Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Risk stratification for short‐term mortality at hospital admission for acute exacerbations of COPD

Background and objective Exacerbations of chronic obstructive pulmonary disease (ECOPD) are associated with increased in-hospital and short-term mortality. Developing an easy-to-use model to predict adverse outcomes will be useful in daily clinical practice and will facilitate management decisions. We aimed to assess mortality rates and potential predictors for short-term mortality after severe ECOPD. Classification and Regression Tree (CART) model was used to identify predictors of adverse outcome. Methods A retrospective observational cohort study, including all patients admitted to Maastricht University Medical Center with ECOPD between June 2011 and December 2014 was performed. The last admission was taken into account, and its demographic, clinical and biochemical data were recorded. Results A total of 364 hospitalized patients were enrolled. Mean (SD) age was 70.5 (10.2) years, 54.4% were male and mean FEV1 45.2% (17.7) of predicted. The in-hospital and 90-day mortality were, respectively, 8.5 and 16.2%. Independent risk factors for 90-day mortality were: PaC0(2) (odds ratio (OR): 1.31; 95% confidence interval (CI): 1.00-0.35), age (OR: 1.09; CI: 0.06-0.11), body mass index (BMI) = 9.1 kPa, age > 80 years, BMI <18.5 kg/m(2) and previous admission for ECOPD as the most discriminatory factors. Conclusion According CART analysis, high PaCO2 and age, low BMI and previous admission for ECOPD in last 2 years were the strongest predictors of 90-day mortality in patients with severe ECOPD. In absence of any of these factors, no patients died, suggesting that this model indeed enables risk stratification

Risk stratification for short-term mortality at hospital admission for acute exacerbations of COPD

Background and objective Exacerbations of chronic obstructive pulmonary disease (ECOPD) are associated with increased in-hospital and short-term mortality. Developing an easy-to-use model to predict adverse outcomes will be useful in daily clinical practice and will facilitate management decisions. We aimed to assess mortality rates and potential predictors for short-term mortality after severe ECOPD. Classification and Regression Tree (CART) model was used to identify predictors of adverse outcome. Methods A retrospective observational cohort study, including all patients admitted to Maastricht University Medical Center with ECOPD between June 2011 and December 2014 was performed. The last admission was taken into account, and its demographic, clinical and biochemical data were recorded. Results A total of 364 hospitalized patients were enrolled. Mean (SD) age was 70.5 (10.2) years, 54.4% were male and mean FEV1 45.2% (17.7) of predicted. The in-hospital and 90-day mortality were, respectively, 8.5 and 16.2%. Independent risk factors for 90-day mortality were: PaC0(2) (odds ratio (OR): 1.31; 95% confidence interval (CI): 1.00-0.35), age (OR: 1.09; CI: 0.06-0.11), body mass index (BMI) = 9.1 kPa, age > 80 years, BMI <18.5 kg/m(2) and previous admission for ECOPD as the most discriminatory factors. Conclusion According CART analysis, high PaCO2 and age, low BMI and previous admission for ECOPD in last 2 years were the strongest predictors of 90-day mortality in patients with severe ECOPD. In absence of any of these factors, no patients died, suggesting that this model indeed enables risk stratification

Predictors for long-term mortality in COPD patients requiring non-invasive positive pressure ventilation for the treatment of acute respiratory failure

Introduction The effectiveness of non-invasive mechanical ventilation (NIV) in the management of COPD patients suffering from acute respiratory failure (ARF) as a consequence of exacerbation of the disease, is well established. However, data on long-term outcomes and their predictors, including the individual response to NIV, are scarce. Objectives To investigate predictors for short- and long-term mortality in this study population. Methods A retrospective cohort study was performed including all patients admitted to the Medium Respiratory Care Unit of Maastricht University Medical Center in Maastricht, the Netherlands, with hospitalized exacerbation of COPD (H-ECOPD) with ARF requiring NIV for the first time between January 2009 and December 2011. An extensive number of potential predictors of outcomes, including the response to NIV, were determined on admission and during hospitalization. Univariate and multivariate logistic regression was used for statistical analysis. Results Seventy-eight consecutive patients with moderate to severe COPD (mean age 71.0 +/- 10.7 years; 48.7% males) were included; In-hospital, 1-year and 2-year mortality rates were 14.1%, 43.6% and 56.4%, respectively. Independent risk factors for 2-year mortality were: advanced age (odds ratio(OR) 1.025; confidence interval (CI) 1.002-1.049;P = 0.037), prolonged NIV use more than 8 days (OR:1.054;CI:1.006-1.104;P = 0.027) and no successful response to NIV (OR:2.392;CI:1.297-4.413;P = 0.005). Conclusion Patients with an H-ECOPD requiring NIV for the first time, constitute a severely ill patient group with high in-hospital and 2-year mortality. This study identified advanced age, NIV use more than 8 days and unsuccessful response to NIV as clinical important independent predictors for long-term mortality

Predictors for long‐term mortality in COPD patients requiring non‐invasive positive pressure ventilation for the treatment of acute respiratory failure

Introduction The effectiveness of non-invasive mechanical ventilation (NIV) in the management of COPD patients suffering from acute respiratory failure (ARF) as a consequence of exacerbation of the disease, is well established. However, data on long-term outcomes and their predictors, including the individual response to NIV, are scarce. Objectives To investigate predictors for short- and long-term mortality in this study population. Methods A retrospective cohort study was performed including all patients admitted to the Medium Respiratory Care Unit of Maastricht University Medical Center in Maastricht, the Netherlands, with hospitalized exacerbation of COPD (H-ECOPD) with ARF requiring NIV for the first time between January 2009 and December 2011. An extensive number of potential predictors of outcomes, including the response to NIV, were determined on admission and during hospitalization. Univariate and multivariate logistic regression was used for statistical analysis. Results Seventy-eight consecutive patients with moderate to severe COPD (mean age 71.0 +/- 10.7 years; 48.7% males) were included; In-hospital, 1-year and 2-year mortality rates were 14.1%, 43.6% and 56.4%, respectively. Independent risk factors for 2-year mortality were: advanced age (odds ratio(OR) 1.025; confidence interval (CI) 1.002-1.049;P = 0.037), prolonged NIV use more than 8 days (OR:1.054;CI:1.006-1.104;P = 0.027) and no successful response to NIV (OR:2.392;CI:1.297-4.413;P = 0.005). Conclusion Patients with an H-ECOPD requiring NIV for the first time, constitute a severely ill patient group with high in-hospital and 2-year mortality. This study identified advanced age, NIV use more than 8 days and unsuccessful response to NIV as clinical important independent predictors for long-term mortality

Phrenic neuropathy and diaphragm dysfunction in neuralgic amyotrophy

OBJECTIVE: To describe the clinical phenotype and recovery of diaphragm dysfunction caused by neuralgic amyotrophy in a large cohort of patients, to improve accurate awareness of this entity, and to encourage adoption of a standardized approach for diagnosis and treatment. METHODS: This observational cohort study recruited adult patients with neuralgic amyotrophy and symptoms of idiopathic phrenic neuropathy from the database of the Dutch expert center for neuralgic amyotrophy and the Dutch centers for home mechanical ventilation. Demographic and clinical information on diagnosis, symptoms, and recovery was obtained from chart review. We attempted to contact all patients for a follow-up interview. RESULTS: Phrenic neuropathy occurs in 7.6% of patients with neuralgic amyotrophy. Unilateral diaphragmatic dysfunction and bilateral diaphragmatic dysfunction are frequently symptomatic, causing exertional dyspnea, orthopnea, disturbed sleep, and excessive fatigue. Diagnostic practices varied widely and were often not optimally targeted. The majority of patients experienced at least moderate recovery within 2 years. CONCLUSION: We recommend screening every patient with neuralgic amyotrophy for diaphragm dysfunction by asking about orthopnea and by performing upright and supine vital capacity screening and diaphragm ultrasound in cases of suspected phrenic neuropathy to optimize diagnosis and care