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Improving early recognition and management of child maltreatment at the emergency department
No full textChild maltreatment is a large public health problem, with long-lasting effects on both the individual and future generations because of intergenerational trauma effects, and society. It is therefore of the utmost importance to increase early recognition and adequate management of (possible) child maltreatment. Studies have shown systematic screening for child maltreatment at the emergency department is effective in improving its detection rate. A multidisciplinary approach including physical, psychological and forensic assessment is specifically necessary in the evaluation of child sexual abuse.The overall objective of this thesis is to improve the early recognition and management of child maltreatment at emergency departments (EDs) in Europe, by exploring areas of improvement, developing and validating a screening instrument, establishing a comprehensive approach for implementation, and evaluating existing procedures of a multidisciplinary and specialized child sexual abuse team.<br/
Chronic inflammatory demyelinating polyradiculoneuropathy in the Netherlands:Epidemiology, diagnosis and treatment
No full textRemodeling human Th17 populations by vitamin D:mechanisms and implications in inflammatory arthritis
No full textInflammatory arthritis comprises a group of immune-mediated inflammatory diseases (IMID) primarily characterized by joint inflammation due to dysregulated activation of immune and stromal cells. Th17 cells are thought to play a critical role in these diseases by producing pro-inflammatory cytokines and interacting with other immune cells and synovial fibroblasts. Suppressing Th17 cell pathogenicity is therefore considered important for controlling inflammation and disease activity. Our previous studies demonstrated the immunoregulatory effect of active vitamin D (1,25(OH)2D3) on human memory CCR6+Th17 cells, which suppresses pro-inflammatory potential while enhancing regulatory capacity. This thesis elucidates the mechanisms by which 1,25(OH)2D3 modulates transcription and metabolic pathways to reprogram human memory CCR6+Th17 cell phenotype and function to Treg-like cells, with implications for its use in inflammatory arthritis. A coordinated regulatory network underlies the suppression of inflammatory potential and induction of regulatory features in these cells. Further in vivo and clinical investigations are needed to determine its efficacy and potential to enhance existing treatment strategies in Th17-mediated inflammatory diseases
Cerebrovascular regulation during increases in systemic blood flow and systemic vascular resistance
No full textIt is unknown whether, under anesthesia, an increase in blood pressure by augmenting cardiac output would exert a different effect on brain perfusion compared with a rise in blood pressure by elevating systemic vascular resistance. In this study, we disentangled these two parameters by monitoring changes in middle cerebral artery blood velocity (MCA Vmean) and frontal cerebral lobe oxygenation (cO2Hb) in 15 patients on cardiopulmonary bypass (CPB) during two experiments. First, we increased systemic vascular resistance, using 100 μg phenylephrine, while CPB flow remained clamped. Second, we increased CPB flow while s-stemic vascular resistance remained unmodified. Mean arterial pressure increased 12 ± 4 mmHg and 11 ± 5 mmHg after raising systemic vascular resistance and cardiac blood flow, respectively (P ¼ 0.60). Systemic vasoconstriction with a constant cardiac blood flow increased the MCA Vmean (17%, P ¼ 0.001) while the cO2Hb declined (-2.2%, P ¼ 0.005). Augmenting cardiac blood flow increased both MCA Vmean and cO2Hb (17%, P < 0.001, and 2.5%, P ¼ 0.02) concordantly. Cerebral perfusion seemed to be dependent on cardiac blood flow, since both cO2Hb and MCA Vmean changed concordantly with an increase in cardiopulmonary bypass flow. A systemic vascular resistance-mediated blood pressure increase with the a1-adrenergic agonist phenylephrine had a comparable rise in MCA Vmean but a discordant effect on cO2Hb, presumably due to both cutaneous and cerebral vasoconstriction. NEW & NOTEWORTHY Elevating blood pressure by increasing cardiac blood flow (Q) _ or by increasing systemic vascular resistance (SVR) results in a comparable increase in middle cerebral artery blood velocity. In contrast, although frontal cerebral lobe oxygenation increased with increasing Q, _ it decreased with increasing SVR. This difference was less pronounced when Q_ was kept constant, suggesting that part of the decrease may be attributed to an SVR-induced decrease in Q.</p
Pulmonary valve repair at the time of the Ross procedure:A safe and durable strategy to address postimplantation aortic regurgitation
No full textBackground: Contemporary evidence supports use of the Ross procedure (pulmonary autograft) to treat patients with aortic valve disease. No studies have evaluated the impact of autograft repair to correct residual aortic regurgitation at the index Ross procedure on late outcomes. Methods: This study includes patients undergoing a Ross procedure followed by concomitant autograft valve repair at 2 institutions. Autograft repair was defined as correction of residual aortic regurgitation during the same admission for the Ross procedure. Results: Between 2011 and 2024, 675 patients underwent a Ross procedure in 2 large-volume institutions. Of them, 22 (3%) underwent autograft repair for postprocedural aortic regurgitation (mean age, 52 years; 23% were female). Fourteen patients had a bicuspid valve (64%), and 5 patients had a unicuspid aortic valve (23%). One patient had a bicuspid autograft. Residual aortic regurgitation was eccentric in 8 patients (36%), commissural in 9 patients (41%), and combined in 5 patients (23%). Aortic regurgitation was corrected using central plication sutures in 13 patients (59%) and commissuroplasty in 14 patients (63%). There were no perioperative deaths. One patient required reintervention and conversion to a Bentall procedure 6 days after the index Ross procedure. All patients but 1 (5%; mild aortic regurgitation) had no or trivial aortic regurgitation on discharge. At a median echocardiographic follow-up of 3 years (Q1-Q3: 2-8), 7 patients have mild aortic regurgitation (32%), and 1 patient developed mild-to-moderate aortic regurgitation after 7 years. All other patients have no or trivial aortic regurgitation. At 5 years, the cumulative incidence of aortic regurgitation greater than 2 is 6% ± 6%.Conclusions: Addressing postprocedural aortic regurgitation after autograft implantation is safe and associated with durable outcomes in the first decade. These findings support correction of postprocedural commissural or eccentric jets at the time of index operation.</p
Challenges in the measurement and interpretation of risk-related behaviour and brain activity in lab studies
No full textVascular models to study migraine:From human isolated blood vessels to vessel-on-chip
Get PDFIn this thesis, the vascular effects of CGRP and novel pharmacological treatment of migraine targeting CGRP (receptors) are investigated. CGRP is a neuropeptide that is involved in migraine pathophysiology, but is also a potent vasodilator that can offer cardiovascular protective effects. Here, human isolated coronary arteries and human isolated middle meningeal arteries are used for functional pharmacological studies. In addition, a vessel-on-chip model is developed to be able to study patient-specific vascular responses. CGRP was shown to induce relaxation of human coronary arteries via Gβγ subunits, in contrast to the cAMP-dependent mechanisms that were hypothesized previously. In addition, sex differences were observed for CGRP-induced relaxation of human middle meningeal arteries and differential expression of receptor subunits was observed between human coronary arteries and human middle meningeal arteries. In addition, some of the CGRP receptor antagonist show different behavior in these two vascular beds, when considering potency and Schild analysis. Moreover, an additional effect was observed when combining CGRP receptor inhibition using the monoclonal antibody erenumab and the small molecule CGRP receptor antagonists and CGRP receptor antagonists were shown to worsen outcomes of cerebral ischemic stroke in mice.The thesis offers new insights in CGRP (receptor) blockade, intracellular signaling pathways, sex differences and receptor expression in the human vasculature. In addition, it describes the development of a novel vessel-on-chip model that can be used to study patient-specific blood vessel responses in the future.<br/
