Human brain networks have topological properties in common with many other complex systems, prompting the following question: what aspects of brain network organization are critical for distinctive ...functional properties of the brain, such as consciousness? To address this question, we used graph theoretical methods to explore brain network topology in resting state functional MRI data acquired from 17 patients with severely impaired consciousness and 20 healthy volunteers. We found that many global network properties were conserved in comatose patients. Specifically, there was no significant abnormality of global efficiency, clustering, small-worldness, modularity, or degree distribution in the patient group. However, in every patient, we found evidence for a radical reorganization of high degree or highly efficient “hub” nodes. Cortical regions that were hubs of healthy brain networks had typically become nonhubs of comatose brain networks and vice versa. These results indicate that global topological properties of complex brain networks may be homeostatically conserved under extremely different clinical conditions and that consciousness likely depends on the anatomical location of hub nodes in human brain networks.
The drivers of critical coronavirus disease 2019 (COVID-19) remain unknown. Given major confounding factors such as age and comorbidities, true mediators of this condition have remained elusive. We ...used a multi-omics analysis combined with artificial intelligence in a young patient cohort where major comorbidities were excluded at the onset. The cohort included 47 “critical” (in the intensive care unit under mechanical ventilation) and 25 “non-critical” (in a non-critical care ward) patients with COVID-19 and 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cell proteomics, cytokine profiling, and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing, and structural causal modeling were used. Patients with critical COVID-19 were characterized by exacerbated inflammation, perturbed lymphoid and myeloid compartments, increased coagulation, and viral cell biology. Among differentially expressed genes, we observed up-regulation of the metalloprotease
. This gene signature was validated in a second independent cohort of 81 critical and 73 recovered patients with COVID-19 and was further confirmed at the transcriptional and protein level and by proteolytic activity. Ex vivo ADAM9 inhibition decreased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, cohort of individuals with COVID-19, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. We further identified
as a driver of disease severity and a candidate therapeutic target.
Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus.
...In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90.
A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval CI, 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group.
In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).
Background
Thromboprophylaxis of COVID-19 patients is a highly debated issue. We aimed to compare the occurrence of thrombotic/ischemic events in COVID-19 patients with acute respiratory distress ...syndrome (ARDS) treated with either prophylactic or therapeutic dosage of heparin. All patients referred for COVID-19 ARDS in two intensive care units (ICUs) from two centers of a French tertiary hospital were included in our cohort study. Patients were compared according to their anticoagulant treatment to evaluate the risk/benefit of prophylactic anticoagulation versus therapeutic anticoagulation. Medical history, symptoms, biological data and imaging were prospectively collected.
Results
One hundred and seventy-nine patients (73% men) were analyzed: 108 in prophylactic group and 71 in therapeutic group. Median age and SAPS II were 62 IQR 51; 70 years and 47 IQR 37; 63 points. ICU mortality rate was 17.3%. Fifty-seven patients developed clinically relevant thrombotic complications during their ICU stay, less frequently in therapeutic group (adjusted OR 0.38 0.14–0.94, p = 0.04). The occurrences of pulmonary embolism (PE), deep vein thrombosis (DVT) and ischemic stroke were significantly lower in the therapeutic group (respective adjusted OR for PE: 0.19 0.03–0.81; DVT: 0.13 0.01–0.89, stroke: 0.06 0–0.68, all p < 0.05). The occurrence of bleeding complications was not significantly different between groups, neither were ICU length of stay or mortality rate. D-dimer levels were significantly lower during ICU stay, and aPTT ratio was more prolonged in the therapeutic group (p < 0.05).
Conclusion
Increasing the anticoagulation of severe COVID-19 patients to a therapeutic level might decrease thrombotic complications without increasing their bleeding risk.
There is insufficient research into the use of mechanical ventilation with increased inspiratory oxygen concentration (FiO
) and fluid resuscitation with hypertonic saline solution in patients with ...septic shock. We tested whether these interventions are associated with reduced mortality.
This two-by-two factorial, multicentre, randomised, clinical trial (HYPERS2S) recruited patients aged 18 years and older with septic shock who were on mechanical ventilation from 22 centres in France. Patients were randomly assigned 1:1:1:1 to four groups by a computer generated randomisation list stratified by site and presence or absence of acute respiratory distress syndrome by use of permuted blocks of random sizes. Patients received, in an open-labelled manner, mechanical ventilation either with FiO
at 1·0 (hyperoxia) or FiO
set to target an arterial haemoglobin oxygen saturation of 88-95% (normoxia) during the first 24 h; patients also received, in a double-blind manner, either 280 mL boluses of 3·0% (hypertonic) saline or 0·9% (isotonic) saline for fluid resuscitation during the first 72 h. The primary endpoint was mortality at day 28 after randomisation in the intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT01722422.
Between Nov 3, 2012, and June 13, 2014, 442 patients were recruited and assigned to a treatment group (normoxia n=223 or hyperoxia n=219; isotonic n=224 or hypertonic n=218). The trial was stopped prematurely for safety reasons. 28 day mortality was recorded for 434 patients; 93 (43%) of 217 patients had died in the hyperoxia group versus 77 (35%) of 217 patients in the normoxia group (hazard ratio HR 1·27, 95% CI 0·94-1·72; p=0·12). 89 (42%) of 214 patients had died in the hypertonic group versus 81 (37%) of 220 patients in the isotonic group (HR 1·19, 0·88-1·61; p=0·25). We found a significant difference in the overall incidence of serious adverse events between the hyperoxia (185 85%) and normoxia groups (165 76%; p=0·02), with a clinically relevant doubling in the hyperoxia group of the number of patients with intensive care unit-acquired weakness (24 11% vs 13 6%; p=0·06) and atelectasis (26 12% vs 13 6%; p=0·04) compared with the normoxia group. We found no statistical difference for serious adverse events between the two saline groups (p=0·23).
In patients with septic shock, setting FiO
to 1·0 to induce arterial hyperoxia might increase the risk of mortality. Hypertonic (3%) saline did not improve survival.
The French Ministry of Health.
Objectives
The aim of this study was to identify the prognostic value of pre-operative imaging to predict post-transplantation survival in critically ill cirrhotic patients with severe ...acute-on-chronic liver failure (ACLF).
Methods
Patients with grade 3 ACLF who underwent liver transplantation between January 2010 and January 2020 and with available contrast-enhanced abdominal computed tomography (CT) performed less than 3 months before LT were retrospectively included (n = 82). Primary endpoint was 1-year mortality. Imaging parameters (sarcopenia, liver morphology and volumetry, and signs of portal hypertension) were screened and tested to build a prognostic score.
Results
In the multivariate analysis, three independent CT-derived prognostic factors were found: splenomegaly (
p
= 0.021; HR = 5.6 (1.29–24.1)), liver atrophy (
p
= 0.05; HR = 2.93 (1.01–10.64)), and vena cava diameter ratio (
p
< 0.0001; HR = 12.7 (3.4–92)). A simple prognostic score was proposed, based on the presence of splenomegaly (5 points), liver atrophy (5 points), and vena cava diameter ratio < 0.2 (12 points). A cutoff at 10 points distinguished a high-risk group (score > 10) from a low-risk group (score ≤ 10) with 1-year survival of 27% vs. 67% respectively (
p
< 0.001). It was found to be an independent predictive factor in association with the Transplantation for ACLF3 Model (TAM) score.
Conclusion
Pre-transplantation contrast-enhanced abdominal CT has a significant impact on selection of patients in ACLF3 in order to predict 1-year survival after LT.
Key Points
• Splenomegaly, liver atrophy, and vena cava diameter ratio are independent CT-derived prognostic factors after transplantation for severe acute-on-chronic liver failure.
• A simple CT-based prognostic score is an independent predictive factor, complementary to clinical and biological parameters.
• The use of the CT-derived score allows stratification based on 1-year mortality for patients with otherwise uncertain prognosis with clinical and biological parameters alone.
Cerebral aspergillosis is associated with a significant morbidity and mortality rate. The imaging data present different patterns and no full consensus exists on typical imaging characteristics of ...the cerebral lesions. We reviewed MRI findings in 21 patients with cerebral aspergillosis and correlated them to the immune status of the patients and to neuropathological findings when tissue was available. The lesions were characterized by their number, topography, and MRI signal. Dissemination to the brain resulted from direct spread from paranasal sinuses in 8 patients, 6 of them being immunocompetent. Hematogenous dissemination was observed in 13 patients, all were immunosuppressed. In this later group we identified a total of 329 parenchymal abscesses involving the whole brain with a predilection for the corticomedullary junction. More than half the patients had a corpus callosum lesion. Hemorrhagic lesions accounted for 13% and contrast enhancement was observed in 61% of the lesions. Patients with hematogenous dissemination were younger (p = 0.003), had more intracranial lesions (p = 0.0004) and had a higher 12-week mortality rate (p = 0.046) than patients with direct spread from paranasal sinuses. Analysis of 12 aneurysms allowed us to highlight two distinct situations. In case of direct spread from the paranasal sinuses, aneurysms are saccular and located on the proximal artery portions, while the hematogenous dissemination in immunocompromised patients is more frequently associated with distal and fusiform aneurysms. MRI is the exam of choice for cerebral aspergillosis. Number and type of lesions are different according to the mode of dissemination of the infection.
•Staphylococcus epidermidis bacteremia is an underestimated cause of septic shock.•Immunocompromised intensive care unit patients with central lines are most at risk.•S. epidermidis-induced septic ...shocks are associated with intensive care unit mortality.•There is growing concern about the resistance of S epidermidis to oxazolidinones.
Staphylococcus epidermidis (SE) is a supposedly low-virulence agent, which may cause proven bloodstream infections (BSIs), with little-known consequences on intensive care unit (ICU) patients. We aimed at studying ICU patients diagnosed with BSIs caused by SE (SE-BSIs).
We constituted a retrospective cohort in two medical ICUs. SE-BSIs were defined by two or more independent SE-positive blood cultures of the same strain, within 48 hours, without concurrent infection.
We included 59 patients; 58% were men (n = 34), with median age of 67 (interquartile range 60-74) years and a simplified acute physiology score II of 59 (36-74) points, and 56% were immunocompromised (n = 33). Among the 37 (63%) patients requiring norepinephrine initiation or increase at the onset of SE-BSI versus patients not requiring vasopressors (37%; n = 22), concomitant arterial lactate levels reached 2.8 (1.9-5.8) versus 1.5 (1.3-2.2) mmol/l (P <0.01), whereas the mean blood pressure was 49 (42-54) versus 61 (56-65) mm Hg (P = 0.01) and the mortality was 46% (n = 17) vs 14% (n = 3) at day 28 (P = 0.01), respectively. Regarding antibiotics, the susceptibility rates toward linezolid and vancomycin were 71% (n = 41/58) and 100% (n = 54/54), respectively. At the time of SE-BSI, all but one patient had a central venous access device.
This work highlights SE-BSIs as a cause of septic shock, mostly in immunocompromised ICU patients, with increasing concerns about resistance to antibiotics and central line management.
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Cerebral complications related to the COVID-19 were documented by brain MRIs during the acute phase. The purpose of the present study was to describe the evolution of these neuroimaging findings (MRI ...and FDG-PET/CT) and describe the neurocognitive outcomes of these patients.
During the first wave of the COVID-19 outbreak between 1 March and 31 May 2020, 112 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI at Strasbourg University hospitals. After recovery, during follow-up, of these 112 patients, 31 (initially hospitalized in intensive care units) underwent additional imaging studies (at least one brain MRI).
Twenty-three men (74%) and eight women (26%) with a mean age of 61 years (range: 18-79) were included. Leptomeningeal enhancement, diffuse brain microhemorrhages, acute ischemic strokes, suspicion of cerebral vasculitis, and acute inflammatory demyelinating lesions were described on the initial brain MRIs. During follow-up, the evolution of the leptomeningeal enhancement was discordant, and the cerebral microhemorrhages were stable. We observed normalization of the vessel walls in all patients suspected of cerebral vasculitis. Four patients (13%) demonstrated new complications during follow-up (ischemic strokes, hypoglossal neuritis, marked increase in the white matter FLAIR hyperintensities with presumed vascular origin, and one suspected case of cerebral vasculitis). Concerning the grey matter volumetry, we observed a loss of volume of 3.2% during an average period of approximately five months. During follow-up, the more frequent FDG-PET/CT findings were hypometabolism in temporal and insular regions.
A minority of initially severe COVID-19 patients demonstrated new complications on their brain MRIs during follow-up after recovery.
Locked-in syndrome and vegetative state are distinct outcomes from coma. Despite their differences, they are clinically difficult to distinguish at the early stage and current diagnostic tools remain ...insufficient. Since some brain functions are preserved in locked-in syndrome, we postulated that networks of spontaneously co-activated brain areas might be present in locked-in patients, similar to healthy controls, but not in patients in a vegetative state.
Five patients with locked-in syndrome, 12 patients in a vegetative state and 19 healthy controls underwent a resting-state fMRI scan. Individual spatial independent component analysis was used to separate spontaneous brain co-activations from noise. These co-activity maps were selected and then classified by two raters as either one of eight resting-state networks commonly shared across subjects or as specific to a subject.
The numbers of spontaneous co-activity maps, total resting-state networks, and resting-state networks underlying high-level cognitive activity were shown to differentiate controls and locked-in patients from patients in a vegetative state. Analyses of each common resting-state network revealed that the default mode network accurately distinguished locked-in from vegetative-state patients. The frontoparietal network also had maximum specificity but more limited sensitivity.
This study reinforces previous reports on the preservation of the default mode network in locked-in syndrome in contrast to vegetative state but extends them by suggesting that other networks might be relevant to the diagnosis of locked-in syndrome. The aforementioned analysis of fMRI brain activity at rest might be a step in the development of a diagnostic biomarker to distinguish locked-in syndrome from vegetative state.
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