Liquid Biopsy for Colorectal Cancer Screening, A Modern Approach for Patients Stratification and Monitoring

Despite great advances have been made in oncologic approaches, the morbidity and mortality caused by colon cancer are still overwhelming. Particularly, the intra- and inter-tumour heterogeneity makes accurate sampling challenging and often leads to failure of even modern therapeutic strategies. Moreover, tumour molecular genotype can suffer alterations over time, triggering suboptimal therapeutic outcomes as a result of irrelevant information provided by histological biopsies. Daily, tumour cells shed into the bloodstream at the early stages of the disease. These circulating tumour cells (CTCs) can be detected and analysed after enrichment, providing this way valuable information in real time. Furthermore, apoptotic and/or necrotic tumour cells discharge DNA fragments into the circulating bloodstream. Elevated levels of these so-called circulating tumour DNA (ctDNA) fragments can be identified in the peripheral blood of patients as compared to healthy individuals. In this view, the detection and characterization of the CTCs and ctDNA are a real-time “liquid biopsy” that has been developed for accurate tumour monitoring and molecular characterization. This modern non-invasive analytical approach allows consecutive sampling to monitor CTC number and tumour genetic changes over time without the need of tissue biopsy. Consequently, “liquid biopsies” can be used to screen for cancer, stratify patients to the optimum treatment and to monitor the patient’s response to treatment or identify treatment resistance. This chapter offers an overview of the following approaches with respect to liquid biopsies: CTCs and ctDNA. Some of the analytical techniques and challenges in the detection of these rare events will also be presented here

Zenker’s diverticulum and squamous esophageal cancer: a case report

Zenker’s diverticulum represents a rare esophageal lesion developed especially in the elderly population due to herniation of esophageal mucosa above the cricopharyngeus muscle. The condition leads to food retention, regurgitation, aspiration, and dysphagia in affected patients. Progressive dysphagia also characterizes malignant diseases of the esophagus like squamous esophageal carcinoma that typically appears in male patients in the seventh decade of life, with a history of cigarette smoking and alcohol abuse. We report a case of a male patient who presented with dysphagia for both solids and liquids along with significant weight loss, and who was diagnosed with medium esophageal cancer associated with Zenker’s diverticulum

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

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

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

Computational reduction strategies for the detection of steady bifurcations in incompressible fluid-dynamics: Applications to Coanda effect in cardiology

We focus on reducing the computational costs associated with the hydrodynamic stability of solutions of the incompressible Navier-Stokes equations for a Newtonian and viscous fluid in contraction-expansion channels. In particular, we are interested in studying steady bifurcations, occurring when non-unique stable solutions appear as physical and/or geometric control parameters are varied. The formulation of the stability problem requires solving an eigenvalue problem for a partial differential operator. An alternative to this approach is the direct simulation of the ow to characterize the asymptotic behavior of the solution. Both approaches can be extremely expensive in terms of computational time. We propose to apply Reduced Order Modeling (ROM) techniques to reduce the demanding computational costs associated with the detection of a type of steady bifurcations in fluid dynamics. The application that motivated the present study is the onset of asymmetries (i.e., symmetry breaking bifurcation) in blood flow through a regurgitant mitral valve, depending on the Reynolds number and the regurgitant mitral valve orifice shape