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"Weidauer, Stephan"
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Impact of Systemic Inflammatory Response Syndrome on Vasospasm, Cerebral Infarction, and Outcome After Subarachnoid Hemorrhage: Exploratory Analysis of CONSCIOUS-1 Database
2010
Background
Systemic inflammatory response syndrome (SIRS) may develop after aneurysmal subarachnoid hemorrhage (SAH). We investigated factors associated with SIRS after SAH, whether SIRS was associated with complications of SAH such as vasospasm, cerebral infarction, and clinical outcome, and whether SIRS could contribute to a difference in outcome between patients treated by endovascular coiling or neurosurgical clipping of the ruptured aneurysm.
Methods
This was exploratory analysis of 413 patients in the CONSCIOUS-1 study. SIRS was diagnosed if the patient had at least 2 of 4 variables (hypothermia/fever, tachycardia, tachypnea, and leukocytosis/leukopenia) within 4 days of admission. Clinical outcome was measured on the Glasgow outcome scale 3 months after SAH. The relationship between clinical and radiologic variables and SIRS, angiographic vasospasm, delayed ischemic neurologic deficit (DIND), cerebral infarction, vasospasm-related infarction, and clinical outcome were modeled with uni- and multivariable analyses.
Results
63% of patients developed SIRS. Many factors were associated with SIRS in univariate analysis, but only poor WFNS grade and pneumonia were independently associated with SIRS in multivariable analysis. SIRS burden (number of SIRS variables per day over the first 4 days) was associated with poor outcome, but not with angiographic vasospasm, DIND, or cerebral infarction. The method of aneurysm treatment was not associated with SIRS.
Conclusion
SIRS was associated with poor outcome but not angiographic vasospasm, DIND, or cerebral infarction after SAH in the CONSCIOUS-1 data. There was no support for the notion that neurosurgical clipping is associated with a greater risk of SIRS than endovascular coiling.
Journal Article
Method of Aneurysm Treatment Does Not Affect Clot Clearance After Aneurysmal Subarachnoid Hemorrhage
2012
Abstract
BACKGROUND
Patients undergoing neurosurgical clipping or endovascular coiling of a ruptured aneurysm may differ in their risk of vasospasm.
OBJECTIVE
Because clot clearance affects vasospasm, we tested the hypothesis that clot clearance differs in patients depending on method of aneurysm treatment.
METHODS
Exploratory analysis was performed on 413 patients from CONSCIOUS-1, a prospective randomized trial of clazosentan for the prevention of angiographic vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). Clot clearance was measured by change in Hijdra score between baseline computed tomography and one performed 24 to 48 hours after aneurysm treatment. Angiographic vasospasm was assessed by the use of catheter angiography 7 to 11 days after SAH, and delayed ischemic neurological deficit (DIND) was determined clinically. Extended Glasgow Outcome Score (GOSE) was assessed 3 months after SAH, and poor outcome was defined as death, vegetative state, or severe disability. Multivariable ordinal and binary logistic regression were used.
RESULTS
There was no significant difference in the rate of clot clearance between patients undergoing clipping or coiling (P = .56). Coiling was independently associated with decreased severity of angiographic vasospasm (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.33-0.86), but not with DIND or GOSE. Greater clot clearance decreased the risk of severe angiographic vasospasm (OR 0.86, 95% CI 0.81-0.91), whereas higher baseline Hijdra score predicted increased angiographic vasospasm (OR 1.17, 95% CI 1.11-1.23) and poor GOSE (OR 1.09, 95% CI 1.04-1.14).
CONCLUSION
Aneurysm coiling and increased clot clearance were independently associated with decreased severity of angiographic vasospasm in multivariate analysis, although no differences in clot clearance were seen between coiled and clipped patients.
Journal Article
Reduction of Sulfoxides to Sulfides in the Presence of Copper Catalysts
2011
Copper complexes catalyze the reduction of aliphatic and aromatic sulfoxides in the presence of silanes as reducing reagent. The influence of different reaction parameters on the catalytic activity is investigated in detail. The scope and limitations of the described catalyst is demonstrated in the reduction of various sulfoxides. In most cases, high conversion and excellent chemoselectivity are obtained.
Graphical Abstract
Journal Article
Nickel-catalyzed C(sp2)–C(sp2) Cross Coupling Reactions of Sulfur-Functionalities and Grignard Reagents
2013
In the present study, the nickel-catalyzed carbon carbon bond formation of a range of sulfur containing substrates with Grignard reagents via desulfurization has been explored. After investigation of different reaction parameters with a well-defined nickel complex an excellent and easy-accessible pre-catalyst was found. The obtained system was capable to convert a broad scope of substrates under mild reaction conditions.
Graphical Abstract
Journal Article
Synthesis of δ- and ε-Cyanoesters by Zinc-Catalyzed Ring-Opening of Cyclic Ethers with Acid Chlorides and Subsequent Cyanation
2012
In the present study, the zinc-catalyzed cleavage of cyclic ethers with acid halides as nucleophiles to yield chloroesters with different chain length has been investigated in detail. In the presence of straightforward and commercially available zinc salts as pre-catalysts excellent yields and selectivities were feasible. After studying the reaction conditions and the scope of the method, several efforts were carried out to understand the reaction mechanism. The obtained chloroesters were subsequently converted to δ- and ε-cyano esters, which are useful precursors in natural product synthesis.
Graphical Abstract
Journal Article
Synthesis of δ- and ζ-cyanoesters by zinc-catalyzed ring-opening of cyclic ethers with acid chlorides and subsequent cyanation
2012
In the present study, the zinc-catalyzed cleavage of cyclic ethers with acid halides as nucleophiles to yield chloroesters with different chain length has been investigated in detail. In the presence of straightforward and commercially available zinc salts as pre-catalysts excellent yields and selectivities were feasible. After studying the reaction conditions and the scope of the method, several efforts were carried out to understand the reaction mechanism. The obtained chloroesters were subsequently converted to δ- and ζ-cyano esters, which are useful precursors in natural product synthesis.
Journal Article
Copper-Catalyzed Dehydration of Primary Amides to Nitriles
2011
In the present study we introduce a copper-catalyzed protocol for the dehydration of primary amides to their corresponding nitriles applying
N
-methyl-
N
-(trimethylsilyl)trifluoroacetamide (MSTFA) as silylation reagent. For that purpose investigations of various reaction parameters (copper source, solvent, temperature, MSTFA and copper loading) have been carried out to find suitable reaction conditions. Simple copper(I) chloride (2.5 mol%) and MSTFA (2.0 equiv) in toluene allow for the straightforward synthesis of a variety of nitriles (15 examples).
Graphical Abstract
Journal Article
Nickel-catalyzed C cross coupling reactions of sulfur-functionalities and Grignard reagents
by
Weidauer, Maik
,
Someya, Chika I
,
Enthaler, Stephan
in
Chemical tests and reagents
,
Nickel
,
Sulfur
2013
In the present study, the nickel-catalyzed carbon carbon bond formation of a range of sulfur containing substrates with Grignard reagents via desulfurization has been explored. After investigation of different reaction parameters with a well-defined nickel complex an excellent and easy-accessible pre-catalyst was found. The obtained system was capable to convert a broad scope of substrates under mild reaction conditions.
Journal Article