Visual stimulation and frequency of focal neurological symptoms engage distinctive neurocognitive resources in migraine with aura patients: a study of resting-state functional networks

IntroductionSeveral functional neuroimaging studies on healthy controls and patients with migraine with aura have shown that the activation of functional networks during visual stimulation is not restricted to the striate system, but also includes several extrastriate networks.MethodsBefore and after 4 min of visual stimulation with a checkerboard pattern, we collected functional MRI in 21 migraine with aura (MwA) patients and 18 healthy subjects (HS). For each recording session, we identified independent resting-state networks in each group and correlated network connection strength changes with clinical disease features.ResultsBefore visual stimulation, we found reduced connectivity between the default mode network and the left dorsal attention system (DAS) in MwA patients compared to HS. In HS, visual stimulation increases functional connectivity between the independent components of the bilateral DAS and the executive control network (ECN). In MwA, visual stimulation significantly improved functional connectivity between the independent component pairs salience network and DAS, and between DAS and ECN. The ECN Z-scores after visual stimulation were negatively related to the monthly frequency of aura.ConclusionsIn individuals with MwA, 4 min of visual stimulation had stronger cognitive impact than in healthy people. A higher frequency of aura may lead to a diminished ability to obtain cognitive resources to cope with transitory but important events like aura-related focal neurological symptoms.     

Early increase of plasma soluble VEGFR-2 is associated with clinical benefit from second-line treatment of paclitaxel and ramucirumab in advanced gastric cancer

Ramucirumab plus paclitaxel is considered the standard of care in the second-line treatment of gastric carcinoma (GC). The aim of this study was to evaluate plasma vascular endothelial growth factor-A (VEGF-A), VEGF-D, and circulating soluble VEGF receptor-2 (sVEGFR-2) as possible markers of resistance or response to ramucirumab administered with paclitaxel in pretreated metastatic GC patients. Plasma samples were collected at different time points (on days 1 and 15 of the first 3 cycles, at best radiologic response and at disease progression). VEGF-A, VEGF-D and sVEGFR-2 were analysed by ELISA. Correlations of biomarker baseline levels or dynamic changes with outcome measures were assessed. Progression-free survival (PFS) was the primary endpoint of the study. Forty-one patients were enrolled. VEGF-A and VEGF-D, but not sVEGFR-2, values significantly increased during treatment compared to baseline (P < 0.001). A positive correlation between VEGF-A and sVEGFR-2 at cycle 2 was found (P=0.045). At univariate analysis, higher baseline levels of VEGF-A were associated with worse OS (P=0.015). Early increase of sVEGFR-2 levels after the first treatment cycle was the only factor associated with longer PFS (6.6 vs. 3.6 months, P=0.049) and OS (18.6 vs. 5.2 months, P=0.008). Significance of sVEGFR-2 early increase was retained at multivariate analysis for OS (HR 0.32; 95% CI 0.12-0.91; P=0.032). The reported results confirmed the prognostic role of baseline VEGF-A and, with the limitations of the limited sample size and the lack of a control arm, suggested that the early increase of sVEGFR-2 after 1 cycle of treatment could be a potential predictive biomarker of benefit from second-line ramucirumab plus paclitaxel in GC.     

COVID-19 as a trigger of irritable bowel syndrome: A review of potential mechanisms

In December 2019 a novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started spreading from Wuhan city of Chinese Hubei province and rapidly became a global pandemic. Clinical symptoms of the disease range from paucisymptomatic disease to a much more severe disease. Typical symptoms of the initial phase include fever and cough, with possible progression to acute respiratory distress syndrome. Gastrointestinal manifestations such as diarrhoea, vomiting and abdominal pain are reported in a considerable number of affected individuals and may be due to the SARS-CoV-2 tropism for the peptidase angiotensin receptor 2. The intestinal homeostasis and microenvironment appear to play a major role in the pathogenesis of COVID-19 and in the enhancement of the systemic inflammatory responses. Long-term consequences of COVID-19 include respiratory disturbances and other disabling manifestations, such as fatigue and psychological impairment. To date, there is a paucity of data on the gastrointestinal sequelae of SARS-CoV-2 infection. Since COVID-19 can directly or indirectly affect the gut physiology in different ways, it is plausible that functional bowel diseases may occur after the recovery because of potential pathophysiological alterations (dysbiosis, disruption of the intestinal barrier, mucosal microinflammation, post-infectious states, immune dysregulation and psychological stress). In this review we speculate that COVID-19 can trigger irritable bowel syndrome and we discuss the potential mechanisms.     

Ambulatory pulse pressure, left ventricular hypertrophy and function in arterial hypertension

BACKGROUND: A wide pulse pressure (PP) can provide important risk assessment information about myocardial infarction, carotid artery atherosclerosis, and global cardiovascular risk. Ambulatory pulse pressure (APP) does not have a well-known prognostic value in hypertensive patients. METHODS:To evaluate the relationship among high APP, atrial volumes, and cardiac function, an observational study was performed on 108 untreated non-elderly hypertensive patients (mean age 54.23 +/- 7.12). Twenty-four-hour ambulatory blood pressure monitoring, Doppler and echocardiographic measurements of systolic, diastolic function, left and right atrial volumes, left ventricular mass index and dimensions, were performed in subjects with both clinic and APP > 60 mmHg (APP1 Group). A control group of hypertensive selected subjects with both clinic and APP < 60 mmHg was chosen (APP 2 Group). RESULTS: The APP1 group showed left atrial volume enlargement, high left ventricular mass index, and impaired diastolic function. A positive correlation was found in the APP1 group results among left ventricular end diastolic diameter (r = 0.39, P < 0.01), left atrial volume (0.38, P < 0.05), and left ventricular mass index (r = 0.33, P < 0.05); clinic PP showed a statistically significant correlation with left atrial volume, left ventricular end diastolic diameter, and left ventricular mass index only in the APP1 group. CONCLUSIONS: These results suggest that elevated APP can be considered an effective predictor of cardiovascular risk in hypertensive subjects. In these patients echocardiographic evaluation of left ventricular function and morphology can increase the prognostic value of PP.     

A compact and automated ex vivo vessel culture system for the pulsatile pressure conditioning of human saphenous veins

Saphenous vein (SV) graft disease represents an unresolved problem in coronary artery bypass grafting (CABG). After CABG, a progressive remodelling of the SV wall occurs, possibly leading to occlusion of the lumen, a process termed 'intima hyperplasia' (IH). The investigation of cellular and molecular aspects of IH progression is a primary end‐point toward the generation of occlusion‐free vessels that may be used as ‘life‐long’ grafts. While animal transplantation models have clarified some of the remodelling factors, the pathology of human SV is far from being understood. This is also due to the lack of devices able to reproduce the altered mechanical load encountered by the SV after CABG. This article describes the design of a novel ex vivo vein culture system (EVCS) capable of replicating the altered pressure pattern experienced by SV after CABG, and reports the results of a preliminary biomechanical conditioning experimental campaign on SV segments. The EVCS applied a CAGB‐like pressure (80–120 mmHg) or a venous‐like perfusion (3 ml/min, 5 mmHg) conditioning to the SVs, keeping the segments viable in a sterile environment during 7 day culture experiments. After CABG‐like pressure conditioning, SVs exhibited a decay of the wall thickness, an enlargement of the luminal perimeter, a rearrangement of the muscle fibres and partial denudation of the endothelium. Considering these preliminary results, the EVCS is a suitable system to study the mechanical attributes of SV graft disease, and its use, combined with a well‐designed biological protocol, may be of help in elucidating the cellular and molecular mechanisms involved in SV graft disease. Copyright © 2013 John Wiley & Sons, Ltd.     

Frequent aberrant promoter hypermethylation of O6-methylguanine-DNA methyltransferase and death-associated protein kinase genes in immunodeficiency-related lymphomas

Aberrant promoter hypermethylation is a mechanism of tumour suppressor gene inactivation. We explored aberrant promoter hypermethylation of multiple genes in 88 human immunodeficiency virus (HIV)-non Hodgkin lymphomas (NHL), 25 post-transplant lymphoproliferative disorders (PTLD) and five common variable immunodeficiency (CVI)-related NHL. Twenty-six of 79 (32.9%) HIV-NHL, eight of 14 (57.1%) PTLD and two of five (40.0%) CVI-NHL showed aberrant hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT). Aberrant hypermethylation of death-associated protein-kinase (DAP-K) occurred in 70 of 84 (83.3%) HIV-NHL, 19 of 25 (72.0%) PTLD and three of five (60.0%) CVI-NHL. These data implicate MGMT and DAP-K hypermethylation in lymphomagenesis of immunodeficient hosts. In particular, promoter hypermethylation of DAP-K represents the most frequent molecular alteration yet identified in immunodeficiency-related lymphomas.     

Patent foramen ovale with paradoxical embolism: mid-term results of transcatheter closure in 256 patients

The purpose of this study was to assess the safety and feasibility of percutaneous interventional closure of patent foramen ovale (PFO) with or without atrial septal aneurysm (ASA) in symptomatic patients. Between June 1999 and June 2002, we performed transcatheter closure of PFO in 256 consecutive symptomatic patients (female/male = 1.45; mean age 48 +/- 16 years; range 14-75): ischemic stroke (n = 101), transient ischemic attack (n = 144), peripheral and coronary arterial embolism (n = 17); multiple events (n = 23); platypnea-orthodeoxia syndrome (n = 2); refractory hypoxemia (n = 1); and migraine aura (n = 27). The implanted devices were an Amplatzer PFO Occluder (n = 248), a Gore-HELEX Septal Occluder (n = 4), and PFO STAR (n = 4). Most procedures (n = 176.69%) were done under two-dimensional intracardiac echocardiography (ICE) guidance alone; in the last 30 patients, 3D/4D ICE reconstruction (TomTec Imaging Systems) 6mbH was obtained. In 30 cases, ICE and contrast enhanced-TCD have been used simultaneously in the catheterization laboratory. The devices were placed correctly in all patients. Mean fluoroscopy time was 9.45 +/- 5 minutes (range = 2.5-35 minutes); mean procedural time was 57 +/- 21 minutes (range = 15-135 minutes). Total occlusion rate at follow-up (mean 19 months, range 1-33) was 98.1%. No significant recurrent neurological events were observed. Transcatheter closure of PFO with or without ASA is a safe and effective, minimally invasive procedure that ensures high closure rate and avoids life-long anticoagulation. Mid-term follow-up results appear favorable with respect to recurrent thromboembolic events.     

Is Sub-occipital Padding Necessary to Maintain Optimal Alignment of the Unstable Spine in the Prehospital Setting? A Preliminary Report

Background

As prehospital emergency rescuers prepare cervical spine-injured adult patients for immobilization and transport to hospital, it is essential that patients be placed in a favorable position. Previously, it was recommended that patients with cervical spine injuries be immobilized in a slightly flexed position using pads placed beneath the head. However, it is unknown how neck flexion created with pad placement affects the unstable spine.

Objective

To determine the effects of three different head positions on the alignment of unstable vertebral segments.

Methods

Five cadavers with a complete segmental instability at the C5 and C6 level were included in the study. The head was either placed directly on the ground (or spine board) or on foam pads. Three conditions were tested: no pad; pads 2.84 cm thick; and pads 4.26 cm thick. Pads were positioned beneath the head to determine their effect on spinal alignment. Anterior-posterior translation, flexion-extension motion, and axial displacement across the unstable segment were compared between conditions.

Results

Although statistical tests failed to identify any significant differences between pad conditions, some meaningful results were noted. In general, the “no pad” condition aligned the spine in a position that best replicated the intact spine.

Conclusions

Because the goal of emergency rescuers is to conserve whatever physiologic or structural integrity of the spinal cord and spinal column that remains, the outcome of this study suggests that this goal may be best achieved using the “no pad” condition. However, it is recommended that more research be conducted to confirm these preliminary findings.