Moderate Traumatic Brain Injury Alters the Gastrointestinal Microbiome in a Time-Dependent Manner.

The microbiome is defined as the collective genomes of the microbes (composed of bacteria, bacteriophage, fungi, protozoa, and viruses) that colonize the human body, and alterations have been associated with a number of disease states. Changes in gut commensals can influence the neurologic system via the brain-gut axis, and systemic insults such as trauma or traumatic brain injury (TBI) may alter the gut microbiome. The objective of this study was to evaluate the gut microbiome in a preclinical TBI cortical impact model. Male rats underwent craniotomy and randomized to a sham group (n = 4), or a moderate TBI (n = 10) using a pneumatic impactor. MRI and behavioral assessments were performed pre-TBI and on days 2, 7, and 14 days thereafter. Microbiome composition was determined with 16s rRNA sequencing from fecal sample DNA pre-TBI and 2 hrs, 1, 3, and 7 days afterward. Alpha- and ß-bacterial diversity, as well as organizational taxonomic units (OTUs), were determined. Significant changes in the gut microbiome were evident as early as 2 h after TBI as compared with pre-injured samples and sham rats. While there were varying trends among the phylogenetic families across time, some changes persisted through 7 days in the absence of therapeutic intervention. While large structural lesions and behavioral deficits were apparent post-TBI, there were modest but significant decreases in α-diversity. Moreover, both changes in representative phyla and α-diversity measures were significantly correlated with MRI-determined lesion volume. These results suggest that changes in the microbiome may represent a novel biomarker to stage TBI severity and predict functional outcome.

Polytrauma independent of therapeutic intervention alters the gastrointestinal microbiome.

BACKGROUND: This study characterizes the gastrointestinal (GI) microbiome in a pre-clinical polytrauma hemorrhage model. METHODS: Rats (n = 6) were anesthetized, hemorrhaged 20% of their blood volume, and subjected to a femur fracture and crush injuries to the small intestine, liver, and limb skeletal muscle without resuscitation. Fecal samples were collected pre-injury and 2 h post-injury. Purified DNA from the samples underwent 16s rRNA sequencing for microbial quantification. Bacterial diversity analysis and taxonomic classification were performed. RESULTS: Following injury, the gut microbial composition was altered with a shift in beta diversity and significant differences in the relative abundance of taxa. The relative abundance of the families Lachnospiraceae and Mogibacteriaceae was increased at 2 h, while Barnesiellaceae and Bacteroidaceae were decreased. Alpha diversity was unchanged. CONCLUSIONS: The GI microbiome is altered in rats subjected to a polytrauma hemorrhage model at 2 h post-injury in the absence of antibiotics or therapeutic interventions.

Magnetic resonance neurography in extraspinal sciatica.

BACKGROUND: Sciatica without evidence of lumbosacral root compression is often attributed to piriformis syndrome. However, specific diagnostic tools have not been available to demonstrate sciatic nerve entrapment by the piriformis muscle. OBJECTIVE: To evaluate the use of magnetic resonance (MR) neurography in identifying abnormalities of the sciatic nerve in patients with unexplained sciatica. DESIGN: Case series from a retrospective medical record review. PATIENTS: Fourteen patients with sciatic distribution pain and normal results on MR imaging for lumbosacral radiculopathy were referred for MR neurography of the lumbosacral plexus and sciatic nerves. RESULTS: In 12 patients, MR neurography demonstrated increased fluid-attenuated inversion recovery signal in the ipsilateral sciatic nerve. In most patients, this abnormal signal was seen at the sciatic notch, at or just inferior to the level of the piriformis muscle. To date, 4 patients have undergone surgical decompression, with excellent relief of symptoms in 3 of them. CONCLUSION: Magnetic resonance neurography often identifies an abnormal increased signal in the proximal sciatic nerve in patients with extraspinal sciatica and allows more accurate diagnosis of sciatic nerve entrapment in suspected cases.

Human growth hormone-related iatrogenic Creutzfeldt-Jakob disease with abnormal imaging.

BACKGROUND: Although more than 160 cases of iatrogenic Creutzfeldt-Jakob disease (iCJD) from human growth hormone (hGH) treatment have been documented, to our knowledge abnormal cerebellar findings on magnetic resonance imaging (MRI) have not been reported. OBJECTIVE: To report a case of hGH-related iCJD with abnormal cerebellar MRI findings on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted MRI (DWI). DESIGN: Case report. SETTING: Outpatient neurology clinic at a university medical center. PATIENT: A 33-year old man who had subacute gait ataxia and blurred vision. RESULTS: Beginning 19 years prior, this patient had received cadaveric pituitary-derived hGH treatment for at least 5 years. Magnetic resonance imaging revealed FLAIR and DWI abnormalities, particularly in the cerebellum. He died 7 months after disease onset of autopsy-confirmed iCJD. Pathological changes corresponded largely to MRI findings. CONCLUSIONS: To our knowledge, this is the first case of hGH-related iCJD with FLAIR and DWI abnormalities within the cerebellum. As symptoms referable to the cerebellum occur early in iCJD, it suggests that these MRI sequences may allow earlier diagnosis of this form of prion disease.

Dermal γδ T-Cells Can Be Activated by Mitochondrial Damage-Associated Molecular Patterns.

BACKGROUND: Gamma delta T-cells have been shown to be important to the early immunoinflammatory response to injury, independent of infection. This unique T-cell population acts to regulate cell trafficking and the release of cytokines and growth factors. We propose this sterile inflammatory response is in part associated with damage associated molecular patterns (DAMPs) generated by major injury, such as burn, and mediated via toll-like receptors (TLRs). It is unknown whether DAMPs can activate resident γδ T-cells that reside in skin. METHODS: Gamma delta T-cells were isolated from the skin of male C57BL/6 mice by enzymatic digestion. Mitochondrial DAMPs (MTDs) were generated from mitochondria isolated from mouse livers by sonication and centrifugation. Dermal γδ T-cells were incubated with MTDs (0-500 µg/ml) for 24 hr and cells and supernatants were collected for analysis. RESULTS: MTDs activated dermal γδ T-cells, as evidenced by increased TLR2 and TLR4 expression following in vitro exposure. MTDs also induced the production of inflammatory cytokines (IL-1ß, IL-6), and growth factors (PDGF and VEGF) by γδ T-cells. CONCLUSIONS: These findings herein support the concept that MTDs released after tissue/cellular injury are capable of activating dermal γδ T-cells. We propose that the activation of this unique T-cell population is central in the initiation of sterile inflammation and also contributes to the subsequent healing processes.

Mass Casualty Incident Management Preparedness: A Survey of the American College of Surgeons Committee on Trauma.

Mass casualty incidents (MCIs) are events resulting in more injured patients than hospital systems can handle with standard protocols. Several studies have assessed hospital preparedness during MCIs. However, physicians and trauma surgeons need to be familiar with their hospital's MCI Plan. The purpose of this survey was to assess hospitals' and trauma surgeon's preparedness for MCIs. Online surveys were e-mailed to members of the American College of Surgeons committee on Trauma Ad Hoc Committee on Disaster and Mass Casualty Management before the March 2012 meeting. Eighty surveys were analyzed (of 258). About 76 per cent were American College of Surgeons Level I trauma centers, 18 per cent were Level II trauma centers. Fifty-seven per cent of Level I and 21 per cent of Level II trauma centers had experienced an MCI. A total of 98 per cent of respondents thought it was likely their hospital would see a future MCI. Severe weather storm was the most likely event (95%), followed by public transportation incident (86%), then explosion (85%). About 83 per cent of hospitals had mechanisms to request additional physician/surgeons, and 80 per cent reported plans for operative triage. The majority of trauma surgeons felt prepared for an MCI and believed an event was likely to occur in the future. The survey was limited by the highly select group of respondents and future surveys will be necessary.