Impaired endogenous fibrinolysis status: a potential prognostic predictor in ischemic stroke.

Stroke confers a severe global healthcare burden, hence exploring risk factors for stroke occurrence and prognosis is important for stroke prevention and post-stroke management strategies. Endogenous fibrinolysis is a spontaneous physiological protective mechanism that dissolves thrombus to maintain vascular patency. Recently, impaired endogenous fibrinolysis has been considered as a potential novel cardiovascular risk factor, but its link with ischaemic stroke in the past has been underappreciated. In this review, we summarize the latest mechanisms of endogenous fibrinolysis, review the current evidence and data on endogenous fibrinolysis in ischemic stroke. It includes the structure of thrombus in ischemic stroke patients, the effect of fibrin structure on the endogenous fibrinolytic efficiency, and the association between intravenous thrombolytic therapy and endogenous fibrinolysis in ischemic stroke. It also includes the single factors (tissue plasminogen activator, urokinase plasminogen activator, plasminogen activator inhibitor-1, thrombin activatable fibrinolysis inhibitor, complement component 3, complement component 5, alpha-2-antiplasmin, plasmin-alpha-2-antiplasmin complex, and lipoprotein[a]), and the global assessments of endogenous fibrinolysis status (thromboelastography, rotational thromboelastometry, and global thrombosis test), and their potential as predictors to identify occurrence or unfavorable functional outcomes of ischemic stroke. All of these assessments present advantages and limitations, and we suggest that the global thrombosis test may be more appropriate for detecting impaired endogenous fibrinolysis status in ischemic stroke patients.

Plasma Biomarkers for Hypertension-Mediated Organ Damage Detection: A Narrative Review.

Hypertension (HT) is a disease that poses a serious threat to human health, mediating organ damage such as the cardiovascular (CV) system, kidneys, central nervous system (CNS), and retinae, ultimately increasing the risk of death due to damage to the entire vascular system. Thus, the widespread prevalence of hypertension brings enormous health problems and socioeconomic burdens worldwide. The goal of hypertension management is to prevent the risk of hypertension-mediated organ damage and excess mortality of cardiovascular diseases. To achieve this goal, hypertension guidelines recommend accurate monitoring of blood pressure and assessment of associated target organ damage. Early identification of organ damage mediated by hypertension is therefore crucial. Plasma biomarkers as a non-invasive test can help identify patients with organ damage mediated by hypertension who will benefit from antihypertensive treatment optimization and improved prognosis. In this review, we provide an overview of some currently available, under-researched, potential plasma biomarkers of organ damage mediated by hypertension, looking for biomarkers that can be detected by simple testing to identify hypertensive patients with organ damage, which is of great significance in clinical work. Natriuretic peptides (NPs) can be utilized as a traditional biomarker to detect hypertension-mediated organ damage, especially for heart failure. Nevertheless, we additionally may need to combine two or more plasma biomarkers to monitor organ damage in the early stages of hypertension.

The current use of proteomics and metabolomics in glomerulonephritis: a systematic literature review.

BACKGROUND: Glomerulonephritis inherently leads to the development of chronic kidney disease. It is the second most common diagnosis in patients requiring renal replacement therapy in the United Kingdom. Metabolomics and proteomics can characterise, identify and quantify an individual's protein and metabolite make-up. These techniques have been optimised and can be performed on samples including kidney tissue, blood and urine. Utilising omic techniques in nephrology can uncover disease pathophysiology and transform the diagnostics and treatment options for glomerulonephritis. OBJECTIVES: To evaluate the utility of metabolomics and proteomics using mass spectrometry and nuclear magnetic resonance in glomerulonephritis. METHODS: The systematic review was registered on PROSPERO (CRD42023442092). Standard and extensive Cochrane search methods were used. The latest search date was March 2023. Participants were of any age with a histological diagnosis of glomerulonephritis. Descriptive analysis was performed, and data presented in tabular form. An area under the curve or p-value was presented for potential biomarkers discovered. RESULTS: Twenty-seven studies were included (metabolomics (n = 9)), and (proteomics (n = 18)) with 1818 participants. The samples analysed were urine (n = 19) blood (n = 4) and biopsy (n = 6). The typical outcome themes were potential biomarkers, disease phenotype, risk of progression and treatment response. CONCLUSION: This review shows the potential of metabolomic and proteomic analysis to discover new disease biomarkers that may influence diagnostics and disease management. Further larger-scale research is required to establish the validity of the study outcomes, including the several proposed biomarkers.

Sarcopenia is linked to higher levels of B-type natriuretic peptide and its N-terminal fragment in heart failure: a systematic review and meta-analysis.

AIMS: Sarcopenia is linked to impaired physical function and exercise tolerance. The aim of this systematic review and meta-analysis was to examine the association of sarcopenia and low appendicular skeletal muscle (ASM) with biomarkers of cardiac function, B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP), in patients with heart failure (HF). METHODS AND RESULTS: From inception until May 2023, a systematic literature search of observational studies was undertaken utilizing the PubMed, Web of Science, Scopus, and Cochrane Library databases. A meta-analysis employing a random-effects model was used to compute the pooled effects (CRD42023418465). Overall, 16 studies were included in this systematic review and meta-analysis. Our main analysis showed that sarcopenia in HF was linked to significantly higher levels of BNP (MD: 87.76, 95% CI 20.74-154.78, I2 = 61%, P = 0.01) and NT-proBNP (MD: 947.45, 95% CI 98.97-1795.93, I2 = 35%, P = 0.03). Similarly, low ASM was associated with significantly higher levels of BNP (MD: 118.95, 95% CI 46.91-191.00, I2 = 93%, P < 0.01) and NT-proBNP (MD: 672.01, 95% CI 383.72-960.30, I2 = 2%, P < 0.01). The quality of the included cohort studies was considered moderate, using the binary AXIS checklist and the Cochrane Tool to Assess the Risk of Bias in Cohort Studies. CONCLUSIONS: In patients with HF, sarcopenia and reduced ASM are associated with considerably higher plasma levels of BNP and NT-proBNP. Future research is required to investigate whether sarcopenia may express dysregulated biomarkers of cardiac function.

Predicting stroke in Asian patients with atrial fibrillation using machine learning: A report from the KERALA-AF registry, with external validation in the APHRS-AF registry.

Atrial fibrillation (AF) is a significant risk factor for stroke. Based on the higher stroke associated with AF in the South Asian population, we constructed a one-year stroke prediction model using machine learning (ML) methods in KERALA-AF South Asian cohort. External validation was performed in the prospective APHRS-AF registry. We studied 2101 patients and 83 were to patients with stroke in KERALA-AF registry. The random forest showed the best predictive performance in the internal validation with receiver operator characteristic curve (AUC) and G-mean of 0.821 and 0.427, respectively. In the external validation, the light gradient boosting machine showed the best predictive performance with AUC and G-mean of 0.670 and 0.083, respectively. We report the first demonstration of ML's applicability in an Indian prospective cohort, although the more modest prediction on external validation in a separate multinational Asian registry suggests the need for ethnic-specific ML models.

Cerebrovascular, Cognitive and Cardiac Benefits of SGLT2 Inhibitors Therapy in Patients with Atrial Fibrillation and Type 2 Diabetes Mellitus: Results from a Global Federated Health Network Analysis.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are effective anti-diabetic drugs improving cardiovascular outcomes in type 2 diabetes mellitus (T2DM) patients. This study investigated cardiovascular, cerebrovascular and cognitive outcomes of SGLT2i therapy in patients with atrial fibrillation (AF) and T2DM. METHODS: Observational study using TriNetX, a global health research network of anonymised electronic medical records from real-world patients between January 2018 and December 2019. The network includes healthcare organisations globally but predominately in the United States. AF patients (ICD-10-CM code: I48) with T2DM were divided according to SGLT2i use or not, and balanced using propensity score matching (PSM). Patients were followed-up for 3-years. The primary endpoints were ischaemic stroke/transient ischemic attack (TIA), intracranial haemorrhage (ICH), and incident dementia. Secondary endpoints were incident heart failure and mortality. RESULTS: We identified 89,356 AF patients with T2DM of which 5061 (5.7%) were taking a SGLT2i. After PSM, 5049 patients (mean age 66.7 ± 10.6 years; 28.9% female) were included in each group. At 3-years follow-up, the risk of ischaemic stroke/TIA was higher in patients not receiving SGLT2i (HR 1.12, 95% CI 1.01-1.24) and for ICH (HR 1.57, 95% CI 1.25-1.99) and incident dementia (HR 1.66, 95% CI 1.30-2.12). Incident heart failure (HR 1.50, 95% CI 1.34-1.68) and mortality (HR 1.77, 95% CI 1.58-1.99) risks were increased in AF patients not receiving SGLT2i. CONCLUSIONS: In our large 'real world' analysis of patients with concomitant AF and T2DM, SGLT2i reduced the risk of cerebrovascular events, incident dementia, heart failure and death.

C-reactive protein levels are associated with early cardiac complications or death in patients with acute ischemic stroke: a propensity-matched analysis of a global federated health from the TriNetX network.

The role of inflammation in predicting early cardiac complications among stroke patients is unclear. Electronic medical records from TriNetX, a global federated health research network, were used for this retrospective analysis. Patients with ischemic stroke and C-Reactive Protein (CRP) levels measured within 24 h post-stroke were categorized into three groups: (i) < 1 mg/L, (ii)1-3 mg/L and (iii) > 3 mg/L. The primary outcome was a composite outcome of cardiac complications (heart failure (HF), ischemic heart disease, atrial fibrillation (AF), ventricular arrhythmias and Takotsubo cardiomyopathy) or death at 30 days from the index event. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). Of the 104,741 patients enrolled, 51% were female and the mean age was 66 ± 16 years. After PSM, a new cardiac complication or death within 30 days occurred in 5624 (33.1%) patients with CRP > 3 mg/L, in 4243 (25.6%) patients with CRP 1-3 mg/L and in 3891 (23.5%) patients with CRP < 1 mg/L. Patients with CRP levels of 1-3 mg/L and > 3 mg/L had higher risk of the composite outcome (HR 1.10, 95%CI 1.05-1.52; HR 1.51, 95%CI 1.45-1.58), death (HR 1.43, 95%CI 1.24-1.64; HR 3.50, 95%CI 3.01-3.96), HF (HR 1.08, 95%CI 1.01-1.16; HR 1.51, 95%CI 1.41-1.61), AF (HR 1.10, 95% CI:1.02-1.18; HR 1.42, 95%CI 1.33-1.52) and ventricular arrhythmias (HR 1.25, 95%CI 1.02-1.52; HR 1.67, 95% CI 1.38-2.01) compared to those with CRP < 1 mg/L. Ischemic heart disease were more common among patients with CRP levels > 3 mg/L compared to those with CRP < 1 mg/L (HR:1.33, 95% CI:1.26-1.40), while no association with Takotsubo cardiomyopathy was found in all the analyses. CRP levels within the first 24 h of an ischemic stroke predict 30-day cardiac complications or death.

An investigation into the effect of potential confounding patient and treatment parameters on human embryo morphokinetics.

OBJECTIVE: To determine the effect of patient and treatment parameters on 19 embryo morphokinetic parameters using pronuclear fading as time zero. DESIGN: Single-site, retrospective cohort analysis. SETTING: Fertility treatment center. PATIENTS(S): Patients undergoing treatment between September 2014 and January 2016 (n = 639) whose embryos were cultured in the EmbryoScope for 6 days (n = 2,376). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Multiple regression analysis of body mass index; maternal age; infertility diagnosis; treatment type; suppression protocol on time to each cellular division (tn): t2, t3, t4, t5, t6, t7, t8, t9, time to start of compaction (tM), start of blastulation (tSB), full blastocyst (tB); and interval measurements: s2, s3, cc2, cc3, cc4, t9-tM, tM-tSB, and tSB-tB. Beta coefficients were analyzed to quantify any significant effects. RESULT(S): Embryos appeared to be subtly affected by patient and treatment parameters, exhibiting complex relationships between various morphokinetic parameters and specific patient and treatment factors, rather than a systemic effect. CONCLUSION(S): These findings outline the need for the consideration of confounding factors when assessing an embryo's ability to achieve implantation. Although morphokinetic parameters have been related to embryo viability, it is likely that this will vary depending on the embryo's origin.

Diagnostic Accuracy of a High-Sensitivity Cardiac Troponin Assay with a Single Serum Test in the Emergency Department.

OBJECTIVES: We sought to evaluate diagnostic accuracy of a high-sensitivity cardiac troponin I (hs-cTnI) assay for acute coronary syndromes (ACS) in the emergency department (ED). The assay has high precision at low concentrations and can detect cTnI in 96.8% of healthy individuals. METHODS: In successive prospective multicenter studies ("testing" and "validation"), we included ED patients with suspected ACS. We drew blood for hs-cTnI [Singulex Clarity® cTnI; 99th percentile, 8.67 ng/L; limit of detection (LoD), 0.08 ng/L] on arrival. Patients also underwent hs-cTnT (Roche Elecsys) testing over ≥3 h. The primary outcome was an adjudicated diagnosis of ACS, defined as acute myocardial infarction (AMI; prevalent or incident), death, or revascularization within 30 days. RESULTS: The testing and validation studies included 665 and 2470 patients, respectively, of which 94 (14.1%) and 565 (22.9%) had ACS. At a 1.5-ng/L cutoff, hs-cTnI had good sensitivity for AMI in both studies (98.7% and 98.1%, respectively) and would have "ruled out" 40.1% and 48.9% patients. However, sensitivity was lower for ACS (95.7% and 90.6%, respectively). At a 0.8-ng/L cutoff, sensitivity for ACS was higher (97.5% and 97.9%, ruling out 28.6% patients in each cohort). The hs-cTnT assay had similar performance at the LoD (24.6% ruled out; 97.2% sensitivity for ACS). CONCLUSIONS: The hs-cTnI assay could immediately rule out AMI in 40% of patients and ACS in >25%, with similar accuracy to hs-cTnT at the LoD. Because of its high precision at low concentrations, this hs-cTnI assay has favorable characteristics for this clinical application.

Diagnostic accuracy of the T-MACS decision aid with a contemporary point-of-care troponin assay.

OBJECTIVES: The rapid turnaround time of point-of-care (POC) cardiac troponin (cTn) assays is highly attractive for crowded emergency departments (EDs). We evaluated the diagnostic accuracy of the Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid with a POC cTn assay. METHODS: In a prospective diagnostic accuracy study at eight EDs, we included patients with suspected acute coronary syndromes (ACS). Blood drawn on arrival and 3 hours later was analysed for POC cTnI (i-Stat, Abbott Point of Care). The primary outcome was a diagnosis of ACS, which included both an adjudicated diagnosis of acute myocardial infarction (AMI) based on serial laboratory cTn testing and major adverse cardiac events (death, AMI or coronary revascularisation) within 30 days. RESULTS: Of 716 patients included, 105 (14.7%) had ACS. Using serial POC cTnI concentrations over 3 hours could have 'ruled out' ACS in 198 (31.2%) patients with a sensitivity of 99.0% (95% CI 94.4% to 100.0%) and negative predictive value 99.5% (95% CI 96.5% to 99.9%). No AMIs were missed. T-MACS 'ruled in' ACS for 65 (10.4%) patients with a positive predictive value of 91.2% (95% CI 82.1% to 95.9%) and specificity 98.9% (97.6% to 99.6%). CONCLUSION: With a POC cTnI assay, T-MACS could 'rule out' ACS for approximately one-third of patients within 3 hours while 'ruling in' ACS for another 10%. The rapid turnaround time and portability of the POC assay make this an attractive pathway for use in crowded EDs or urgent care centres. Future work should also evaluate use in the prehospital environment.

Acetylcholine Inhibits Monomeric C-Reactive Protein Induced Inflammation, Endothelial Cell Adhesion, and Platelet Aggregation; A Potential Therapeutic?

Objectives: In this study, we examined the possibility of using targeted antibodies and the potential of small molecular therapeutics (acetylcholine, nicotine and tacrine) to block the pro-inflammatory and adhesion-related properties of monomeric C-reactive protein (mCRP). Methods: We used three established models (platelet aggregation assay, endothelial leucocyte binding assay and monocyte inflammation via ELISA and Western blotting) to assess the potential of these therapeutics. Results: The results of this study showed that monocyte induced inflammation (raised tumor necrosis factor-alpha-TNF-α) induced by mCRP was significantly blocked in the presence of acetylcholine and nicotine, whilst tacrine and targeted antibodies (clones 8C10 and 3H12) had less of or no significant effects. Western blotting confirmed the ability of acetylcholine to inhibit mCRP-induced cell signaling phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2), p38 and nuclear factor-kappa B (NF-κB). There was no evidence of direct binding between small molecules and mCRP. mCRP also induced endothelial cell-monocyte adhesion in a dose dependent fashion, however, both acetylcholine and nicotine as well as targeting antibodies notably inhibited adhesion. Finally, we investigated their effects on mCRP-induced platelet aggregation. All three small molecules significantly attenuated platelet aggregation as did the antibody 8C10, although 3H12 had a weaker effect. Discussion: Acetylcholine and to a lesser extent nicotine show potential for therapeutic inhibition of mCRP-induced inflammation and cell and platelet adhesion. These results highlight the potential of targeted antibodies and small molecule therapeutics to inhibit the binding of mCRP by prevention of membrane interaction and subsequent activation of cellular cascade systems, which produce the pro-inflammatory effects associated with mCRP.

Preliminary investigation of the prevalence and implantation potential of abnormal embryonic phenotypes assessed using time-lapse imaging.

This retrospective, single site observational study aimed to delineate five abnormal embryonic developmental phenotypes, assessing their prevalence, development potential and suitability for inclusion in embryo selection models for IVF. In total, 15,819 embryos from 4559 treatment cycles cultured in EmbryoScope® incubators between January 2014 and January 2016 were included. Time-lapse images were assessed retrospectively for five abnormal embryo phenotypes: direct cleavage, reverse cleavage, absent cleavage, chaotic cleavage and cell lysis. The prevalence of each abnormal phenotype was assessed. Final embryo disposition, embryo quality and implantation rate were determined and compared with a control embryo cohort. The collective prevalence for the five abnormal phenotypes was 11.4%; chaotic cleavage and direct cleavage together constituted 9.7%. Implantation rates were 17.4%, 0%, 25%, 2.1% and 0% for direct, reverse, absent, chaotic cleavage and cell lysis, respectively. The overall implantation rate for all abnormal embryos with known implantation status was significantly lower compared with the control population (6.9% versus 38.7%, P < 0.0001). The proportion of good quality embryos in each category of abnormal cleavage remained below 25%. Embryos exhibiting an abnormal phenotype may have reduced developmental capability, manifested in both embryo quality and implantation potential, when compared with embryos of normal phenotype.

Examining the efficacy of six published time-lapse imaging embryo selection algorithms to predict implantation to demonstrate the need for the development of specific, in-house morphokinetic selection algorithms.

OBJECTIVE: To study the efficacy of six embryo-selection algorithms (ESAs) when applied to a large, exclusive set of known implantation embryos. DESIGN: Retrospective, observational analysis. SETTING: Fertility treatment center. PATIENT(S): Women undergoing a total of 884 in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment cycles (977 embryos) between September 2014 and September 2015 with embryos cultured using G-TL (Vitrolife) at 5% O2, 89% N2, 6% CO2, at 37°C in EmbryoScope instruments. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Efficacy of each ESA to predict implantation defined using specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), area under the receiver operating characteristic curve (AUC), and likelihood ratio (LR), with differences in implantation rates (IR) in the categories outlined by each ESA statistically analyzed (Fisher's exact and Kruskal-Wallis tests). RESULT(S): When applied to an exclusive cohort of known implantation embryos, the PPVs of each ESA were 42.57%, 41.52%, 44.28%, 38.91%, 38.29%, and 40.45%. The NPVs were 62.12%, 68.26%, 71.35%, 76.19%, 61.10%, and 64.14%. The sensitivity was 16.70%, 75.33%, 72.94%, 98.67%, 51.19%, and 62.33% and the specificity was 85.83%, 33.33%, 42.33%, 2.67%, 48.17%, and 42.33%, The AUC were 0.584, 0.558, 0.573, 0.612, 0.543, and 0.629. Two of the ESAs resulted in statistically significant differences in the embryo classifications in terms of IR. CONCLUSION(S): These results highlight the need for the development of in-house ESAs that are specific to the patient, treatment, and environment. These data suggest that currently available ESAs may not be clinically applicable and lose their diagnostic value when externally applied.

Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid: single biomarker re-derivation and external validation in three cohorts.

BACKGROUND: The original Manchester Acute Coronary Syndromes model (MACS) 'rules in' and 'rules out' acute coronary syndromes (ACS) using high sensitivity cardiac troponin T (hs-cTnT) and heart-type fatty acid binding protein (H-FABP) measured at admission. The latter is not always available. We aimed to refine and validate MACS as Troponin-only Manchester Acute Coronary Syndromes (T-MACS), cutting down the biomarkers to just hs-cTnT. METHODS: We present secondary analyses from four prospective diagnostic cohort studies including patients presenting to the ED with suspected ACS. Data were collected and hs-cTnT measured on arrival. The primary outcome was ACS, defined as prevalent acute myocardial infarction (AMI) or incident death, AMI or coronary revascularisation within 30 days. T-MACS was built in one cohort (derivation set) and validated in three external cohorts (validation set). RESULTS: At the 'rule out' threshold, in the derivation set (n=703), T-MACS had 99.3% (95% CI 97.3% to 99.9%) negative predictive value (NPV) and 98.7% (95.3%-99.8%) sensitivity for ACS, 'ruling out' 37.7% patients (specificity 47.6%, positive predictive value (PPV) 34.0%). In the validation set (n=1459), T-MACS had 99.3% (98.3%-99.8%) NPV and 98.1% (95.2%-99.5%) sensitivity, 'ruling out' 40.4% (n=590) patients (specificity 47.0%, PPV 23.9%). T-MACS would 'rule in' 10.1% and 4.7% patients in the respective sets, of which 100.0% and 91.3% had ACS. C-statistics for the original and refined rules were similar (T-MACS 0.91 vs MACS 0.90 on validation). CONCLUSIONS: T-MACS could 'rule out' ACS in 40% of patients, while 'ruling in' 5% at highest risk using a single hs-cTnT measurement on arrival. As a clinical decision aid, T-MACS could therefore help to conserve healthcare resources.

Embryos cultured in a time-lapse system result in superior treatment outcomes: a strict matched pair analysis.

A retrospective strict matched-pair analysis of 728 treatment cycles between January 2011 and September 2014 was performed. A total of 364 treatment cycles, where all embryos were cultured and examined in EmbryoScope®, were matched to treatment cycles where all the embryos were cultured in a standard incubator with conventional morphological examination. Matching was performed for patient age, number of oocytes collected, treatment type and date of oocyte collection (± six months). The clinical (CPR), implantation (IR), live birth (LBR) and miscarriage rates (MR) were calculated and considered significant when p < 0.05 (Chi-square test). CPR, IR and LBR were found to be significantly higher in the time-lapse system (TLS) group compared to the standard incubation group (CPR = 44.8% versus 36.5%, p = 0.02; IR = 39.3% versus 32.2%, p = 0.03; and LBR = 43.1% versus 33.8%, p = 0.01). Although there was a 5.5% decrease in the MR for the TLS group when compared to the standard incubation group, this result was not statistically significant (18.9% versus 24.4%, p = 0.19). There is a paucity of well-designed studies to confirm that embryos cultured and examined in TLS can result in superior treatment outcomes, and this strict-matched pair analysis with a large cohort of treatment cycles indicates the advantage of using TLS.

Mesenchymal Stem Cells Loaded with p5, Derived from CDK5 Activator p35, Inhibit Calcium-Induced CDK5 Activation in Endothelial Cells.

The potential use of stem cells as therapeutics in disease has gained momentum over the last few years and recently phase-I clinical trials have shown favourable results in treatment of a small cohort of acute stroke patients. Similarly, they have been used in preclinical models drug-loaded for the effective treatment of solid tumours. Here we have characterized uptake and release of a novel p5-cyclin-dependent kinase 5 (CDK5) inhibitory peptide by mesenchymal stem cells and showed release levels capable of blocking aberrant cyclin-dependent kinase 5 (CDK5) signaling pathways, through phosphorylation of cyclin-dependent kinase 5 (CDK5) and p53. These pathways represent the major acute mechanism stimulating apoptosis after stroke and hence its modulation could benefit patient recovery. This work indicates a potential use for drug-loaded stem cells as delivery vehicles for stroke therapeutics and in addition as anticancer receptacles particularly, if a targeting and/or holding mechanism can be defined.

The interobserver reliability of a novel qualitative point of care assay for heart-type fatty acid binding protein.

BACKGROUND: Heart-type fatty acid-binding protein (h-FABP) may help to improve the early diagnosis of acute coronary syndromes in patients presenting to the Emergency Department (ED) with chest pain. A novel qualitative point of care h-FABP lateral flow immunoassay (True Rapid, FABPulous BV) could provide results to clinicians within just 5min. Given the qualitative nature of this test and prior to evaluation in a large diagnostic study, we aimed to determine inter-observer reliability when interpreted contemporaneously by staff in the ED. METHODS: In a nested prospective cohort study including adult patients with suspected cardiac chest pain, venous blood samples were tested for h-FABP (FABPulous BV) on arrival and 3h later. Each test result was independently interpreted by two different investigators after 5min. The investigators were blinded to each other's interpretation and recorded their findings on separate case report forms. We determined interobserver reliability by calculating the Cohen's kappa score and 95% confidence intervals. RESULTS: A total of 43 test results (from 31 patients) were each interpreted by two independent investigators. Absolute agreement between investigators was 93.0%, with a Cohen's kappa of 0.81 (95% CI 0.6-1.0), indicating near perfect agreement. In total there were three (7.0%) disagreements. In each case one investigator reported a 'weak positive' result while the other interpreted the result as 'negative'. CONCLUSIONS: These findings demonstrate the interobserver reliability of a qualitative point of care h-FABP assay. Further work must evaluate diagnostic accuracy and determine the clinical implications of the small rate of disagreement.