ObjectiveTo assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.BackgroundMigraine has been linked to IBD and celiac... Show moreObjectiveTo assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.BackgroundMigraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition.MethodsLinkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed.ResultsMigraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99–1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99–1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96–1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79–1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00–1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92–0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02–1.29, p = 0.025). However, the results were not significant after multiple testing correction.ConclusionsWe found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes. Show less
Rheumatoid Arthritis (RA) is an autoimmune disease that mainly affects joints in the wrist and hands. It typically results in inflamed and painful joints. MRI is one of the most common imaging...Show moreRheumatoid Arthritis (RA) is an autoimmune disease that mainly affects joints in the wrist and hands. It typically results in inflamed and painful joints. MRI is one of the most common imaging modalities to detect and monitor possible inflamed RA-related areas, enabling rheumatologists to treat patients more timely and efficiently. Despite the importance of finding and tracking inflamed areas associated with RA in MRI, there is no previously published work on finding pixel-by-pixel changes related to RA between baseline and follow-up MRIs. Therefore, this paper proposes a hypothesis-free deep learning-based model to discover changes in wrist MRIs on a pixel level to detect changes in inflamed areas related to RA without using prior anatomical information. To do this, a combination of a U-Net-based network and image thresholding was utilised to find pixel-level non-trivial changes between baseline and follow-up MRI images. A wrist MRI dataset including 99 individual pairs of MRI images (each pair constructed of baseline and follow-up images) was used to evaluate the proposed model. Data were collected from patients with clinically suspected arthralgia (CSA), defined as patients at risk of developing RA according to their rheumatologist and already had subclinical inflammation on MRI but could not be diagnosed with RA (yet) since they had not developed clinically detectable arthritis. The obtained results were evaluated using an observer study. The evaluation showed that our proposed model is a promising first step toward developing an automatic model to find RA-related inflammatory changes. Show less
Purpose The purpose of this study was to explore the lived experience of dancing with Parkinson's and Multiple Sclerosis in an inclusive dance group called ReDiscoverMe (RDM). Methods Participatory... Show morePurpose The purpose of this study was to explore the lived experience of dancing with Parkinson's and Multiple Sclerosis in an inclusive dance group called ReDiscoverMe (RDM). Methods Participatory research approaches and interpretative phenomenological analysis were used to make sense of the lived experience captured in interviews and observations. Arthur Frank's conceptual framework on embodied storytelling from his book The Wounded Storyteller was the study's theoretical lens. Themes are both described and represented in images made by an RDM participant. Findings Dancing in a nonjudgmental environment was described by participants as a way to rediscover themselves while continually adapting to living with chronic illness. We interpreted this experience of rediscovery as an active, recursive process involving three "movements": escaping, expanding, and embracing. Through these movements, participants could rise above the self and illness. Conclusions The lived experience of dancing in this group was characterized by transformations of the body, self, and life. Through escaping, expanding, and embracing, participants could more easily embrace the body's contingency, integrate the self and body by becoming dancers, connect with others living with illness, and produce desire through passion. Participants could therefore experience illness as a journey and gain something from the experience. Show less
Borm, F.J.; Smit, J.; Bakker, J.; Wondergem, M.; Smit, E.F.; Langen, A.J. de; Gruijl, T.D. de 2023
Better biomarkers for programmed death - (ligand) 1 (PD-(L)1) checkpoint blockade in non-small cell lung cancer (NSCLC) are needed. We explored the predictive value of early response evaluation... Show moreBetter biomarkers for programmed death - (ligand) 1 (PD-(L)1) checkpoint blockade in non-small cell lung cancer (NSCLC) are needed. We explored the predictive value of early response evaluation using Fluor-18-deoxyglucose positron emission tomography and pre- and on-treatment flowcytometric T-cell profiling in peripheral blood and tumor-draining lymph nodes (TDLN). The on-treatment evaluation was performed 7–14 days after the start of PD-1 blockade in NSCLC patients. These data were related to (pathological) tumor response, progression-free survival, and overall survival (OS). We found that increases in total lesion glycolysis (TLG) had a strong reverse correlation with OS (r = −0.93, p = 0.022). Additionally, responders showed decreased and progressors increased Treg frequencies on-treatment. Frequencies of detectable PD-1-expressing CD8+ T cells decreased in responders but remained stable in progressors. This was especially found in the TDLN. Changes in activated Treg rates in TDLN were strongly but, due to low numbers of data points, non-significantly correlated with ΔTLG and reversely correlated with OS. Show less
Noortman, W.A.; Vriens, D.; Geus-Oei, L.F. de; Slump, C.H.; Aarntzen, E.H.; Berkel, A. van; ... ; Velden, F.H.P. van 2023
Objectives Based on germline and somatic mutation profiles, pheochromocytomas and paragangliomas (PPGLs) can be classified into different clusters. We investigated the use of [18F]FDG-PET/CT... Show moreObjectives Based on germline and somatic mutation profiles, pheochromocytomas and paragangliomas (PPGLs) can be classified into different clusters. We investigated the use of [18F]FDG-PET/CT radiomics, SUVmax and biochemical profile for the identification of the genetic clusters of PPGLs. Methods In this single-centre cohort, 40 PPGLs (13 cluster 1, 18 cluster 2, 9 sporadic) were delineated using a 41% adaptive threshold of SUVpeak ([18F]FDG-PET) and manually (low-dose CT; ldCT). Using PyRadiomics, 211 radiomic features were extracted. Stratified 5-fold cross-validation for the identification of the genetic cluster was performed using multinomial logistic regression with dimensionality reduction incorporated per fold. Classification performances of biochemistry, SUVmax and PET(/CT) radiomic models were compared and presented as mean (multiclass) test AUCs over the five folds. Results were validated using a sham experiment, randomly shuffling the outcome labels. Results The model with biochemistry only could identify the genetic cluster (multiclass AUC 0.60). The three-factor PET model had the best classification performance (multiclass AUC 0.88). A simplified model with only SUVmax performed almost similarly. Addition of ldCT features and biochemistry decreased the classification performances. All sham AUCs were approximately 0.50. Conclusion PET radiomics achieves a better identification of PPGLs compared to biochemistry, SUVmax, ldCT radiomics and combined approaches, especially for the differentiation of sporadic PPGLs. Nevertheless, a model with SUVmax alone might be preferred clinically, weighing model performances against laborious radiomic analysis. The limited added value of radiomics to the overall classification performance for PPGL should be validated in a larger external cohort. Key Points • Radiomics derived from [18F]FDG-PET/CT has the potential to improve the identification of the genetic clusters of pheochromocytomas and paragangliomas. • A simplified model with SUVmax only might be preferred clinically, weighing model performances against the laborious radiomic analysis. • Cluster 1 and 2 PPGLs generally present distinctive characteristics that can be captured using [18F]FDG-PET imaging. Sporadic PPGLs appear more heterogeneous, frequently resembling cluster 2 PPGLs and occasionally resembling cluster 1 PPGLs. Show less
Depression can be understood as a complex dynamic system where depressive symptoms interact with one another. Cortisol is suggested to play a major role in the pathophysiology of depression, but... Show moreDepression can be understood as a complex dynamic system where depressive symptoms interact with one another. Cortisol is suggested to play a major role in the pathophysiology of depression, but knowledge on the temporal interplay between cortisol and depressive symptoms is scarce. We aimed to analyze the temporal connectivity between salivary cortisol and momentary affective states in depressed individuals and controls. Thirty pair-matched depressed and non-depressed participants completed questionnaires on momentary positive (PA) and negative (NA) affect and collected saliva three times a day for 30 days. The association between cortisol and affect was analyzed by dynamic time warp (DTW) analyses. These analyses involved lag-1 backward to lag-1 forward undirected analyses and lag-0 and lag-1 forward directed analyses. Large inter- and intra-individual variability in the networks were found. At the group level, with undirected analysis PA and NA were connected in the networks in depressed individuals and in controls. Directed analyses indicated that increases in cortisol preceded specific NA items in controls, but tended to follow upon specific affect items increase in depressed individuals. To conclude, at group level, changes in cortisol levels in individuals diagnosed with a depression may be a result of changes in affect, rather than a cause. Show less
BackgroundMolecular components in blood, such as proteins, are used as biomarkers to detect or predict disease states, guide clinical interventions and aid in the development of therapies. While... Show moreBackgroundMolecular components in blood, such as proteins, are used as biomarkers to detect or predict disease states, guide clinical interventions and aid in the development of therapies. While multiplexing proteomics methods promote discovery of such biomarkers, their translation to clinical use is difficult due to the lack of substantial evidence regarding their reliability as quantifiable indicators of disease state or outcome. To overcome this challenge, a novel orthogonal strategy was developed and used to assess the reliability of biomarkers and analytically corroborate already identified serum biomarkers for Duchenne muscular dystrophy (DMD). DMD is a monogenic incurable disease characterized by progressive muscle damage that currently lacks reliable and specific disease monitoring tools.MethodsTwo technological platforms are used to detect and quantify the biomarkers in 72 longitudinally collected serum samples from DMD patients at 3 to 5 timepoints. Quantification of the biomarkers is achieved by detection of the same biomarker fragment either through interaction with validated antibodies in immuno-assays or through quantification of peptides by Parallel Reaction Monitoring Mass Spectrometry assay (PRM-MS).ResultsFive, out of ten biomarkers previously identified by affinity-based proteomics methods, were confirmed to be associated with DMD using the mass spectrometry-based method. Two biomarkers, carbonic anhydrase III and lactate dehydrogenase B, were quantified with two independent methods, sandwich immunoassays and PRM-MS, with Pearson correlations of 0.92 and 0.946 respectively. The median concentrations of CA3 and LDHB in DMD patients was elevated in comparison to those in healthy individuals by 35- and 3-fold, respectively. Levels of CA3 vary between 10.26 and 0.36 ng/ml in DMD patients whereas those of LDHB vary between 15.1 and 0.8 ng/ml.ConclusionsThese results demonstrate that orthogonal assays can be used to assess the analytical reliability of biomarker quantification assays, providing a means to facilitate the translation of biomarkers to clinical practice. This strategy also warrants the development of the most relevant biomarkers, markers that can be reliably quantified with different proteomics methods. Show less
Background: COVID-19 infection prevention measures can negatively impact nursing home resi-dents' well-being. Society has been concerned about the imbalance between infection prevention and... Show moreBackground: COVID-19 infection prevention measures can negatively impact nursing home resi-dents' well-being. Society has been concerned about the imbalance between infection prevention and residents' well-being, and about nursing home residents' autonomy in COVID-19 policymaking.Objective: This study explores consensus among nursing home staff about which measures they found to be most important in contributing to preventing infections and to maintaining well-being of residents during COVID-19 outbreaks. In addition, this study explores the decision-making processes regarding COVID-19 measures and the involvement of residents or their representatives.Design: Mixed methods based on an online nominal group technique. Setting(s): Dutch nursing homes, June-November 2020.Participants: Managers, policy advisors, elderly care physicians, psychologists, a spiritual coun-selor, nurses, care assistants, and resident representatives (N = 35).Methods: Four panels from the viewpoint of infection prevention, and four panels from the viewpoint of well-being were performed with 3 to 7 participants per panel. Participants indi-vidually selected the measure they found most important, discussed these measures together in an online conversation, and rated the importance and urgency of these measures during COVID-19 outbreaks on a 5-point Likert scale. The measures that were rated as (very) important and (very) urgent by all members of that panel were defined as 'prioritized in consensus'. Panels also dis-cussed the decision-making process regarding COVID-19 measures and the involvement of resi-dents or their representatives. These conversations were transcribed verbatim and thematically coded using an inductive approach.Results: The infection prevention panels prioritized isolation measures; testing measures; testing and isolation combinations; use of personal protective equipment around (suspected) infected Show less
BackgroundMost network analyses on central symptoms in eating disorders (EDs) have been cross-sectional. Longitudinal within-person analyses of therapy processes are scarce. Our aim was to... Show moreBackgroundMost network analyses on central symptoms in eating disorders (EDs) have been cross-sectional. Longitudinal within-person analyses of therapy processes are scarce. Our aim was to investigate central change processes in therapy in a transdiagnostic sample, considering the influence of childhood maltreatment.MethodWe employed dynamic time warping analyses to identify clusters of symptoms that tended to change similarly across therapy on a within-person level. Symptoms were measured by a 28-item Eating Disorder Examination Questionnaire (EDE-Q). Furthermore, we examined the temporal direction of symptom change to identify symptoms that tended to precede and predict other symptoms. Finally, we estimated two directed, temporal networks in patients with and without a history of childhood maltreatment.ResultsOur analysis included 122 ED patients (mean age = 30.9, SD = 9.7; illness duration = 14.2 years, SD = 8.9; prior treatment = 5.6 years, SD = 5.1). The initial network revealed three robust clusters of symptoms over time: (1) ED behavior, (2) inhibition, and (3) cognitions and feelings about body and weight. Overvaluation of shape had the highest out-strength preceding and predicting other symptoms. Dissatisfaction with weight preceded and predicted other symptoms in the maltreatment network. The non-maltreatment network showed a similar structure to the transdiagnostic network.ConclusionTargeting and monitoring feelings and cognitions related to shape may be crucial for achieving lasting symptom improvement in a transdiagnostic sample. Furthermore, our findings highlight the need for further investigation into the different processes driving EDs based on maltreatment status. Show less
Does, F.H.S. van der; Nagamine, M.; Wee, N.J.A. van der; Chiba, T.; Edo, N.; Kitano, M.; ... ; Giltay, E.J. 2023
Background: After the Great East Japan Earthquake [GEJE], approximately 70,000 Japan Ground Self Defense Force [JGSDF] personnel were deployed, risking Post-Traumatic Stress Disorder [PTSD]. The... Show moreBackground: After the Great East Japan Earthquake [GEJE], approximately 70,000 Japan Ground Self Defense Force [JGSDF] personnel were deployed, risking Post-Traumatic Stress Disorder [PTSD]. The network approach to psychopathology suggests that symptoms may cause and exacerbate each other, resulting in the emergence and maintenance of disorders, including PTSD. It is therefore important to further explore the temporal interplay between symptoms. Most studies assessing the factor structure of the Impact of Event Scale-Revised [IES-R] have used cross-sectional designs. In this study, the structure of the IES-R was re-evaluated while incorporating the temporal interplay between symptoms.Methods: Using Dynamic Time Warping [DTW] the distances between PTSD symptoms on the IES-R were modelled in 1120 JGSDF personnel. Highly correlated symptoms were clustered at the group level using Distatis three-way principal component analyses of the distance matrices. The resulting clusters were compared to the original three subscales of the IES-R using a Confirmatory Factor Analysis (CFA).Results: The DTW analysis yielded four symptom clusters: Intrusion (five items), Hyperarousal (six items), Avoidance (six items), and Dissociation (five items). CFA yielded better fit estimates for this four-factor solution (RMSEA = 0.084, CFI = 0.918, TLI = 0.906), compared to the original three subscales of the IES-R (RMSEA = 0.103, CFI = 0.873, TLI = 0.858).Conclusions: DTW offers a new method of modelling the temporal relationships between symptoms. It yielded four IES-R symptom clusters, which may facilitate understanding of PTSD as a complex dynamic system. Show less
BackgroundSmoking prevalence is still high, which requires effective interventions that help many people who smoke at once in addition to time-consuming individual interventions. ‘I Quit’ is a... Show moreBackgroundSmoking prevalence is still high, which requires effective interventions that help many people who smoke at once in addition to time-consuming individual interventions. ‘I Quit’ is a large-scale smoking cessation course in The Netherlands. This qualitative study explored I Quit participants’ experiences during and after the course, and perceptions of whether and how the course may have altered their smoking behavior.MethodsWe performed individual semi-structured interviews with course participants (N = 21) who had either quit successfully, attempted to quit but relapsed, or had continued to smoke after ‘I Quit’. Shortly after qualitative data collection was completed, Foundation I Quit was accused in the media of a number of misbehaviors. Although unplanned, this provided a unique opportunity to explore participants’ views on alleged fraud in a second round of interviews (N = 16). Data were collected from 2016 to 2018.ResultsQualitative findings showed two psychosocial processes that may explain smoking cessation after course attendance. First, the confrontation with a large group of people who smoke, of whom some had already developed smoking-related complaints, triggered identity processes both towards and away from quitting smoking. Unorthodox methods used in the course appeared to trigger identity processes. Second, social support after the course from participants’ own social network facilitated maintenance of successful quitting. The study also found that interview participants’ opinions on I Quit did not change much after allegations of fraud in the media.ConclusionsFindings suggest that a one-time course might initiate psychosocial processes that could help certain smokers to gain motivation to quit, requiring a minimum of resources. Identity processes triggered by the course seem tricky as people have different ways of dealing with identity threat, some of which can be counterproductive and even result in more difficulty quitting. More research is needed to examine who can benefit from a one-time course, and who needs more support in order to quit successfully. Show less
Making a career choice is a multifaceted process and support for medical students on career choice is pivotal. Not all medical schools have programs or guidelines to support having meaningful... Show moreMaking a career choice is a multifaceted process and support for medical students on career choice is pivotal. Not all medical schools have programs or guidelines to support having meaningful conversations with medical students. However, medical students have questions and are seeking answers. This article presents twelve tips for having meaningful conversations with medical students for educators, mentors and internship tutors. The twelve tips have been grouped into three categories: the conversation, the reflection and the actions students can take in the process of their specialty career choice. Show less
Introduction: The rVSVDG-ZEBOV-GP (Ervebo®) vaccine is both immunogenic and protective against Ebola. However, the vaccine can cause a broad range of transient adverse reactions, from headache to... Show moreIntroduction: The rVSVDG-ZEBOV-GP (Ervebo®) vaccine is both immunogenic and protective against Ebola. However, the vaccine can cause a broad range of transient adverse reactions, from headache to arthritis. Identifying baseline reactogenicity signatures can advance personalized vaccinology and increase our understanding of the molecular factors associated with such adverse events.Methods: In this study, we developed a machine learning approach to integrate prevaccination gene expression data with adverse events that occurred within 14 days post-vaccination.Results and Discussion: We analyzed the expression of 144 genes across 343 blood samples collected from participants of 4 phase I clinical trial cohorts: Switzerland, USA, Gabon, and Kenya. Our machine learning approach revealed 22 key genes associated with adverse events such as local reactions, fatigue, headache, myalgia, fever, chills, arthralgia, nausea, and arthritis, providing insights into potential biological mechanisms linked to vaccine reactogenicity. Show less
Ge, Y.; Roon, L. van; Chen, H.S.; Methorst, R.; Paton, M.; DeRuiter, M.C.; ... ; Jongbloed, M.R.M. 2023
The cardiac autonomic nervous system is crucial in controlling cardiac function, such as heart rate and cardiac contractility, and is divided into sympathetic and parasympathetic branches. Normally... Show moreThe cardiac autonomic nervous system is crucial in controlling cardiac function, such as heart rate and cardiac contractility, and is divided into sympathetic and parasympathetic branches. Normally, there is a balance between these two branches to maintain homeostasis. However, cardiac disease states such as myocardial infarction, heart failure, and hypertension can induce the remodeling of cells involved in cardiac innervation, which is associated with an adverse clinical outcome.Although there are vast amounts of data for the histological structure and function of the cardiac autonomic nervous system, its molecular biological architecture in health and disease is still enigmatic in many aspects. Novel technologies such as single-cell RNA sequencing (scRNA-seq) hold promise for the genetic characterization of tissues at single-cell resolution. However, the relatively large size of neurons may impede the standardized use of these techniques. Here, this protocol exploits droplet-based single-nucleus RNA sequencing (snRNA-seq), a method to characterize the biological architecture of cardiac sympathetic neurons in health and disease. A stepwise approach is demonstrated to perform snRNA-seq of the bilateral superior cervical (SCG) and stellate ganglia (StG) dissected from adult mice.This method enables long-term sample preservation, maintaining an adequate RNA quality when samples from multiple individuals/experiments cannot be collected all at once within a short period of time. Barcoding the nuclei with hashtag oligos (HTOs) enables demultiplexing and the trace-back of distinct ganglionic samples post sequencing. Subsequent analyses revealed successful nuclei capture of neuronal, satellite glial, and endothelial cells of the sympathetic ganglia, as validated by snRNA-seq. In summary, this protocol provides a stepwise approach for snRNA-seq of sympathetic extrinsic cardiac ganglia, a method that has the potential for broader application in studies of the innervation of other organs and tissues. Show less
Olthof, P.B.; Franssen, S.; Keulen, A.M. van; Geest, L.G. van der; Hoogwater, F.J.H.; Coenraad, M.; ... ; DHCG 2023
BackgroundMost data on the treatment and outcomes of intrahepatic cholangiocarcinoma (iCCA) derives from expert centers. This study aimed to investigate the treatment and outcomes of all patients... Show moreBackgroundMost data on the treatment and outcomes of intrahepatic cholangiocarcinoma (iCCA) derives from expert centers. This study aimed to investigate the treatment and outcomes of all patients diagnosed with iCCA in a nationwide cohort.MethodsData on all patients diagnosed with iCCA between 2010 and 2018 were obtained from the Netherlands Cancer Registry.ResultsIn total, 1747 patients diagnosed with iCCA were included. Resection was performed in 292 patients (17%), 548 patients (31%) underwent palliative systemic treatment, and 867 patients (50%) best supportive care (BSC). The OS median and 1-, and 3-year OS were after resection: 37.5 months (31.0–44.0), 79.2%, and 51.6%,; with systemic therapy, 10.0 months (9.2–10.8), 38.4%, and 5.1%, and with BSC 2.2 months (2.0–2.5), 10.4%, and 1.3% respectively. The resection rate for patients who first presented in academic centers was 33% (96/292) compared to 13% (195/1454) in non-academic centers (P < 0.001).DiscussionHalf of almost 1750 patients with iCCA over an 8 year period did not receive any treatment with a 1-year OS of 10.4%. Three-year survival was about 50% after resection, while long-term survival was rare after palliative treatment. The resection rate was higher in academic centers compared to non-academic centers. Show less
Sepriano, A.; Dijk, B. van; Ramiro, S.; Helm-van Mil, A. van der; Combe, B.; Schaardenburg, D. van; ... ; Landewé, R. 2023
Objectives The objective of this study is to evaluate whether there are differences in the long-term prognosis across various phenotypes of early arthritis (EA).Methods Three EA cohorts (Reade,... Show moreObjectives The objective of this study is to evaluate whether there are differences in the long-term prognosis across various phenotypes of early arthritis (EA).Methods Three EA cohorts (Reade, Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) and Early Arthritis Clinic (EAC)) were analysed. Clinical data were collected up to 24 years. Hands and feet radiographs were scored according to the Sharp van der Heijde (SvdH) method. Latent class analysis was applied to determine the EA phenotypes at baseline. Each class received a label reflecting its most prominent features. Prognostic outcomes included Health Assessment Questionnaire (HAQ), Short Form 36 (SF36) and SvdH score. The association between class membership and outcomes over time was tested in multivariable models.Results In total, 390 (Reade), 798 (ESPOIR) and 3991 (EAC) patients were analysed separately. Two classes with symmetrical polyarthritis emerged; one of these labelled as autoimmune inflammatory polyarthritis (AIPA), had high likelihood of acute phase reactants (APR) elevation and autoantibody positivity, while the other (mild-inflammatory polyarthritis; MIPA) had not. A third class had oligoarthritis of upper limbs (OAUL) and could be subdivided into autoimmune OAUL and mild-inflammatory OAUL. A fifth class had oligoarthritis of lower limbs. The SvdH scores were worse in patients with APR/autoantibodies (AIPA) than in those without (MIPA). No clinically meaningful differences across classes in HAQ or SF36 over time were found.Conclusion Radiographic progression over time primarily occurs in EA patients with APR/autoantibodies. The absence of these markers, however, does not necessarily translate into better long-term function and quality of life. Clinicians should not only aim at preventing joint damage, but look beyond structural progression in order to further improve the lives of people with EA. Show less
Background: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of... Show moreBackground: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection.Methods: COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4–10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected.Results: After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level.Conclusions: LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level. Show less
Witte, J.A.; Birnie, E.; Braunstahl, G.J.; Akker, E. van den; Litsenburg, W.J.M. van; Chavannes, N.H.; ... ; In't Veen, J.C.C.M. 2023
ObjectiveTo evaluate the implementation of a guideline-based, integrated, standardised, personal approach in patients with Chronic Obstructive Pulmonary Disease (COPD) or Asthma in a real-life... Show moreObjectiveTo evaluate the implementation of a guideline-based, integrated, standardised, personal approach in patients with Chronic Obstructive Pulmonary Disease (COPD) or Asthma in a real-life situation.MethodsPatients at the outpatient clinic of the department of pulmonary disease were included in a controlled cohort study, comparing the use of diagnostic items and ‘Personalised care plans' (PCPs) in patients with obstructive lung disease before (2013) and after (2015) implementation of a personalised diagnostic pathway. Results were compared with reference data (2016) from two control hospitals that used the same guidelines but did not implement this pathway.Results100 patients were selected for all three cohorts. After implementing the diagnostic pathway in 2015, 35 % of patients visited attended all pre-planned appointments, whereas 65 % of patients did not: they were diagnosed using usual care. Factors contributing to patients not attending the diagnostic care pathway were: the logistical complexity and intensity of the 2-day pathway, patients willingness to participate in a personalised pathway, and low social economic status or low literacy. After the implementation of the pathway, a significant improvement was seen in the number of PCPs (P < 0.001) and the number of diagnostic items registered recorded in the patients' electronic medical records (P < 0.001).ConclusionImplementing a standardised diagnostic pathway in a real-life population significantly improved the number of personalised care plans, demonstrating that the implementation of holistic care planning is feasible in this population. Nevertheless, the pathway needs further improvements to maximize the number of patients benefitting from it, including logistical streamlining, removing unnecessary diagnostic tools, and increasing the focus on low literacy. Additionally, we found that implementing existing guidelines in a real life context is complex. Therefore, it is required to prioritize the translation of current guidelines into every-day practice, before expanding existing guidelines and protocols. Show less
Reijm, S.; Kwekkeboom, J.C.; Blomberg, N.J.; Suurmond, J.; Woude, D. van der; Toes, R.E.M.; Scherer, H.U. 2023
Many autoimmune diseases (AIDs) are characterized by the persistence of autoreactive B cell responses, which have been directly implicated in disease pathogenesis. How and why these cells are... Show moreMany autoimmune diseases (AIDs) are characterized by the persistence of autoreactive B cell responses, which have been directly implicated in disease pathogenesis. How and why these cells are generated or how they are maintained for years is largely unknown. Rheumatoid arthritis (RA) is among the most common AIDs and is characterized by autoantibodies recognizing proteins with posttranslational modifications (PTMs). This PTM-directed autoreactive B cell compartment is ill defined. Here, we visualized the B cell response against the three main types of PTM antigens implicated in RA by spectral flow cytometry. Our results showed extensive cross-reactivity of PTM-directed B cells against all three PTM antigens (citrulline, homocitrulline, and acetyllysine). Unsupervised clustering revealed several distinct memory B cell (mBC) populations. PTM-directed cells clustered with the most recently activated class-switched mBC phenotype, with high CD80, low CD24, and low CD21 expression. Notably, patients also harbored large fractions of PTM-directed plasmablasts (PBs). Both PTM-directed mBCs and PBs showed high expression of CXCR3, a receptor for chemokines present in abundance in arthritic joints. Together, our data provide detailed insight into the biology of B cell autoreactivity and its remarkable, seemingly exhaustless persistence in a prominent human AID. Show less
