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Background The infectious disease phenotype of acute stroke associated with COVID-19 has been poorly characterized. Objective We investigated the neurovascular and infectious disease phenotype of stroke patients with and without COVID-19 infection, and their effect on in-hospital mortality. Methods This is a retrospective cohort study of consecutive patients with acute stroke, admitted to any ward of a hub hospital for stroke in Lombardy, Italy, during the first wave of COVID-19. Demographic, neurovascular, infectious disease, and respiratory characteristics were collected. The effect of clinical variables on survival was evaluated using logistic regression models. Results One hundred thirty-seven patients with acute stroke were recruited; 30 (21.9%) patients had COVID-19 and represented 2.5% of the 1218 COVID-19 patients hospitalized in the study period. Demographics, comorbidities, stroke type, stroke severity, and etiology did not differ between COVID + stroke patients and non-COVID stroke patients, except for an excess of multi-embolic ischemic stroke in the COVID + group. Most COVID + stroke patients had symptomatic infection (60%) and interstitial pneumonia (70%). COVID + stroke patients required more frequently respiratory support (77% versus 29%; p p = 0.0005) than non-COVID stroke patients. Mortality was independently associated with symptomatic interstitial pneumonia (aOR 6.7; 95% CI 2.0–22.5; p = 0.002) and, to a lesser extent, with NIHSS on admission (aOR 1.1; 95% CI 1.03–1.2; p = 0.007) and recanalization therapies (aOR 0.2; 95% CI 0.04–0.98; p = 0.046). Conclusion Symptomatic interstitial pneumonia was the major driver of in-hospital mortality in COVID + stroke patients. more...

Cerebral complications are common in perioperative settings even in non-neurosurgical procedures. These include postoperative cognitive dysfunction or delirium as well as cerebrovascular accidents. During surgery, it is essential to ensure an adequate degree of sedation and analgesia, and at the same time, to provide hemodynamic and respiratory stability in order to minimize neurological complications. In this context, the role of neuromonitoring in the operating room is gaining interest, even in the non-neurolosurgical population. The use of multimodal neuromonitoring can potentially reduce the occurrence of adverse effects during and after surgery, and optimize the administration of anesthetic drugs. In addition to the traditional focus on monitoring hemodynamic and respiratory systems during general anesthesia, the ability to constantly monitor the activity and maintenance of brain homeostasis, creating evidence-based protocols, should also become part of the standard of care: in this challenge, neuromonitoring comes to our aid. In this review, we aim to describe the role of the main types of noninvasive neuromonitoring such as those based on electroencephalography (EEG) waves (EEG, Entropy module, Bispectral Index, Narcotrend Monitor), near-infrared spectroscopy (NIRS) based on noninvasive measurement of cerebral regional oxygenation, and Transcranial Doppler used in the perioperative settings in non-neurosurgical intervention. We also describe the advantages, disadvantage, and limitation of each monitoring technique. more...

BackgroundAppropriate perioperative fluid management is of pivotal importance to reduce postoperative complications, which impact on early and long-term patient outcome. The so-called perioperative goal-directed therapy (GDT) approach aims at customizing perioperative fluid management on the individual patients’ hemodynamic response. Whether or not the overall amount of perioperative volume infused in the context of GDT could influence postoperative surgical outcomes is unclear.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of GDT approach between study population and control group in reducing postoperative complications and perioperative mortality, using MEDLINE, EMBASE and the Cochrane Controlled Clinical trials register. The enrolled studies were grouped considering the amount infused intraoperatively and during the first 24 h after the admission in the critical care unit (perioperative fluid).ResultsThe metanalysis included 21 RCTs enrolling 2729 patients with a median amount of perioperative fluid infusion of 4500 ml. In the studies reporting an overall amount below or above this threshold, the differences in postoperative complications were not statically significant between controls and GDT subgroup [43.4% vs. 34.2%,pvalue = 0.23 and 54.8% vs. 39.8%;pvalue = 0.09, respectively].Overall, GDT reduced the overall rate of postoperative complications, as compared to controls [pooled risk difference (95% CI) = − 0.10 (− 0.14, − 0.07); Chi2 = 30.97;pvalue pvalue = 0.07]. Considering the rate of organ-related postoperative events, GDT did not reduce neither renal (pvalue = 0.52) nor cardiovascular (pvalue = 0.86) or pulmonary (pvalue = 0.14) or neurological (pvalue = 0.44) or infective (pvalue = 0.12) complications.ConclusionsIrrespectively to the amount of perioperative fluid administered, GDT strategy reduces postoperative complications, but not perioperative mortality.Trial RegistrationCRD42020168866; Registration: February 2020https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=168866 more...

To describe the effects of timing of intubation in COVID-19 patients that fail helmet continuous positive airway pressure (h-CPAP) on progression and severity of disease.COVID-19 patients that failed h-CPAP, required intubation, and underwent chest computed tomography (CT) at two levels of positive end-expiratory pressure (PEEP, 8 and 16 cmHFifty-two patients were included and classified in early (h-CPAP for ≤2 days, N = 26) and late groups (h-CPAP for2 days, N = 26). Patients in the late compared to early intubation group presented: 1) lower respiratory system compliance (median difference, MD -7 mL/cmHIn COVID-19 patients receiving h-CPAP, late intubation was associated with worse clinical presentation at ICU admission and more advanced disease. The possible detrimental effects of delaying intubation should be carefully considered in these patients. more...

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607-0.682), 0.670 (0.626-0.714) and 0.682 (0.580-0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most. more...

Refractory intracranial hypertension after traumatic brain injury (TBI) is defined as recurrent increase of intracranial pressure above 20-22 mmHg for sustained period of time (10-15 min), despite conventional therapies, such as osmotic therapy, cerebral spinal fluid drainage and mild hyperventilation. As such, more aggressive treatments should be taken into consideration. In particular, therapeutic hypothermia, barbiturates administration and decompressive craniectomy are considered as tier-three or "salvage" interventions, as they have shown to be able to control refractory hypertension; however, they are also associated with an increased risk of significant side effects. Therefore, the aim of this review was to describe the evidence supporting the use of these tier-three therapies in the management of refractory intracranial hypertension in TBI patients. more...

Background Postoperative complications impact on early and long-term patients’ outcome. Appropriate perioperative fluid management is pivotal in this context; however, the most effective perioperative fluid management is still unclear. The enhanced recovery after surgery pathways recommend a perioperative zero-balance, whereas recent findings suggest a more liberal approach could be beneficial. We conducted this trial to address the impact of restrictive vs. liberal fluid approaches on overall postoperative complications and mortality. Methods Systematic review and meta-analysis, including randomised controlled trials (RCTs). We performed a systematic literature search using MEDLINE (via Ovid), EMBASE (via Ovid) and the Cochrane Controlled Clinical trials register databases, published from 1 January 2000 to 31 December 2019. We included RCTs enrolling adult patients undergoing elective abdominal surgery and comparing the use of restrictive/liberal approaches enrolling at least 15 patients in each subgroup. Studies involving cardiac, non-elective surgery, paediatric or obstetric surgeries were excluded. Results After full-text examination, the metanalysis finally included 18 studies and 5567 patients randomised to restrictive (2786 patients; 50.0%) or liberal approaches (2780 patients; 50.0%). We found no difference in the occurrence of severe postoperative complications between restrictive and liberal subgroups [risk difference (95% CI) = 0.009 (− 0.02; 0.04); p value = 0.62; I2 (95% CI) = 38.6% (0–66.9%)]. This result was confirmed also in the subgroup of five studies having a low overall risk of bias. The liberal approach was associated with lower overall renal major events, as compared to the restrictive [risk difference (95% CI) = 0.06 (0.02–0.09); p value = 0.001]. We found no difference in either early (p value = 0.33) or late (p value = 0.22) postoperative mortality between restrictive and liberal subgroups Conclusions In major abdominal elective surgery perioperative, the choice between liberal or restrictive approach did not affect overall major postoperative complications or mortality. In a subgroup analysis, a liberal as compared to a restrictive perioperative fluid policy was associated with lower overall complication renal major events, as compared to the restrictive. Trial Registration CRD42020218059; Registration: February 2020, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=218059. more...

Background: Tracheostomy can be performed safely in patients with coronavirus disease 2019 (COVID-19). However, little is known about the optimal timing, effects on outcome, and complications. Methods: A multicenter, retrospective, observational study. This study included 153 tracheostomized COVID-19 patients from 11 intensive care units (ICUs). The primary endpoint was the median time to tracheostomy in critically ill COVID-19 patients. Secondary endpoints were survival rate, length of ICU stay, and post-tracheostomy complications, stratified by tracheostomy timing (early versus late) and technique (surgical versus percutaneous). Results: The median time to tracheostomy was 15 (1–64) days. There was no significant difference in survival between critically ill COVID-19 patients who received tracheostomy before versus after day 15, nor between surgical and percutaneous techniques. ICU length of stay was shorter with early compared to late tracheostomy (p &lt, 0.001) and percutaneous compared to surgical tracheostomy (p = 0.050). The rate of lower respiratory tract infections was higher with surgical versus percutaneous technique (p = 0.007). Conclusions: Among critically ill patients with COVID-19, neither early nor percutaneous tracheostomy improved outcomes, but did shorten ICU stay. Infectious complications were less frequent with percutaneous than surgical tracheostomy. more...

Background: The incidence and clinical presentation of neurological manifestations of coronavirus disease 2019 (COVID-19) remain unclear. No data regarding the use of neuromonitoring tools in this group of patients are available. Methods: This is a retrospective study of prospectively collected data. The primary aim was to assess the incidence and type of neurological complications in critically ill COVID-19 patients and their effect on survival, as well as on hospital and intensive care unit (ICU) length-of-stay. The secondary aim was to describe cerebral hemodynamic changes detected by noninvasive neuromonitoring modalities such as transcranial doppler (TCD), optic nerve sheath diameter (ONSD), and pupillometry. Results: Ninety-four patients with COVID-19 receiving mechanical ventilation and admitted to an ICU from February 28 to June 30, 2020, were included in this study. Fifty-three patients underwent noninvasive neuromonitoring. Neurological complications were detected in 47/94 patients (50%), with delirium as the most common manifestation. Patients with neurological complications, compared to those without, had longer hospital (36.8±25.1 vs. 19.4±16.9 days, p Conclusions: In conclusion, neurological complications are common in critically ill patients with COVID-19 receiving invasive mechanical ventilation and are associated with prolonged ICU length-of-stay. Multimodal noninvasive neuromonitoring systems are useful tools for early detection of cerebrovascular changes in COVID-19. Registration number: 163/2020 more...

Cerebrospinal fluid (CSF)/plasma HIV-RNA ratio has been associated with residual neurocognitive impairment on cART, leading us to hypothesize a specific peripheral and/or CSF immune feature in patients with high CSF/plasma ratio (≥ 1). In patients with diverse pre-cART CSF/plasma ratio (61/70 with CSF/plasma ratio more...

In this chapter, we aim to highlight some of the new developments and trends in the emergency treatment of the gastrointestinal emergencies. There are only four pathologic processes that occur as an emergency of the inflammatory conditions and obstruction of the gastrointestinal tract: hemorrhage, ischemia, obstruction, and infection. Most abdominal pathology involves one or a combination of these processes and may give rise to severe clinical conditions of sufficient gravity to constitute an emergency. Gastrointestinal emergencies due to an acute inflammatory diseases and acute obstruction of the abdominal viscera and their complications may be roughly classified as follows: peritonitis, intussusception, torsion, perforation with abscess formation, complications involving chronic lesions of the upper part of the digestive tract such as acute perforation of peptic ulcer, duodenal obstruction, and bleeding. Despite the new and ever-expanding array of medications for the treatment of inflammatory diseases, there are still clear indications for operative management for the majority of complications of acute inflammatory conditions. We present here an overview of indications, procedures, considerations, and controversies in the diagnostic strategies and therapies for the most important gastrointestinal emergencies. more...

We examine the effects that the modelling of a Boxy/Peanut (B/P) bulge will have on the estimates of the stellar gravitational potential, forces, orbital structure and bar strength of barred galaxies. We present a method for obtaining the potential of disc galaxies from surface density images, assuming a vertical density distribution (height function), which is let to vary with position, thus enabling it to represent the geometry of a B/P. We construct a B/P height function after the results from a high-resolution, N-body+SPH simulation of an isolated galaxy and compare the resulting dynamical model to those obtained with the commonly used, position-independent "flat" height functions. We show that methods that do not allow for a B/P can induce errors in the forces in the bar region of up to 40% and demonstrate that this has a significant impact on the orbital structure of the model, which in turn determines its kinematics and morphology. Furthermore, we show that the bar strength is reduced in the presence of a B/P. We conclude that neglecting the vertical extent of a B/P can introduce considerable errors in the dynamical modelling. We also examine the errors introduced in the model due to uncertainties in the parameters of the B/P and show that even for generous but realistic values of the uncertainties, the error will be noticeably less than that of not modelling a B/P bulge at all., Comment: Accepted for publication in MNRAS more...

Background Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are increasingly used for the treatment of superficial gastrointestinal neoplasia. However, the limits and the indications for each technique are still debated. Our retrospective study aimed to compare these techniques in patients with gastric flat lesions larger than 20 mm without the non-lifting sign. Methods Between January 2013 and July 2016, a total of 36 patients with early gastric flat lesions larger than 20 mm and without the non-lifting sign were resected by ESD and were followed up by endoscopy. As a control group, 40 EMR cases from our database were matched. En bloc and curative resection were compared between the two groups according to histological assessment, tumor size, recurrence, complication rate, and procedure time. A Kaplan-Meier comparison was performed for both groups with a log-rank test to compare the survival curves; the chi-square test was employed for other parameters. Results En bloc resection rate and curative resection rate were significantly higher in the ESD group than in the EMR group. Procedure time was significantly longer in the ESD group. No significant differences were found in the recurrence and complication rates, although the former were higher in the EMR group and the latter in the ESD group. Survival curves were similar for both groups. Conclusions Our retrospective analysis seems to confirm a clear advantage for ESD over EMR in removing early superficial gastric neoplasm. Although ESD has expanded the endoscopic resectability of endoscopic gastric lesions, EMR may still be considered one of the therapeutic options for flat gastric lesions without the non-lifting sign. more...

Dynamical simulations are a fundamental tool for studying the secular evolution of disc galaxies. Even at their maximum resolution, they still follow a limited number of particles and typically resolve scales of the order of a few tens of parsecs. Generally, the spatial resolution is defined by (some multiple of) the softening length, whose value is set as a compromise between the desired resolution and the need for limiting small-scale noise. Several works have studied the question whether a softening scale fixed in space and time provides a good enough modelling of an astrophysical system. Here we address this question within the context of dynamical simulations and disc instabilities. We first follow the evolution of a galaxy-like object in isolation and then set up a simulation of an idealised merger event. Alongside a run using the standard fixed-softening approach, we performed simulations where the softening lengths were let to vary from particle to particle according to the evolution of the local density field in space and time. Even though during the most violent phases of the merging the fixed-softening simulation tends to underestimate the resulting matter densities, as far as the evolution of the disc component is concerned we found no significant differences among the runs. We conclude that using an appropriate fixed softening scale is a safe approach to the problem of modelling an N-body, non-cosmological disc galaxy system., Comment: 12 pages, 13 figures. Accepted for publication in MNRAS more...

The multifactorial pathogenesis of HIV-associated neurocognitive disorders may explain the inconsistent association between neurocognitive impairment and cerebrospinal fluid (CSF) HIV RNA. Clinical and viro-immunological (CSF and plasma HIV RNA, CSF/plasma HIV RNA ratio, circulating T-cell phenotypes) parameters were investigated in 155 HIV-infected, antiretroviral-naive, asymptomatic study participants undergoing a neuropsychological evaluation. HIV associated neurocognitive disorders (HAND) was independently associated with AIDS events and a CSF/plasma ratio of at least one, after adjustment for CD4 nadir of less than 200 cells/mmc, suggesting a role for active central nervous system (CNS) viral replication in the pathogenesis of neurocognitive impairment. more...

Galaxies inhabiting a cluster environment experience significant evolution in their orbital motions throughout time; this is accompanied by changes in the anisotropy parameter, measuring the relative importance of radial and tangential motions for a given class of objects. Along with orbital changes, galaxies in clusters are well known to undergo severe alteration in their hot/cold gas content and star formation properties. Understanding the link between the changes in the internal properties of galaxies and their orbital motion is of crucial importance in the study of galaxy evolution, as it could unveil the primary mechanism responsible for its environmental dependence. Do the changes in the internal properties happen in parallel with those in the orbital motion? Or are the orbital features at the time of infall what determines the fate of the member galaxies? Alternatively: are the properties of galaxies at a given time related to the coeval orbital anisotropy or are they better related to the anisotropy at infall? In order to answer these questions, we studied the orbital evolution of different galaxy populations in the semi-analytic models of Guo et al. (2011) applied on to the Millennium Simulation. For each class of objects, characterised by different internal properties (such as age, star formation rate and colour), we studied the anisotropy profile at redshift zero and its evolution by tracing the progenitors back in time. We conclude that the orbital properties at infall strongly influence the subsequent evolution of the internal features of galaxies and that the overall anisotropy of the galaxy population tends to increase with time. more...

Cosmological simulations of structure formation follow the collisionless evolution of dark matter starting from a nearly homogeneous field at early times down to the highly clustered configuration at redshift zero. The density field is sampled by a number of particles in number infinitely smaller than those believed to be its actual components and this limits the mass and spatial scales over which we can trust the results of a simulation. Softening of the gravitational force is introduced in collisionless simulations to limit the importance of close encounters between these particles. The scale of softening is generally fixed and chosen as a compromise between the need for high spatial resolution and the need to limit the particle noise. In the scenario of cosmological simulations, where the density field evolves to a highly inhomogeneous state, this compromise results in an appropriate choice only for a certain class of objects, the others being subject to either a biased or a noisy dynamical description. We have implemented adaptive gravitational softening lengths in the cosmological simulation code GADGET; the formalism allows the softening scale to vary in space and time according to the density of the environment, at the price of modifying the equation of motion for the particles in order to be consistent with the new dependencies introduced in the system's Lagrangian. We have applied the technique to a number of test cases and to a set of cosmological simulations of structure formation. We conclude that the use of adaptive softening enhances the clustering of particles at small scales, a result visible in the amplitude of the correlation function and in the inner profile of massive objects, thereby anticipating the results expected from much higher resolution simulations. more...

We present the first numerical, N-body, hydrodynamical, chemical simulations of cosmic structure formation in the framework of non-Gaussian models. We study the impact of primordial non-Gaussianities on early chemistry (e, H, H+, H-, He, He+, He++, H2, H2+, D, D+, HD, HeH+), molecular and atomic gas cooling, star formation, metal (C, O, Si, Fe, Mg, S) enrichment, population III (popIII) and population II-I (popII) transition, and on the evolution of "visible" objects. We find that non-Gaussianities can have some consequences on baryonic structure formation at very early epochs, but the subsequent evolution at later times washes out any difference among the various models. When assuming reasonable values for primordial non-Gaussian perturbations, it turns out that they are responsible for: (i) altering early molecular fractions in the cold, dense gas phase of ~10 per cent; (ii) inducing small temperature fluctuations of ~15, and of the popIII/popII transition of up to some 10^7yr; (iv) determining variations of more...

[abridged] We present a detailed comparison of fundamental dark matter halo properties retrieved by a substantial number of different halo finders. These codes span a wide range of techniques including friends-of-friends (FOF), spherical-overdensity (SO) and phase-space based algorithms. We further introduce a robust (and publicly available) suite of test scenarios that allows halo finder developers to compare the performance of their codes against those presented here. This set includes mock haloes containing various levels and distributions of substructure at a range of resolutions as well as a cosmological simulation of the large-scale structure of the universe. All the halo finding codes tested could successfully recover the spatial location of our mock haloes. They further returned lists of particles (potentially) belonging to the object that led to coinciding values for the maximum of the circular velocity profile and the radius where it is reached. All the finders based in configuration space struggled to recover substructure that was located close to the centre of the host halo and the radial dependence of the mass recovered varies from finder to finder. Those finders based in phase space could resolve central substructure although they found difficulties in accurately recovering its properties. Via a resolution study we found that most of the finders could not reliably recover substructure containing fewer than 30-40 particles. However, also here the phase space finders excelled by resolving substructure down to 10-20 particles. By comparing the halo finders using a high resolution cosmological volume we found that they agree remarkably well on fundamental properties of astrophysical significance (e.g. mass, position, velocity, and peak of the rotation curve). more...

Background/Aims The MELD defines a score used to prioritize patients awaiting liver transplantation and includes results for bilirubin, creatinine and PT expressed as INR. It is assumed that the MELD for individual patients is the same regardless of the laboratory method used for testing, thus ensuring parity of organ allocation. Previous studies showed that the INR calibrated for patients on vitamin K antagonists (INR vka ) does not normalize results across thromboplastins, whereas an alternative calibration called INR liver does. However, implementation of INR liver calibration for thromboplastins is difficult in practice. This study aimed to assess whether easy-to-run whole-blood coagulation monitors (widely used for patients on VKA) can be calibrated to measure efficiently the INR liver and minimize the interlaboratory variability. Methods PT values for 61 cirrhotic patients were measured on native-blood with 2 monitors calibrated in terms of INR vka . PTs for these subjects were also measured with a WHO-standard for thromboplastin. Paired-PTs with the monitors and the standard were subsequently used to calibrate the monitors in terms of INR liver . INR vka and INR liver were then compared to assess for statistical significance. Results The mean INR vka obtained with the monitors and the standard were significantly different ( p liver were not. Conclusions The INR liver calibration as previously described for thromboplastins works also for the easy-to-run whole-blood coagulation monitors. Once the monitors are calibrated by the manufacturer in terms of INR liver they could be used as near-patient-testing devices directly by the personnel of liver units making the determination of the INR for patients awaiting liver transplantation much easier and standardized. more...

Background Current guidelines recommend beta-blockers for primary prevention of variceal haemorrhage in cirrhotic patients, and band ligation for patients with contraindications or intolerance to beta-blockers. However, it has been suggested that these patients may respond poorly to band ligation. Aim We evaluated the usefulness of a strategy in which band ligation was used to treat patients with contraindications or intolerance and patients not responding to beta-blockers identified by hepatic vein pressure gradient measurement. Haemodynamic responders and patients refusing hepatic vein pressure gradient measurement were given long-term beta-blockers. Methods One hundred and thirty-five consecutive patients with high-risk oesophageal varices and no prior bleeding were enrolled. Twenty-five patients with contraindications (group A), 26 with intolerance to beta-blockers (group B) and 25 showing a poor haemodynamic response (Group C) underwent band ligation. Twenty-two haemodynamic responders (Group D) and 37 refusing hepatic vein pressure gradient measurement (Group E) were treated with beta-blockers. Results Median follow-up was 32 months. 12/135 patients (8.9%) bled: 3/25 (12%) in group A, 1/26 (3.8%) in group B, 0/25 (0%) in group C, 0/22 (0%) in group D and 8/37 (22.2%) in group E. Mortality was 8/135 (5.9%). Conclusions Patients with contraindications, intolerance or not responding to beta-blockers treated with band ligation achieve protection from variceal bleeding comparable to that of good responders to beta-blockers. more...

We study the imprints of boxy/peanut structures on the 2D line-of-sight kinematics of simulated disk galaxies. The models under study belong to a family with varying initial gas fraction and halo triaxiality, plus few other control runs with different structural parameters; the kinematic information was extracted using the Voronoi-binning technique and parametrised up to the fourth order of a Gauss-Hermite series. Building on a previous work for the long-slit case, we investigate the 2D kinematic behaviour in the edge-on projection as a function of the boxy/peanut strength and position angle; we find that for the strongest structures the highest moments show characteristic features away from the midplane in a range of position angles. We also discuss the masking effect of a classical bulge and the ambiguity in discriminating kinematically this spherically-symmetric component from a boxy/peanut bulge seen end-on. Regarding the face-on case, we extend existing results to encompass the effect of a second buckling and find that this phenomenon spurs an additional set of even deeper minima in the fourth moment. Finally, we show how the results evolve when inclining the disk away from perfectly edge-on and face-on. The behaviour of stars born during the course of the simulations is discussed and confronted to that of the pre-existing disk. The general aim of our study is providing a handle to identify boxy/peanut structure and their properties in latest generation IFU observations of nearby disk galaxies., Comment: 27 pages, 32 figures. Accepted for publication in MNRAS. High-resolution version and supplementary material will be available on the journal's website more...

We describe a NOVel form of Adaptive softening (NovA) for collisionless $N$-body simulations, implemented in the Ramses adaptive mesh refinement code. We introduce a refinement criterion that the particle distribution within each cell be sufficiently isotropic, as measured by its moment of inertia tensor. In this way, collapse is only refined if it occurs along all three axes, ensuring that the softening $\epsilon$ is always of order twice the largest inter-particle spacing in a cell. This more conservative force softening criterion is designed to minimise spurious two-body effects, while maintaining high force resolution in collapsed regions of the flow. We test NovA using an antisymmetric perturbed plane wave collapse (`Valinia' test) before applying it to warm dark matter (WDM) simulations. For the Valinia test, we show that -- unlike the standard $N$-body method -- NovA produces no numerical fragmentation while still being able to correctly capture fine caustics and shells around the collapsing regions. For the WDM simulations, we find that NovA converges significantly more rapidly than standard $N$-body, producing little or no spurious halos on small scales. We show, however, that determining whether or not halos exist below the free streaming mass $M_{\rm fs}$ is complicated by the fact that our halo finder (AHF) likely incorrectly labels some caustics and criss-crossing filaments as halos, while one or two particularly massive filaments appear to fragment in any version of NovA where refinement is allowed. Such massive filaments may be physically unstable to collapse, as is the case for infinite, static, self-gravitating cylinders. We will use NovA in forthcoming papers to study the issue of halo formation below $M_{\rm fs}$; filament stability; and to obtain new constraints on the temperature of dark matter., Comment: 12 pages, 7 figures. To be submitted to MNRAS more...

Background HIV can spread into the central nervous system (CNS) early in the course of infection and this turns into intrathecal inflammation and neuronal damage. We aimed to investigate clinical and immunological parameters associated with elevated CSF VL in HIV-infected ART-naïve patients. Materials and Methods HIV+ ART-naïve patients underwent a comprehensive battery of neurocognitive (NC) tests and lumbar puncture (LP) for CSF HIV-RNA detection. Plasma HIV-RNA and peripheral T-cell immune-phenotypes (CD38/CD45RA/CD45R0/CD127 on CD4/CD8) were also assessed (flow cytometry). High-CSF HIV RNA was defined as≥10000cp/mL (H-CSF), while CSF HIV RNA10000 cp/mL. Table 1 shows the features of H- versus L-CSF patients. Compared to L-CSF patients, H-CSF patients displayed lower current CD4+%, lower CD4/CD8 ratio and higher CD8%. No differences in NC tests performance were observed between groups (p=0.6). Regarding T-cell immuno-phenotypes, H-CSF patients displayed a higher proportion of CD45R0+CD38+CD8+ (11 vs 7%, p=0.02) and lower expression of CD45RA+CD8+ % (16 vs 20%, p=0.007), in comparison to L-CSF patients. In multivariate analysis CD45RA+CD8+ T-cells % (OR 0.917, CI 95% 0.852–0.987, p=0.002) was associated with H-CSF, even after adjustment for plasma VL, CD8 and CD4 count. Globally, in univariate CSF VL inversely correlated with CD45RA+CD8+ % (r=−0.223, p=0.0217) and CD127+CD4+ % (r= −0.204, p= 0.0225), while a positive association was found between CSF and plasma VL (r=0.303, p=0.0004) and CD8 % (r=0.211, p=0.016). In multivariate linear regression, in addition to positive association between plasma and CSF VL (β: 0.212, 95% CI 0.02–0.41, p=0.032), also CD45RA+CD8+ % were confirmed inversely associated to CSF VL (β: 0.21, 95% CI −0.5 to −0.002, p=0.036), adjusting for CD4/CD8 and CD4CD127 %. Conclusions We hereby describe a 32% prevalence of H-CSF in a cohort of HIV+ ART-naïve patients. Subjects with high-CSF viral replication are mostly with higher systemic immune activation, in particular the percentage of naïve CD8 T-cell is positively associated with CSF VL, irrespective of plasma VL. In HIV+ ART-naïve patients, especially if featuring a hyperactivated T-cell immune-phenotype, lumbar puncture should be considered to further guide CNS-targeted cART. more...

Portal hypertension is defined as an increase of the pressure in the portal vein system. Nowadays portal hypertension is generally assessed using HVPG measurement. 10 mmHg is the threshold for clinically significant portal hypertension when complications of portal hypertension (i.e., esophageal variceal bleeding, ascites) can arise. HVPG measurement, if performed properly, can give important prognostic information and guide the treatment of patients in primary and secondary prophylaxis and in case of acute variceal bleeding. Several studies have shown that the decrease of HVPG to ≤12 mmHg by chronic treatment, in primary and secondary prophylaxis completely prevents variceal bleeding. In case of a reduction ≥20 % from baseline, even though not below 12 mmHg, there is still a protection from variceal bleeding. About 30–40 % of patients in primary prophylaxis and 40–50 % in secondary prophylaxis achieve a reduction in HVPG to ≤12 mmHg or ≥20 % during chronic medical treatment for portal hypertension and can be considered good hemodynamic responders. Those patients who do not achieve an hemodynamic response are considered nonresponders and their risk of bleeding is about 30–40 % at 2–3 years in primary prophylaxis and 46–65 % in secondary prophylaxis. In the setting of acute variceal bleeding, the finding of HVPG values ≥20 mmHg was a predictor of high risk of treatment failure; these “high risk” patients may benefit from treatment with “early TIPS” placement. more...

The standard equipment necessary to perform a small bowel video capsule endoscopy (SBCE) procedure is summarized in Table 4.1. A video capsule designed for small bowel evaluation is required. Measuring 26 mm × 11 mm, current models operate at either a fixed frame rate of 4 frames per second (Fig. 4.1) or an adaptive frame rate of 2–6 frames per second. Each capsule is sealed in a small box and marked with an identifiable number and expiration date. The capsule is activated upon opening the box and has a minimum battery life of 12 h. Specific technological detail was discussed further in Chap. 3. more...

Background Influence of portal vein thrombosis on efficacy of endoscopic variceal banding in patients with cirrhosis or extrahepatic portal vein obstruction has never been evaluated. Aim of the study was to assess influence of thrombosis on rate and time to eradication in cirrhosis and extrahepatic portal vein obstruction undergoing banding, compared to cirrhotic patients without thrombosis. Methods Retrospective analysis of 235 consecutive patients (192 with cirrhosis without thrombosis, 22 cirrhosis and thrombosis and 21 extrahepatic portal vein obstruction) who underwent banding. Banding was performed every 2–3 weeks until eradication; endoscopic follow-up was performed at 1, 3, 6 months, then annually. Results Eradication was achieved in 233 patients. Median time to eradication in cirrhotic patients with portal vein thrombosis vs. cirrhotic patients without thrombosis was 50.9 days (12–440) vs. 43.4 days (13–489.4); log-rank: 0.04; patients with extrahepatic portal vein obstruction vs. cirrhotic patients without thrombosis 63.9 days (31–321.6) vs. 43.4 days (13.0–489.4); log-rank: 0.008. Thrombosis was shown to be the only risk factor for longer time to eradication. Conclusions Portal vein thrombosis per se appears to be the cause of a longer time to achieve eradication of varices but, once eradication is achieved, it does not influence their recurrence. more...

Patients with cirrhosis possess an imbalance in procoagulant versus anticoagulant activity due to increased factor VIII and decreased protein C. This imbalance can be detected by thrombin-generation assays performed in the presence/absence of thrombomodulin (predicate assay) that are not readily available in clinical laboratories. We sought to assess this hypercoagulability with a simpler thrombin-generation assay performed in the presence/absence of Protac, a snake venom that activates protein C in a manner similar to thrombomodulin (new assay). We analyzed blood from 105 patients with cirrhosis and 105 healthy subjects (controls). Results for the predicate-assay or the new-assay were expressed as ratio (with:without thrombomodulin) or as Protac-induced coagulation inhibition (PICI%). By definition, high ratios or low PICI% translate into hypercoagulability. The median(range) PICI% was lower in patients (74% [31%-97%]) than controls (93% [72%-99%]; P < 0.001), indicating that patients with cirrhosis are resistant to the action of Protac. This resistance resulted in greater plasma hypercoagulability in patients who were Child class C than those who were A or B. The hypercoagulability of Child C cirrhosis (63% [31%-92%]) was similar to that observed for patients with factor V Leiden (69% [15%-80%]; P = 0.59). The PICI% values were correlated with the levels of protein C (rho = 0.728, P < 0.001) or factor VIII (rho = −0.517, P < 0.001). Finally, the PICI% values were correlated with the predicate assay (rho = −0.580, P < 0.001). Conclusion: The hypercoagulability of plasma from patients with cirrhosis can be detected with the new assay, which compares favorably with the other markers of hypercoagulability (i.e., high factor VIII and low protein C) and with the predicate-assay based on thrombin-generation with/without thrombomodulin. Advantages of the new assay over the predicate assay are easy performance and standardized results. Prospective trials are needed to ascertain whether it is useful to predict thrombosis in patients with cirrhosis. HEPATOLOGY 2010 more...

Several inflationary models predict the possibility that the primordial perturbations of the density field may contain a degree of non-Gaussianity which would influence the subsequent evolution of cosmic structures at large scales. In order to study their impact, we use a set of three cosmological DM-only simulations starting from initial conditions with different levels of non-Gaussianity: f_NL=0,+/-100. More specifically, we focus on the distribution of galaxy clusters at different redshifts and, using suitable scaling relations, we determine their X-ray and SZ signals. Our analysis allows us to estimate the differences in the logN-logS and logN-logY due to the different initial conditions and to predict the cluster counts at different redshifts expected for future surveys (eROSITA and SPT). We also use a second set of simulations assuming a different cosmological scenario to estimate how the dependence on f_NL is degenerate with respect to other parameters. Our results indicate that the effects introduced by a realistic amount of primordial non-Gaussianity are small when compared to the ones connected with current uncertainties in cosmological parameters, particularly with sigma_8. However, if future surveys will be associated with optical follow-up campaigns to determine the cluster redshift, an analysis of the samples at z>1 can provide significant constraints on f_NL. In particular we predict that the SPT cluster survey will be able to detect ~1000 clusters at z>1 for the Gaussian case, with a difference of 15-20 per cent associated to f_NL=+/-100., 11 pages, 8 figures, 2 tables. Submitted to MNRAS more...

The description of halo abundance and clustering for non-Gaussian initial conditions has recently received renewed interest, motivated by the forthcoming large galaxy and cluster surveys, which can potentially detect primordial non-Gaussianity of the local form with a non-Gaussianity parameter | f NL | of order unity. This is particularly exciting because, while the simplest single-field slow-roll models of inflation predict a primordial | f NL | ≪ 1 , this signal sources extra contributions to the effective f NL of large-scale structures that are expected to be above the predicted detection threshold [C. Carbone, L. Verde, and S. Matarrese, ApJL 684 (2008) L1]. We present tests on N-body simulations of analytical formulae describing the halo abundance and clustering for non-Gaussian initial conditions. In particular, when we calibrate the analytic non-Gaussian mass function of [S. Matarrese, L. Verde, L. and R. Jimenez, ApJL 541 (2000) 10] and [M. LoVerde, A. Miller, S. Shandera and L. Verde, JCAP 04 (2008) 014] and the analytic description of halo clustering for non-Gaussian initial conditions on N-body simulations, we find excellent agreement between the simulations and the analytic predictions if we make the substitutions δ c → δ c × q and δ c → δ c × q where q ≃ 0.75 , in the density threshold for gravitational collapse and in the non-Gaussian fractional correction to the halo bias, respectively. We discuss the implications of these corrections on present and forecasted primordial non-Gaussianity constraints. We confirm that the non-Gaussian halo bias offers a robust and highly competitive test of primordial non-Gaussianity. more...

Variceal bleeding is one of the most severe complications of portal hypertension related to liver cirrhosis. Primary prophylaxis is considered mandatory in patients with cirrhosis and high-risk oesophageal varices, and once varices have bled, every effort should be made to arrest the haemorrhage and prevent further bleeding episodes. In acute variceal bleeding, vasoactive drugs that lower portal pressure should be started even before endoscopy, and should be maintained for up to 5 days. The choice of vasoactive drug should be made according to local resources. Terlipressin, somatostatin and octreotide can be used; vasopressin plus transdermal nitroglycerin may be used if no other drug is available. In variceal bleeding, antibiotic therapy is also mandatory. In primary and secondary prophylaxis, beta-blockers are the mainstay of therapy. In secondary prophylaxis (but not in primary prophylaxis) these drugs can be combined with organic nitrates. more...

Prevention of the first variceal haemorrhage should start when the patients have developed medium-sized to large varices. Non-selective beta-blockers and band ligation are equally effective in preventing the first bleeding episode. Rubber band ligation is the first choice for patients with contraindications or intolerance to beta-blockers. Treatment of acute bleeding should aim at controlling bleeding and preventing early rebleeding and complications, especially infections. Combined endoscopic (band ligation or sclerotherapy) and pharmacological treatment with vasoactive drugs can control bleeding in up to 90% of patients. Antibiotic prophylaxis is an integral part of the treatment of acute variceal haemorrhage, and must be started as soon as possible. Emergency transjugular intrahepatic portosystemic stent shunt (TIPS) is the standard rescue therapy for patients failing combined endoscopic and pharmacological treatment. All patients who survive a variceal bleed should be treated with beta-blockers or band ligation to prevent rebleeding. All patients in whom bleeding cannot be controlled or who continue to rebleed can be treated with salvage TIPS or, in selected cases, with surgical shunts. Liver transplantation should be considered for patients with severe liver insufficiency in which first-line treatments fail. more...

Background Colorectal polyps of mesenchymal origin represent a small percentage of gastrointestinal (GI) lesions. Nevertheless, they are encountered with increasing frequency since the widespread adoption of colonoscopy screening. Case presentation We report a case of a small colonic polyp that presented as intramucosal diffuse spindle cell proliferation with a benign cytological appearance, strong and diffuse immunoreactivity for S-100 protein, and pure Schwann cell phenotype. Careful morphological, immunohistochemical and clinical evaluation emphasize the differences from other stromal colonic lesions and distinguish it from schwannoma, a circumscribed benign nerve sheath tumor that rarely arises in the GI tract. Conclusion As recently proposed, this lesion was finally described as mucosal Schwann cell hamartoma. more...