Ashutosh Lal, Esteban Gomez, Cassandra Calloway
Suresh Gopi Kalathil, Amit Anand Lugade, Austin Miller, Renuka Iyer, Yasmin Thanavala
Zoheb B. Kazi, Sean N. Prater, Joyce A. Kobori, David Viskochil, Carrie Bailey, Renuka Gera, David W. Stockton, Paul McIntosh, Amy S. Rosenberg, Priya S. Kishnani
BACKGROUND. Children treated with cerebrospinal fluid (CSF) shunts to manage hydrocephalus frequently develop shunt failure and/or infections, conditions that present with overlapping symptoms. The potential life-threatening nature of shunt infections requires rapid diagnosis; however, traditional microbiology is time consuming, expensive, and potentially unreliable. We set out to identify a biomarker that would identify shunt infection.
METHODS. CSF was assayed for the soluble membrane attack complex (sMAC) by ELISA in patients with suspected shunt failure or infection. CSF was obtained at the time of initial surgical intervention. Statistical analysis was performed to assess the diagnostic potential of sMAC in pyogenic-infected versus noninfected patients.
RESULTS. Children with pyogenic shunt infection had significantly increased sMAC levels compared with noninfected patients (3,211 ± 1,111 ng/ml vs. 26 ± 3.8 ng/ml,
CONCLUSION. Elevated CSF sMAC levels are both sensitive and specific for diagnosing pyogenic shunt infection and may serve as a useful prognostic biomarker during recovery from infection.
FUNDING. This work was supported in part by the Impact Fund of Children’s of Alabama.
Theresa N. Ramos, Anastasia A. Arynchyna, Tessa E. Blackburn, Scott R. Barnum, James M. Johnston
Michael P. Whyte, Katherine L. Madson, Dawn Phillips, Amy L. Reeves, William H. McAlister, Amy Yakimoski, Karen E. Mack, Kim Hamilton, Kori Kagan, Kenji P. Fujita, David D. Thompson, Scott Moseley, Tatjana Odrljin, Cheryl Rockman-Greenberg
Marlise R. Luskin, Phyllis A. Gimotty, Catherine Smith, Alison W. Loren, Maria E. Figueroa, Jenna Harrison, Zhuoxin Sun, Martin S. Tallman, Elisabeth M. Paietta, Mark R. Litzow, Ari M. Melnick, Ross L. Levine, Hugo F. Fernandez, Selina M. Luger, Martin Carroll, Stephen R. Master, Gerald B.W. Wertheim
Victor Gura, Matthew B. Rivara, Scott Bieber, Raj Munshi, Nancy Colobong Smith, Lori Linke, John Kundzins, Masoud Beizai, Carlos Ezon, Larry Kessler, Jonathan Himmelfarb
BACKGROUND. Paneth cell dysfunction has been implicated in a subset of Crohn’s disease (CD) patients. We previously stratified clinical outcomes of CD patients by using Paneth cell phenotypes, which we defined by the intracellular distribution of antimicrobial proteins. Animal studies suggest that Paneth cells shape the intestinal microbiome. However, it is unclear whether Paneth cell phenotypes alter the microbiome complexity in CD subjects. Therefore, we analyzed the correlation of Paneth cell phenotypes with mucosal microbiome composition and ileal RNA expression in pediatric CD and noninflammatory bowel disease (non-IBD) patients.
METHODS. Pediatric CD (
RESULTS. The prevalence of abnormal Paneth cells was higher in pediatric versus adult CD cohorts. For pediatric CD patients, those with abnormal Paneth cells showed significant changes in their ileal mucosal microbiome, highlighted by reduced protective microbes and enriched proinflammatory microbes. Ileal transcriptome profiles showed reduced transcripts for genes that control oxidative phosphorylation in CD patients with abnormal Paneth cells. These transcriptional changes in turn were correlated with specific microbiome alterations. In non-IBD patients, a subset contained abnormal Paneth cells. However, this subset was not associated with alterations in the microbiome or host transcriptome.
CONCLUSION. Paneth cell abnormalities in human subjects are associated with mucosal dysbiosis in the context of CD, and these changes are associated with alterations in oxidative phosphorylation, potentially in a feedback loop.
FUNDING. The research was funded by Helmsley Charitable Trust (to T.S. Stappenbeck, R.J. Xavier, and D.P.B. McGovern), Crohn’s and Colitis Foundation of America (to N.H. Salzman, T.S. Stappenbeck, R.J. Xavier, and C. Huttenhower), and Doris Duke Charitable Foundation grant 2014103 (to T.C. Liu).
Ta-Chiang Liu, Bhaskar Gurram, Megan T. Baldridge, Richard Head, Vy Lam, Chengwei Luo, Yumei Cao, Pippa Simpson, Michael Hayward, Mary L. Holtz, Pavlos Bousounis, Joshua Noe, Diana Lerner, Jose Cabrera, Vincent Biank, Michael Stephens, Curtis Huttenhower, Dermot P.B. McGovern, Ramnik J. Xavier, Thaddeus S. Stappenbeck, Nita H. Salzman
Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.
Maria Lucia L. Madariaga, Philip J. Spencer, Kumaran Shanmugarajah, Kerry A. Crisalli, David C. Chang, James F. Markmann, Nahel Elias, A. Benedict Cosimi, David H. Sachs, Tatsuo Kawai
BACKGROUND. Kidney function decreases with age. A potential mechanistic explanation for kidney and allograft half-life has evolved through the realization that linear reduction in glomerular podocyte density could drive progressive glomerulosclerosis to impact both native kidney and allograft half-lives.
METHODS. Predictions from podometrics (quantitation of podocyte parameters) were tested using independent pathologic, functional, and outcome data for native kidneys and allografts derived from published reports and large registries.
RESULTS. With age, native kidneys exponentially develop glomerulosclerosis, reduced renal function, and end-stage kidney disease, projecting a finite average kidney life span. The slope of allograft failure rate versus age parallels that of reduction in podocyte density versus age. Quantitative modeling projects allograft half-life at any donor age, and rate of podocyte detachment parallels the observed allograft loss rate.
CONCLUSION. Native kidneys are designed to have a limited average life span of about 100–140 years. Allografts undergo an accelerated aging-like process that accounts for their unexpectedly short half-life (about 15 years), the observation that older donor age is associated with shorter allograft half-life, and the fact that long-term allograft survival has not substantially improved. Podometrics provides potential readouts for these processes, thereby offering new approaches for monitoring and intervention.
FUNDING: National Institutes of Health.
Abhijit S. Naik, Farsad Afshinnia, Diane Cibrik, Jeffrey B. Hodgin, Fan Wu, Min Zhang, Masao Kikuchi, Larysa Wickman, Milagros Samaniego, Markus Bitzer, Jocelyn E. Wiggins, Akinlolu Ojo, Yi Li, Roger C. Wiggins
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