Biomarkers For Prediction Of Outcomes Research Articles

18F-FDG PET/CT- and MRI-Based Locally Advanced Cervical Cancer Early-Response Assessment after Concurrent Chemo- and Radiotherapy-Impact on Patient Outcomes and Survival Prediction.

With one third of patients with locally advanced cervical cancer (LACC) expected to develop cancer recurrence in the first two years after therapy, accurate assessment of the response and timely detection of cancer recurrence after concurrent chemo- and radiotherapy (CCRT) treatment is of great importance. Although there is neither definite consensus about the preferred imaging modality, nor the time interval until the first diagnostic examination after CCRT, the National Comprehensive Cancer Network (NCCN) recommends the use of MRI and 18F-FDG PET/CT as a post-treatment LACC response-assessment imaging tools. In this study, we tried to appraise the early therapy response in LACC patients by both 18F-FDG PET/CT and MRI in regard to the follow-up imaging results and their mutual interrelationship, and to ascertain if the post-treatment 18F-FDG PET/CT and MRI results were related to the progression-free and overall survival rate in women with LACC after CCRT. We also aimed to estimate the early and follow-up diagnostic imaging impact on further therapy management. Based on our results, we concluded that 18F-FDG PET/CT did surpass MRI in the early assessment of therapeutic response in LACC patients after CCRT. Both modalities provided information that may serve as predictive biomarkers of outcome and LACC patients' survival.

Association between intracellular adenosine triphosphate content of CD4+ T lymphocytes and mortality in sepsis patients: A prospective observational study.

This study aimed to link intracellular adenosine triphosphate content in CD4+ T lymphocytes (CD4+ iATP) with sepsis patient mortality, seeking a new predictive biomarker for outcomes and enhanced management. 61 sepsis patients admitted to the Intensive Care Unit between October 2021 and November 2022 were enrolled. iATP levels were gauged using whole blood CD4+ T cells stimulated with mitogen PHA-L. Based on CD4+ iATP levels (<132.24 and ≥132.24 ng/mL), patients were categorized into two groups. The primary endpoint was all-cause mortality. To identify factors associated with mortality, both univariate and multivariate Cox proportional hazard analyses were conducted. Of the patients, 40 had high CD4+ iATP levels (≥132.24 ng/mL) and 21 had low levels (<132.24 ng/mL). In a 28-day follow-up, 21 (34.4%) patients perished. Adjusting for confounders like SOFA score, APACHE II score, lactic acid, and albumin, those with low CD4+ iATP had three- to fivefold higher mortality risk compared to high CD4+ iATP patients (61.9% vs. 20.0%; hazard ratio [95% confidence interval], Model 1: 4.515 [1.276-15.974], p = .019, Model 2: 3.512 [1.197-10.306], p = .022). CD4+ iATP correlated positively with white blood cell and neutrophil counts but not with lymphocytes, CD3, and CD4 counts. Low CD4+ iATP levels were associated with a higher risk of mortality in sepsis patients. Measurement of CD4+ iATP may serve as a useful tool for identifying patients at a higher risk of mortality and could potentially provide a basis for clinical treatment. Further research is warranted to fully elucidate the underlying mechanisms of this association.

Regional Brain Net Water Uptake in Computed Tomography after Cardiac Arrest – A Novel Biomarker for Neuroprognostication

BackgroundSelective water uptake by neurons and glial cells and subsequent brain tissue oedema are key pathophysiological processes of hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA). Although brain computed tomography (CT) is widely used to assess the severity of HIE, changes of brain radiodensity over time have not been investigated. These could be used to quantify regional brain net water uptake (NWU), a potential prognostic biomarker. MethodsWe conducted an observational prognostic accuracy study including a derivation (single center cardiac arrest registry) and a validation (international multicenter TTM2 trial) cohort. Early (<6 h) and follow-up (>24 h) head CTs of CA patients were used to determine regional NWU for grey and white matter regions after co-registration with a brain atlas. Neurological outcome was dichotomized as good versus poor using the Cerebral Performance Category Scale (CPC) in the derivation cohort and Modified Rankin Scale (mRS) in the validation cohort. ResultsWe included 115 patients (81 derivation, 34 validation) with out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA). Regional brain water content remained unchanged in patients with good outcome. In patients with poor neurological outcome, we found considerable regional water uptake with the strongest effect in the basal ganglia. NWU >8% in the putamen and caudate nucleus predicted poor outcome with 100% specificity (95%-CI: 86–100%) and 43% (moderate) sensitivity (95%-CI: 31–56%). ConclusionThis pilot study indicates that NWU derived from serial head CTs is a promising novel biomarker for outcome prediction after CA. NWU >8% in basal ganglia grey matter regions predicted poor outcome while absence of NWU indicated good outcome. NWU and follow-up CTs should be investigated in larger, prospective trials with standardized CT acquisition protocols.

Subarachnoid Hemorrhagic Volume: A Biomarker for Prediction of Outcome and Complications (P2-5.007)

Subarachnoid Hemorrhagic Volume: A Biomarker for Prediction of Outcome and Complications (P2-5.007)

CT-guided high dose rate brachytherapy can induce multiple systemic proteins of proliferation and angiogenesis predicting outcome in HCC

Background and purposeTo determine the potential prognostic value of proliferation and angiogenesis plasma proteins following CT-guided high dose rate brachytherapy (HDR-BT) of hepatocellular carcinoma (HCC). Materials and methodsFor this prospective study, HDR-BT (1 × 15 Gy) was administered to 24 HCC patients. Plasma was obtained and analyzed using an Olink proteomics Target-96 immuno-oncology-panel that included multiple markers of angiogenesis and proliferation. Fold-change (FC) ratios were calculated by comparing baseline and 48 h post HDR-BT paired samples. Patients were classified as responders (n = 12) if they had no local progression within 6 months or systemic progression within 2 years. Non-responders (n = 12) had recurrence within 6 months and/or tumor progression or extrahepatic disease within 2 years. ResultsProliferation marker EGF was significantly elevated in non-responders compared to responders (p = 0.0410) while FGF-2, HGF, and PlGF showed no significant differences. Angiogenesis markers Angiopoietin-1 and PDGF-B were likewise significantly elevated in non-responders compared to responders (p = 0.0171, p = 0.0462, respectively) while Angiopoietin-2, VEGF-A, and VEGFR-2 did not differ significantly. Kaplan-Meier analyses demonstrated significantly shorter time to systemic progression in patients with increased EGF and Angiopoietin-1 (p = 0.0185, both), but not in patients with one of the remaining proteins elevated (all p > 0.1). Pooled analysis for these 9 proteins showed significantly shorter time to systemic progression for FC ≥1.3 and ≥1.5 for at least 3 proteins elevated (p = 0.0415, p = 0.0193, respectively). ConclusionIncreased plasma levels of EGF and Angiopoietin-1 after HDR-BT for HCC are associated with poor response and may therefore function as predictive biomarkers of outcome.

Prediction of overall survival in patients with locally advanced pancreatic cancer using longitudinal diffusion-weighted MRI.

Biomarkers for prediction of outcome in patients with pancreatic cancer are wanted in order to personalize the treatment. This study investigated the value of longitudinal diffusion-weighted magnetic resonance imaging (DWI) for prediction of overall survival (OS) in patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiotherapy (SBRT). The study included 45 patients with LAPC who received 5 fractions of 10 Gy on a 1.5T MRI-Linac. DWI was acquired prior to irradiation at each fraction. The analysis included baseline values and time-trends of the apparent diffusion coefficient (ADC) and DWI parameters obtained using a decomposition method. A multivariable Cox proportional hazards model for OS was made using best-subset selection, using cross-validation based on Bootstrap. The median OS from the first day of SBRT was 15.5 months (95% CI: 13.2-20.6), and the median potential follow-up time was 19.8 months. The best-performing multivariable model for OS included two decomposition-based DWI parameters: one baseline and one time-trend parameter. The C-Harrell index describing the model's discriminating power was 0.754. High baseline ADC values were associated with reduced OS, whereas no association between the ADC time-trend and OS was observed. Decomposition-based DWI parameters indicated value in the prediction of OS in LAPC. A DWI time-trend parameter was included in the best-performing model, indicating a potential benefit of acquiring longitudinal DWI during the SBRT course. These findings support both baseline and longitudinal DWI as candidate prognostic biomarkers, which may become tools for personalization of the treatment of patients with LAPC.

Platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio as predictive biomarkers for outcome and length of stay in patients with ischemic stroke

Platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio as predictive biomarkers for outcome and length of stay in patients with ischemic stroke

Accuracy of D-dimer as a Predictive Biomarker for Outcome in Head Injured Patients at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia

Introduction: D-dimer reflects the upregulation of the overall hemostatic system upon admission. If D-dimer levels increase, coagulation disorders appear. This is considered a poor prognostic factor. High D-dimer levels reflect the severity of brain injury. Activation of systemic coagulation causes extensive intravascular fibrin deposition and a decrease in platelets and coagulation factors. This study aimed to assess the accuracy of D-dimer as a predictive biomarker for outcomes in head injury patients at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia.&#x0D; Methods: This study is a prospective prognostic test study to test the sensitivity and specificity of D-dimer for prediction mortality in patients with severe head injuries at Dr. Mohammad Hoesin General Hospital (RSMH) Palembang in the period June 2023 to August 2023. A total of 47 research subjects participated in this study.&#x0D; Results: Post 24-hour D-dimer levels have a cut-off point of 11.78 mg/L, which has high accuracy in poor outcomes. D-dimer levels after 5 days have a cut-off point value of 2.3 mg/L and have high sensitivity in predicting poor outcomes, and the value of the difference in changes in D-dimer based on poor outcome patients have a cut-off point of 3.33 mg/L, which has a high sensitivity in predicting a poor prognosis.&#x0D; Conclusion: D-dimer levels are quite accurate as a predictive biomarker for outcomes in head injury patients at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia.

A Platinum Resistance-Related lncRNA Signature for Risk Classification and Prognosis Prediction in Patients with Serous Ovarian Cancer.

Accurate risk stratification for patients with serous ovarian cancer (SOC) is pivotal for treatment decisions. In this study, we identified a lncRNA-based signature for predicting platinum resistance and prognosis stratification for SOC patients. We analyzed the RNA-sequencing data and the relevant clinical information of 295 SOC samples obtained from The Cancer Genome Atlas (TCGA) database and 180 normal ovarian tissues from the Genotype-Tissue Expression (GTEx) database. A total of 284 differentially expressed lncRNAs were screened out between platinum-sensitive and platinum-resistant groups by univariate Cox regression analysis. Then, a signature consisting of eight prognostic lncRNAs was used to construct a lncRNA score model by least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis. The ROC analysis showed that this signature had a good predictive performance for chemotherapy response in the training set (AUC = 0.8524) and the testing and whole sets with 0.8142 and 0.8393 of AUC, respectively. Dichotomized by the risk score of lncRNAs (lncScore), the high-risk patients showed significantly shorter progression-free survival (PFS) and overall survival (OS). Based on the final Cox model, a nomogram comprising the 8-lncRNA signature and 3 clinicopathological risk factors was then established for clinical application to predict the 1, 2, and 3-year PFS of SOC patients. The gene set enrichment analysis (GSEA) revealed that genes in the high-risk group were active in ATP synthesis, coupled electron transport, and mitochondrial respiratory chain complex assembly. Overall, our findings demonstrated the potential clinical significance of the 8-lncRNA-based classifier as a novel biomarker for outcome prediction and therapy decisions in SOC patients with platinum treatment.

Characteristics of Albumin Levels and Liver Function in Patients With COVID-19 at H. Adam Malik Hospital, Medan

Background: COVID-19 (Corona Virus Disease-2019) pandemic has a high mortality rate especially in Medan, Indonesia. Serum albumin and liver function tests are believed to be predictive biomarkers for prognosis in patients with infectious diseases, including COVID-19. This study aimed to investigate the association between the mortality events and severely ill COVID-19 patients' serum albumin and liver enzymes. Method: This is a cross-sectional study using secondary data from the medical records of H. Adam Malik Hospital patients with COVID-19 who were confirmed by RT-PCR from August to December 2020. All patients were analyzed for age, sex, hypoalbuminemia, increased liver enzymes and outcome using Chi-square tests (P&lt;0.05). Results: The average age of severe COVID-19 patients at H. Adam Malik Hospital ranged from 41 to 60 years, with more women prevalence than men. Most of the patients had hypoalbuminemia (84.2%), an increase in AST (59.4)% and ALT (45.5%). There was no significant association between hypoalbuminemia and the disease outcome (P=0.12). There was a significant association between elevated liver enzymes and mortality in severely ill COVID-19 patients (P&lt;0.001). Conclusion: We found that hypoalbuminemia is common in patients with severe COVID-19. However, we found that albumin levels had no association with the patients' mortality rate. Liver enzymes levels appear to be a predictive biomarker for outcomes in COVID-19 patients of H. Adam Malik Hospital. We found that higher ALT and AST levels were associated with significantly higher mortality.

Transcriptomic and immunologic implications of the epithelial-mesenchymal transition model reveal a novel role of SFTA2 in prognosis of non-small-cell lung carcinoma.

Non-small-cell lung cancer (NSCLC) is the second most common cancer worldwide, and most deaths are associated with epithelial–mesenchymal transition (EMT). Therefore, this study aimed to explore the role of EMT-related transcriptomic profiles in NSCLC and the effect of EMT-based signatures on clinical diagnosis, prognosis, and treatment responses for patients with NSCLC. After integrating the transcriptomics and clinicopathological data, we first constructed EMT clusters (C1 and C2) using machine learning algorithms, found the significant relationship between EMT clusters and survival outcomes, and then explored the impact of EMT clusters on the tumor heterogeneity, drug efficiency, and immune microenvironment of NSCLC. Prominently, differential-enriched tumor-infiltrated lymphocytes were found between EMT clusters, especially the macrophages and monocyte. Next, we identified the most significantly down-regulated gene SFTA2 in the EMT clusters C2 with poor prognosis. Using RT-qPCR and RNA-seq data from the public database, we found prominently elevated SFTA2 expression in NSCLC tissues compared with normal lung tissues, and the tumor suppressor role of SFTA2 in 82 Chinese patients with NSCLC. After Cox regression and survival analysis, we demonstrated that higher SFTA2 expression in tumor samples significantly predicts favorable prognosis of NSCLC based on multiple independent cohorts. In addition, the prognostic value of SFTA2 expression differs for patients with lung adenocarcinoma and squamous cell carcinoma. In conclusion, this study demonstrated that the EMT process is involved in the malignant progression and the constructed EMT clusters exerted significant predictive drug resistance and prognostic value for NSCLC patients. In addition, we first identified the high tumoral expression of SFTA2 correlated with better prognosis and could serve as a predictive biomarker for outcomes and treatment response of NSCLC patients.

EPEN-24. Biological markers of ependymoma in children and adolescents (BIOMECA): Systematic comparison of methods for the precise evaluation of biomarkers for ependymoma diagnosis and prognostication

The identification and validation of prognostic and diagnostic biomarkers is a key element of The SIOP Ependymoma II trial, realised through the Biomarkers of Ependymoma in Children and Adolescents study (BIOMECA). BIOMECA aims to identify and validate biomarkers for prediction of outcome whilst enhancing stratification for the next generation of ependymoma trials. We outline our findings from the first 147 consecutive BIOMECA cases (posterior fossa, PF=111; supratentorial, ST=32; spinal, SP=4). We compared various methods for biomarker assessment, across six European laboratories to determine key analysis methods. Methods included: methylation-based classification (EPIC 850K DNA methylation array) (n=141); immunohistochemistry (IHC) for nuclear p65-RELA (n=32), H3K27me3 (n=115), and Tenascin-C (TNC) (n=147); copy number (CN) analysis by FISH, MLPA (1q, CDKN2A) (n=147), and MIP (molecular inversion probe) and DNA methylation array (1q, CDKN2A, 6q, 11q, 13q, 22q) (n=141); analysis of ZFTA- and YAP1-fusions by RT-PCR, sequencing, Nanostring assays and break-apart FISH (n=32). Using DNA methylation-based classification, 91% (n=101/111) of PF cases classified as PF ependymoma group A (PFA) and 69% (n=22/32) of ST cases as ST ependymoma, ZFTA fusion-positive (ZFTA). Most PFAs demonstrated inter-centre agreement for loss of H3K27me3, and were TNC positive, representing surrogate markers for PFA identification. Combinations of p65-RELA IHC, FISH analysis, and RNA-based methods were suitable to identify ZFTA- and YAP1- fused ST ependymomas. Predictive CN alterations were identified by high-resolution, quantitative MIP technology.The integration of histopathology assessment and molecular typing is now critical as the updated 2021 WHO CNS5 classification of ependymomas lists seven molecularly distinct entities. This study highlights the importance of evaluating different methods in a prospective trial cohort. Here, advanced molecular techniques represent powerful tools for the classification of ependymoma entities (DNA methylation array) and for the detection of CN alterations (MIP) and specific fusions, enabling the correct classification and identification of prognostic markers.

Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis

Background and ObjectiveAlthough anti-programmed cell death protein 1 (PD-1) antibodies have exerted remarkable anticancer activity in non-small cell lung cancer (NSCLC), it remains a challenge to identify patients who can benefit from these treatments. Immune-related adverse events (irAEs) may be associated with improved clinical outcomes after immune checkpoint inhibition. However, no conclusive evidence of this correlation has been summarized in patients with NSCLC receiving PD-1 inhibitors. We performed a systematic review and meta-analysis to evaluate the association between irAEs induced by anti-PD-1 antibodies and clinical outcomes in patients with NSCLC.MethodsVarious databases were searched from their inception to January 9, 2021, followed by screening of eligible studies. Hazard ratios were used for the pooled analysis of overall survival (OS) and progression-free survival (PFS), while odds ratios (ORs) were utilized to pool objective response rates (ORRs) and disease control rates (DCRs). A random-effects model was applied to all analyses.ResultsA total of 26 cohorts, including 8,452 patients with NSCLC receiving anti-PD-1 antibodies, were enrolled in the study. Significantly improved OS (HR: 0.51; 95% CI: 0.44-0.60; P < 0.01) and PFS (HR: 0.50; 95% CI: 0.43-0.58; P < 0.01) were found to be correlated with irAEs. In addition, patients with NSCLC who developed irAEs after PD-1 inhibition demonstrated better responses to therapies, confirmed by pooled ORs of ORRs (OR: 3.41; 95% CI: 2.66-4.35; P < 0.01) and DCRs (OR: 4.08; 95% CI: 2.30-7.24; P < 0.01). Furthermore, subgroup analysis suggested that both skin and endocrine irAEs are closely correlated with a reduced risk of death, whereas pulmonary irAEs showed no association with longer OS.ConclusionsIn patients with NSCLC treated with anti-PD-1 therapies, the presence of irAEs was strongly correlated with better survival and response, suggesting its potential role as a predictive biomarker for outcomes after PD-1 inhibition.

Novel biomarkers for prediction of outcome and therapeutic response in juvenile idiopathic arthritis

Introduction The search for biomarkers in juvenile idiopathic arthritis (JIA) is a promising and rapidly expanding field of investigation. The biomarkers identified so far may help to dissect the clinical heterogeneity of the illness, measure the level of disease activity, predict clinical remission, relapse, response to medications, course over time, complications, and forestall disease flares. Areas covered We provide a summary of the most recent advances in the development and application of biomarkers in JIA. We performed a PubMed search for significant articles combining predetermined keywords related to biomarkers in non-systemic and systemic JIA, chronic uveitis, and macrophage activation syndrome (MAS).The biomarkers available or under study are presented and discussed separately for non-systemic and systemic subtypes and for the two main disease complications, uveitis and MAS. Expert opinion The incorporation of valid and reliable biomarkers in standard clinical care may help to design better patient-tailored treatment regimens and to improve the therapeutic strategies based on the treat-to-target approach. The establishment of biomarkers that predict the risk of disease flare may lead to define the optimal modalities for treatment discontinuation after the achievement of clinical remission.

Lipiodol as an intra-procedural imaging biomarker for liver tumor response to transarterial chemoembolization: Post-hoc analysis of a prospective clinical trial

BackgroundThe use of the ethiodized oil- Lipiodol in conventional trans-arterial chemoembolization (cTACE) ensures radiopacity to visualize drug delivery in the process of providing selective drug targeting to hepatic cancers and arterial embolization. Lipiodol functions as a carrier of chemo drugs for targeted therapy, as an embolic agent, augmenting the drug effect by efflux into the portal veins as well as a predictor for the tumor response and survival. PurposeTo prospectively evaluate the role of 3D quantitative assessment of intra-procedural Lipiodol deposition in liver tumors on CBCT immediately after cTACE as a predictive biomarker for the outcome of cTACE. Materials & methodsThis was a post-hoc analysis of data from an IRB-approved prospective clinical trial. Thirty-two patients with hepatocellular carcinoma or liver metastases underwent contrast enhanced CBCT obtained immediately after cTACE, unenhanced MDCT at 24 h after cTACE, and follow-up imaging 30-, 90- and 180-days post-procedure. Lipiodol deposition was quantified on CBCT after cTACE and was characterized by 4 ordinal levels: ≤25%, >25–50%, >50–75%, >75%. Tumor response was assessed on follow-up MRI. Lipiodol deposition on imaging, correlation between Lipiodol deposition and tumor response criteria, and correlation between Lipiodol coverage and median overall survival (MOS) were evaluated. ResultsImage analysis demonstrated a high degree of agreement between the Lipiodol deposition on CBCT and the 24 h post-TACE CT, with a Bland-Altman plot of Lipiodol deposition on imaging demonstrated a bias of 2.75, with 95%-limits-of-agreement: −16.6 to 22.1%. An inverse relationship between Lipiodol deposition in responders versus non-responders for two-dimensional EASL reached statistical significance at 30 days (p = 0.02) and 90 days (p = 0.05). Comparing the Lipiodol deposition in Modified Response Evaluation Criteria in Solid Tumors (mRECIST) responders versus non-responders showed a statistically significant higher volumetric deposition in responders for European Association for the Study of the Liver (EASL)-30d, EASL-90d, and quantitative EASL-180d. The correlation between the relative Lipiodol deposition and the change in enhancing tumor volume showed a negative association post-cTACE (30-day: p < 0.001; rho = −0.63). A Kaplan-Meier analysis for patients with high vs. low Lipiodol deposition showed a MOS of 46 vs. 33 months (p = 0.05). Conclusion3D quantification of Lipiodol deposition on intra-procedural CBCT is a predictive biomarker of outcome in patients with primary or metastatic liver cancer undergoing cTACE. There are spatial and volumetric agreements between 3D quantification of Lipiodol deposition on intra-procedural CBCT and 24 h post-cTACE MDCT. The spatial and volumetric agreement between Lipiodol deposition on intra-procedural CBCT and 24 h post-cTACE MDCT could suggest that acquiring MDCT 24 h after cTACE is redundant. Importantly, the demonstrated relationship between levels of tumor coverage with Lipiodol and degree and timeline of tumor response after cTACE underline the role of Lipiodol as an intra-procedural surrogate for tumor response, with potential implications for the prediction of survival.

Higher albumin levels on admission predict better prognosis in patients with confirmed COVID-19.

BackgroundResearch surrounding COVID-19 (coronavirus disease 2019) is rapidly increasing, including the study of biomarkers for predicting outcomes. There is little data examining the correlation between serum albumin levels and COVID-19 disease severity. The purpose of this study is to evaluate whether admission albumin levels reliably predict outcomes in COVID-19 patients.MethodsWe retrospectively reviewed 181 patients from two hospitals who had COVID-19 pneumonia confirmed by polymerase chain reaction (PCR) testing and radiologic imaging, who were hospitalized between March and July 2020. We recorded demographics, COVID-19 testing techniques, and day of admission labs. The outcomes recorded included the following: venous thromboembolism (VTE), acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, discharge with new or higher home oxygen supplementation, readmission within 90 days, in-hospital mortality, and total adverse events. A multivariate modified Poisson regression analysis was then performed to determine significant predictors for increased adverse events in patients with COVID-19 pneumonia.ResultsA total of 109 patients (60.2%) had hypoalbuminemia (albumin level < 3.3 g/dL). Patients with higher albumin levels on admission had a 72% decreased risk of developing venous thromboembolism (adjusted relative risk [RR]:0.28, 95% confidence interval [CI]:0.14–0.53, p<0.001) for every 1 g/dL increase of albumin. Moreover, higher albumin levels on admission were associated with a lower risk of developing ARDS (adjusted RR:0.73, 95% CI:0.55–0.98, p = 0.033), admission to the ICU (adjusted RR:0.64, 95% CI:0.45–0.93, p = 0.019), and were less likely to be readmitted within 90 days (adjusted RR:0.37, 95% CI:0.17–0.81, p = 0.012). Furthermore, higher albumin levels were associated with fewer total adverse events (adjusted RR:0.65, 95% CI:0.52–0.80, p<0.001).ConclusionsAdmission serum albumin levels appear to be a predictive biomarker for outcomes in COVID-19 patients. We found that higher albumin levels on admission were associated with significantly fewer adverse outcomes, including less VTE events, ARDS development, ICU admissions, and readmissions within 90 days. Screening patients may lead to early identification of patients at risk for developing in-hospital complications and improve optimization and preventative efforts in this cohort.

Cerebral Blood Flow Predicts Recovery in Children with Persistent Post-Concussion Symptoms after Mild Traumatic Brain Injury.

Persistent post-concussion symptoms (PPCS) following pediatric mild traumatic brain injury (mTBI) are associated with differential changes in cerebral blood flow (CBF). Given its potential as a therapeutic target, we examined CBF changes during recovery in children with PPCS. We hypothesized that CBF would decrease and that such decreases would mirror clinical recovery. In a prospective cohort study, 61 children and adolescents (mean age 14 [standard deviation = 2.6] years; 41% male) with PPCS were imaged with three-dimensional (3D) pseudo-continuous arterial spin-labelled (pCASL) magnetic resonance imaging (MRI) at 4-6 and 8-10 weeks post-injury. Exclusion criteria included any significant past medical history and/or previous concussion within the past 3 months. Twenty-three participants had clinically recovered at the time of the second scan. We found that relative and mean absolute CBF were higher in participants with poor recovery, 44.0 (95% confidence interval [CI]: 43.32, 44.67) than in those with good recovery, 42.19 (95% CI: 41.77, 42.60) mL/min/100 g gray tissue and decreased over time (β = -1.75; p < 0.001). The decrease was greater in those with good recovery (β = 2.29; p < 0.001) and predicted outcome in 77% of children with PPCS (odds ratio [OR] 0.54, 95% CI: 0.36, 0.80; p = 0.002). Future studies are warranted to validate the utility of CBF as a useful predictive biomarker of outcome in PPCS.

Blood-brain barrier permeability imaging as a predictor for delayed cerebral ischaemia following subarachnoid haemorrhage. A narrative review.

Aneurysmal subarachnoid haemorrhage is associated with significant morbidity and mortality due to the myriad of complications contributing to early brain injury and delayed cerebral ischaemia. There is increasing interest in the exploration of the association between blood-brain barrier integrity and risks of delayed cerebral ischaemia and poor outcomes. Despite recent advances in cerebral imaging, radiographic imaging of blood-brain barrier disruption, as a biomarker for outcome prediction, has not been adopted in clinical practice. We performed a narrative review by searching for articles describing molecular changes or radiological identification of changes in BBB permeability following subarachnoid haemorrhage (SAH) on MEDLINE. Preclinical studies were analysed if reported structural changes and clinical studies were included if they investigated for radiological markers of BBB disruption and its correlation with delayed cerebral ischaemia. There is ample preclinical evidence to suggest that there are structural changes in BBB permeability following SAH. The available clinical literature has demonstrated correlations between permeability imaging and outcomes following aneurysmal subarachnoid haemorrhage (aSAH). Radiological biomarkers offer a potential non-invasive prognostication tool and may also allow early identifications of patients who may be at risk of DCI.

Glasgow Prognostic Score as a Marker of Mortality after TAVI.

IntroductionThe Glasgow prognostic score (GPS) reflects host systemic inflammatory response and has been reported to be significant as a prognostic indicator in cancer-bearing patients. The aim of this study was to evaluate the predictive value of GPS in outcomes of patients with severe aortic stenosis who were treated with transcatheter aortic valve implantation (TAVI).MethodsThe study population consisted of 79 patients who underwent TAVI due to severe aortic stenosis between January 2018 and March 2019 in our clinic. Echocardiographic and laboratory data were recorded before the procedure and GPS was scored as 0, 1, or 2, based on serum albumin and C-reactive protein levels. European System for Cardiac Operative Risk Evaluation II scoring system was used for risk stratification. The primary endpoints of the study were postoperative in-hospital mortality, hospitalization due to cardiac causes, or mortality within a year.ResultsThe 79 patients were classified into two groups according to outcomes. Fifteen patients (19%) reached the primary endpoints at one year of follow-up. Compared to the patients who did not reach the endpoints, these 15 patients were not different in terms of age, preoperative mean gradient, and ejection fraction (P>0.05 for all). GPS was the only laboratory parameter with statistically significant difference between the groups (P=0.008) and multivariate analysis showed that GPS was independent predictor of primary endpoints (P=0.012, odds ratio 4.51, 95% confidence interval 1.39-14.60).ConclusionGPS is an easy, noninvasive laboratory test which may be used as a predictive biomarker for outcomes in patients undergoing TAVI.

Serum neurofilament light chain as outcome marker for intensive care unit patients

ObjectiveNeurofilament light chain (NfL) in serum indicates neuro-axonal damage in diseases of the central and peripheral nervous system. Reliable markers to enable early estimation of clinical outcome of intensive care unit (ICU) patients are lacking. The aim of this study was to investigate, whether serum NfL levels are a possible biomarker for prediction of outcome of ICU patients.MethodsThirty five patients were prospectively examined from admission to ICU until discharge from the hospital or death. NfL levels were measured longitudinally by a Simoa assay.ResultsNfL was elevated in all ICU patients and reached its maximum at day 35 of ICU treatment. Outcome determined by modified Rankin Scale at the end of the follow-up period correlated with NfL level at admission, especially in the group of patients with impairment of the central nervous system (n = 25, r = 0.56, p = 0.02).ConclusionNfL could be used as a prognostic marker for outcome of ICU patients, especially in patients with impairment of the central nervous system.