Early prone positioning does not improve the outcome of patients with mild pneumonia due to SARS-CoV-2: results from an open-label randomised controlled trial - the EPCoT study.

Background: Prone positioning is routinely used among patients with COVID-19 requiring mechanical ventilation. However, its utility among spontaneously breathing patients is still debated. Methods: In an open-label randomised controlled trial, we enrolled patients hospitalised with mild COVID-19 pneumonia, whose arterial oxygen tension to inspiratory oxygen fraction ratio (PaO2/FIO2) was >200 mmHg and who did not require mechanical ventilation or continuous positive airway pressure at hospital admission. Patients were randomised 1:1 to prone positioning on top of standard of care (intervention group) versus standard of care only (controls). The primary composite outcome included death, mechanical ventilation, continuous positive airway pressure and PaO2/FIO2 <200 mmHg; secondary outcomes were oxygen weaning and hospital discharge. Results: A total of 61 subjects were enrolled, 29 adjudicated to prone positioning and 32 to the control group. By day 28, 24 out of 61 patients (39.3%) met the primary outcome: 16 because of a PaO2/FIO2 ratio <200 mmHg, five because of the need for continuous positive airway pressure and three because of the need for mechanical ventilation. Three patients died. Using an intention-to-treat approach, 15 out of 29 patients in the prone positioning group versus nine out of 32 controls met the primary outcome, corresponding to a significantly higher risk of progression among those randomised to prone positioning (HR 2.38, 95% CI 1.04-5.43; p=0.040). Using an as-treated approach, which included in the intervention group only patients who maintained prone positioning for ≥3 h·day-1, no significant differences were found between the two groups (HR 1.77, 95% CI 0.79-3.94; p=0.165). Also, we did not find any statistically significant difference in terms of time to oxygen weaning or hospital discharge between study arms in any of the analyses conducted. Conclusions: We observed no clinical benefit from prone positioning among spontaneously breathing patients with COVID-19 pneumonia requiring conventional oxygen therapy.

Do statins decrease vascular inflammation in patients at risk for large-vessel vasculitis? A retrospective observational study with FDG-PET/CT in polymyalgia rheumatica, giant cell arteritis and fever of unknown origin.

OBJECTIVES: [18F] Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) can detect the presence of large-vessel vasculitis (LVV) in patients with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) and fever of unknown origin (FUO). The aim of this study was to evaluate whether statins could reduce FDG-PET/CT-assessed vascular inflammation in this group of patients. METHODS: Clinical, demographic, laboratory data, current pharmacological treatments, and cardiovascular risk factors of patients with PMR, GCA and FUO, who underwent FDG-PET/CT, were recorded. FDG uptake was measured at prespecified arterial sites with the mean standardised uptake value (SUV), and with a qualitative visual score, summed up to obtain a total vascular score (TVS). LVV was diagnosed if arterial FDG visual uptake was equal or higher of liver uptake. RESULTS: 129 patients were included (96 with PMR, 16 with GCA, 13 with both PMR and GCA, and 4 with FUO), of whom 75 (58.1%) showed LVV. Twenty out of 129 (15.5%) patients were taking statins. TVS was significantly lower in patients treated with statins (p=0.02), especially in the aorta (p=0.023) and femoral arteries (p=0.027). CONCLUSIONS: Our preliminary results suggest that statins may exert a potential protective role on vascular inflammation in patients with PMR and GCA. Statin use could spuriously decrease FDG uptake of the vessel walls.

Neurovascular and infectious disease phenotype of acute stroke patients with and without COVID-19.

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 < 0.0001) and had higher in-hospital mortality (40% versus 12%; 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.

Early versus late intubation in COVID-19 patients failing helmet CPAP: A quantitative computed tomography study.

PURPOSE: 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. METHODS: 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 cmH2O) were included in this retrospective study. Patients were divided in two groups (early versus late) based on the duration of h-CPAP before intubation. Endpoints included percentage of non-aerated lung tissue at PEEP of 8 cmH2O, respiratory system compliance and oxygenation. RESULTS: Fifty-two patients were included and classified in early (h-CPAP for ≤2 days, N = 26) and late groups (h-CPAP for >2 days, N = 26). Patients in the late compared to early intubation group presented: 1) lower respiratory system compliance (median difference, MD -7 mL/cmH2O, p = 0.044) and PaO2/FiO2 (MD -29 mmHg, p = 0.047), 2) higher percentage of non-aerated lung tissue (MD 7.2%, p = 0.023) and 3) similar lung recruitment increasing PEEP from 8 to 16 cmH2O (MD 0.1%, p = 0.964). CONCLUSIONS: In 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.

Effects of positive end-expiratory pressure on lung ultrasound patterns and their correlation with intracranial pressure in mechanically ventilated brain injured patients.

BACKGROUND: The effects of positive end-expiratory pressure (PEEP) on lung ultrasound (LUS) patterns, and their relationship with intracranial pressure (ICP) in brain injured patients have not been completely clarified. The primary aim of this study was to assess the effect of two levels of PEEP (5 and 15 cmH2O) on global (LUStot) and regional (anterior, lateral, and posterior areas) LUS scores and their correlation with changes of invasive ICP. Secondary aims included: the evaluation of the effect of PEEP on respiratory mechanics, arterial partial pressure of carbon dioxide (PaCO2) and hemodynamics; the correlation between changes in ICP and LUS as well as respiratory parameters; the identification of factors at baseline as potential predictors of ICP response to higher PEEP. METHODS: Prospective, observational study including adult mechanically ventilated patients with acute brain injury requiring invasive ICP. Total and regional LUS scores, ICP, respiratory mechanics, and arterial blood gases values were analyzed at PEEP 5 and 15 cmH2O. RESULTS: Thirty patients were included; 19 of them (63.3%) were male, with median age of 65 years [interquartile range (IQR) = 66.7-76.0]. PEEP from 5 to 15 cmH2O reduced LUS score in the posterior regions (LUSp, median value from 7 [5-8] to 4.5 [3.7-6], p = 0.002). Changes in ICP were significantly correlated with changes in LUStot (rho = 0.631, p = 0.0002), LUSp (rho = 0.663, p < 0.0001), respiratory system compliance (rho = - 0.599, p < 0.0001), mean arterial pressure (rho = - 0.833, p < 0.0001) and PaCO2 (rho = 0.819, p < 0.0001). Baseline LUStot score predicted the increase of ICP with PEEP. CONCLUSIONS: LUS-together with the evaluation of respiratory and clinical variables-can assist the clinicians in the bedside assessment and prediction of the effect of PEEP on ICP in patients with acute brain injury.

Cerebral Autoregulation in Non-Brain Injured Patients: A Systematic Review.

Introduction: Cerebral autoregulation (CA) plays a fundamental role in the maintenance of adequate cerebral blood flow (CBF). CA monitoring, through direct and indirect techniques, may guide an appropriate therapeutic approach aimed at improving CBF and reducing neurological complications; so far, the role of CA has been investigated mainly in brain-injured patients. The aim of this study is to investigate the role of CA in non-brain injured patients. Methods: A systematic consultation of literature was carried out. Search terms included: "CA and sepsis," "CA and surgery," and "CA and non-brain injury." Results: Our research individualized 294 studies and after screening, 22 studies were analyzed in this study. Studies were divided in three groups: CA in sepsis and septic shock, CA during surgery, and CA in the pediatric population. Studies in sepsis and intraoperative setting highlighted a relationship between the incidence of sepsis-associated delirium and impaired CA. The most investigated setting in the pediatric population is cardiac surgery, but the role and measurement of CA need to be further elucidated. Conclusion: In non-brain injured patients, impaired CA may result in cognitive dysfunction, neurological damage, worst outcome, and increased mortality. Monitoring CA might be a useful tool for the bedside optimization and individualization of the clinical management in this group of patients.

Tier-three therapies for refractory intracranial hypertension in adult head trauma.

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.

Tracheostomy Timing and Outcome in Severe COVID-19: The WeanTrach Multicenter Study.

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 < 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.

Perioperative liberal versus restrictive fluid strategies and postoperative outcomes: a systematic review and metanalysis on randomised-controlled trials in major abdominal elective surgery.

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 .

Neuromonitoring during general anesthesia in non-neurologic surgery.

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.

Association between perioperative fluid administration and postoperative outcomes: a 20-year systematic review and a meta-analysis of randomized goal-directed trials in major visceral/noncardiac surgery.

BACKGROUND: Appropriate 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. METHODS: We 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). RESULTS: The 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%, p value = 0.23 and 54.8% vs. 39.8%; p value = 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; p value < 0.0001], but not to a reduction of perioperative mortality [pooled risk difference (95%CI) = - 0.016 (- 0.0334; 0.0014); p value = 0.07]. Considering the rate of organ-related postoperative events, GDT did not reduce neither renal (p value = 0.52) nor cardiovascular (p value = 0.86) or pulmonary (p value = 0.14) or neurological (p value = 0.44) or infective (p value = 0.12) complications. CONCLUSIONS: Irrespectively to the amount of perioperative fluid administered, GDT strategy reduces postoperative complications, but not perioperative mortality. TRIAL REGISTRATION: CRD42020168866; Registration: February 2020 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=168866.

Automatic Lung Segmentation and Quantification of Aeration in Computed Tomography of the Chest Using 3D Transfer Learning.

BACKGROUND: Identification of lung parenchyma on computer tomographic (CT) scans in the research setting is done semi-automatically and requires cumbersome manual correction. This is especially true in pathological conditions, hindering the clinical application of aeration compartment (AC) analysis. Deep learning based algorithms have lately been shown to be reliable and time-efficient in segmenting pathologic lungs. In this contribution, we thus propose a novel 3D transfer learning based approach to quantify lung volumes, aeration compartments and lung recruitability. METHODS: Two convolutional neural networks developed for biomedical image segmentation (uNet), with different resolutions and fields of view, were implemented using Matlab. Training and evaluation was done on 180 scans of 18 pigs in experimental ARDS (u2Net Pig ) and on a clinical data set of 150 scans from 58 ICU patients with lung conditions varying from healthy, to COPD, to ARDS and COVID-19 (u2Net Human ). One manual segmentations (MS) was available for each scan, being a consensus by two experts. Transfer learning was then applied to train u2Net Pig on the clinical data set generating u2Net Transfer . General segmentation quality was quantified using the Jaccard index (JI) and the Boundary Function score (BF). The slope between JI or BF and relative volume of non-aerated compartment (S JI and S BF , respectively) was calculated over data sets to assess robustness toward non-aerated lung regions. Additionally, the relative volume of ACs and lung volumes (LV) were compared between automatic and MS. RESULTS: On the experimental data set, u2Net Pig resulted in JI = 0.892 [0.88 : 091] (median [inter-quartile range]), BF = 0.995 [0.98 : 1.0] and slopes S JI = -0.2 {95% conf. int. -0.23 : -0.16} and S BF = -0.1 {-0.5 : -0.06}. u2Net Human showed similar performance compared to u2Net Pig in JI, BF but with reduced robustness S JI = -0.29 {-0.36 : -0.22} and S BF = -0.43 {-0.54 : -0.31}. Transfer learning improved overall JI = 0.92 [0.88 : 0.94], P < 0.001, but reduced robustness S JI = -0.46 {-0.52 : -0.40}, and affected neither BF = 0.96 [0.91 : 0.98] nor S BF = -0.48 {-0.59 : -0.36}. u2Net Transfer improved JI compared to u2Net Human in segmenting healthy (P = 0.008), ARDS (P < 0.001) and COPD (P = 0.004) patients but not in COVID-19 patients (P = 0.298). ACs and LV determined using u2Net Transfer segmentations exhibited < 5% volume difference compared to MS. CONCLUSION: Compared to manual segmentations, automatic uNet based 3D lung segmentation provides acceptable quality for both clinical and scientific purposes in the quantification of lung volumes, aeration compartments, and recruitability.

Neurological Complications and Noninvasive Multimodal Neuromonitoring in Critically Ill Mechanically Ventilated COVID-19 Patients.

Purpose: The incidence and the 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 the 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, optic nerve sheath diameter (ONSD), and automated pupillometry. Results: Ninety-four patients with COVID-19 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 50% of patients, 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 < 0.001) and ICU (31.5 ± 22.6 vs. 11.5±10.1 days, p < 0.001) stay. The duration of mechanical ventilation was independently associated with the risk of developing neurological complications (odds ratio 1.100, 95% CI 1.046-1.175, p = 0.001). Patients with increased intracranial pressure measured by ONSD (19% of the overall population) had longer ICU stay. Conclusions: 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 the early detection of variations in cerebrovascular parameters in COVID-19.

Plasma miRNA-based signatures in CRC screening programs.

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.

Endoscopic submucosal dissection versus endoscopic mucosal resection for type 0-II superficial gastric lesions larger than 20 mm.

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.

Clinical and viro-immunological correlates of HIV associated neurocognitive disorders (HAND) in a cohort of antiretroviral-naïve HIV-infected patients.

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-naïve, 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.

Viro-immunological characterization of naïve patients with high cerebrospinal fluid (CSF) HIV RNA.

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 RNA<10000cp/mL characterized low VL patients (L-CSF). Chi-square and Mann-Whitney tests were used. Parameters independently associated with CSF VL were explored by multivariate regression. RESULTS: A total of 131 patients were retrospectively enrolled. Forty-two patients (32%) had CSF VL >10000 cp/mL. 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.

Impact of portal vein thrombosis on the efficacy of endoscopic variceal band ligation.

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.

Schwann cell hamartoma: case report.

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.

Detection of the imbalance of procoagulant versus anticoagulant factors in cirrhosis by a simple laboratory method.

UNLABELLED: 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.