抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

https://caltcm.memberclicks.net/assets/documents/acc_aha_chf_2013_guidelines.pdf

2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines

XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.

Severe focal ischemia leads to neuronal death within minutes. Due to the cerebral collateral network, in most instances occlusion of a major intracranial artery causes variable degrees of ischemia and oxygen supply within different parts of the vessel’s territory. The ability of brain tissue to survive under ischemic conditions is time-dependent [4]. Restoring cerebral blood flow by recanalization of the occluded artery may help to decrease the extent of ischemic necrosis. Recently, new thrombus-selective thrombolytic agents such as recombinant tissue plasminogen activator (rt-PA) and single-chain urokinase plasminogen activator (scu-PA) have become available and are being successfully used in the treatment of ischemic heart disease. Encouraged by reports of successful arterial recanalization associated with favorable clinical outcome following intra-arterial infusion of streptokinase or urokinase [2, 3, 8–10], we studied the efficacy and safety of intravenous rt-PA in patients with acute thromboembolic vertebrobasilar and middle cerebral artery stroke. The purpose of this study was to find the dosage of alteplase (rt-PA) which is safe with respect to intracranial hemorrhage and effective with respect to thrombolysis and clinical outcome in preparation for a controlled study.

Intravenous Recombinant Tissue Plasminogen Activator in Acute Stroke

Objective: To develop and externally validate a prediction model for major bleeding in patients with a TIA or ischemic stroke on antiplatelet agents.

Methods: We combined individual patient data from 6 randomized clinical trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial were performed to study the association between predictors and major bleeding. A risk prediction model was derived and validated in the PERFORM trial. Performance was assessed with the c statistic and calibration plots.

Results: Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI] 4.4%–4.9%). Predictors were male sex, smoking, type of antiplatelet agents (aspirin-clopidogrel), outcome on modified Rankin Scale ≥3, prior stroke, high blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes (S2TOP-BLEED). The S2TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60–0.64) and showed good calibration in the development data. Major bleeding risk ranged from 2% in patients aged 45–54 years without additional risk factors to more than 10% in patients aged 75–84 years with multiple risk factors. In external validation, the model had a c statistic of 0.61 (95% CI 0.59–0.63) and slightly underestimated major bleeding risk.

Conclusions: The S2TOP-BLEED score can be used to estimate 3-year major bleeding risk in patients with a TIA or ischemic stroke who use antiplatelet agents, based on readily available characteristics. The discriminatory performance may be improved by identifying stronger predictors of major bleeding.

https://n.neurology.org/content/neurology/89/9/936.full.pdf

Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED

Decompressive surgery has since long been a promising therapeutic approach for patients with acute severe brain injury at risk to develop severe brain edema. The underlying rationale of removing part of the cranium is to create space for the expanding brain to prevent secondary damage to vital brain tissue. However, until recently, randomized controlled trials that demonstrate the efficacy of decompressive surgery or benefit for outcome were missing. This has changed since the results of 3 randomized trials on hemicraniectomy in malignant infarction of the middle cerebral artery have been published in 2007. In this article, the current evidence for decompressive surgery in the treatment of cerebral ischemia, intracranial hemorrhage, traumatic brain injury, inflammatory diseases, or severe metabolic derangements is reviewed. Although there is increasing evidence for the efficacy of decompressive surgery in reducing intracranial pressure and even mortality, a critical point remains the definition of good or acceptable outcome.

Decompressive Surgery for Severe Brain Edema

Susac's syndrome: improvement with combined antiplatelet and calcium antagonist therapy.

Publisher Summary The underlying rationale for the introduction and application of thrombolytic agents is the lysis of an obliterating thrombus and subsequent re-establishment of cerebral blood flow by cerebrovascular recanalization The characterization of potentially reversible versus irreversible loss of function is based on the concept of the ischemic penumbra Neuroradiological intervention with intra-arterial or intravenous thrombolysis to date is the only life-saving therapy that has demonstrated benefit with regard to mortality and outcome, albeit not in a randomized trial Educating the general public to regard stroke as a treatable emergency and training emergency caregivers in the use of thrombolysis can decrease these problems but demands a continuous effort Healthcare institutions should be made aware of the potential in long-term cost savings, once stroke management is optimized and thrombolysis is more widely available Patients and their relatives should be informed about the hazards of thrombolytic therapy and about its potential benefits and thus the risk of not being treated Intra-arterial thrombolysis with or without devices and/or combination therapies such as GP IIb/IIIa inhibitors is under further investigation in the anterior circulation

Werner Hacke

Papers

Intravenous Recombinant Tissue Plasminogen Activator in Acute Stroke

Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED

Decompressive Surgery for Severe Brain Edema

Susac's syndrome: improvement with combined antiplatelet and calcium antagonist therapy.

Chapter 57 Thrombolytic therapy for acute stroke