Cerebrospinal Fluid α-Synuclein Predicts Cognitive Decline in Parkinson Disease Progression in the DATATOP Cohort

Most patients with Parkinson disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although α-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and α-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess α-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing α-synuclein (phase 1 to phase 2 change of −0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between α-synuclein and motor symptoms. Longitudinally, lower α-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall α-synuclein × time interaction effect coefficient, −0.12 (P = 0.037); delayed recall, −0.05 (P = 0.002); New Dot Test, −0.03 (P = 0.002)]. Thus, α-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation

Right ventricle to pulmonary artery coupling after transcatheter aortic valve implantation—Determinant factors and prognostic impact

IntroductionRight ventricular (RV) dysfunction and pulmonary hypertension (PH) have been previously associated with unfavorable outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI), but little is known about the effect of right ventricle (RV) to pulmonary artery (PA) coupling. Our study aimed to evaluate the determinant factors and the prognostic value of RV-PA coupling in patients undergoing TAVI.MethodsOne hundred sixty consecutive patients with severe AS were prospectively enrolled, between September 2018 and May 2020. They underwent a comprehensive echocardiogram before and 30 days after TAVI, including speckle tracking echocardiography (STE) for myocardial deformation analysis of the left ventricle (LV), left atrium (LA), and RV function. Complete data on myocardial deformation was available in 132 patients (76.6 ± 7.5 years, 52.5% men) who formed the final study population. The ratio of RV free wall longitudinal strain (RV-FWLS) to PA systolic pressure (PASP) was used as an estimate of RV-PA coupling. Patients were analyzed according to baseline RV-FWLS/PASP cut-off point, determined through time-dependent ROC curve analysis, as follows: normal RV-PA coupling group (RV-FWLS/PASP ≥0.63, n = 65) and impaired RV-PA coupling group (RV-FWLS/PASP &lt; 0.63, n = 67).ResultsA significant improvement of RV-PA coupling was observed early after TAVI (0.75 ± 0.3 vs. 0.64 ± 0.3 before TAVI, p &lt; 0.001), mainly due to PASP decrease (p &lt; 0.001). LA global longitudinal strain (LA-GLS) is an independent predictor of RV-PA coupling impairment before and after TAVI (OR = 0.837, p &lt; 0.001, OR = 0.848, p &lt; 0.001, respectively), while RV diameter is an independent predictor of persistent RV-PA coupling impairment after TAVI (OR = 1.174, p = 0.002). Impaired RV-PA coupling was associated with a worse survival rate (66.3% vs. 94.9%, p-value &lt; 0.001) and emerged as an independent predictor of mortality (HR = 5.97, CI = 1.44–24.8, p = 0.014) and of the composite endpoint of death and rehospitalization (HR = 4.14, CI = 1.37–12.5, p = 0.012).ConclusionOur results confirm that relief of aortic valve obstruction has beneficial effects on the baseline RV-PA coupling, and they occur early after TAVI. Despite significant improvement in LV, LA, and RV function after TAVI, RV-PA coupling remains impaired in some patients, it is mainly related to persistent pulmonary hypertension and is associated with adverse outcomes

α-Synuclein, a chemoattractant, directs microglial migration via H 2 O 2 -dependent Lyn phosphorylation

α-Synuclein (α-syn) aggregates released from neurons activate microglia, leading to chronic neuroinflammation that causes damage to neurons in brains with synucleinopathies, such as Parkinson’s disease (PD). However, little is known about the mechanism by which α-syn affects microglial activity, especially motility, and why microglia migrate toward the injured neurons and preferentially accumulate along with α-syn aggregates in the affected areas, e.g., in the substantia nigra of PD brains. Here we show that neuron-derived α-syn aggregates are chemoattractants that direct microglial migration by acting on NADPH oxidase and several specific downstream proteins. Blocking the targets involved in α-syn–mediated microglial directional migration may represent a therapeutic strategy to protect against progressive neuronal loss in PD and related synucleinopathies

Respiratory maneuvers in echocardiography: a review of clinical applications

During echocardiographic examination, respiration induces cyclic physiological changes of intracardiac haemodynamics, causing normal variations of the right and left ventricle Doppler inflows and outflows and physiological variation of extracardiac flows. The respiration related hemodynamic variation in intra and extracardiac flows may be utilized in the echocardiography laboratory to aid diagnosis in different pathological states. Nevertheless, physiologic respiratory phases can cause excessive translational motion of cardiac structures, lowering 2D image quality and interfering with optimal Doppler interrogation of flows or tissue motion

Data sharing: A new editorial initiative of the international committee of medical journal editors. Implications for the editors´ network

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship -emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors´ Network of the European Society of Cardiolog

Data sharing: A new editorial initiative of the international committee of medical journal editors. Implications for the editors´ network

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship -emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors´ Network of the European Society of Cardiolog

Authorship: From credit to accountability. Reflections from the Editors´ Network

The Editors´ Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasised that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices

Myocardial infarction and patent coronary arteries - an uneventful association?

Background: Although many studies addressed the issue of the occurrence of acute myocardial infarction (MI) in patients with angiographically patent coronary arteries, controversies exist concerning the pathophysiology and clinical outcome in this syndrome.Aim: To evaluate the clinical course of patients with MI and patent coronary arteries as well as to assess the post-infarction short-term prognosis.Methods: A retrospective analysis of patients with acute MI admitted to our institution over a period of 8 years (1995-2002) was performed. The study group consisted of 62 patients with MI and angiographically patent coronary arteries, examined within the first 30 days after the infarction, and the age and gender-matched control group of 62 patients with acute MI and significant coronary artery stenoses.Results: Cardiovascular risk factors found in the study group versus the control group were: smoking 47 (66.1%) vs 54 (87.1%) patients (NS); dyslipidemia 18 (29.0%) vs 44 (74.2%) patients (

Hemodynamic Monitoring in Sepsis—A Conceptual Framework of Macro- and Microcirculatory Alterations

Circulatory failure in sepsis is common and places a considerable burden on healthcare systems. It is associated with an increased likelihood of mortality, and timely recognition is a prerequisite to ensure optimum results. While there is consensus that aggressive source control, adequate antimicrobial therapy and hemodynamic management constitute crucial determinants of outcome, discussion remains about the best way to achieve each of these core principles. Sound cardiovascular support rests on tailored fluid resuscitation and vasopressor therapy. To this end, an overarching framework to improve cardiovascular dynamics has been a recurring theme in modern critical care. The object of this review is to examine the nature of one such framework that acknowledges the growing importance of adaptive hemodynamic support combining macro- and microhemodynamic variables to produce adequate tissue perfusion