University Medical Center Groningen Research Articles

Calculating Tumor Volume Using Three-Dimensional Models in Preoperative Soft-Tissue Sarcoma Surgical Planning: Does Size Matter?

This feasibility study aims to explore the use of three-dimensional virtual surgical planning to preoperatively determine the need for reconstructive surgery following resection of an extremity soft-tissue sarcoma. As flap reconstruction is performed more often in advanced disease, we hypothesized that tumor volume would be larger in the group of patients that had undergone flap reconstruction. All patients that were treated by surgical resection for an extremity soft-tissue sarcoma between 1 January 2016 and 1 October 2019 in the University Medical Center Groningen were included retrospectively. Three-dimensional models were created using the diagnostic magnetic resonance scan. Tumor volume was calculated for all patients. Three-dimensional tumor volume was 107.8 (349.1) mL in the group of patients that had undergone primary closure and 29.4 (47.4) mL in the group of patients in which a flap reconstruction was performed, p = 0.004. Three-dimensional tumor volume was 76.1 (295.3) mL in the group of patients with a complication following ESTS treatment, versus 57.0 (132.4) mL in patients with an uncomplicated course following ESTS treatment, p = 0.311. Patients who had undergone flap reconstruction had smaller tumor volumes compared to those in the group of patients treated by primary closure. Furthermore, a larger tumor volume did not result in complications for patients undergoing ESTS treatment. Therefore, tumor volume does not seem to influence the need for reconstruction. Despite the capability of three-dimensional virtual surgical planning to measure tumor volume, we do not recommend its utilization in the multidisciplinary extremity soft-tissue sarcoma treatment, considering the findings of the study.

Cardiac and intramuscular adaptations following short-term exercise prehabilitation in unfit patients scheduled to undergo hepatic or pancreatic surgery: study protocol of a multinuclear MRI study

IntroductionShort-term exercise prehabilitation programmes have demonstrated promising results in improving aerobic capacity of unfit patients prior to major abdominal surgery. However, little is known about the cardiac and skeletal muscle...

Effective questionnaire-based prediction models for type 2 diabetes across several ethnicities: a model development and validation study

Type 2 diabetes disproportionately affects individuals of non-White ethnicity through a complex interaction of multiple factors. Therefore, early disease detection and prediction are essential and require tools that can be deployed on a large scale. We aimed to tackle this problem by developing questionnaire-based prediction models for type 2 diabetes prevalence and incidence for multiple ethnicities. In this proof of principle analysis, logistic regression models to predict type 2 diabetes prevalence and incidence, using questionnaire-only variables reflecting health state and lifestyle, were trained on the White population of the UK Biobank (n=472,696 total, aged 37-73 years, data collected 2006-2010) and validated in five other ethnicities (n=29,811 total) and externally in Lifelines (n=168,205 total, aged 0-93 years, collected between 2006 and 2013). In total, 631,748 individuals were included for prevalence prediction and 67,083 individuals for the eight-year incidence prediction. Type 2 diabetes prevalence in the UK Biobank ranged between 6% in the White population to 23.3% in the South Asian population, while in Lifelines, the prevalence was 1.9%. Predictive accuracy was evaluated using the area under the receiver operating characteristic curve (AUC), and a detailed sensitivity analysis was conducted to assess potential clinical utility. We compared the questionnaire-only models to models containing physical measurements and biomarkers as well as to clinical non-laboratory type 2 diabetes risk tools and conducted a reclassification analysis. Our algorithms accurately predicted type 2 diabetes prevalence (AUC=0.901) and eight-year incidence (AUC=0.873) in the White UK Biobank population. Both models replicated well in the Lifelines external validation, with AUCs of 0.917 and 0.817 for prevalence and incidence, respectively. Both models performed consistently well across different ethnicities, with AUCs of 0.855-0.894 for prevalence and 0.819-0.883 for incidence. These models generally outperformed two clinically validated non-laboratory tools and correctly reclassified >3,000 additional cases. Model performance improved with the addition of blood biomarkers but not with the addition of physical measurements. Our findings suggest that easy-to-implement, questionnaire-based models could be used to predict prevalent and incident type 2 diabetes with high accuracy across several ethnicities, providing a highly scalable solution for population-wide risk stratification. Future work should determine the effectiveness of these models in identifying undiagnosed type 2 diabetes, validated in cohorts of different populations and ethnic representation. University Medical Center Groningen.

Rebalancing of mitochondrial homeostasis through an NAD+-SIRT1 pathway preserves intestinal barrier function in severe malnutrition

The intestine of children with severe malnutrition (SM) shows structural and functional changes that are linked to increased infection and mortality. SM dysregulates the tryptophan-kynurenine pathway, which may impact processes such as SIRT1- and mTORC1-mediated autophagy and mitochondrial homeostasis. Using a mouse and organoid model of SM, we studied the repercussions of these dysregulations on malnutrition enteropathy and the protective capacity of maintaining autophagy activity and mitochondrial health. SM was induced through feeding male weanling C57BL/6 mice a low protein diet (LPD) for 14-days. Mice were either treated with the NAD+-precursor, nicotinamide; an mTORC1-inhibitor, rapamycin; a SIRT1-activator, resveratrol; or SIRT1-inhibitor, EX-527. Malnutrition enteropathy was induced in enteric organoids through amino-acid deprivation. Features of and pathways to malnutrition enteropathy were examined, including paracellular permeability, nutrient absorption, and autophagic, mitochondrial, and reactive-oxygen-species (ROS) abnormalities. LPD-feeding and ensuing low-tryptophan availability led to villus atrophy, nutrient malabsorption, and intestinal barrier dysfunction. In LPD-fed mice, nicotinamide-supplementation was linked to SIRT1-mediated activation of mitophagy, which reduced damaged mitochondria, and improved intestinal barrier function. Inhibition of mTORC1 reduced intestinal barrier dysfunction and nutrient malabsorption. Findings were validated and extended using an organoid model, demonstrating that resolution of mitochondrial ROS resolved barrier dysfunction. Malnutrition enteropathy arises from a dysregulation of the SIRT1 and mTORC1 pathways, leading to disrupted autophagy, mitochondrial homeostasis, and ROS. Whether nicotinamide-supplementation in children with SM could ameliorate malnutrition enteropathy should be explored in clinical trials. This work was supported by the Bill and Melinda Gates Foundation, the Sickkids Research Institute, the Canadian Institutes of Health Research, and the University Medical Center Groningen.

Preconception clinical factors related to adverse pregnancy outcomes in patients with systemic lupus erythematosus or primary Sjögren’s syndrome: a retrospective cohort study

ObjectiveTo identify preconception clinical factors associated with adverse pregnancy outcomes (APO) in patients with systemic lupus erythematosus (SLE) or primary Sjögren’s syndrome (pSS).MethodsA single-centre, retrospective cohort study was conducted, which...

Diagnostic potential of plasma biomarkers and exhaled volatile organic compounds in predicting the different stages of acute mesenteric ischaemia: protocol for a multicentre prospective observational study (TACTIC study)

IntroductionAcute mesenteric ischaemia (AMI) is a life-threatening condition with short-term mortality of up to 80%. The diagnosis of AMI has remained troublesome due to the non-specific clinical presentation, symptoms and...

Treatment of iron deficiency in patients scheduled for pancreatic surgery: implications for daily prehabilitation practice in pancreatic surgery

BackgroundPreoperative anemia is a frequent complication in pancreatic surgical patients, and it adversely affects morbidity, mortality, and postoperative red blood cell (RBC) transfusion rates. Iron deficiency (ID) is often the underlying cause of anemia and constitutes a modifiable risk factor.MethodsSingle-center, longitudinal prospective cohort study conducted between May 2019 and August 2022 at the University Medical Center Groningen in the Netherlands. Patients scheduled for pancreatic surgery were referred to the outpatient prehabilitation clinic for preoperative optimization of patient-related risk factors. Patients were screened for anemia (< 12.0 g/dL in women and < 13.0 g/dL in men) and ID (either absolute [ferritin < 30 µg/L] or functional [ferritin ≥ 30 µg/L + transferrin saturation < 20% + C-reactive protein > 5 mg/L]). Intravenous iron supplementation (IVIS) (1,000 mg ferric carboxymaltose) was administered to patients with ID at the discretion of the consulting internist. Pre- and postoperative hemoglobin (Hb) levels were assessed, and perioperative outcomes were compared between patients receiving IVIS (IVIS-group) or standard care (SC-group).ResultsFrom 164 screened patients, preoperative anemia was observed in 55 (33.5%) patients, and in 23 (41.8%) of these patients, ID was the underlying cause. In 21 patients, ID was present without concomitant anemia. Preoperative IVIS was administered to 25 patients, out of 44 patients with ID. Initial differences in mean Hb levels (g/dL) between the IVIS-group and SC-group at the outpatient clinic and one day prior to surgery (10.8 versus 13.2, p < 0.001, and 11.8 versus 13.4, p < 0.001, respectively) did not exist at discharge (10.6 versus 11.1, p = 0.13). Preoperative IVIS led to a significant increase in mean Hb levels (from 10.8 to 11.8, p = 0.03). Fewer SSI were observed in the IVIS-group (4% versus 25.9% in the SC-group, p = 0.02), which remained significant in multivariable regression analysis (OR 7.01 (1.68 – 49.75), p = 0.02).ConclusionID is prevalent in patients scheduled for pancreatic surgery and is amendable to preoperative correction. Preoperative IVIS increased Hb levels effectively and reduced postoperative SSI. Screening and correction of ID is an important element of preoperative care and should be a standard item in daily prehabilitation practice.

Appropriate Implantable Cardioverter-Defibrillator Therapy in Patients with Ventricular Arrhythmia of Unclear Cause in Secondary Prevention of Sudden Cardiac Death.

In this study, we sought to investigate the occurrence of appropriate implantable cardioverter-defibrillator (ICD) therapies and inappropriate shocks in secondary prevention ICD recipients with ventricular arrhythmia of unclear cause and ventricular arrhythmia in the context of underlying heart disease. In this retrospective study, consecutive patients with an ICD implanted for secondary prevention in the University Medical Center Groningen (UMCG), the Netherlands between 1 January 2012 and 31 December 2018 were included. Patients were classified as having ventricular arrhythmia of unclear cause if no clear cause was found which could explain the index ventricular arrhythmia. The primary outcome was appropriate ICD therapy. The study population consisted of 257 patients. In 220 patients, an underlying heart disease could be identified as the cause of ventricular arrhythmia, while 37 patients had an unclear cause of ventricular arrhythmia. The median age was 64 years (interquartile range (IQR) 53-72 years). Forty-five (18%) patients were women. During a median duration of follow-up of 6.2 years (IQR 4.8-7.8 years), appropriate ICD therapy occurred in 95 (37%) patients. This number was 90 (41%) in the group with a clear etiology and 5 (14%) in the group with an unclear etiology. In multivariable analysis, index ventricular arrhythmia of unclear cause was associated with fewer appropriate ICD therapies (HR 0.37 [95% CI 0.14-0.99]; p = 0.048), as well as an increased risk of inappropriate ICD shocks (HR 3.71 [95% CI 1.17-11.80]; p = 0.026). Index ventricular arrhythmia of unclear cause was significantly associated with fewer appropriate ICD therapies.

Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry

IntroductionPortal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the...

Usability of an app-based clinical decision support system to monitor psychotropic drug prescribing appropriateness in dementia

BackgroundGuidelines recommend reluctant psychotropic drug (PD) prescribing in nursing home residents with dementia and neuropsychiatric symptoms (NPS), as efficacy of PDs is limited, and side effects are common. Nevertheless, PDs are commonly prescribed to reduce NPS. A smartphone application that evaluates appropriateness of PD prescriptions and provides recommendations from the revised Dutch guideline on problem behaviour in dementia may promote guideline adherence and increase appropriate prescribing. ObjectiveThis study aimed to assess user experiences, barriers and facilitators of the Dutch ‘Psychotropic Drug Tool’ smartphone application (PDT) in the context of appropriate prescribing of PDs to nursing home residents with dementia and NPS. Methods/designThe PDT was developed according to the recommendations of the Dutch guideline for treatment of NPS in people with dementia. Feedback provided during usability testing with two end-users was applied to improve the PDT before implementation in day-to-day practice. Sixty-three prescribers were asked to use the PDT at their own convenience for four months. User expectations and experiences were assessed at baseline and after four months with the System Usability Scale and the Assessment of Barriers and Facilitators for Implementation. ResultsExpected usability (M = 72.59; SD = 11.84) was similar to experienced usability after four months (M = 69.13; SD = 16.48). Appreciation of the PDTs user-friendliness (on average 6.7 out of 10) and design (7.3) were moderately positive, in contrast to the global rating of the PDT (5.7). Perceived barriers for PDT use were time consumption and lack of integration with existing electronic systems. Perceived facilitators were ease of use and attractive lay out. For broader implementation, physicians suggested a change in direction of the PDT: start assessment of appropriateness based on the list of NPS instead of PD as primary input. ConclusionsIn this pragmatic prospective cohort study we found that the PDT was used by elderly care physicians, with mediocre user satisfaction. The PDT will be optimized based on user feedback regarding experienced usability, barriers and facilitators, after which broader implementation can be initialized.The Medical Ethics Review Board of the University Medical Center Groningen declared this is a non-WMO study (UMCG RR Number: 201800284).

Validation of a Length-Adjusted Abdominal Arterial Calcium Score Method for Contrast-Enhanced CT Scans.

The Agatston score on noncontrast computed tomography (CT) scans is the gold standard for calcium load determination. However, contrast-enhanced CT is commonly used for patients with atherosclerotic cardiovascular diseases (ASCVDs), such as peripheral arterial occlusive disease (PAOD) and abdominal aortic aneurysm (AAA). Currently, there is no validated method to determine calcium load in the aorta and peripheral arteries with a contrast-enhanced CT. This study validated a length-adjusted calcium score (LACS) method for contrast-enhanced CT scans. The LACS (calcium volume in mm3/arterial length in cm) in the abdominal aorta was calculated using four-phase liver CT scans of 30 patients treated between 2017 and 2021 at the University Medical Center Groningen (UMCG) with no aortic disease. Noncontrast CT scans were segmented with a 130 Hounsfield units (HU) threshold, and a patient-specific threshold was used for contrast-enhanced CTs. The LACS was calculated and compared from both segmentations. Secondly, the interobserver variability and the influence of slice thickness (0.75 mm vs. 2.0 mm) was determined. There was a high correlation between the LACS from contrast-enhanced CT scans and the LACS of noncontrast CTs (R2 = 0.98). A correction factor of 1.9 was established to convert the LACS derived from contrast-enhanced CT to noncontrast CT scans. LACS interobserver agreement on contrast-enhanced CT was excellent (1.0, 95% confidence interval = 1.0-1.0). The 0.75 mm CT threshold was 541 (459-625) HU compared with 500 (419-568) HU on 2 mm CTs (p = 0.15). LACS calculated with both thresholds was not significantly different (p = 0.63). The LACS seems to be a robust method for scoring calcium load on contrast-enhanced CT scans in arterial segments with various lengths.

Proposal of early CT morphological criteria for response of liver metastases to systemic treatments in gastroenteropancreatic neuroendocrine tumors: Alternatives to RECIST.

RECIST 1.1 criteria are commonly used with computed tomography (CT) to evaluate the efficacy of systemic treatments in patients with neuroendocrine tumors (NETs) and liver metastases (LMs), but their relevance is questioned in this setting. We aimed to explore alternative criteria using different numbers of measured LMs and thresholds of size and density variation. We retrospectively studied patients with advanced pancreatic or small intestine NETs with LMs, treated with systemic treatment in the first-and/or second-line, without early progression, in 14 European expert centers. We compared time to treatment failure (TTF) between responders and non-responders according to various criteria defined by 0%, 10%, 20% or 30% decrease in the sum of LM size, and/or by 10%, 15% or 20% decrease in LM density, measured on two, three or five LMs, on baseline (≤1 month before treatment initiation) and first revaluation (≤6 months) contrast-enhanced CT scans. Multivariable Cox proportional hazard models were performed to adjust the association between response criteria and TTF on prognostic factors. We included 129 systemic treatments (long-acting somatostatin analogs 41.9%, chemotherapy 26.4%, targeted therapies 31.8%), administered as first-line (53.5%) or second-line therapies (46.5%) in 91 patients. A decrease ≥10% in the size of three LMs was the response criterion that best predicted prolonged TTF, with significance at multivariable analysis (HR 1.90; 95% CI: 1.06-3.40; p = .03). Conversely, response defined by RECIST 1.1 did not predict prolonged TTF (p = .91), and neither did criteria based on changes in LM density. A ≥10% decrease in size of three LMs could be a more clinically relevant criterion than the current 30% threshold utilized by RECIST 1.1 for the evaluation of treatment efficacy in patients with advanced NETs. Its implementation in clinical trials is mandatory for prospective validation. Criteria based on changes in LM density were not predictive of treatment efficacy. CLINICAL TRIAL REGISTRATION: Registered at CNIL-CERB, Assistance publique hopitaux de Paris as "E-NETNET-L-E-CT" July 2018. No number was assigned. Approved by the Medical Ethics Review Board of University Medical Center Groningen.

Thromboembolic events in peripartum cardiomyopathy: Results from the ESC EORP PPCM registry.

European Journal of Heart FailureAccepted Articles Short Report Thrombo-embolic events in peripartum cardiomyopathy: results from the ESC EORP PPCM registry Jasper Tromp, Jasper Tromp Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore Duke-NUS Medical School Singapore, SingaporeSearch for more papers by this authorAlice M Jackson, Alice M Jackson British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UKSearch for more papers by this authorMagdy Abdelhamid, Magdy Abdelhamid Cairo University, EgyptSearch for more papers by this authorDoaa Fouad, Doaa Fouad Assiut University Heart Hospital, Assiut, EgyptSearch for more papers by this authorGhada Youssef, Ghada Youssef Cardiology Department, Kasr Al Ainy Hospitals, Cairo University, Cairo, EgyptSearch for more papers by this authorMark C Petrie, Mark C Petrie British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UKSearch for more papers by this authorJohann Bauersachs, Johann Bauersachs Department of Cardiology and Angiology, Hannover Medical School, Hannover, GermanySearch for more papers by this authorKaren Sliwa, Karen Sliwa Hatter Institute for Cardiovascular Research in Africa, Faculty of Health Sciences, Department of Medicine and Cardiology, University of Cape Town, Cape Town, South AfricaSearch for more papers by this authorPeter van der Meer, Corresponding Author Peter van der Meer [email protected] Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands On behalf of the Investigators of the ESC EORP PPCM Registry Corresponding author. Peter van der Meer, MD, PhD, Department of Cardiology, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, the Netherlands, Tel. +31 50 3616161; Fax +31 50 3618062, Email: [email protected]Search for more papers by this author Jasper Tromp, Jasper Tromp Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore Duke-NUS Medical School Singapore, SingaporeSearch for more papers by this authorAlice M Jackson, Alice M Jackson British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UKSearch for more papers by this authorMagdy Abdelhamid, Magdy Abdelhamid Cairo University, EgyptSearch for more papers by this authorDoaa Fouad, Doaa Fouad Assiut University Heart Hospital, Assiut, EgyptSearch for more papers by this authorGhada Youssef, Ghada Youssef Cardiology Department, Kasr Al Ainy Hospitals, Cairo University, Cairo, EgyptSearch for more papers by this authorMark C Petrie, Mark C Petrie British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UKSearch for more papers by this authorJohann Bauersachs, Johann Bauersachs Department of Cardiology and Angiology, Hannover Medical School, Hannover, GermanySearch for more papers by this authorKaren Sliwa, Karen Sliwa Hatter Institute for Cardiovascular Research in Africa, Faculty of Health Sciences, Department of Medicine and Cardiology, University of Cape Town, Cape Town, South AfricaSearch for more papers by this authorPeter van der Meer, Corresponding Author Peter van der Meer [email protected] Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands On behalf of the Investigators of the ESC EORP PPCM Registry Corresponding author. Peter van der Meer, MD, PhD, Department of Cardiology, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, the Netherlands, Tel. +31 50 3616161; Fax +31 50 3618062, Email: [email protected]Search for more papers by this author First published: 24 April 2023 https://doi.org/10.1002/ejhf.2871 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/ejhf.2871. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

Physicians and nurses view on their roles in communication and collaboration with families: A qualitative study.

Families are introduced as new partners in interprofessional communication and collaboration during hospitalisation of an adult patient. Their introduction into the healthcare team has consequences for the roles and responsibilities of all healthcare professionals. Role clarification is thus needed to create optimal communication and collaboration with families. To gain insight into how physicians and nurses view their own roles and each other's roles in communication and collaboration with families in the care of adult patients. A qualitative interpretive interview design was used. Fourteen semi-structured interviews, with seven physicians and seven nurses, were conducted. Data were analysed according to the steps of thematic analysis. For the study design and analysis of the results, the guidelines of the consolidated criteria for reporting qualitative studies (COREQ) were followed. The ethical committee of the University Medical Center Groningen approved the study protocol (research number 202100640). Thematic analysis resulted in three themes, each consisting of two or three code groups. Two themes "building a relationship" and "sharing information" were described as roles that both nurses and physicians share regarding communication and collaboration with families. The role expectations differed between physicians and nurses, but these differences were not discussed with each other. The theme "providing support to family" was regarded a nurse-specific role by both professions. Physicians and nurses see a role for themselves and each other in communication and collaboration with families. However, the division of roles and expectations thereof are different, overlapping, and unclear. To optimise the role and position of family during hospital care, clarification and division of the roles between physicians and nurses in this partnership is necessary.

Decreased Muscle Strength in Children With Repaired Tetralogy of Fallot: Relation With Exercise Capacity.

Background The aim of this study is to describe muscle strength in pediatric patients with repaired tetralogy of Fallot compared with healthy peers and to analyze the correlation between muscle strength and peak oxygen uptake, exercise capacity (mL/min). Methods and Results A prospective, cross-sectional study was carried out in the University Medical Center Groningen between March 2016 and December 2019, which included 8 -to-19-year-old patients with repaired tetralogy of Fallot. Exclusion criteria comprised the following: Down syndrome, unstable pulmonary disease and severe scoliosis affecting pulmonary function, neuromuscular disease, and mental or physical limitations that prohibit the execution of the functional tests. Muscle strength was compared with 2 healthy pediatric cohorts from the Northern Netherlands. Handgrip strength, maximal voluntary isometric contraction, and dynamic muscle strength in correlation with peak oxygen uptake, exercise capacity (mL/min) were the main outcomes of the study. The 67 patients with repaired tetralogy of Fallot (42% female; aged 12.9 [interquartile range, 10.0-16.3] years old) were compared with healthy children. The patients showed reduced grip strength (z-score [mean±SD] -1.5±1.2, P<0.001), and total muscle strength (z-score -0.9±1.3, P<0.001). Dynamic strength (Bruininks-Oseretsky test) was significantly reduced (z-score -0.3±0.8, P=0.001), but running, speed, and agility were normal (z-score 0.1±0.7, P=0.4). Univariate correlation analyses showed strong correlations between absolute peak oxygen uptake, exercise capacity (mL/min), and muscle strength (grip strength r=0.83, total muscle strength r=0.88; P<0.001). In multivariate analyses, including correction for age and sex, total muscle strength (B 0.3; P=0.009), and forced vital capacity (B 0.5; P=0.02) correlated with peak oxygen uptake, exercise capacity (mL/min), independent of conventional cardiovascular parameters. Conclusions Children with repaired tetralogy of Fallot show reduced muscle strength, which strongly correlated with their exercise performance.

Morphological Variation of the Mandible in the Orthognathic Population-A Morphological Study Using Statistical Shape Modelling.

The aim of this study was to investigate the value of 3D Statistical Shape Modelling for orthognathic surgery planning. The goal was to objectify shape variations in the orthognathic population and differences between male and female patients by means of a statistical shape modelling method. Pre-operative CBCT scans of patients for whom 3D Virtual Surgical Plans (3D VSP) were developed at the University Medical Center Groningen between 2019 and 2020 were included. Automatic segmentation algorithms were used to create 3D models of the mandibles, and the statistical shape model was built through principal component analysis. Unpaired t-tests were performed to compare the principal components of the male and female models. A total of 194 patients (130 females and 64 males) were included. The mandibular shape could be visually described by the first five principal components: (1) The height of the mandibular ramus and condyles, (2) the variation in the gonial angle of the mandible, (3) the width of the ramus and the anterior/posterior projection of the chin, (4) the lateral projection of the mandible's angle, and (5) the lateral slope of the ramus and the inter-condylar distance. The statistical test showed significant differences between male and female mandibular shapes in 10 principal components. This study demonstrates the feasibility of using statistical shape modelling to inform physicians about mandible shape variations and relevant differences between male and female mandibles. The information obtained from this study could be used to quantify masculine and feminine mandibular shape aspects and to improve surgical planning for mandibular shape manipulations.

BRCA1/2 testing rates in epithelial ovarian cancer: a focus on the untested patients

BackgroundSince 2015, Dutch guidelines have recommended BRCA1/2 pathogenic variant testing for all patients with epithelial ovarian cancer. Recently, recommendations shifted from germline testing to the tumor-first approach, in which tumor...

Home-based guided hypnotherapy for children with functional abdominal pain and irritable bowel syndrome in primary care: study protocol for a randomised controlled trial

IntroductionChildren often present to primary care with functional abdominal pain (FAP) or irritable bowel syndrome (IBS), and around half still have abdominal complaints 1 year later. Hypnotherapy is an evidence-based...

Influence of health system and patient characteristics on expectations and outcome in total hip arthroplasty patients in the Dutch-German border region: protocol for a mixed-methods prospective observational comparative study (hip across)

IntroductionTotal hip arthroplasty (THA) is the treatment of choice for end-stage osteoarthritis of the hip. Management of THA differs between countries, and it is hypothesised that this can influence patients’...

After an initial balance favoring collagen formation and mineralization, bone turnover markers return to pre-treatment levels during long-term TNF-α inhibition in patients with ankylosing spondylitis.

Bone turnover balance favors bone formation, especially mineralization, during the first 3 years of treatment with TNF-α inhibitors (TNFi). Our aim was to evaluate the course of serum bone turnover markers (BTM) and to investigate if facilitation of mineralization reflected by BTM BALP continues to increase during 6 years of TNFi treatment in patients with ankylosing spondylitis (AS) in daily clinical practice. Included were outpatients from the University Medical Center Groningen (UMCG) participating in the Groningen Leeuwarden Axial SpA (GLAS) cohort who were treated with TNFi for at least 6 years. Serum markers of collagen resorption, bone regulation, collagen formation and facilitator of bone mineralization (sCTX, OC, PINP and BALP, respectively) were measured at baseline, 3 and 6 months, 1, 2, 4 and 6 years. Z-scores were calculated to correct for age and gender. 53 AS patients were eligible for analyses (66% male, mean age 39±11 years). Disease activity showed rapid and sustained improvement after start of TNFi. Evaluating BTM, sCTX did not significantly change during 6 years of treatment. OC was only significantly increased at 3 months compared to baseline, with median change in Z-score of +0.5. PINP significantly increased at 3 and 6 months and 2 years of treatment, with maximum median change in Z-score of +0.3. Interestingly, BALP was significantly increased at all time points up to and including 2 years of TNFi treatment, with maximum change in median Z-score of +1.2, and decreased thereafter. In AS patients receiving long-term TNFi, bone turnover balance favored collagen formation and facilitation of mineralization during the first 2 years of treatment. Thereafter, at 4 and 6 years of follow-up, BTM Z-scores returned to pre-treatment levels.