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.
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).
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
= 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.
Irrespectively to the amount of perioperative fluid administered, GDT strategy reduces postoperative complications, but not perioperative mortality.
CRD42020168866; Registration: February 2020 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=168866.
Abstract
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
.
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
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
) 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.
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
O.
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
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
(rho = 0.819, p < 0.0001). Baseline LUStot score predicted the increase of ICP with PEEP.
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.
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.
What's new?
Colon cancer screening currently focusses on stool samples, but precancerous adenomas are not reliably recognized by occult blood‐based or immunochemical tests. Here the authors identify three plasma circulating miRNA‐based signatures that can detect among the individuals positive for the fecal immunochemical test those with precancerous and cancerous lesions. They propose that a blood test based on these signatures could be an additional analysis in individuals with positive fecal test to limit the number of colonoscopies to those likely to benefit most.
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 idealized 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.
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
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.
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.
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,
< 0.001) and ICU (31.5 ± 22.6 vs. 11.5±10.1 days,
< 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,
= 0.001). Patients with increased intracranial pressure measured by ONSD (19% of the overall population) had longer ICU stay.
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.
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.
A systematic consultation of literature was carried out. Search terms included: "CA and sepsis," "CA and surgery," and "CA and non-brain injury."
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.
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.
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.
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 (
2
) 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 (
2
). One manual segmentations (MS) was available for each scan, being a consensus by two experts. Transfer learning was then applied to train
2
on the clinical data set generating
2
. General segmentation quality was quantified using the Jaccard index (
) and the Boundary Function score (
). The slope between
or
and relative volume of non-aerated compartment (
and
, 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.
On the experimental data set,
2
resulted in
= 0.892 0.88 : 091 (median inter-quartile range),
= 0.995 0.98 : 1.0 and slopes
= -0.2 {95% conf. int. -0.23 : -0.16} and
= -0.1 {-0.5 : -0.06}.
2
showed similar performance compared to
2
in
,
but with reduced robustness
= -0.29 {-0.36 : -0.22} and
= -0.43 {-0.54 : -0.31}. Transfer learning improved overall
= 0.92 0.88 : 0.94,
< 0.001, but reduced robustness
= -0.46 {-0.52 : -0.40}, and affected neither
= 0.96 0.91 : 0.98 nor
= -0.48 {-0.59 : -0.36}.
2
improved
compared to
2
in segmenting healthy (
= 0.008), ARDS (
< 0.001) and COPD (
= 0.004) patients but not in COVID-19 patients (
= 0.298). ACs and LV determined using
2
segmentations exhibited < 5% volume difference compared to MS.
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.
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 (
P
aO
2
/
F
IO
2
) 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
P
aO
2
/
F
IO
2
<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
P
aO
2
/
F
IO
2
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.
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