The radiological interpretation of possible microbleeds after moderate or severe traumatic brain injury: a longitudinal study.

INTRODUCTION: In order to augment the certainty of the radiological interpretation of "possible microbleeds" after traumatic brain injury (TBI), we assessed their longitudinal evolution on 3-T SWI in patients with moderate/severe TBI. METHODS: Standardized 3-T SWI and T1-weighted imaging were obtained 3 and 26 weeks after TBI in 31 patients. Their microbleeds were computer-aided detected and classified by a neuroradiologist as no, possible, or definite at baseline and follow-up, separately (single-scan evaluation). Thereafter, the classifications were re-evaluated after comparison between the time-points (post-comparison evaluation). We selected the possible microbleeds at baseline at single-scan evaluation and recorded their post-comparison classification at follow-up. RESULTS: Of the 1038 microbleeds at baseline, 173 were possible microbleeds. Of these, 53.8% corresponded to no microbleed at follow-up. At follow-up, 30.6% were possible and 15.6% were definite. Of the 120 differences between baseline and follow-up, 10% showed evidence of a pathophysiological change over time. Proximity to extra-axial injury and proximity to definite microbleeds were independently predictive of becoming a definite microbleed at follow-up. The reclassification level differed between anatomical locations. CONCLUSIONS: Our findings support disregarding possible microbleeds in the absence of clinical consequences. In selected cases, however, a follow-up SWI-scan could be considered to exclude evolution into a definite microbleed.

Cerebrolysin after moderate to severe traumatic brain injury: prospective meta-analysis of the CAPTAIN trial series.

INTRODUCTION: This prospective meta-analysis summarizes results from the CAPTAIN trial series, evaluating the effects of Cerebrolysin for moderate-severe traumatic brain injury, as an add-on to usual care. MATERIALS AND METHODS: The study included two phase IIIb/IV prospective, randomized, double-blind, placebo-controlled clinical trials. Eligible patients with a Glasgow Coma Score (GCS) between 6 and 12 received study medication (50 mL of Cerebrolysin or physiological saline solution per day for ten days, followed by two additional treatment cycles with 10 mL per day for 10 days) in addition to usual care. The meta-analysis comprises the primary ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses based on multivariate, directional tests. RESULTS: A total 185 patients underwent meta-analysis (mean admission GCS = 10.3, mean age = 45.3, and mean Baseline Prognostic Risk Score = 2.8). The primary endpoint, a multidimensional ensemble of functional and neuropsychological outcome scales indicated a "small-to-medium" sized effect in favor of Cerebrolysin, statistically significant at Day 30 and at Day 90 (Day 30: MWcombined = 0.60, 95%CI 0.52 to 0.66, p = 0.0156; SMD = 0.31; OR = 1.69; Day 90: MWcombined = 0.60, 95%CI 0.52 to 0.68, p = 0.0146; SMD = 0.34, OR = 1.77). Treatment groups showed comparable safety and tolerability profiles. DISCUSSION: The meta-analysis of the CAPTAIN trials confirms the safety and efficacy of Cerebrolysin after moderate-severe TBI, opening a new horizon for neurorecovery in this field. Integration of Cerebrolysin into existing guidelines should be considered after careful review of internationally applicable criteria.

Biomarkers in traumatic brain injury: new concepts.

Traumatic brain injury is a multifaceted condition that encompasses a spectrum of injuries: contusions, axonal injuries in specific brain regions, edema, and hemorrhage. Brain injury determines a broad clinical and disability spectrum due to the implication of various cellular pathways, genetic phenotypes, and environmental factors. It is challenging to predict patient outcomes, to appropriately evaluate the patients, to determine a suitable treatment strategy and rehabilitation program, and to communicate with patient relatives. Biomarkers detected from body fluids are potential evaluation tools for traumatic brain injury patients. These may serve as internal indicators of cerebral damage, delivering valuable information about the dynamic cellular, biochemical, and molecular environments. The diagnostic and prognostic value of biomarkers tested both in animal models of traumatic brain injury is still under question, despite a considerable scientific literature. Recent publications emphasize that a more realistic approach involves combining multiple types of biomarkers with other investigative tools (imaging, outcome scales, and genetic polymorphisms). Additionally, there is increasing interest in the use of biomarkers as tools for treatment monitoring and as surrogate outcome variables to facilitate the design of distinct randomized controlled trials. This review highlights the latest available evidence regarding biomarkers in adults after traumatic brain injury and discusses new approaches in the evaluation of this patient group.

Efficacy and safety of cerebrolysin in neurorecovery after moderate-severe traumatic brain injury: results from the CAPTAIN II trial.

INTRODUCTION: The objective of this trial was to evaluate the efficacy and safety of Cerebrolysin in treating patients after moderate to severe traumatic brain injury (TBI) as an adjunct to standard care protocols. The trial was designed to investigate the clinical effects of Cerebrolysin in the acute (neuroprotective) stage and during early and long-term recovery as part of a neurorestorative strategy. MATERIALS AND METHODS: The study was a phase IIIb/IV single-center, prospective, randomized, double-blind, placebo-controlled clinical trial. Eligible patients with a Glasgow Coma Score (GCS) between 7 and 12 received study medication (50 ml of Cerebrolysin or physiological saline solution per day for 10 days, followed by two additional treatment cycles with 10 ml per day for 10 days) in addition to standard care. We tested ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses using a multivariate, directional test, to reflect the global status of patients after TBI. RESULTS: The study enrolled 142 patients, of which 139 underwent formal analysis (mean age = 47.4, mean admission GCS = 10.4, and mean Baseline Prognostic Risk Score = 2.6). The primary endpoint, a multidimensional ensemble of 13 outcome scales, indicated a "small-to-medium"-sized effect in favor of Cerebrolysin, statistically significant at day 90 (MWcombined = 0.59, 95% CI 0.52 to 0.66, P = 0.0119). Safety and tolerability observations were comparable between treatment groups. CONCLUSION: Our trial confirms previous beneficial effects of the multimodal, biological agent Cerebrolysin for overall outcome after moderate to severe TBI, as measured by a multidimensional approach. Study findings must be appraised and aggregated in conjunction with existing literature, as to improve the overall level of insight regarding therapeutic options for TBI patients. The widely used pharmacologic intervention may benefit from a large-scale observational study to map its use and to establish comparative effectiveness in real-world clinical settings.

Use of multiparametric MRI to characterize uterine fibroid tissue types.

BACKGROUND: Although the biological characteristics of uterine fibroids (UF) have implications for therapy choice and effectiveness, there is limited MRI data about these characteristics. Currently, the Funaki classification and Scaled Signal Intensity (SSI) are used to predict treatment outcome but both screening-tools appear to be suboptimal. Therefore, multiparametric and quantitative MRI was studied to evaluate various biological characteristics of UF. METHODS: 87 patients with UF underwent an MRI-examination. Differences between UF tissues and myometrium were investigated using T2-mapping, Apparent Diffusion Coefficient (ADC) maps with different b-value combinations, contrast-enhanced T1-weighted and T2-weighted imaging. Additionally, the Funaki classification and SSI were calculated. RESULTS: Significant differences between myometrium and UF tissue in T2-mapping (p = 0.001), long-TE ADC low b-values (p = 0.002), ADC all b-values (p < 0.001) and high b-values (p < 0.001) were found. Significant differences between Funaki type 3 versus type 1 and 2 were observed in SSI (p < 0.001) and T2-values (p < 0.001). Significant correlations were found between SSI and T2-mapping (p < 0.001; ρs = 0.82), ADC all b-values (p = 0.004; ρs = 0.31), ADC high b-values (p < 0.001; ρs = 0.44) and long-TE ADC low b-values (p = 0.004; ρs = 0.31). CONCLUSIONS: Quantitative MR-data allowed us to distinguish UF tissue from myometrium and to discriminate different UF tissue types and may, therefore, be a useful tool to predict treatment outcome/determine optimal treatment modality.

Causes and Consequences of Treatment Variation in Moderate and Severe Traumatic Brain Injury: A Multicenter Study.

OBJECTIVES: Although guidelines have been developed to standardize care in traumatic brain injury, between-center variation in treatment approach has been frequently reported. We examined variation in treatment for traumatic brain injury by assessing factors influencing treatment and the association between treatment and patient outcome. DESIGN: Secondary analysis of prospectively collected data. SETTING: Five level I trauma centers in the Netherlands (2008-2009). PATIENTS: Five hundred three patients with moderate or severe traumatic brain injury (Glasgow Coma Scale, 3-13). INTERVENTIONS: We examined variation in seven treatment parameters: direct transfer, involvement of mobile medical team, mechanical ventilation, intracranial pressure monitoring, vasopressors, acute neurosurgical intervention, and extracranial operation. MEASUREMENTS AND MAIN RESULTS: Data were collected on patient characteristics, treatment, and 6-month Glasgow Outcome Scale-Extended. Multivariable logistic regression models were used to assess the extent to which treatment was determined by patient characteristics. To examine whether there were between-center differences in treatment, we used unadjusted and adjusted random effect models with the seven treatment parameters as dependent variables. The influence of treatment approach in a center (defined as aggressive and nonaggressive based on the frequency intracranial pressure monitoring) on outcome was assessed using multivariable random effect proportional odds regression models in those patients with an indication for intracranial pressure monitoring. Sensitivity analyses were performed to test alternative definitions of aggressiveness. Treatment was modestly related to patient characteristics (Nagelkerke R range, 0.12-0.52) and varied widely among centers, even after case-mix correction. Outcome was more favorable in patients treated in aggressive centers than those treated in nonaggressive centers (OR, 1.73; 95% CI, 1.05-3.15). Sensitivity analyses, however, illustrated that the aggressiveness-outcome association was dependent on the definition used. CONCLUSIONS: The considerable between-center variation in treatment for patients with brain injury can only partly be explained by differences in patient characteristics. An aggressive treatment approach may imply better outcome although further confirmation is required.

Abnormal connectivity in the sensorimotor network predicts attention deficits in traumatic brain injury.

The aim of this study was to explore modifications of functional connectivity in multiple resting-state networks (RSNs) after moderate to severe traumatic brain injury (TBI) and evaluate the relationship between functional connectivity patterns and cognitive abnormalities. Forty-three moderate/severe TBI patients and 34 healthy controls (HC) underwent resting-state fMRI. Group ICA was applied to identify RSNs. Between-subject analysis was performed using dual regression. Multiple linear regressions were used to investigate the relationship between abnormal connectivity strength and neuropsychological outcome. Forty (93%) TBI patients showed moderate disability, while 2 (5%) and 1 (2%) upper severe disability and low good recovery, respectively. TBI patients performed worse than HC on the domains attention and language. We found increased connectivity in sensorimotor, visual, default mode (DMN), executive, and cerebellar RSNs after TBI. We demonstrated an effect of connectivity in the sensorimotor RSN on attention (p < 10-3) and a trend towards a significant effect of the DMN connectivity on attention (p = 0.058). A group-by-network interaction on attention was found in the sensorimotor network (p = 0.002). In TBI, attention was positively related to abnormal connectivity within the sensorimotor RSN, while in HC this relation was negative. Our results show altered patterns of functional connectivity after TBI. Attention impairments in TBI were associated with increased connectivity in the sensorimotor network. Further research is needed to test whether attention in TBI patients is directly affected by changes in functional connectivity in the sensorimotor network or whether the effect is actually driven by changes in the DMN.

Comparing health-related quality of life of Dutch and Chinese patients with traumatic brain injury: do cultural differences play a role?

BACKGROUND: There is growing interest in health related quality of life (HRQoL) as an outcome measure in international trials. However, there might be differences in the conceptualization of HRQoL across different socio-cultural groups. The objectives of current study were: (I) to compare HRQoL, measured with the short form (SF)-36 of Dutch and Chinese traumatic brain injury (TBI) patients 1 year after injury and; (II) to assess whether differences in SF-36 profiles could be explained by cultural differences in HRQoL conceptualization. TBI patients are of particular interest because this is an important cause of diverse impairments and disabilities in functional, physical, emotional, cognitive, and social domains that may drastically reduce HRQoL. METHODS: A prospective cohort study on adult TBI patients in the Netherlands (RUBICS) and a retrospective cohort study in China were used to compare HRQoL 1 year post-injury. Differences on subscales were assessed with the Mann-Whitney U-test. The internal consistency, interscale correlations, item-internal consistency and item-discriminate validity of Dutch and Chinese SF-36 profiles were examined. Confirmatory factor analysis was performed to assess whether Dutch and Chinese data fitted the SF-36 two factor-model (physical and mental construct). RESULTS: Four hundred forty seven Dutch and 173 Chinese TBI patients were included. Dutch patients obtained significantly higher scores on role limitations due to emotional problems (p < .001) and general health (p < .001), while Chinese patients obtained significantly higher scores on physical functioning (p < .001) and bodily pain (p = .001). Scores on these subscales were not explained by cultural differences in conceptualization, since item- and scale statistics were all sufficient. However, differences among Dutch and Chinese patients were found in the conceptualization of the domains vitality, mental health and social functioning. CONCLUSIONS: One year after TBI, Dutch and Chinese patients reported a different pattern of HRQoL. Further, there might be cultural differences in the conceptualization of some of the SF-36 subscales, which has implications for outcome evaluation in multi-national trials.

Reliability of the NINDS common data elements cranial tomography (CT) rating variables for traumatic brain injury (TBI).

BACKGROUND: Non-contrast head computer tomography (CT) is widely used to evaluate eligibility of patients after acute traumatic brain injury (TBI) for clinical trials. The NINDS Common Data Elements (CDEs) TBI were developed to standardize collection of CT variables. The objectives of this study were to train research assistants (RAs) to rate CDEs and then to evaluate their performance. The aim was to assess inter-rater reliability (IRR) of CDEs between trained RAs and a neurologist and to evaluate applicability of CDEs in acute and sub-acute TBI to test the feasibility of using CDE CT ratings in future trials and ultimately in clinical practice. The second aim was to confirm that the ratings of CDEs reflect pathophysiological events after TBI. METHODS AND RESULTS: First, a manual was developed for application of the CDEs, which was used to rate brain CTs (n = 100). An excellent agreement was found in combined kappas between RAs on admission and on 24-hour follow-up CTs (Iota = 0.803 and 0.787, respectively). Good IRR (kappa > 0.61) was shown for six CDEs on admissions and for seven CDEs on follow-up CTs. Low IRR (kappa < 0.4) was determined for five CDEs on admission and for four CDEs on follow-up CT. Combined IRR of each assistant with the neurologist were good on admission (Iota = 0.613 and 0.787) and excellent on follow-up CT (Iota = 0.906 and 0.977). Second, Principal Component Analysis (PCA) was applied to cluster the rated CDEs (n = 255) and five major components were found that explain 53% of the variance. CONCLUSIONS: CT CDEs are useful in clinical studies of TBI. Trained RAs can reliably collect variables. PCA identifies CDE clusters with clinical and biologic plausibility. ABBREVIATIONS: RA, research assistant; CT, Cranial Tomography; TBI, Traumatic Brain Injury; CDE, Common Data Elements; IRR, inter-rater reliability; PCA, Principal Component Analysis; GCS, Glasgow Coma Scale; R, rater; CI, confidence interval; CCC, Concordance correlation coefficient; IVH, Intraventricular haemorrhage; DCA, Discriminant Component analysis; SAH, Subarachnoid Haemorrhage.

What is the definition of sports-related concussion: a systematic review.

OBJECTIVES: Various definitions for concussion have been proposed, each having its strengths and weaknesses. We reviewed and compared current definitions and identified criteria necessary for an operational definition of sports-related concussion (SRC) in preparation of the 5th Concussion Consensus Conference (Berlin, Germany). We also assessed the role of biomechanical studies in informing an operational definition of SRC. DESIGN: This is a systematic literature review. DATA SOURCES: Data sources include MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Clinical Trials and SPORT Discus (accessed 14 September 2016). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligibility criteria were studies reporting (clinical) criteria for diagnosing SRC and studies containing SRC impact data. RESULTS: Out of 1601 articles screened, 36 studies were included (2.2%), 14 reported on criteria for SRC definitions and 22 on biomechanical aspects of concussions. Six different operational definitions focusing on clinical findings and their dynamics were identified. Biomechanical studies were obtained almost exclusively on American football players. Angular and linear head accelerations linked to clinically confirmed concussions demonstrated considerable individual variation. SUMMARY/CONCLUSIONS: SRC is a traumatic brain injury that is defined as a complex pathophysiological process affecting the brain, induced by biomechanical forces with several common features that help define its nature. Limitations identified include that the current criteria for diagnosing SRC are clinically oriented and that there is no gold/standard to assess their diagnostic properties. A future, more valid definition of SRC would better identify concussed players by demonstrating high predictive positive/negative values. Currently, the use of helmet-based systems to study the biomechanics of SRC is limited to few collision sports. New approaches need to be developed to provide objective markers for SRC.

Everything we always wanted to know about furosemide but were afraid to ask.

Furosemide is a widely used, potent natriuretic drug, which inhibits the Na(+)-K(+)-2Cl(-) cotransporter (NKCC)-2 in the ascending limb of the loop of Henle applied to reduce extracellular fluid volume expansion in heart and kidney disease. Undesirable consequences of furosemide, such as worsening of kidney function and unpredictable effects on sodium balance, led to this critical evaluation of how inhibition of NKCC affects renal and cardiovascular physiology. This evaluation reveals important knowledge gaps, involving furosemide as a drug, the function of NKCC2 (and NKCC1), and renal and systemic indirect effects of NKCC inhibition. Regarding renal effects, renal blood flow and glomerular filtration rate could become compromised by activation of tubuloglomerular feedback or by renin release, particularly if renal function is already compromised. Modulation of the intrarenal renin angiotensin system, however, is ill-defined. Regarding systemic effects, vasodilation followed by nonspecific NKCC inhibition and changes in venous compliance are not well understood. Repetitive administration of furosemide induces short-term (braking phenomenon, acute diuretic resistance) and long-term (chronic diuretic resistance) adaptations, of which the mechanisms are not well known. Modulation of NKCC2 expression and activity in kidney and heart failure is ill-defined. Lastly, furosemide's effects on cutaneous sodium stores and on uric acid levels could be beneficial or detrimental. Concluding, a considerable knowledge gap is identified regarding a potent drug with a relatively specific renal target, NKCC2, and renal and systemic actions. Resolving these questions would increase the understanding of NKCCs and their actions and improve rational use of furosemide in pathophysiology of fluid volume expansion.

Middle Childhood Support-Seeking Behavior During Stress: Links With Self-Reported Attachment and Future Depressive Symptoms.

This study tested whether children's more anxious and avoidant attachment is linked to decreased support-seeking behavior toward their mother during stress in middle childhood, and whether children's decreased support-seeking behavior enhances the impact of experiencing life events on the increase of depressive symptoms 18 months later. Ninety-eight 8- to 12-year-old children filled out questionnaires assessing their level of anxious and avoidant attachment and depressive symptoms. Children's support-seeking behavior was observed through measuring the time children waited before calling for their mother's help while carrying out a stressful task. Results supported the hypothesis that more anxiously or avoidantly attached children waited longer before seeking maternal support. Moreover, waiting longer was related to increased depressive symptoms at follow-up in children who reported more experienced life events.

The juvenile head trauma syndrome: a trauma triggered migraine?

BACKGROUND: The underlying mechanism of the juvenile head trauma syndrome (JHTS) is still uncertain, but it has been suggested that there is a role in cortical spreading depression, a phenomenon that is assumed to be a part of the pathophysiology of migraine. HYPOTHESIS: We postulate that children affected by the JHTS are more susceptible to cortical spreading depression, caused by a genetic etiology similar to genetic factors in migraine. METHODS: Children with the JHTS were selected and evaluated retrospectively in an observational case-control study in two Dutch trauma centers in the period between January 2008 and July 2012. RESULTS: We included 33 patients with the JHTS, who were accounted for approximately 2.5% of the total number (1,342) of children seen at the emergency department with a mild head trauma. The prevalence of migraine in cases compared with controls did not differ. The proportion of patients with a first-degree relative with migraine was significantly higher in cases compared with controls (odds ratio, 2.69; 95% confidence interval, 1.16-6.22; p = 0.010). CONCLUSION: The JHTS is a relatively rare phenomenon, seen in approximately 2.5% of all children seen at the emergency department with mild brain injury. This study demonstrates a significant relationship between the JHTS and a positive history of migraine in first-degree relatives.

CT perfusion during delayed cerebral ischemia after subarachnoid hemorrhage: distinction between reversible ischemia and ischemia progressing to infarction.

INTRODUCTION: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) can be reversible or progress to cerebral infarction. In patients with a deterioration clinically diagnosed as DCI, we investigated whether CT perfusion (CTP) can distinguish between reversible ischemia and ischemia progressing to cerebral infarction. METHODS: From a prospectively collected series of aSAH patients, we included those with DCI, CTP on the day of clinical deterioration, and follow-up imaging. In qualitative CTP analyses (visual assessment), we calculated positive and negative predictive value (PPV and NPV) with 95% confidence intervals (95%CI) of a perfusion deficit for infarction on follow-up imaging. In quantitative analyses, we compared perfusion values of the least perfused brain tissue between patients with and without infarction by using receiver-operator characteristic curves and calculated a threshold value with PPV and NPV for the perfusion parameter with the highest area under the curve. RESULTS: In qualitative analyses of 33 included patients, 15 of 17 patients (88%) with and 6 of 16 patients (38%) without infarction on follow-up imaging had a perfusion deficit during clinical deterioration (p = 0.002). Presence of a perfusion deficit had a PPV of 71% (95%CI: 48-89%) and NPV of 83% (95%CI: 52-98%) for infarction on follow-up. Quantitative analyses showed that an absolute minimal cerebral blood flow (CBF) threshold of 17.7 mL/100 g/min had a PPV of 63% (95%CI: 41-81%) and a NPV of 78% (95%CI: 40-97%) for infarction. CONCLUSIONS: CTP may differ between patients with DCI who develop infarction and those who do not. For this purpose, qualitative evaluation may perform marginally better than quantitative evaluation.

Different CT perfusion algorithms in the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Tracer delay-sensitive perfusion algorithms in CT perfusion (CTP) result in an overestimation of the extent of ischemia in thromboembolic stroke. In diagnosing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH), delayed arrival of contrast due to vasospasm may also overestimate the extent of ischemia. We investigated the diagnostic accuracy of tracer delay-sensitive and tracer delay-insensitive algorithms for detecting DCI. METHODS: From a prospectively collected series of aSAH patients admitted between 2007-2011, we included patients with any clinical deterioration other than rebleeding within 21 days after SAH who underwent NCCT/CTP/CTA imaging. Causes of clinical deterioration were categorized into DCI and no DCI. CTP maps were calculated with tracer delay-sensitive and tracer delay-insensitive algorithms and were visually assessed for the presence of perfusion deficits by two independent observers with different levels of experience. The diagnostic value of both algorithms was calculated for both observers. RESULTS: Seventy-one patients were included. For the experienced observer, the positive predictive values (PPVs) were 0.67 for the delay-sensitive and 0.66 for the delay-insensitive algorithm, and the negative predictive values (NPVs) were 0.73 and 0.74. For the less experienced observer, PPVs were 0.60 for both algorithms, and NPVs were 0.66 for the delay-sensitive and 0.63 for the delay-insensitive algorithm. CONCLUSION: Test characteristics are comparable for tracer delay-sensitive and tracer delay-insensitive algorithms for the visual assessment of CTP in diagnosing DCI. This indicates that both algorithms can be used for this purpose.

The influence of APACHE II score on the average noise level in an intensive care unit: an observational study.

BACKGROUND: Noise levels in hospitals, especially in intensive care units (ICUs) are known to be high, potentially affecting not only the patients' well-being but also their clinical outcomes. In an observational study, we made a long-term measurement of noise levels in an ICU, and investigated the influence of various factors on the noise level, including the acute physiology and chronic health evaluation II (APACHE II) score. METHODS: The average noise level was continuously measured for three months in all (eight) patient rooms in an ICU, while the patient data were also registered, including the APACHE II score. The 24-hour trend of the noise level was obtained for the patients of length-of-stay (LOS) ≥1 day, which was compared to the timeline of the ICU routine events. For the patients with LOS ≥4 days, the average noise levels in the first four days were analyzed, and regression models were established using the stepwise search method based on the Akaike information criterion. RESULTS: Features identified in the 24-hour trends (n = 55) agreed well with the daily routine events in the ICU, where regular check-ups raised the 10-minute average noise level by 2~3 dBA from the surrounding values at night, and the staff shift changes consistently increased the noise level by 3~5 dBA. When analyzed in alignment with the patient's admission (n=22), the daytime acoustic condition improved from Day 1 to 2, but worsened from Day 2 to 4, most likely in relation to the various phases of patient's recovery. Regression analysis showed that the APACHE II score, room location, gender, day of week and the ICU admission type could explain more than 50% of the variance in the daily average noise level, LAeq,24h. Where these factors were argued to have causal relations to LAeq,24h, the APACHE II score was found to be most strongly correlated: LAeq,24h increased by 1.3~1.5 dB when the APACHE II score increased by 10 points. CONCLUSIONS: Patient's initial health condition is one important factor that influences the acoustic environment in an ICU, which needs to be considered in observational and interventional studies where the noise in healthcare environments is the subject of investigation.

White matter changes in comatose survivors of anoxic ischemic encephalopathy and traumatic brain injury: comparative diffusion-tensor imaging study.

PURPOSE: To analyze white matter pathologic abnormalities by using diffusion-tensor (DT) imaging in a multicenter prospective cohort of comatose patients following cardiac arrest or traumatic brain injury (TBI). MATERIALS AND METHODS: Institutional review board approval and informed consent from proxies and control subjects were obtained. DT imaging was performed 5-57 days after insult in 49 cardiac arrest and 40 TBI patients. To control for DT imaging-processing variability, patients' values were normalized to those of 111 control subjects. Automated segmentation software calculated normalized axial diffusivity (λ1) and radial diffusivity (λ⊥) in 19 predefined white matter regions of interest (ROIs). DT imaging variables were compared by using general linear modeling, and side-to-side Pearson correlation coefficients were calculated. P values were corrected for multiple testing (Bonferroni). RESULTS: In central white matter, λ1 differed from that in control subjects in six of seven TBI ROIs and five of seven cardiac arrest ROIs (all P < .01). The λ⊥ differed from that in control subjects in all ROIs in both patient groups (P < .01). In hemispheres, λ1 was decreased compared with that in control subjects in three of 12 TBI ROIs (P < .05) and nine of 12 cardiac arrest ROIs (P < .01). The λ⊥ was increased in all TBI ROIs (P < .01) and in seven of 12 cardiac arrest ROIs (P < .05). Cerebral hemisphere λ1 was lower in cardiac arrest than in TBI in six of 12 ROIs (P < .01), while λ⊥ was higher in TBI than in cardiac arrest in eight of 12 ROIs (P < .01). Diffusivity values were symmetrically distributed in cardiac arrest (P < .001 for side-to-side correlation) but not in TBI patients. CONCLUSION: DT imaging findings are consistent with the known predominance of cerebral hemisphere axonal injury in cardiac arrest and chiefly central myelin injury in TBI. This consistency supports the validity of DT imaging for differentiating axon and myelin damage in vivo in humans.

Prostate cancer: computer-aided diagnosis with multiparametric 3-T MR imaging--effect on observer performance.

PURPOSE: To determine the effect of computer-aided diagnosis (CAD) on less-experienced and experienced observer performance in differentiation of benign from malignant prostate lesions at 3-T multiparametric magnetic resonance (MR) imaging. MATERIALS AND METHODS: The institutional review board waived the need for informed consent. Retrospectively, 34 patients were included who had prostate cancer and had undergone multiparametric MR imaging, including T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced MR imaging prior to radical prostatectomy. Six radiologists less experienced in prostate imaging and four radiologists experienced in prostate imaging were asked to characterize different regions suspicious for cancer as benign or malignant on multiparametric MR images first without and subsequently with CAD software. The effect of CAD was analyzed by using a multiple-reader, multicase, receiver operating characteristic analysis and a linear mixed-model analysis. RESULTS: In 34 patients, 206 preannotated regions, including 67 malignant and 64 benign regions in the peripheral zone (PZ) and 19 malignant and 56 benign regions in the transition zone (TZ), were evaluated. Stand-alone CAD had an overall area under the receiver operating characteristic curve (AUC) of 0.90. For PZ and TZ lesions, the AUCs were 0.92 and 0.87, respectively. Without CAD, less-experienced observers had an overall AUC of 0.81, which significantly increased to 0.91 (P = .001) with CAD. For experienced observers, the AUC without CAD was 0.88, which increased to 0.91 (P = .17) with CAD. For PZ lesions, less-experienced observers increased their AUC from 0.86 to 0.95 (P < .001) with CAD. Experienced observers showed an increase from 0.91 to 0.93 (P = .13). For TZ lesions, less-experienced observers significantly increased their performance from 0.72 to 0.79 (P = .01) with CAD and experienced observers increased their performance from 0.81 to 0.82 (P = .42). CONCLUSION: Addition of CAD significantly improved the performance of less-experienced observers in distinguishing benign from malignant lesions; when less-experienced observers used CAD, they reached similar performance as experienced observers. The stand-alone performance of CAD was similar to performance of experienced observers.

Design of COSMIC: a randomized, multi-centre controlled trial comparing conservative or early surgical management of incomplete cervical cord syndrome without spinal instability.

BACKGROUND: Incomplete cervical cord syndrome without spinal instability is a very devastating event for the patient and the family. It is estimated that up to 25% of all traumatic spinal cord lesions belong to this category. The treatment for this type of spinal cord lesion is still subject of discussion. From a biological point of view early surgery could prevent secondary damage due to ongoing compression of the already damaged spinal cord. Historically, however, conservative treatment was propagated with good clinical results. Proponents for early surgery as well those favoring conservative treatment are still in debate. The proposed trial will contribute to the discussion and hopefully also to a decrease in the variability of clinical practice. METHODS/DESIGN: A randomized controlled trial is designed to compare the clinical outcome of early surgical strategy versus a conservative approach. The primary outcome is clinical outcome according to mJOA. This also measured by ASIA score, DASH score and SCIM III score. Other endpoints are duration of the stay at a high care department (medium care, intensive care), duration of the stay at the hospital, complication rate, mortality rate, sort of rehabilitation, and quality of life. A sample size of 36 patients per group was calculated to reach a power of 95%. The data will be analyzed as intention-to-treat at regular intervals, but the end evaluation will take place at two years post-injury. DISCUSSION: At the end of the study, clinical outcomes between treatments attitudes can be compared. Efficacy, but also efficiency can be determined. A goal of the study is to determine which treatment will result in the best quality of life for the patients. This study will certainly contribute to more uniformity of treatment offered to patients with a special sort of spinal cord injury. TRIAL REGISTRATION: Gov: NCT01367405.