Prior traumatic brain injury is a risk factor for in-hospital mortality in moderate to severe traumatic brain injury: a TRACK-TBI cohort study.

OBJECTIVES: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort. METHODS: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury. RESULTS: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months. CONCLUSIONS: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed. LEVEL OF EVIDENCE: IV. TRIAL REGISTRATION NUMBER: NCT02119182

Investigation of Genetic Variation Underlying Central Obesity amongst South Asians

The LOLIPOP study is supported by the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust, the British Heart Foundation (SP/04/002), the Medical Research Council (G0601966,G0700931), the Wellcome Trust (084723/Z/08/Z), and the NIHR (RP-PG-0407-10371). The work was carried out in part at the NIHR/Wellcome Trust Imperial Clinical Research Facility. The Sikh Diabetes Study is supported by National Institute of Health grants KO1TW006087, funded by the Fogarty International Center, R01DK082766, funded by National Institute of Diabetes and Digestive and Kidney Diseases, and a seed grant from University of Oklahoma Health Sciences Center, Oklahoma City, USA. The Mauritius Family Study is supported by the Mauritius Ministry of Health and Quality of Life, Australian Government National Health and Medical Research Council NHMRC project grant numbers 1020285 and 1037916, the Victorian Government’s OIS Program, and partly funded by US National Institutes of Health Grant DK-25446. We thank the participants and research staff who made the study possible.South Asians are 1/4 of the world’s population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P<5x10-8; variants showing equivocal association with WHR (P<1x10-5) did not replicate at P<0.05 in an independent cohort of South Asians (N = 1,922) or in published, predominantly European meta-analysis data. In the targeted analyses of 122,391 population-specific SNPs we also found no associations with WHR in South Asians at P<0.05 after multiple testing correction. Exome-wide analyses showed no new associations between genetic variants and WHR in South Asians, either individually at P<1.5x10-6 or grouped by gene locus at P<2.5x10−6. At known WHR loci, risk allele frequencies were not higher in South Asians compared to Europeans (P = 0.77), while effect sizes were unexpectedly smaller in South Asians than Europeans (P<5.0x10-8). Our findings argue against an important contribution for population-specific or cosmopolitan genetic variants underlying the increased risk of central obesity in South Asians compared to Europeans.Yeshttp://www.plosone.org/static/editorial#pee

Ion homeostasis in the Chloroplast

peer reviewedThe chloroplast is an organelle of high demand for macro- and micro-nutrient ions, which are required for the maintenance of the photosynthetic process. To avoid deficiency while preventing excess, homeostasis mechanisms must be tightly regulated. Here, we describe the needs for nutrient ions in the chloroplast and briefly highlight their functions in the chloroplastidial metabolism. We further discuss the impact of nutrient deficiency on chloroplasts and the acclimation mechanisms that evolved to preserve the photosynthetic apparatus. We finally present what is known about import and export mechanisms for these ions. Whenever possible, a comparison between cyanobacteria, algae and plants is provided to add an evolutionary perspective to the description of ion homeostasis mechanisms in photosynthesis

The Effect of Oral Care on Intracranial Pressure in Critically Ill Adults

A major goal in the care of patients with neurological problems is to prevent or minimize episodes of increased intracranial pressure (ICP). Elevations in ICP in response to nursing interventions have been acknowledged since the 1960s when ICP monitoring was first introduced in the clinical setting. Until recently, few studies have specifically examined the effect of oral care on ICP, and oral care and other hygiene measures were combined or not specified, prohibiting a direct interpretation of the influence of oral care alone on ICP. The purpose of this study was to describe the relationship between routine oral care interventions and the changes in ICP specifically focusing on the effect of intensity and duration of this intervention. Twenty-three patients with a clinical condition requiring ICP monitoring were enrolled over a 12-month period. Oral care provided by neuroscience intensive care nurses was observed and videotaped. Characteristics of the intervention were documented including products used, patient positioning, and duration of the intervention. A 1-5 subjective scale was used to score intensity of oral care. Wrist actigraphy data were collected from the nurses to provide an objective measure of intensity. Patient physiologic data were collected at 12-second epochs 5 minutes before, during, and 5 minutes after oral care. The mixed-effect repeated measures analysis of variance model indicated that there was a statistically significant increase in ICP in response to oral care (p = .0031). There was, however, no clinically significant effect on ICP. This study provides evidence that oral care is safe to perform in patients in the absence of preexisting elevated ICP

Outcome measures for clinical trials in neurotrauma

Under the auspices of the American Brain Injury Consortium and the Joint Section of Neurotrauma and Critical Care of the American Association of Neurological Surgeons, the authors have reviewed and formulated opinions based on the evidence on protocol design and the outcome measures used for clinical trials in patients with a severe or moderate traumatic brain injury (TBI). First, in view of the heterogeneity of the population under study, the authors suggest that block randomization and stratification should always be used in the design of neurotrauma trials. Second, although the Glasgow Outcome Scale (GOS) remains the most widely used and accepted instrument for TBI trials, the authors believe the eight-point expanded scale that has recently been designed will ultimately provide greater discrimination, and narrower categories and will ultimately prove superior for detecting more subtle changes in outcome. Furthermore, the authors recommend, in view of the profound cognitive impairment in survivors of TBI, that neuropsychological tests be explored further as an adjunct to the GOS. Future research should focus on the development of more sensitive and specific surrogate outcome measures such as magnetic resonance imaging, neurochemical, neuropsychological, and quality of life measures in order to detect a neuroprotective effect in patients with TBI

An Open-Label Study of CP-101,606 in Subjects with a Severe Traumatic Head Injury or Spontaneous Intracerebral Hemorrhage

CP‐101,606 is a postsynaptic antagonist of N‐methyl‐d‐aspartate (NMDA) receptors bearing the NR2B subunit. When administered intravenously (i.v.), it decreases the effects of traumatic brain injury (TBI) and focal ischemia in animal models. Therapeutic plasma concentrations (200 ng/ml) in animals, have been well tolerated in healthy human volunteers. The purpose of the present dose escalation study was to assess the safety, tolerability, and pharmacokinetics of CP‐101,606 in subjects who had suffered either an acute severe TBI (Glasgow Coma Scale 3–8) or spontaneous intracerebral hemorrhage. Thirty patients, 20 with a TBI and 10 with a stroke, were enrolled in the trial and began receiving an i.v. infusion of CP‐101,606 for 2 hours, 24 hours, or 72 hours within 12 hours of brain injury. For the first two hours, the drug was given a rate of 0.75 mg/kg/hr and then stopped ( n= 17 ) or continued for 22 ( n= 2 ) or 70 hours ( n= 11 ) at 0.37 mg/kg/hr. Plasma and cerebrospinal fluid (CSF) were collected at serial times during and after treatment. There were no consistent changes in blood pressure or pulse nor any clinically significant hematological or electrocardiogram (ECG) abnormalities attributable to CP‐101,606. No adverse events or behavioral changes were considered to be related to the drug. Plasma concentrations of CP‐101,606 over 200 ng/ml were rapidly achieved in the blood and CSF within two hours and were sustained there as long as the drug was infused. CSF concentrations were slightly higher than that in plasma by the end of infusion suggesting good penetration of CP‐101,606 into the CSF. Outcome in the severe TBI patients, as measured by the Glasgow Outcome Score at six months, suggested that a two‐hour infusion yielded a range of scores similar to contemporary patients with a severe TBI treated at our hospital while the outcomes of the patients treated with either a 24‐ or 72‐hour infusion were better on average. Thus, these results indicate that CP‐101,606 infused for up to 72 hours is well tolerated, penetrates the CSF and brain, and may improve outcome in the brain‐injured patient