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The aim of this study was to perform a systematic review of the literature on the temporomandibular joint (TMJ) prosthesis as a treatment option after mandibular condyle fracture. Three databases were searched (PubMed, Embase, Cochrane Library) and 2670 unique papers were identified. A total of 337 studies were included (121 case reports, 89 case series, and 127 cohort/clinical studies). In total 14,396 patients and 21,560 prostheses were described. Of the 127 cohort or clinical studies, 100 (79%) reported inclusion criteria, 54 (43%) reported exclusion criteria, and 96 (76%) reported the inclusion period. The base population from which patients were recruited was reported in 57 studies (45%). The reason for TMJ prosthesis implantation was reported for 4177 patients (29.0%). A history of condylar fracture was present in 83 patients (2.0%); a history of mandibular trauma was present in 580 patients (13.9%). The meta-analysis showed a pooled prevalence of condylar fracture of 1.6% (95% confidence interval 0.9-2.4%) and a pooled prevalence of trauma or condylar fracture of 11.3% (95% confidence interval 7.1-16.0%). Heterogeneity was highly significant (P < 0.001). The TMJ prosthesis appears to be reserved for patients with persistent pain, bony or fibrous ankylosis, or osteomyelitis after primary closed or open treatment of fractures of the mandibular condyle.

Synthetic polymers typically show dispersity in molecular weight and potentially in chemical composition. For the analysis of the chemical-composition distribution (CCD) gradient liquid chromatography may be used. The CCD obtained using this method is often convoluted with an underlying molecular-weight distribution (MWD). In this paper we demonstrate that the influence of the MWD can be reduced using very steep gradients and that such gradients are best realized utilizing recycling gradient liquid chromatography (LC↻LC). This method allows for a more-accurate determination of the CCD and the assessment of (approximate) critical conditions (if these exist), even when high-molecular-weight standards of narrow dispersity are not readily available. The performance and usefulness of the approach is demonstrated for several polystyrene standards, and for the separation of statistical copolymers consisting of styrene/methyl methacrylate and methyl methacrylate/butyl methacrylate. For the latter case, approximate critical compositions of the copolymers were calculated from the critical compositions of two homopolymers and one copolymer of known chemical composition, allowing for a determination of the CCD of unknown samples. Using this approach it is shown that the copolymers elute significantly closer to the predicted critical compositions after recycling of the gradient. This is most clear for the lowest-molecular-weight copolymer (Mw = 4.2 kDa), for which the difference between measured and predicted elution composition decreases from 7.9% without recycling to 1.4% after recycling.

Objectives The addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of coronary CT angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD). Methods This retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACEs) during the 1-year follow-up using chi-square tests for independence. Kaplan–Meier curves were used to visualize the occurrence of safety outcomes over time. Results A total of 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group, and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA group, and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA), and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA, and three (2.2%) SPECT (p p = 0.15). However, patients in the CCTA group more often underwent revascularization (p = 0.007). Conclusion Addition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after 1 year. Key Points • Previous studies have shown that computed tomography–derived fractional flow reserve improves the accuracy of coronary computed tomography angiography without changes in acquisition protocols. • This study shows that use of computed tomography-derived fractional flow reserve as gatekeeper to invasive coronary angiography in patients suspected of stable coronary artery disease leads to less invasive testing and revascularization without observed difference in outcomes after 1 year. • This could lead to a significant reduction in costs, complications and (retrospectively unnecessary) usage of diagnostic testing capacity, and a significant increase in patient satisfaction.

The detailed analysis of polymeric materials is one of the necessary steps to elucidate the relationship between the chemical distributions of a polymer and the functional properties of a material. Within the UNMATCHED project (UNderstanding MATerials by CHaracterizing Essential Distributions) many techniques have been investigated – or further developed – to aid in the analysis of such materials. The primary focus of this thesis was on using liquid chromatography (LC) in innovative ways to analyze polymer chemical distributions. Additionally, chemometric strategies that help improve the interpretability of the data obtained from these methods were investigated and documented in later chapters.

BACKGROUND: Changes in near-infrared spectroscopy-derived regional tissue oxygen saturation (StO2) during a vascular occlusion test (VOT; ischemic provocation of microcirculation by rapid inflation and deflation of a tourniquet) allow estimating peripheral tissue O2 consumption (desaturation slope; DS), vascular reactivity (recovery slope; RS) and post-ischemic hyperperfusion (AUC-H). The effects of isolated alterations in the inspiratory fraction of O2 (FiO2) and changes in expiratory CO2 remain to be elucidated. Therefore, in this secondary analysis we determined the effects of standardized isolated instances of hypoxia, hyperoxia, hypocapnia and hypercapnia on the VOT-induced StO2 changes in healthy volunteers (n = 20) to establish reference values for future physiological studies.METHODS: StO2 was measured on the thenar muscle. Multiple VOTs were performed in a standardized manner: i.e. at room air (baseline), during hyperoxia (FiO2 1.0), mild hypoxia (FiO2 ≈ 0.11), and after a second baseline, during hypocapnia (end-tidal CO2 (etCO2) 2.5-3.0 vol%) and hypercapnia (etCO2 7.0-7.5 vol%) at room air. Differences in DS, RS, and AUC-H were tested using repeated-measures ANOVA.RESULTS: DS and RS remained constant during all applied conditions. AUC-H after hypoxia was smaller compared to hyperoxia (963 %*sec vs hyperoxia 1702 %*sec, P = 0.005), while there was no difference in AUC-H duration between hypoxia and baseline. The StO2 peak (after tourniquet deflation) during hypoxia was lower compared to baseline and hyperoxia (92 % vs 94 % and 98 %, P < 0.001).CONCLUSION: We conclude that in healthy volunteers at rest, common situations observed during anesthesia and intensive care such as exposure to hypoxia, hyperoxia, hypocapnia, or hypercapnia, did not affect peripheral tissue O2 consumption and vascular reactivity as assessed by VOT-induced changes in StO2. These observations may serve as reference values for future physiological studies.TRIAL REGISTRATION: This study represents a secondary analysis of an original study which has been registered at ClinicalTrials.gov nr: NCT02561052.

In this PhD-thesis, the treatment of fractures of the mandibular condyle, the part of the lower jaw that lies near the temporomandibular joint, is analysed. The treatment of these fractures can often be done without surgery. In this so-called closed treatment, the fracture heals according to the patient's occlusion.In this study it was shown, in groups of more than 100 patients, that jaw functioning (e.g. chewing and speaking) and mouth opening generally recover well with closed treatment. This recovery can take up to one year. In some patients, for example the elderly, or patients with bilateral fractures, the recovery is less favourable.Sometimes an operative treatment is chosen, in which the mandibular condyle is surgically repositioned and fixed in the right position. Based on the best available evidence from the literature, this PhD-thesis proposes a guideline in which situations it is best to choose a closed or an operative treatment for mandibular condylar fractures.To further investigate the reasons for differences in treatment choices, patient populations were compared from two different regions: Groningen and Dresden. The treatment in Groningen was mainly closed and in Dresden both closed and operative. These differences appeared to be due to differences in the patient population, but also in the health care system and the radiographs used.If the mandibular condyle is even more damaged, it is possible to place a temporomandibular joint prosthesis. A systematic literature review showed that a temporomandibular joint prosthesis was rarely placed after a fracture of the mandibular condyle.

Background Dystonia is a rare movement disorder, in which patients suffer from involuntary twisting movements or abnormal posturing. Next to these motor symptoms, patients have a high prevalence of psychiatric comorbidity, suggesting a role for serotonin in its pathophysiology. This study investigates the percentage of DNA methylation of the gene encoding for the serotonin reuptake transporter (SLC6A4) in dystonia patients and the associations between methylation levels and presence and severity of psychiatric symptoms. Methods Patients with cervical dystonia (n = 49), myoclonus dystonia (n = 41) and dopa-responsive dystonia (DRD) (n = 27) and a group of healthy controls (n = 56) were included. Psychiatric comorbidity was evaluated with validated questionnaires. Methylation levels of 20 CpG sites situated 69 to 213 base pairs upstream of the start codon of SLC6A4 were investigated. Methylation in dystonia patients was compared to healthy controls, correcting for age, and correlated with psychiatric comorbidity. Results Bootstrapped quantile regression analysis showed that being a dystonia patient compared to a healthy control significantly explains the methylation level at two CpG sites (CpG 24: pseudo-R2 = 0.05, p = 0.04, CpG 32: pseudo-R2 = 0.14, p = 0.03). Subgroup analysis revealed that being a DRD patient significantly explained a part of the variance of methylation levels at two CpG sites (CpG 21: pseudo-R2 = 0.03, p = 0.00, CpG 24: pseudo-R2 = 0.06, p = 0.03). Regression analysis showed that methylation level at CpG 38 significantly explained a small proportion of the variance of severity score for anxiety (R2 = 0.07, p = 0.04) and having a diagnosis of depression (Nagelkerke R2: 0.11, p = 0.00). Genotype of the 5-HTTLPR polymorphism had no additional effect on these associations. Conclusions This study showed an association between percentage of methylation at several specific sites of the promoter region of SLCA64 and (dopa-responsive) dystonia patients compared to healthy controls. Furthermore, methylation levels were associated with severity of anxiety and presence of a depressive disorder in the dystonia group. This study suggests alterations in the serotonergic metabolism in dystonia patients, and its relation with the non-motor symptoms.

INTRODUCTION: In dystonia, dopaminergic alterations are considered to be responsible for the motor symptoms. Recent attention for the highly prevalent non-motor symptoms suggest also a role for serotonin in the pathophysiology. In this study we investigated the dopaminergic, serotonergic and noradrenergic metabolism in blood samples of dystonia patients and its relation with (non-)motor manifestations.METHODS: Concentrations of metabolites of dopaminergic, serotonergic and noradrenergic pathways were measured in platelet-rich plasma in 41 myoclonus-dystonia (M-D), 25 dopa-responsive dystonia (DRD), 50 cervical dystonia (CD) patients and 55 healthy individuals. (Non-)motor symptoms were assessed using validated instruments, and correlated with concentrations of metabolites.RESULTS: A significantly higher concentration of 3-methoxytyramine (0.03 vs. 0.02 nmol/L, p < 0.01), a metabolite of dopamine, and a reduced concentration of tryptophan (50 vs. 53 μmol/L, p = 0.03), the precursor of serotonin was found in dystonia patients compared to controls. The dopamine/levodopa ratio was higher in CD patients compared to other dystonia groups (p < 0.01). Surprisingly, relatively high concentrations of levodopa were found in the untreated DRD patients. Low concentrations of levodopa were associated with severity of dystonia (rs = -0.3, p < 0.01), depression (rs = -0.3, p < 0.01) and fatigue (rs = -0.2, p = 0.04).CONCLUSION: This study shows alterations in the dopaminergic and serotonergic metabolism of patients with dystonia, with dystonia subtype specific changes. Low concentrations of levodopa, but not of serotonergic metabolites, were associated with both motor and non-motor symptoms. Further insight into the dopaminergic and serotonergic systems in dystonia with a special attention to the kinetics of enzymes involved in these pathways, might lead to better treatment options.