Puffer, Ross C.

OBJECTIVE The objective of this study was to isolate extracellular vesicles (EVs) from plasma in a cohort of patients with traumatic brain injury (TBI) and analyze their contents for novel biomarkers that could prove useful for rapid diagnosis and classification of brain injury during initial evaluation. METHODS Plasma EVs were isolated by serial ultracentrifugation from patients with TBI (n = 15) and healthy controls (n = 5). Samples were obtained from the TRACK-TBI biorepository (2010–present). Size and concentration were determined by nanoparticle tracking. Glial fibrillary acidic protein (GFAP) concentration was determined in EV protein. EV RNA was isolated and deep sequencing of short noncoding RNA was performed. RESULTS Plasma EVs are physically similar but contained approximately 10 times more GFAP in TBI patients with altered consciousness than patients and controls with normal consciousness. Eleven highly differentially expressed microRNAs (miRNAs) were identified between these groups. Genes targeted by these miRNAs are highly associated with biologically relevant cellular pathways, including organismal injury, cellular development, and organismal development. Multiple additional coding and noncoding RNA species with potential biomarker utility were identified. CONCLUSIONS Isolating plasma EVs in patients with TBI is feasible. Increased GFAP concentration—a validated plasma TBI marker—in EVs from TBI patients with altered consciousness, along with differential expression of multiple miRNAs targeting TBI-relevant pathways, suggests that EVs may be a useful source of TBI biomarkers. Additional evaluation in larger patient cohorts is indicated.

OBJECTIVEThe authors sought to assess whether Hounsfield units (HU) increase following teriparatide treatment and to compare HU increases with changes in bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry (DEXA).METHODSA retrospective chart review was performed from 1997 to 2018 across all campuses at our institution. The authors identified patients who had been treated with at least 6 months of teriparatide and compared HU and BMD as measured on DEXA scans before and after treatment.RESULTSFifty-two patients were identified for analysis (46 women and 6 men, average age 67 years) who underwent an average of 20.9 ± 6.5 months of teriparatide therapy. The mean ± standard deviation HU increase throughout the lumbar spine (L1–4) was from 109.8 ± 53 to 133.9 ± 61 HU (+22%, 95% CI 1.2–46, p value = 0.039). Based on DEXA results, lumbar spine BMD increased from 0.85 to 0.93 g/cm2 (+9%, p value = 0.044). Lumbar spine T-scores improved from −2.4 ± 1.5 to −1.7 ± 1.5 (p value = 0.03). Average femoral neck T-scores improved from −2.5 ± 1.1 to −2.3 ± 1.0 (p value = 0.31).CONCLUSIONSTeriparatide treatment increased both HU and BMD on DEXA in the lumbar spine, without a change in femoral BMD. The 22% improvement in HU surpassed the 9% improvement determined with DEXA. These results support some surgeons’ subjective sense that intraoperative bone quality following teriparatide treatment is better than indicated by DEXA results. To the authors’ knowledge, this is the first study demonstrating an increase in HU with teriparatide treatment.

Abstract BACKGROUND Synovial sarcoma of the nerve is a rare entity with several cases and case series reported in the literature. Despite an improved understanding of the biology, the clinical course is difficult to predict. OBJECTIVE To compile a series of patients with synovial sarcoma of the peripheral nerve (SSPN) and assess clinical and pathological factors and their contribution to survival and recurrence. METHODS Cases from 2 institutions collected in patients undergoing surgical intervention for SSPN. Systematic review including PubMed and Scopus databases were searched for related articles published from 1970 to December 2018. Eligibility criteria: (1) case reports or case series reporting on SSPN, (2) clinical course and/or pathological features of the tumor reported, and (3) articles published in English. RESULTS From patients treated at our institutions (13) the average follow-up period was 3.2 yr. Tumor recurrence was seen in 4 cases and death in 3. Systematic review of the literature yielded 44 additional cases with an average follow-up period of 3.6 yr. From pooled data, there were 10 recurrences and 7 deaths (20% and 14%, respectively). Adjuvant treatment used in 62.5% of cases. Immunohistochemical markers used in diagnosis varied widely; the most common are the following: Epithelial membrane antigen (EMA), cytokeratin, vimentin, cluster of differentiation (CD34), and transducin-like enhancer of split 1 (TLE1). Statistical analysis illustrated tumor size and use of chemotherapy to be negative predictors of survival. No other factors, clinically or from pathologist review, were correlated with recurrence or survival. CONCLUSION By combining cases from our institution with historical data and performing statistical analysis we show correlation between tumor size and death.

Favorable long-term functional outcomes after severe traumatic brain injury (TBI) may be underestimated. We analyzed 24-month functional outcomes from a consecutive series of severe TBI survivors. A prospective, observational database of severe TBI survivors from a single institution was analyzed. Glasgow Outcome Scale-Extended (GOS-E) scores were obtained at 3, 6, 12, and 24 months post-injury. GOS-E scores were dichotomized into unfavorable and favorable outcomes, and the proportion of survivors changing from unfavorable to favorable outcomes was calculated using Wilcoxon signed-rank tests. Surviving adults ( N = 304; mean age ± standard deviation = 35.06 ± 15.11; 80.92% male; mode of initial GCS = 7) were analyzed. A statistically significant mean increase in GOS-E was noted from 3 to 6, 6 to 12, 12 to 24, and 6 to 24 months after injury (0.65 [ p < 0.0001], 0.42 [ p < 0.0001], 0.23 [ p = 0.020], and 0.61 [ p < 0.0001], respectively). Moreover, 43% of survivors from 3 to 6 months, 36% from 6 to 12 months, 38% from 12 to 24 months, and 54% from 6 to 24 months progressed from an unfavorable to a favorable outcome. Two thirds of survivors in the unfavorable category at 3 months had favorable outcomes at 2 years. Overall, 74% of surviving adults with a documented GOS-E at 2 years after injury had a favorable outcome. Severe TBI survivors demonstrated significant improvement in functional outcomes from 3 to 24 months after injury. At 2 years, three fourths of survivors had a favorable outcome. Long-term prognosis in severe TBI is better than broadly appreciated.

Background: Interfascicular resection is a surgical technique used to safely treat benign peripheral nerve sheath tumors through careful dissection of functional neural elements off the tumor surface 1,2 . Description: Proper operative technique is essential to improving symptoms, preserving neurologic function, and minimizing the chance for recurrence. Accurate tumor localization, ideal patient positioning, and placement of a longitudinal incision permit adequate exposure. Prior to tumor resection, normal nerve should be identified proximally and distally and controlled with vessel loops. This allows functional fascicles streaming around the tumor in the pseudocapsule to be visualized during resection. A fascicle-free window is identified on the tumor surface through visual inspection and intraoperative neurophysiology monitoring if desired. The pseudocapsule layers are divided with a sharp instrument until a smooth and shiny true capsule layer is found. This plane should have minimal resistance and is developed circumferentially until the tumor can be enucleated in toto. At the poles of the tumor, a single nonfunctional nerve fascicle that courses into the tumor is typically found. If there is >1 fascicle running into the tumor, further pseudocapsule layers should be undermined to sweep fascicles off the true capsule surface. The entering-exiting fascicle can be tested for function and is cut sharply. The specimen should be sent to pathology for permanent sectioning. The sides of the pseudocapsule are spread in opposite directions to evaluate for residual tumor, and any remaining tumor is removed if it can be done safely. Meticulous hemostasis is achieved, and the surgical site is closed in anatomical layers. Alternatives: Pain is the most common presenting symptom, and neuroleptic medications should be used in escalating dosage prior to surgical intervention. Nonoperative medical therapy does not typically result in symptom freedom, and patients often opt for resection. For tumors that are suspected of being malignant, an image-guided percutaneous or open biopsy and staging (positron emission tomography and/or computed tomography scans of the chest, abdomen, and pelvis) are recommended prior to treatment planning. For symptomatic benign extremity lesions, surgical resection is the treatment of choice, and adjuvant therapies like radiation and/or chemotherapy are not recommended. For malignant lesions, more aggressive surgery (wide resection or amputation) and preoperative, intraoperative, or postoperative radiation with or without chemotherapy are often utilized. Rationale: The treatment approach depends on a variety of presenting features such as onset, progression, symptom severity, tumor size, location, imaging features, presence of a syndrome, and patient age. There is little benefit from the resection of an incidentally found, small, nongrowing lesion. The most common reasons for removal of extremity lesions are a painful mass and/or radiating “nerve” pain. There is a high likelihood of relieving the symptoms and minimizing the risk of recurrence, and a relatively low risk of causing neurologic injury. The procedure provides a definitive diagnosis. For patients with severe pain, progressive weakness, rapid tumor growth, or concerning imaging characteristics, biopsy should be considered to determine malignant potential.

OBJECTIVEFollowing traumatic brain injury (TBI), midline shift of the brain at the level of the septum pellucidum is often caused by unilateral space-occupying lesions and is associated with increased intracranial pressure and worsened morbidity and mortality. While outcome has been studied in this population, the recovery trajectory has not been reported in a large cohort of patients with TBI. The authors sought to utilize the Citicoline Brain Injury Treatment (COBRIT) trial to analyze patient recovery over time depending on degree of midline shift at presentation.METHODSPatient data from the COBRIT trial were stratified into 4 groups of midline shift, and outcome measures were analyzed at 30, 90, and 180 days postinjury. A recovery trajectory analysis was performed identifying patients with outcome measures at all 3 time points to analyze the degree of recovery based on midline shift at presentation.RESULTSThere were 892, 1169, and 895 patients with adequate outcome data at 30, 90, and 180 days, respectively. Rates of favorable outcome (Glasgow Outcome Scale–Extended [GOS-E] scores 4–8) at 6 months postinjury were 87% for patients with no midline shift, 79% for patients with 1–5 mm of shift, 64% for patients with 6–10 mm of shift, and 47% for patients with > 10 mm of shift. The mean improvement from unfavorable outcome (GOS-E scores 2 and 3) to favorable outcome (GOS-E scores 4–8) from 1 month to 6 months in all groups was 20% (range 4%–29%). The mean GOS-E score for patients in the 6- to 10-mm group crossed from unfavorable outcome (GOS-E scores 2 and 3) into favorable outcome (GOS-E scores 4–8) at 90 days, and the mean GOS-E of patients in the > 10-mm group nearly reached the threshold of favorable outcome by 180 days postinjury.CONCLUSIONSIn this secondary analysis of the Phase 3 COBRIT trial, TBI patients with less than 10 mm of midline shift on admission head CT had significantly improved functional outcomes through 180 days after injury compared with those with greater than 10 mm of midline shift. Of note, nearly 50% of patients with > 10 mm of midline shift achieved a favorable outcome (GOS-E score 4–8) by 6 months postinjury.