Search

IntroductionA recent questionnaire-based study suggested that bruxism and painful temporomandibular disorders (TMD pain) may be more prevalent in patients with Parkinson’s disease (PD) compared with controls. The presence of both bruxism and TMD pain may negatively influence patients’ quality of life. The present study is designed to clinically and more objectively investigate the presence of bruxism and TMD pain in patients with PD. The secondary aim of the study is to identify factors associated with bruxism and TMD pain in patients with PD, such as disease severity and dopaminergic medication usage. Furthermore, the presence of tooth wear in patients with PD will be studied as this can be a major consequence of bruxism. Finally, deviations in saliva composition that may contribute to tooth wear will be studied.Methods and analysisThis is a single-centre observational outpatient study at the Amsterdam University Medical Centres, location VUmc. All patients with a clinical diagnosis of PD will be eligible for inclusion. Participants will fill in a set of questionnaires. Subsequently, patients will be examined clinically for, among others, TMD pain, presence and severity of tooth wear, and deviations in saliva composition. Sleep-time registrations will take place for 5 nights with the GrindCare GC4 (ie, a portable, single-channel electromyographic recorder) to assess sleep bruxism and simultaneously by the use of the BruxApp for 5 days to assess awake bruxism. We will partly use data collected during standard clinical care to minimise patient burden.Ethics and disseminationThe scientific and ethical aspects of this study protocol have been approved by the Medical Ethics Review Committee of the Amsterdam UMC, location VUmc; NL. 2019.143. Informed consent will be obtained from all participants. The results will be published in a peer-reviewed journal, if relevant presented at conferences, and published as part of a PhD thesis.Trial registration numberNL8307.

Background: Parkinson's disease (PD) is commonly known as a disorder that affects the smooth performance of body movements. In addition to the motor impairments, patients with PD often experience pain. Both motor impairments and pain can occur throughout the body, hence including the orofacial region. However, currently, there is a lack of knowledge on the orofacial manifestations. Since orofacial pain and dysfunction can, amongst others, reduce the quality of life of patients with PD, it is important to explore the prevalence of these symptoms in the PD population. Objective: To provide a broad overview of the relevant literature on orofacial pain and dysfunction in patients with PD. Furthermore, we aim to generate hypotheses for future research on this topic. Databases and data treatment: A literature search (in PubMed, Embase.com, Web of Science [Core collection], and Cochrane Library) was performed on 20 January 2022, in collaboration with a medical librarian. In total, 7180 articles were found, of which 50 were finally included in this scoping review. Results: In the included studies, pain (e.g. orofacial pain (N = 2) and temporomandibular disorder pain (N = 2)), orofacial motor dysfunction (e.g. limited jaw movements (N = 10), reduced maximum muscle output (N = 3), chewing difficulties (N = 9), unspecified TMD (N = 3), sensory disturbances (N = 1)), and bruxism (N = 3) were observed more often in patients with PD than in healthy controls. Conclusion: Patients with PD experience more pain in the orofacial area and more dysfunction of the masticatory system than their healthy peers. Significance: This scoping review can increase health care providers' awareness of the problems that can be encountered in the orofacial area of PD patients, especially pain syndromes also occur in the orofacial region and not only in the extremities. Besides, dysfunction of the orofacial area is elaborated in this scoping review, which helps to understand that this limits PD patients' quality of life. Further, the outcomes of this scoping review can assist in encouraging collaboration between medicine and dentistry. Finally, this scoping review suggests new research areas, based on the gaps identified in the current literature on this topic. Ultimately, this will improve individualized strategies for reducing orofacial pain and/or dysfunction in PD patients.

Objectives: We aimed to provide an overview of the available literature that includes both objective assessments (namely hypersalivation and hyposalivation) and the subjective experience (namely xerostomia and drooling) of salivary problems in patients with Parkinson's disease. Background: In patients with Parkinson's disease, there may be complaints of salivary problems such as xerostomia or drooling. This can have consequences for their oral health and quality of life. To date, systematic reviews have focused on drooling only. Materials and methods: A literature search in 4 databases was performed up to 12 February 2021. Two researchers independently assessed studies for eligibility. Results: In total, 63 studies were included. The prevalence of self-reported xerostomia ranged from 49% to 77%, and that of self-reported drooling ranged from 5% to 80%. Ten articles reported a significantly lower mean salivary flow in patients with Parkinson's disease than in controls. None of the articles with both a control group and a patient group reported a significantly higher salivary flow in patients with Parkinson's disease. When questioned about subjective salivary problems, a significantly higher prevalence of both xerostomia (7 studies) and drooling (14 studies) was found in patients with Parkinson's disease than in controls. Patients with Parkinson's disease have a lower salivary flow rate and higher prevalence of both xerostomia and drooling than controls. Conclusion: The complexity of salivary problems present in patients with Parkinson's disease necessitates a multidisciplinary approach in order to avoid mutually counteracting treatments from different healthcare professionals.

Background Advances in the survival of patients with invasive aspergillosis (IA) are jeopardized by the emergence of azole resistance in Aspergillus fumigatus, which has been associated with high probability of azole treatment failure. The clinical implications of azole-resistant IA compared to azole-susceptible IA remain unclear. Thus, we seek to describe the epidemiology and to determine the efficacy of antifungal therapy in patients with documented azole-resistant IA compared to azole-susceptible IA in patients with hematological malignancy. Methods For proven and probable IA (EORTC/MSG 2019) caused by A. fumigatus in patients with hematological malignancies retrospective data were documented, comprising demographics, diagnosis, treatment, response, and outcome. Sites provided susceptibility results or respective isolates for analysis in a central laboratory. Results Sites in 16 countries worldwide enrolled 187 cases diagnosed with IA between 2010 and 2019; 31 (16.6%) were resistant to at least one of the clinical azoles. Fungal isolates were available from 42 cases. A mixed fungal infection was reported for 32 patients (17.1%), most were related to non-fumigatus Aspergillus and non-Aspergillus molds (n=22, 69%). Most patients were male (66.8%) and overall the majority of patients were in the age groups between 50 and 89 years (71%). Amphotericin B was used for treatment in 24 (77%) patients with azole-resistant IA, compared to 76 (49%) in the azole-susceptible group (lipid-based formulation in 98%); only five (16%) patients with azole-resistant IA were treated with an azole alone vs. 57 (36%) of those with azole-susceptible IA. Overall, all-cause mortality rate was higher for patients with azole-resistant compared to azole-susceptible IA (74.2% vs. 53.8%, log rank P=0.004), the 8 patients with an azole-resistant IA treated in the intensive care unit died within 1 month (Figure 1). Details on underlying disease and survival are given in Table 1. Table 1. Underlying hematological malignancy and clinical outcome of patients with azole-resistant and azole-susceptible invasive aspergillosis Figure 1. Intensive care unit 1-year survival probability for patients with azole-resistant and azole-susceptible invasive aspergillosis Conclusion Azole-resistance in IA is associated with worse outcome, especially in critically ill patients. Susceptibility testing should be considered in patients with a suspected azole-resistant IA to support treatment decisions. Disclosures Danila Seidel, PhD, Basilea (Other Financial or Material Support, travel grant) Oliver Cornely, Prof., Actelion (Grant/Research Support)Actelion (Other Financial or Material Support, Personal fees)Al Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Other Financial or Material Support, Personal fees)Amplyx (Other Financial or Material Support, Personal fees)Amplyx (Grant/Research Support)Astellas (Grant/Research Support)Astellas (Other Financial or Material Support, Personal fees)Basilea (Other Financial or Material Support, Personal fees)Basilea (Grant/Research Support)Biosys UK Limited (Other Financial or Material Support, Personal fees)Cidara (Other Financial or Material Support, Personal fees)Cidara (Grant/Research Support)Da Volterra (Grant/Research Support)Da Volterra (Other Financial or Material Support, Personal fees)Entasis (Other Financial or Material Support, Personal fees)F2G (Other Financial or Material Support)F2G (Grant/Research Support)Gilead (Grant/Research Support)Gilead (Other Financial or Material Support, Personal fees)Grupo Biotoscana (Other Financial or Material Support, Personal fees)Janssen Pharmaceuticals (Grant/Research Support)Matinas (Other Financial or Material Support, Personal fees)Medicines Company (Grant/Research Support)MedPace (Grant/Research Support)MedPace (Other Financial or Material Support, Personal fees)Melinta Therapeutics (Grant/Research Support)Menarini Ricerche (Other Financial or Material Support, Personal fees)Merck/MSD (Other Financial or Material Support, Personal fees)Merck/MSD (Grant/Research Support)Mylan Pharmaceuticals (Consultant)Nabriva Therapeutics (Other Financial or Material Support, Personal fees)Octapharma (Other Financial or Material Support, Personal fees)Paratek Pharmaceuticals (Other Financial or Material Support, Personal fees)Pfizer (Other Financial or Material Support, Personal fees)Pfizer (Grant/Research Support)PSI (Other Financial or Material Support, Personal fees)Rempex (Other Financial or Material Support, Personal fees)Roche Diagnostics (Other Financial or Material Support, Personal fees)Scynexis (Other Financial or Material Support, Personal fees)Scynexis (Grant/Research Support)Seres Therapeutics (Other Financial or Material Support, Personal fees)Tetraphase (Other Financial or Material Support, Personal fees) Philipp Koehler, MD, Akademie für Infektionsmedizin e.V., (Other Financial or Material Support, Personal fees)Astellas Pharma GmbH (Other Financial or Material Support, Personal fees)Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany (Other Financial or Material Support, Other)Gilead Sciences GmbH (Other Financial or Material Support, Personal fees)GPR Academy Ruesselsheim (Speaker’s Bureau)Miltenyi Biotec GmbH (Other Financial or Material Support, Non-financial support)MSD Sharp & Dohme GmbH (Other Financial or Material Support, Personal fees)Noxxon N.V. (Speaker’s Bureau)University Hospital, LMU Munich (Other Financial or Material Support, Personal fees) Katrien Lagrou, n/a, FUJIFILM WAKO (Speaker’s Bureau)Gilead (Consultant, Speaker’s Bureau)MSD (Consultant, Speaker’s Bureau, Other Financial or Material Support, travel grant)Pfizer (Speaker’s Bureau, travel grant)SMB Laboratoires Brussels (Consultant) Zdenek Racil, n/a, Astellas (Grant/Research Support, Speaker’s Bureau, travel grant) Blandine Rammaert, n/a, Gilead (Speaker’s Bureau, Other Financial or Material Support, travel grant)Merck/MSD (Speaker’s Bureau)Pfizer (Other Financial or Material Support, travel grant) Nikolay Klimko, n/a, Astellas (Speaker’s Bureau)Gilead (Speaker’s Bureau)Merck/MSD (Speaker’s Bureau)Pfizer (Speaker’s Bureau) Sung-Yeon Cho, MD, Gilead (Grant/Research Support, Speaker’s Bureau)Merck Sharp & Dohme (Grant/Research Support, Speaker’s Bureau)Pfizer (Grant/Research Support, Speaker’s Bureau)

Candida auris is a rapidly emerging multidrug-resistant pathogenic yeast. In recent years, an increasing number of C. auris invasive infections and colonized patients have been reported, and C. auris has been associated with hospital outbreaks worldwide, mainly in intensive care units (ICUs). Here, we describe the first two cases of C. auris in The Netherlands. Both cases were treated in a healthcare facility in India prior to admission. The patients were routinely placed in contact precautions in a single room after admission, which is common practice in The Netherlands for patients with hospitalization outside The Netherlands. No transmission of C. auris was noticed in both hospitals. Routine admission screening both for multidrug-resistant (MDR) bacteria and MDR yeasts should be considered for patients admitted from foreign hospitals or countries with reported C. auris transmission.

Background Depression is a common neuropsychiatric symptom in Parkinson9s disease (PD). In previous research, PD-related depression was associated with striatal dopaminergic deficits, presumably due to degeneration of brainstem dopaminergic projections. Segregated areas of the striatum are crucially involved in various parallelly arranged cortical-striatal-thalamocortical circuits and serve functions in, among others, motor control or emotion. This suggests regional specificity of dopaminergic deficits in the striatum in motor and depressive symptoms in PD. Methods In this cross-sectional retrospective study, we correlated severity scores of depressive and motor symptoms in 100 non-demented PD patients (median Hoehn & Yahr stage: 2) with dopamine loss in specific regions of the striatum as measured by [ 123 I]FP-CIT SPECT tracer binding to the dopamine transporter (DaT). Results Depressive symptoms were related to lower DaT binding in the right caudate nucleus, while motor symptoms were associated with decreased DaT binding in the right putamen. This double dissociation was most pronounced in early-stage PD patients. Conclusions These results suggest that depressive symptoms in PD are associated with dopamine loss in the caudate nucleus, possibly related to degeneration of dopaminergic projections from the ventral tegmental area, while motor symptoms are associated with low dopamine signalling to the putamen and loss of nigrostriatal projections. This is consistent with the neuroanatomy of partially segregated cortical-striatal-thalamocortical circuits and supports the role of dysfunctional associative and motivational circuits in PD-related depression.

Contains fulltext : 167923.pdf (Publisher’s version ) (Open Access) Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression.

The locus ceruleus is among the earliest affected brain regions in Parkinson's disease (PD) showing Lewy body pathology and neuronal loss. To improve our understanding of the pathogenesis of PD, we performed the first proteomic analysis ever of post‐mortem locus ceruleus tissue of six pathologically confirmed PD patients, and six age‐ and gender‐matched non‐neurological controls. In total 2495 proteins were identified, of which 87 proteins were differentially expressed in the locus ceruleus of PD patients compared with controls. The majority of these differentially expressed proteins are known to be involved in processes that have been implicated in the pathogenesis of PD previously, including mitochondrial dysfunction, oxidative stress, protein misfolding, cytoskeleton dysregulation and inflammation. Several individual proteins were identified that have hitherto not been associated with PD, such as regucalcin, which plays a role in maintaining intracellular calcium homeostasis, and isoform 1 of kinectin, which is involved in transport of cellular components along microtubules. In addition, pathway analysis suggests a pathogenetic role for aminoacyl‐tRNA‐biosynthesis. These findings indicate that the proteome of the locus ceruleus of PD patients and non‐neurological controls provides data that are relevant to the pathogenesis of PD, reflecting both known and potentially novel pathogenetic pathways.