Deep Into the Fibers! Postmortem Diffusion Tensor Imaging in Forensic Radiology.

PURPOSE In traumatic brain injury, diffusion-weighted and diffusion tensor imaging of the brain are essential techniques for determining the pathology sustained and the outcome. Postmortem cross-sectional imaging is an established adjunct to forensic autopsy in death investigation. The purpose of this prospective study was to evaluate postmortem diffusion tensor imaging in forensics for its feasibility, influencing factors and correlation to the cause of death compared with autopsy. METHODS Postmortem computed tomography, magnetic resonance imaging, and diffusion tensor imaging with fiber tracking were performed in 10 deceased subjects. The Likert scale grading of colored fractional anisotropy maps was correlated to the body temperature and intracranial pathology to assess the diagnostic feasibility of postmortem diffusion tensor imaging and fiber tracking. RESULTS Optimal fiber tracking (>15,000 fiber tracts) was achieved with a body temperature at 10°C. Likert scale grading showed no linear correlation (P > 0.7) to fiber tract counts. No statistically significant correlation between total fiber count and postmortem interval could be observed (P = 0.122). Postmortem diffusion tensor imaging and fiber tracking allowed for radiological diagnosis in cases with shearing injuries but was impaired in cases with pneumencephalon and intracerebral mass hemorrhage. CONCLUSIONS Postmortem diffusion tensor imaging with fiber tracking provides an exceptional in situ insight "deep into the fibers" of the brain with diagnostic benefit in traumatic brain injury and axonal injuries in the assessment of the underlying cause of death, considering influencing factors for optimal imaging technique.

Fatal steamer accident; blunt force injuries and drowning in post-mortem MSCT and MRI.

Steamer accidents, through contact with the bucket wheel, are very seldom today. No publication of such a kind of fatal accident could be found in literature. We present the case of a fatal steamer accident, in which the findings of a blunt traumatization of a person by the ship was completely documented by post-mortem combined multi-slice computed tomography (MSCT) and magnetic resonance imaging (MRI) examinations. A rupture of the aorta was detected using both radiological methods without use of radiopaque material. Radiological examination revealed a comminuted fracture of the thorax vertebrae at the same level as the aortic rupture. Injuries of the soft tissues of the back, caused by the bucket wheel of the steamer, were also diagnosed. In addition to the signs of blunt force trauma the findings of drowning such as an over inflation of the lungs, fluid in the stomach and duodenum were revealed. Furthermore, algological analysis detected diatoms in the lung tissue and blood from the left heart. Therefore, the cause of death was considered being a combination of fatal hemorrhage, caused by the aortic rupture, and drowning. We conclude that virtual autopsy using combined post-mortem MSCT and MRI is a useful tool for documentation, visualisation and analysis of the findings of blunt force trauma and drowning with a large potential in forensic medicine.

Virtopsy--fatal motor vehicle accident with head injury.

A man wearing no protective helmet was struck by a motor vehicle while riding a bicycle. He was loaded on his left side, and the impact point of his head was his occiput on the car roof girder. He was immediately transported to the general hospital, where he passed away. Postmortem examination using multi-slice computed tomography (MSCT) revealed an extensively comminuted fracture of the posterior part and the base of the skull. Observed were deep direct and contrecoup brain bruises, with the independent fractures of the roof of the both orbits. Massive subdural and subarachnoidal hemorrhage with cerebral edema and shifting of the mid-line towards left side were also detected. MSCT and autopsy results were compared and the body injuries were correlated to vehicle damages. In conclusion, postmortem imaging is a good forensic visualization tool with great potential for documentation and examination of body injuries and pathology.

Mechanical endovascular thrombectomy for acute ischemic stroke: a retrospective multicenter study in Belgium.

Clinical trials have shown a beneficial effect of mechanical thrombectomy in acute ischemic stroke patients treated within six up to even 12 h after symptom onset. This treatment was already performed in selected hospitals in Belgium before completion of the randomized controlled trials. Outcome data on these procedures in Belgium have not been published. We performed a retrospective multicenter study of all patients with acute ischemic stroke treated with mechanical endovascular therapy in four hospitals in Belgium. Clinical outcomes, as measured by the modified Rankin Scale (mRS), site of arterial occlusion, reperfusion and the association between these variables were studied. The study included 80 patients: 65 patients with an occlusion in the anterior circulation and 15 with an occlusion in the posterior circulation. Good functional outcome (GFO) rates, defined as mRS 0-2 at 90 days, were 42 % in all patients, 44 % in anterior circulation stroke and 34 % in posterior circulation stroke. Reperfusion was achieved in 78 % of patients; more (100 %) in patients with posterior compared to patients with anterior circulation stroke (72 %; p = 0.02). The rate of GFO was greater in patients with reperfusion versus patients in whom reperfusion was not achieved (adjusted OR 8.2, 95 % CI 2.0-34.2). Symptomatic intracerebral hemorrhage was documented in 5 % of all patients. Endovascular treatment with mechanical devices for acute ischemic stroke in Belgium results in GFO and reperfusion rates similar to recently published results in the endovascular-treated arms of randomized clinical trials. Rates of symptomatic intracranial hemorrhage are low and comparable to other cohort studies and clinical trials.

TICI and Age: What's the Score?

BACKGROUND AND PURPOSE Previous studies have suggested that advanced age predicts worse outcome following mechanical thrombectomy. We assessed outcomes from 2 recent large prospective studies to determine the association among TICI, age, and outcome. MATERIALS AND METHODS Data from the Solitaire FR Thrombectomy for Acute Revascularization (STAR) trial, an international multicenter prospective single-arm thrombectomy study and the Solitaire arm of the Solitaire FR With the Intention For Thrombectomy (SWIFT) trial were pooled. TICI was determined by core laboratory review. Good outcome was defined as an mRS score of 0-2 at 90 days. We analyzed the association among clinical outcome, successful-versus-unsuccessful reperfusion (TICI 2b-3 versus TICI 0-2a), and age (dichotomized across the median). RESULTS Two hundred sixty-nine of 291 patients treated with Solitaire in the STAR and SWIFT data bases for whom TICI and 90-day outcome data were available were included. The median age was 70 years (interquartile range, 60-76 years) with an age range of 25-88 years. The mean age of patients 70 years of age or younger was 59 years, and it was 77 years for patients older than 70 years. There was no significant difference between baseline NIHSS scores or procedure time metrics. Hemorrhage and device-related complications were more common in the younger age group but did not reach statistical significance. In absolute terms, the rate of good outcome was higher in the younger population (64% versus 44%, P < .001). However, the magnitude of benefit from successful reperfusion was higher in the 70 years of age and older group (OR, 4.82; 95% CI, 1.32-17.63 versus OR 7.32; 95% CI, 1.73-30.99). CONCLUSIONS Successful reperfusion is the strongest predictor of good outcome following mechanical thrombectomy, and the magnitude of benefit is highest in the patient population older than 70 years of age.

Occlusion Location of Middle Cerebral Artery Stroke and Outcome after Endovascular Treatment.

BACKGROUND The aim of this study was to analyze the influence of the location of middle cerebral artery (MCA) occlusion on recanalization, complications and outcome after endovascular therapy. METHODS Four-hundred sixty-four patients with acute MCA occlusions were treated with endovascular therapy. RESULTS Two-hundred ninety-three patients had M1 occlusions, 116 had M2, and 55 had M3/4 occlusions. Partial or complete recanalization was more frequently achieved in M1 (76.8%) than in M2 (59.1%) or M3/4 (47.3%, p < 0.001) occlusions, but favorable outcome (modified Rankin Scale 0-2) was less frequent in M1 (50.9%) than M2 (63.7%) or M3/4 (72.7%, p = 0.018) occlusions. Symptomatic intracerebral hemorrhage (ICH) did not differ between occlusion sites, but asymptomatic ICH was more common in M1 (22.6%) than in M2 occlusions (8.6%, p = 0.003). Recanalization was associated with favorable outcome in M1 (p < 0.001) and proximal M2 (p = 0.003) but not in distal M2 or M3/4 occlusions. CONCLUSIONS Recanalization with endovascular therapy was more frequently achieved in patients with proximal than distal MCA occlusions, but recanalization was associated with favorable outcome only in M1 and proximal M2 occlusions. Outcome was better with distal than proximal occlusions. This study shows that recanalization can be used as a surrogate marker for clinical outcome only in patients with proximal occlusions.

Death after Sexual Intercourse

Sexuality is an essential aspect of quality of life. Nevertheless, sexual intercourse is physically challenging and leads to distinct changes in blood pressure, heart, and respiratory rate that may lead to vital complications. We present a case report of a 22-year-old female suffering from subarachnoid hemorrhage after sexual intercourse. The patient was immediately transported to hospital by emergency medical services and, after diagnosis, transferred to a tertiary hospital with neurosurgical expertise but died within 24 hours. After postcoital headaches, subarachnoid hemorrhage is the second most common cause of neurological complications of sexual intercourse and therefore patients admitted to an emergency department with headache after sexual intercourse should always be carefully evaluated by cerebral imaging.

Prevention of Rebleeding From Esophageal Varices in Patients With Cirrhosis Receiving Small-Diameter Stents Versus Hemodynamically Controlled Medical Therapy

BACKGROUND & AIMS Patients with cirrhosis and variceal hemorrhage have a high risk of rebleeding. We performed a prospective randomized trial to compare the prevention of rebleeding in patients given a small-diameter covered stent vs those given hepatic venous pressure gradient (HVPG)-based medical therapy prophylaxis. METHODS We performed an open-label study of patients with cirrhosis (92% Child class A or B, 70% alcoholic) treated at 10 medical centers in Germany. Patients were assigned randomly more than 5 days after variceal hemorrhage to groups given a small covered transjugular intrahepatic portosystemic stent-shunt (TIPS) (8 mm; n = 90), or medical reduction of portal pressure (propranolol and isosorbide-5-mononitrate; n = 95). HVPG was determined at the time patients were assigned to groups (baseline) and 2 weeks later. In the medical group, patients with an adequate reduction in HVPG (responders) remained on the drugs whereas nonresponders underwent only variceal band ligation. The study was closed 10 months after the last patient was assigned to a group. The primary end point was variceal rebleeding. Survival, safety (adverse events), and quality of life (based on the Short Form-36 health survey) were secondary outcome measures. RESULTS A significantly smaller proportion of patients in the TIPS group had rebleeding within 2 years (7%) than in the medical group (26%) (P = .002). A slightly higher proportion of patients in the TIPS group experienced adverse events, including encephalopathy (18% vs 8% for medical treatment; P = .05). Rebleeding occurred in 6 of 23 patients (26%) receiving medical treatment before hemodynamic control was possible. Per-protocol analysis showed that rebleeding occurred in a smaller proportion of the 32 responders (18%) than in nonresponders who received variceal band ligation (31%) (P = .06). Fifteen patients from the medical group (16%) underwent TIPS placement during follow-up evaluation, mainly for refractory ascites. Survival time and quality of life did not differ between both randomized groups. CONCLUSIONS Placement of a small-diameter, covered TIPS was straightforward and prevented variceal rebleeding in patients with Child A or B cirrhosis more effectively than drugs, which often required step-by-step therapy. However, TIPS did not increase survival time or quality of life and produced slightly more adverse events. Clinical Trial no: ISRCTN 16334693.

Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair).

BACKGROUND Preterm infants suffering from intraventricular hemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (rEPO) improves long-term cognitive outcome in infants with IVH. Recent studies revealed a beneficial effect of early high-dose rEPO on white matter development in preterm infants determined by magnetic resonance imaging (MRI). OBJECTIVES To summarize the current evidence and to delineate the study protocol of the EpoRepair trial (Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants). METHODS The study involves a review of the literature and the design of a double-blind, placebo-controlled, multicenter trial of repetitive high-dose rEPO administration, enrolling 120 very preterm infants with moderate-to-severe IVH diagnosed by cranial ultrasound in the first days of life, qualitative and quantitative MRI at term-equivalent age and long-term neurodevelopmental follow-up until 5 years of age. RESULTS AND CONCLUSIONS The hypothesis generated by observational data that rEPO may improve long-term cognitive outcomes of preterm infants suffering from IVH are to be confirmed or refuted by the randomized controlled trial, EpoRepair.

Direct Mechanical Intervention Versus Combined Intravenous and Mechanical Intervention in Large Artery Anterior Circulation Stroke: A Matched-Pairs Analysis.

BACKGROUND AND PURPOSE Five randomized controlled trials have consistently shown that mechanical thrombectomy (MT) in addition to best medical treatment (±intravenous tissue-type plasminogen activator) improves outcome after acute ischemic stroke in patients with large artery anterior circulation stroke. Whether direct MT is equally effective as combined intravenous thrombolysis with MT (ie, bridging thrombolysis) remains unclear. METHODS We retrospectively compared clinical and radiological outcomes in 167 bridging patients with 255 patients receiving direct MT because of large artery anterior circulation stroke. We matched all patients from the direct MT group who would have qualified for intravenous tissue-type plasminogen activator with controls from the bridging group, using multivariate and propensity score analyses. Functional independence was defined as modified Rankin Scale score of 0 to 2. RESULTS From February 2009 to August 2014, 40 patients from the direct MT group would have qualified for bridging thrombolysis but were treated with MT only. Clinical and radiological characteristics did not differ from the bridging cohort, except for higher rates of hypercholesterolemia (P=0.019), coronary heart disease (P=0.039), and shorter intervals from symptom onset to endovascular intervention (P=0.01) in the direct MT group. Functional independence, mortality, and intracerebral hemorrhage rates did not differ (P>0.1). After multivariate matching analysis outcome in both groups did not differ, except for lower rates of asymptomatic intracerebral hemorrhage (P=0.023) and lower mortality (P=0.007) in the direct MT group. CONCLUSIONS In patients with large anterior circulation stroke, direct mechanical intervention seems to be equally effective as bridging thrombolysis. A randomized trial comparing direct MT with bridging therapy is warranted.

No Routine Postoperative Head CT following Elective Craniotomy - A Paradigm Shift?

INTRODUCTION Patient management following elective cranial surgery often includes routine postoperative computed tomography (CT). We analyzed whether a regime of early extubation and close neurological monitoring without routine CT is safe, and compared the rate of postoperative emergency neurosurgical intervention with published data. METHODS Four hundred ninety-two patients were prospectively analyzed; 360 had supra- and 132 had infratentorial lesions. Extubation within one hour after skin closure was aimed for in all cases. CT was performed within 48 hours only in cases of unexpected neurological findings. RESULTS Four-hundred sixty-nine of the 492 patients (95.3%) were extubated within one hour, 20 (4.1%) within 3 hours, and three (0.6%) within 3 to 10 hours. Emergency CT within 48 hours was performed for 43/492 (8.7%) cases. Rate of recraniotomy within 48 hours for patients with postoperative hemorrhage was 0.8% (n = 4), and 0.8% (n = 4) required placement of an external ventricular drain (EVD). Of 469 patients extubated within one hour, 3 required recraniotomy and 2 required EVD placements. Of 23 patients with delayed extubation, 1 recraniotomy and 2 EVDs were required. Failure to extubate within one hour was associated with a significantly higher risk of surgical intervention within 48 hours (rate 13.0%, p = 0.004, odds ratio 13.9, 95% confidence interval [3.11-62.37]). DISCUSSION Early extubation combined with close neurological monitoring is safe and omits the need for routine postoperative CT. Patients not extubated within one hour do need early CT, since they had a significantly increased risk of requiring emergency neurosurgical intervention. TRIAL REGISTRATION ClinicalTrials.gov NCT01987648.

Functional analysis of BMP4 signaling in mouse neural development

During early mouse neural development, bone morphogenetic protein (BMP) signaling patterns the dorsal neural tube and defines distinct neural progenitor cell domains along the dorsoventral axis. Unlike the ventral signaling molecule Sonic hedgehog, which has long-range activity by establishing a concentration gradient in the ventral neural tube, these dorsally expressed BMPs appear to have a limited domain of action. This raises questions as to how BMP activity is restricted locally and how restricted BMP signaling directs dorsal neural patterning and differentiation. I hypothesize that BMPs are restricted in the dorsal neural tube for correct dorsoventral patterning. ^ Previous studies have shown that the positively charged basic amino acids located at the N-terminus of several BMPs are essential for heparin binding and diffusion. This provides a novel tool to address these questions. Here I adapted a UAS/GAL4 bigenic mouse system to control the ectopic expression of BMP4 and a mutant form of BMP4 that lacks a subset of the N-terminal basic amino acids. The target genes, UAS-Bmp4 and UAS-mBmp4 , were introduced into the Hprt locus by gene targeting in mouse embryonic stem cells. The expression of the GAL4 transactivator was driven by a roof plate specific Wnt1 promoter. ^ The bigenic mouse embryos exhibit phenotype variations, ranging from mid/hindbrain defects, hemorrhage, and eye abnormalities to vasculture formation. Embryonic death starts around E11.5 because of severe hemorrhage. The different expression levels of the activated transgene may account for the phenotype variation. Further marker analysis reveals that mutant BMP4 induces ectopic expression of the dorsal markers MSX1/2 and PAX7 in the ventral neural tube. In addition, the expression of the ventral neural marker NKX2.2 is affected by the expanded BMP4 activity, indicating that ectopic BMP signaling can antagonize ventral signaling. Comparison of the phenotypes of the Wnt1/ Bmp4 and Wnt1/mBmp4 bigenic embryos that express transgenes at the same level, respectively, shows that mutant BMP4 causes the expansion of dorsal neural fates ventrally while wild type BMP4 does not, suggesting that mutant BMP4 acts farther than wild type BMP4. Together, these data suggest that the N-terminus basic amino acid core controls BMP4 long-range activity in neural development, and that BMP signaling patterns the dorsal neural tube through a secondary signaling pathway that involves homeodomain transcription factors MSX1/2 and PAX7. ^

Changing epidemiology of trauma deaths leads to a bimodal distribution

Introduction. Injury mortality was classically described with a tri-modal distribution, with immediate deaths at the scene, early deaths due to hemorrhage, and late deaths from organ failure. We hypothesized that trauma systems development have improved pre-hospital care, early resuscitation, and critical care, and altered this pattern. ^ Methods. This is a population-based study of all trauma deaths in an urban county with a mature trauma system (n=678, median age 33 years, 81% male, 43% gunshot, 20% motor vehicle crashes). Deaths were classified as immediate (scene), early (in hospital, ≤ 4 hours from injury), or late (>4 hours post injury). Multinomial regression was used to identify independent predictors of immediate and early vs. late deaths, adjusted for age, gender, race, intention, mechanism, toxicology and cause of death. ^ Results. There were 416 (61%) immediate, 199 (29%) early, and 63 (10%) late deaths. Immediate deaths remained unchanged and early deaths occurred much earlier (median 52 minutes vs. 120). However, unlike the classic trimodal distribution, there was no late peak. Intentional injuries, alcohol intoxication, asphyxia, and injuries to the head and chest were independent predictors of immediate deaths. Alcohol intoxication and injuries to the chest were predictors of early deaths, while pelvic fractures and blunt assaults were associated with late deaths. ^ Conclusion. Trauma deaths now have a bimodal distribution. Elimination of the late peak likely represents advancements in resuscitation and critical care that have reduced organ failure. Further reductions in mortality will likely come from prevention of intentional injuries, and injuries associated with alcohol intoxication. ^

The determinants of improvements in health outcomes and of cost reduction in hospital inpatient care

This study aims to address two research questions. First, ‘Can we identify factors that are determinants both of improved health outcomes and of reduced costs for hospitalized patients with one of six common diagnoses?’ Second, ‘Can we identify other factors that are determinants of improved health outcomes for such hospitalized patients but which are not associated with costs?’ The Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database from 2003 to 2006 was employed in this study. The total study sample consisted of hospitals which had at least 30 patients each year for the given diagnosis: 954 hospitals for acute myocardial infarction (AMI), 1552 hospitals for congestive heart failure (CHF), 1120 hospitals for stroke (STR), 1283 hospitals for gastrointestinal hemorrhage (GIH), 979 hospitals for hip fracture (HIP), and 1716 hospitals for pneumonia (PNE). This study used simultaneous equations models to investigate the determinants of improvement in health outcomes and of cost reduction in hospital inpatient care for these six common diagnoses. In addition, the study used instrumental variables and two-stage least squares random effect model for unbalanced panel data estimation. The study concluded that a few factors were determinants of high quality and low cost. Specifically, high specialty was the determinant of high quality and low costs for CHF patients; small hospital size was the determinant of high quality and low costs for AMI patients. Furthermore, CHF patients who were treated in Midwest, South, and West region hospitals had better health outcomes and lower hospital costs than patients who were treated in Northeast region hospitals. Gastrointestinal hemorrhage and pneumonia patients who were treated in South region hospitals also had better health outcomes and lower hospital costs than patients who were treated in Northeast region hospitals. This study found that six non-cost factors were related to health outcomes for a few diagnoses: hospital volume, percentage emergency room admissions for a given diagnosis, hospital competition, specialty, bed size, and hospital region.^

Venous thromboembolism in patients with acute leukemia: Prevalence, incidence, recurrence of thrombosis, risk factors, and impact on survival

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most preventable cardiovascular disease and a growing public health problem in the United States. The incidence of VTE remains high with an annual estimate of more than 600,000 symptomatic events. DVT affects an estimated 2 million American each year with a death toll of 300,000 persons per year from DVT-related PE. Leukemia patients are at high risk for both hemorrhage and thrombosis; however, little is known about thrombosis among acute leukemia patients. The ultimate goal of this dissertation was to obtain deep understanding of thrombotic issue among acute leukemia patients. The dissertation was presented in a format of three papers. First paper mainly looked at distribution and risk factors associated with development of VTE among patients with acute leukemia prior to leukemia treatment. Second paper looked at incidence, risk factors, and impact of VTE on survival of patients with acute lymphoblastic leukemia during treatment. Third paper looked at recurrence and risk factors for VTE recurrence among acute leukemia patients with an initial episode of VTE. Descriptive statistics, Chi-squared or Fisher's exact test, median test, Mann-Whitney test, logistic regression analysis, Nonparametric Estimation Kaplan-Meier with a log-rank test or Cox model were used when appropriate. Results from analyses indicated that acute leukemia patients had a high prevalence, incidence, and recurrent rate of VTE. Prior history of VTE, obesity, older age, low platelet account, presence of Philadelphia positive ALL, use of oral contraceptives or hormone replacement therapy, presence of malignancies, and co-morbidities may place leukemia patients at an increased risk for VTE development or recurrence. Interestingly, development of VTE was not associated with a higher risk of death among hospitalized acute leukemia patients.^