Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares ...many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products, and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the "liquid brain biopsy." A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.
Tricuspid annular plane systolic excursion (TAPSE) is an echocardiographic measurement to assess right ventricular systolic function in adults. The aim of this study was to determine growth-related ...changes in TAPSE to establish references values.
A prospective study was conducted in a group of 640 healthy pediatric patients (age range, 1 day to 18 years; body surface area range, 0.12-2.25 m(2)). The effects of age and body surface area on TAPSE were determined.
TAPSE ranged from a mean of 0.91 cm (z score +/- 3, 0.56-1.26 cm) in neonates to 2.47 cm (z score +/- 3, 1.84-3.10 cm) in 18-year-olds. TAPSE values showed positive correlations with age and body surface area. There was no significant difference in TAPSE values between female or male children.
In this study, z scores of TAPSE values were calculated and percentile charts were established to serve as reference data for ready application in patients with congenital heart disease in the future.
Individualizing blood pressure targets could improve organ perfusion compared with current practices. In this study we assess whether hypotension defined by cerebral autoregulation monitoring vs ...standard definitions is associated with elevation in the brain-specific injury biomarker glial fibrillary acidic protein plasma levels (GFAP).
Plasma GFAP levels were measured in 121 patients undergoing cardiac operations after anesthesia induction, at the conclusion of the operation, and on postoperative day 1. Cerebral autoregulation was monitored during the operation with the cerebral oximetry index, which correlates low-frequency changes in mean arterial pressure (MAP) and regional cerebral oxygen saturation. Blood pressure was recorded every 15 minutes in the intensive care unit. Hypotension was defined based on autoregulation data as an MAP below the optimal MAP (MAP at the lowest cerebral oximetry index) and based on standard definitions (systolic blood pressure decrement >20%, >30% from baseline, or <100 mm Hg, or both).
MAP (mean ± standard deviation) in the intensive care unit was 74 ± 7.3 mm Hg; optimal MAP was 78 ± 12.8 mm Hg (p = 0.008). The incidence of hypotension varied from 22% to 37% based on standard definitions but occurred in 54% of patients based on the cerebral oximetry index (p < 0.001). There was no relationship between standard definitions of hypotension and plasma GFAP levels, but MAP of less than optimal was positively related with postoperative day 1 GFAP levels (coefficient, 1.77; 95% confidence interval, 1.27 to 2.48; p = 0.001) after adjusting for GFAP levels at the conclusion of the operation and low cardiac output syndrome.
Individualizing blood pressure management using cerebral autoregulation monitoring may better ensure brain perfusion than current practice.
Acute kidney injury (AKI) is a common complication after cardiac surgery. While AKI severity is known to be associated with increased risk of short-term outcomes, its long-term impact is less well ...understood.
Adult patients undergoing isolated coronary artery bypass graft surgery at eight centers were enrolled into the Northern New England biomarker registry (n = 1,610). Patients were excluded if they had renal failure (n = 15) or died during index admission (n = 38). Severity of AKI was defined using the Acute Kidney Injury Network (AKIN). We linked our cohort to national Medicare and state all-payer claims to ascertain readmissions and to the National Death Index to ascertain survival. Kaplan-Meier and multivariate Cox proportional hazards modeling was conducted for time to readmission and death over 5 years.
Within 5 years, 513 patients (33.8%) had AKI with AKIN stage 1 (29.9%) and stage 2 to 3 (3.9%). There were 620 readmissions (39.9%) and 370 deaths (23.8%). After adjustment, stage 1 AKI patients had a 31% increased risk of readmission (95% confidence interval CI: 1.10 to 1.57), whereas stage 2 or 3 patients had a 98% increased risk (95% CI: 1.41 to 2.78) compared with patients having no AKI. Relative to patients without AKI, stage 1 patients had a 56% increased risk of mortality (95% CI: 1.14 to 2.13), whereas stage 2 or 3 patients had a 3.5 times higher risk (95% CI: 2.16 to 5.60).
Severity of AKI using the AKIN stage criteria is associated with a significantly increased risk of 5-year readmission and mortality. Our findings suggest that efforts to reduce AKI in the perioperative period may have a significant long-term impact on patients and payers in reducing mortality and health care utilization.
The Lung Master Protocol (Lung-MAP, S1400) is a groundbreaking clinical trial designed to advance the efficient development of targeted therapies for squamous cell carcinoma (SCC) of the lung. There ...are no approved targeted therapies specific to advanced lung SCC, although The Cancer Genome Atlas project and similar studies have detected a significant number of somatic gene mutations/amplifications in lung SCC, some of which are targetable by investigational agents. However, the frequency of these changes is low (5%-20%), making recruitment and study conduct challenging in the traditional clinical trial setting. Here, we describe our approach to development of a biomarker-driven phase II/II multisubstudy "Master Protocol," using a common platform (next-generation DNA sequencing) to identify actionable molecular abnormalities, followed by randomization to the relevant targeted therapy versus standard of care.
Brain-derived neurotrophic factor (BDNF) is important for neuronal survival and regeneration. We investigated the diagnostic and prognostic values of serum BDNF in traumatic brain injury (TBI). We ...examined serum BDNF in two independent cohorts of TBI cases presenting to the emergency departments (EDs) of the Johns Hopkins Hospital (JHH; n = 76) and San Francisco General Hospital (SFGH, n = 80), and a control group of JHH ED patients without TBI (n = 150). Findings were subsequently validated in the prospective, multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot study (n = 159). We investigated the association between BDNF, glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1) and recovery from TBI at 6 months in the TRACK-TBI Pilot cohort. Incomplete recovery was defined as having either post-concussive syndrome or a Glasgow Outcome Scale Extended score <8 at 6 months. Median day-of-injury BDNF concentrations (ng/mL) were lower among TBI cases (JHH TBI, 17.5 and SFGH TBI, 13.8) than in JHH controls (60.3; p = 0.0001). Among TRACK-TBI Pilot subjects, median BDNF concentrations (ng/mL) were higher in mild (8.3) than in moderate (4.3) or severe TBI (4.0; p = 0.004. In the TRACK-TBI cohort, the 75 (71.4%) subjects with very low BDNF values (i.e., <the 1st percentile for non-TBI controls, <14.2 ng/mL) had higher odds of incomplete recovery than those who did not have very low values (odds ratio, 4.0; 95% confidence interval CI: 1.5-11.0). The area under the receiver operator curve for discriminating complete and incomplete recovery was 0.65 (95% CI: 0.52-0.78) for BDNF, 0.61 (95% CI: 0.49-0.73) for GFAP, and 0.55 (95% CI: 0.43-0.66) for UCH-L1. The addition of GFAP/UCH-L1 to BDNF did not improve outcome prediction significantly. Day-of-injury serum BDNF is associated with TBI diagnosis and also provides 6-month prognostic information regarding recovery from TBI. Thus, day-of-injury BDNF values may aid in TBI risk stratification.
A novel organic field effect transistor (OFET)‐based biosensor is described for label‐free glial fibrillary acidic protein detection. This study reports the first use of an extended solution gate ...structure where the sensing area and the organic semiconductor are separated, and a reference electrode is not needed. Different molecular weight polyethylene glycols (PEGs) are mixed into the bioreceptor layer to help extend the Debye screening length. The drain current change is significantly increased with the help of higher molecular weight PEGs, as they are known to reduce the dielectric constant. This study also investigates the sensing performance under different gate voltage (V
g). The sensitivity increases after the V
g is decreased from −5 to −2 V because the lower V
g is much closer to the OFET threshold voltage and the influence of attached negatively charged proteins becomes more apparent. Finally, the selectivity experiments toward different interferents are performed. The stability and selectivity are promising for clinical applications.
A novel organic field effect transistor‐based biosensor is described for label‐free glial fibrillary acidic protein detection. Different molecular weight polyethylene glycols are mixed into the bioreceptor layer to help extend the Debye screening length. The sensitivity increases while V
g decreases since lower V
g is much closer to the OFET threshold voltage and the influence of attached proteins becomes more apparent.
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