Characterization of the nasopharyngeal and middle ear microbiota in gastroesophageal reflux-prone versus gastroesophageal reflux non-prone children

Otitis media (OM) is one of the most common pediatric infections worldwide, but the complex microbiology associated with OM is poorly understood. Previous studies have shown an association between OM and gastroesophageal reflux (GER) in children. Therefore, in order to bridge the gap in our current understanding of the interaction between GER and OM, we investigated the nasopharyngeal and middle ear microbiota of children suffering from GER-associated OM and OM only, using culture-independent 16S rRNA gene sequencing. Middle ear fluid, nasopharyngeal swabs, and clinical data were collected as part of a prospective pilot study conducted at the Department of Otorhinolaryngology of the Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands. A total of 30 children up to 12 years of age who suffered from recurrent acute otitis media (AOM) (5), chronic otitis media with effusion (OME) (23), or both (2), and who were listed for tympanostomy tube placement, were included in the study. Nine children were included in the GER-associated OM cohort and 21 in the OM-only cohort. We found no obvious effect of GER on the nasopharyngeal and middle ear microbiota between the two groups of children. However, our results highlight the need to assess the true role of Alloiococcus spp. and Turicella spp. in children presenting with a high prevalence of recurrent AOM and chronic OME

Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study

Contains fulltext : 96669.pdf (publisher's version ) (Open Access)INTRODUCTION: Identifying ankylosing spondylitis (AS) patients who are likely to benefit from tumor necrosis factor-alpha (TNF-alpha) blocking therapy is important, especially in view of the costs and potential side effects of these agents. Recently, the AS Disease Activity Score (ASDAS) has been developed to assess both subjective and objective aspects of AS disease activity. However, data about the predictive value of the ASDAS with respect to clinical response to TNF-alpha blocking therapy are lacking. The aim of the present study was to identify baseline predictors of response and discontinuation of TNF-alpha blocking therapy in AS patients in daily clinical practice. METHODS: AS outpatients who started TNF-alpha blocking therapy were included in the Groningen Leeuwarden Ankylosing Spondylitis (GLAS) study, an ongoing prospective longitudinal observational cohort study with follow-up visits according to a fixed protocol. For the present analysis, patients were excluded if they had previously received anti-TNF-alpha treatment. Predictor analyses of response and treatment discontinuation were performed using logistic and Cox regression models, respectively. RESULTS: Between November 2004 and April 2010, 220 patients started treatment with infliximab (n = 32), etanercept (n = 137), or adalimumab (n = 51). At three and six months, 68% and 63% of patients were Assessments in Ankylosing Spondylitis (ASAS)20 responders, 49% and 46% ASAS40 responders, and 49% and 50% Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)50 responders, respectively. Baseline predictors of response were younger age, male gender, higher ASDAS score, higher erythrocyte sedimentation rate (ESR) level, higher C-reactive protein (CRP) level, presence of peripheral arthritis, higher patient's global assessment of disease activity, and lower modified Schober test. In August 2010, 64% of patients were still using their TNF-alpha blocking agent with a median follow-up of 33.1 months (range 2.4 to 68.2). Baseline predictors of discontinuation of TNF-alpha blocking therapy were female gender, absence of peripheral arthritis, higher BASDAI, lower ESR level, and lower CRP level. CONCLUSIONS: Besides younger age and male gender, objective variables such as higher inflammatory markers or ASDAS score were identified as independent baseline predictors of response and/or continuation of TNF-alpha blocking therapy. In contrast, higher baseline BASDAI score was independently associated with treatment discontinuation. Based on these results, it seems clinically relevant to include more objective variables in the evaluation of anti-TNF-alpha treatment

A view from the clinic – Perspectives from Dutch patients and professionals on high myopia care

Purpose: To understand and compare perspectives of patients and professionals on current ophthalmologic care for high myopia, and to identify challenges and future opportunities. Methods: Self-reported data were collected through two online questionnaires. Patient perspective was obtained from highly myopic members of a patient organisation based in the Netherlands using a 17-item questionnaire consisting of open and multiple-choice questions regarding personal experience with myopia care. The ophthalmologist perspective was obtained from practising Dutch ophthalmologists with a 12-item questionnaire of multiple-choice questions on work-related demographics, myopia care in daily practice and need for improvement. The response rate for patients was 27% (n = 136/500) and for ophthalmologists, 24% (n = 169/716). Results: Patients were highly concerned about personal progressive loss of vision (69%) and feared their psychological well-being (82%) in case this would happen. The quality of performance of care provided by ophthalmologists was rated as excellent or satisfactory by 64% of the patients. These ratings for multidisciplinary care and insurance reimbursement were as low as 28% and 18% respectively. The mean concern among ophthalmologists about the rise in high myopia was 6.9 (SEM 0.1) on a 10-point scale. Sixty-nine per cent of the ophthalmologists reported that asymptomatic myopic patients should not be examined regularly at outpatient clinics. Ophthalmologists urged the development of clinical guidelines (74%), but did report (95%) that they informed patients about risk factors and complications. This contrasted with the view of patients, of whom 42% were discontent with information provided by ophthalmologists. Conclusions: These questionnaires demonstrated that the current clinical care delivered to highly myopic patients is in need of improvement. The expected higher demand for myopia care in the near future requires preferred practice patterns, professionals specifically trained to manage myopic pathology, accurate and comprehensive information exchange and collaboration of in- and out-of-hospital professionals across the full eye care chain.</p

DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia (DECONNECT):research protocol for a cross-sectional pilot study

Introduction Pre-eclampsia is a hypertensive disorder affecting up to 8% of pregnancies. After pre-eclampsia, women are at increased risk of cognitive problems, and cerebrovascular and cardiovascular disorders. These sequelae could result from microvascular dysfunction persisting after pre-eclampsia. This study will explore differences in cerebral and myocardial microvascular function between women after pre-eclampsia and women after normotensive gestation. We hypothesise that pre-eclampsia alters cerebral and myocardial microvascular functions, which in turn are related to diminished cognitive and cardiac performance. Methods and analysis The cross-sectional € DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia' (DECONNECT) pilot study includes women after pre-eclampsia and controls after normotensive pregnancy between 6 months and 20 years after gestation. We recruit women from the Queen of Hearts study, a study investigating subclinical heart failure after pre-eclampsia. Neuropsychological tests are employed to assess different cognitive domains, including attention, processing speed, and cognitive control. Cerebral images are recorded using a 7 Tesla MRI to assess blood-brain barrier integrity, perfusion, blood flow, functional and structural networks, and anatomical dimensions. Cardiac images are recorded using a 3 Tesla MRI to assess cardiac perfusion, strain, dimensions, mass, and degree of fibrosis. We assess the effect of a history of pre-eclampsia using multivariable regression analyses. Ethics and dissemination This study is approved by the Ethics Committee of Maastricht University Medical Centre (METC azM/UM, NL47252.068.14). Knowledge dissemination will include scientific publications, presentations at conferences and public forums, and social media. Trial registration number NCT02347540.</p

Genetic Evaluation in a Cohort of 126 Dutch Pulmonary Arterial Hypertension Patients

Pulmonary arterial hypertension (PAH) is a severe, life-threatening disease, and in some cases is caused by genetic defects. This study sought to assess the diagnostic yield of genetic testing in a Dutch cohort of 126 PAH patients. Historically, genetic testing in the Netherlands consisted of the analysis of BMPR2 and SMAD9. These genes were analyzed in 70 of the 126 patients. A (likely) pathogenic (LP/P) variant was detected in 22 (31%) of them. After the identification of additional PAH associated genes, a next generation sequencing (NGS) panel consisting of 19 genes was developed in 2018. Additional genetic testing was offered to the 48 BMPR2 and SMAD9 negative patients, out of which 28 opted for NGS analysis. In addition, this gene panel was analyzed in 56 newly identified idiopathic (IPAH) or pulmonary veno occlusive disease (PVOD) patients. In these 84 patients, NGS panel testing revealed LP/P variants in BMPR2 (N = 4), GDF2 (N = 2), EIF2AK4 (N = 1), and TBX4 (N = 3). Furthermore, 134 relatives of 32 probands with a LP/P variant were tested, yielding 41 carriers. NGS panel screening offered to IPAH/PVOD patients led to the identification of LP/P variants in GDF2, EIF2AK4, and TBX4 in six additional patients. The identification of LP/P variants in patients allows for screening of at-risk relatives, enabling the early identification of PAH

Kepler Flares II: The Temporal Morphology of White-Light Flares on GJ 1243

We present the largest sample of flares ever compiled for a single M dwarf, the active M4 star GJ 1243. Over 6100 individual flare events, with energies ranging from $10^{29}$ to $10^{33}$ erg, are found in 11 months of 1-minute cadence data from Kepler. This sample is unique for its completeness and dynamic range. We have developed automated tools for finding flares in short-cadence Kepler light curves, and performed extensive validation and classification of the sample by eye. From this pristine sample of flares we generate a median flare template. This template shows that two exponential cooling phases are present during the white-light flare decay, providing fundamental constraints for models of flare physics. The template is also used as a basis function to decompose complex multi-peaked flares, allowing us to study the energy distribution of these events. Only a small number of flare events are not well fit by our template. We find that complex, multi-peaked flares occur in over 80% of flares with a duration of 50 minutes or greater. The underlying distribution of flare durations for events 10 minutes and longer appears to follow a broken power law. Our results support the idea that sympathetic flaring may be responsible for some complex flare events.Comment: 12 pages, 9 figures, accepted for publication in Ap

Consumption of plant food supplements in the Netherlands.

The use of food supplements containing herbs or other botanical ingredients (plant food supplements, PFS) is on the rise. In some cases, PFS can contain compounds that are toxic and may pose a health risk. To assess the potential health risks, information on the consumption of PFS is required, however, this was lacking for the Netherlands. In the current study, the consumption of PFS was investigated for several subgroups in the Dutch population, including children. Data from the Dutch National Food Consumption Surveys were used to get a first impression on the consumption of PFS. To obtain more detailed information, a specific PFS consumption survey was performed using online questionnaires. First, a screening survey was performed among a representative sample of 75 100 adults and children of the Dutch population, followed by a main survey among 739 selected PFS users in eight different age and gender subgroups. The prevalence of PFS users in the Dutch population was approximately 10% for men, 17% for women and 13% for children. A wide variety of PFS was used, with around 600 different PFS reported, containing 345 different botanicals. The most frequently used botanicals were echinacea (Echinacea purpurea), ginkgo (Ginkgo biloba), cranberry (Vaccinium macrocarpon), ginseng (Panax ginseng) and algae (such as species belonging to the genus Spirulina or Chlorella). Because PFS are widely used in the Dutch population, it is important to evaluate the potential risks associated with PFS consumption in the Netherlands, including potential herb-drug interactions. The data collected in this study are of great value to assess these risks

COVID-19 vaccination in patients with immune thrombocytopenia

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by low platelet count and increased bleeding risk. COVID-19 vaccination has been described as risk factor for de novo ITP, but the effects of COVID-19 vaccination in patients with ITP are unknown. Our aims were to investigate the effects of COVID-19 vaccination in ITP patients on platelet count, bleeding complications and ITP exacerbation (any of: ≥50% decline in platelet count; or nadir platelet count 20% decrease from baseline; or use of rescue therapy). Platelet counts of ITP patients and healthy controls were collected immediately before, 1 and 4 weeks after first and second vaccination. Linear mixed-effects modelling was applied to analyze platelet counts over time. We included 218 ITP patients (50.9% female, mean age 55 years and median platelet count of 106x109/L) and 200 healthy controls (60.0% female, mean age 58 years and median platelet count of 256x109/L). Platelet counts decreased by 6.3% after vaccination. We observed no difference in decrease between the groups. Thirty ITP patients (13.8%, 95%CI 9.5%-19.1%) had an exacerbation and 5 (2.2%, 95%CI 0.7%-5.3%) suffered from a bleeding event. Risk factors for ITP exacerbation were platelet count <50x109/L (OR 5.3, 95%CI 2.1-13.7), ITP treatment at time of vaccination (OR 3.4, 95%CI 1.5-8.0) and age (OR 0.96 per year, 95%CI 0.94-0.99). Our study highlights safety of COVID-19 vaccination in ITP patients and importance of close monitoring platelet counts in a subgroup of ITP patients. ITP patients with exacerbation responded well on therapy

Additional rare variant analysis in Parkinson's Disease cases with and without known pathogenic mutations: evidence for oligogenic inheritance

Oligogenic inheritance implies a role for several genetic factors in disease etiology. We studied oligogenic inheritance in Parkinson’s (PD) by assessing the potential burden of additional rare variants in established Mendelian genes and/or GBA, in individuals with and without a primary pathogenic genetic cause in two large independent cohorts totaling 7,900 PD cases and 6,166 controls. An excess (≥30%) of cases with a recognized primary genetic cause had ≥1 additional rare variants in Mendelian PD genes, as compared with no known mutation PD cases (17%) and unaffected controls (16%), supporting our hypothesis. Carriers of additional Mendelian gene variants have younger ages at onset (AAO). The effect of additional Mendelian variants in LRRK2 G2019S mutation carriers, of which ATP13A2 variation is particularly common, may account for some of the variation in penetrance. About 10% of no known mutation PD cases harbor a rare GBA variant compared to known pathogenic mutation PD cases (8%) and controls (5%), with carriers having earlier AAOs. Together, the data suggest that the oligogenic inheritance of rare Mendelian variants may be important in patient with a primary pathogenic cause, whereas GBA increases risk across all forms of PD. This study highlights potential genetic complexity of Mendelian PD. The identification of potential modifying variants provides new insights into disease mechanisms by potentially separating relevant from benign variants and by the interaction between genes in specific pathways. In the future this may be relevant to genetic testing and counselling of PD patients and their families

Intrathoracic vs Cervical Anastomosis After Totally or Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer A Randomized Clinical Trial

Background: Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the preferred location of the anastomosis after transthoracic MIE. Objective: To compare an intrathoracic with a cervical anastomosis in a randomized clinical trial. Design, Setting, and Participants: This open, multicenter randomized clinical superiority trial was performed at 9 Dutch high-volume hospitals. Patients with midesophageal to distal esophageal or gastroesophageal junction cancer planned for curative resection were included. Data collection occurred from April 2016 through February 2020. Intervention: Patients were randomly assigned (1:1) to transthoracic MIE with intrathoracic or cervical anastomosis. Main Outcomes and Measures: The primary end point was anastomotic leakage requiring endoscopic, radiologic, or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality, and quality of life. Results: Two hundred sixty-two patients were randomized, and 245 were eligible for analysis. Anastomotic leakage necessitating reintervention occurred in 15 of 122 patients with intrathoracic anastomosis (12.3%) and in 39 of 123 patients with cervical anastomosis (31.7%; risk difference, -19.4% [95% CI, -29.5% to -9.3%]). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference, -21.9% [95% CI, -32.1% to -11.6%]). Intensive care unit length of stay, mortality rates, and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with fewer severe complications (risk difference, -11.3% [-20.4% to -2.2%]), lower incidence of recurrent laryngeal nerve palsy (risk difference, -7.3% [95% CI, -12.1% to -2.5%]), and better quality of life in 3 subdomains (mean differences: dysphagia, -12.2 [95% CI, -19.6 to -4.7]; problems of choking when swallowing, -10.3 [95% CI, -16.4 to 4.2]; trouble with talking, -15.3 [95% CI, -22.9 to -7.7]). Conclusions and Relevance: In this randomized clinical trial, intrathoracic anastomosis resulted in better outcome for patients treated with transthoracic MIE for midesophageal to distal esophageal or gastroesophageal junction cancer. Trial Registration: Trialregister.nl Identifier: NL4183 (NTR4333)