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

methods Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. results A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients.

/pdf/radiotherapy-plus-concomitant-and-adjuvant-temozolomide-for-421wvfhcfx.pdf

Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma

Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to assess for the presence of selective reporting against completed reviews, and, when made publicly available, reduce duplication of efforts and potentially prompt collaboration. Evidence documenting the existence of selective reporting and excessive duplication of reviews on the same or similar topics is accumulating and many calls have been made in support of the documentation and public availability of review protocols. Several efforts have emerged in recent years to rectify these problems, including development of an international register for prospective reviews (PROSPERO) and launch of the first open access journal dedicated to the exclusive publication of systematic review products, including protocols (BioMed Central's Systematic Reviews). Furthering these efforts and building on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, an international group of experts has created a guideline to improve the transparency, accuracy, completeness, and frequency of documented systematic review and meta-analysis protocols--PRISMA-P (for protocols) 2015. The PRISMA-P checklist contains 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol.This PRISMA-P 2015 Explanation and Elaboration paper provides readers with a full understanding of and evidence about the necessity of each item as well as a model example from an existing published protocol. This paper should be read together with the PRISMA-P 2015 statement. Systematic review authors and assessors are strongly encouraged to make use of PRISMA-P when drafting and appraising review protocols.

/pdf/preferred-reporting-items-for-systematic-review-and-meta-mgb1uy0yle.pdf

Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation.

ACE
: angiotensin-converting enzyme
ACS
: acute coronary syndrome
ADP
: adenosine diphosphate
AF
: atrial fibrillation
AMI
: acute myocardial infarction
AV
: atrioventricular
AIDA-4
: Abciximab Intracoronary vs. intravenously Drug Application
APACHE II
: Acute Physiology Aand Chronic

/pdf/esc-guidelines-for-the-management-of-acute-myocardial-vy5rt9aiqe.pdf

ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting With ST-Segment Elevation

Jeffrey L. Anderson, MD, FACC, FAHA, Chair 

Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect 

Nancy M. Albert, PhD, RN, FAHA

Biykem Bozkurt, MD, PhD, FACC, FAHA

Ralph G. Brindis, MD, MPH, MACC

Mark A. Creager, MD, FACC, FAHA[#][1]

Lesley H. Curtis, PhD, FAHA

David DeMets, PhD[#][1]

Robert A

/pdf/2014-aha-acc-hrs-guideline-for-the-management-of-patients-1v8ficsqox.pdf

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society

The language and conceptual framework of “research reproducibility” are nonstandard and unsettled across the sciences. In this Perspective, we review an array of explicit and implicit definitions of reproducibility and related terminology, and discuss how to avoid potential misunderstandings when these terms are used as a surrogate for “truth.”

What does research reproducibility mean

The second article on evidence-based statistics explores the inductive Bayesian approach to measuring evidence and combining information and addresses the epistemologic uncertainties that affect al...

/pdf/toward-evidence-based-medical-statistics-2-the-bayes-factor-1xw7ah64dc.pdf

Toward Evidence-Based Medical Statistics. 2: The Bayes Factor

ContextProgressive heart failure is the most common mechanism of death among
patients with advanced heart failure. Cardiac resynchronization, a pacemaker-based
therapy for heart failure, enhances cardiac performance and quality of life,
but its effect on mortality is uncertain.ObjectiveTo determine whether cardiac resynchronization reduces mortality from
progressive heart failure.Data SourcesMEDLINE (1966-2002), EMBASE (1980-2002), the Cochrane Controlled Trials
Register (Second Quarter, 2002), The National Institutes of Health ClinicalTrials.gov
database, the US Food and Drug Administration Web site, and reports presented
at scientific meetings (1994-2002). Search terms included pacemaker, pacing, heart
failure, dual-site, multisite, biventricular, resynchronization, and left ventricular preexcitation.Study SelectionEligible studies were randomized controlled trials of cardiac resynchronization
for the treatment of chronic symptomatic left ventricular dysfunction. Eligible
studies reported death, hospitalization for heart failure, or ventricular
arrhythmia as outcomes. Of the 6883 potentially relevant reports initially
identified, 11 reports of 4 randomized trials with 1634 total patients were
included in the meta-analysis.Data ExtractionTrial reports were reviewed independently by 2 investigators in an unblinded
standardized manner.Data SynthesisFollow-up in the included trials ranged from 3 to 6 months. Pooled data
from the 4 selected studies showed that cardiac resynchronization reduced
death from progressive heart failure by 51% relative to controls (odds ratio
[OR], 0.49; 95% confidence interval [CI], 0.25-0.93). Progressive heart failure
mortality was 1.7% for cardiac resynchronization patients and 3.5% for controls.
Cardiac resynchronization also reduced heart failure hospitalization by 29%
(OR, 0.71; 95% CI, 0.53-0.96) and showed a trend toward reducing all-cause
mortality (OR, 0.77; 95% CI, 0.51-1.18). Cardiac resynchronization was not
associated with a statistically significant effect on non–heart failure
mortality (OR, 1.15; 95% CI, 0.65-2.02). Among patients with implantable cardioverter
defibrillators, cardiac resynchronization had no clear impact on ventricular
tachycardia or ventricular fibrillation (OR, 0.92; 95% CI, 0.67-1.27).ConclusionsCardiac resynchronization reduces mortality from progressive heart failure
in patients with symptomatic left ventricular dysfunction. This finding suggests
that cardiac resynchronization may have a substantial impact on the most common
mechanism of death among patients with advanced heart failure. Cardiac resynchronization
also reduces heart failure hospitalization and shows a trend toward reducing
all-cause mortality.

Cardiac resynchronization and death from progressive heart failure: a meta-analysis of randomized controlled trials.

Background Surgical oncologists rely heavily on the histopathological assessment of surgical margins to ensure total excision of the tumor in patients with head and neck cancer. However, current techniques may not detect small numbers of cancer cells at the margins of resection or in cervical lymph nodes. Methods We used molecular techniques to determine whether clonal populations of infiltrating tumor cells harboring mutations of the p53 gene could be detected in histopathologically negative surgical margins and cervical lymph nodes of patients with squamous-cell carcinoma of the head and neck. Results We identified 25 patients with primary squamous-cell carcinoma of the head and neck containing a p53 mutation who appeared to have had complete tumor resection on the basis of a negative histopathological assessment. In 13 of these 25 patients, molecular analysis was positive for a p53 mutation in at least one tumor margin. In 5 of 13 patients with positive margins by this method (38 percent), the carcinom...

https://www.nejm.org/doi/pdf/10.1056/NEJM199502163320704

Molecular Assessment of Histopathological Staging in Squamous-Cell Carcinoma of the Head and Neck

During tumorigenesis, positive selection is exerted upon those tumor cells that alter rate-limiting regulatory pathways. A corollary of this principle is that mutation of one gene abrogates the need for alteration of another gene in the same pathway and also that the coexistence in a single tumor of mutations in different genes implies their involvement in distinct tumor-suppressive pathways. We studied 42 pancreatic adenocarcinomas for genetic alterations in the K-ras oncogene and the p16, p53, and DPC4 tumor suppressor genes. All of them had the K-ras gene mutated. Thirty-eight % of the tumors had four altered genes, another 38% had three altered genes, 15% had two altered genes, and 8% of the tumors had one altered gene. Interestingly, we noted a high concordance of DPC4 and p16 inactivations (P = 0.007), suggesting that the genetic inactivation of p16 increases the selective advantage of subsequent mutation in DPC4. No statistically significant association was identified between the alteration of these cancer genes and pathological or clinical parameters. This type of multigenic analysis in human tumors may serve to substantiate experimental tumor models and thus increase our understanding of the truly physiologically relevant tumor-suppressive pathways that are abrogated during human tumorigenesis.

https://cancerres.aacrjournals.org/content/canres/57/9/1731.full.pdf

Steven N. Goodman

Papers

What does research reproducibility mean

Toward Evidence-Based Medical Statistics. 2: The Bayes Factor

Cardiac resynchronization and death from progressive heart failure: a meta-analysis of randomized controlled trials.

Molecular Assessment of Histopathological Staging in Squamous-Cell Carcinoma of the Head and Neck

Tumor-suppressive Pathways in Pancreatic Carcinoma