Purpose
To assess the ability of quantitative pupillometry using the Neurological Pupil index (NPi) to predict an unfavorable neurological outcome after cardiac arrest (CA).
Methods
We performed a ...prospective international multicenter study (10 centers) in adult comatose CA patients. Quantitative NPi and standard manual pupillary light reflex (sPLR)—blinded to clinicians and outcome assessors—were recorded in parallel from day 1 to 3 after CA. Primary study endpoint was to compare the value of NPi versus sPLR to predict 3-month Cerebral Performance Category (CPC), dichotomized as favorable (CPC 1–2: full recovery or moderate disability) versus unfavorable outcome (CPC 3–5: severe disability, vegetative state, or death).
Results
At any time between day 1 and 3, an NPi ≤ 2 (
n
= 456 patients) had a 51% (95% CI 49–53) negative predictive value and a 100% positive predictive value PPV; 0% (0–2) false-positive rate, with a 100% (98–100) specificity and 32% (27–38) sensitivity for the prediction of unfavorable outcome. Compared with NPi, sPLR had significantly lower PPV and significantly lower specificity (
p
< 0.001 at day 1 and 2;
p
= 0.06 at day 3). The combination of NPi ≤ 2 with bilaterally absent somatosensory evoked potentials (SSEP;
n
= 188 patients) provided higher sensitivity 58% (49–67) vs. 48% (39–57) for SSEP alone, with comparable specificity 100% (94–100).
Conclusions
Quantitative NPi had excellent ability to predict an unfavorable outcome from day 1 after CA, with no false positives, and significantly higher specificity than standard manual pupillary examination. The addition of NPi to SSEP increased sensitivity of outcome prediction, while maintaining 100% specificity.
Gray–white-matter ratio (GWR) calculated from head CT is a radiologic index of tissue changes associated with hypoxic-ischemic encephalopathy after cardiac arrest (CA). Evidence from previous studies ...indicates high specificity for poor outcome prediction at GWR thresholds of 1.10–1.20. We aimed to determine the relationship between accuracy of neurologic prognostication by GWR and timing of CT.
We included 195 patients admitted to the ICU following CA. GWR was calculated from CT radiologic densities in 16 regions of interest. Outcome was determined upon intensive care unit discharge using the cerebral performance category (CPC). Accuracy of outcome prediction of GWR was compared for 3 epochs (<6, 6–24, and >24 h after CA).
125 (64%) patients had poor (CPC4–5) and 70 (36%) good outcome (CPC1–3). Irrespective of timing, specificity for poor outcome prediction was 100% at a GWR threshold of 1.10. Among 50 patients with both early and late CT, GWR decreased significantly over time (p = 0.002) in patients with poor outcome, sensitivity for poor outcome prediction was 12% (7–20%) with early CTs (<6 h) and 48% (38–58%) for late CTs (>24 h). Across all patients, sensitivity of early and late CT was 17% (9–28%) and 39% (28–51%), respectively.
A GWR below 1.10 predicts poor outcome (CPC4–5) in patients after CA with high specificity irrespective of time of acquisition of CT. Because GWR decreases over time in patients with severe HIE, sensitivity for prediction of poor outcome is higher for late CTs (>24 h after CA) as compared to early CTs (<6 h after CA).
OBJECTIVE:Outcome prediction after cardiac arrest is important to decide on continuation or withdrawal of intensive care. Neuron-specific enolase is an easily available, observer-independent ...prognostic biomarker. Recent studies have yielded conflicting results on its prognostic value after targeted temperature management.
DESIGN, SETTING, AND PATIENTS:We analyzed neuron-specific enolase serum concentrations 3 days after nontraumatic in-hospital cardiac arrest and out-of-hospital cardiac arrest and outcome of patients from five hospitals in Germany, Austria, and Italy. Patients were treated at 33°C for 24 hours. Cerebral Performance Category was evaluated upon ICU discharge. We performed case reviews of good outcome patients with neuron-specific enolase greater than 90 μg/L and poor outcome patients with neuron-specific enolase less than or equal to 17 μg/L (upper limit of normal).
MEASUREMENTS AND MAIN RESULTS:A neuron-specific enolase serum concentration greater than 90 μg/L predicted Cerebral Performance Category 4–5 with a positive predictive value of 99%, false positive rate of 0.5%, and a sensitivity of 48%. All three patients with neuron-specific enolase greater than 90 μg/L and Cerebral Performance Category 1–2 had confounders for neuron-specific enolase elevation. An neuron-specific enolase serum concentration less than or equal to 17 μg/L excluded Cerebral Performance Category 4–5 with a negative predictive value of 92%. The majority of 14 patients with neuron-specific enolase less than or equal to 17 μg/L who died had a cause of death other than hypoxic-ischemic encephalopathy. Specificity and sensitivity for prediction of poor outcome were independent of age, sex, and initial rhythm but higher for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients.
CONCLUSION:High neuron-specific enolase serum concentrations reliably predicted poor outcome at ICU discharge. Prediction accuracy differed and was better for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. Our “in-the-field” data indicate 90 μg/L as a threshold associated with almost no false positives at acceptable sensitivity. Confounders of neuron-specific enolase elevation should be actively consideredneuron-specific enolase–producing tumors, acute brain diseases, and hemolysis. We strongly recommend routine hemolysis quantification. Neuron-specific enolase serum concentrations less than or equal to 17 μg/L argue against hypoxic-ischemic encephalopathy incompatible with reawakening.
In patients who recover consciousness after cardiac arrest (CA), a subsequent death from non-neurological causes may confound the assessment of long-term neurological outcome. We investigated the ...prevalence and causes of death after awakening (DAA) in a multicenter cohort of CA patients.
Observational multicenter cohort study on patients resuscitated from CA in eight European intensive care units (ICUs) from January 2007 to December 2014. DAA during the hospital stay was extracted retrospectively from patient medical records. Demographics, comorbidities, initial CA characteristics, concomitant therapies, prognostic tests (clinical examination, electroencephalography (EEG), somatosensory evoked potentials (SSEPs)), and cause of death were identified.
From a total 4646 CA patients, 2478 (53%) died in-hospital, of whom 196 (4.2%; ranges 0.6-13.0%) had DAA. DAA was less frequent among out-of-hospital than in-hospital CA (82/2997 2.7% vs. 114/1649 6.9%; p < 0.001). Median times from CA to awakening and from awakening to death were 2 1-5 and 9 3-18 days, respectively. The main causes of DAA were multiple organ failure (n = 61), cardiogenic shock (n = 61), and re-arrest (n = 26). At day 3 from admission, results from EEG (n = 56) and SSEPs (n = 60) did not indicate poor outcome.
In this large multicenter cohort, DAA was observed in 4.2% of non-survivors. Information on DAA is crucial since it may influence epidemiology and the design of future CA studies evaluating neuroprognostication and neuroprotection.
Bilateral absent N20 responses of median nerve somatosensory evoked potentials (SEPs) reliably predict poor prognosis after cardiac arrest. However, the studies supporting this fact were carried out ...before hypothermia was established as standard treatment. Recent evidence suggests that hypothermia treatment affects the predictive value of clinical findings in cardiac arrest patients, raising the question whether the predictive value of N20 responses has changed as well.
We retrospectively studied 185 consecutive patients treated with hypothermia after cardiac arrest. SEP recordings were available for 112 patients. SEPs were classified as bilateral absent N20, pathologic N20, or normal. Baseline and follow-up information were obtained from our database.
We identified 36 patients with bilateral absent N20, 35 (97%) of whom had poor outcome. One patient had prolonged high amplitude peripheral SEP, but bilaterally absent N20 3 days after cardiac arrest and regained consciousness with normal cognitive functions and reproducible N20 responses. One further patient had minimally detectable N20 at day 3 and recovered consciousness and normal N20 responses on follow-up.
Our data indicate that recovery of consciousness and cognitive functions is possible in spite of absent or minimally present N20 responses more than 24 hours after cardiac arrest in a very small proportion of patients. N20 responses may recover beyond this time window. The predictive value of bilateral absent N20 responses needs to be reevaluated in larger prospective studies. Until these studies are available, decisions to stop therapy in cardiac arrest survivors should not be based on N20 responses alone.
P-Type ATPases are part of the regulatory system of the cell where they are responsible for transporting ions and lipids through the cell membrane. These pumps are found in all eukaryotes and their ...malfunction has been found to cause several severe diseases. Knowing which substrate is pumped by a certain P-Type ATPase is therefore vital. The P-Type ATPases can be divided into 11 subtypes based on their specificity, that is, the substrate that they pump. Determining the subtype experimentally is time-consuming. Thus it is of great interest to be able to accurately predict the subtype based on the amino acid sequence only. We present an approach to P-Type ATPase sequence classification based on the k-nearest neighbors, similar to a homology search, and show that this method provides performs very well and, to the best of our knowledge, better than any existing method despite its simplicity. The classifier is made available as a web service at http://services.birc.au.dk/patbox/ which also provides access to a database of potential P-Type ATPases and their predicted subtypes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Long-term analyses of biodiversity data highlight a 'biodiversity conservation paradox': biological communities show substantial species turnover over the past century
, but changes in species ...richness are marginal
. Most studies, however, have focused only on the incidence of species, and have not considered changes in local abundance. Here we asked whether analysing changes in the cover of plant species could reveal previously unrecognized patterns of biodiversity change and provide insights into the underlying mechanisms. We compiled and analysed a dataset of 7,738 permanent and semi-permanent vegetation plots from Germany that were surveyed between 2 and 54 times from 1927 to 2020, in total comprising 1,794 species of vascular plants. We found that decrements in cover, averaged across all species and plots, occurred more often than increments; that the number of species that decreased in cover was higher than the number of species that increased; and that decrements were more equally distributed among losers than were gains among winners. Null model simulations confirmed that these trends do not emerge by chance, but are the consequence of species-specific negative effects of environmental changes. In the long run, these trends might result in substantial losses of species at both local and regional scales. Summarizing the changes by decade shows that the inequality in the mean change in species cover of losers and winners diverged as early as the 1960s. We conclude that changes in species cover in communities represent an important but understudied dimension of biodiversity change that should more routinely be considered in time-series analyses.
Abstract Aim Prognosis after cardiac arrest in the era of modern critical care is still poor with a high mortality of approximately 90%. Around 30% of the survivors have neurological impairments. ...Targeted temperature management (TTM) is the only treatment option which can improve mortality and neurological outcome. It is so far unclear if bleeding complications occur more often in patients undergoing TTM treatment. Methods We conducted a systematic literature research in September 2013 including three major databases i.e. MEDLINE, EMBASE and CENTRAL. All studies were rated in respect to the ILCOR Guidelines and concerning their level of evidence and quality. We then performed a meta-analysis on bleeding disposition under TTM. Results We initially found 941 studies out of which 34 matched our requirements and were thus included in our overview. Five studies including 599 patients were summarized in a meta-analysis concerning bleeding complications of all severities. There was a trend toward higher bleeding in patients treated with TTM (RR: 1.30, 95% CI: 0.97–1.74) which did not reach significance ( p = 0.085). Seven studies with an overall 599 patients were included in our meta-analysis on bleeding requiring transfusion. There was no significant difference in the incidence of severe bleeding with a risk ratio of 0.97 (95% CI: 0.61–1.56, p = 0.909). Conclusions The data included in our meta-analysis indicate that, concerning the risk of bleeding, TTM is a safe method for patients after cardiac arrest. We did not observe a significantly higher risk for bleeding in patients undergoing TTM.
The pressure-induced structural phase transitions in the lanthanide elements provide insight into changes in their electronic structures at high densities. After a series of transitions via ...close-packed structures, the regular trivalent lanthanides (La to Lu, excluding Ce, Eu and Yb) undergo first-order transitions to so-called collapsed phases, the structures of which have long been reported as monoclinic. However, the diffraction data from these phases are not well fitted by this monoclinic structure, and the patterns from Nd and Sm are distinctly different to those from the higher-Z lanthanides (Gd→). Here we present results from recent diffraction studies on Tb, Gd, Sm, Nd and Y to above 300 GPa, which reveal that there are two different collapsed structures, neither of which is monoclinic. High-precision equation of state studies of the same elements reveal distinct changes in compressibility once the collapsed phases are obtained. We also show that these new structures are strikingly similar to those observed in the higher-Z actinides at high pressure, greatly strengthening the structural systematics of the 4f and 5f elements.
To establish a deep learning model for the detection of hypoxic-ischemic encephalopathy (HIE) features on CT scans and to compare various networks to determine the best input data format.
168 head CT ...scans of patients after cardiac arrest were retrospectively identified and classified into two categories: 88 (52.4%) with radiological evidence of severe HIE and 80 (47.6%) without signs of HIE. These images were randomly divided into a training and a test set, and five deep learning models based on based on Densely Connected Convolutional Networks (DenseNet121) were trained and validated using different image input formats (2D and 3D images).
All optimized stacked 2D and 3D networks could detect signs of HIE. The networks based on the data as 2D image data stacks provided the best results (
AUC: 94%, ACC: 79%,
AUC: 93%, ACC: 79%). We provide visual explainability data for the decision making of our AI model using Gradient-weighted Class Activation Mapping.
Our proof-of-concept deep learning model can accurately identify signs of HIE on CT images. Comparing different 2D- and 3D-based approaches, most promising results were achieved by 2D image stack models. After further clinical validation, a deep learning model of HIE detection based on CT images could be implemented in clinical routine and thus aid clinicians in characterizing imaging data and predicting outcome.
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