scispace - formally typeset
Search or ask a question
Author

Raj G. Kumar

Bio: Raj G. Kumar is an academic researcher from Icahn School of Medicine at Mount Sinai. The author has contributed to research in topics: Traumatic brain injury & Medicine. The author has an hindex of 16, co-authored 55 publications receiving 928 citations. Previous affiliations of Raj G. Kumar include University of Pittsburgh & Chandka Medical College.

Papers published on a yearly basis

Papers
More filters
Journal ArticleDOI
TL;DR: The authors' subacute cytokine load score classifies individuals at risk for unfavorable outcomes following injury as higher proinflammatory burden with IL-6, relative to the anti-inflammatory marker IL-10, is significantly associated with outcome.
Abstract: Objective Examine associations between chronic inflammatory profiles and outcome 6 to 12 months following severe traumatic brain injury (TBI). Setting University-affiliated level 1 trauma center and community. Participants Adults with severe TBI (n = 87); healthy controls (n = 7). Design Prospective cohort study. Main measures Glasgow Outcome Scale; serum cytokines (interleukin [IL]-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, tumor necrosis factor α), 2 weeks to 3 months, 4- to 6-month averages, 6- and 12-month levels. Results Serum levels of IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor α were elevated over 3 months following TBI. Multivariate analysis showed that increased cytokine load score was associated with a 1.21 (95% confidence interval, 1.06-1.38) and 1.18 (95% confidence interval, 1.02-1.37) increase in odds of unfavorable Glasgow Outcome Scale score at 6 and 12 months, respectively. Also, elevated IL-6/IL-10 ratios were associated with increased odds of unfavorable outcomes at 6 months (adjusted odds ratio = 1.76; 95% confidence interval, 1.08-2.88). Conclusions Chronic inflammation has not been well characterized following TBI. Our subacute cytokine load score classifies individuals at risk for unfavorable outcomes following injury. Higher proinflammatory burden with IL-6, relative to the anti-inflammatory marker IL-10, is significantly associated with outcome. Further research should examine whether inflammatory genes and other inflammatory biomarkers affect risk for unfavorable outcomes and TBI complications.

145 citations

Journal ArticleDOI
TL;DR: Evidence is provided that sustained, elevated levels of CSF IL-6 are associated with an increased inflammatory load, and these increases areassociated with increased odds for unfavorable global outcomes in the first year following TBI.
Abstract: Traumatic brain injury (TBI) results in a significant inflammatory burden that perpetuates the production of inflammatory mediators and biomarkers. Interleukin-6 (IL-6) is a pro-inflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. We hypothesized that cohort heterogeneity, temporal inflammatory profiles, and concurrent inflammatory marker associations are critical to characterize when targeting subpopulations for anti-inflammatory therapies. Toward this objective, we used serial cerebrospinal fluid (CSF) samples to generate temporal acute IL-6 trajectory (TRAJ) profiles in a prospective cohort of adults with severe TBI (n=114). We examined the impact of injury type on IL-6 profiles, and how IL-6 profiles impact sub-acute (2weeks-3months) serum inflammatory marker load and long-term global outcome 6-12months post-injury. There were two distinct acute CSF IL-6 profiles, a high and low TRAJ group. Individuals in the high TRAJ had increased odds of unfavorable Glasgow Outcome Scale (GOS) scores at 6months (adjusted OR=3.436, 95% CI: 1.259, 9.380). Individuals in the high TRAJ also had higher mean acute CSF inflammatory load compared to individuals in the low TRAJ (p⩽0.05). The two groups did not differ with respect acute serum profiles; however, individuals in the high CSF IL-6 TRAJ also had higher mean sub-acute serum IL-1β and IL-6 levels compared with the low TRAJ group (p⩽0.05). Lastly, injury type (isolated TBI vs. TBI+polytrauma) was associated with IL-6 TRAJ group (χ(2)=5.31, p=0.02). Specifically, there was 70% concordance between those with TBI+polytrauma and the low TRAJ; in contrast, isolated TBI was similarly distributed between TRAJ groups. These data provide evidence that sustained, elevated levels of CSF IL-6 are associated with an increased inflammatory load, and these increases are associated with increased odds for unfavorable global outcomes in the first year following TBI. Future studies should explore additional factors contributing to IL-6 elevations, and therapies to mitigate its detrimental effects on outcome.

104 citations

Journal ArticleDOI
TL;DR: Acute CSF IBR scores show promise for identifying individuals at risk forPTD and should explore anti-inflammatory treatments for PTD, as well as prevention and screening protocols, and link inflammatory biomarkers to symptom tracking.
Abstract: OBJECTIVE:: To examine whether acute inflammation profiles predict posttraumatic depression (PTD) risk 6 and 12 months after traumatic brain injury. SETTING:: University-affiliated level 1 trauma center and community. PARTICIPANTS:: Adults with moderate to severe traumatic brain injury (acute serum levels: n = 50; acute cerebrospinal fluid (CSF) levels: n = 41). DESIGN:: Prospective cohort study. MAIN MEASURES:: Patient Health Questionnaire; inflammatory biomarkers (interleukin [IL]-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, tumor necrosis factor α, soluble vascular adhesion molecule [sVCAM-1], soluble intracellular adhesion molecule [sICAM-1], soluble Fas [sFAS]). RESULTS:: Higher levels of acute CSF cytokine surface markers (sVCAM-1, sICAM-1, and sFAS) in an inflammatory biomarker risk (IBR) score were associated with a 3.920-fold increase in the odds of developing PTD at 6 months (95% confidence interval: 1.163-8.672). Having sICAM-1, sVCAM-1, or sFAS above the 75th percentile had a positive predictive value of 85.7% for PTD risk at 6 months. An IBR score including inflammatory biomarkers IL-7 and IL-8 showed a trending association with 12-month PTD risk (odds ratio = 3.166, 95% confidence interval: 0.936-10.708). CONCLUSION:: Acute CSF IBR scores show promise for identifying individuals at risk for PTD. Further research should assess acute CSF inflammatory biomarkers' relationships to chronic inflammation as a mechanism of PTD and should explore anti-inflammatory treatments for PTD, as well as prevention and screening protocols, and link inflammatory biomarkers to symptom tracking. Language: en

78 citations

Journal ArticleDOI
TL;DR: Preliminary data suggest a biological to behavioral pathway of suicidality after TBI, from TNFα to disinhibition to suicidal endorsement.
Abstract: Purpose To examine the relationship of Tumor Necrosis Factor (TNF)-α to disinhibition and suicidal endorsement after traumatic brain injury (TBI). Participants Adults with moderate to severe TBI (acute serum levels: n = 48, n = 543 samples; acute CSF levels: n = 37, n = 389 samples; chronic serum levels: n = 48, n = 326 samples). Main measures TNFα levels (CSF, Serum) from time of injury to 12 months post-injury; Frontal Systems Behavior Scale – Disinhibition Subscale at 6 and 12 months post-injury; Patient Health Questionnaire at 6 and 12 months post-injury. Results Participants with TBI had significantly higher CSF and serum TNFα levels than healthy controls ( p p = 0.009, p = 0.029 respectively), and 6 month disinhibition was associated with suicidal endorsement at both 6 and 12 months ( p = 0.045, p = 0.033 respectively) and disinhibition at 12 months post-injury ( p Conclusion These preliminary data suggest a biological to behavioral pathway of suicidality after TBI, from TNFα to disinhibition to suicidal endorsement. Future investigation is warranted to validate these findings and clarify what biological mechanisms might underlie these relationships.

71 citations

Journal ArticleDOI
TL;DR: Data suggest complex relationships between BDNF and TBI mortality that interact with age to influence survival predictions beyond clinical variables alone, and evidence supporting dynamic, temporal balances of pro-survival/pro-apoptotic target receptors may explain injury and age-related gene associations.
Abstract: Background. Mortality predictions following traumatic brain injury (TBI), and our understanding of TBI pathology, may be improved by including genetic risk in addition to traditional prognostic variables. One promising target is the gene coding for brain-derived neurotrophic factor (BDNF), a ubiquitous neurotrophin important for neuronal survival and neurogenesis. Objective. We hypothesized the addition of BDNF genetic variation would improve mortality prediction models and that BDNF Met-carriers (rs6265) and C-carriers (rs7124442) would have the highest mortality rates post-TBI. Methods. This study examined BDNF functional single nucleotide polymorphisms rs6265 (val66met) and rs7124442 (T>C) in relation to mortality in a prospective, longitudinal cohort with severe TBI. We examined 315 individuals receiving care for a closed head injury within the University of Pittsburgh Medical Center, aged 16 to 74 years. Mortality was examined acutely (0-7 days postinjury) and postacutely (8-365 days postinjury). A g...

67 citations


Cited by
More filters
01 Jan 2016
TL;DR: The applied missing data analysis is universally compatible with any devices to read and is available in the digital library an online access to it is set as public so you can download it instantly.
Abstract: Thank you for downloading applied missing data analysis. Maybe you have knowledge that, people have look hundreds times for their favorite readings like this applied missing data analysis, but end up in infectious downloads. Rather than enjoying a good book with a cup of tea in the afternoon, instead they juggled with some malicious bugs inside their laptop. applied missing data analysis is available in our digital library an online access to it is set as public so you can download it instantly. Our digital library hosts in multiple locations, allowing you to get the most less latency time to download any of our books like this one. Merely said, the applied missing data analysis is universally compatible with any devices to read.

1,924 citations

Reference EntryDOI
15 Jul 2008

830 citations

Journal Article
01 Jan 2008-Nature
TL;DR: It is shown that bright fluorescent nanodiamonds can be produced in large quantities by irradiating synthetic diamond nanocrystallites with helium ions, and the fluorescence is sufficiently bright and stable to allow three-dimensional tracking of a single particle within the cell by means of either one- or two-photon-excited fluorescence microscopy.
Abstract: Fluorescent nanodiamond is a new nanomaterial that possesses several useful properties, including good biocompatibility1, excellent photostability1,2 and facile surface functionalizability2,3. Moreover, when excited by a laser, defect centres within the nanodiamond emit photons that are capable of penetrating tissue, making them well suited for biological imaging applications1,2,4. Here, we show that bright fluorescent nanodiamonds can be produced in large quantities by irradiating synthetic diamond nanocrystallites with helium ions. The fluorescence is sufficiently bright and stable to allow three-dimensional tracking of a single particle within the cell by means of either one- or two-photon-excited fluorescence microscopy. The excellent photophysical characteristics are maintained for particles as small as 25 nm, suggesting that fluorescent nanodiamond is an ideal probe for long-term tracking and imaging in vivo, with good temporal and spatial resolution.

643 citations

Journal ArticleDOI
TL;DR: A new framework of targeted immunomodulation after TBI is proposed that incorporates factors such as the time from injury, mechanism of injury, and secondary insults in considering potential treatment options and highlights findings that could offer novel therapeutic targets for translational and clinical research.
Abstract: The 'silent epidemic' of traumatic brain injury (TBI) has been placed in the spotlight as a result of clinical investigations and popular press coverage of athletes and veterans with single or repetitive head injuries. Neuroinflammation can cause acute secondary injury after TBI, and has been linked to chronic neurodegenerative diseases; however, anti-inflammatory agents have failed to improve TBI outcomes in clinical trials. In this Review, we therefore propose a new framework of targeted immunomodulation after TBI for future exploration. Our framework incorporates factors such as the time from injury, mechanism of injury, and secondary insults in considering potential treatment options. Structuring our discussion around the dynamics of the immune response to TBI - from initial triggers to chronic neuroinflammation - we consider the ability of soluble and cellular inflammatory mediators to promote repair and regeneration versus secondary injury and neurodegeneration. We summarize both animal model and human studies, with clinical data explicitly defined throughout this Review. Recent advances in neuroimmunology and TBI-responsive neuroinflammation are incorporated, including concepts of inflammasomes, mechanisms of microglial polarization, and glymphatic clearance. Moreover, we highlight findings that could offer novel therapeutic targets for translational and clinical research, assimilate evidence from other brain injury models, and identify outstanding questions in the field.

619 citations