviewed osteocyte functions in bone, as well as the interaction of osteocytes with other bone cells, and their role in bone remodeling. We hypothesize that osteocytes may have a pivotal role in bone regeneration as well, and thus that bone regeneration may be enhanced effectively and rapidly by optimal usage and stimulation of osteocytes. Currently available synthetic bone grafts are biocompatible and osteoconductive, but the majority of these biomaterials lack osteoinductivity. Biomaterials coated with various growth factors, proteins, and/or drugs promote the expansion and osteogenic differentiation of precursor cells. However, these growth factors or drugs might cause local and systemic adverse effects that hinder the clinical application for bone regeneration. Therefore, the search for safe and effective biomaterials to promote bone regeneration is still ongoing. In Chapter 3, we concluded that our results indicate a possible role of k-carrageenan in pre-osteoblast adhesion, spreading, migration, metabolic activity, proliferation, and osteogenic differentiation. This study fully explored the influence of k-carrageenan on cell function from different aspects that are needed for bone regeneration. The current results suggest that k-carrageenan might be a promising factor to functionalize bone graft and for enhanced osseointegration of implants. The search for cost-effective bioactive agents that can be incorporated in biomimetic calcium phosphate coating on an implant surface to improve implant osseointegration is still ongoing. k-Carrageenan could be a potent factor to improve implant osteoinductivity and osseointegration when incorporated in a calcium phosphate coating on titanium implants. In Chapter 4, we successfully incorporated k-carrageenan in an octa-calcium phosphate (OCP) coating on a titanium surface using a biomimetic co-precipitation technique. We found that k-carrageenan in the OCP coating increased pre-osteoblast spreading, proliferation, and metabolic activity, as well as alkaline phosphatase (ALP) activity, matrix mineralization, and osteogenic gene expression suggesting that k-carrageenan-functionalized OCP coating might improve osseointegration of titanium dental or orthopedic implants. Confined cell-cell and/or cell-scaffold interactions in three-dimensional (3D)-printed scaffolds containing β-tricalcium phosphate (TCP) limit bone regeneration and large bone defect repair. Stem cell culture systems have attracted considerable attention as a way to better mimic the complex interactions between individual cells and scaffolds that occur in vivo. Spheroids might be a promising strategy to improve cell-cell and/or cell-scaffold interactions to achieve ideal bone regeneration. In Chapter 5, we successfully developed self-assembled stem cells from human exfoliated deciduous teeth (SHEDs) µ-spheroids that enhanced the osteogenic potential of 3D-printed hydroxypropyl methylcellulose/polyethylenimine/β-TCP composite scaffolds in vitro and in vivo, suggesting that SHEDs µ-spheroids may be promising in bone tissue engineering for bone regeneration. Collectively, natural polymers and osteogenic cells do affect bone tissue regeneration. Bone regeneration modulated by osteocytes, k-carrageenan, and SHEDs µ-spheroids is promising in bone tissue engineering. Investigation of these processes provides further opportunities to learn and elucidate the mechanisms involved, leading to the development of new strategies for bone regeneration.

Background: Antibiotic use prior to biopsy acquisition in people with diabetes and osteomyelitis of the foot (DFO) might influence bacterial yield in cultures or induce bacterial resistance. Obtaining reliable culture results is pivotal to guide antibiotics for conservative treatment of DFO. Methods: We prospectively analysed cultures of ulcer bed and percutaneous bone biopsies of people with DFO and investigated if antibiotics administered prior to (

Background: Children with cerebral palsy often show deviating calf muscle activation patterns during gait, with excess activation during early stance and insufficient activation during push-off. Research question: Can children with cerebral palsy improve their calf muscle activation patterns during gait using one session of biofeedback-driven gaming? Methods: Eighteen children (6–17 y) with spastic cerebral palsy received implicit game-based biofeedback on electromyographic activity of the calf muscle (soleus or gastrocnemius medialis) while walking on a treadmill during one session. Biofeedback alternately aimed to reduce early stance activity, increase push-off activity, and both combined. Early stance and push-off activity and the double-bump-index (early stance divided by push-off activity) were determined during baseline and walking with feedback. Changes were assessed at group level using repeated measures ANOVA with simple contrast or Friedman test with post-hoc Wilcoxon signed rank test, as well as individually using independent t-tests or Wilcoxon rank sum tests. Perceived competence and interest-enjoyment were assessed through a questionnaire. Results: Children successfully decreased their electromyographic activity during early stance feedback trials (relative decrease of 6.8 ± 12.2 %, P = 0.025), with a trend during the combined feedback trials (6.5 ± 13.9 %, P = 0.055), and increased their electromyographic activity during push-off feedback trials (8.1 ± 15.8 %, P = 0.038). Individual improvements were seen in twelve of eighteen participants. All children experienced high levels of interest-enjoyment (8.4/10) and perceived competence (8.1/10). Significance: This exploratory study suggests that children with cerebral palsy can achieve small within-session improvements of their calf muscle activation pattern when provided with implicit biofeedback-driven gaming in an enjoyable manner. Follow-up gait training studies can incorporate this method to assess retention and long-term functional benefits of electromyographic biofeedback-driven gaming.

Introduction: Video-based clinical rating plays an important role in assessing dystonia and monitoring the effect of treatment in dyskinetic cerebral palsy (CP). However, evaluation by clinicians is time-consuming, and the quality of rating is dependent on experience. The aim of the current study is to provide a proof-of-concept for a machine learning approach to automatically assess scoring of dystonia using 2D stick figures extracted from videos. Model performance was compared to human performance.Methods: A total of 187 video sequences of 34 individuals with dyskinetic CP (8–23 years, all non-ambulatory) were filmed at rest during lying and supported sitting. Videos were scored by three raters according to the Dyskinesia Impairment Scale (DIS) for arm and leg dystonia (normalized scores ranging from 0–1). Coordinates in pixels of the left and right wrist, elbow, shoulder, hip, knee and ankle were extracted using DeepLabCut, an open source toolbox that builds on a pose estimation algorithm. Within a subset, tracking accuracy was assessed for a pretrained human model and for models trained with an increasing number of manually labeled frames. The mean absolute error (MAE) between DeepLabCut’s prediction of the position of body points and manual labels was calculated. Subsequently, movement and position features were calculated from extracted body point coordinates. These features were fed into a Random Forest Regressor to train a model to predict the clinical scores. The model performance trained with data from one rater evaluated by MAEs (model-rater) was compared to inter-rater accuracy.Results: A tracking accuracy of 4.5 pixels (approximately 1.5 cm) could be achieved by adding 15–20 manually labeled frames per video. The MAEs for the trained models ranged from 0.21 ± 0.15 for arm dystonia to 0.14 ± 0.10 for leg dystonia (normalized DIS scores). The inter-rater MAEs were 0.21 ± 0.22 and 0.16 ± 0.20, respectively.Conclusion: This proof-of-concept study shows the potential of using stick figures extracted from common videos in a machine learning approach to automatically assess dystonia. Sufficient tracking accuracy can be reached by manually adding labels within 15–20 frames per video. With a relatively small data set, it is possible to train a model that can automatically assess dystonia with a performance comparable to human scoring.

Balance recovery after tripping often requires an active adaptation of foot placement. Thus far, few attempts have been made to actively assist forward foot placement for balance recovery employing wearable devices. This study aims to explore the possibilities of active forward foot placement through two paradigms of actuation: assistive moments exerted with the reaction moments either internal or external to the human body, namely ‘joint’ moments and ‘free’ moments, respectively. Both paradigms can be applied to manipulate the motion of segments of the body (e.g., the shank or thigh), but joint actuators also exert opposing reaction moments on neighbouring body segments, altering posture and potentially inhibiting tripping recovery. We therefore hypothesised that a free moment paradigm is more effective in assisting balance recovery following tripping. The simulation software SCONE was used to simulate gait and tripping over various ground-fixed obstacles during the early swing phase. To aid forward foot placement, joint moments and free moments were applied either on the thigh to augment hip flexion or on the shank to augment knee extension. Two realizations of joint moments on the hip were simulated, with the reaction moment applied to either the pelvis or the contralateral thigh. The simulation results show that assisting hip flexion with either actuation paradigm on the thigh can result in full recovery of gait with a margin of stability and leg kinematics closely matching the unperturbed case. However, when assisting knee extension with moments on the shank, free moment effectively assist balance but joint moments with the reaction moment on the thigh do not. For joint moments assisting hip flexion, placement of the reaction moment on the contralateral thigh was more effective in achieving the desired limb dynamics than placing the reaction on the pelvis. Poor choice of placement of reaction moments may therefore have detrimental consequences for balance recovery, and removing them entirely (i.e., free moment) could be a more effective and reliable alternative. These results challenge conventional assumptions and may inform the design and development of a new generation of minimalistic wearable devices to promote balance during gait.

Objective: Children and adults with talipes equinovarus (TEV) have smaller calves and shorter feet compared to non-affected controls. Do these changes have a prenatal onset?. Methods: A prospective cohort study (January 2020–July 2021) was conducted with serial ultrasonographic measurements at 20 and 28 weeks gestation and measurements directly and 6 weeks after birth. Calf circumference and width, foot length and length of humerus, ulna, radius, femur, tibia and fibula were measured in TEV and were compared to a control population. Calculated sample size necessitated a minimal population of 10 cases with TEV and 50 controls. Results: Twenty cases with TEV and 62 controls were included. Fetal calf circumference (p

Background Foot and ankle joint kinematics are measured during clinical gait analyses with marker-based multi-segment foot models. To improve on existing models, measurement errors due to soft tissue artifacts (STAs) and marker misplacements should be reduced. Therefore, the aim of this study is to define a clinically informed, universally applicable multi-segment foot model, which is developed to minimize these measurement errors. Methods The Amsterdam foot model (AFM) is a follow-up of existing multi-segment foot models. It was developed by consulting a clinical expert panel and optimizing marker locations and segment definitions to minimize measurement errors. Evaluation of the model was performed in three steps. First, kinematic errors due to STAs were evaluated and compared to two frequently used foot models, i.e. the Oxford and Rizzoli foot models (OFM, RFM). Previously collected computed tomography data was used of 15 asymptomatic feet with markers attached, to determine the joint angles with and without STAs taken into account. Second, the sensitivity to marker misplacements was determined for AFM and compared to OFM and RFM using static standing trials of 19 asymptomatic subjects in which each marker was virtually replaced in multiple directions. Third, a preliminary inter- and intra-tester repeatability analysis was performed by acquiring 3D gait analysis data of 15 healthy subjects, who were equipped by two testers for two sessions. Repeatability of all kinematic parameters was assessed through analysis of the standard deviation (σ) and standard error of measurement (SEM). Results The AFM was defined and all calculation methods were provided. Errors in joint angles due to STAs were in general similar or smaller in AFM (≤2.9°) compared to OFM (≤4.0°) and RFM (≤6.7°). AFM was also more robust to marker misplacement than OFM and RFM, as a large sensitivity of kinematic parameters to marker misplacement (i.e. > 1.0°/mm) was found only two times for AFM as opposed to six times for OFM and five times for RFM. The average intra-tester repeatability of AFM angles was σ:2.2[0.9°], SEM:3.3 ± 0.9° and the inter-tester repeatability was σ:3.1[2.1°], SEM:5.2 ± 2.3°. Conclusions Measurement errors of AFM are smaller compared to two widely-used multi-segment foot models. This qualifies AFM as a follow-up to existing foot models, which should be evaluated further in a range of clinical application areas.

biBackground:/i/bBecause the behavioral variant of frontotemporal dementia (bvFTD) shows major clinical overlap with primary psychiatric disorders (PPD) that affect similar neuroanatomical circuits, a common genetic vulnerability between FTD and PPD was hypothesized.biAims:/i/bWe studied whether PPD are more prevalent in families of patients with sporadic frontotemporal dementia compared with healthy controls (HC), subjects with Alzheimer's disease (AD), and individuals with bipolar disorder (BD).biMethods:/i/bIn this case-control study performed between January 2013 and February 2019, we investigated the first-degree family history concerning depression, psychosis (including schizophrenia), BD, and autism spectrum disorder for 73 bvFTD patients, 153 patients with BD, 108 patients with AD, and 101 HC with a semistructured questionnaire (QFTD-NL 1.0) according toiDSM-IV/i,iDSM-5/i, oriICD-10/icriteria.biResults:/i/bPatients with bvFTD had a 2.58-fold higher odds of having a first-degree family member with depression compared to HC (iP/i = .04). Furthermore, they showed 3.26-fold higher odds of having a first-degree relative with psychosis compared to HC (iP/i = .09).biConclusions:/i/bOur results implicate a link between dementia, including sporadic bvFTD, and depression. Further study into the genetic overlap between bvFTD and PPD might provide clues to targeting common disease mechanisms.

BackgroundDiabetic foot osteomyelitis (DFO) poses a major disease burden. It can generally be treated with long-term antibacterial therapy. International guidelines recommend to base antibacterial therapy choices on percutaneous bone biopsy culture, while in practice, therapy is frequently based on (less invasive) ulcer bed cultures. It is currently unknown if treatment outcomes of DFO differ depending on the chosen diagnostic strategy.MethodsThe BeBoP trial is a multicentre; randomised controlled; physician-, researcher- and subject-blinded; clinical trial comparing two diagnostic strategies in persons with DFO. Culture-directed antibacterial therapy will be based on either percutaneous bone biopsy culture results (intervention group) or ulcer bed biopsy culture results (comparison group). We will enrol 80 subjects with diabetes mellitus (≥ 18 years) and DFO, and we will use block randomisation stratified per centre to randomise them in a 1:1 allocation. The primary outcome is remission of DFO 12 months after enrolment. The secondary outcomes are the time to remission, signs of inflammation or ulceration at the primary location of infection at 6 and 12 months, microbiological and molecular profiles of culture outcomes, surgical interventions including amputation, total antibacterial therapy duration, infection-free survival days, adverse events, quality of life and survival. We will compare the outcomes by intention-to-treat and per-protocol analysis.DiscussionWe aim to compare clinical remission in persons with DFO treated with antibacterial therapy based on either percutaneous bone biopsy culture results or ulcer bed biopsy culture results.Trial registrationNetherlands Trial RegisterNL 7582. Registered on 05 March 2019

Purpose: Investigate pain, fatigue, depressive symptoms and sleep disturbance in young adults with cerebral palsy compared to references. Materials and methods: Young adults with cerebral palsy (n = 97, aged 21–34 years) and age-matched references from the general population (n = 190) rated pain using a numeric rating scale and fatigue, depressive symptoms, sleep disturbance and global health using Patient-Reported Outcomes Measurement Information System® short forms. Scores were compared between cerebral palsy subgroups and the reference population. Correlation coefficients and linear regression analyses assessed interrelationships of health issues and associations with global health. Results: Individuals with Gross Motor Function Classification System level I had less pain, fatigue and depressive symptoms, while individuals with levels II and III–V had more pain (53% and 56%, p < 0.001) and those with levels III–V more fatigue (39%, p = 0.035) than references (pain: 26%, fatigue: 14%). Pain and fatigue were more interrelated (correlation coefficients: 0.71 vs. 0.41) and stronger associated with global mental health in individuals with cerebral palsy. Conclusions: Young adults with Gross Motor Function Classification System levels II–V report more pain and those with levels III–V report more fatigue than references. Pain and fatigue are highly interrelated and specifically relate to mental health in individuals with cerebral palsy.Implications for rehabilitation Except for those in the highest level of motor function, young adults with cerebral palsy report higher levels of pain and fatigue compared to the general population of the same age. Pain and fatigue are strongly interrelated and associated with mental health in young adults with cerebral palsy. The present study recommends to monitor pain and fatigue in young adults with cerebral palsy with low levels of gross motor function. We advise rehabilitation professionals to consider combined treatment for both pain and fatigue.

Despite the high incidence of developmental dysplasia of the hip (DDH), treatment is very diverse. Therefore, the Dutch Orthopedic Society developed a clinical practice guideline with recommendations for optimal and uniform treatment of DDH. This article summarizes the guideline on centered DDH (i.e. Graf types 2A–C). The guideline development followed the criteria of Appraisal of Guidelines for Research and Evaluation II. A systematic literature review was performed to identify randomized controlled trials and comparative cohort studies including children Out of 430 potentially relevant articles, 5 comparative studies were included. Final guideline recommendations were (1) initially observe 3-month-old patients with centered DDH, start abduction treatment if the hip does not normalize after 6–12 weeks; (2) prescribe a Pavlik harness to children 6 months; (3) assess patients every 6 weeks; and (4) discontinue the abduction device when the hip has normalized or when the child is 12 months. This paper presents a summary of part 1 of the first evidence-based guideline for treatment of centered DDH in children

Purpose Different bacteria lead to divers diabetic foot infections (DFIs), and some bacteria probably lead to higher amputation and mortality risks. We assessed mortality and amputation risk in relation to bacterial profiles in people DFI and investigated the role of sampling method. Methods We included people (> 18 years) with DFI in this retrospective study (2011–2020) at a Dutch tertiary care hospital. We retrieved cultures according to best sampling method: (1) bone biopsy; (2) ulcer bed biopsy; and (3) swab. We aggregated data into a composite determinant, consisting of unrepeated bacteria of one episode of infection, clustered into 5 profiles: (1) Streptococcus and Staphylococcus aureus; (2) coagulase-negative Staphylococcus, Cutibacterium, Corynebacterium and Enterococcus; (3) gram-negative; (4) Anaerobic; and (5) less common gram-positive bacteria. We calculated Hazard Ratio’s (HR’s) using time-dependent-Cox regression for the analyses and investigated effect modification by sampling method. Results We included 139 people, with 447 person-years follow-up and 459 episodes of infection. Sampling method modified the association between bacterial profiles and amputation for profile 2. HR’s (95% CI’s) for amputation for bacterial profiles 1–5: 0.7 (0.39–1.1); stratified analysis for profile 2: bone biopsy 0.84 (0.26–2.7), ulcer bed biopsy 0.89 (0.34–2.3), swab 5.9*(2.9–11.8); 1.3 (0.78–2.1); 1.6 (0.91–2.6); 1.6 (0.58–4.5). HR’s (95% CI’s) for mortality for bacterial profiles 1–5: 0.89 (0.49–1.6); 0.73 (0.38–1.4); 2.6*(1.4–4.8); 1.1(0.58–2.2); 0.80(0.19–3.3). Conclusions In people with DFI, there was no association between bacterial profiles in ulcer bed and bone biopsies and amputation. Only in swab cultures, low-pathogenic bacteria (profile 2), were associated with a higher amputation risk. Infection with gram-negative bacteria was associated with a higher mortality risk. This study underlined the possible negative outcome of DFI treatment based on swabs cultures.

This study investigates patients’ access to surgical care for burns in a low- and middle-income setting by studying timeliness, surgical capacity, and affordability. A survey was conducted in a regional referral hospital in Manyara, Tanzania. In total, 67 patients were included. To obtain information on burn victims in need of surgical care, irrespective of time lapsed from the burn injury, both patients with burn wounds and patients with contractures were included. Information provided by patients and/or caregivers was supplemented with data from patient files and interviews with hospital administration and physicians. In the burn wound group, 50% reached a facility within 24 hours after the injury. Referrals from other health facilities to the regional referral hospital were made within 3 weeks for 74% in this group. Of contracture patients, 74% had sought healthcare after the acute burn injury. Of the same group, only 4% had been treated with skin grafts beforehand, and 70% never received surgical care or a referral. Together, both groups indicated that lack of trust, surgical capacity, and referral timeliness were important factors negatively affecting patient access to surgical care. Accounting for hospital fees indicated patients routinely exceeded the catastrophic expenditure threshold. It was determined that healthcare for burn victims is without financial risk protection. We recommend strengthening burn care and reconstructive surgical programs in similar settings, using a more comprehensive health systems approach to identify and address both medical and socioeconomic factors that determine patient mortality and disability.

Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP-1, IL-8, IL-18 and IL-23 levels have a strong correlation with HS (P 2: 0.727) showed an improved AUC indicating a better correlation with HS than single cytokine analysis. These combination models produce good prognostic results over a broad probability range (sensitivity: 93.8%, specificity 86.7%, accuracy 90,25% between probability 0.3 and 0.7). Furthermore, the HS group had a lower IT than the NS group and an accuracy of 68%. In conclusion, very fundamental immunological differences exist between individuals who develop HS and those who do not, whereas the cytokine assay forms the basis of a predictive prognostic test for HS formation, the less invasive, easily performed irritant skin patch test is more accessible for daily practice.

A panel of European experts was convened to establish consensus on a treat-to-target strategy in osteoporosis. Panellists agreed that the ultimate goals of treating osteoporosis are recovering pre-fracture functional level and reducing subsequent fracture risk; there was consensus that total hip bone mineral density is currently the most appropriate treatment target in clinical practice. Introduction A modified Delphi approach was convened to establish consensus among European experts on best practice management for patients with fragility fractures and whether a treat-to-target (T2T) strategy is applicable in osteoporosis. Methods A panel of 12 clinical experts (from eight European countries) voted on 13 final statements relating to a T2T strategy for osteoporosis across three rounds of blinded, remotely conducted electronic surveys (Likert scale: 'strongly disagree', 'disagree', 'unable to answer', 'agree', 'strongly agree'). When panellists disagreed, they were asked how the statement could be adjusted to allow for a positive response, which was used to refine the statement for the following round. Consensus was defined as >= 75% agreement with a statement. Panellists were selected by UCB Pharma, which provided financial and logistical support. Results Consensus was reached for 13/13 statements. Panellists agreed that the most important goals for fragility fracture patients are recovery of pre-fracture functional level and reduction of subsequent fracture risk. There was also consensus that a T2T strategy is applicable to osteoporosis and that bone mineral density (BMD) is currently the most clinically appropriate target. With regard to the definition of a specific BMD treatment target and timeframes applicable to T2T in osteoporosis, no clear consensus was reached; panellists emphasised that these would need to be individually determined. Conclusions According to a panel of European experts, the main goals of fracture management are to recover pre-fracture functional level and reduce fracture risk. Total hip BMD seems to be the most clinically appropriate treatment target within a T2T strategy. This study was sponsored by UCB Pharma and Amgen Inc. Support for study conception and design, acquisition of data, and analysis and interpretation of data, provided by Ogilvy Health, was funded by UCB Pharma and Amgen Inc. Support for third-party writing assistance for this article, provided by Kristian Clausen, MPH, Madeleine Warner, PhD, and Simon Foulcer, PhD, Costello Medical, UK was funded by UCB Pharma and Amgen Inc. in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). Timoshanko, J (corresponding author), UCB Pharma, Slough, Berks, England. jen.timoshanko@ucb.com

Background Genital gender-affirming surgery (gGAS) with urethral lengthening (UL) in transgender men is associated with high urological complication and reoperation rates. Since 2009, we offer gGAS without UL to avoid these complications. Aim The aim of this study was to assess what portion of the transgender men opted for gGAS without UL and to assess functional, surgical outcomes, and patient satisfaction after gGAS without UL. Material and methods Retrospective data were collected from patients’ charts. The International Prostate Symptom Score, uroflowmetry, and 24-hour frequency voiding chart were used to assess voiding, and a self-constructed semistructured questionnaire was used to assess patient-reported outcomes. Transgender men who underwent gGAS without UL between January 2009 and January 2018 were included, and 56 transgender men were approached to complete the patient-reported outcome measurement. The simple statistical analysis combined with the Mann-Whitney U test and the Wilcoxon signed-rank test was used. Outcomes 68 transgender men were included. Median follow-up time was 24 (6–129) months. Uroflowmetry and the International Prostate Symptom Score were completed by 44 transgender men, whereas 13 completed the frequency voiding chart preoperatively and postoperatively, respectively. The patient-reported outcome measurement was completed by 40 of 56 (71%) transgender men. Result Postoperative surgical and urological complications occurred in 9 of 68 (13%) and 8 of 68 (12%) patients, respectively. Storage and voiding function remained unchanged. The median quality of life because of urinary symptoms was scored as “pleased.” Sexual functioning and voiding were scored satisfactory and very satisfactory in 18 of 40 (45%) and 21 of 40 (53%) patients, respectively. The number of patients satisfied with the penis and neoscrotum was 25 of 40 (63%) and 26 of 40 (65%), respectively. Increased self-esteem was reported by 32 of 40 (80%), 32 of 40 (80%) would undergo the surgery again, and 28 of 40 (70%) would recommend it to others. Clinical Implications gGAS without UL should be part of the surgical armamentarium in centers performing gender-affirming surgery. Strengths and limitations Strengths of this study comprise the number of patients, the completeness of data, incorporation of patient-reported outcomes, and description of a relatively new surgical approach that may be well-suitable for a subgroup of transgender men. Limitations are the retrospective study design and the lack of validated questionnaires. Conclusion gGAS without UL shows good surgical and urological outcomes. After extensive counseling, the majority of this selective group of patients shows favorable patient-reported outcomes.

Objective: To elucidate patients’ knowledge and counseling perspective on aspirin reducing the risk of hypertensive disorders of pregnancy (HDP). Methods: A quantitative survey was performed including women who are members of the patient orgasnization Dutch HELLP Foundation due to a history of HDP. Results: Awareness of the risk-reducing effect of aspirin on HDP was present in 51.9% of the 189 women. The majority was informed by their gynecologist (89.8%) and preferred to be informed by a gynecologist (79.4%), at the postpartum checkup (42.3%) or in the consecutive pregnancy (30.7%), both orally and written (62.4%). Conclusion: Half of the women with a history of HDP were aware of the risk-reducing effect of aspirin in a consecutive pregnancy.

Objectives: In this cadaveric study, the accuracy of CAS guided mandibular and maxillary reconstruction including immediate dental implant placement in different Brown defect classes is assessed. Materials and methods: The virtual planning and surgical procedure was conducted according to a newly proposed Amsterdam UMC reconstruction protocol. Postoperative evaluation was performed according to a previously proposed evaluation guideline. Results: Fourteen mandibular and 6 maxillary reconstructions were performed. Average mandibular angle deviations were 1.52°±1.32, 1.85°±1.58, 1.37°±1.09, 1.78°±1.37, 2.43°±1.52 and 2.83°±2.37, respectively for the left and right axial angles, left and right coronal angles and left and right sagittal angles. A total of 62 dental implants were placed in neomandibles with an average dXYZ values of 3.68 ± 2.21 mm and 16 in neomaxillas with an average dXYZ values of 3.24 ± 1.7 mm. Conclusion: Promising levels of accuracy were achieved for all mandibular angles. Dental implant positions approached the preoperative preferred positions well, within the margin to manufacture prosthetic devices.

© 2022 The AuthorsBackground: Gait adaptability is of utmost importance for keeping balance during gait in patients with knee osteoarthritis, also after total knee arthroplasty (TKA). The aims of this explorative study are: (1) assess the effect of age, knee osteoarthritis and TKA on gait adaptability; (2) assess changes in gait adaptability pre-to post-TKA and (3) their relation to functional outcomes. Methods: Gait adaptability was measured using a Target Stepping Test (TST) in knee osteoarthritis patients before (preTKA) and 12 months after TKA (postTKA) and compared to asymptomatic old (AsOld) and young adults (AsYng). TST imposed an asymmetrical gait pattern with projected stepping targets at high walking speed. Gait adaptability was determined through stepping accuracy on the targets. The Oxford Knee Score (OKS) and Timed-Up-and-Go test (TUG) measured patients’ physical function. Results: 12 preTKA, 8 postTKA, 18 AsYng, 21 AsOld were tested. Age showed no effect on TST-stepping accuracy. PreTKA showed worse TST-stepping accuracy compared to AsYng and AsOld (7.7; 6.2 cm difference). PostTKA showed an improvement of 52% in TST-stepping accuracy compared to preTKA (3.2 cm). Higher stepping accuracy preTKA predicted higher stepping accuracy post-TKA. In addition, low preTKA stepping accuracy predicted more improvement postTKA. Pre-to post-TKA improvement of stepping accuracy was related to improvement on the TUG (Beta = 0.17, p = 0.024), but not to OKS. Conclusions: Gait adaptability is improved following TKA in knee osteoarthritis patients and no longer significantly worse than asymptomatic adults. The relation of gait adaptability to function is shown by its relation to the TUG and shows to have predictive value pre-to post-TKA.

Surgical construction of a vagina may be indicated in transgender women and cisgender women with congenital or acquired vaginal absence. It has a positive effect on quality of life and generally en...

Background: The Oxford Foot Model (OFM) and Rizzoli Foot Model (RFM) are the two most frequently used multi-segment models to measure foot kinematics. However, a comprehensive comparison of the kinematic output of these models is lacking. Research question: What are the differences in kinematic output between OFM and RFM during normal gait and typical pathological gait patterns in healthy adults?. Methods: A combined OFM and RFM marker set was placed on the right foot of ten healthy subjects. A static standing trial and six level walking trials were collected for normal gait and for four voluntarily adopted gait types: equinus, crouch, toe-in and toe-out. Joint angles were calculated for every trial for the hindfoot relative to shank (HF-SH), forefoot relative to hindfoot (FF-HF) and hallux relative to forefoot (HX-FF). Average static joint angles of both models were compared between models. After subtracting these offsets, the remaining dynamic angles were compared using statistical parametric mapping repeated measures ANOVAs and t-tests. Furthermore, range of motion was compared between models for every angle. Results: For the static posture, RFM compared to OFM measured more plantar flexion (Δ = 6°) and internal rotation (Δ = 7°) for HF-SH, more plantar flexion (Δ = 34°) and inversion (Δ = 13°) for FF-HF and more dorsal flexion (Δ = 37°) and abduction (Δ = 12°) for HX-FF. During normal walking, kinematic differences were found in various parts of the gait cycle. Moreover, range of motion was larger in the HF-SH for OFM and in FF-HF and HX-FF for RFM. The differences between models were not the same for all gait types. Equinus and toe-out gait demonstrated most pronounced differences. Significance: Differences are present in kinematic output between OFM and RFM, which also depend on gait type. Therefore, kinematic output of foot and ankle studies should be interpreted with careful consideration of the multi-segment foot model used.

PURPOSE: This study evaluated intraobserver reliability and construct validity of the squat test to assess lower extremity strength in children with cerebral palsy (CP) and spastic diplegia.METHODS: Children with CP performed 2 trials of the squat test and calculated the intraclass correlation coefficient to evaluate intraobserver reliability. Correlations between outcomes of hand-held dynamometry (HHD) of knee extensor strength and an 8-repetition maximum (8RM) leg press test and the squat test were calculated to evaluate construct validity.RESULTS: Excellent intraobserver reliability was observed for the squat test. Correlations between squat test performance and HHD knee extension and 8RM leg press test demonstrated good construct validity.CONCLUSIONS: The squat test is a reliable and valid tool to assess lower extremity strength in children with CP and spastic diplegia. The squat test is inexpensive and less time-consuming, and therefore particularly suitable for clinicians.

AIMS: The aim of this study was to explore the relationships between ischaemic burden and changes in absolute myocardial perfusion following chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS AND RESULTS: A total of 193 consecutive patients underwent [15O]H2O positron emission tomography prior to and three months after successful CTO PCI. Change in perfusion defect size, quantitative hyperaemic myocardial blood flow (MBF) and coronary flow reserve (CFR) within the CTO area were compared among patients with limited (0-1 segment, N=15), moderate (2-3 segments, N=61) and large (≥4 segments, N=117) perfusion defects. Median reductions in defect size were 1 [0-1], 2 [1-3], and 4 [2-5] segments in patients with a limited, moderate and large defect (all comparisons p

OBJECTIVE: Sarcopenia is highly prevalent in older adults. Knowledge among community-dwelling adults is important for effective prevention and treatment of sarcopenia. This study aims to assess current knowledge about sarcopenia, investigate willingness for treatment and prevention, and awareness of muscle health.METHOD: Participants who attended health educational events completed a questionnaire on knowledge about sarcopenia. Self-perceived muscle health was assessed by visual analog scale. Objective muscle measures included muscle mass, handgrip strength, and gait speed.RESULTS: Included participants were 197 (median aged 67.9 years [interquartile range = 57.0-75.1]). Eighteen participants (9%) reported to know what sarcopenia is. Participants' self-perceived muscle health showed a low correlation with all objective muscle measures. 76% were willing, in case of sarcopenia diagnosis, to start treatment and 71% were willing to prevent sarcopenia.DISCUSSION: Knowledge about sarcopenia is limited while participants were willing to start treatment and prevention. Strategies to increase knowledge among community-dwelling adults are needed.

© 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.Mechanical stress determines bone mass and structure. It is not known whether mechanical loading affects expression of bone regulatory genes in a combined deficiency of estrogen and vitamin D. We studied the effect of mechanical loading on the messenger RNA (mRNA) expression of bone regulatory genes during vitamin D and/or estrogen deficiency. We performed a single bout in vivo axial loading with 14 N peak load, 2 Hz frequency and 360 cycles in right ulnae of nineteen weeks old female control Wistar rats with or without ovariectomy (OVX), vitamin D deficiency and the combination of OVX and vitamin D deficiency (N = 10/group). Total bone RNA was isolated 6 hours after loading, and mRNA expression was detected of Mepe, Fgf23, Dmp1, Phex, Sost, Col1a1, Cyp27b1, Vdr, and Esr1. Serum levels of 25(OH)D, 1,25(OH)2D and estradiol were also measured at this time point. The effect of loading, vitamin D and estrogen deficiency and their interaction on bone gene expression was tested using a mixed effect model analysis. Mechanical loading significantly increased the mRNA expression of Mepe, and Sost, whereas it decreased the mRNA expression of Fgf23 and Esr1. Mechanical loading showed a significant interaction with vitamin D deficiency with regard to mRNA expression of Vdr and Esr1. Mechanical loading affected gene expression of Mepe, Fgf23, Sost, and Esr1 independently of vitamin D or estrogen, indicating that mechanical loading may affect bone turnover even during vitamin D deficiency and after menopause.

Summary Background & aims Optimal nutritional support during the acute phase of critical illness remains controversial. We hypothesized that patients with low skeletal muscle area and -density may specifically benefit from early high protein intake. Aim of the present study was to determine the association between early protein intake (day 2–4) and mortality in critically ill intensive care unit (ICU) patients with normal skeletal muscle area, low skeletal muscle area, or combined low skeletal muscle area and -density. Methods Retrospective database study in mechanically ventilated, adult critically ill patients with an abdominal CT-scan suitable for skeletal muscle assessment around ICU admission, admitted from January 2004 to January 2016 (n = 739). Patients received protocolized nutrition with protein target 1.2–1.5 g/kg/day. Skeletal muscle area and -density were assessed on abdominal CT-scans at the 3rd lumbar vertebra level using previously defined cut-offs. Results Of 739 included patients (mean age 58 years, 483 male (65%), APACHE II score 23), 294 (40%) were admitted with normal skeletal muscle area and 445 (60%) with low skeletal muscle area. Two hundred (45% of the low skeletal muscle area group) had combined low skeletal muscle area and -density. In the normal skeletal muscle area group, no significant associations were found. In the low skeletal muscle area group, higher early protein intake was associated with lower 60-day mortality (adjusted hazard ratio (HR) per 0.1 g/kg/day 0.82, 95%CI 0.73–0.94) and lower 6-month mortality (HR 0.88, 95%CI 0.79–0.98). Similar associations were found in the combined low skeletal muscle area and -density subgroup (HR 0.76, 95%CI 0.64–0.90 for 60-day mortality and HR 0.80, 95%CI 0.68–0.93 for 6-month mortality). Conclusions Early high protein intake is associated with lower mortality in critically ill patients with low skeletal muscle area and -density, but not in patients with normal skeletal muscle area on admission. These findings may be a further step to personalized nutrition, although randomized studies are needed to assess causality.

Purpose To examine whether general fatigue and fatigue during or after walking are related to energy demands during walking and physical fitness in children and young adults with physical disabilities. Methods Sixty-eight individuals with physical disabilities participated. General fatigue (Checklist Individual Strength [CIS8R] questionnaire), walking-induced fatigue (OMNI [OMNIwalk] scale after walking for 6 min), gross and net energy costs (ECs) of walking, physical strain of walking, and aerobic and anaerobic fitness were measured. Results Regression analyses showed no relations with the CIS8R. For all participants, a higher net EC was weakly related to an increased OMNIwalk. For teenagers only, low anaerobic fitness and high physical strain of walking values were moderately related to high OMNIwalk scores. Conclusion Low anaerobic fitness and high physical strain values partly explain fatigue after walking in teenagers with cerebral palsy, but not in younger children. General fatigue was not explained by low fitness levels or high energy demands of walking.

Objective: Although breast reconstruction has become an important treatment modality following mastectomy, few studies assessed predictors of postoperative sexual outcomes after breast reconstruction. Therefore, we aimed to study three sexual outcomes following implant-based breast reconstruction (IBBR), and associate multiple biopsychosocial factors with these outcomes. Methods: Data collection was part of a multicenter prospective study on IBBR. A predictive model was tested including medical, background and psychological predictors, partner relationship factors and physical sexual function. Data collection included clinical and questionnaire data (preoperatively and 1 year following reconstruction) using the BREAST-Q Sexual well-being scale (BQ5), and questions regarding sexual dysfunction and sexual satisfaction questions (Female Sexual Function Index). Results: The study sample consisted of 88 women who underwent mastectomy and IBBR. Mean postoperative BQ5 scores were lower than before surgery (M = 58 [SD = 18] vs 65 [SD = 20]; P =.01, Wilks' Lamdba =.88). Sexual dysfunctions were related strongest to orgasm inability and vaginal lubrication issues. The tested models predicted 37%-46% of the sexual outcomes: sexual outcomes were mostly predicted by psychosocial well-being, physical sexual function and partner support. Preoperative sexual and psychosocial well-being were positively associated with postoperative sexual well-being (r = 0.45 and r = 0.47). Conclusions: Although moderately positive sexual outcomes were reported after IBBR, some women reported issues with vaginal lubrication, breast sensation and orgasm. Sexual dysfunctions were predicted by vaginal lubrication and medical treatments, while sexual well-being and satisfaction were more predicted by psychosocial well-being and partner support. We advocate supportive care that includes partners and psychosocial functioning to optimize sexual outcomes after IBBR.

In children with cerebral palsy (CP), rigid ventral shell ankle-foot orthoses (vAFOs) are often prescribed to reduce excessive knee flexion in stance and lower the energy cost of walking (ECW). However, how vAFOs affect ECW is a complex issue, as vAFOs may have an impact on lower limb biomechanics, upper body movements, and balance. Besides, the vAFO’s biomechanical effect have been shown to be dependent on its stiffness around the ankle joint. We examined whether vAFO stiffness influences trunk movements and gait stability in CP, and whether there is a relationship between these factors and ECW. Fifteen children with spastic CP were prescribed vAFOs. Stiffness was varied into a rigid, stiff and flexible configuration. At baseline (shoes-only) and for each vAFO stiffness configuration, 3D-gait analyses and ECW-tests were performed. From the gait analyses, we derived trunk tilt, lateroflexion, and rotation range of motion (RoM) and the mediolateral and anteroposterior Margins of Stability (MoS) and their variability as measures of gait stability. With the ECW-test we determined the netEC. We found that wearing vAFOs significantly increased trunk laterflexion (Wald χ2=33.7, p

Right ventricular (RV) function and autonomic dysfunction are important determinants of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although successful in animal studies, effects of beta-blocker therapy on RV function in clinical trials were disappointing. To understand this discrepancy, we studied whether beta-blocker therapy changes RV sympathetic activity. Idiopathic PAH (IPAH) patients received beta-blocker therapy (uptitrated to a maximal tolerated dose) and underwent cardiac magnetic resonance imaging, right heart catheterization, and a [ 11 C]-hydroxyephedrine positron emission tomography ([ 11 C]HED PET) scan at baseline to determine, respectively, RV ejection fraction (RVEF), RV pressures, and sympathetic activity. [ 11 C]HED, a norepinephrine analogue, allows determination of sympathetic innervation of the RV. [ 11 C]HED retention index reflects norepinephrine transporter activity. As a consequence of excessive catecholamine levels in the synaptic cleft, this transporter may be downregulated. Therefore, low [ 11 C]HED retention index indicates high sympathetic activity. 13 IPAH patients underwent [ 11 C]HED PET scans at baseline and after bisoprolol treatment. Although heart rate was reduced, systemic modulation of autonomic activity by bisoprolol did not affect local RV sympathetic nerve activity, RV function, or RV wall tension. In PAH patients, RV [ 11 C]HED retention index was lower compared to LV tracer uptake (p

Purpose: Loss of selective muscle activation after stroke contributes to impaired arm function, is difficult to quantify and is not systematically assessed yet. The aim of this study was to describe and validate a technique for quantification of selective muscle activation of wrist flexor and extensor muscles in a cohort of post-stroke patients. Patterns of selective muscle activation were compared to healthy volunteers and test-retest reliability was assessed. Materials and methods: Activation Ratios describe selective activation of a muscle during its expected optimal activation as agonist and antagonist. Activation Ratios were calculated from electromyography signals during an isometric maximal torque task in 31 post-stroke patients and 14 healthy volunteers. Participants with insufficient voluntary muscle activation (maximal electromyography signal Results: Activation Ratios at the wrist were reliably quantified (Intraclass correlation coefficients 0.77–0.78). Activation Ratios were significantly lower in post-stroke patients compared to healthy participants (p Conclusion: Activation Ratios allow for muscle-specific quantification of selective muscle activation at the wrist in post-stroke patients. Loss of selective muscle activation may be a relevant determinant in assigning and evaluating therapy to improve functional outcome.Implications for RehabilitationLoss of selective muscle activation after stroke contributes to impaired arm function, is difficult to quantify and is not systematically assessed yet.The ability for selective muscle activation is a relevant determinant in assigning and evaluating therapy to improve functional outcome, e.g., botulinum toxin.Activation Ratios allow for reliable and muscle-specific quantification of selective muscle activation in post-stroke patients. Loss of selective muscle activation after stroke contributes to impaired arm function, is difficult to quantify and is not systematically assessed yet. The ability for selective muscle activation is a relevant determinant in assigning and evaluating therapy to improve functional outcome, e.g., botulinum toxin. Activation Ratios allow for reliable and muscle-specific quantification of selective muscle activation in post-stroke patients.

Objective.Cardiovascular (CV) disease (CVD) risk is increased in rheumatoid arthritis (RA). However, longterm followup studies investigating this risk are scarce.Methods.The CARRÉ (CARdiovascular research and RhEumatoid arthritis) study is a prospective cohort study investigating CVD and its risk factors in 353 patients with longstanding RA. CV endpoints were assessed at baseline and 3, 10, and 15 years after the start of the study and are compared to a reference cohort (n = 2540), including a large number of patients with type 2 diabetes (DM).Results.Ninety-five patients with RA developed a CV event over 2973 person-years, resulting in an incidence rate of 3.20 per 100 person-years. Two hundred fifty-seven CV events were reported in the reference cohort during 18,874 person-years, resulting in an incidence rate of 1.36 per 100 person-years. Age- and sex-adjusted HR for CV events were increased for RA (HR 2.07, 95% CI 1.57–2.72, p < 0.01) and DM (HR 1.51, 95% CI 1.02–2.22, p = 0.04) compared to the nondiabetic participants. HR was still increased in RA (HR 1.82, 95% CI 1.32–2.50, p < 0.01) after additional adjustment for CV risk factors. Patients with both RA and DM or insulin resistance had the highest HR for developing CVD (2.21, 95% CI 1.01–4.80, p = 0.046 and 2.67, 95% CI 1.30–5.46, p < 0.01, respectively).Conclusion.The incidence rate of CV events in established RA was more than double that of the general population. Patients with RA have an even higher risk of CVD than patients with DM. This risk remained after adjustment for traditional CV risk factors, suggesting that systemic inflammation is an independent contributor to CV risk.

Introduction A considerable number of patients experience some long-term weight regain after bariatric surgery. Body contouring surgery (BCS) is thought to strengthen post-bariatric surgery patients in their weight control and maintenance of achieved improvements in comorbidities. Objectives To examine the impact of BCS on long-term weight control and comorbidities after bariatric surgery. Methods We performed a retrospective study in a prospective database. All patients who underwent primary Roux-en-Y gastric bypass (RYGB) and presented for preoperative consultation of BCS in the same hospital were included in the study. Linear and logistic mixed-effect model analyses were used to evaluate the longitudinal relationships between patients who were accepted or rejected for BCS and their weight loss outcomes or changes in comorbidities. Results Of the 1150 patients who underwent primary RYGB between January 2010 and December 2014, 258 patients (22.4%) presented for preoperative consultation of BCS. Of these patients, 126 patients eventually underwent BCS (48.8%). Patients who were accepted for BCS demonstrated significant better ∆body mass index (BMI) on average over time (− 1.31 kg/m2/year, 95% confidence interval (CI) −2.52 − −0.10, p = 0.034) and percent total weight loss (%TWL) was significantly different at 36 months (5.79, 95%CI 1.22 – 10.37, p = 0.013) and 48 months (6.78, 95%CI 0.93 – 12.63, p = 0.023) after body contouring consultation. Patients who were accepted or rejected did not differ significantly in the maintenance of achieved improvements in comorbidities. Conclusion BCS could not be associated with the maintenance of achieved improvements in comorbidities after bariatric surgery, whereas it could be associated with improved weight loss maintenance at 36 and 48 months after body contouring consultation. This association should be further explored in a large longitudinal study.

Background. Addressing the role of somatosensory impairment, that is, afferent pathway integrity, in poststroke motor recovery may require neurophysiological assessment. Objective. We investigated the longitudinal construct validity of position-cortical coherence (PCC), that is, the agreement between mechanically evoked wrist perturbations and electroencephalography (EEG), as a measure of afferent pathway integrity. Methods. PCC was measured serially in 48 patients after a first-ever ischemic stroke in addition to Fugl-Meyer motor assessment of the upper extremity (FM-UE) and Nottingham Sensory Assessment hand-finger subscores (EmNSA-HF, within 3 and at 5, 12, and 26 weeks poststroke. Changes in PCC over time, represented by percentage presence of PCC (%PCC), mean amplitude of PCC over the affected (Amp-A) and nonaffected hemisphere (Amp-N) and a lateralization index (L-index), were analyzed, as well as their association with FM-UE and EmNSA-HF. Patients were retrospectively categorized based on FM-UE score at baseline and 26 weeks poststroke into high- and low-baseline recoverers and non-recoverers. Results. %PCC increased from baseline to 12 weeks poststroke (β = 1.6%, CI = 0.32% to 2.86%, P = .01), which was no longer significant after adjusting for EmNSA-HF and FM-UE. A significant positive association was found between %PCC, Amp-A, and EmNSA-HF. Low-baseline recoverers (n = 8) showed longitudinally significantly higher %PCC than high-baseline recoverers (n = 23). Conclusions. We demonstrated the longitudinal construct validity of %PCC and Amp-A as a measure of afferent pathway integrity. A high %PCC in low-baseline recoverers suggests that this measure also contains information on cortical excitability. Use of PCC as an EEG-based measure to address the role of somatosensory integrity to motor recovery poststroke requires further attention.

Objective: Spontaneous recovery is an important determinant of upper extremity recovery after stroke and has been described by the 70% proportional recovery rule for the Fugl–Meyer motor upper extremity (FM-UE) scale. However, this rule is criticized for overestimating the predictability of FM-UE recovery. Our objectives were to develop a longitudinal mixture model of FM-UE recovery, identify FM-UE recovery subgroups, and internally validate the model predictions. Methods: We developed an exponential recovery function with the following parameters: subgroup assignment probability, proportional recovery coefficient r k, time constant in weeks τ k, and distribution of the initial FM-UE scores. We fitted the model to FM-UE measurements of 412 first-ever ischemic stroke patients and cross-validated endpoint predictions and FM-UE recovery cluster assignment. Results: The model distinguished 5 subgroups with different recovery parameters (r 1 = 0.09, τ 1 = 5.3, r 2 = 0.46, τ 2 = 10.1, r 3 = 0.86, τ 3 = 9.8, r 4 = 0.89, τ 4 = 2.7, r 5 = 0.93, τ 5 = 1.2). Endpoint FM-UE was predicted with a median absolute error of 4.8 (interquartile range [IQR] = 1.3–12.8) at 1 week poststroke and 4.2 (IQR = 1.3–9.8) at 2 weeks. Overall accuracy of assignment to the poor (subgroup 1), moderate (subgroups 2 and 3), and good (subgroups 4 and 5) FM-UE recovery clusters was 0.79 (95% equal-tailed interval [ETI] = 0.78–0.80) at 1 week poststroke and 0.81 (95% ETI = 0.80–0.82) at 2 weeks. Interpretation: FM-UE recovery reflects different subgroups, each with its own recovery profile. Cross-validation indicates that FM-UE endpoints and FM-UE recovery clusters can be well predicted. Results will contribute to the understanding of upper limb recovery patterns in the first 6 months after stroke. ANN NEUROL 2020;87:383–393 Ann Neurol 2020;87:383–393.

Purpose To compare cardiac magnetic resonance imaging (CMR) with [15O]H2O positron emission tomography (PET) for quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with coronary artery disease (CAD). Methods Fifty-nine patients with stable CAD underwent CMR and [15O]H2O PET. The CMR imaging protocol included late gadolinium enhancement to rule out presence of scar tissue and perfusion imaging using a dual sequence, single bolus technique. Absolute MBF was determined for the three main vascular territories at rest and during vasodilator stress. Results CMR measurements of regional stress MBF and MFR showed only moderate correlation to those obtained using PET (r = 0.39; P r = 0.36; P 15O]H2O PET-derived stress MBF ≤ 2.3 mL/min/g and MFR ≤ 2.5. Using these cutoff values, CMR and PET were concordant in 137 (77%) vascular territories for stress MBF and 135 (80%) vascular territories for MFR. Conclusion CMR measurements of stress MBF and MFR showed modest agreement to those obtained with [15O]H2O PET. Nevertheless, stress MBF and MFR were concordant between CMR and [15O]H2O PET in 77% and 80% of vascular territories, respectively.

Aim To determine development curves of communication and social interaction from childhood into adulthood for individuals with cerebral palsy (CP). Method This Pediatric Rehabilitation Research in the Netherlands (PERRIN)‐DECADE study longitudinally assessed 421 individuals with CP, aged from 1 to 20 years at baseline, after 13 years (n=121 at follow‐up). Communication and social interactions were assessed using the Vineland Adaptive Behavior Scales. We estimated the average maximum performance limit (level) and age at which 90% of the limit was reached (age90) using nonlinear mixed‐effects modeling. Results One‐hundred individuals without intellectual disability were aged 21 to 34 years at follow‐up (39 females, 61 males) (mean age [SD] 28y 5mo [3y 11mo]). Limits of individuals without intellectual disability, regardless of Gross Motor Function Classification System (GMFCS) level, approached the maximum score and were significantly higher than those of individuals with intellectual disability. Ages90 ranged between 3 and 4 years for receptive communication, 6 and 7 years for expressive communication and interrelationships, 12 and 16 years for written communication, 13 and 16 years for play and leisure, and 14 and 16 years for coping. Twenty‐one individuals with intellectual disability were between 21 and 27 years at follow‐up (8 females, 13 males) (mean age [SD] 24y 7mo [1y 8mo]). Individuals with intellectual disability in GMFCS level V showed the least favourable development, but variation between individuals with intellectual disability was large. Interpretation Individuals with CP and without intellectual disability show developmental curves of communication and social interactions similar to typically developing individuals, regardless of their level of motor function. Those with intellectual disability reach lower performance levels and vary largely in individual development. What this paper adds Communication and social interactions in individuals with cerebral palsy without intellectual disability develop similarly to typically developing individuals.Communication and social interactions of individuals with intellectual disability develop less favourably and show large variation., What this paper adds Communication and social interactions in individuals with cerebral palsy without intellectual disability develop similarly to typically developing individuals.Communication and social interactions of individuals with intellectual disability develop less favourably and show large variation. This article's abstract has been translated into Spanish and Portuguese. Follow the links from the http://onlinelibrary.wiley.com/doi/10.1111/dmcn.14351/abstract to view the translations.

Contains fulltext : 229194.pdf (Publisher’s version ) (Closed access) OBJECTIVES: The current substudy of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial explores the impact of computed tomography (CT)-derived unfavorable plaque features on both hyperemic and non-hyperemic flow indices. BACKGROUND: Next to lesion severity, plaque vulnerability as assessed using coronary CT angiography affects fractional flow reserve (FFR), which is associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator-free assessment with iFR is associated with plaque stability similarly as FFR. METHODS: Of 120 patients (62% men, age 58.3 +/- 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice coronary CT angiography to assess stenosis severity and plaque features (positive remodeling [PR], low attenuation plaque [LAP], spotty calcification [SC], and napkin ring sign [NRS]), as well as intracoronary pressure measurements (FFR, iFR, Pd/Pa, and pressure ratio during adenosine within the wave-free period [iFRa]). CT-derived plaque characteristics were related to these invasive pressure measurements. RESULTS: Atherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was significantly associated with impaired FFR, iFR, Pd/Pa, and iFRa. Multivariable analysis revealed that FFR and iFR were independently related to >/=70% stenosis (-0.10, p < 0.001 and -0.09, p = 0.003, respectively) and plaque volume (-0.02, p = 0.020 and -0.02, p = 0.030, respectively). Additionally, PR and SC were also independent predictors of an impaired FFR (-0.10, p < 0.001 and -0.07, p = 0.021, respectively), but adverse plaque characteristics were not independently related to the vasodilator-free iFR. CONCLUSIONS: CT-derived vulnerable plaque characteristics are independently associated with hyperemic flow indices as assessed with FFR and iFRa, but not with non-hyperemic indices such as iFR and Pd/Pa. These findings suggest that the effects of hyperemia on pressure-derived indices might depend not only on hemodynamic stenosis severity but also on plaque characteristics.

Objectives The objective of this study is to investigate possible changes in aspirin resistance during and after pregnancy over time. Study design A longitudinal cohort study in obstetric high risk women with an indication for aspirin usage during pregnancy to prevent placenta mediated pregnancy complications. Main outcome measures Aspirin resistance measured in the first, second and third trimester of pregnancy and at least three months postpartum by four complementary test: PFA-200, VerifyNow®, Chronolog light transmission aggregometry (Chronolog LTA) and serum thromboxane B2 (TxB2) level measurements. Correlation between the devices was investigated. Results In total, 23 pregnant women participated in the present study. Aspirin resistance according to the PFA-200, VerifyNow®, Chronolog LTA and serum TxB2, was 30.4%, 17.4%, 26.1% and 23.8% respectively. Resistance by any device was 69.6%. Aspirin resistance measured by the VerifyNow®, Chronolog LTA, serum TxB2 and aspirin resistance by any device during pregnancy was demonstrated more frequently than aspirin resistance after pregnancy. Correlation between the different devices was weak. Conclusion Aspirin resistance was found in a considerable part of the participants. Considerable variation between participants, within participants over time and between the different devices was found. Prevalence of aspirin resistance during pregnancy differs from after pregnancy. More research on aspirin resistance and clinical obstetric outcome is needed.

Background: The Foot Profile Score (FPS) is a single score that summarises foot posture and dynamic foot motion during the gait cycle based on the kinematic data of the Oxford Foot Model. The FPS enables clinicians and researchers to quantify foot abnormalities during gait, to monitor change in foot/ankle motion over time, and to measure the outcome of intervention. With the creation of a new outcome measure, it is important to test its responsiveness in a clinical population for whom it may be sensitive to change. Aim: To evaluate the responsiveness of the FPS in a clinical population following isolated foot and ankle surgery. Methods: Using previous work completed to validate the FPS, we defined the minimal clinically important difference (MCID) for the FPS. Using this MCID, we applied it to a clinical population of 37 children with cerebral palsy, spastic hemiplegia, comparing their FPS before and after foot and ankle surgery. A regression analysis looked at potential relationships between the change in FPS and their pre-operative FPS, age at surgery, and time since surgery. Results: An MCID of 2.4 degrees was calculated through regression analysis. The mean change from the pre-operative FPS to the post-operative FPS was 4.6 (SD 3.7 with a range from −0.1 to 13.4). Twenty-eight children (76%) had a change in their FPS greater than the MCID. A regression analyses only showed a clear regression between pre-operative FPS and change in FPS (R2 = 0.58 p < 0.01).

Summary Purpose The use of free vascularized fibula grafts (FVFG) in complex spinal deformity surgery intends to allow for life-long stability of the spine with good long-term clinical outcome. However, these long-term outcomes of this technique are still lacking. The objective of this study is to report the long-term postoperative outcomes and establish the long-term viability of this method for spinal reconstruction. Methods A retrospective cohort study was conducted in all patients who underwent spinal reconstructive surgery utilizing a FVFG at a tertiary medical centre. Questionnaires taken from the participants were the Numeric Pain Rating Scale (NPRS), Oswestry Low Back Pain Disability (also known as Oswestry Disability Index (ODI)), Scoliosis Research Society 22r (SRS-22), the EQ-5D-5L and a self-assembled questionnaire regarding donor site comorbidities and patient satisfaction. Results Over a period of 24 years (1995–2019), we used FVFG for spinal reconstruction in 31 patients. A total of 25 patients were included in this study, 8 patients were deceased at the time of this study, and sixteen patients responded to the questionnaires. Patient satisfaction was rated 6.8 out of 10, the average SRS-22r score was 3.6, EQ-5D-5L score was 0.725, and the ODI score showed a minimal disability (0–20%) postoperatively. Overall complication-free survival was 8.9 years. Nine patients underwent a re-operation in the spinal area; five for the removal of the spinal instrumentation. Conclusion Patients reported satisfied and good long-term outcomes following FVFG surgical procedure for complex spinal deformities. Therefore, considering the alternatives, this procedure provides a good long-term solution for complex spinal deformity surgery.

In this article, author name “T.R.I. den Dungen” should be corrected to “T.R.I. van den Dungen”. The original article has been corrected.

Background Osteoradionecrosis of the jaw is a severe complication of radiotherapy in head and neck cancer patients. If conservative treatment and surgical debridement have been unsuccessful, the preferred treatment for symptomatic mandibular osteoradionecrosis (mORN) is radical surgery and subsequent reconstruction with a free vascularized flap. This study aims to assess the outcomes of free vascularized flap reconstruction in mORN. Methods A retrospective study was conducted on all patients who underwent a free vascularized flap reconstruction for mORN between 1995 and 2021 in Amsterdam UMC – VUmc, The Netherlands. Results In our cohort study, three of the twenty-eight flap reconstructions failed (10.7%). No recurrences of mORN were observed during a mean follow-up of 8 years. Conclusions The success rate of free vascularized flap reconstruction for mORN is high. The fibula is the preferred free flap for mandibular reconstruction in mORN cases. However, this type of surgery is at risk for complications and patients need to be informed that these complications may require surgical re-intervention. Level of evidence: Level IV, Therapeutic; Risk/Prognostic.

OBJECTIVE: The aims of this study were to visualize and quantify relative bone positions in the feet of individuals with cerebral palsy (CP) with a foot deformity and compare bone positions with those of typically developed (TD) controls. MATERIALS AND METHODS: Weight-bearing CT images of 14 individuals with CP scheduled for tendon transfer and/or bony surgery and of 20 TD controls were acquired on a Planmed Verity WBCT scanner. Centroids of the navicular and calcaneus with respect to the talus were used to quantify foot deformities. All taluses were aligned and the size and dimensions of the individuals' talus were scaled to correct for differences in bone sizes. In order to visualize and quantify variations in relative bone positions, 95% CI ellipsoids and standard deviations in its principle X-, Y-, and Z-directions were determined. RESULTS: In individuals with CP (age 11-17), a large variation in centroid positions was observed compared to data of TD controls. Radiuses of the ellipsoids, representing the standard deviations of the 95% CI in the principle X-, Y-, and Z-directions, were larger in individuals with CP compared to TD controls for both the calcaneus (3.16 vs 1.86 mm, 4.26 vs 2.60 mm, 9.19 vs 3.60 mm) and navicular (4.63 vs 1.55 mm, 5.18 vs 2.10 mm, 16.07 vs 4.16 mm). CONCLUSION: By determining centroids of the calcaneus and navicular with respect to the talus on WBCT images, normal and abnormal relative bone positions can be visualized and quantified in individuals with CP with various foot deformities.

Accurate assessment of burn wound depth and the associated healing potential is vital in determining the need for surgical treatment in burns. Infrared thermography measures the temperature of the burn wound noninvasively, thereby providing indirect information on its blood flow. Previous research demonstrated that a small, low-priced, handheld thermal imager has an excellent reliability, but a moderate validity for measuring burn wound healing potential. A new and more sensitive version of this convenient device has become available. The aim of this study was to evaluate the validity of thermography for measuring burn wound healing potential, compared to Laser Doppler Imaging (LDI) as a reference standard. Thermal images and LDI scans were obtained from burn wounds between 2 and 5 days postburn. Temperature differences between burned and nonburned skin (ΔT) were calculated. To evaluate validity, ΔT values were compared to the healing potential categories assessed by LDI. Two receiver operating characteristic curves were created and two ΔT cutoff values were calculated to illustrate the ability to discriminate between burn wounds that heal in a time period of less than 14 days, between 14 and 21 days, and more than 21 days. Between June and October 2018, 43 burn wounds in 32 patients were measured. ΔT cutoff values of 0.6°C (sensitivity 68%, specificity 95%) and −2.3°C (sensitivity 30%, specificity 95%) were calculated to discriminate between burn wounds that heal in 21 days, respectively. This study shows a good validity of the feasible thermal imager for the assessment of burn wound healing potential. Therefore, we consider it a promising technique to be used for triage in local hospitals and general practices, and as a valuable addition to clinical evaluation in burn centers.