Prevalence and short-term changes of cognitive dysfunction in young ischaemic stroke patients.

BACKGROUND AND PURPOSE: Information on the prevalence and course of post-stroke cognitive impairment in young stroke patients is limited. The aim was to assess a consecutive sample of acute young ischaemic stroke patients (18-55 years) for the presence and development of neuropsychological deficits. METHODS: Patients prospectively underwent a comprehensive clinical and cognitive assessment, examining general cognitive function, processing speed, attention, flexibility/executive function and word fluency within the first 3 weeks after hospital admission (median assessment at day 6) and at a 3 months' follow-up (FU). Cognitive dysfunction was defined in comparison to age-standardized published norms. RESULTS: At baseline (N = 114), deficits were highly prevalent in processing speed (56.0%), flexibility/executive function (49.5%), attention (46.4%) and general cognitive function (42.1%). These frequencies were comparable for those with FU assessment (N = 87). In most domains, cognitive performance improved within 3 months, except for word fluency. However, in about one-third of patients, cognitive deficits (as defined by 1.5 standard deviations below the standardized mean) were still present 3 months after stroke. At FU, 44.0% were impaired in the domain flexibility/executive function, 35.0% in processing speed and 30.0% in attention. CONCLUSIONS: The high prevalence of cognitive deficits in acute young patients with ischaemic stroke highlights the importance of early post-stroke cognitive assessment to capture a patient's dysfunction in a comprehensive manner and to offer adequate rehabilitation. The role of factors which promote neuropsychological deficits needs further exploration.

Geochemistry and Microtextures of Vein Calcites Pervading the Izu-Bonin Forearc and Rear Arc Crust: New Insights From IODP Expeditions 352 and 351.

International Ocean Discovery Program Expeditions 352 and 351 drilled into the Western Pacific Izu-Bonin forearc and rear arc. The drill cores revealed that the forearc is composed of forearc basalts (FAB) and boninites and the rear arc consists of FAB-like rocks. These rocks are pervaded by calcite veins. Blocky vein microtextures enclosing host rock fragments dominate in all locations and suggest hydrofracturing and advective fluid flow. Significant diffusion-fed and crystallization pressure-driven antitaxial veining is restricted to the rear arc. The lack of faults and presence of an Eocene sedimentary cover in the rear arc facilitated antitaxial veining. Rare earth element and isotopic (δ18O, δ13C, 87Sr/86Sr, and Δ47) tracers indicate varying parental fluid compositions ranging from pristine to variably modified seawater. The most pristine seawater signatures are recorded by FAB-hosted low-T (<30 °C) vein calcites. Their 87Sr/86Sr ratios intersect the 87Sr/86Sr seawater curve at ~35-33 and ~22 Ma. These intersections are interpreted as precipitation ages, which concur with Pacific slab rollback. Boninite-hosted low-T (<30 °C) vein calcites precipitated from seawater that was modified by fluid-rock interactions. Mixing calculations yield a mixture of >95% seawater and <5% basaltic 87Sr/86Sr. In the rear arc, low-T rock alteration lowered the circulating seawater in δ18O and 87Sr/86Sr. Thus, vein calcites precipitated from modified seawater with up to 20-30% basaltic 87Sr/86Sr at temperatures up to 74 ± 12 °C. These results show how the local geology and vein growth dynamics affect microtextures and geochemical compositions of vein precipitates.

Serum matrix metalloprotease-1 and vascular endothelial growth factor--a predict cardiac allograft rejection.

Cardiac allograft rejection is currently diagnosed from endomyocardial biopsies (EMB) that are invasive and impractical to repeat. A serological marker could facilitate rejection monitoring and minimize EMB-associated risks. We investigated the relation of serum matrix metalloprotease (MMP)-1 and vascular endothelial growth factor (VEGF)-A concentrations to cardiac allograft rejection, using 1176 EMBs and serum samples obtained from 208 recipients. Acute cellular rejection was diagnosed in 186 EMBs. Mean week 1 and week 2 serum MMP-1 concentrations predicted rejection (p = 0.001, AUC = 0.80). At the optimal cut-off level of >or=7.5 ng/mL, MMP-1 predicted rejection with 82% sensitivity and 72% specificity. Initial serum MMP-1 <5.3 ng/mL (lowest quartile) was associated with rejection-free outcome in 80% of patients. Both MMP-1 (p < 0.001, AUC = 0.67-0.75) and VEGF-A (p < 0.01, AUC = 0.62-0.67) predicted rejection on the next EMB, while rejection at EMB was identified only by VEGF-A (p < 0.02, AUC = 0.70-0.77). Patients receiving combined cyclosporine-A and everolimus had the lowest serum MMP-1 concentrations. While serum MMP-1 predicts rejection-free outcome and VEGF-A identifies rejection on EMB, both markers predict rejection in follow-up of cardiac transplant recipients. Combination of serum MMP-1 and VEGF-A concentration may be a noninvasive prognostic marker of cardiac allograft rejection, and could have important implications for choice of surveillance and immunosuppression protocols.

Geochemistry of Vein Calcites Hosted in the Troodos Pillow Lavas and Their Implications for the Timing and Physicochemical Environment of Fracturing, Fluid Circulation, and Vein Mineral Growth.

Calcite veins hosted in pillow lavas of the Late Cretaceous Troodos suprasubduction zone ophiolite provide insights into the timing and physicochemical environment of postmagmatic fracturing and fluid circulation through oceanic crust. This study presents rare earth element and yttrium (REE+Y) concentrations, δ13C, δ18O, 87Sr/86Sr, and clumped isotopic (Δ47) compositions of vein calcites in order to investigate their fluid sources, formation temperatures, and precipitation ages. These geochemical data are combined with microtextural analyses. Intersections of 87Sr/86Sr ratios of vein calcites with the Sr isotope seawater curve suggest two distinct calcite veining phases. Major calcite veining within an interval of ~10 Myr after crust formation is characterized by microtextures that point to extensional fracturing related to crack and sealing, host rock brecciation, and advective fluid flow. These vein calcites show REE+Y characteristics, 87Sr/86Sr ratios, and clumped isotopic compositions indicative of precipitation from seawater at <50 °C. Extended fluid residence times intensified fluid-rock interactions and lowered Y/Ho ratios of some blocky vein calcites, whereas crack and sealing resulted in pristine seawater signatures. Low 87Sr/86Sr ratios of localized high-temperature blocky vein calcites point to the involvement of hydrothermal fluids. These calcites show Mn-controlled oscillatory growth zonations that probably developed in a closed system out of equilibrium. Later calcite veining (<75 Ma) may have coincided with rotation and/or uplift of the Troodos ophiolite. Microtextures of these vein calcites indicate fluid diffusion and fracture-independent crystallization pressure-driven veining. Their variably modified seawater signatures resulted from diffusion-related fluid interaction with hydrothermal sediments.

Postmagmatic Tectonic Evolution of the Outer Izu-Bonin Forearc Revealed by Sediment Basin Structure and Vein Microstructure Analysis: Implications for a 15 Ma Hiatus Between Pacific Plate Subduction Initiation and Forearc Extension.

International Ocean Discovery Program Expedition 352 recovered sedimentary-volcaniclastic successions and extensional structures (faults and extensional veins) that allow the reconstruction of the Izu-Bonin forearc tectonic evolution using a combination of shipboard core data, seismic reflection images, and calcite vein microstructure analysis. The oldest recorded biostratigraphic ages within fault-bounded sedimentary basins (Late Eocene to Early Oligocene) imply a ~15 Ma hiatus between the formation of the igneous basement (52 to 50 Ma) and the onset of sedimentation. At the upslope sites (U1439 and U1442) extension led to the formation of asymmetric basins reflecting regional stretch of ~16-19% at strain rates of ~1.58 × 10-16 to 4.62 × 10-16 s-1. Downslope Site U1440 (closer to the trench) is characterized by a symmetric graben bounded by conjugate normal faults reflecting regional stretch of ~55% at strain rates of 4.40 × 10-16 to 1.43 × 10-15 s-1. Mean differential stresses are in the range of ~70-90 MPa. We infer that upper plate extension was triggered by incipient Pacific Plate rollback ~15 Ma after subduction initiation. Extension was accommodated by normal faulting with syntectonic sedimentation during Late Eocene to Early Oligocene times. Backarc extension was assisted by magmatism with related Shikoku and Parece-Vela Basin spreading at ~25 Ma, so that parts of the arc and rear arc, and the West Philippine backarc Basin were dismembered from the forearc. This was followed by slow-rift to postrift sedimentation during the transition from forearc to arc rifting to spreading within the Shikoku-Parece-Vela Basin system.

Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: results of a prospective study.

Chronic graft-versus-host disease (GVHD) remains a serious complication after allogeneic hematopoietic stem cell transplantation (HCT). In 2005 the National Institutes of Health (NIH) established new criteria for chronic GVHD based on retrospective data and expert recommendations. We prospectively evaluated the incidence of NIH-defined chronic GVHD and its prognostic impact in 178 consecutive patients. The cumulative incidence of chronic GVHD at 3 years was 64, 48 and 16% for chronic classic GVHD and overlap syndrome. Prior acute GVHD and myeloablative conditioning were significantly associated with increased risk of chronic GVHD. Three-year survival (overall survival (OS)) for late-acute GVHD, chronic classic and overlap chronic GVHD when assigned on day 100 were 69, 83 and 73%. OS was significantly worse for patients with platelet counts below 100 g/l at onset of chronic GVHD (35% versus 86%, P<0.0001) and progressive as compared with de novo and quiescent onset of chronic GVHD (54.5% versus 89.5% versus 84%, P = 0.022 and 0.001). Peak severity of chronic GVHD had no impact on non-relapse mortality (NRM) and OS. Recurrent acute GVHD, platelet counts below 100 g/l at diagnosis of chronic GVHD, progressive onset of chronic GVHD and advanced disease stage prior to HCT were significantly associated with increased NRM. This prospective analysis provides for the first-time data on the incidence rates of NIH-defined chronic GVHD categories and identified risk factors for the occurrence of chronic GVHD. A prognostic value of thrombocytopenia and progressive onset type of chronic GVHD for survival after HCT was observed in NIH-defined chronic GVHD.

Recipient vascular endothelial growth factor serum levels predict primary lung graft dysfunction.

Primary graft dysfunction (PGD) is a severe complication in lung transplantation. Therapeutic strategies are limited and there exist no predictive markers for PGD. To investigate whether vascular endothelial growth factor (VEGF) that regulates vascular permeability could predict PGD, pretransplant VEGF serum concentrations were measured in 150 lung transplant patients and 12 controls by ELISA. PGD was scored from 0 to 3 using chest radiographs and PaO(2)/FiO(2) ratios according to the International Society for Heart and Lung Transplantation guidelines. The mean graft ischemia time was 5 h 47 min and the donors' PaO(2)/FiO(2) ratios were >300. PGD grades 0-3 occurred in 23%, 44%, 21%, and 11% of patients, respectively. Pre-operative VEGF serum concentrations were significantly higher in PGD grade 3 (p < 0.0001) versus grade 0-2 and controls. VEGF concentrations significantly predicted PGD grade 3 versus 0-2 in logistic regression analysis (p < 0.0001) and receiver operating analysis (AUC = 0.778). At a cut-off level of > or =650 pg/mL VEGF had 86% sensitivity and 62% specificity to identify PGD grade 3 versus 0-2. Pre-operative VEGF serum concentrations could identify lung transplant recipients with high PGD risk.

Donor myocardial HIF-1alpha is an independent predictor of cardiac allograft dysfunction: a 7-year prospective, exploratory study.

Knowledge on interplay between the cardiac molecular response to transplantation-induced stress and primary graft dysfunction (PGD) is limited. A cDNA array identified HIF-1, EGR-1, NAB-2, VEGF-A and uPA as mediators of cardiac tissue response to transplantation-induced stress. mRNA expression of these molecules was measured in left ventricular biopsies from 200 donors before and after aortic cross-clamping and at 10-, 30- and 60-min reperfusion by real-time RT-PCR. HIF-1alpha expression at two time points was significantly associated with PGD, as shown by univariate analysis, receiver operating characteristic curve and multivariate logistic regression. At a cut-off level of 200 arbitrary units, HIF-1alpha after aortic cross-clamping in donors (78% sensitivity, 83% specificity) and at 10-min reperfusion (85% sensitivity, 83% specificity) identified PGD. HIF-1alpha demonstrates the potential to be a predictive marker for PGD; however, as multiple factors were tested at different time points, prospective evaluation is clearly necessary to confirm this observation.