This study investigated the releasing dynamics of serum ST2 and calprotectin in patients with acute IS. The study included acute IS patients (N = 20) with an NIH Stroke Scale score ≥8. Sampling was performed at seven time points: after admission (T0) and at the following 24 h consecutive intervals (T1-T6). Primary outcome at 90 days was evaluated using the modified Rankin scale: 0-2 for good and 3-6 for poor functional outcome. The secondary outcome was all-cause mortality after 90 days. Fifteen patients had a poor outcome, and eight died. Results showed a statistically significant difference in ST2 concentrations between good and poor outcomes at T0 (p = 0.04), T1 (p = 0.006), T2 (p = 0.01), T3 (p = 0.021), T4 (p = 0.007), T5 (p = 0.032), and for calprotectin T6 (p = 0.034). Prognostic accuracy was highest for ST2 at T1 for a cut-off > 18.9 µg/L (sensitivity 80% and specificity 100.0%) and for calprotectin at T5 for a cut-off > 4.5 mg/L (sensitivity 64.3% and specificity 100.0%). Serum ST2 and calprotectin-releasing dynamics showed a valuable prognostic accuracy for IS outcomes.

This study determined the expression of five novel biomarker candidates in IDH wild-type glioblastoma (GBM) tissues compared to non-malign brain parenchyma, as well as their prognostic relevance for the GBM patients\' outcomes. The markers were analysed by immunohistochemistry in tumour tissues (n = 186) and healthy brain tissues (n = 54). The association with the patients\' overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier and log-rank test. The prognostic value of the markers was determined using multivariate Cox proportional hazard models. AGTRAP, DIVERSIN, cytoplasmic NEDD8 (NEDD8c) and RRM1 were significantly overexpressed in tumour tissues compared to the healthy brain, while the opposite was observed for ALKBH3. AGTRAP, ALKBH3, NEDD8c and RRM1 were significantly associated with OS in univariate analysis. AGTRAP and RRM1 were also independent prognostic factors for OS in multivariate analysis. For PFS, only AGTRAP and NEDD8c reached significance in univariate analysis. Additionally, AGTRAP was an independent prognostic factor for PFS in multivariate models. Finally, combined analysis of the markers enhanced their prognostic accuracy. The combination AGTRAP/ALKBH3 had the strongest prognostic value for the OS of GBM patients. These findings contribute to a better understanding of the GBM pathophysiology and may help identify novel therapeutic targets in this type of cancer.

UNASSIGNED: We compared the prognostic accuracy of in-hospital mortality of the initial Sequential Organ Failure Assessment (SOFAini) score at the time of sepsis recognition and resuscitation and the maximum SOFA score (SOFAmax) using the worst variables in the 24 h after the initial score measurement in emergency department (ED) patients with septic shock.
UNASSIGNED: This was a retrospective observational study using a multicenter prospective registry of septic shock patients in the ED between October 2015 and December 2019. The primary outcome was in-hospital mortality. The prognostic accuracies of SOFAini and SOFAmax were evaluated using the area under the receiver operating characteristic (AUC) curve.
UNASSIGNED: A total of 4860 patients was included, and the in-hospital mortality was 22.1%. In 59.7% of patients, SOFAmax increased compared with SOFAini, and the mean change of total SOFA score was 2.0 (standard deviation, 2.3). There was a significant difference in in-hospital mortality according to total SOFA score and the SOFA component scores, except cardiovascular SOFA score. The AUC of SOFAmax (0.71; 95% confidence interval [CI], 0.69-0.72) was significantly higher than that of SOFAini (AUC, 0.67; 95% CI, 0.66-0.69) in predicting in-hospital mortality. The AUCs of all scores of the six components were higher for the maximum values.
UNASSIGNED: The prognostic accuracy of the initial SOFA score at the time of sepsis recognition was lower than the 24-h maximal SOFA score in ED patients with septic shock. Follow-up assessments of organ failure may improve discrimination of the SOFA score for predicting mortality.

Presence of circulating tumor DNA (ctDNA) is prognostic in solid tumors treated with curative intent. Studies have evaluated ctDNA at specific \"landmark\" or multiple \"surveillance\" time points. However, variable results have led to uncertainty about its clinical validity.
A PubMed search identified relevant studies evaluating ctDNA monitoring in solid tumors after curative intent therapy. Odds ratios for recurrence at both landmark and surveillance time points for each study were calculated and pooled in a meta-analysis using the Peto method. Pooled sensitivity and specificity weighted by individual study inverse variance were estimated and meta-regression using linear regression weighted by inverse variance was performed to explore associations between patient and tumor characteristics and the odds ratio for disease recurrence.
Of 39 studies identified, 30 (1924 patients) and 24 studies (1516 patients) reported on landmark and surveillance time points, respectively. The pooled odds ratio for recurrence at landmark was 15.47 (95% confidence interval = 11.84 to 20.22) and at surveillance was 31.0 (95% confidence interval = 23.9 to 40.2). The pooled sensitivity for ctDNA at landmark and surveillance analyses was 58.3% and 82.2%, respectively. The corresponding specificities were 92% and 94.1%, respectively. Prognostic accuracy was lower with tumor agnostic panels and higher with longer time to landmark analysis, number of surveillance draws, and smoking history. Adjuvant chemotherapy negatively affected landmark specificity.
Although prognostic accuracy of ctDNA is high, it has low sensitivity, borderline high specificity, and therefore modest discriminatory accuracy, especially for landmark analyses. Adequately designed clinical trials with appropriate testing strategies and assay parameters are required to demonstrate clinical utility.

To determine the clinical feasibility of novel serum biomarkers in out-of-hospital cardiac arrest (OHCA) patients treated with target temperature management (TTM).
This study was a prospective observational study conducted on OHCA patients who underwent TTM. We measured conventional biomarkers, neuron‑specific enolase and S100 calcium-binding protein (S-100B), as well as novel biomarkers, including tau protein, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1), at 0, 24, 48, and 72 h after the return of spontaneous circulation identified by SIMOA immunoassay. The primary outcome was poor neurological outcome at 6 months after OHCA.
A total of 100 patients were included in this study from August 2018 to May 2020. Among the included patients, 46 patients had good neurologic outcomes at 6 months after OHCA. All conventional and novel serum biomarkers had the ability to discriminate between the good and poor neurological outcome groups (p < 0.001). The area under the curves of the novel serum biomarkers were highest at 72 h after cardiac arrest (CA) (0.906 for Tau, 0.946 for NFL, 0.875 for GFAP, and 0.935 for UCH-L1). The NFL at 72 h after CA had the highest sensitivity (77.1%, 95% CI 59.9-89.6) in predicting poor neurological outcomes while maintaining 100% specificity.
Novel serum biomarkers reliably predicted poor neurological outcomes for patients with OHCA treated with TTM when life-sustaining therapy was not withdrawn. Cutoffs from two large existing studies (TTM and COMACARE substudy) were externally validated in our study. The predictive power of the novel biomarkers was the highest at 72 h after CA.

Most children with fever without source (FWS) require diagnostic laboratory tests to exclude a serious bacterial infection (SBI), often followed by admission and empirical antibiotics. As febrile children with a viral infection are less likely to have a SBI, identifying patients with systemic viral infection could contribute to exclude SBI. We evaluated whether the presence of virus in the blood could be used as a biomarker to rule out SBI. Children < 3 years old with FWS were prospectively enrolled and had real-time (reverse-transcription) PCR performed on the blood for adenovirus, enterovirus, parechovirus, and HHV6. 20/135 patients had SBI, and in 47/135, at least one virus was detected in the blood. Viremia had a higher sensitivity and negative predictive value (90% and 96%) to rule out SBI compared to CRP (65% and 93%) and PCT (55% and 90%). The odds ratio (OR) for the presence of SBI among non-viremic patients was 5.8 (p = 0.0225), compared to 5.5 for CRP ≥ 40 mg/l (p = 0.0009) and 3.7 for PCT ≥ 0.5 ng/mL (0.0093). This remained significant after adjusting for CRP and PCT (OR 5.6 and 5.9, respectively; p = 0.03 for both). Area under the ROC curve for CRP and PCT were 0.754 and 0.779, respectively, but increased to 0.803 and 0.832, respectively, when combined with viremia.
CONCLUSIONS: The presence of viremia had a better performance than commonly used biomarkers to rule-out SBI and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS. Larger studies should evaluate the role of point-of-care testing of viruses by (revere-transcription) PCR in the plasma in management algorithms of children with FWS.
BACKGROUND: • Most children with FWS have a viral infection, but up to 15% have a SBI; most require laboratory tests, and many admission and empirical antibiotics. • Children with a viral infection are less likely to have a SBI.
BACKGROUND: • Children with a systemic viral infection are less likely to have an SBI. • Viremia is a better predictor of absence of SBI than commonly used biomarkers and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Previous studies on GBM biomarkers focused on the effect of the biomarkers on overall survival (OS). Until now, no study has been published that evaluates the performance of biomarkers for prognosing OS. We examined the performance of microRNAs, gene expressions, gene signatures, and methylation that were previously identified to be prognostic. In addition, we investigated whether using clinical risk factors in combination with biomarkers can improve the prognostic performance.
METHODS: The Cancer Genome Atlas, which provides both biomarkers and OS information, was used in this study. The time-dependent receiver operating characteristic (ROC) curve was used to evaluate the prognostic accuracy.
RESULTS: For prognosis of OS by 2 years from diagnosis, the area under the ROC curve (AUC) of microRNAs, Mir21 and Mir222, was 0.550 and 0.625, respectively. When age was included in the risk prediction score of these biomarkers, the AUC increased to 0.719 and 0.701, respectively. The SAMSN1 gene expression attains an AUC of 0.563, and the \"8-gene\" signature identified by Bao achieves an AUC of 0.613.
CONCLUSIONS: Although some biomarkers are significantly associated with OS, the ability of these biomarkers for prognosing OS events is limited. Incorporating clinical risk factors, such as age, can greatly improve the prognostic performance.

Survival prediction is highly valued in end-of-life care clinical practice, and patient performance status evaluation stands as a predominant component in survival prognostication. While current performance status evaluation tools are limited to their subjective nature, the advent of wearable technology enables continual recordings of patients\' activity and has the potential to measure performance status objectively. We hypothesize that wristband actigraphy monitoring devices can predict in-hospital death of end-stage cancer patients during the time of their hospital admissions. The objective of this study was to train and validate a long short-term memory (LSTM) deep-learning prediction model based on activity data of wearable actigraphy devices. The study recruited 60 end-stage cancer patients in a hospice care unit, with 28 deaths and 32 discharged in stable condition at the end of their hospital stay. The standard Karnofsky Performance Status score had an overall prognostic accuracy of 0.83. The LSTM prediction model based on patients\' continual actigraphy monitoring had an overall prognostic accuracy of 0.83. Furthermore, the model performance improved with longer input data length up to 48 h. In conclusion, our research suggests the potential feasibility of wristband actigraphy to predict end-of-life admission outcomes in palliative care for end-stage cancer patients. Clinical Trial Registration: The study protocol was registered on ClinicalTrials.gov (ID: NCT04883879).

UNASSIGNED: This study aimed to determine the prognostic accuracy of SOFA in comparison to quick-SOFA (qSOFA) and systemic inflammatory response syndrome (SIRS) in predicting 28-day mortality in the emergency department (ED) patients with infections.
UNASSIGNED: A secondary analysis of data from a prospective study of adult patients with documented or suspected infections admitted to an ED in Denmark from Oct-2017 to Mar-2018. The SOFA scores were calculated after adjustment for chronic diseases. The prognostic accuracy was assessed by analysis of sensitivity, specificity, predictive values, likelihood ratios, and area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI).
UNASSIGNED: A total of 2045 patients with a median age of 73.2 (IQR: 60.9-82.1) years were included. The overall 28-day mortality was 7.7%. In patients meeting a SOFA score ≥2, qSOFA score ≥2, and SIRS criteria ≥2 the 28-day mortality was 13.6% (11.2-16.3), 17.8% (12.4-24.3) and 8.3% (6.7-10.2), respectively. SOFA ≥2 had a sensitivity of 61.4% (53.3-69.0) and specificity of 67.3% (65.1-69.4), qSOFA ≥2 had a sensitivity of 19.6% (13.7-26.7) and specificity of 92.4% (91.1-93.6), and SIRS ≥2 had a sensitivity of 52.5% (44.4-60.5) and specificity of 51.5% (49.2-53.7). The AUROC for SOFA compared to SIRS was: 0.68 vs 0.52; p<0.001 and compared to qSOFA: 0.68 vs 0.63; p=0.018.
UNASSIGNED: A SOFA score of at least two had better prognostic accuracy for 28-day mortality than SIRS and qSOFA. However, the overall accuracy of SOFA was poor for the prediction of 28-day mortality.

Crohn\'s disease is a lifelong condition that can affect any segment of the gastrointestinal tract. Some people with Crohn\'s disease may be at higher risk of following a severe course of disease than others and being able to identify the level of risk a patient has could lead to personalised management.
To assess the prognostic test accuracy, clinical impact and cost-effectiveness of two tools for the stratification of people with a diagnosis of Crohn\'s disease by risk of following a severe course of disease.
The data sources MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were searched to inform the systematic reviews on prognostic accuracy, clinical impact of the prognostic tools, and economic evaluations. Additional data sources to inform the review of economic evaluations were NHS Economic Evaluation Database, Database of Abstracts of Reviews of Effects and the Health Technology Assessment Database.
Systematic reviews of electronic databases were carried out from inception to June 2019 for studies assessing the prognostic accuracy and clinical impact of the IBDX® (Crohn\'s disease Prognosis Test; Glycominds Ltd, Lod, Israel) biomarker stratification tool and the PredictSURE-IBD™ (PredictImmune Ltd, Cambridge, UK) tool. Systematic reviews of studies reporting on the cost-effectiveness of treatments for Crohn\'s disease were run from inception to July 2019. Two reviewers independently agreed on studies for inclusion, assessed the quality of included studies and validated the data extracted from studies. Clinical and methodological heterogeneity across studies precluded the synthesis of data for prognostic accuracy. A de novo economic model was developed to compare the costs and consequences of two treatment approaches - the \'top-down\' and \'step-up\' strategies, with step-up considered standard care - in people at high risk of following a severe course of Crohn\'s disease. The model comprised a decision tree and a Markov cohort model.
Sixteen publications, including eight original studies (n = 1478), were deemed relevant to the review of prognostic accuracy. Documents supplied by the companies marketing the prognostic tools were also reviewed. No study meeting the eligibility criteria reported on the sensitivity or specificity of the IBDX biomarker stratification tool, whereas one study provided estimates of sensitivity, specificity and negative predictive value for the PredictSURE-IBD tool. All identified studies were observational and were considered to provide weak evidence on the effectiveness of the tools. Owing to the paucity of data on the two tools, in the base-case analysis the accuracy of PredictSURE-IBD was assumed to be 100%. Accuracy of IBDX was assumed to be 100% in a scenario analysis, with the cost of the tests being the only difference between the analyses. The incremental analysis of cost-effectiveness demonstrated that top-down (via the use of PredictSURE-IBD in the model) is more expensive and generates fewer quality-adjusted life-years than step-up (via the standard care arm of the model).
Despite extensive systematic searches of the literature, no robust evidence was identified of the prognostic accuracy of the biomarker stratification tools IBDX and PredictSURE-IBD.
Although the model indicates that standard care dominates the tests, the lack of evidence of prognostic accuracy of the two tests and the uncertainty around the benefits of the top-down and step-up treatment approaches mean that the results should be interpreted as indicative rather than definitive.
This study is registered as PROSPERO CRD42019138737.
This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 23. See the NIHR Journals Library website for further project information.
Crohn’s disease is a condition in which parts of the digestive system become inflamed (swollen). People of any age can develop Crohn’s disease. It is a lifelong condition for which there is no cure. In the UK, Crohn’s disease affects about 1 in every 650 people. Any part of the digestive system can be affected, and the severity of the disease can vary from person to person. Symptoms come and go, and there can be times when there are no symptoms at all. Common symptoms of Crohn’s disease are diarrhoea, stomach-ache and blood in faeces. Treatment is given to reduce or control symptoms and to try to stop inflammation from coming back. Some people with Crohn’s disease are more likely than others to have more relapses and to develop complications of Crohn’s disease that might require surgery. This project looked at how well two tools worked at identifying people with Crohn’s disease who might develop complications or need surgery. Identifying those who have a higher chance of experiencing complications of Crohn’s disease could help them and their doctor to choose their treatment, with the goal of reducing the number of relapses and the risk of surgery in the longer term. In addition, the review assessed whether or not the tools offered value for money. We found limited evidence of how well the tools worked in identifying people who were more likely to develop complications of Crohn’s disease. The lack of evidence on the tools meant that the cost-effectiveness analysis could only assess the value for money of the treatment that is given in clinical practice at this time or of more intensive treatments for people who are more likely to develop complications. The analysis found that current standard care offers more value for money than intensive treatments for people with a higher chance of developing complications of Crohn’s disease.