Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours : results from the COPPADIS cohort

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Von Willebrand factor levels predict clinical outcome in patients with cirrhosis and portal hypertension

Background and aims: Endothelial dysfunction is a major determinant of the increased hepatic vascular tone of cirrhotic livers. Von Willebrand factor (vWF), P-selectin and 8-iso-PGF2\u3b1 (isoprostanes), surrogate markers of endothelial dysfunction, are increased in patients with cirrhosis. This study was aimed at exploring in patients with cirrhosis and portal hypertension the relation of these endothelial factors with systemic and hepatic haemodynamics and their possible clinical prognostic value. Methods: 42 consecutive patients with cirrhosis and portal hypertension had measurement of the hepatic venous pressure gradient (HVPG), cardiopulmonary pressures and vWF, P-selectin and isoprostane levels in blood samples from hepatic and peripheral veins. Patients were followed up to 2 years, death or liver transplantation and any clinical event were recorded. Results: vWF, P-selectin and isoprostanes were increased in patients with cirrhosis compared with controls (p<0.001). vWF levels significantly correlated with HVPG, Child-Pugh score and MELD. Cox model analysis disclosed an independent indirect association of peripheral vWF with survival free of portal hypertension-related events and of transplantation. The vWF cut-off value of 216 U/dl (Youden index) disclosed two different populations of patients with cirrhosis with a highly different probability of survival free of portal hypertension-related events and transplantation (87% vs 22%, p=0.001). The prognostic role of vWF persisted after adjusting for parameters of liver dysfunction and for HVPG. Conclusions: In patients with cirrhosis and portal hypertension vWF levels correlate with liver function and HVPG and independently predict clinical outcome

Patients whose first episode of bleeding occurs while taking a &#946;-blocker have high long-term risks of rebleeding and death

Background & Aims: Patients who have their first episode of variceal bleeding despite primary prophylaxis with a nonselective \u3b2-adrenergic receptor antagonist (also called a nonselective \u3b2-blocker [NSBB]) receive additional treatment by endoscopic band ligation to prevent further bleeding. However, little is known about their long-term outcomes. Methods: We collected data on 89 consecutive patients with cirrhosis who were admitted to the Liver Unit of Hospital Cl\uednic, Barcelona, with acute esophageal variceal bleeding between June 2007 and February 2011. Thirty-four patients were receiving primary prophylaxis with NSBBs when they had their first episode of variceal bleeding, whereas 55 were not receiving NSBBs (controls). All patients were subsequently treated with a combination of endoscopic band ligation and NSBBs. Patients were examined after 1, 3, and 6 months and every 6 months thereafter until 2 years. Results: After 2 years, a greater proportion of patients who had their first episode of bleeding while on NSBBs had further bleeding, compared with controls (48% vs 24%; P = .01). Primary prophylaxis with NSBBs and serum levels of bilirubin were independent predictors of rebleeding. Overall, 11 patients died, and 5 underwent liver transplantation. Liver transplantation-free survival was lower among patients who had their first episode of bleeding while taking NSBBs (66% vs 88% for controls; P = .02). Primary prophylaxis with NSBBs and Child-Pugh class were independently associated with liver transplantation-free survival. Conclusions: Patients who have their first episode of variceal bleeding while on primary prophylaxis with a \u3b2-blocking agent have an increased risk of further bleeding and death, despite adding endoscopic band ligation. These patients possibly require alternative treatment approaches

Metabolomics discloses potential biomarkers to predict the acute HVPG response to propranolol in patients with cirrhosis

Background: In cirrhosis, a decrease in hepatic venous pressure gradient (HVPG)&nbsp;&gt;&nbsp;10% after acute iv propranolol (HVPG response) is associated with a lower risk of decompensation and death. Only a part of patients are HVPG responders and there are no accurate non-invasive markers to identify them. We aimed at discovering metabolomic biomarkers of HVPG responders to propranolol. Methods: Sixty-six patients with cirrhosis and HVPG&nbsp; 65&nbsp;10&nbsp;mm Hg in whom the acute HVPG response to propranolol was assessed, were prospectively included. A targeted metabolomic serum analysis using ultrahigh-performance liquid chromatography coupled to mass spectrometry was performed. Different combinations of 2-3 metabolites identifying HVPG responders (HVPG reduction&nbsp;&gt;&nbsp;10%) were obtained by stepwise logistic regression. The best of these model (AUROC, Akaike criterion) underwent internal cross-validation and cut-offs to classify responders/non-responders was proposed. Results: A total of 41/66 (62%) patients were HVPG responders. Three hundred and eighty-nine metabolites were detected and 177 were finally eligible. Eighteen metabolites were associated to the HVPG response at univariate analysis; at multivariable analysis, a model including a phosphatidylcholine (PC(P-16:0/22:6)) and a free fatty acid (20:2(n-6), eicosadienoic acid) performed well for HVPG response, with an AUROC of 0.801 (0.761 at internal validation). The cut-off 0.629 was the most efficient for overall classification (49/66 patients correctly classified). Two cut-off values allowed identifying responders (0.688, PPV 84%) and non-responders (0.384, NPV 82%) with undetermined values for 17/66 patients. Clinical variables did not add to the model. Conclusions: The combination of two metabolites helps at identifying HVPG responders to acute propranolol. It could be a useful non-invasive test to classify the HVPG response to propranolol