OBJECTIVE: Surgical site infection (SSI) following spine surgery causes major morbidity and greatly impedes functional recovery. In the modern era of advanced operative techniques and improved perioperative care, SSI remains a problematic complication that may be reduced with institutional practices. The objectives of this study were to 1) characterize the SSI rate and microbial etiology following spine surgery for various thoracolumbar diseases, and 2) identify risk factors that were associated with SSI despite current perioperative management.METHODS: All patients treated with thoracic or lumbar spine operations on the neurosurgery service at the University of California, San Francisco from April 2012 to April 2016 were formally reviewed for SSI using the National Healthcare Safety Network (NHSN) guidelines. Preoperative risk variables included age, sex, BMI, smoking, diabetes mellitus (DM), coronary artery disease (CAD), ambulatory status, history of malignancy, use of preoperative chlorhexidine gluconate (CHG) showers, and the American Society of Anesthesiologists (ASA) classification. Operative variables included surgical pathology, resident involvement, spine level and surgical technique, instrumentation, antibiotic and steroid use, estimated blood loss (EBL), and operative time. Multivariable logistic regression was used to evaluate predictors for SSI. Odds ratios and 95% confidence intervals were reported.RESULTS: In total, 2252 consecutive patients underwent thoracolumbar spine surgery. The mean patient age was 58.6 ± 13.8 years and 49.6% were male. The mean hospital length of stay was 6.6 ± 7.4 days. Sixty percent of patients had degenerative conditions, and 51.9% underwent fusions. Sixty percent of patients utilized presurgery CHG showers. The mean operative duration was 3.7 ± 2 hours, and the mean EBL was 467 ± 829 ml. Compared to nonfusion patients, fusion patients were older (mean 60.1 ± 12.7 vs 57.1 ± 14.7 years, p < 0.001), were more likely to have an ASA classification > II (48.0% vs 36.0%, p < 0.001), and experienced longer operative times (252.3 ± 120.9 minutes vs 191.1 ± 110.2 minutes, p < 0.001). Eleven patients had deep SSI (0.49%), and the most common causative organisms were methicillin-sensitive Staphylococcus aureus and methicillin-resistant S. aureus. Patients with CAD (p = 0.003) or DM (p = 0.050), and those who were male (p = 0.006), were predictors of increased odds of SSI, and presurgery CHG showers (p = 0.001) were associated with decreased odds of SSI.CONCLUSIONS: This institutional experience over a 4-year period revealed that the overall rate of SSI by the NHSN criteria was low at 0.49% following thoracolumbar surgery. This was attributable to the implementation of presurgery optimization, and intraoperative and postoperative measures to prevent SSI across the authors’ institution. Despite prevention measures, having a history of CAD or DM, and being male, were risk factors associated with increased SSI, and presurgery CHG shower utilization decreased SSI risk in patients.

The prevalence of neuropsychiatric disorders following traumatic brain injury (TBI) is 20%–50%, and disorders of mood and cognition may remain even after recovery of neurologic function is achieved. Selective serotonin reuptake inhibitors (SSRI) block the reuptake of serotonin in presynaptic cells to lead to increased serotonergic activity in the synaptic cleft, constituting first-line treatment for a variety of neurocognitive and neuropsychiatric disorders. This review investigates the utility of SSRIs in treating post-TBI disorders. In total, 37 unique reports were consolidated from the Cochrane Central Register and PubMed (eight randomized-controlled trials (RCTs), nine open-label studies, 11 case reports, nine review articles). SSRIs are associated with improvement of depressive but not cognitive symptoms. Pooled analysis using the Hamilton Depression Rating Scale demonstrate a significant mean decrease of depression severity following sertraline compared to placebo—a result supported by several other RCTs with similar endpoints. Evidence from smaller studies demonstrates mood improvement following SSRI administration with absent or negative effects on cognitive and functional recovery. Notably, studies on SSRI treatment effects for post-traumatic stress disorder after TBI remain absent, and this represents an important direction of future research. Furthermore, placebo-controlled studies with extended follow-up periods and concurrent biomarker, neuroimaging and behavioral data are necessary to delineate the attributable pharmacological effects of SSRIs in the TBI population.

Systemic inflammation impacts outcome after traumatic brain injury (TBI), but most TBI biomarker studies have focused on brain-specific proteins. C-reactive protein (CRP) is a widely used biomarker of inflammation with potential as a prognostic biomarker after TBI. The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study prospectively enrolled TBI patients within 24 h of injury, as well as orthopedic injury and uninjured controls; biospecimens were collected at enrollment. A subset of hospitalized participants had blood collected on day 3, day 5, and 2 weeks. High-sensitivity CRP (hsCRP) and glial fibrillary acidic protein (GFAP) were measured. Receiver operating characteristic analysis was used to evaluate the prognostic ability of hsCRP for 6-month outcome, using the Glasgow Outcome Scale-Extended (GOSE). We included 1206 TBI subjects, 122 orthopedic trauma controls (OTCs), and 209 healthy controls (HCs). Longitudinal biomarker sampling was performed in 254 hospitalized TBI subjects and 19 OTCs. hsCRP rose between days 1 and 5 for TBI and OTC subjects, and fell by 2 weeks, but remained elevated compared with HCs (p < 0.001). Longitudinally, hsCRP was significantly higher in the first 2 weeks for subjects with death/severe disability (GOSE <5) compared with those with moderate disability/good recovery (GOSE ≥5); AUC was highest at 2 weeks (AUC = 0.892). Combining hsCRP and GFAP at 2 weeks produced AUC = 0.939 for prediction of disability. Serum hsCRP measured within 2 weeks of TBI is a prognostic biomarker for disability 6 months later. hsCRP may have utility as a biomarker of target engagement for anti-inflammatory therapies.

Background and Objectives: The annual global incidence of traumatic brain injury (TBI) is over 10 million. An estimated 29% of TBI patients with negative computed tomography (CT−) have positive magnetic resonance imaging (MRI+) findings. Judicious use of serum biomarkers with MRI may aid in diagnosis of CT-occult TBI. The current manuscript aimed to evaluate the diagnostic, therapeutic and risk-stratification utility of known biomarkers and intracranial MRI pathology. Materials and Methods: The PubMed database was queried with keywords (plasma OR serum) AND (biomarker OR marker OR protein) AND (brain injury/trauma OR head injury/trauma OR concussion) AND (magnetic resonance imaging/MRI) (title/abstract) in English. Seventeen articles on TBI biomarkers and MRI were included: S100 calcium-binding protein B (S100B; N = 6), glial fibrillary acidic protein (GFAP; N = 3), GFAP/ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1; N = 2), Tau (N = 2), neurofilament-light (NF-L; N = 2), alpha-synuclein (N = 1), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor peptide (AMPAR; N = 1). Results: Acute GFAP distinguished CT−/MRI+ from CT−/MRI− (AUC = 0.777, 0.852 at 9–16 h). GFAP discriminated CT−/diffuse axonal injury (DAI+) from controls (AUC = 0.903). Tau correlated directly with number of head strikes and inversely with white matter fractional anisotropy (FA), and a cutoff > 1.5 pg/mL discriminated between DAI+ and DAI− (sensitivity = 74%/specificity = 69%). NF-L had 100% discrimination of DAI in severe TBI and correlated with FA. Low alpha-synuclein was associated with poorer functional connectivity. AMPAR cutoff > 0.4 ng/mL had a sensitivity of 91% and a specificity of 92% for concussion and was associated with minor MRI findings. Low/undetectable S100B had a high negative predictive value for CT/MRI pathology. UCH-L1 showed no notable correlations with MRI. Conclusions: An acute circulating biomarker capable of discriminating intracranial MRI abnormalities is critical to establishing diagnosis for CT-occult TBI and can triage patients who may benefit from outpatient MRI, surveillance and/or follow up with TBI specialists. GFAP has shown diagnostic potential for MRI findings such as DAI and awaits further validation. Tau shows promise in detecting DAI and disrupted functional connectivity. Candidate biomarkers should be evaluated within the context of analytical performance of the assays used, as well as the post-injury timeframe for blood collection relative to MRI abnormalities.

Background and Objectives: The injury burden after head trauma is exacerbated by secondary sequelae, which leads to further neuronal loss. B-cell lymphoma 2 (Bcl-2) is an anti-apoptotic protein and a key modulator of the programmed cell death (PCD) pathways. The current study evaluates the clinical evidence on Bcl-2 and neurological recovery in patients after traumatic brain injury (TBI). Materials and Methods: All studies in English were queried from the National Library of Medicine PubMed database using the following search terms: (B-cell lymphoma 2/Bcl-2/Bcl2) AND (brain injury/head injury/head trauma/traumatic brain injury) AND (human/patient/subject). There were 10 investigations conducted on Bcl-2 and apoptosis in TBI patients, of which 5 analyzed the pericontutional brain tissue obtained from surgical decompression, 4 studied Bcl-2 expression as a biomarker in the cerebrospinal fluid (CSF), and 1 was a prospective randomized trial. Results: Immunohistochemistry (IHC) in 94 adults with severe TBI showed upregulation of Bcl-2 in the pericontusional tissue. Bcl-2 was detected in 36–75% of TBI patients, while it was generally absent in the non-TBI controls, with Bcl-2 expression increased 2.9- to 17-fold in TBI patients. Terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick-end labeling (TUNEL) positivity for cell death was detected in 33–73% of TBI patients. CSF analysis in 113 TBI subjects (90 adults, 23 pediatric patients) showed upregulation of Bcl-2 that peaked on post-injury day 3 and subsequently declined after day 5. Increased Bcl-2 in the peritraumatic tissue, rising CSF Bcl-2 levels, and the variant allele of rs17759659 are associated with improved mortality and better outcomes on the Glasgow Outcome Score (GOS). Conclusions: Bcl-2 is upregulated in the pericontusional brain and CSF in the acute period after TBI. Bcl-2 has a neuroprotective role as a pro-survival protein in experimental models, and increased expression in patients can contribute to improvement in clinical outcomes. Its utility as a biomarker and therapeutic target to block neuronal apoptosis after TBI warrants further evaluation.