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1.
OBJECTIVE:: This purpose of this consensus conference was to determine whether surgical atrial fibrillation (AF) ablation during cardiac surgery improves clinical and resource outcomes compared with cardiac surgery alone in adults undergoing cardiac surgery for valve or coronary artery bypass grafting. METHODS:: Before the consensus conference, the consensus panel reviewed the best available evidence, whereby systematic reviews, randomized trials, and nonrandomized trials were considered in descending order of validity and importance. Evidence-based statements were created, and consensus processes were used to determine the ensuing recommendations. The American Heart Association/American College of Cardiology system was used to label the level of evidence and class of recommendation. RESULTS:: The consensus panel agreed on the following statements in patients with AF undergoing cardiac surgery concomitant surgical ablation: CONCLUSIONS:: Given these evidence-based statements, the consensus panel stated that, in patients with persistent and permanent AF undergoing cardiac surgery, concomitant surgical ablation is recommended to increase incidence of sinus rhythm at short- and long-term follow-up (class 1, level A); to reduce the risk of stroke and thromboembolic events (class 2a, level B); to improve EF (class 2a, level A); and to exercise tolerance (class 2a, level A) and long-term survival (class 2a, level B).  相似文献   

2.
OBJECTIVE:: This meta-analysis sought to determine whether endoscopic vascular graft harvesting (EVH) improves clinical and resource outcomes compared with conventional open graft harvesting (OVH) in adults undergoing coronary artery bypass surgery. METHODS:: A comprehensive search was undertaken to identify all randomized and nonrandomized trials of EVH versus OVH up to April 2005. The primary outcome was wound complications. Secondary outcomes included any other clinical morbidity and resource utilization. Odds ratios (OR), weighted mean differences (WMD), or standardized mean differences (SMD) and their 95% confidence intervals (95% CI) were analyzed. RESULTS:: Thirty-six trials of 9,632 patients undergoing saphenous vein harvest met the inclusion criteria (13 randomized; 23 nonrandomized). Risk of wound complications was significantly reduced by EVH compared with OVH (OR 0.31, 95% CI 0.23-0.41). Similarly, the risk of wound infections was significantly reduced (OR 0.23, 95% CI 0.20-0.53; P < 0.0001). Need for surgical wound intervention was also significantly reduced (OR 0.16, 95% CI 0.08-0.29). The incidence of pain, neuralgia, and patient satisfaction was improved with EVH compared with OVH. Postoperative myocardial infarction, stroke, reintervention for ischemia or angina recurrence, and mortality were not significantly different. Operative time was significantly increased (WMD 15.26 minutes; 95% CI 0.01, 30.51), hospital length of stay was reduced (WMD -0.85 days; 95% CI -1.55, -0.15), and readmissions were reduced (OR 0.53, 95% CI 0.29-0.98). Costs were insufficiently reported to allow for aggregate analysis. CONCLUSIONS:: Endoscopic vascular graft harvesting of the saphenous vein reduces wound complications and improves patient satisfaction and resource utilization. Further research is required to determine the incremental cost-effectiveness of EVH versus OVH.  相似文献   

3.
OBJECTIVE:: The purpose of this consensus conference was to determine whether video-assisted thoracic surgery (VATS) improves clinical and resource outcomes compared with conventional thoracotomy (OPEN) in adults undergoing lobectomy for lung cancer, and to outline evidence-based recommendations for the use of VATS in performing lobectomy for lung cancer. METHODS:: Before the consensus conference, the best available evidence was reviewed in that systematic reviews, randomized trials, and nonrandomized trials were considered in descending order of validity and importance. At the consensus conference, evidence-based statements were created, and consensus processes were used to determine the ensuing recommendations. The American Heart Association/American College of Cardiology system was used to label the level of evidence and class of recommendation. RESULTS AND RECOMMENDATIONS:: The consensus panel agreed upon the following statements and recommendations in patients with clinical stage I nonsmall cell lung cancer undergoing lung lobectomy:  相似文献   

4.
OBJECTIVE:: The purpose of this consensus conference was to determine whether stentless bioprosthetic valves improve clinical and resource outcomes compared with stented valves in patients undergoing aortic valve replacement, and to outline evidence-based recommendations for the use of stentless and stented bioprosthetic valves in adult aortic valve replacement. METHODS:: Before the consensus conference, the best available evidence was reviewed in that systematic reviews, randomized trials, and nonrandomized trials were considered in descending order of validity and importance. At the consensus conference, evidence-based statements were created, and consensus processes were used to determine the ensuing recommendations. The American Heart Association/American College of Cardiology system was used to label the level of evidence and class of recommendation. RESULTS AND RECOMMENDATIONS:: Seventeen randomized studies published in 23 articles involving 1317 patients, and 14 nonrandomized trial published in 18 articles involving 2485 patients were included in the meta-analysis and consensus conference. All randomized trials inserted the stentless bioprosthetic valves in the subcoronary configuration. The consensus panel agreed upon the following statements and recommendations in patients undergoing aortic valve replacement:Because there were no randomized control trial comparing subcoronary stentless prosthetic valve and root replacement, the following recommendations are derived from expert opinion:  相似文献   

5.
《Endocrine practice》2021,27(3):174-184
ObjectivesTo provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state-of-the-art practices and the value of surgical experience in the management of this unusual and challenging disease in children.MethodsA literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.).ResultsTwenty-five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus.ConclusionPediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high-volume centers by high-volume surgeons.  相似文献   

6.
BACKGROUND:: The purpose of this evidence-based consensus statement is to systematically review and meta-analyze the randomized and nonrandomized evidence comparing off-pump (OPCAB) to conventional coronary artery bypass (CCAB) surgery and to provide consensus on the role of OPCAB in low- and high-risk surgical patients. METHODS AND RESULTS:: This consensus conference was conducted according to the American College of Cardiology (ACC)/American Heart Association (AHA) standards for development of clinical practice guidelines. The Steering Committee collated all published studies of OPCAB versus CCAB through May 2004 and developed six questions central to controversies surrounding OPCAB surgery in mortality, morbidity, and resource utilization. For mixed-risk patient populations, meta-analysis of 37 randomized clinical trials (3,369 patients, Level A) reported across a total of 53 papers, and two meta-analyses of nonrandomized trials (Level B) comparing OPCAB versus CCAB were identified. For high-risk patient populations, we performed a meta-analysis of 3 randomized and 42 nonrandomized trials (26,349 patients, Level B). CONCLUSION:: Meta-analysis of Level A and B evidence provided the basis for the following consensus statements in patients undergoing surgical myocardial revascularization: (1) OPCAB should be considered a safe alternative to CCAB with respect to risk of mortality [Class I, Level A]; (2) With appropriate use of modern stabilizers, heart positioning devices, and adequate surgeon experience, similar completeness of revascularization and graft patency can be achieved [Class IIa, Level A]; (3) OPCAB is recommended to reduce perioperative morbidity [Class I, Level A]; (4) OPCAB may be recommended to minimize midterm cognitive dysfunction [Class IIa, Level A]; (5) OPCAB should be considered as an equivalent alternative to CCAB in regard to quality of life [Class I, Level A]; (6) OPCAB is recommended to reduce the duration of ventilation, ICU and hospital stay, and resource utilization [Class I, Level A]; (7) OPCAB should be considered in high-risk patients to reduce perioperative mortality, morbidity, and resource utilization [Class IIa, Level B].  相似文献   

7.
K E Prehoda  D J Lee  W A Lim 《Cell》1999,97(4):471-480
The Enabled/VASP homology 1 (EVH1; also called WH1) domain is an interaction module found in several proteins implicated in actin-based cell motility. EVH1 domains bind the consensus proline-rich motif FPPPP and are required for targeting the actin assembly machinery to sites of cytoskeletal remodeling. The crystal structure of the mammalian Enabled (Mena) EVH1 domain complexed with a peptide ligand reveals a mechanism of recognition distinct from that used by other proline-binding modules. The EVH1 domain fold is unexpectedly similar to that of the pleckstrin homology domain, a membrane localization module. This finding demonstrates the functional plasticity of the pleckstrin homology fold as a binding scaffold and suggests that membrane association may play an auxiliary role in EVH1 targeting.  相似文献   

8.
《BMJ (Clinical research ed.)》1994,308(6922):159-168
OBJECTIVE--To determine the efficacy of antiplatelet therapy in maintaining vascular patency in various categories of patients. DESIGN--Overviews of 46 randomised trials of antiplatelet therapy versus control and 14 randomised trials comparing one antiplatelet regimen with another. SETTING--Randomised trials that could have been available by March 1990 and in which vascular graft or arterial patency was to be studied systematically. SUBJECTS--About 8000 patients at varying degrees of risk of vascular occlusion (by virtue of disease or of having some vascular procedure) were in trials of antiplatelet therapy versus control and 4000 such patients were in trials directly comparing different antiplatelet regimens. RESULTS--Overall, antiplatelet therapy produced a highly significant (2P < 0.0001) reduction in vascular occlusion, with similar proportional reductions in several different types of patients. Hence the absolute reductions tended to be largest among patients at highest risk of occlusion, with smaller but still significant absolute reductions among lower risk patients. The proportions of patients with confirmed occlusion among those allocated antiplatelet therapy versus appropriately adjusted control proportions (and mean scheduled treatment durations and net absolute benefits) were: (a) among about 4000 patients with coronary artery grafts, 21% antiplatelet therapy v 30% control (seven month benefit about 90 patients protected per 1000 allocated antiplatelet therapy (2P < 0.00001)); (b) among about 800 patients after coronary angioplasty, 4% antiplatelet therapy v 8% control (six month benefit about 40/1000 (2P = 0.02)); (c) among about 3000 patients with peripheral artery procedures or disease, 16% antiplatelet therapy v 25% control (19 month benefit about 90/1000 (2P < 0.00001)); (d) among about 400 renal patients with a shunt or fistula placed for haemodialysis access, 17% antiplatelet therapy v 39% control (two month benefit about 200/1000 (2P < 0.00001)). Indirect comparisons between the effects of starting treatment before these vascular procedures and starting soon after them indicated similar sized benefits. As well as preventing subclinical occlusion, antiplatelet therapy produced a significant (2P = 0.002) reduction of about one quarter in the odds of suffering a "vascular event" (non-fatal myocardial infarction, non-fatal stroke, or vascular death). Various antiplatelet regimens (chiefly aspirin alone or aspirin plus dipyridamole) were studied but there was no significant evidence of differences between their effects on arterial occlusion or vascular events. Data on bleeding were incomplete but no large excess with antiplatelet therapy was apparent. CONCLUSION--Antiplatelet therapy (chiefly aspirin alone or aspirin plus dipyridamole) greatly reduces the risk of vascular occlusion in a wide range of patients at high risk of this complication. Further studies are required to determine exactly when treatment should start (to limit any perioperative bleeding while still preventing most early occlusion) and for how long it should be continued.  相似文献   

9.
虽然,美国已有关于幽门螺杆菌(Helicobacter pylori,H.pylori)检测和治疗的指南,但对患者进行治疗前后H.pylori检测的建议通常没有得到遵循。来自美国不同地区研究成人和儿童H.pylori感染处理的11名专家参加了"休斯敦共识会议",并在会议中讨论诊断H.pylori感染的关键因素:确定目标人群进行H.pylori检测;抗生素药物敏感性对检测和治疗的影响;确认H.pylori感染和确认根除治疗结果的合适方法。专家被分为多组,采用改良的Delphi小组讨论法来评定需行H.pylori检测的目标人群,抗生素药物敏感性检测方法和治疗方法、根除治疗后的结果确认及相关检测方法。证据质量和建议强度均采用GRADE系统进行评估。各工作小组的结果将提交给所有小组成员进行最后的共识表决。在专家共识会议之后,这些结论将提交给一个独立的胃肠病学专家小组进行验证,并对会议中提出的29项声明进行认同程度评估。最后的建议是基于现有最佳证据提出,并提供带参考文献的共识声明,以便在全美各地的医疗保健体系中实施。  相似文献   

10.
11.

Objectives

We developed clinical guidelines for the management of bone health in Rett syndrome through evidence review and the consensus of an expert panel of clinicians.

Methods

An initial guidelines draft was created which included statements based upon literature review and 11 open-ended questions where literature was lacking. The international expert panel reviewed the draft online using a 2-stage Delphi process to reach consensus agreement. Items describe the clinical assessment of bone health, bone mineral density assessment and technique, and pharmacological and non-pharmacological interventions.

Results

Agreement was reached on 39 statements which were formulated from 41 statements and 11 questions. When assessing bone health in Rett syndrome a comprehensive assessment of fracture history, mutation type, prescribed medication, pubertal development, mobility level, dietary intake and biochemical bone markers is recommended. A baseline densitometry assessment should be performed with accommodations made for size, with the frequency of surveillance determined according to individual risk. Lateral spine x-rays are also suggested. Increasing physical activity and initiating calcium and vitamin D supplementation when low are the first approaches to optimizing bone health in Rett syndrome. If individuals with Rett syndrome meet the ISCD criterion for osteoporosis in children, the use of bisphosphonates is recommended.

Conclusion

A clinically significant history of fracture in combination with low bone densitometry findings is necessary for a diagnosis of osteoporosis. These evidence and consensus-based guidelines have the potential to improve bone health in those with Rett syndrome, reduce the frequency of fractures, and stimulate further research that aims to ameliorate the impacts of this serious comorbidity.  相似文献   

12.
BackgroundConsensus statements and clinical practice guidelines are widely available for enhancing the care of cancer patients. Despite subtle differences in their definition and purpose, these terms are often used interchangeably. We systematically assessed the methodological quality of consensus statements and clinical practice guidelines published in three commonly read, geographically diverse, cancer-specific journals. Methods Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine’s standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents.MethodsConsensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine''s standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents.FindingsThirty-four consensus statements and 67 clinical practice guidelines were evaluated. The rigour of development score for consensus statements over the three journals was 32% lower than that of clinical practice guidelines. The editorial independence score was 15% lower for consensus statements than clinical practice guidelines. One journal scored consistently lower than the others over both domains. No journals adhered to all the items related to the transparency of document development. One journal’s consensus statements endorsed a product made by the sponsoring pharmaceutical company in 64% of cases.ConclusionGuidance documents are an essential part of oncology care and should be subjected to a rigorous and validated development process. Consensus statements had lower methodological quality than clinical practice guidelines using AGREE II. At a minimum, journals should ensure that that all consensus statements and clinical practice guidelines adhere to AGREE II criteria. Journals should consider explicitly requiring guidelines to declare pharmaceutical company sponsorship and to identify the sponsor’s product to enhance transparency.  相似文献   

13.

Background

Intra-aortic balloon pumps (IABP) have generally been used for patients undergoing high-risk mechanical coronary revascularization. However, there is still insufficient evidence to determine whether they can improve outcomes in reperfusion therapy patients, mainly by percutaneous coronary intervention (PCI) with stenting or coronary artery bypass graft (CABG). This study was designed to determine the difference between high-risk mechanical coronary revascularization with and without IABPs on mortality, by performing a meta-analysis on randomized controlled trials of the current era.

Methods

Pubmed and Embase databases were searched from inception to May 2015. Unpublished data were obtained from the investigators. Randomized clinical trials of IABP and non-IABP in high-risk coronary revascularization procedures (PCI or CABG) were included. In the case of PCI procedures, stents should be used in more than 80% of patients. Numbers of events at the short-term and long-term follow-up were extracted.

Results

A total of 12 randomized trials enrolling 2155 patients were included. IABPs did not significantly decrease short-term mortality (relative risk (RR) 0.66; 95% CI, 0.42–1.01), or long-term mortality (RR 0.79; 95% CI, 0.47–1.35), with low heterogeneity across the studies. The findings remained stable in patients with acute myocardial infarction with or without cardiogenic shock. But in high-risk CABG patients, IABP was associated with reduced mortality (71 events in 846 patients; RR 0.40; 95%CI 0.25–0.67).

Conclusion

In patients undergoing high-risk coronary revascularization, IABP did not significantly decrease mortality. But high-risk CABG patients may be benefit from IABP. Rigorous criteria should be applied to the use of IABPs.  相似文献   

14.
BackgroundRadiotherapy (RT) is an essential element in cancer treatment: 50–70% of cancer patients receive RT at some time of the course of their disease. Of these, almost 95% experience some grade of radiation dermatitis (RD). RD can affect patient’s quality of life during and after treatment. Consequently, the management of RD is important. There are few randomized controlled clinical trials on interventions used to prevent and treat RD and no standardized consensus on RD management. A panel of opinion leaders of the Mexican Society of Radiotherapy (SOMERA) took part in a study of oncologic practice in Mexico. The following clinical guide is referenced both by the national practice reality and international evidence.Materials and methodsThis RD management guide is based on input provided by 25 Mexican radiation oncologists, whose criteria were gathered using the Delphi Method and article review.ResultsTwenty-one questions about experience in RD treatment were voted. More than 80% of the panel agreed with: the use of dermocosmetics/medical device in prevention and in treatment of RD grades 1–2. As for grade 3, they recommend individualizing each case and dermatologist evaluation. Topical steroids should be used when there is skin itching or pain. Consider the use of natural soaking elements. Skin care must be continued to avoid or reduce severity of late radiation skin lesions.ConclusionThis consensus was developed as a supportive educational tool that can be adapted to individual clinical needs, useful for professionals involved in the treatment of RT patients.  相似文献   

15.

Background

This study aimed to generate prioritised goals for oral health services for people with disabilities as a first step in meeting the need for evidence based oral health services for people with disabilities in Ireland.

Methods

The study used a three round modified e-Delphi method, involving dental service professionals and people with disabilities or their representatives, in Ireland. Three rounds were completed online using SurveyMonkey. Round 1 asked: “List what you think dental services for people with disabilities in Ireland should be like.” Items for subsequent rounds were generated from responses to Round 1. Round 2 and Round 3 used 5 point Likert scales to rank these items by priority: from No Priority (1) to Top Priority (5). Consensus was achieved on each item where at least 80% of respondents considered an item either High or Top Priority. A consensus meeting concluded the process.

Results

Sixty-one panelists started and 48 completed the survey. The Delphi panel agreed on level of priority for 69 items and generated 16 consensus statements. These statements covered a range of topics such as access to care, availability of information and training, quality of care, dental treatment and cost. A recurrent theme relating to the appropriateness of care to individual need arose across topics suggesting a need to match service delivery according to the individual''s needs, wants and expectations rather than the disability type/diagnosis based service which predominates today.

Conclusions

This process produced a list of prioritised goals for dental services for people with disabilities. This creates a foundation for building evidence-based service models for people with disabilities in Ireland.  相似文献   

16.
Ena/VASP proteins are implicated in cytoskeletal reorganization during actin-dependent motility processes. Recruitment to subcellular sites of actin polymerization is mediated by the highly conserved N-terminal EVH1 domain, which interacts with target proteins containing proline-rich motifs. The VASP EVH1 domain specifically binds peptides with the consensus motif FPPPP present in all its binding partners, including the Listerial ActA protein. Previous studies have shown that the Phe and first and final Pro residues are highly conserved and cannot be substituted with any other natural amino acid without significant loss of binding affinity. We have incorporated peptoid building blocks (sarcosine derived, non-natural amino acids) into the peptide SFEFPPPPTEDEL from the Listerial ActA protein and were able to substitute the most highly conserved residues of this motif while maintaining binding to the VASP EVH1 domain with affinities in the range of 45-180 microm. We then used NMR chemical shift perturbations to locate specific domain residues involved in particular interactions. These studies may open up the way for designing selective modulators of VASP function for biological studies and for the development of novel therapeutics for diseases involving pathologically altered cell adhesion or cell motility.  相似文献   

17.
Antenatal glucocorticoids are used to promote the maturation of fetuses at risk for preterm delivery. While perinatal glucocorticoid exposure has clear immediate benefits to cardiorespiratory function, there is emerging evidence of adverse long-term effects. To determine if antenatal betamethasone alters vascular reactivity, we examined isometric contraction of endothelium-intact coronary and mesenteric arteries isolated from twin fetal sheep at 121-124 days gestation (term being 145 days). One twin received betamethasone (10 microg/h iv) while the second twin received vehicle (0.9% NaCl) for 48 h immediately before the final physiological measurements and tissue harvesting. Fetuses that received betamethasone had higher mean arterial blood pressures than the saline-treated twin controls (53 +/- 1 vs. 48 +/- 1 mmHg, P < 0.05). Coronary vessels from betamethasone-treated fetuses exhibited enhanced peak responses to ANG II (72 +/- 17 vs. 23 +/- 6% of the maximal response to 120 mM KCl, P < 0.05). There was no significant difference in response of the coronary arteries to other vasoactive compounds [KCl, U-46619, sodium nitroprusside, 8-bromo-cGMP (8-BrcGMP), isoproterenol, and forskolin]. Contractile responses to ANG II were similar in betamethasone and control mesenteric arteries (48 +/- 17 vs. 36 +/- 12% of the maximal response to 10-6 M U-46619). Western blot analysis revealed AT1 receptor protein expression was increased by betamethasone in coronary but not in mesenteric arteries. These findings demonstrate that antenatal betamethasone exposure enhances coronary but not mesenteric artery vasoconstriction to ANG II by selectively upregulating coronary artery AT1 receptor protein expression.  相似文献   

18.
To update evidence‐based best practice guidelines for obtaining informed consent from weight loss surgery (WLS) patients, with an emphasis on appropriate content and communications approaches that might enhance patient understanding of the information, we performed a systematic search of English‐language literature published between April 2004 and May 2007 in MEDLINE and the Cochrane database. Keywords included WLS and informed consent, comprehension, health literacy, and patient education; and WLS and outcomes, risk, patient safety management, and effectiveness. Recommendations are based on the most current literature and the consensus of the expert panel; they were graded according to systems used in established evidence‐based models. We identified over 120 titles, 38 of which were reviewed in detail. Evidence suggests that WLS outcomes, including long‐term rates of relapse, vary by procedure. For some weight loss surgeries, long‐term outcomes may not be known. Risks also vary by patient and provider characteristics. Informed consent should incorporate realistic projections of the short‐ and long‐term risks, benefits, and consequences of surgery, as well as alternatives to WLS. For consent to be informed, the education process should continue until the patient demonstrates comprehension of all relevant material and concepts. Confirmation of comprehension can protect patients engaged in the process of consent for WLS. Future research should focus on the outcomes and consequences of WLS, and different approaches that facilitate patient understanding of, and decision making about, WLS.  相似文献   

19.
Protein phosphatase 4 (PP4) is an evolutionarily conserved and essential Ser/Thr phosphatase that regulates cell division, development and DNA repair in eukaryotes. The major form of PP4, present from yeast to human, is the PP4c-R2-R3 heterotrimeric complex. The R3 subunit is responsible for substrate-recognition via its EVH1 domain. In typical EVH1 domains, conserved phenylalanine, tyrosine and tryptophan residues form the specific recognition site for their target''s proline-rich sequences. Here, we identify novel binding partners of the EVH1 domain of the Drosophila R3 subunit, Falafel, and demonstrate that instead of binding to proline-rich sequences this EVH1 variant specifically recognizes atypical ligands, namely the FxxP and MxPP short linear consensus motifs. This interaction is dependent on an exclusively conserved leucine that replaces the phenylalanine invariant of all canonical EVH1 domains. We propose that the EVH1 domain of PP4 represents a new class of the EVH1 family that can accommodate low proline content sequences, such as the FxxP motif. Finally, our data implicate the conserved Smk-1 domain of Falafel in target-binding. These findings greatly enhance our understanding of the substrate-recognition mechanisms and function of PP4.  相似文献   

20.
PURPOSE OF REVIEW: To summarize the evidence from recent clinical trials and metaanalyses on the efficacy of statin therapy to reduce death, myocardial infarction and stroke, and to review the effects of statins in patients with low LDL cholesterol, diabetes, end-stage renal disease, and acute coronary syndrome. RECENT FINDINGS: In large metaanalyses of randomized controlled trials relative risk reductions from statins compared with placebo for patients with manifest or with risk factors for coronary artery disease were 13% for overall mortality, 26% for fatal and nonfatal myocardial infarction, and 18% for fatal and nonfatal stroke. Evidence from large trials suggests that patients with type II diabetes compared with patients without diabetes have similar risk reductions from statins for cardiovascular events, but this benefit is not seen in patients with diabetes and end-stage renal disease. In patients with acute coronary syndrome, early treatment with high-dose atorvastatin reduces cardiovascular morbidity after the first 4 months following the event, but the impact on mortality endpoints remains less clear. Results from recent trials in patients with stable coronary artery disease or type II diabetes suggest that statins provide benefit at considerable low LDL cholesterol levels. Therefore, target values for LDL cholesterol of less than 1.8 mmol/l (<70 mg/dl) should be considered for all patients with coronary artery disease or equivalent coronary risk. SUMMARY: For patients at high risk of coronary artery disease there is growing evidence for the concept of 'the lower, the better' regarding LDL cholesterol levels. Ongoing trials are further investigating the safety of lower target values in patients at various risk of coronary artery disease.  相似文献   

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