Background The management of chronic kidney disease–mineral and bone disorder requires the assessment of bone turnover, which most often is based on parathyroid hormone (PTH) concentration, the ...utility of which remains controversial. Study Design Cross-sectional retrospective diagnostic test study. Setting & Participants 492 dialysis patients from Brazil, Portugal, Turkey, and Venezuela with prior bone biopsy and stored (−20°C) serum. Index Tests Samples were analyzed for PTH (intact iPTH and whole PTH), bone-specific alkaline phosphatase (bALP), and amino-terminal propeptide of type 1 procollagen (P1NP). Reference Test Bone histomorphometric assessment of turnover (bone formation rate/bone surface BFR/BS) and receiver operating characteristic curves for discriminating diagnostic ability. Results The biomarkers iPTH and bALP or combinations thereof allowed discrimination of low from nonlow and high from nonhigh BFR/BS, with an area under the receiver operating characteristic curve > 0.70 but < 0.80. Using iPTH level, the best cutoff to discriminate low from nonlow BFR/BS was <103.8 pg/mL, and to discriminate high from nonhigh BFR/BS was >323.0 pg/mL. The best cutoff for bALP to discriminate low from nonlow BFR/BS was <33.1 U/L, and for high from nonhigh BFR/BS, 42.1 U/L. Using the KDIGO practice guideline PTH values of greater than 2 but less than 9 times the upper limit of normal, sensitivity and specificity of iPTH level to discriminate low from nonlow turnover bone disease were 65.7% and 65.3%, and to discriminate high from nonhigh were 37.0% and 85.8%, respectively. Limitations Cross-sectional design without consideration of therapy. Potential limited generalizability with samples from 4 countries. Conclusions The serum biomarkers iPTH, whole PTH, and bALP were able to discriminate low from nonlow BFR/BS, whereas iPTH and bALP were able to discriminate high from nonhigh BFR/BS. Prospective studies are required to determine whether evaluating trends in biomarker concentrations could guide therapeutic decisions.
Abstract Purpose To establish prognostic genomic biomarkers for patients with metastatic clear cell renal cell carcinoma (ccRCC). Materials and methods We identified 60 patients who presented with ...metastatic ccRCC at our institution between 2001 and 2015 and had genomic sequencing on their primary tumor. We pooled these patients with 107 other patients with the same inclusion criteria from three well-known public databases. Five commonly mutated genes were chosen for analysis: VHL , PBRM1 , BAP1 , SETD2 , and KDM5C . Overall survival (OS) was estimated using the Kaplan-Meier method and the log-rank test was used for comparisons between groups. Results Median OS in the cohort was 2.5 years. Higher Fuhrman grade was associated with decreased median OS ( P <0.001). Mutations in SETD2 ( P = 0.027) and KDM5C ( P = 0.019) were associated with reduced risk of death (hazard ratio HR = 0.58 95% CI: 0.35–0.94 and HR = 0.43 95% CI: 0.22–0.85, respectively). BAP1 mutations ( P = 0.008) were associated with increased risk of death (HR = 1.81 95% CI: 1.16–2.83). There were significantly more female patients with a BAP1 mutation than females in the overall cohort ( P = 0.001). Conclusions Mutations in BAP1 negatively affected OS, whereas SETD2 and KDM5C mutations were associated with prolonged OS in our pooled cohort of 167 patients with metastatic ccRCC. Our results expand upon efforts at understanding genomic biomarkers in localized disease. Those efforts set the stage for our novel investigation examining associations of select recurrent somatic mutations in stage IV patients with ccRCC.
Objectives To identify variables that predict extubation success in extremely preterm infants born <28 weeks gestational age (GA), and to compare outcomes between those who had successful or failed ...extubation. Study design A secondary analysis of data from a randomized trial of postextubation respiratory support that included 174 extremely preterm infants. “Extubation success” was defined as not requiring reintubation within 7 days, and “extubation failure” the converse. Predictive variables that were different between groups were included in a multivariable logistic regression model. Results Sixty-eight percent of infants were successfully extubated. Compared with those infants who had extubation failure, they had a higher GA and birth weight, were extubated earlier, were more often exposed to prolonged ruptured membranes, more often avoided intubation in the delivery room, had a higher pre-extubation pH, and had lower mean pre-extubation fraction of inspired oxygen and partial pressure of carbon dioxide (PCO2 ). Only GA and PCO2 remained significant in the multivariable analysis (area under a receiver operating characteristic curve = 0.81). Extubation failure was associated with death, bronchopulmonary dysplasia, severe retinopathy of prematurity, patent ductus arteriosus ligation, and longer durations of respiratory support, oxygen supplementation, and hospitalization. When adjusted for allocated treatment in the randomized trial, GA, and birth weight z-score, extubation failure remained associated with death before discharge and prolonged respiratory support and hospitalization. Conclusions In extremely preterm infants, higher GA and lower pre-extubation PCO2 predicted extubation success. Infants in whom extubation failed were more likely to die and have prolonged respiratory support and hospitalization. Trial registration Australian New Zealand Clinical Trials Network: ACTRN12610000166077.
Abstract Manley GT, Diaz-Arrastia R, Brophy M, Engel D, Goodman C, Gwinn K, Veenstra TD, Ling G, Ottens AK, Tortella F, Hayes RL. Common data elements for traumatic brain injury: recommendations from ...the Biospecimens and Biomarkers Working Group. Recent advances in genomics, proteomics, and biotechnology have provided unprecedented opportunities for translational research and personalized medicine. Human biospecimens and biofluids represent an important resource from which molecular data can be generated to detect and classify injury and to identify molecular mechanisms and therapeutic targets. To date, there has been considerable variability in biospecimen and biofluid collection, storage, and processing in traumatic brain injury (TBI) studies. To realize the full potential of this important resource, standardization and adoption of best practice guidelines are required to insure the quality and consistency of these specimens. The aim of the Biospecimens and Biomarkers Working Group was to provide recommendations for core data elements for TBI research and develop best practice guidelines to standardize the quality and accessibility of these specimens. Consensus recommendations were developed through interactions with focus groups and input from stakeholders participating in the interagency workshop on Standardization of Data Collection in TBI and Psychological Health held in Washington, DC, in March 2009. With the adoption of these standards and best practices, future investigators will be able to obtain data across multiple studies with reduced costs and effort and accelerate the progress of genomic, proteomic, and metabolomic research in TBI.
Summary Effective resuscitation of the newborn infant has the potential to save many lives around the world and reduce disabilities in children who survive peripartum asphyxia. In this Series paper, ...we highlight some of the important advances in the understanding of how best to resuscitate newborn infants, which includes monitoring techniques to guide resuscitative efforts, increasing awareness of the adverse effects of hyperoxia, delayed umbilical cord clamping, the avoidance of routine endotracheal intubation for extremely preterm infants, and therapeutic hypothermia for hypoxic–ischaemic encephalopathy. Despite the challenges of performing high-quality clinical research in the delivery room, researchers continue to refine and advance our knowledge of effective resuscitation of newborn infants through scientific experiments and clinical trials.
OBJECTIVES: We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate–severe traumatic brain injury (TBI) and 2) examine the association of early ...beta-blocker exposure with functional and clinical outcomes following injury. DESIGN: Retrospective cohort study. SETTING: ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. PATIENTS: Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate–severe TBI (Glasgow Coma Scale of <13) were admitted to the ICU after a blunt TBI. INTERVENTIONS: None. MEASUREMENTS: Primary exposure was a beta blocker during the first 7 days in the ICU, with a primary outcome of 6-month Glasgow Outcome Scale-Extended (GOSE). Secondary outcomes included: length of hospital stay, in-hospital mortality, 6-month and 12-month mortality, 12-month GOSE score, and 6-month and 12-month measures of disability, well-being, quality of life, and life satisfaction. MAIN RESULTS: Of the 450 eligible participants, 57 (13%) received early beta blockers (BB + group). The BB + group was on average older, more likely to be on a preinjury beta blocker, and more likely to have a history of hypertension. In the BB + group, 34 participants (60%) received metoprolol only, 19 participants (33%) received propranolol only, 3 participants (5%) received both, and 1 participant (2%) received atenolol only. In multivariable regression, there was no difference in the odds of a higher GOSE score at 6 months between the BB + group and BB – group (odds ratio = 0.86; 95% CI, 0.48–1.53). There was no association between BB exposure and secondary outcomes. CONCLUSIONS: About one-sixth of subjects in our study received early beta blockers, and within this group, dose, and timing of beta-blocker administration varied substantially. No significant differences in GOSE score at 6 months were demonstrated, although our ability to draw conclusions is limited by overall low total doses administered compared with prior studies.
The reactions γp→ηp and γp→η^{'}p are measured from their thresholds up to the center-of-mass energy W=1.96 GeV with the tagged-photon facilities at the Mainz Microtron, MAMI. Differential cross ...sections are obtained with unprecedented statistical accuracy, providing fine energy binning and full production-angle coverage. A strong cusp is observed in the total cross section for η photoproduction at the energies in the vicinity of the η^{'} threshold, W=1896 MeV (E_{γ}=1447 MeV). Within the framework of a revised ηMAID isobar model, the cusp, in connection with a steep rise of the η^{'} total cross section from its threshold, can only be explained by a strong coupling of the poorly known N(1895)1/2^{-} state to both ηp and η^{'}p. Including the new high-accuracy results in the ηMAID fit to available η and η^{'} photoproduction data allows the determination of the N(1895)1/2^{-} properties.
Abstract Objective Mild traumatic brain injury (mTBI) patients are frequently admitted to high levels of care despite limited evidence suggesting benefit. Such decisions may contribute to the ...significant cost of caring for mTBI patients. Understanding the factors that drive disposition decision making and how disposition is associated with outcomes is necessary for developing an evidence-base supporting disposition decisions. We evaluated factors associated with emergency department triage of mTBI patients to 1 of 3 levels of care: home, inpatient floor, or intensive care unit (ICU). Methods This multicenter, prospective, cohort study included patients with isolated head trauma, a cranial computed tomography as part of routine care, and a Glasgow Coma Scale (GCS) score of 13 to 15. Data analysis was performed using multinomial logistic regression. Results Of the 304 patients included, 167 (55%) were discharged home, 76 (25%) were admitted to the inpatient floor, and 61 (20%) were admitted to the ICU. In the multivariable model, admission to the ICU, compared with floor admission, varied by study site, odds ratio (OR) 0.18 (95% confidence interval CI, 0.06-0.57); antiplatelet/anticoagulation therapy, OR 7.46 (95% CI, 1.79-31.13); skull fracture, OR 7.60 (95% CI, 2.44-23.73); and lower GCS, OR 2.36 (95% CI, 1.05-5.30). No difference in outcome was observed between the 3 levels of care. Conclusion Clinical characteristics and local practice patterns contribute to mTBI disposition decisions. Level of care was not associated with outcomes. Intracranial hemorrhage, GCS 13 to 14, skull fracture, and current antiplatelet/anticoagulant therapy influenced disposition decisions.
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