Microvascular Dysfunction Is Associated With Worse Cognitive Performance: The Maastricht Study.

Microvascular dysfunction may be associated with worse cognitive performance. Most previous studies did not adjust for important confounders, evaluated only individual measures of microvascular dysfunction, and showed inconsistent results. We evaluated the association between a comprehensive set of measures of microvascular dysfunction and cognitive performance in the population-based Maastricht Study. We used cross-sectional data including 3011 participants (age 59.5±8.2; 48.9% women; 26.5% type 2 diabetes mellitus [oversampled by design]). Measures of microvascular dysfunction included magnetic resonance imaging features of cerebral small vessel disease, plasma biomarkers of microvascular dysfunction, albuminuria, flicker light-induced retinal arteriolar and venular dilation response and heat-induced skin hyperemia. These measures were summarized into a microvascular dysfunction composite score. Cognitive domains assessed were memory, processing speed, and executive function. A cognitive function score was calculated as the sum of the scores on these 3 cognitive domains. The microvascular dysfunction score was associated with a worse cognitive function score (standardized ß, -0.087 [95% CI, -0.127 to -0.047]), independent of age, education level, sex, type 2 diabetes mellitus, smoking, alcohol use, hypertension, total/HDL (high-density lipoprotein) cholesterol ratio, triglycerides, lipid-modifying medication, prior cardiovascular disease, depression and plasma biomarkers of low-grade inflammation. The fully adjusted ß-coefficient of the association between the microvascular dysfunction score and the cognitive function score was equivalent to 2 (range, 1-3) years of aging for each SD higher microvascular dysfunction score. The microvascular dysfunction score was associated with worse memory and processing speed but not with worse executive function. The present study shows that microvascular dysfunction is associated with worse cognitive performance.

[Management of Hemoptysis: Results of an Algorithm-Based Interdisciplinary Treatment Scheme]. / Management von Hämoptysen: Ergebnisse einer algorithmusbasierten interdisziplinären Versorgung.

INTRODUCTION: Hemoptysis is a worrying symptom for the majority of patients, is frequently a sign for a severe disease and can develop into a life-threatening situation. Various therapeutic methods and medical specialties can be involved in the management of these patients. Guidelines or evidence-based recommendations on this issue are not available. Based on our long-term experience and considering all established diagnostic and therapeutic means, we propose an algorithm to manage this condition. PATIENTS AND METHODS: This is a retrospective analysis of a cohort from a single thoracic surgical institution. Data regarding the used diagnostic and therapeutic methods with focus on outcome parameters are presented. Based on our experience and the published data we discuss the proposed algorithm. RESULTS: Between 01.2009 and 12.2013, 204 patients were hospitalised and treated for hemoptysis. Malignancies were the most frequent (50 %) cause of hemoptysis, followed by infectious/inflammatory diseases (25 %), cardiovascular disorders (6 %), rare (12 %) and unclear (7 %) circumstances. In 71 cases the bleeding stopped spontaneously, in 124 (61 %) one invasive measure (interventional bronchoscopy 43, bronchial artery embolisation 34 or operation 12) or a combination of methods (35 combinations of two or all three methods) were necessary to stop the hemoptysis. Six patients died without intervention. The bronchial artery embolisation showed a 79 % success rate and a morbidity of 11 %. Lung resections were performed in 30 cases (morbidity 43 %, mortality 0 %). The mortality directly due to massive hemoptysis was 4.5 %. CONCLUSIONS: Even small hemoptysis can be the warning signal for serious conditions and immediate diagnostic evaluation and therapy, preferentially in an inpatient setting, is often mandatory. A prompt diagnostic bronchoscopy is advocated. The therapeutic method of first choice is non-surgical for the most cases (interventional bronchoscopy, bronchial artery embolisation). Lung resections retain an important role in the management of hemoptysis and are the only available therapy for some diseases. It is advisable to delay surgery until the bleeding is controlled and the patient is stabilised. Best results for managing hemoptysis can be achieved with a multidisciplinary approach (interventional bronchoscopy, angiology and thoracic surgery) in a high expertise centre.

Dendritic cell reconstitution is associated with relapse-free survival and acute GVHD severity in children after allogeneic stem cell transplantation.

DCs are potent APCs and key regulators of innate and adaptive immunity. After allo-SCT, their reconstitution in the peripheral blood (PB) to levels similar to those in healthy individuals tends to be slow. We investigate the age- and sex-dependant immune reconstitution of myeloid (mDC) and plasmacytoid DC (pDC) in the PB of 45 children with leukaemia or myelodysplastic syndrome (aged 1-17 years, median 10) after allo-SCT with regard to relapse, acute GVHD (aGVHD) and relapse-free survival. Low pDC/µL PB up to day 60 post SCT are associated with higher incidence of moderate or severe aGVHD (P=0.035), whereas high pDC/µL PB up to day 60 are associated with higher risk of relapse (P<0.001). The time-trend of DCs/µL PB for days 0-200 is a significant predictor of relapse-free survival for both mDCs (P<0.001) and pDCs (P=0.020). Jointly modelling DC reconstitution and complications improves on these simple criteria. Compared with BM, PBSC transplants tend to show slower mDC/pDC reconstitution (P=0.001, 0.031, respectively), but have no direct effect on relapse-free survival. These results suggest an important role for both mDCs and pDCs in the reconstituting immune system. The inclusion of mDCs and pDCs may improve existing models for complication prediction following allo-SCT.

Myeloid and plasmacytoid dendritic cells: reference ranges in the peripheral blood of healthy children.

To date, few publications report on dendritic cells values in healthy children and mostly are found as control groups in studies focused on either allergic and autoimmune diseases or malignancies. This report provides an overview of 8 publications regarding absolute dendritic cells quantification in the peripheral blood of healthy children by using minimum manipulated samples processed within 24 hours.

Age-matched dendritic cell subpopulations reference values in childhood.

Dendritic cells (DCs) are the most potent antigen-presenting cells and are the key link between the innate and adaptive immune response. Only a few reports with study populations of up to 50 individuals have been published with age-based reference values for DC subpopulations in healthy children. Therefore, we aimed to establish reference ranges in a larger study population of 100 healthy children, which allowed age-matched subgroups. Most previous studies were performed using a dual-platform approach. In this study, a single-platform approach in a lyse no-wash procedure was used. DC subpopulations were defined as follows: CD45(+) CD85k(+) HLA-DR(+) CD14(-) CD16(-) CD33(+) cells as myeloid DCs (mDCs) and CD45(+) CD85k(+) HLA-DR(+) CD14(-) CD16(-) CD123(+) cells as plasmacytoid DCs (pDCs). Reference ranges were established using a semi-parametric regression of age-matched absolute and relative DC counts. We found a significant decline with increasing age in the medians of mDCs (P = 0.0003) and pDCs per µl peripheral blood (PB) (P = 0.004) and in the 50%, 90% and 95% reference ranges. We also identified significantly lower absolute cell counts of mDCs per µl PB in girls than in boys for all age groups (P = 0.0015). Due to the larger paediatric study population and single-platform approach, this study may give a more precise overview of the normal age-matched development of DC subpopulations and may provide a basis for analyzing abnormal DC counts in different illnesses or therapies such as post stem cell transplantation.

Detection of disseminated tumour cells in mediastinoscopic lymph node biopsies and endobronchial ultrasonography-guided transbronchial needle aspiration in patients with suspected lung cancer.

PURPOSE: Ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes (EBUS-TBNA) is apparently more accurate for cancer diagnosis than standard transbronchial needle aspiration (TBNA), but it is less sensitive than mediastinoscopy. The detection of disseminated tumour cells in transbronchial needle aspiration and mediastinoscopic biopsies could improve staging and might be helpful concerning indications for neoadjuvant regimen. The goal of this study was to develop a quantitative method for the detection of disseminated tumour cells (DTCs) in lymph node samples from patients with suspected lung cancer. PATIENTS AND METHODS: We compared in a prospective trail EBUS-TBNA (n=58 patients, 86 samples) and mediastinoscopy (n=22 patients, 37 samples) in two largely independent cohorts of lung cancer patients. Eleven patients, 14 samples were analysed using both methods. Patients without evidence of malignant disease were available as controls for EBUS-TBNA (n=20 patients, 28 samples) and mediastinoscopy (n=6 patients, 8 samples). Real-time quantitative mRNA analysis was performed for the cytokeratin 19 (CK19) and MAGE-A genes (MAGE-A 1-6, MAGE-A12) as markers, using a LightCycler 480 instrument. RESULTS: CK19 mRNA expression in EBUS-TBNA samples was detected in 84/86 (98%) and in 28/28 control samples (100%). After mediastinoscopy 16/37 (43%) samples of lung cancer patients were CK19 mRNA positive while controls showed no CK19 mRNA expression (0/8). MAGE-A expression was detectable in 42/86 (49%) EBUS-TBNA samples and in 13/37 (35%) mediastinoscopy samples. MAGE-A expression was detected in EBUS-TBNA controls in 3/28 (11%) and 1/8 (12%) mediastinoscopy controls. High MAGE-A expression correlated with increased tumour stage. CONCLUSION: Since CK19 expression was detected in all EBUS-TBNA samples from the control patients, but not in mediastinoscopy samples, we conclude that CK19 is not suitable as a marker for disseminated tumour cells in samples attained by EBUS-TBNA. One possible explanation is a contamination with epithelial cells from the bronchial tubes. MAGE-A genes are promising markers for disseminated tumour cells in lymph nodes in patients with suspected lung cancer which merit further investigation.

Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in PD--a comparison of neuropsychological effects.

OBJECTIVE: To compare the cognitive and behavioural effects of unilateral pallidotomy and bilateral subthalamic nucleus (STN) stimulation. METHODS: After baseline examination 34 patients were randomly assigned to unilateral pallidotomy (4 left-sided, 10 right-sided) or bilateral STN stimulation (n = 20). At baseline and six and twelve months after surgery we administered neuropsychological tests of language, memory, visuospatial function, mental speed and executive functions. Also a depression rating scale, and self and proxy ratings of memory and dysexecutive symptoms were administered. RESULTS: Six months after surgery, the STN group and the pallidotomy group differed significantly in change from baseline in number of errors on two tests of executive functioning. After 12 months the STN group reported less positive affect compared with baseline than the pallidotomy group. One patient in the STN group showed an overall cognitive deterioration due to complications. CONCLUSIONS: Although we need larger groups to draw firm conclusions, our results suggest that bilateral STN stimulation has slightly more negative effects on executive functioning than unilateral pallidotomy.

Metatarsophalangeal joint capsule tears: an analysis by arthrography, a new classification system and surgical management.

Metatarsalgia is a common presenting symptom with an established list of differential diagnoses. The authors present a classification system and surgical treatment algorithm for chronic metatarsophalangeal pain due to metatarsophalangeal joint capsule tear. A series of 58 metatarsophalangeal joints with partial tear diagnosed by arthrogram and treated by surgical repair are reviewed. The authors propose a classification system based on preoperative arthrography and a surgical repair procedure for each type of three distinct patterns. A study was developed and funded to perform postoperative arthrograms on 15 patients who had undergone surgical repair using the procedures presented. The purpose of the study was to validate the utility of the arthrogram in the diagnosis and clarification of the nature of the capsular tear. The authors were also able to demonstrate that the arthrographic findings became normal postoperatively, and that surgical repair of a seemingly innocuous capsule tear relieves pain. Fifty-six patients in the series reported relief of their preoperative symptoms. Postoperative arthrograms in 15 patients demonstrated a normal pattern in 73%, 20% had decreased extravasation, and 7% were unchanged.