Optimal cerebral perfusion pressure in patients with intracerebral hemorrhage: an observational case series

Introduction: Current guidelines for spontaneous intracerebral hemorrhage (ICH) recommend maintaining cerebral perfusion pressure (CPP) between 50 and 70 mmHg, depending on the state of autoregulation. We continuously assessed dynamic cerebral autoregulation and the possibility of determination of an optimal CPP (CPPopt) in ICH patients. Associations between autoregulation, CPPopt and functional outcome were explored. Methods: Intracranial pressure (ICP), mean arterial pressure (MAP) and CPP were continuously recorded in 55 patients, with 38 patients included in the analysis. The pressure reactivity index (PRx) was calculated as moving correlation between MAP and ICP. CPPopt was defined as the CPP associated with the lowest PRx values. CPPopt was calculated using hourly updated of 4 hour windows. The modified Rankin Scale (mRS) was assessed at 3 months and associations between PRx, CPPopt and outcomes were explored using Pearson correlation and Fisher’s exact test. Multivariate stepwise logistic regression models were calculated including standard outcome predictors along with percentage of time with PRx >0.2 and percentage of time within the CPPopt range. Results: An overall PRx indicating impairment of pressure reactivity was found in 47% of patients (n = 18). The mean PRx and the time spent with a PRx > 0.2 significantly correlated with mRS at 3 months (r = 0.50, P = 0.002; r = 0.46, P = 0.004). CPPopt was calculable during 57% of the monitoring time. The median CPP was 78 mmHg, the median CPPopt 83 mmHg. Mortality was lowest in the group of patients with a CPP close to their CPPopt. However, for none of the CPPopt variables a significant association to outcome was found. The percentage of time with impaired autoregulation and hemorrhage volume were independent predictors for acceptable outcome (mRS 1 to 4) at three months. Conclusions: Failure of pressure reactivity seems common following severe ICH and is associated with unfavorable outcome. Real-time assessment of CPPopt is feasible in ICH and might provide a tool for an autoregulation-oriented CPP management. A larger trial is needed to explore if a CPPopt management results in better functional outcomes

Impact of statin use and lipid profile on symptomatic intracerebral haemorrhage, outcome and mortality after intravenous thrombolysis in acute stroke

Background: It is unclear if a certain lipid profile and/or statin use contribute to symptomatic intracerebral haemorrhage (sICH), poor outcome or mortality after intravenous thrombolysis for ischaemic stroke. The aim of the current study was to assess the impact of statin use and lipid profile on sICH, outcome and mortality following thrombolysis in acute stroke. Methods: From 2001 to 2010, all patients admitted to our hospital and undergoing intravenous thrombolysis for acute ischaemic stroke were included into an open, prospective database. Initial stroke severity was assessed using the National Institute of Health Stroke Scale. Demographics, vascular risk factors, admission blood pressure, glucose levels, previous medication including statin use, lipid profiles including low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride levels were recorded. Outcome measures included sICH according to the European Cooperative Acute Stroke Study II criteria, modified Rankin scale and mortality at 3 months. Results: 1,066 patients were included in the analysis; 5.3% (57 patients) had sICH. Mortality at 3 months was 17.6% (188 patients). A favourable outcome (modified Rankin scale 0-1) at 3 months was attained by 35.6% (379 patients). Prior statin use was not associated with increased odds for sICH (OR 1.05, 95% CI 0.55–2.04, p = 0.864), mortality (OR 1.32, 95% CI 0.90–1.93, p = 0.152) or favourable outcome (OR 0.89, 95% CI 0.65–1.24, p = 0.507). Similar results were found for the different lipid variables: high LDL (OR 0.96, 95% CI 0.36–2.60, p = 0.942), high triglyceride (OR 1.74, 95% CI 0.84–3.56, p = 0.132) and low HDL (OR 1.78, 95% CI 0.68–4.65, p = 0.279) were not associated with increased odds for sICH. Likewise, neither mortality nor functional outcome at 3 months was significantly associated with any of the lipid variables in the univariable analysis following Bonferroni adjustment for multiple comparisons. The same results were found in the multivariable analysis adjusting for imbalances in baseline characteristics. Conclusions: In contrast to previous studies, we found that in stroke patients receiving thrombolysis therapy, neither the lipid profile nor prior statin use were associated with increased odds for sICH, functional outcome or mortality at 3 months

Exactly solvable Richardson–Gaudin models and their applications

3 pages, 1 table, 1 figure.--PACS nrs.: 21.60.Cs, 21.60.Fw, 02.30.Ik.--Arxiv pre-print available at: http://arxiv.org/abs/math-ph/0609022v1We first show that the quantum pairing problem can be mapped exactly on to a classical electrostatic problem in two dimensions and then use this analogy to obtain a pictorial representation of how superconductivity arises in a finite fermionic system. Specific application to the nuclei 114−116Sn suggests some new insight into the evolution of pairing correlations in a quantum system with few active particles. We also summarize other recent work on exactly solvable pairing models, including their applications in a wide variety of strongly correlated quantum systems.The work reported herein was supported in part by the US National Science Foundation under grant no PHY-0140036 and in part by the Spanish DGI under grant no BFM2003-05316-C02-02.Peer reviewe

The Onconeural Antigen cdr2 Is a Novel APC/C Target that Acts in Mitosis to Regulate C-Myc Target Genes in Mammalian Tumor Cells

Cdr2 is a tumor antigen expressed in a high percentage of breast and ovarian tumors and is the target of a naturally occurring tumor immune response in patients with paraneoplastic cerebellar degeneration, but little is known of its regulation or function in cancer cells. Here we find that cdr2 is cell cycle regulated in tumor cells with protein levels peaking in mitosis. As cells exit mitosis, cdr2 is ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) and rapidly degraded by the proteasome. Previously we showed that cdr2 binds to the oncogene c-myc, and here we extend this observation to show that cdr2 and c-myc interact to synergistically regulate c-myc-dependent transcription during passage through mitosis. Loss of cdr2 leads to functional consequences for dividing cells, as they show aberrant mitotic spindle formation and impaired proliferation. Conversely, cdr2 overexpression is able to drive cell proliferation in tumors. Together, these data indicate that the onconeural antigen cdr2 acts during mitosis in cycling cells, at least in part through interactions with c-myc, to regulate a cascade of actions that may present new targeting opportunities in gynecologic cancer

β-Blockers, Pneumonia, and Outcome After Ischemic Stroke: Evidence From Virtual International Stroke Trials Archive

Increased sympathetic drive after stroke is involved in the pathophysiology of several complications including poststroke immunudepression. β-Blocker (BB) therapy has been suggested to have neuroprotective properties and to decrease infectious complications after stroke. We aimed to examine the effects of random pre- and on-stroke BB exposure on mortality, functional outcome, and occurrence of pneumonia after ischemic stroke. Data including standard demographic and clinical variables as well as prestroke and on-stroke antihypertensive medication, incidence of pneumonia, functional outcome defined using modified Rankin Scale and mortality at 3 months were extracted from the Virtual International Stroke Trials Archive. For statistical analysis multivariable Poisson regression was used. In total, 5212 patients were analyzed. A total of 1155 (22.2%) patients were treated with BB before stroke onset and 244 (4.7%) patients were newly started with BB in the acute phase of stroke. Mortality was 17.5%, favorable outcome (defined as modified Rankin Scale, 0-2) occurred in 58.2% and pneumonia in 8.2% of patients. Prestroke BB showed no association with mortality. On-stroke BB was associated with reduced mortality (adjusted risk ratio, 0.63; 95% confidence interval, 0.42-0.96). Neither prestroke BB nor on-stroke BB showed an association with functional outcome. Both prestroke and on-stroke BB were associated with reduced frequency of pneumonia (adjusted risk ratio, 0.77; 95% confidence interval, 0.6-0.98 and risk ratio, 0.49; 95% confidence interval, 0.25-0.95). In this large nonrandomized comparison, on-stroke BB was associated with reduced mortality. Prestroke and on-stroke BB were inversely associated with incidence of nosocomial pneumonia. Randomized trials investigating the potential of β-blockade in acute stroke may be warranted