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1.
J Cardiothorac Vasc Anesth ; 33(10): 2685-2694, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31064730

RESUMO

OBJECTIVE: Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings. DESIGN: A systematic review of the literature followed by a consensus-based voting process. SETTING: A web-based international consensus conference. PARTICIPANTS: Two hundred fifty-one physicians from 46 countries. INTERVENTIONS: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines. MEASUREMENTS AND MAIN RESULTS: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed. CONCLUSION: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.

2.
J Cardiothorac Vasc Anesth ; 33(5): 1430-1439, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30600204

RESUMO

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians' opinions and routine practices to understand the clinicians' response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to "do you agree" and "do you use") showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location.


Assuntos
Cuidados Críticos/métodos , Estado Terminal/mortalidade , Internet , Médicos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Inquéritos e Questionários , Cuidados Críticos/tendências , Estado Terminal/terapia , Humanos , Unidades de Terapia Intensiva/tendências , Internet/tendências , Mortalidade/tendências , Médicos/tendências
3.
Org Biomol Chem ; 16(27): 4963-4967, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29947415

RESUMO

A Pd-catalyzed borylation of 2-fluoroallyl chlorides with B2pin2 in the presence of [(2-MeAll)PdCl]2/TMEDA or [(2-MeAll)Pd(IPr)Cl] was developed to afford (2-fluoroallyl)pinacolboronates with high Z-selectivity. The products proved to be useful for anti-selective 2-fluoroallylboration of aromatic and aliphatic aldehydes.

4.
J Cardiothorac Vasc Anesth ; 32(2): 762-770, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29409711

RESUMO

OBJECTIVE: There is experimental evidence that phosphocreatine (PCr) can decrease ischemia/reperfusion injury of the heart. The authors investigated if PCr would improve heart performance as compared with standard treatment in cardiac surgery. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Hospitals. PARTICIPANTS: Adult and pediatric patients undergoing cardiac surgery. INTERVENTIONS: The ability of PCr to improve cardiac outcomes as compared with standard treatment was investigated. MEASUREMENTS AND MAIN RESULTS: PubMed/Medline, Embase, Scopus, Cochrane Library, China National Knowledge Infrastructure, WANGFANG DATA, and VIP Paper Check System were searched to March 1 2017. The authors included 26 randomized controlled trials comprising 1,948 patients. Random and fixed-effects models were used to estimate odds ratio (OR) and mean difference (MD) with 95% confidence interval (CI). PCr use was associated with reduced rates of intraoperative inotropic support (27% v 44%; OR 0.47, 95% CI 0.35-0.61; p < 0.001), major arrhythmias (16% v 28%; OR 0.44, 95% CI 0.27-0.69; p < 0.001), as well as increased spontaneous recovery of the cardiac rhythm immediately after aortic declamping (50% v 34%; OR 2.45, 95% CI 1.82-3.30; p < 0.001) as compared with standard treatment. The use of PCr decreased myocardial damage and augmented left ventricular ejection fraction in the postoperative period; however, MD for these outcomes were small and do not seem to be clinically significant. CONCLUSIONS: In randomized trials, PCr administration was associated with reduced rates of intraoperative inotropic support and major arrhythmias, and increased spontaneous recovery of the cardiac rhythm after aortic declamping. Large multicenter evidence is needed to validate these findings.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Cardiotônicos/administração & dosagem , Fosfocreatina/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Administração Intravenosa , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Complicações Pós-Operatórias/epidemiologia
5.
J Org Chem ; 78(22): 11126-46, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23964731

RESUMO

Fluoroform-derived CuCF3 recently discovered in our group exhibits remarkably high reactivity toward aryl and heteroaryl halides, performing best in the absence of extra ligands. A broad variety of iodoarenes undergo smooth trifluoromethylation with the "ligandless" CuCF3 at 23-50 °C to give the corresponding benzotrifluorides in nearly quantitative yield. A number of much less reactive aromatic bromides also have been trifluoromethylated, including pyridine, pyrimidine, pyrazine, and thiazole derivatives as well as aryl bromides bearing electron-withdrawing groups and/or ortho substituents. Only the most electrophilic chloroarenes can be trifluoromethylated, e.g., 2-chloronicotinic acid. Exceptionally high chemoselectivity of the reactions (no side-formation of arenes, biaryls, and C2F5 derivatives) has allowed for the isolation of a large number of trifluoromethylated products in high yield on a gram scale (up to 20 mmol). The CuCF3 reagent is destabilized by CuX coproduced in the reaction, the magnitude of the effect paralleling the Lewis acidity of CuX: CuCl > CuBr > CuI. While S(N)Ar and S(RN)1 mechanisms are not operational, there is a well-pronounced ortho effect, i.e., the enhanced reactivity of ortho-substituted aryl halides 2-RC6H4X toward CuCF3. Intriguingly, this ortho-effect is observed for R = NO2, COOH, CHO, COOEt, COCH3, OCH3, and even CH3, but not for R = CN. The fluoroform-derived CuCF3 reagent and its reactions with haloarenes provide an unmatched combination of reactivity, selectivity, and low cost.


Assuntos
Clorofluorcarbonetos de Metano/química , Cobre/química , Hidrocarbonetos Halogenados/química , Hidrocarbonetos Halogenados/síntese química , Compostos Organometálicos/química , Modelos Moleculares , Estrutura Molecular
6.
Asian Cardiovasc Thorac Ann ; 20(6): 675-81, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23284109

RESUMO

BACKGROUND AND OBJECTIVES: this prospective study was carried out to evaluate oxidative stress and liver monooxygenase function after cardiac surgery in patients with acquired valvular heart disease. METHODS: 97 patients were studied. Oxidative stress was quantified with malondialdehyde, coupled trienes, hepatocuprein, and catalase activity. Liver monooxygenase function was evaluated with antipyrine pharmacokinetics. For statistical analyses, the Dunnett test and Pearson's correlation coefficient were used. RESULTS: on the 1st-2nd postoperative days, high lipid peroxidation activation (malondialdehyde: 9.6 ± 2.7 vs. 6.9 ± 2.0 nmol mL(-1), p <0.05) and a significant decrease in liver monooxygenase function (antipyrine clearance: 18.3 ± 11.1 vs. 39.0 ± 18.9 mL kg(-1)h(-1), p <0.05) were revealed. On the 3rd-4th and 11th-12th postoperative days, the intensity of oxidative stress decreased and monooxygenase function returned to baseline (antipyrine clearance: 45.6 ± 17.9 vs. 39.0 ± 18.9 mL kg(-1)h(-1)). The analysis showed a negative relationship between oxidative stress and liver monooxygenase function. CONCLUSION: patients undergoing surgery for acquired valvular heart disease have considerable oxidative stress and a decrease in liver monooxygenase function on the 1st-2nd postoperative days. Activation of lipid peroxidation is one of the main reasons for suppression of microsomal monooxygenases activity. A slowdown of liver microsomal oxidation might change the pharmacokinetic response of patients under drug therapy.


Assuntos
Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Fígado/enzimologia , Oxigenases de Função Mista/metabolismo , Estresse Oxidativo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos
7.
J Am Chem Soc ; 133(51): 20901-13, 2011 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-22136628

RESUMO

We have found the first reaction of direct cupration of fluoroform, the most attractive CF(3) source for the introduction of the trifluoromethyl group into organic molecules. Treatment of CuX (X = Cl, Br, I) with 2 equiv of MOR (M = K, Na) in DMF or NMP produces novel alkoxycuprates that readily react with CF(3)H at room temperature and atmospheric pressure to give CuCF(3) derivatives. The CuCl and t-BuOK (1:2) combination provides best results, furnishing the CuCF(3) product within seconds in nearly quantitative yield. As demonstrated, neither CF(3)(-) nor CF(2) mediate the Cu-CF(3) bond formation, which accounts for its remarkably high selectivity. The fluoroform-derived CuCF(3) solutions can be efficiently stabilized with TREAT HF to produce CuCF(3) reagents that readily trifluoromethylate organic and inorganic electrophiles in the absence of additional ligands such as phenanthroline. A series of novel Cu(I) complexes have been structurally characterized, including K(DMF)[Cu(OBu-t)(2)] (1), Na(DMF)(2)[Cu(OBu-t)(2)] (2), [K(8)Cu(6)(OBu-t)(12)(DMF)(8)(I)](+) I(-) (3), and [Cu(4)(CF(3))(2)(C(OBu-t)(2))(2)(µ(3)-OBu-t)(2)] (7).


Assuntos
Clorofluorcarbonetos de Metano/química , Cobre/química , Compostos Organometálicos/química , Estrutura Molecular
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