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Exploring the role of gastrointestinal brake mechanisms in the management of obesity with focus on bariatric surgery
Get PDFThis thesis examined gut hormone secretion, gastric emptying, small bowel transit, gut barrier function, and gut bacteria in obesity and after weight loss surgery. It also reviewed intestinal brake mechanisms—feedback systems regulating appetite via hormonal and neural pathways. In obesity, the gut barrier in the stomach and duodenum is impaired, allowing harmful bacteria to enter the bloodstream and trigger inflammation. Gut bacteria composition is also altered. After sleeve gastrectomy and gastric bypass, gastric emptying and satiety hormones (GLP-1, PYY) increased, reducing appetite. Small bowel transit accelerated only after sleeve gastrectomy. Post-surgery, the gut barrier improved, inflammation decreased, and gut bacteria changed. In conclusion, obesity is associated with reduced satiety, impaired gut barrier, and altered gut microbiota. Weight loss surgery improves these parameters, contributing to appetite reduction and better health
Long-term cognitive functioning following COVID-19:Negligible neuropsychological changes over time
No full textObjective: Objective cognitive impairment has been shown in a minority of hospitalized COVID-19 patients, and longitudinal studies with a relatively long follow-up duration are scarce. We sought to investigate the presence and long-term change of objective cognitive functioning. Method: Forty-six initially hospitalized (18 ± 19 days) COVID-19 survivors (male/female: 30/16; age: 61 ± 11) underwent extensive neuropsychological assessment (including performance validity) approximately 1 (T1) and 2.5 years (T2) post-infection. Cognitive domains assessed were: memory, attention, executive functioning, processing speed, and language (n = 14 (sub)tests). We used normative data to derive age, sex, and education-adjusted T-scores (T ≤ 35 [≤–1.5SD], deficit cut-off). Repeated measures AN(C)OVAs were used to investigate cognitive functioning over time. Results: Mean neuropsychological performance (n = 14 tests) was within normal range at both timepoints, and number of individuals with objective cognitive deficits ranged from 0–20% (T1), and 2–22% (T2). Number of subjective cognitive complaints remained unchanged. A minority (17%) showed objective cognitive deficits on ≥2 tests at both 1 and 2.5 years post-infection, but not consistently within one cognitive domain. Longitudinal analyses on the total sample showed improvement in performance over time on phonemic fluency (p<.001), but stable cognitive performance on all other tests, independent of prior comorbidities, subjective cognitive complaints, depressive symptoms, and ICU admission. Conclusions: There were no consistent objective cognitive deficits or major cognitive disorders years after SARS-CoV-2 infection in the majority of cases. Neuropsychological functioning remained essentially unchanged over time. Future larger longitudinal studies are necessary to unravel COVID-19-related cognitive phenotypes of persisting deficits and how these can be modulated.</p
Validation of an in-house Dutch Forensic Death Coding system (FDC)
No full textBackground: The International Classification of Diseases (ICD-11), developed by the WHO, is widely used to code and classify causes of death. While it is a suitable system for clinical data, it is not tailored for forensic diagnoses. This article explores the basic principles and methods for classification of cause of death in a forensic setting. An in-house Dutch coding system, the FDC system, was developed in the Netherlands. Purpose: To determine the validity and applicability of the FDC system. Methods: The FDC system was used to code 138 deaths based on the forensic autopsy reports of the Netherlands Forensic Institute. This was performed by three investigators (one forensic pathologist and two forensic physicians, all of whom are forensic experts) to compute the inter-investigator agreement using Krippendorff's alpha (kalpha) statistics. To measure the intra-investigator agreement, 46 cases per investigator (for each investigator different cases) were presented twice in random order. The coding system has five parameters: Main category, Subcategory, Other contributing factor category, Mode of death category, and Certainty of death category. Results: The Krippendorff's alphas (kalphas) for the inter-investigator agreement were as follows: Main category 0.91, Subcategory 0.74, Mode category 0.49 and Certainty category 0.55. Inter-investigator agreement showed high kalpha scores for both Main category and Subcategory. There was a good intra-investigator agreement. The kalphas were as follows: Main category 0.95, Subcategory 0.87, Mode category 0.65, and Certainty category 0.78. Conclusion: The FDC system is an in-house Dutch system that is useful for coding causes of death from a forensic perspective. This system could make the notation of forensic pathologists and forensic physicians less ambiguous, which could improve the understanding of cases by professionals such as public prosecutors, lawyers and judges who have to make decisions based on autopsy reports. In the future, this system could also be used in forensic medicine by forensic physicians and for (forensic) mortality reporting in public health statistics
Will adaptive deep brain stimulation for Parkinson’s disease become a real option soon? A Delphi consensus study
No full textWhile conventional deep brain stimulation (cDBS) treatment delivers continuous electrical stimuli, new adaptive DBS (aDBS) technology provides dynamic symptom-related stimulation. Research data are promising, and devices are already available, but are we ready for it? We asked leading DBS experts worldwide (n = 21) to discuss a research agenda for aDBS research in the near future to allow full adoption. A 5-point Likert scale questionnaire, along with a Delphi method, was employed. In the next 10 years, aDBS will be clinical routine, but research is needed to define which patients would benefit more from the treatment; second, implantation and programming procedures should be simplified to allow actual generalized adoption; third, new adaptive algorithms, and the integration of aDBS paradigm with new technologies, will improve control of more complex symptoms. Since the next years will be crucial for aDBS implementation, the research should focus on improving precision and making programming procedures more accessible
Suspension bioprinted whole intervertebral disc analogues enable regional stiffness- and hypoxia-regulated matrix secretion by primary human nucleus pulposus and annulus fibrosus cells
No full textIntervertebral disc (IVD) degeneration is a leading cause of back pain, and while studies have revealed the roles resident nucleus pulposus (NP) and annulus fibrosus (AF) cells play in degeneration, tissue-engineered IVD models are needed to better investigate the mechanisms underpinning these cell-driven changes. This study therefore integrated suspension baths with bioprinting to create four multi-material, whole IVD analogues and investigated the combined effect of reduced oxygen tension and increased regional matrix stiffness on disc cell phenotype since these factors correlate with IVD degeneration. Primary NP and AF cells were seeded into alginate-collagen hydrogels and bioprinted into biphasic IVD structures. The nascent area, intensity, and integrated density of pro-collagen type I, collagen type VI, aggrecan, and hyaluronic acid were quantified using immunofluorescence staining in each region. Stiffness-mediated collagen and glycosaminoglycan production was observed in the AF, and increased stiffness downregulated collagen type VI in the AF but upregulated it in NP. Oxygen tension impacted proteoglycan production, with hypoxia increasing aggrecan and hyaluronic acid in both regions. This work represents a step towards the automated biofabrication of whole IVD analogues and expands the state-of-the-art in suspension bioprinting using regionally specific matrix cues. The findings provide important insights into two key microenvironmental factors driving IVD degeneration. STATEMENT OF SIGNIFICANCE: This manuscript outlines an original application of suspended layer additive manufacturing to biofabricate novel, biphasic intervertebral disc analogues containing patient-derived primary human cells. Significantly, the bioprinted models demonstrated biological function and were used to assess the effect of stiffness and oxygen concentration on regional matrix production using a range of internationally-recognized phenotypic intervertebral disc cell markers. The study therefore furthers the state-of-the-art in suspended bioprinting using regionally specific matrix cues and paves the way for future bioprinted disc models that can serve as biosimulators capable of generating insights into key mechanisms governing tissue development, homeostasis, and degeneration
INTERLINK-1:A Phase III, Randomized, Placebo-Controlled Study of Monalizumab Plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
No full textPURPOSE: Treatment options for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) after failure of immune checkpoint inhibitor treatment and platinum-based chemotherapy are limited. Preliminary data suggested that monalizumab plus cetuximab had clinical activity in R/M HNSCC. PATIENTS AND METHODS: INTERLINK-1 (NCT04590963) was a double-blind, phase III study. Participants with R/M HNSCC who had received immune checkpoint inhibitor therapy and progressed despite platinum-based chemotherapy were randomized 2:1 to monalizumab (750 mg, every 2 weeks) or placebo, plus cetuximab (400 mg/m2 loading dose, then 250 mg/m2, weekly). The primary endpoint was overall survival (OS) in participants with non-oropharyngeal cancer or human papillomavirus (HPV)-negative oropharyngeal cancer (HPV-unrelated analysis set). Secondary endpoints included progression-free survival and objective response rate. RESULTS: At data cutoff, 216 participants were randomized in the HPV-unrelated analysis set: 145 to monalizumab plus cetuximab and 71 to placebo plus cetuximab. Median OS was 8.8 months for monalizumab plus cetuximab versus 8.6 months for placebo plus cetuximab (HR, 1.00; 95% confidence interval, 0.66-1.54); median progression-free survival was 3.6 versus 3.8 months, respectively (HR, 1.11; 95% confidence interval, 0.79-1.57); and the objective response rate was 15.2% versus 23.9%, respectively. INTERLINK-1 was terminated after a preplanned interim analysis showed that futility criteria were met (predetermined futility HR >0.874). Grade 3/4 treatment-related adverse events were reported in 18.3% and 17.2% of participants treated in the monalizumab and placebo arms, respectively. CONCLUSIONS: Monalizumab plus cetuximab did not improve OS compared with placebo plus cetuximab. The safety profile of the combination was consistent with safety observations for cetuximab monotherapy.</p
Individualized MRI-Based Stroke Prediction Score Using Plaque Vulnerability for Symptomatic Carotid Artery Disease Patients (IMPROVE)
No full textBACKGROUND: In symptomatic carotid stenosis, treatment decisions are currently primarily based on stenosis degree. We developed a clinical prediction model (Individualized Magnetic Resonance Imaging-Based Stroke Prediction Score Using Plaque Vulnerability for Patients With Symptomatic Carotid Artery Disease [IMPROVE]) incorporating the strong predictor, intraplaque hemorrhage on magnetic resonance imaging, stenosis degree, and risk factors to identify patients with high stroke risk. METHODS: IMPROVE was developed on data from 5 cohorts of 760 patients with symptomatic carotid disease on optimal medical treatment. Inclusion criteria included a recent transient ischemic attack/stroke (<6 months), magnetic resonance imaging-based information on intraplaque hemorrhage, no atrial fibrillation, and no immediate revascularization. IMPROVE was based on Cox regression using 5 expert-selected predictors and converted to 3-year ipsilateral ischemic stroke risk after internal validation. IMPROVE-based stratification was compared with care-as-usual using illustrative cutoffs: high risk was defined in IMPROVE as ≥ median 3-year IMPROVE risk, whereas in care-as-usual, it was ≥50% carotid stenosis. RESULTS: Sixty-five ipsilateral ischemic strokes occurred during a median follow-up of 1.2 years (interquartile range, 0.5-4.1). The IMPROVE model includes 5 predictors (hazard ratio [95% CI]): degree of stenosis (<50%: reference, 50%-69%: 4.54 [2.46-8.38], 70%-99% stenosis: 7.42 [3.45-15.95]), presence of intraplaque hemorrhage (5.61 [2.92-10.77]), classification of last event (ocular: reference, cerebral: 3.72 [1.11-12.52]), male sex (1.26 [0.64-2.48]), and age (1.14 [0.84-1.55] per 10-year increase). Internal validation revealed good accuracy (C statistic, 0.82 [95% CI, 0.77-0.87]) and no evidence of miscalibration (calibration slope, 0.93). Sensitivity for the illustrative IMPROVE cutoff was 92.6% (90.7-94.5) versus 80.6% (77.8-83.4) for care-as-usual. Specificity was 54.2% (50.7-57.8) for IMPROVE versus 52.9% (49.3-56.4) for care-as-usual. Patients stratified by IMPROVE as high risk had a higher incidence of ipsilateral ischemic stroke (24.0%) compared with the care-as-usual classification (20.7%). Among patients classified as lower-risk by IMPROVE and care-as-usual, 2.1% and 5.3%, respectively, experienced an ipsilateral ischemic stroke during follow-up. CONCLUSIONS: Using the presence of intraplaque hemorrhage on magnetic resonance imaging and 4 conventional parameters, the IMPROVE model provides accurate individual stroke risk estimates, which may facilitate stratification for revascularization after external validation.</p
Dynamic visual acuity assessment on a treadmill: a cross-sectional comparison of dynamic visual acuity loss and dropout rate between people with bilateral vestibulopathy and healthy age- and sex-matched participants
Get PDFAbstractImportance Walking and other dynamic conditions impair visual acuity in individualswith bilateral vestibulopathy (BVP). Dynamic visual acuity (DVA) can be assessed on atreadmill while participants walk at different speeds and this has proven to be a usefulassessment in classifying people with BVP. However, there are open questions relating tothe effects and interactions of age, presence of BVP and walking speed on DVA loss(DVAL) and DVA assessment dropout.Objective To investigate the effects of BVP, age and walking speed on DVAL and DVAassessment dropout, by comparing these outcomes between participants with BVP andhealthy age-sex-matched participants..Design, Setting and Participants Fifty-two participants with BVP and 52 age-sex-matchedhealthy participants completed a treadmill-based DVA assessment in this cross-sectionalstudy. Data were collected in Maastricht University Medical Centre from June 2021 toAugust 2024.Main Outcomes and Measures The measurement included a static condition at 0km/hand walking conditions at 2, 4, and 6km/h. The DVAL was measured as the differencebetween visual acuity in the static and walking conditions. At all speeds, the drop-outrate, handrail use and DVAL were examined in relation to BVP, age, and the relationshipbetween DVAL and speed in BVP and healthy controls.Results Age significantly increased the odds of dropping-out (odds ratio = 1.160,P<0.001), while BVP did not increase the odds of dropping-out (odds ratio = 0.792,P=0.733). A significant Group*Speed (P=0.004) interaction effect was found for DVAL,with DVAL being significantly worse in people with BVP across all walking speeds, gettingprogressively worse as speed increased, which was not seen in the healthy participants.Age did not have a significant effect on DVAL (P=0.06).Conclusions and Relevance BVP does not appear to restrict the ability to walk at thehigher speeds of a DVA assessment and cause an increase in dropout rate, whereas agedoes. BVP significantly impacts DVA, with increasing DVAL at increasing walking speeds
The impact of formative assessment on pupil academic achievement: An empirical study of the effects of a formative assessment practices program that was co-designed in a teacher community
No full textBackgroundThe empirical evidence-base for effects of formative assessment on pupil academic achievement is inconclusive, despite its potential claim to improve teaching and learning. Contemporary views conceptualize formative assessment as a unified practice of integrated strategies. However, studies that investigated the effects of formative assessment on pupil academic achievement in primary education focused on separate components with different methods.AimsThis study investigates whether a co-designed program of unified formative assessment strategies affects pupil academic achievement.SampleParticipants were 976 Dutch elementary school pupils (10–11 years).MethodsA quasi-experimental pretest/posttest research design was used with a pre-established intervention and control group. The intervention group consisted of all pupils who were taught by elementary school teachers that participated in a teacher co-designed formative assessment program. Teachers belonging to the control group did not partake in the co-design. Standardized mathematics test scores were used to investigate whether the co-designed formative assessment practices program had an effect on pupil learning achievement using multilevel modelling.ResultsAfter controlling for pre-intervention gain, and school-specific pupil population complexity, the pupils of teachers that participated in the formative assessment co-design did not significantly outperform the pupils in the control group. The multilevel analysis also revealed non-significant effects of the interaction between the formative assessment intervention and performance levels on mathematical gain.ConclusionsThis study provides valuable insights in the challenges that lie in both implementing (effective) formative assessment practices and investigating the effectiveness of a teacher community co-designed formative assessment practices program on pupil academic results
