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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); Chi 2  = 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

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; I 2 (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 .

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 cmH 2 O) 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 (PaCO 2 ) 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 cmH 2 O. 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 cmH 2 O 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 PaCO 2 (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.

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.

Background There is a paucity of data concerning the optimal ventilator management in patients with COVID-19 pneumonia; particularly, the optimal levels of positive-end expiratory pressure (PEEP) are unknown. We aimed to investigate the effects of two levels of PEEP on alveolar recruitment in critically ill patients with severe COVID-19 pneumonia. Methods A single-center cohort study was conducted in a 39-bed intensive care unit at a university-affiliated hospital in Genoa, Italy. Chest computed tomography (CT) was performed to quantify aeration at 8 and 16 cmH 2 O PEEP. The primary endpoint was the amount of alveolar recruitment, defined as the change in the non-aerated compartment at the two PEEP levels on CT scan. Results Forty-two patients were included in this analysis. Alveolar recruitment was median [interquartile range] 2.7 [0.7–4.5] % of lung weight and was not associated with excess lung weight, PaO 2 /FiO 2 ratio, respiratory system compliance, inflammatory and thrombophilia markers. Patients in the upper quartile of recruitment (recruiters), compared to non-recruiters, had comparable clinical characteristics, lung weight and gas volume. Alveolar recruitment was not different in patients with lower versus higher respiratory system compliance. In a subgroup of 20 patients with available gas exchange data, increasing PEEP decreased respiratory system compliance (median difference, MD − 9 ml/cmH 2 O, 95% CI from − 12 to − 6 ml/cmH 2 O, p  < 0.001) and the ventilatory ratio (MD − 0.1, 95% CI from − 0.3 to − 0.1, p  = 0.003), increased PaO 2 with FiO 2  = 0.5 (MD 24 mmHg, 95% CI from 12 to 51 mmHg, p  < 0.001), but did not change PaO 2 with FiO 2  = 1.0 (MD 7 mmHg, 95% CI from − 12 to 49 mmHg, p  = 0.313). Moreover, alveolar recruitment was not correlated with improvement of oxygenation or venous admixture. Conclusions In patients with severe COVID-19 pneumonia, higher PEEP resulted in limited alveolar recruitment. These findings suggest limiting PEEP strictly to the values necessary to maintain oxygenation, thus avoiding the use of higher PEEP levels.

Abstract BackgroundThe infectious disease phenotype of acute stroke associated with COVID-19 has been poorly characterized.ObjectiveWe investigated the neurovascular and infectious disease phenotype of stroke patients with and without COVID-19 infection, and their effect on in-hospital mortality.MethodsThis 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.ResultsOne 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).ConclusionSymptomatic interstitial pneumonia was the major driver of in-hospital mortality in COVID + stroke patients.

Abstract Background Remdesivir has been associated with accelerated recovery of severe coronavirus disease 2019 (COVID-19). However, whether it is also beneficial in patients requiring mechanical ventilation is uncertain. Methods All consecutive intensive care unit (ICU) patients requiring mechanical ventilation due to COVID-19 were enrolled. Univariate and multivariable Cox models were used to explore the possible association between in-hospital death or hospital discharge, considered competing-risk events, and baseline or treatment-related factors, including the use of remdesivir. The rate of extubation and the number of ventilator-free days were also calculated and compared between treatment groups. Results One hundred thirteen patients requiring mechanical ventilation were observed for a median of 31 days of follow-up; 32% died, 69% were extubated, and 66% were discharged alive from the hospital. Among 33 treated with remdesivir (RDV), lower mortality (15.2% vs 38.8%) and higher rates of extubation (88% vs 60%), ventilator-free days (median [interquartile range], 11 [0–16] vs 5 [0–14.5]), and hospital discharge (85% vs 59%) were observed. Using multivariable analysis, RDV was significantly associated with hospital discharge (hazard ratio [HR], 2.25; 95% CI, 1.27–3.97; P = .005) and with a nonsignificantly lower mortality (HR, 0.73; 95% CI, 0.26–2.1; P = .560). RDV was also independently associated with extubation (HR, 2.10; 95% CI, 1.19–3.73; P = .011), which was considered a competing risk to death in the ICU in an additional survival model. Conclusions In our cohort of mechanically ventilated patients, RDV was not associated with a significant reduction of mortality, but it was consistently associated with shorter duration of mechanical ventilation and higher probability of hospital discharge, independent of other risk factors.

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.

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. 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.

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.