A simplified cranial cavity model to understand the relationship between intracranial pressure and dural sinus pressure.

Although accurate intracranial pressure (ICP) monitoring is essential for the diagnosis and treatment of severe brain diseases, current methods are performed invasively. Therefore, a safe and less invasive ICP measurement is required. The purpose of our study was to develop a simplified cranial cavity model for a better understanding of the relationship between the ICP and the pressure measurement within the dural venous sinus (DVS) to support the validity of using sinus pressure as the surrogate of the ICP. The in-house cranial cavity model had three components: the brain part, the DVS part, and the subarachnoid space (SAS) part. Pressure in other parts was measured when the pressure in the SAS part and, separately, brain part was increased from 0 (baseline) to 50 mmHg at intervals of 10 mmHg. When the pressure in the SAS part was increased from 10 to 50 mmHg at 10 mmHg interval, pressures of both the brain and DVS parts increased without significant difference (all P > 0.05). However, pressures in both the SAS and DVS parts differed while the pressure in the brain part was increased. The pressures in both parts showed about 70% of the increase in the brain part. Nevertheless, the pressures in the SAS and DVS parts were not significantly different (P > 0.05). A simplified in-house cranial cavity model was developed consisting of three compartments to represent the actual intracranial spaces. The pressure measurement within the DVS was feasible to use as a surrogate for the ICP measurement.

Facemask ventilation and vocal cord angle following neuromuscular blockade: a prospective observational study.

Numerous studies support the idea that neuromuscular blockade facilitates facemask ventilation after induction of anaesthesia. Although improved airway patency or pulmonary compliance and a resolution of laryngospasm have been suggested as possible causes, the exact mechanism remains unclear. We aimed to assess whether neuromuscular blockade improves facemask ventilation and to clarify whether this phenomenon is associated with the vocal cord angle. This prospective observational study included patients aged between 20 and 65 years scheduled for elective surgery under general anaesthesia. After induction of anaesthesia, patients' lungs were ventilated with pressure-controlled ventilation using a facemask. During facemask ventilation, a flexible bronchoscope was inserted through a self-sealing diaphragm at the elbow connector attached to the facemask and breathing circuit and positioned to allow a continuous view of the vocal cords. The mean tidal volume and vocal cord angle were measured before and after administration of neuromuscular blocking drugs. Of 108 patients, 100 completed the study. Mean (SD) tidal volume ((11.0 (3.9) ml.kg-1 vs. 13.6 (2.6) ml.kg-1 ; p < 0.001) and mean (SD) vocal cord angle (17° (10°) vs. 26° (5°); p < 0.001) increased significantly after neuromuscular blockade. The proportional increase in mean tidal volume after neuromuscular blockade was positively correlated with vocal cord angle (Spearman's ρ = 0.803; p < 0.001). In conclusion, neuromuscular blockade facilitated facemask ventilation, and the improvement was correlated with further opening of the vocal cords.

Accuracy of hospital-based surveillance systems for surgical site infection after adult spine surgery: a Bayesian latent class analysis.

BACKGROUND: Surgical site infections (SSIs) of the spine are morbid and costly complications. An accurate surveillance system is required to properly describe the disease burden and the impact of interventions that mitigate SSI risk. Unfortunately, uniform approaches to conducting SSI surveillance are lacking because of varying SSI case definitions, the lack of a perfect reference case definition and heterogeneous data sources. AIM: To assess the accuracy of four independent data sources that capture SSIs after spine surgery, with estimation of a measurement-error-adjusted SSI incidence. METHODS: A Bayesian latent class model assessed the sensitivity/specificity of each data source to identify SSI and to estimate a measurement-error-adjusted incidence. The four data sources used were: the discharge abstract database (DAD), the National Surgical Quality Improvement Program (NSQIP) database, the Infection Prevention and Control Canada (IPAC) database, and the Spine Adverse Events Severity database. FINDINGS: A total of 904 patients underwent spine surgery in 2017. The most sensitive data source was DAD (0.799; 95% credible interval (CrI): 0.597-0.943); the least sensitive was NSQIP (0.497; 95% CrI: 0.308-0.694). The most specific data source was IPAC (0.997; 95% CrI: 0.993-1.000) and the least specific was DAD (0.969; 95% CrI: 0.956-0.981). The measurement-error-adjusted SSI incidence was 0.030 (95% CrI: 0.019-0.045). The crude incidence using the DAD overestimated the incidence, and the three other data sources underestimated it. CONCLUSION: SSI surveillance in the spine surgery population is feasible using several data sources, provided that measurement error is considered.

Psoriasis is associated with an increased risk of osteoporosis: follow-up and nested case-control studies using a national sample cohort.

A total of 25,306 psoriasis participants were matched to 101,224 controls, and the occurrence of osteoporosis was analyzed. Additionally, 79,212 osteoporosis patients were matched to 79,212 controls and a previous history of psoriasis was analyzed. Psoriasis increased the risk of osteoporosis among participants aged ≥ 40 years. INTRODUCTION: The aim of the present study was to evaluate the association between psoriasis and osteoporosis using two different studies. METHODS: Data from the Korean National Health Insurance Service-Health Screening Cohort of participants aged ≥ 40 years were collected from 2002 to 2013. Psoriasis and osteoporosis were included using International Classification of Diseases (ICD)-10 codes. In study I (a follow-up study), a total of 25,306 psoriasis participants were matched to 101,224 controls with respect to age, sex, income, and region of residence, and the occurrence of osteoporosis was analyzed. Crude (simple) and adjusted hazard ratios (HRs) were analyzed using a stratified Cox proportional hazard model. In study II (a nested case-control study), a total of 79,212 osteoporosis patients were matched to 79,212 controls and a previous history of psoriasis was analyzed. Crude and adjusted odds ratios (ORs) were analyzed using a conditional logistic regression analysis. Subgroup analyses were conducted according to age group and sex. RESULTS: The adjusted HR of osteoporosis was 1.09 (95% confidence interval [CI] = 1.05-1.13, P < 0.001) in study I. In the subgroup analysis according to age and sex, the results were consistent except for ≥ 60-year-old women. The adjusted OR of psoriasis was 1.21 (95% CI = 1.16-1.27, P < 0.001) in study II. All subgroups demonstrated high adjusted ORs of osteoporosis for psoriasis. CONCLUSIONS: Psoriasis increased the risk of osteoporosis among participants aged ≥ 40 years in Korea.

Diagnostic value of bronchoalveolar lavage and bronchial washing in sputum-scarce or smear-negative cases with suspected pulmonary tuberculosis: a randomized study.

OBJECTIVES: Bronchoalveolar lavage (BAL) and bronchial washing (BW) are two major methods used to obtain high-quality respiratory specimens from patients with suspected pulmonary tuberculosis (TB) but a sputum-scarce or smear-negative status. We aimed to compare the value of BAL and BW in the diagnosis of TB in such patients. METHODS: We enrolled patients with suspected pulmonary TB but with a sputum-scarce or smear-negative status who were referred for bronchoscopy between October 2013 and January 2016. Participants were randomized into the BAL and BW groups for evaluation. The primary outcome was the diagnostic yield for TB detection. Secondary outcomes included culture positivity, positivity of nucleic acid amplification tests (NAATs) for Mycobacterium tuberculosis and procedure-related complications. RESULTS: A total of 94 patients were assessed and 91 (43 in the BAL group, 48 in the BW group) were analysed. Twenty-one patients (48.8%) in the BAL group and 30 (62.5%) in the BW group had a final diagnosis of pulmonary TB. The detection rate of M. tuberculosis by culture or NAAT was significantly higher in BAL specimens than in BW specimens (85.7% vs 50.0%, p 0.009). The procedure-related complications were hypoxic events, 2/43 (4.7%) in the BAL group and 5/48 (10.4%) in the BW group; and post-bronchoscopic fever, 3/43 (7.0%) in the BAL group and 4/48 (8.3%) in the BW group. DISCUSSION: As long as it is tolerable, BAL rather than BW, should be used to obtain specimens for the diagnosis of pulmonary TB in sputum-scarce or smear-negative cases.

Mortality and cause of death postoperatively in patients with a hip fracture: a national cohort longitudinal follow-up study.

Aims: The aim of this study was to compare the rate of mortality and causes of death in Korean patients who undergo surgery for a fracture of the hip, up to 11 years after the injury, with a control group from the general population. Materials and Methods: National cohort data from Korean Health Insurance Review and Assessment Service - National Sample Cohort were used. A ratio of 1:4 matched patients with a fracture who underwent surgery (3383, fracture group) between 2003 and 2012, and controls (13 532) were included. The matches were processed for age, gender, income, and region of residence. We also undertook analyses of subgroups according to age and gender. The mean follow-up was 4.45 years (1 to 11). Results: The prevalence of hypertension, diabetes, and stroke was significantly higher in the fracture group and dyslipidemia in the controls. Both crude and adjusted hazard ratios (HR) for the rate of mortality in the fracture group were > 2 (crude HR 2.03, 95% confidence interval (CI) 1.91 to 2.17, p < 0.001; adjusted HR 2.07, 95% CI 1.94 to 2.21, p < 0.001). The HRs were also > 2 for both men and women, and for both those aged ≥ 50 years and < 50 years. However, for those aged < 50 years, they were insignificant. The rates of mortality due to all 11 major causes of death classified following Korean standard classification of diseases were significantly higher in the fracture group compared with the control group, except those in the mental and behavioral disorders category. Conclusion: The rate of mortality in the fracture group was significantly higher than in the control group up to 11 years after the surgery. The rate of death due to almost every major cause was significantly higher in the fracture group compared with the control group. Cite this article: Bone Joint J 2018;100-B:436-42.

Locally delivered ethyl-2,5-dihydroxybenzoate using 3D printed bone implant for promotion of bone regeneration in a osteoporotic animal model.

Osteoporosis is a disease characterized by low bone mass, most commonly caused by an increase in bone resorption that is not matched by sufficient bone formation. The most common complications of postmenopausal osteoporosis are bone-related defects and fractures. Fracture healing is a multifactorial bone regeneration process, influenced by both biological and mechanical factors related to age, osteoporosis and stability of the osteosynthesis. During the treatment of bone defects in osteoporotic conditions, imbalanced bone remodeling is the leading cause for implant failure. To overcome these problems, ethyl-2,5-dihydroxybenzoate (E-2,5-DHB), a drug that promotes bone formation and inhibits bone resorption, was used. E-2,5-DHB-incorporating titanium (Ti) implants using poly(lactic-co-glycolic acid) (PLGA) coating for local delivery of E-2,5-DHB were developed and the effects on bone healing of femoral defects were evaluated in an osteoporotic model. The release of E-2,5-DHB resulted in decreased bone resorption and increased bone formation around the implant. Thus, it was confirmed that, in the osteoporotic model, bone healing was increased and implant fixation was enhanced. These results suggested that E-2,5-DHB-coated Ti implants have great potential as an ultimate local drug delivery system for bone tissue scaffolds.

iNKT cells prevent obesity-induced hepatic steatosis in mice in a C-C chemokine receptor 7-dependent manner.

Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism. Our results demonstrated that body and liver weights were higher in the CCR7-/- mice than in the wild-type (WT) mice when they were fed a high-fat diet. Further, glucose tolerance and insulin sensitivity were markedly diminished in CCR7-/- mice. The number of invariant natural killer T (iNKT) cells was reduced in the livers of the CCR7-/- mice. Moreover, liver inflammation was detected in obese CCR7-/- mice, which was ameliorated by the adoptive transfer of hepatic mononuclear cells from WT mice, but not through the transfer of hepatic mononuclear cells from CD1d-/- or interleukin-10-deficient (IL-10-/-) mice. Overall, these results suggest that CCR7+ mononuclear cells in the liver could regulate obesity-induced hepatic steatosis via induction of IL-10-expressing iNKT cells.

Predictors of responses to immune checkpoint blockade in advanced melanoma.

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.

The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage.

We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not improve forelimb function nor did it significantly reduce MPO levels in the hemi-contused cord. To determine if the disparate results using the CD11d mAb were due to the biomechanical nature of the cord injury (compression SCI versus contusion SCI) or to the spinal level of the injury (12th thoracic level versus cervical) we further evaluated the CD11d mAb treatment after a T12 contusion SCI. In contrast to the T12 clip compression SCI, the CD11d mAb treatment did not improve locomotor recovery or significantly reduce MPO levels after T12 contusion SCI. Lesion analyses revealed increased levels of hemorrhage after contusion SCI compared to clip-compression SCI. SCI that is accompanied by increased intraspinal hemorrhage would be predicted to be refractory to the CD11d mAb therapy as this approach targets leukocyte diapedesis through the intact vasculature. These results suggest that the disparate results of the anti-CD11d treatment in contusion and clip-compression models of SCI are due to the different pathophysiological mechanisms that dominate these two types of spinal cord injuries.

Changes of cortical activation in swallowing following high frequency repetitive transcranial magnetic stimulation in older adults.

BACKGROUND: This study explored whether high-frequency repetitive transcranial magnetic stimulation (rTMS) can induce positive changes in the cortical areas of older adults who do not have functional difficulties in swallowing. METHODS: Ten healthy, right-handed, elderly volunteers were subjected to 18F-labeled fluorodeoxyglucose positron emission tomography(FDG-PET) scans when at rest, swallowing before rTMS, and swallowing after rTMS. During the swallowing study, water was infused orally via a catheter at a rate of 600 mL/h. Subjects swallowed water every 20 seconds following a light flash for 30 minutes. During rest, the light source was active, but subjects were requested not to swallow. The rTMS consisted of 5 Hz applied to a pharyngeal motor hot spot in the right hemisphere for 10 minutes every weekday for 2 weeks. The intensity of the stimulation was set at 90% of the thenar motor threshold of the same hemisphere. The differences between each patient's active image and the control images (P<.05) on a voxel-by-voxel basis were examined to find significant increases in metabolism using statistical parametric mapping software. KEY RESULTS: The cortical areas activated by swallowing before rTMS included the bilateral sensorimotor cortex (Brodmann's areas 3 and 4) and showed symmetry. The cortical areas activated by swallowing after rTMS were the same as the areas before rTMS. There was no statistical difference between the two swallowing activation areas. CONCLUSIONS AND INFERENCES: Older adults displayed the symmetry of cortical control of swallowing function. High frequency rTMS did not affect the activation in the swallowing sensorimotor cortices of elderly people.

An analysis of ideal and actual time to surgery after traumatic spinal cord injury in Canada.

STUDY DESIGN: Retrospective analysis of a prospective registry and surgeon survey. OBJECTIVES: To identify surgeon opinion on ideal practice regarding the timing of decompression/stabilization for spinal cord injury and actual practice. Discrepancies in surgical timing and barriers to ideal timing of surgery were explored. SETTING: Canada. METHODS: Patients from the Rick Hansen Spinal Cord Registry (RHSCIR, 2004-2014) were reviewed to determine actual timing of surgical management. Following data collection, a survey was distributed to Canadian surgeons, asking for perceived to be the optimal and actual timings of surgery. Discrepancies between actual data and surgeon survey responses were then compared using χ2 tests and logistic regression. RESULTS: The majority of injury patterns identified in the registry were treated operatively. ASIA Impairment Scale (AIS) C/D injuries were treated surgically less frequently in the RHSCIR data and surgeon survey (odds ratio (OR)= 0.39 and 0.26). Significant disparities between what surgeons identified as ideal, actual current practice and RHSCIR data were demonstrated. A great majority of surgeons (93.0%) believed surgery under 24 h was ideal for cervical AIS A/B injuries and 91.0% for thoracic AIS A/B/C/D injuries. Definitive surgical management within 24 h was actually accomplished in 39.0% of cervical and 45.0% of thoracic cases. CONCLUSION: Ideal surgical timing for traumatic spinal cord injury (tSCI) within 24 h of injury was identified, but not accomplished. Discrepancies between the opinions on the optimal and actual timing of surgery in tSCI patients suggest the need for strategies for knowledge translation and reduction of administrative barriers to early surgery.

Enhanced Th2 cell differentiation and function in the absence of Nox2.

BACKGROUND: Patients with chronic granulomatous disease (CGD), whom inherit abnormal function of NADPH oxidase 2 (Nox2), suffer from hyperinflammatory responses in lung as well as bacterial and fungal infection. There have been studies to reveal the function of Nox2 in hyperinflammatory diseases, especially in asthma, but the exact role of Nox2 in asthma is still unclear and controversial. Therefore, we attempted to clarify the exact role of Nox2 in asthma, using various experimental asthma models. METHODS: Asthma phenotypes were analyzed in response to various allergen-induced experimental asthma using Nox2-deficient mice and recombinase gene-activating-1-deficient mice. To understand the underlying mechanisms of exaggerated Th2 effector functions, we investigated the degree of T-cell activation, levels of activation-induced cell death (AICD), and regulatory T (Treg)-cell differentiation in Nox2-deficient T cells. RESULTS: Asthma phenotypes were increased through enhanced Th2 differentiation and function in Nox2-null mice regardless of dose and route of various allergens. Nox2-deficient T cells also showed hyperactivation, reduced AICD, and diminished Treg-cell differentiation through increased AKT phosphorylation (T308/S473) and enhanced mitochondrial ROS production. CONCLUSION: Our findings indicate that Nox2 deficiency results in exaggerated experimental asthma, which is caused by enhanced Th2 effector function in a T-cell-intrinsic manner.

The differential effects of norepinephrine and dopamine on cerebrospinal fluid pressure and spinal cord perfusion pressure after acute human spinal cord injury.

STUDY DESIGN: Prospective vasopressor cross-over interventional studyObjectives:To examine how two vasopressors used in acute traumatic spinal cord injury (SCI) affect intrathecal cerebrospinal fluid pressure and the corresponding spinal cord perfusion pressure (SCPP). SETTING: Vancouver, British Columbia, Canada. METHODS: Acute SCI patients over the age of 17 with cervical or thoracic ASIA Impairment Scale (AIS). A, B or C injuries were enrolled in this study. Two vasopressors, norepinephrine and dopamine, were evaluated in a 'crossover procedure' to directly compare their effect on the intrathecal pressure (ITP). The vasopressor cross-over procedures were performed in the intensive care unit where ITP, mean arterial pressure (MAP) and heart rate were being continuously measured. The SCPP was calculated as the difference between MAP and ITP. RESULTS: A total of 11 patients were enrolled and included in our analysis. There were 6 patients with AIS A, 3 with AIS B and 2 with AIS C injuries at baseline. We performed 24 cross-over interventions in these 11 patients. There was no difference in MAP with the use of norepinephrine versus dopamine (84±1 mm Hg for both; P=0.33). Conversely, ITP was significantly lower with the use of norepinephrine than with dopamine (17±1 mm Hg vs 20±1 mm Hg, respectively, P<0.001). This decrease in ITP with norepinephrine resulted in an increased SCPP during the norepinephrine infusion when compared with dopamine (67±1 mm Hg vs 65±1 mm Hg respectively, P=0.0049). CONCLUSION: Norepinephrine was able to maintain MAP with a lower ITP and a correspondingly higher SCPP as compared with dopamine in this study. These results suggest that norepinephrine may be preferable to dopamine if vasopressor support is required post SCI to maintain elevated MAPs in accordance with published guidelines.

Gut commensal Bacteroides acidifaciens prevents obesity and improves insulin sensitivity in mice.

In humans, the composition of gut commensal bacteria is closely correlated with obesity. The bacteria modulate metabolites and influence host immunity. In this study, we attempted to determine whether there is a direct correlation between specific commensal bacteria and host metabolism. As mice aged, we found significantly reduced body weight and fat mass in Atg7ΔCD11c mice when compared with Atg7f/f mice. When mice shared commensal bacteria by co-housing or feces transfer experiments, body weight and fat mass were similar in both mouse groups. By pyrosequencing analysis, Bacteroides acidifaciens (BA) was significantly increased in feces of Atg7ΔCD11c mice compared with those of control Atg7f/f mice. Wild-type C57BL/6 (B6) mice fed with BA were significantly more likely to gain less weight and fat mass than mice fed with PBS. Of note, the expression level of peroxisome proliferator-activated receptor alpha (PPARα) was consistently increased in the adipose tissues of Atg7ΔCD11c mice, B6 mice transferred with fecal microbiota of Atg7ΔCD11c mice, and BA-fed B6 mice. Furthermore, B6 mice fed with BA showed elevated insulin levels in serum, accompanied by increased serum glucagon-like peptide-1 and decreased intestinal dipeptidyl peptidase-4. These finding suggest that BA may have potential for treatment of metabolic diseases such as diabetes and obesity.

Multidetector CT angiography in the diagnosis and classification of carotid-cavernous fistula.

AIM: To evaluate the performance of multidetector computed tomography angiography (MDCTA) in identifying and classifying carotid-cavernous fistulas (CCFs). MATERIALS AND METHODS: The neuro-interventional database was searched for patients with CCFs at four different institutions and for normal controls at one of the four institutions. Thirty-four patients were divided into the case group (direct type, n=8; indirect type, n=8) and the control group (n=18). Two readers retrospectively evaluated thin-section CTA images for the presence and laterality of four findings: (1) engorged ophthalmic vein, (2) engorged cavernous sinus, (3) similar enhancement of the cavernous sinus (CS) and internal carotid artery (ICA), and (4) greater enhancement of the CS than the transverse sinus (TS). Dehiscent ICA for the direct type was assessed only in the case group. Sensitivity, specificity, and inter-reader agreement were determined. Attenuation differences between the ICA and CS and between the CS and TS were compared across groups. RESULTS: The sensitivity/specificity for two engorgement and two enhancement findings were 81%/100%, 88%/94%, 100%/100%, and 88%/100%, respectively, for Reader 1, and 75%/100%, 75%/100%, 88%/100%, and 88%/100%, respectively, for Reader 2. Agreement between readers was excellent for all findings (κ>0.80). Dehiscent ICA identified the direct type with a sensitivity/specificity of 100%/75% for Reader 1 and 100%/88% for Reader 2 (κ=0.871). In the case group, the difference between ICA and CS attenuation values was significantly lower (180.1±76.6 versus 7.5±23.7; ⤳<0.001) and that between CS and TS were higher (-31.2±69 versus 102.6±59.3; ⤳<0.001). The area under the curve for the latter values was 0.95. CONCLUSION: The engorgement and enhancement categories in MDCTA may perform comparably in identifying CCFs and measurements of vessel attenuation differences may be of high diagnostic value. Dehiscent ICA can greatly aid in identifying the direct type.

Perspectives on strategies and challenges in the conversation about stem cells for spinal cord injury.

STUDY DESIGN: Qualitative study. OBJECTIVE: To examine how trusted communication between individuals with spinal cord injury (ISCIs) and physicians who care for ISCIs is affected by the discussion of advances in stem cell research and interventions locally and abroad. SETTING: Canada and the United States (US). METHODS: Semi-structured interviews with ISCIs and physicians. A thematic analysis approach was applied to more than 12 h of data to derive prominent themes and describe relationships between them. RESULTS: A convergence of factors involving transparency impact trusted communication between ISCIs and physicians about stem cells and spinal cord injury (SCI). ISCIs expressed that trusted communication is strengthened when physicians exhibit caring, attentive and positive attitudes that are underpinned by domain-specific knowledge and scholarship. Perceived reluctance to communicate or lack of knowledge poses significant challenges. Physicians also emphasised the importance of transparency for trusted communication but expressed that the still limited clinical reality of treatment choices for SCI and the pressures imposed by external resources are significant stressors that complicate the communication landscape. Both groups cited the range and variable quality of information sources, and the difficulty associated with navigating them, as priorities for action that would remediate these tensions. CONCLUSIONS: (1) Epistemic transparency should be privileged over silence. (2) A new generation of innovations in research and clinical trial dissemination about stem cells for SCI is needed to remedy the perceived inadequacies of existing information content and accessibility.

Developing a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part III: outcomes.

STUDY DESIGN: Focus Group. OBJECTIVES: To develop a unified, regional spinal cord injury (SCI) research strategy for Australia and New Zealand. SETTING: Australia. METHODS: A 1-day structured stakeholder dialogue was convened in 2013 in Melbourne, Australia, by the National Trauma Research Institute in collaboration with the SCI Network of Australia and New Zealand. Twenty-three experts participated, representing local and international research, clinical, consumer, advocacy, government policy and funding perspectives. Preparatory work synthesised evidence and articulated draft principles and options as a starting point for discussion. RESULTS: A regional SCI research strategy was proposed, whose objectives can be summarised under four themes. (1) Collaborative networks and strategic partnerships to increase efficiency, reduce duplication, build capacity and optimise research funding. (2) Research priority setting and coordination to manage competing studies. (3) Mechanisms for greater consumer engagement in research. (4) Resources and infrastructure to further develop SCI data registries, evaluate research translation and assess alignment of research strategy with stakeholder interests. These are consistent with contemporary international SCI research strategy development activities. CONCLUSION: This first step in a regional SCI research strategy has articulated objectives for further development by the wider SCI research community. The initiative has also reinforced the importance of coordinated, collective action in optimising outcomes following SCI.

Structural biomarkers in the cerebrospinal fluid within 24 h after a traumatic spinal cord injury: a descriptive analysis of 16 subjects.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To characterize the cerebrospinal fluid (CSF) concentrations of glial fibrillary acidic protein, neuron specific enolase (NSE), S-100ß, tau and neurofilament heavy chain (NFH) within 24 h of an acute traumatic spinal cord injury (SCI), and to correlate these concentrations with the baseline severity of neurologic impairment as graded by the American Spinal Injury Association impairment scale (AIS). METHODS: A lumbar puncture was performed to obtain CSF from 16 acute traumatic SCI patients within 24 h post injury. Neurological examinations were performed within 24 h of injury and again at 6 or 12 months post injury. The correlations between the CSF concentrations and initial AIS were calculated by using Pearson correlation coefficients. In addition, an independent Student's t-test was used to test for differences in CSF concentrations between patients of different AIS grades. RESULTS: The CSF NSE concentrations were significantly correlated with the baseline neurologic impairment being either 'motor complete' (AIS A, B) or 'motor incomplete' (AIS C, D) (r=0.520, P<0.05). The mean S-100ß concentration in motor complete patients was significantly higher compared with motor incomplete patients; 377.2 µg l(-1) (s.d.±523 µg l(-1)) vs 57.1 µg l(-1) (s.d.±56 µg l(-1)) (P<0.05), respectively. Lastly, the mean NFH concentration in motor complete patients was significantly higher compared with motor incomplete patient, 11 813 ng l(-1) (s.d.±16 195 ng l(-1)) vs 1446.8 ng l(-1) (s.d.±1533 ng l(-1)), (P<0.05), respectively. CONCLUSION: In this study we identified differences in the structural CSF biomarkers NSE, S-100ß and NFH between motor complete and motor incomplete SCI patients. Our data showed no clear differences in any of the protein concentrations between the different AIS grades.