One Step Away from Technology but One Step Towards Domain Experts-MDRBridge: A Template-Based ISO 11179-Compliant Metadata Processing Pipeline.

BACKGROUND: Secondary use of routine medical data relies on a shared understanding of given information. This understanding is achieved through metadata and their interconnections, which can be stored in metadata repositories (MDRs). The necessity of an MDR is well understood, but the local work on metadata is a time-consuming and challenging process for domain experts. OBJECTIVE: To support the identification, collection, and provision of metadata in a predefined structured manner to foster consolidation. A particular focus is placed on user acceptance. METHODS: We propose a software pipeline MDRBridge as a practical intermediary for metadata capture and processing, based on MDRSheet, an ISO 11179-3 compliant template using popular spreadsheet software. It serves as a practical mediator for metadata acquisition and processing in a broader pipeline. Due to the different origins of the metadata, both manual entry and automatic extractions from application systems are supported. To enable the export of collected metadata into external MDRs, a mapping of ISO 11179 to Clinical Data Interchange Standards Consortium (CDISC) Operational Data Model (ODM) was developed. RESULTS: MDRSheet is embedded in the processing pipeline MDRBridge and delivers metadata in the CDISC ODM format for further use in MDRs. This approach is used to interactively unify core datasets, import existing standard datasets, and automatically extract all defined data elements from source systems. The involvement of clinical domain experts improved significantly due to minimal changes within their usual work routine. CONCLUSION: A high degree of acceptance was achieved by adapting the working methods of clinical domain experts. The designed process is capable of transforming all relevant data elements according to the ISO 11179-3 format. MDRSheet is used as an intermediate format to present the information at a glance and to allow editing or supplementing by domain experts.

A Generic Method and Implementation to Evaluate and Improve Data Quality in Distributed Research Networks.

BACKGROUND: With the increasing personalization of clinical therapies, translational research is evermore dependent on multisite research cooperations to obtain sufficient data and biomaterial. Distributed research networks rely on the availability of high-quality data stored in local databases operated by their member institutions. However, reusing data documented by independent health providers for the purpose of care, rather than research ("secondary use"), reveal a high variability in terms of data formats, as well as poor data quality, across network sites. OBJECTIVES: The aim of this work is the provision of a process for the assessment of data quality with regard to completeness and syntactic accuracy across independently operated data warehouses using common definitions stored in a central (network-wide) metadata repository (MDR). METHODS: For assessment of data quality across multiple sites, we employ a framework of so-called bridgeheads. These are federated data warehouses, which allow the sites to participate in a research network. A central MDR is used to store the definitions of the commonly agreed data elements and their permissible values. RESULTS: We present the design for a generator of quality reports within a bridgehead, allowing the validation of data in the local data warehouse against a research network's central MDR. A standardized quality report can be produced at each network site, providing a means to compare data quality across sites, as well as to channel feedback to the local data source systems, and local documentation personnel. A reference implementation for this concept has been successfully utilized at 10 sites across the German Cancer Consortium. CONCLUSIONS: We have shown that comparable data quality assessment across different partners of a distributed research network is feasible when a central metadata repository is combined with locally installed assessment processes. To achieve this, we designed a quality report and the process for generating such a report. The final step was the implementation in a German research network.

Functional expression of breast cancer resistance protein and cholesterol effect in human erythrocyte membranes.

In human erythrocyte membranes, various influx and efflux transporters are functionally expressed. However, their transport characteristics and modulation under disease states are not fully understood. In this study, we first examined the expression and detailed transport characteristics of breast cancer resistance protein (BCRP), an efflux ABC transporter, using inside-out membrane vesicles (IOVs) prepared from human erythrocytes, and then studied the effect of membrane cholesterol on BCRP function. The expression of BCRP was confirmed by western blotting; most of them being homodimers. The uptake of lucifer yellow (LY), a fluorescent BCRP substrate, into IOVs was time-, temperature-, and ATP-dependent, and the concentration of ATP which induced half-maximal stimulation of LY uptake was calculated to be 0.39 mM. The uptake of LY by IOVs was saturable with a Km value of 166 µM, and was inhibited by various BCRP inhibitors and substrates, such as fumitremorgin C and mitoxantrone. When membrane cholesterol content was increased by treating IOVs with cholesteryl hemisuccinate, LY uptake decreased with increasing cholesterol content. These results suggest that transport activity of BCRP in human erythrocyte membranes may be suppressed under disease states, such as hypercholesterolemia, that increase membrane cholesterol content.

Direct percutaneous carotid artery stenting for a patient with absence of the common carotid artery.

A 54-year-old man with symptomatic internal carotid artery stenosis with absence of the common carotid artery (CCA), who had been treated with surgery and postoperative radiotherapy for tonsillar carcinoma, underwent direct percutaneous carotid artery stenting (CAS). To our knowledge, this is the first report of direct percutaneous carotid artery stenting (CAS) for a patient with absent CCA.

Superior sagittal sinus dural arteriovenous fistulas treated by stent placement for an occluded sinus and transarterial embolization. A case report.

We describe a case of dural arteriovenous fistulas (DAVFs) involving the superior sagittal sinus (SSS) successfully treated with stent placement for an occluded sinus and transarterial embolization. A 61-year-old man who had been treated with anticoagulation for a known SSS thrombosis presented with a sudden onset of headache. CT scan revealed an intraventricular hemorrhage and cerebral angiography revealed DAVFs involving the SSS which had severe venous congestion and sinus occlusion. We treated this case with a staged endovascular approach which consisted of stent placement for the occluded sinus and transarterial intravenous embolization resulting in complete eradication of DAVFs. Recanalization of an occluded sinus by stent placement can reduce venous congestion and transarterial intravenous embolization can obliterate dural arteriovenous shunts. This staged strategy is feasible and should be considered a first option of treatment, especially for DAVFs which presented with intracranial hemorrhage and aggressive venous hypertension.

Simultaneous combined intravenous recombinant tissue plasminogen activator and endovascular therapy for hyperacute middle cerebral artery m1 occlusion.

We investigated the efficacy and safety of combined intravenous (IV) recombinant tissue plasminogen activator (rtPA) and simultaneous endovascular therapy (ET) for hyperacute middle cerebral artery (MCA) M1 occlusion. Between October 2005 and April 2007, in the combined group, 22 patients eligible for IV rtPA, who were diagnosed as having MCA M1 occlusion, were treated with IV rtPA and simultaneous ET was initiated as soon as possible. The other patients were treated with IV rtPA alone (IV group A: n = 11). Between May 2007 and November 2008, all patients eligible for IV rtPA, who were diagnosed as having MCA M1 occlusion, underwent thrombolysis by IV rtPA alone (IV group B: n = 24). The improvement of the National Institutes of Health Stroke Scale score at 24 hours was highest in the combined group (10 ± 4.1). In contrast, it was 5.1 ± 4.7 in the IV group A (P = 0.017) and 5.6 ± 5.6 in IV group B (P = 0.006). In the combined group, successful recanalization was observed in 18 of 22 patients with one symptomatic intracranial hemorrhage. The rate of mRS0-2 at three months was highest in the combined group, 36% in the IV group A and 33% in the IV group B (P = 0.008).Simultaneous treatment with IV rtPA and ET improved the clinical outcome of MCA M1 occlusion without a significant increase of adverse effects in our study.

Technique for shaping microcatheter tips in coil embolization of paraclinoid aneurysms using full-scale volume rendering images of 3D rotational angiography.

INTRODUCTION: In coil embolization of paraclinoid aneurysms, it is sometimes difficult to introduce and stabilize microcatheter tips in the aneurysms. We report a new technique for shaping microcatheter tips in the coil embolization of paraclinoid aneurysms. METHODS: From May 2007 to May 2008, this new technique was applied to 10 paraclinoid aneurysms undergoing coil embolization. Before coil embolization, 3D rotational angiography was performed, and volume-rendering images were reconstructed. Vinyl-coated handicraft wire was shaped 3-dimensionally to fit full-scale volume-rendering images on the monitor, from the C5 portion of the internal carotid artery to the center of the dome of the aneurysm from various angles. The microcatheter tip was then shaped with steam to fit the vinyl-coated wire. Thereafter, the microcatheter tip was introduced into the aneurysm and coil embolization was performed. RESULTS: Microcatheter tips could be easily shaped and could be introduced smoothly into aneurysms, and were stable during coil embolization. CONCLUSION: This technique is feasible for shaping microcatheter tips precisely for coil embolization of paraclinoid aneurysms.

Ecotoxicity of the degradation products of triphenylborane pyridine (TPBP) antifouling agent.

Triphenylborane pyridine (TPBP) is an alternative to organotin antifouling compounds. This work aimed to identify the unknown Peak #1, and to evaluate the ecotoxicity of TPBP and its degradation products. Peak #1 was produced from TPBP dissolved in acetonitrile under UV-A photolysis using a high-pressure mercury lamp. The Peak #1 fraction was purified using two-step column chromatography from a TPBP-acetonitrile solution. The major compound of the fraction was identified as being biphenyl from the 1H NMR and 13C NMR spectra. The ecotoxicity of four degradation products (diphenylborane hydroxide, phenylborane dihydroxide, phenol, and biphenyl) and TPBP towards two marine planktons were assessed. The 48 h LC(50) values of the crustacean, Artemia salina, were 0.13 mg L(-1) for TPBP, 14 mg L(-1) for biphenyl, 17 mg L(-1) for phenol, and > 50 mg L(-1) for the other degradation products. The 72 h EC(50) values of the diatom, Skeletonema costatum, were 0.0022 mg L(-1) for TPBP, 1.2 mg L(-1) for biphenyl, and > 2 mg L(-1) for the other degradation products. Thus, the ecotoxicity of biphenyl and the other degradation products were not high compared to the parent compound, TPBP.

Simultaneous treatment with intravenous recombinant tissue plasminogen activator and endovascular therapy for acute ischemic stroke within 3 hours of onset.

BACKGROUND AND PURPOSE: Because intravenous (IV) recombinant tissue plasminogen activator (rtPA) does not always lead to a good outcome in a considerable proportion of patients, combined IV rtPA and rescue endovascular therapy (ET) have been performed in several recent studies. However, rescue therapy after completion of IV rtPA often results in late ineffective recanalization. We examined the efficacy and safety of combined IV rtPA and simultaneous ET as primary rather than rescue therapy for hyperacute middle cerebral artery (MCA) occlusion. MATERIALS AND METHODS: A total of 29 patients eligible for IV rtPA, who were diagnosed as having MCA (M1 or M2) occlusion within 3 hours of onset, underwent thrombolysis. In the combined group, patients were treated by IV rtPA (0.6 mg/kg for 60 minutes) and simultaneous ET (intra-arterial rtPA, mechanical thrombus disruption with microguidewire, and balloon angioplasty) initiated as soon as possible. In the IV group, patients were treated by IV rtPA only. RESULTS: The improvement of the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours was 11 +/- 4.8 in the combined group versus 5 +/- 4.3 in the IV group (P < .001). In the combined group, successful recanalization was observed in 14 (88%) of 16 patients with no symptomatic intracranial hemorrhage, and 10 (63%) of 16 patients had favorable outcomes (modified Rankin Scale [mRS] 0, 1) at 3 months. CONCLUSIONS: Aggressive combined therapy with IV rtPA and simultaneous ET markedly improved the clinical outcome of hyperacute MCA occlusion without significant adverse effect. Additional randomized study is needed to confirm our results.

Intravenous 3D digital subtraction angiography in the diagnosis of unruptured intracranial aneurysms.

Recent progress in digital subtraction angiography (DSA) devices makes it possible to perform rotational angiography with high resolution and high sensitivity. We tried intravenous (IV) 3D DSA in patients who had undergone MR angiography (MRA) suggestive of unruptured intracranial aneurysms. IV 3D DSA can be used as an alternative method for imaging unruptured intracranial aneurysms suggested on MRA.

Complete Cure of Superior Sagittal Sinus Dural Arteriovenous Fistulas by Transvenous Embolization through the Thrombosed Sinus in a Single Therapeutic Session. A Case Report.

SUMMARY: Endovascular treatment often fails to completely eliminate dural arteriovenous fistulas (dural AVFs) involving the superior sagittal sinus (SSS). We report a successful case of dural AVF involving the SSS using transvenous embolization through the thrombosed sinus in a single therapeutic session.

A neuroendoscopic approach to the aqueduct via the fourth ventricle combined with suboccipital craniectomy.

OBJECTIVES: We have tried to approach the aqueduct less invasively with the endoscope in combination with a small suboccipital craniectomy, especially for lesions of the aqueduct close to the fourth ventricle. METHODS: The patient is placed in the prone position and a small suboccipital craniectomy is performed. After elevating the bilateral tonsils with retractors, the sheath of the endoscope is inserted from a small skin incision made on the posterior midline of the neck, far from the craniectomy site. The skin incision for endoscopic insertion is planned on the linear extension connecting the aqueduct and the foramen of Magendi on the craniocervical MRI. A rigid endoscope is inserted through the fourth ventricle to the aqueduct for exploration and surgical manipulation. RESULTS: Two cases with hydrocephalus due to aqueductal stenosis, with gait disturbance were operated. After exploration of the aqueduct via the fourth ventricle, endoscopic aqueductal plasty was performed. The postoperative courses were uneventful. The patients' symptoms disappeared. CONCLUSIONS: This approach can be applied for less invasive endoscopic exploration and surgery around the aqueduct close to the fourth ventricle with a rigid endoscope, without overflexion of the neck, or a large craniectomy, or overretraction of the tonsils, or incision of the inferior vermis.

Identification of malignant brain edema after hemispheric stroke by PET-imaging and microdialysis.

Cerebral blood flow (CBF) and extent of irreversible tissue damage as well as the time course of extracellular concentration of amino acids, substrates of energy metabolism, and purine metabolites, intracranial pressure and tissue oxygen tension were assessed in 34 patients with large strokes covering more than 50% of the MCA territory. The results were compared to findings in the experimental model of transient (for 3 hours) MCA occlusion in cats. In the experimental model as well as in the clinical setting development of malignant brain infarcts (due to formation of space occupying brain edema) was predicted by the size of critically hypoperfused tissue and the volume of irreversibly damaged tissue. The course of malignant infarcts was characterized by progressive increase in concentrations of excitatory amino acids, lactate, pyruvate, glycerol, hypoxanthine and in intracranial pressure, while cerebral perfusion pressure and tissue oxygen tension decreased. These results clearly differentiate a malignant from a benign course of large hemispheric infarction. The methods can be used to identify patients at risk for formation of space occupying edema and to select patients who could benefit from invasive therapeutic strategies.

Prediction of malignant infarction: perifocal neurochemical monitoring following prolonged MCA occlusion in cats.

Neurochemical monitoring in the ischemic core predicts malignancy in focal ischemia in cats. Since perifocal regions are more suitable for clinical microdialysis (MD) applications, we tested whether monitoring at such site predicts also malignancy.--Laser Doppler (LD) probes, pressure microsensors, and MD/HPLC measured cerebral blood flow (CBF), intracranial pressure (ICP), and extracellular glutamate (Glu), respectively. The middle cerebral artery was occluded (MCAO) for 3 hours followed by 6 hours reperfusion. Additionally, LD measured CBF in ischemic core.--MCAO reduced CBF in the core in all below 25% of control. In animals exhibiting malignancy (eye dilatation during reperfusion), MCAO decreased CBF in the perifocal site to around 35%. CBF primarily recovered following recirculation but decreased thereafter as ICP rose due to progressive edema formation. Glu increased concomitantly. In cats exhibiting a benign course, MCAO decreased CBF in the perifocal site to around 55%. Recirculation normalized CBF, and Glu did not increase. During MCAO, Glu differences between both groups were not significant.--Glu determinations in perifocal sites taken during MCAO do not predict fatal outcome. This contrasts with determinations in the core. After reperfusion, Glu elevation in perifocal sites may serve as a rather late predictor of malignancy.

[Mixed-type autoimmune hemolytic anemia after splenectomy for idiopathic thrombocytopenic purpura].

A 30-year-old woman was admitted because of anemia and jaundice in 1999. She had been diagnosed as having idiopathic thrombocytopenic purpura (ITP) in 1996, but had shown no response to prednisolone (PSL). Subsequent splenectomy in 1998, followed by further treatment with PSL, had also been ineffective. On admission in 1999, the direct and indirect Coombs tests gave positive results, the cold agglutinin titer was high with anti-I specificity (IgM), and warm-type autoantibody (IgG) was positive. Autoagglutination of the patient's red blood cells was 3+ at 37 degrees C. A diagnosis of mixed-type autoimmune hemolytic anemia (AIHA) associated with ITP was made. Mixed-type AIHA occurring after splenectomy for ITP is very rare, only one case having been reported to date.

Elevation of extracellular glutamate in the final, ischemic stage of progressive epidural mass lesion in cats.

Epidural mass lesions may cause ischemia due to progressive intracranial hypertension. In order to investigate the impact of intracranial pressure on accumulation of neuroactive substances, we gradually raised intracranial pressure in five halothane anesthetized cats by inflation of an epidural balloon. We evaluated in the parietal cortex contralateral to the site of balloon inflation, alterations of extracellular glutamate and purine catabolites and of the lactate/pyruvate ratio in relation to changes of intracranial, cerebral perfusion and mean arterial blood pressure. In a complementary experiment, regional cerebral blood flow was assessed by sequential positron emission tomography. In this simplified mass lesion model, extracellular glutamate increased in all cats at a late, critical stage after tentorial herniation, when intracranial pressure had increased to more than 90 mm Hg, cerebral perfusion pressure had decreased below 40-50 mm Hg. Positron emission tomography assessments revealed that the ischemic threshold for glutamate accumulation was in the range of 15-20 mL/100 g/min. Purine catabolites and the lactate/pyruvate ratio increased somewhat earlier than glutamate, but also after reaching the critical, terminal stage. We conclude that in this model of progressive epidural compression, glutamate-mediated excitotoxic processes at sites remote from the initial focal lesion depend on processes such as delayed ischemia in combination with tentorial herniation and systemic hypotension. These processes seem to be initiated by a decrease of cerebral perfusion pressure below a threshold of 40-50 mm Hg.

Measurement of coronary sinus flow using transesophageal echocardiography in patients undergoing coronary artery bypass grafting.

STUDY OBJECTIVE: To measure coronary sinus blood flow during coronary artery bypass graft (CABG) with transesophageal echocardiography (TEE). DESIGN: Prospective study. SETTING: Elective cardiac surgery at a university hospital. PATIENTS: Thirty-one ASA physical status III and IV adult patients free of significant coexisting disease and undergoing CABG. INTERVENTION: We measured coronary sinus blood flow velocity by using TEE and hemodynamic variables, before and after cardiopulmonary bypass (CPB) and after CPB. MEASUREMENTS AND MAIN RESULTS: We obtained a complete set of control measurements for 29 subjects (94%) and a complete set of post-CPB measurements in 28 patients (90%). In the normal group, peak velocity, and velocity time integral (VTI) of coronary sinus blood flow in the post-CPB period increased significantly compared with the pre-CPB period with CABG (n = 23). In the group of new regional wall motion abnormalities in the post-CPB period, peak velocity and VTI of coronary sinus blood flow in the post-CPB period did not increase significantly compared with the pre-CPB period by CABG (n = 5). CONCLUSIONS: We were able to measure the coronary sinus flow velocity by pulse-Doppler TEE during CABG. The peak velocity and VTI of coronary sinus blood flow in the post-CPB period increased significantly compared with in the pre-CPB period by CABG. The results of this preliminary study show the feasibility of clinical evaluation of CABG intraoperatively.

Hemodynamic evaluation of the prone position by transesophageal echocardiography.

STUDY OBJECTIVE: To evaluate the hemodynamic response in the prone position in surgical patients by measuring the effects of prone positioning on cardiac function using transesophageal echocardiography (TEE). DESIGN: Prospective study. SETTING: Elective surgery at a university hospital. PATIENTS: 15 adult ASA physical status I and II patients free of significant coexisting disease undergoing lumbar laminectomy. INTERVENTIONS AND MEASUREMENTS: Approximately 15 minutes after the induction of general anesthesia, we measured heart rate, blood pressure, and central venous pressure. We also measured left ventricular area (LVA) and fractional area change (FAC) automatically and calculated left ventricular volume (LVV), stroke volume index (SVI), cardiac index (CI), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), pulmonary venous flow velocity (PVFV), and pulmonary venous velocity time integral (PVVTI) via TEE. The same measurements were performed approximately 15 minutes after changing to the prone position with longitudinal bolsters. MAIN RESULTS: In the prone position, there was significant reduction in end-systolic and end-diastolic LVA and LVV. There was a significant increase in LVEF, LVFS, and FAC in the prone position. In addition, there was diminishment of systolic PVFV and PVVTI and enhancement of diastolic PVFV and PVVTI. SVI and CI did not change significantly in the prone position. CONCLUSION: The prone position caused LVV to decrease. The prone position also led to decreased systolic PVFV and PVVTI and enhancement of diastolic PVFV and PVVTI. These changes were probably due to a decrease in the venous return due to inferior vena caval compression, and decreased left ventricular compliance due to increased intrathoracic pressure in the prone position.