Publications by authors named "Sander M J van Kuijk"

160 Publications

A retrospective study on patients with chronic knee pain treated with ultrasound-guided radiofrequency of the genicular nerves (RECORGEN trial).

Pain Pract 2021 Oct 30. Epub 2021 Oct 30.

Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Therapy, Hospital Oost-Limburg, Genk, Belgium.

Introduction: Radiofrequency (RF) treatment of the genicular nerves is a promising treatment for chronic osteoarthritic and persistent postsurgical knee pain (PPSP), refractory to conventional medical management.

Methods: The RECORGEN study is a retrospective single-center cohort study of patients treated with ultrasound-guided conventional RF of the genicular nerves for chronic knee pain in Hospital Oost-Limburg, Genk from September 2017 to June 2020. Subgroup analysis based on etiology of pain (PPSP and degenerative knee pain) was performed in addition to the total study population analysis. Outcome parameters were global perceived effect (GPE), Numeric Rating Scale for pain, consumption of strong opioids, and safety of the treatment at 6 weeks and cross-sectionally at a variable time point. Treatment success was defined as GPE≥50%.

Results: Sixty-eight cases were screened of which 59 (46 diagnosed with PPSP and 13 with degenerative knee pain) were included in the study. Treatment success at 6 weeks was achieved in 19 of 59 interventions (32.2%) and was similar in both groups. Seventeen responders were evaluated at follow-up. 45.1% (8/17) continued to have a positive effect at the second time point. The mean duration of effect of the RF treatment was 8.3 months. Safety analysis at 6 weeks and at the second time point showed a good safety profile of the treatment.

Conclusion: Conventional RF of the genicular nerves was clinically successful in more than 30% of the study population refractory to conventional medical management. Overall, the treatment was well tolerated. The mean duration of effect was 8.3 months.
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http://dx.doi.org/10.1111/papr.13088DOI Listing
October 2021

Perioperative goal-directed therapy in high-risk abdominal surgery. A multicenter randomized controlled superiority trial.

J Clin Anesth 2021 Dec 15;75:110506. Epub 2021 Sep 15.

Department of Anesthesiology, Maastricht University Medical Center, Maastricht, the Netherlands. Electronic address:

Study Objective: The potential of perioperative goal-directed therapy (PGDT) to improve outcome after high-risk abdominal surgery remains subject of debate. In particular, there is a need for large, multicenter trials focusing on relevant patient outcomes to confirm the evidence found in small, single center studies including minor complications in their composite endpoints. The present study therefore aims to investigate the effect of an arterial waveform analysis based PGDT algorithm on the incidence of major complications including mortality after high-risk abdominal surgery.

Design: Prospective randomized controlled multicenter trial.

Setting: Operating theatres and Post-Anesthesia/Intensive Care units (PACU/ICU) of four tertiary hospitals in The Netherlands.

Patients: A total number of 482 patients undergoing elective, abdominal surgery that is considered high-risk due to the extent of the procedure and/or patient comorbidities.

Interventions: Hemodynamic therapy using an age-specific PGDT algorithm including cardiac index (CI) and stroke volume variation (SVV) measurements during a 24-h perioperative period starting at induction of anesthesia.

Measurements: The average number of major complications (including mortality) within 30 days after surgery, the number of minor complications, hospital and PACU/ICU length of stay (LOS), amounts of fluids and vasoactive medications used. Complications were graded using the Accordion severity grading system.

Results: The average number of major complications per patient was 0.79 (PGDT group) versus 0.69 (control group) (p = 0.195). There were no statistically significant differences in the number of minor complications, hospital LOS, PACU/ICU LOS, or grading of complications. Patients in the PGDT group received more fluids intraoperatively, more dobutamine intra- and postoperatively, while patients in the control group received more phenylephrine during the operation.

Conclusions: PGDT based on a CI and SVV driven algorithm did not result in improved outcomes after high-risk abdominal surgery.

Clinical Trial Registration: Netherlands Trial Registry: NTR3380.
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http://dx.doi.org/10.1016/j.jclinane.2021.110506DOI Listing
December 2021

Association between bone shape and the presence of a fracture in patients with a clinically suspected scaphoid fracture.

J Biomech 2021 Nov 30;128:110726. Epub 2021 Aug 30.

Department of Internal Medicine, VieCuri Medical Center, Venlo, the Netherlands; NUTRIM School for Nutrition and Translational Research in Metabolism, Faculty of Health Medicine and Life Sciences, Maastricht University Medical Center, Maastricht, the Netherlands; Department of Internal Medicine, Subdivision of Rheumatology, Maastricht University Medical Center, Maastricht, the Netherlands; Faculty of Medicine and Life Sciences, Hasselt University, Belgium. Electronic address:

Scaphoid fractures are difficult to diagnose with current imaging modalities. It is unknown whether the shape of the scaphoid bone, assessed by statistical shape modeling, can be used to differentiate between fractured and non-fractured bones. Therefore, the aim of this study was to investigate whether the presence of a scaphoid fracture is associated with shape modes of a statistical shape model (SSM). Forty-one high-resolution peripheral quantitative computed tomography (HR-pQCT) scans were available from patients with a clinically suspected scaphoid fracture of whom 15 patients had a scaphoid fracture. The scans showed no motion artefacts affecting bone shape. The scaphoid bones were semi-automatically contoured, and the contours were converted to triangular meshes. The meshes were registered, followed by principal component analysis to determine mean shape and shape modes describing shape variance. The first five out of the forty shape modes cumulatively explained 87.8% of the shape variance. Logistic regression analysis was used to study the association between shape modes and fracture presence. The regression models were used to classify the 41 scaphoid bones as fractured or non-fractured using a cut-off value that maximized the sum of sensitivity and specificity. The classification of the models was compared with fracture diagnosis on HR-pQCT. A regression model with four shape modes had an area under the ROC-curve of 72.3% and correctly classified 75.6% of the scaphoid bones (fractured: 60.0%, non-fractured: 84.6%). To conclude, fracture presence in patients with a clinically suspected scaphoid fracture appears to be associated with the shape of the scaphoid bone.
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http://dx.doi.org/10.1016/j.jbiomech.2021.110726DOI Listing
November 2021

Non-Conveyance Due to Patient-Initiated Refusal in Emergency Medical Services: A Retrospective Population-Based Registry Analysis Study in Riyadh Province, Saudi Arabia.

Int J Environ Res Public Health 2021 09 2;18(17). Epub 2021 Sep 2.

Department of Health Services Research, CAPHRI School for Public Health and Primary Care, Maastricht University, 6229 GT Maastricht, The Netherlands.

This research study aimed to investigate the association between demographic and operational factors and emergency medical services (EMS) missions ending in non-conveyance (NC) due to patient-initiated refusal (PIR). We conducted a retrospective population-based registry study by analyzing 67,620 EMS missions dispatched to the scene during 2018 in the Riyadh province. First, the number and percentages of conveyances statuses were calculated. Then, using crude and adjusted linear and logistic regression analysis, we determined which characteristics were predictors of NC due to PIR. We found that 23,991 (34.4%) of missions ended in NC due to PIR, and 5969 ended in EMS-initiated refusal (8.6%). NC rates due to PIR were higher for women, adults, for missions in Riyadh city, during nighttime, for medical emergencies, and for advanced life support (ALS) crews. We also found the following additional predictors significantly associated with the odds of NC due to PIR in crude regression analyses: age category, geographical location, EMS-shift, time of call, emergency type, and response time. We conclude that the NC rate represents half of all missions for patients requesting EMS, and the rate in Riyadh city has increased compared to previous studies. Most NC cases occur for the highest urgency level of medical emergency type in Riyadh city during the nighttime with ALS crews. NC due to PIR involves younger patients more than elderly, and females more than males. This study's findings have provided empirical evidence that indicate that conducting further studies involving EMS providers, patients, and the public to identify precise and detailed reasons is required.
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http://dx.doi.org/10.3390/ijerph18179252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431479PMC
September 2021

Does Day-to-Day Variability in Stool Consistency Link to the Fecal Microbiota Composition?

Front Cell Infect Microbiol 2021 20;11:639667. Epub 2021 Jul 20.

Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands.

Introduction: Stool consistency has been associated with fecal microbial composition. Stool consistency often varies over time, in subjects with and without gastrointestinal disorders, raising the question whether variability in the microbial composition should be considered in microbiota studies. We evaluated within-subject day-to-day variability in stool consistency and the association with the fecal microbiota in irritable bowel syndrome (IBS) and healthy subjects, over seven days.

Methods: Twelve IBS patients and 12 healthy subjects collected fecal samples during seven consecutive days. Stool consistency was determined by the patient-reported Bristol Stool Scale (BSS) and fecal dry weight percentage. 16S rRNA V4 gene sequencing was performed and microbial richness (alpha diversity; Chao1 index, observed number of species, effective Shannon index) and microbial community structure (beta diversity; Bray-Curtis distance, generalized UniFrac, and taxa abundance on family level) were determined.

Results: Linear mixed-effects models showed significant associations between stool consistency and microbial richness, but no time effect. This implies that between-subject but not within-subject variation in microbiota over time can partially be explained by variation in stool consistency. Redundancy analysis showed a significant association between stool consistency and microbial community structure, but additional linear mixed-effects models did not demonstrate a time effect on this.

Conclusion: This study supports an association between stool consistency and fecal microbiota, but no effect of day-to-day fluctuations in stool consistency within seven days. This consolidates the importance of considering stool consistency in gut microbiota research, though confirms the validity of single fecal sampling to represent an individual's microbiota at a given time point. NCT00775060.
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http://dx.doi.org/10.3389/fcimb.2021.639667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386168PMC
September 2021

Association between individual surgeon volume and outcome in mitral valve surgery: a systematic review.

J Thorac Dis 2021 Jul;13(7):4500-4510

Department of Cardiothoracic Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.

Background: Surgeon volume has been identified as a possible factor that influences outcomes in mitral valve (MV) surgery. The aim of this study was to systematically review all published studies on the association between individual surgeon volume and outcome in MV surgery.

Methods: PubMed was searched last on 19 November 2020. The reporting of this systematic review was done in accordance with PRISMA guidelines. Manuscripts were eligible when these studied individual surgeon volumes and its association with repair rate, mortality or reoperation. The methodological quality of the studies was assessed with the Newcastle-Ottawa Scale (NOS). Absolute numbers and percentages of the outcome measures, odds ratios (ORs), P values and threshold values regarding surgeon volume were collected.

Results: A total of 7 retrospective cohort studies were included in the qualitative analysis with total of 158488 patients. Definitions of surgeon volumes were found to be heterogenic and therefore pooling of data was not possible. Surgeon volume was significantly associated with repair rate (OR =1.25-5.5) and mortality (OR =0.46-0.84 and OR =1.50-2.27 depending on the reference group). Regarding reoperation, results were not consistent and did not always show a significant lower reoperation rate when surgeon volume increased. A mean threshold of minimally 30 MV surgeries per year was found.

Discussion: Higher surgeon volume is significantly associated with improved outcomes of repair rate and mortality. MV should preferentially be performed by high-volume surgeons and centralization of MV surgery might be necessary.
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http://dx.doi.org/10.21037/jtd-21-578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339780PMC
July 2021

Systematic Review on Epidural Steroid Injections: Quo Vadis?

Clin J Pain 2021 11;37(11):863-865

Department of Anesthesiology, Critical Care, Emergency Medicine and Multidisciplinary Pain Center, Ziekenhuis Oost-Limburg, Bessemerstraat, Lanaken Belgium.

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http://dx.doi.org/10.1097/AJP.0000000000000973DOI Listing
November 2021

Rate control drugs differ in the prevention of progression of atrial fibrillation.

Europace 2021 Aug 20. Epub 2021 Aug 20.

Department of Cardiology, Martini Hospital, Van Swietenplein 1, 9728 NT Groningen, The Netherlands.

Aims: We hypothesize that in patients with paroxysmal atrial fibrillation (AF), verapamil is associated with lower AF progression compared to beta blockers or no rate control.

Methods And Results: In this pre-specified post hoc analysis of the RACE 4 randomized trial, the effect of rate control medication on AF progression in paroxysmal AF was analysed. Patients using Vaughan-Williams Class I or III antiarrhythmic drugs were excluded. The primary outcome was a composite of first electrical cardioversion (ECV), chemical cardioversion (CCV), or atrial ablation. Event rates are displayed using Kaplan-Meier curves and multivariable Cox regression analyses are used to adjust for baseline differences. Out of 666 patients with paroxysmal AF, 47 used verapamil, 383 used beta blockers, and 236 did not use rate control drugs. The verapamil group was significantly younger than the beta blocker group and contained more men than the no rate control group. Over a mean follow-up of 37 months, the primary outcome occurred in 17% in the verapamil group, 33% in the beta blocker group, and 33% in the no rate control group (P = 0.038). After adjusting for baseline characteristics, patients using verapamil have a significantly lower chance of receiving ECV, CCV, or atrial ablation compared to patients using beta blockers [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.19-0.83] and no rate control (HR 0.64, 95% CI 0.44-0.93).

Conclusion: In patients with newly diagnosed paroxysmal AF, verapamil was associated with less AF progression, as compared to beta blockers and no rate control.
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http://dx.doi.org/10.1093/europace/euab191DOI Listing
August 2021

Targeting Autoregulation-Guided Cerebral Perfusion Pressure after Traumatic Brain Injury (COGiTATE): A Feasibility Randomized Controlled Clinical Trial.

J Neurotrauma 2021 Oct 16;38(20):2790-2800. Epub 2021 Aug 16.

Department of Intensive Care Medicine, University Maastricht (KEMTA), Maastricht University Medical Center+, Maastricht, The Netherlands.

Managing traumatic brain injury (TBI) patients with a cerebral perfusion pressure (CPP) near to the cerebral autoregulation (CA)-guided "optimal" CPP (CPPopt) value is associated with improved outcome and might be useful to individualize care, but has never been prospectively evaluated. This study evaluated the feasibility and safety of CA-guided CPP management in TBI patients requiring intracranial pressure monitoring and therapy (TBIicp patients). The CPPopt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) parallel two-arm feasibility trial took place in four tertiary centers. TBIicp patients were randomized to either the Brain Trauma Foundation (BTF) guideline CPP target range (control group) or to the individualized CA-guided CPP targets (intervention group). CPP targets were guided by six times daily software-based alerts for up to 5 days. The primary feasibility end-point was the percentage of time with CPP concordant (±5 mm Hg) with the set CPP targets. The main secondary safety end-point was an increase in therapeutic intensity level (TIL) between the control and intervention group. Twenty-eight patients were randomized to the control and 32 patients to the intervention group. CPP in the intervention group was in the target range for 46.5% (interquartile range, 41.2-58) of the monitored time, significantly higher than the feasibility target specified in the published protocol (36%;  < 0.001). There were no significant differences between groups for TIL or for other safety end-points. Conclusively, targeting an individual and dynamic CA-guided CPP is feasible and safe in TBIicp patients. This encourages a prospective trial powered for clinical outcomes.
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http://dx.doi.org/10.1089/neu.2021.0197DOI Listing
October 2021

Access flow volume (Qa) and survival in a hemodialysis population: An analysis of 5208 Qa measurements over a 9-year period.

Nephrol Dial Transplant 2021 Aug 12. Epub 2021 Aug 12.

Department of Surgery, Máxima MC, Veldhoven, The Netherlands.

Background: Aim of the study was to determine associations between characteristics of arteriovenous access (AVA) access flow volume (Qa, mL/min) and four year freedom from cardiovascular mortality (4yr-CVM) in hemodialysis (HD) patients.

Methods: HD patients who received a primary AVA between January 2010 and December 2017 in one center were analyzed. Initial Qa was defined as the first Qa value obtained in a well-functioning AVA by a two-needle dilution technique. Actual Qa was defined as access flow at a random point of time. Changes in actual Qa were expressed per 3-month periods. CVM was assessed according to the ERA-EDTA classification. The optimal cut-off point for initial Qa was identified by a receiver operating characteristic curve. A joint modelling statistical technique determined longitudinal associations between Qa characteristics and 4yr-CVM.

Results: A total of 5208 Qa measurements (165 patients, male n = 103; age 70±12 years, autologous AVA n = 146, graft n = 19) were analyzed. During follow-up (Dec 2010-Jan 2018, median 36 months), 79 patients (48%) died. An initial Qa < 900 mL/min was associated with an increased 4y-CVM risk (HR: 4.05; 95% CI [1.94-8.43], P<0.001). After 4 years, freedom from CVM was 34% lower in patients with a Qa < 900 mL/min (53 ±7% vs. Qa ≥ 900 mL/min: 87 ±4%, P <0.001). An association between increases in actual Qa over 3-month periods and mortality was found (HR: 4.48 per 100mL/min, 95% CI [1.44-13.97], P =0.010) indicating that patients demonstrating increasing Qa were more likely to die. By contrast, actual Qa per se was not related to survival.

Conclusions: Studying novel arteriovenous access Qa characteristics may contribute to understanding excess CVM in HD patients.
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http://dx.doi.org/10.1093/ndt/gfab242DOI Listing
August 2021

A prognostic model for the preoperative identification of patients at risk for receiving transfusion of packed red blood cells in cardiac surgery.

Transfusion 2021 08 22;61(8):2336-2346. Epub 2021 Jul 22.

Department of Epidemiology, MCL Academy, Medical Center Leeuwarden, Leeuwarden, The Netherlands.

Background: Patients undergoing cardiothoracic surgery are at substantial risk for blood transfusion. Increased awareness and patient blood management have resulted in a significant reduction over the past years. The next step is preoperative treatment of patients at high risk for packed red blood cells (RBC) transfusion, with the ultimate goal to eventually prevent RBC transfusion. A prediction model was developed to select patients at high risk for RBC transfusion.

Materials And Methods: Data of all patients that underwent cardiac surgery in our center between 2008 and 2013 (n = 2951) were used for model development, and between 2014 and 2016 for validation (n = 1136). Only preoperative characteristics were included in a multinomial regression model with three outcome categories (no, RBC, other transfusion). The accuracy of the estimated risks and discriminative ability of the model were assessed. Clinical usefulness was explored.

Results: Risk factors included are sex, type of surgery, redo surgery, age, height, body mass index, preoperative hemoglobin level, and preoperative platelet count. The model has excellent discriminative ability for predicting RBC transfusion versus no transfusion (area under the curve [AUC] = 94%) and good discriminative ability for RBC transfusion versus other transfusion (AUC = 84%). With a cut-off value of RBC risk of 16.8% and higher, the model is well able to identify a high proportion of patients at risk for RBC transfusion (sensitivity = 87.1%, specificity = 82.3%).

Conclusion: In the current study, a prediction tool was developed to be used for risk stratification of patients undergoing elective cardiac surgery at risk for blood transfusions.
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http://dx.doi.org/10.1111/trf.16438DOI Listing
August 2021

Influence of Contrast Material Temperature on Patient Comfort and Image Quality in Computed Tomography of the Abdomen: A Randomized Controlled Trial.

Invest Radiol 2021 Jul 2. Epub 2021 Jul 2.

From the Department of Radiology and Nuclear Medicine, Maastricht University Medical Center CARIM School for Cardiovascular Diseases, Maastricht University Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center Department of Internal Medicine, Division of Medical Oncology GROW-School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht, the Netherlands.

Background: International guideline recommendations on safe use of contrast media (CM) are conflicting regarding the necessity to prewarm iodinated CM.

Purpose: Aim of the study was to evaluate the effects of room temperature CM compared with prewarmed CM on image quality, safety, and patient comfort in abdominal computed tomography (CT).

Methods: CATCHY (Contrast Media Temperature and Patient Comfort in Computed Tomography of the Abdomen) is a double-blinded, randomized noninferiority trial. Between February and August 2020, 218 participants referred for portal venous abdominal CT were prospectively and randomly assigned to 1 of 2 groups. All patients received iopromide at 300 mg I/mL: group 1 at room temperature (~23°C [~73°F]) and group 2 prewarmed to body temperature (37°C [99°F]). A state-of-the-art individualized CM injection protocol was used, based on body weight and adapted to tube voltage. Primary outcome was absolute difference in mean liver attenuation between groups, calculated with a 2-sided 95% confidence interval. The noninferiority margin was set at -10 HU. Secondary outcomes were objective (signal-to-noise ratio and contrast-to-noise ratio) and subjective image quality; CM extravasations and other adverse events; and participant comfort (5-point scale questionnaire) and pain (numeric rating scale). This trial is registered with ClinicalTrials.gov (NCT04249479).

Results: The absolute difference in mean attenuation between groups was + 4.23 HU (95% confidence interval, +0.35 to +8.11; mean attenuation, 122.2 ± 13.1 HU in group 1, 118.0 ± 15.9 HU in group 2; P = 0.03). Signal-to-noise ratio, contrast-to-noise ratio, and subjective image quality were not significantly different between groups (P = 0.53, 0.23, and 0.99 respectively). Contrast extravasation occurred in 1 patient (group 2), and no other adverse events occurred. Comfort scores were significantly higher in group 1 than in group 2 (P = 0.03); pain did not significantly differ (perceived P > 0.99; intensity P = 0.20).

Conclusions: Not prewarming iodinated CM was found noninferior in abdominal CT imaging. Prewarming conferred no beneficial effect on image quality, safety, and comfort, and might therefore no longer be considered a prerequisite in state-of-the art injection protocols for parenchymal imaging.
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http://dx.doi.org/10.1097/RLI.0000000000000807DOI Listing
July 2021

Chyme Reinfusion Restores the Regulatory Bile Salt-FGF19 Axis in Patients With Intestinal Failure.

Hepatology 2021 Nov 26;74(5):2670-2683. Epub 2021 Aug 26.

Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands.

Background And Aims: Automated chyme reinfusion (CR) in patients with intestinal failure (IF) and a temporary double enterostomy (TDE) restores intestinal function and protects against liver injury, but the mechanisms are incompletely understood. The aim was to investigate whether the beneficial effects of CR relate to functional recovery of enterohepatic signaling through the bile salt-FGF19 axis.

Approach And Results: Blood samples were collected from 12 patients, 3 days before, at start, and 1, 3, 5, and 7 weeks after CR initiation. Plasma FGF19, total bile salts (TBS), 7-α-hydroxy-4-cholesten-3-one (C4; a marker of bile salt synthesis), citrulline (CIT), bile salt composition, liver tests, and nutritional risk indices were determined. Paired small bowel biopsies prior to CR and after 21 days were taken, and genes related to bile salt homeostasis and enterocyte function were assessed. CR induced an increase in plasma FGF19 and decreased C4 levels, indicating restored regulation of bile salt synthesis through endocrine FGF19 action. TBS remained unaltered during CR. Intestinal farnesoid X receptor was up-regulated after 21 days of CR. Secondary and deconjugated bile salt fractions were increased after CR, reflecting restored microbial metabolism of host bile salts. Furthermore, CIT and albumin levels gradually rose after CR, while abnormal serum liver tests normalized after CR, indicating restored intestinal function, improved nutritional status, and amelioration of liver injury. CR increased gene transcripts related to enterocyte number, carbohydrate handling, and bile salt homeostasis. Finally, the reciprocal FGF19/C4 response after 7 days predicted the plasma CIT time course.

Conclusions: CR in patients with IF-TDE restored bile salt-FGF19 signaling and improved gut-liver function. Beneficial effects of CR are partly mediated by recovery of the bile salt-FGF19 axis and subsequent homeostatic regulation of bile salt synthesis.
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http://dx.doi.org/10.1002/hep.32017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596508PMC
November 2021

Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort.

Thromb J 2021 May 31;19(1):35. Epub 2021 May 31.

Department of Intensive Care Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Background: The incidence of pulmonary thromboembolism is high in SARS-CoV-2 patients admitted to the Intensive Care. Elevated biomarkers of coagulation (fibrinogen and D-dimer) and inflammation (c-reactive protein (CRP) and ferritin) are associated with poor outcome in SARS-CoV-2. Whether the time-course of fibrinogen, D-dimer, CRP and ferritin is associated with the occurrence of pulmonary thromboembolism in SARS-CoV-2 patients is unknown. We hypothesise that patients on mechanical ventilation with SARS-CoV-2 infection and clinical pulmonary thromboembolism have lower concentrations of fibrinogen and higher D-dimer, CRP, and ferritin concentrations over time compared to patients without a clinical pulmonary thromboembolism.

Methods: In a prospective study, fibrinogen, D-dimer, CRP and ferritin were measured daily. Clinical suspected pulmonary thromboembolism was either confirmed or excluded based on computed tomography pulmonary angiography (CTPA) or by transthoracic ultrasound (TTU) (i.e., right-sided cardiac thrombus). In addition, patients who received therapy with recombinant tissue plasminogen activator were included when clinical instability in suspected pulmonary thromboembolism did not allow CTPA. Serial data were analysed using a mixed-effects linear regression model, and models were adjusted for known risk factors (age, sex, APACHE-II score, body mass index), biomarkers of coagulation and inflammation, and anticoagulants.

Results: Thirty-one patients were considered to suffer from pulmonary thromboembolism ((positive CTPA (n = 27), TTU positive (n = 1), therapy with recombinant tissue plasminogen activator (n = 3)), and eight patients with negative CTPA were included. After adjustment for known risk factors and anticoagulants, patients with, compared to those without, clinical pulmonary thromboembolism had lower average fibrinogen concentration of - 0.9 g/L (95% CI: - 1.6 - - 0.1) and lower average ferritin concentration of - 1045 μg/L (95% CI: - 1983 - - 106) over time. D-dimer and CRP average concentration did not significantly differ, 561 μg/L (- 6212-7334) and 27 mg/L (- 32-86) respectively. Ferritin lost statistical significance, both in sensitivity analysis and after adjustment for fibrinogen and D-dimer.

Conclusion: Lower average concentrations of fibrinogen over time were associated with the presence of clinical pulmonary thromboembolism in patients at the Intensive Care, whereas D-dimer, CRP and ferritin were not. Lower concentrations over time may indicate the consumption of fibrinogen related to thrombus formation in the pulmonary vessels.
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http://dx.doi.org/10.1186/s12959-021-00286-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165953PMC
May 2021

Nationwide implementation of a decision aid on vaginal birth after cesarean: a before and after cohort study.

J Perinat Med 2021 Sep 31;49(7):783-790. Epub 2021 May 31.

Department of Obstetrics and Gynecology, Maastricht University Medical Center+, Maastricht, The Netherlands.

Objectives: Woman with a history of a previous cesarean section (CS) can choose between an elective repeat CS (ERCS) and a trial of labor (TOL), which can end in a vaginal birth after cesarean (VBAC) or an unplanned CS. Guidelines describe women's rights to make an informed decision between an ERCS or a TOL. However, the rates of TOL and vaginal birth after CS varies greatly between and within countries. The objective of this study is to asses nation-wide implementation of counselling with a decision aid (DA) including a prediction model, on intended delivery compared to care as usual. We hypothesize that this may result in a reduction in practice variation without an increase in cesarean rates or complications.

Methods: In a multicenter controlled before and after cohort study we evaluate the effect of nation-wide implementation of a DA. Practice variation was defined as the standard deviation (SD) of TOL percentages.

Results: A total of 27 hospitals and 1,364 women were included. A significant decrease was found in practice variation (SD TOL rates: 0.17 control group vs. 0.10 intervention group following decision aid implementation, p=0.011). There was no significant difference in the ERCS rate or overall CS rates. A 21% reduction in the combined maternal and perinatal adverse outcomes was seen.

Conclusions: Nationwide implementation of the DA showed a significant reduction in practice variation without an increase in the rate of cesarean section or complications, suggesting an improvement in equality of care.
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http://dx.doi.org/10.1515/jpm-2021-0007DOI Listing
September 2021

Adaptation of left ventricular diastolic function to pregnancy: a systematic review and meta-analysis.

J Hypertens 2021 10;39(10):1934-1941

Department of Cardiology, Maastricht University Medical Center (MUMC+), The Netherlands.

Objective: To meta-analytically determine the adaptation of left ventricular diastolic function (LVDF)-indices to singleton normotensive pregnancies.

Methods: Literature was retrieved from PubMed and Embase. We included studies that reported a nonpregnant reference measurement and LVDF indices (mitral inflow signals, left atrial volume and tissue Doppler measurements). Mean differences between pregnant and reference measurements and weighted means of absolute values were calculated using a random-effects model.

Results: We included 34 eligible studies. Normotensive pregnancies were characterized by an initially larger increase in the passive left ventricular filling (E-wave peak velocity, 13%) compared to active left ventricular filling during diastole (A-wave peak velocity, 6%) resulting in a 16% increase of the E/A ratio in the first trimester. The E/A ratio progressively decreased during advancing gestation to -18% at term, resulting from stabilizing E-wave peak velocity and increased A-wave peak velocity. The E/e' ratio was increased between 22 and 35 weeks (a maximal increase of 13%) in normotensive pregnancy. Left atrial volume (LAV) progressively increased from 15 weeks onwards with a maximal increase of 30% between 36 and 41 weeks.

Conclusion: LVDF in normotensive pregnancy was improved in the first trimester after which LVDF progressively worsened. Large-scale studies in normotensive and hypertensive complicated pregnancies are needed for a more precise insight into LVDF changes during pregnancy.
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http://dx.doi.org/10.1097/HJH.0000000000002886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452327PMC
October 2021

Noninvasive Home Mechanical Ventilation in Adult Myotonic Dystrophy Type 1: A Systematic Review.

Respiration 2021;100(8):816-825. Epub 2021 May 7.

Department of Pulmonary Diseases and Home Mechanical Ventilation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Introduction: Chronic hypercapnic respiratory failure induces considerable morbidity and mortality in patients with myotonic dystrophy type 1 (DM1). This study systematically reviews the effects of noninvasive home mechanical ventilation (HMV) on gas exchange, quality of life, survival, and compliance in DM1 patients.

Methods: A systematic Medline and Embase search was performed (January 1995 to January 2020). Records were screened for eligibility criteria, data were extracted from included studies, and risk of bias was assessed. We present findings mainly using a narrative synthesis.

Results: Twenty-eight relevant full-text articles were screened for eligibility criteria. Nine studies were included. Randomized controlled trials were not found. Studies had either an observational (n = 8) or interventional (n = 1) design. In the pooled data analysis, HMV showed to improve mean oxygen saturation with 4.8% and decreased mean carbon dioxide values with 3 mm Hg. Compliance varied widely between studies, from no use to more than 12 h per day. Quality of life was not studied extensively, but some studies reported positive effects of HMV on symptoms of chronic respiratory failure. HMV may improve survival in DM1 patients with chronic hypercapnic respiratory failure.

Conclusion: This review shows that HMV can improve gas exchange and relieve symptoms with a possible survival benefit in DM1 patients with chronic hypercapnic respiratory failure. Future studies should focus on developing strategies to optimize the timing of HMV initiation and to promote compliance.
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http://dx.doi.org/10.1159/000515453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491482PMC
May 2021

Predicting Recurrent Venous Thromboembolism in Patients With Deep-Vein Thrombosis: Development and Internal Validation of a Potential New Prediction Model (Continu-8).

Front Cardiovasc Med 2021 6;8:655226. Epub 2021 Apr 6.

Laboratory of Clinical Thrombosis and Haemostasis, Thrombosis Expertise Center, Cardiovascular Research Institute, Maastricht University Medical Center, Maastricht, Netherlands.

Previous prediction models for recurrent thromboembolism (VTE) are often complicated to apply and have not been implemented widely. To develop and internally validate a potential new prediction model for recurrent VTE that can be used without stopping anticoagulant treatment for D-dimer measurements in patients with provoked and unprovoked DVT. Cohort data of 479 patients treated in a clinical care pathway at Maastricht University Medical Center were used. Predictors for the Cox proportional hazards model (unprovoked DVT, male gender, factor VIII levels) were derived from literature and using forward selection procedure. The scoring rule was internally validated using bootstrapping techniques and the predictive ability was compared to existing prediction models. Patients were followed for a median of 3.12 years after stopping anticoagulation treatment (IQR 0.78, 3.90). Sixty-four of 479 patients developed recurrent VTE (13%). The scoring rule consisted of unprovoked DVT (yes: 2 points), male sex (yes: 1 point), and factor VIII > 213 % (yes: 2 points) and was categorized into three groups [i.e., low risk (score 0), medium risk (scores 1, 2, or 3) and high risk (scores 4 and 5)]. The concordance statistic was 0.68 (95% CI: 0.61, 0.75). The discriminative ability of the new Continu-8 score was adequate. Future studies shall verify this score in an independent setting without stopping anticoagulation treatment.
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http://dx.doi.org/10.3389/fcvm.2021.655226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055939PMC
April 2021

The Effect of Bolus Vitamin D Supplementation on Distal Radius Fracture Healing: A Randomized Controlled Trial Using HR-pQCT.

J Bone Miner Res 2021 08 3;36(8):1492-1501. Epub 2021 Jun 3.

NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.

Vitamin D is an important factor in bone metabolism. Animal studies have shown a positive effect of vitamin D supplementation on fracture healing, but evidence from clinical trials is inconclusive. A randomized controlled trial was performed to assess the effects of vitamin D supplementation on fracture healing using HR-pQCT-based outcome parameters. Thirty-two postmenopausal women with a conservatively treated distal radius fracture were included within 2 weeks postfracture and randomized to a low-dose (N = 10) and a high-dose (N = 11) vitamin D intervention group receiving a 6-week bolus dose, equivalent to 700 and 1800 IU vitamin D supplementation per day, respectively, in addition to a control group (N = 11) receiving no supplementation. After the baseline visit 1-2 weeks postfracture, follow-up visits were scheduled at 3-4, 6-8, and 12 weeks postfracture. At each visit, HR-pQCT scans of the fractured radius were performed. Cortical and trabecular bone density and microarchitectural parameters and microfinite element analysis-derived torsion, compression, and bending stiffness were assessed. Additionally, serum markers of bone resorption (CTX) and bone formation (PINP) were measured. Baseline serum levels of 25OHD were <50 nmol/L in 33% of all participants and <75 nmol/L in 70%. Compared with the control group, high-dose vitamin D supplementation resulted in a decreased trabecular number (regression coefficient β: -0.22; p < 0.01) and lower compression stiffness (B: -3.63; p < 0.05, together with an increase in the bone resorption marker CTX (B: 0.062; p < 0.05). No statistically significant differences were observed between the control and low-dose intervention group. In conclusion, the bolus equivalent of 700 U/day vitamin D supplementation in a Western postmenopausal population does not improve distal radius fracture healing and an equivalent dose of 1800 IU/day may be detrimental in restoring bone stiffness during the first 12 weeks of fracture healing. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453928PMC
August 2021

Preventing Recurrent Preeclampsia by Tailored Treatment of Nonphysiologic Hemodynamic Adjustments to Pregnancy.

Hypertension 2021 Jun 5;77(6):2045-2053. Epub 2021 Apr 5.

Department of Obstetrics and Gynecology (E.G.M., E.C., V.A.L.v.B., V.M.M.M.S., R.J.A., M.E.A.S.), Maastricht University Medical Centre, the Netherlands.

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16502DOI Listing
June 2021

Effect of a dedicated mitral heart team compared to a general heart team on survival: a retrospective, comparative, non-randomized interventional cohort study based on prospectively registered data.

Eur J Cardiothorac Surg 2021 07;60(2):263-273

Department of Cardiothoracic Surgery, Maastricht University Medical Center (MUMC+), Maastricht, Netherlands.

Objectives: Although in both the US and European guidelines the 'heart team approach' is a class I recommendation, supporting evidence is still lacking. Therefore, we sought to provide comparative survival data of patients with mitral valve disease referred to the general and the dedicated heart team.

Methods: In this retrospective cohort, patients evaluated for mitral valve disease by a general heart team (2009-2014) and a dedicated mitral valve heart team (2014-2018) were included. Decision-making was recorded prospectively in heart team electronic forms. The end point was overall survival from decision of the heart team.

Results: In total, 1145 patients were included of whom 641 (56%) were discussed by dedicated heart team and 504 (44%) by general heart team. At 5 years, survival probability was 0.74 [95% confidence interval (CI) 0.68-0.79] for the dedicated heart team group compared to 0.70 (95% CI 0.66-0.74, P = 0.040) for the general heart team. Relative risk of mortality adjusted for EuroSCORE II, treatment groups (surgical, transcatheter and non-intervention), mitral valve pathology (degenerative, functional, rheumatic and others) and 13 other baseline characteristics for patients in the dedicated heart team was 29% lower [hazard ratio (HR) 0.71, 95% CI 0.54-0.95; P = 0.019] than for the general heart team. The adjusted relative risk of mortality was 61% lower for patients following the advice of the heart team (HR 0.39, 95% CI 0.25-0.62; P < 0.001) and 43% lower for patients following the advice of the general heart team (HR 0.57, 95% CI 0.37-0.87; P = 0.010) compared to those who did not follow the advice of the heart team.

Conclusions: In this retrospective cohort, patients treated for mitral valve disease based on a dedicated heart team decision have significantly higher survival independent of the allocated treatment, mitral valve pathology and baseline characteristics.
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http://dx.doi.org/10.1093/ejcts/ezab065DOI Listing
July 2021

Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy.

Neurology 2021 05 25;96(20):e2534-e2545. Epub 2021 Mar 25.

From the Department of Neurology (M.G., B.T.A.d.G., M.S., J.G.J.H., C.G.F., I.S.J.M.), School of Mental Health and Neuroscience, and Department of Clinical Epidemiology and Medical Technology Assessment (S.M.J.v.K.), Maastricht University Medical Center+; Department of Rehabilitation Adelante/Maastricht University Medical Center+ (M.S.), the Netherlands; and Department of Neurology (I.S.J.M.), Curaçao Medical Center, Willemstad, Curaçao.

Objective: This is the first double-blind randomized controlled trial evaluating the efficacy and safety of IV immunoglobulin (IVIG) vs placebo in patients with idiopathic small fiber neuropathy (I-SFN).

Methods: Between July 2016 and November 2018, 60 Dutch patients with skin biopsy-proven I-SFN randomly received a starting dose of IVIG (2 g/kg body weight) or matching placebo (0.9% saline). Subsequently, 3 additional infusions of IVIG (1 g/kg) or placebo were administered at 3-week intervals. The primary outcome was a 1-point change in Pain Intensity Numerical Rating Scale score at 12 weeks compared to baseline.

Results: Thirty patients received IVIG, and 30 received placebo. In both groups, 29 patients completed the trial. In 40% of patients receiving IVIG, the mean average pain was decreased by at least 1 point compared to 30% of the patients receiving placebo ( = 0.588, odds ratio 1.56, 95% confidence interval 0.53-4.53). No significant differences were found on any of the other prespecified outcomes, including general well-being, autonomic symptoms, and overall functioning and disability.

Conclusions: This randomized controlled trial showed that IVIG treatment had no significant effect on pain in patients with painful I-SFN.

Trial Registration Information: ClinicalTrials.gov Identifier: NCT02637700, EudraCT 2015-002624-31.

Classification Of Evidence: This study provides Class I evidence that for patients with painful I-SFN, IVIG did not significantly reduce pain compared to placebo.
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http://dx.doi.org/10.1212/WNL.0000000000011919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205474PMC
May 2021

Cardiovascular magnetic resonance accurately detects obstructive coronary artery disease in suspected non-ST elevation myocardial infarction: a sub-analysis of the CARMENTA Trial.

J Cardiovasc Magn Reson 2021 03 22;23(1):40. Epub 2021 Mar 22.

Department of Cardiology, Maastricht UMC+, Maastricht, The Netherlands.

Background: Invasive coronary angiography (ICA) is still the reference test in suspected non-ST elevation myocardial infarction (NSTEMI), although a substantial number of patients do not have obstructive coronary artery disease (CAD). Early cardiovascular magnetic resonance (CMR) may be a useful gatekeeper for ICA in this setting. The main objective was to investigate the accuracy of CMR to detect obstructive CAD in NSTEMI.

Methods: This study is a sub-analysis of a randomized controlled trial investigating whether a non-invasive imaging-first strategy safely reduced the number of ICA compared to routine clinical care in suspected NSTEMI (acute chest pain, non-diagnostic electrocardiogram, high sensitivity troponin T > 14 ng/L), and included 51 patients who underwent CMR prior to ICA. A stepwise approach was used to assess the diagnostic accuracy of CMR to detect (1) obstructive CAD (diameter stenosis ≥ 70% by ICA) and (2) an adjudicated final diagnosis of acute coronary syndrome (ACS). First, in all patients the combination of cine, T2-weighted and late gadolinium enhancement (LGE) imaging was evaluated for the presence of abnormalities consistent with a coronary etiology in any sequence. Hereafter and only when the scan was normal or equivocal, adenosine stress-perfusion CMR was added.

Results: Of 51 patients included (63 ± 10 years, 51% male), 34 (67%) had obstructive CAD by ICA. The sensitivity, specificity and overall accuracy of the first step to diagnose obstructive CAD were 79%, 71% and 77%, respectively. Additional vasodilator stress-perfusion CMR was performed in 19 patients and combined with step one resulted in an overall sensitivity of 97%, specificity of 65% and accuracy of 86%. Of the remaining 17 patients with non-obstructive CAD, 4 (24%) had evidence for a myocardial infarction on LGE, explaining the modest specificity. The sensitivity, specificity and overall accuracy to diagnose ACS (n = 43) were 88%, 88% and 88%, respectively.

Conclusion: CMR accurately detects obstructive CAD and ACS in suspected NSTEMI. Non-obstructive CAD is common with CMR still identifying an infarction in almost one-quarter of patients. CMR should be considered as an early diagnostic approach in suspected NSTEMI.

Trial Registration: The CARMENTA trial has been registered at ClinicalTrials.gov with identifier NCT01559467.
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http://dx.doi.org/10.1186/s12968-021-00723-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983380PMC
March 2021

Survival and reasons for revision of the uncemented Symax hip stem: A Dutch Arthroplasty Register study.

PLoS One 2021 12;16(3):e0248483. Epub 2021 Mar 12.

Department of Orthopaedic Surgery, Research School Caphri, Maastricht University Medical Centre, Maastricht, The Netherlands.

Aims: Previous studies have already shown early proximal ingrowth, fast osseous integration, and a stable fit of the uncemented Symax hip stem, with excellent clinical and radiographic performance. Aims were to evaluate cumulative revision rates and reasons for revision of the Symax hip stem using Dutch Arthroplasty Register (LROI) data and to assess possible associations between patient characteristics and revision rate of the Symax hip stem.

Patients And Methods: All total hip arthroplasties with the uncemented Symax hip stem registered in the LROI between 2007 and 2017 were included (n = 5,013). Kaplan-Meier survival analysis was performed to assess the cumulative 1, 5 and 7-year revision percentages. Cox proportional hazard regression analysis was performed to assess the association between patient and procedural characteristics, and revision arthroplasty of the stem.

Results: Cumulative 1, 5, and 7-year revision rates (with 95% confidence interval (CI)) for revision of any component were 1.5% (CI 1.2%-1.8%), 3.2% (CI 2.7%-3.7%), and 3.8% (CI 3.1%-4.4%) respectively. Cumulative 1, 5, and 7-year stem revision rates of the Symax hip stem were 0.9% (CI 0.6%-1.1%), 1.5% (CI 1.1%-1.9%), and 1.7% (CI 1.3%-2.1%) respectively. Periprosthetic fractures (n = 35) and loosening of the stem (n = 30) were the most common reasons for revision of the stem. Revision of the stem was associated with acute fracture as primary diagnosis (Hazard Ratio (HR) 2.4 (CI 1.3-4.3)), or history of a previous surgery to the affected hip (HR 2.7 (CI 1.4-5.2)).

Conclusion: This population-based registry study shows revision rates for the Symax hip stem comparable to those for best performing uncemented total hip arthroplasties in the Netherlands. Primary diagnosis of an acute fracture, and history of previous surgery on the affected hip, were significantly associated risk factors for revision of the Symax hip stem, and we discourage the use of the Symax hip stem in these patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248483PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954353PMC
October 2021

[Clinical course of COVID-19 in the Netherlands: an overview of 2607 patients in hospital during the first wave].

Ned Tijdschr Geneeskd 2021 01 11;165. Epub 2021 Jan 11.

Maastricht UMC.

Objective: To systematically collect clinical data from patients with a proven COVID-19 infection in the Netherlands.

Design: Data from 2579 patients with COVID-19 admitted to 10 Dutch centers in the period February to July 2020 are described. The clinical data are based on the WHO COVID case record form (CRF) and supplemented with patient characteristics of which recently an association disease severity has been reported.

Methods: Survival analyses were performed as primary statistical analysis. These Kaplan-Meier curves for time to (early) death (3 weeks) have been determined for pre-morbid patient characteristics and clinical, radiological and laboratory data at hospital admission.

Results: Total in-hospital mortality after 3 weeks was 22.2% (95% CI: 20.7% - 23.9%), hospital mortality within 21 days was significantly higher for elderly patients (> 70 years; 35, 0% (95% CI: 32.4% - 37.8%) and patients who died during the 21 days and were admitted to the intensive care (36.5% (95% CI: 32.1% - 41.3%)). Apart from that, in this Dutch population we also see a risk of early death in patients with co-morbidities (such as chronic neurological, nephrological and cardiac disorders and hypertension), and in patients with more home medication and / or with increased urea and creatinine levels.

Conclusion: Early death due to a COVID-19 infection in the Netherlands appears to be associated with demographic variables (e.g. age), comorbidity (e.g. cardiovascular disease) but also disease char-acteristics at admission.
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January 2021

Performance of prediction models for short-term outcome in COVID-19 patients in the emergency department: a retrospective study.

Ann Med 2021 12;53(1):402-409

Department of Internal Medicine, Division of General Internal Medicine, Section Acute Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.

Introduction: Coronavirus disease 2019 (COVID-19) has a high burden on the healthcare system. Prediction models may assist in triaging patients. We aimed to assess the value of several prediction models in COVID-19 patients in the emergency department (ED).

Methods: In this retrospective study, ED patients with COVID-19 were included. Prediction models were selected based on their feasibility. Primary outcome was 30-day mortality, secondary outcomes were 14-day mortality and a composite outcome of 30-day mortality and admission to medium care unit (MCU) or intensive care unit (ICU). The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC).

Results: We included 403 patients. Thirty-day mortality was 23.6%, 14-day mortality was 19.1%, 66 patients (16.4%) were admitted to ICU, 48 patients (11.9%) to MCU, and 152 patients (37.7%) met the composite endpoint. Eleven prediction models were included. The RISE UP score and 4 C mortality scores showed very good discriminatory performance for 30-day mortality (AUC 0.83 and 0.84, 95% CI 0.79-0.88 for both), significantly higher than that of the other models.

Conclusion: The RISE UP score and 4 C mortality score can be used to recognise patients at high risk for poor outcome and may assist in guiding decision-making and allocating resources.
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http://dx.doi.org/10.1080/07853890.2021.1891453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919920PMC
December 2021

Prognostic and Predictive Value of Integrated Qualitative and Quantitative Magnetic Resonance Imaging Analysis in Glioblastoma.

Cancers (Basel) 2021 02 10;13(4). Epub 2021 Feb 10.

Department of Medical Oncology, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre+, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.

Glioblastoma (GBM) is the most malignant primary brain tumor for which no curative treatment options exist. Non-invasive qualitative (Visually Accessible Rembrandt Images (VASARI)) and quantitative (radiomics) imaging features to predict prognosis and clinically relevant markers for GBM patients are needed to guide clinicians. A retrospective analysis of GBM patients in two neuro-oncology centers was conducted. The multimodal Cox-regression model to predict overall survival (OS) was developed using clinical features with VASARI and radiomics features in isocitrate dehydrogenase ()-wild type GBM. Predictive models for -mutation, 06-methylguanine-DNA-methyltransferase ()-methylation and epidermal growth factor receptor () amplification using imaging features were developed using machine learning. The performance of the prognostic model improved upon addition of clinical, VASARI and radiomics features, for which the combined model performed best. This could be reproduced after external validation (C-index 0.711 95% CI 0.64-0.78) and used to stratify Kaplan-Meijer curves in two survival groups (-value < 0.001). The predictive models performed significantly in the external validation for amplification (area-under-the-curve (AUC) 0.707, 95% CI 0.582-8.25) and -methylation (AUC 0.667, 95% CI 0.522-0.82) but not for -mutation (AUC 0.695, 95% CI 0.436-0.927). The integrated clinical and imaging prognostic model was shown to be robust and of potential clinical relevance. The prediction of molecular markers showed promising results in the training set but could not be validated after external validation in a clinically relevant manner. Overall, these results show the potential of combining clinical features with imaging features for prognostic and predictive models in GBM, but further optimization and larger prospective studies are warranted.
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http://dx.doi.org/10.3390/cancers13040722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916478PMC
February 2021
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