Experimental Studies of Immunologically Mediated Enteropathy

We have attempted to investigate the relative roles of specific cytotoxic T lymphocytes (CTL) and allospecific suppressor T cells (Ts) in the systemic and intestinal manifestations of acute graft-versus-host reaction (GvHR) in mice. Treatment of adult (C57B1/10 x DBA/2)F1 (BDF1) mice with the suppressor cell-specific toxin 2'-deoxyguanosine (dGuo) inhibited the weight loss and mortality which normally occur after induction of GvHR and C57Bl donor cells. dGuo also delayed the development of a destructive enteropathy as typified by jejunal villus atrophy. Paradoxically, dGuo completely prevented villus atrophy during an acute GvHR in neonatal (CBA x BALB/c)F1 hosts, despite having only a slight ability to inhibit the systemic disease. In both models, dGuo had no effect on the generation of splenomegaly or anti-host CTL, and dGuo-treated mice with GvHR actually had increased proliferative alterations in the intestine, as assessed by crypt hyperplasia. In parallel, dGuo prevented the loss of NK cells which normally occurs in acute GvHR. Thus dGuo inhibits many of the destructive features of systemic and intestinal GvHR without affecting the development of CTL. We conclude that a dGuo-sensitive mechanism causes the transition from a proliferative to a destructive GvHR.     

Nutrition Delivery Affects Outcomes in Pediatric Acute Respiratory Distress Syndrome

Background: Malnutrition is prevalent in critically ill children. We aim to describe nutrition received by children with acute respiratory distress syndrome (ARDS) and to determine whether provision of adequate nutrition is associated with improved clinical outcomes. Materials and Methods: We studied characteristics and outcomes of 2 groups of patients: (1) those who received adequate calories (defined as ≥80% of predicted resting energy expenditure) and (2) those who received adequate protein (defined as ≥1.5g/kg/d of protein). Outcomes of interest were mortality, ventilator‐free days (VFDs), intensive care unit (ICU)–free days, multiorgan dysfunction, and need for extracorporeal membrane oxygenation. Categorical variables were analyzed using the Fisher exact test, and continuous variables were analyzed using the Mann‐Whitney U test. Univariate and multivariate logistic regression models were used to identify associated risk factors related to these outcomes of interest. Results: In total, 107 patients with ARDS were identified. There was a reduction in ICU mortality in patients who received adequate calories (34.6% vs 60.5%, P = .025) and adequate protein (14.3% vs 60.2%, P = .002) compared with those that did not. Patients with adequate protein intake also had more VFDs (median [interquartile range], 12 [3.0–19.0] vs 0 [0.0–14.8] days; P = .005). After adjusting for severity of illness, adequate protein remained significantly associated with decreased mortality (adjusted odds ratio [95% confidence interval], 0.09 [0.01–0.94]; P = .044). Conclusion: Our study demonstrated that adequate nutrition delivery in children with ARDS was associated with improved clinical outcomes. Protein delivery may have potentially more impact than overall caloric delivery.     

Epicutaneous sensitization to food allergens in atopic dermatitis: What do we know?

Atopic dermatitis (AD) is a chronic inflammatory skin disease mainly affecting children, which has no definitive curative therapy apart from natural outgrowing. AD is persistent in 30%-40% of children. Epithelial barrier dysfunction in AD is a significant risk factor for the development of epicutaneous food sensitization, food allergy, and other allergic disorders. There is evidence that prophylactic emollient applications from birth may be useful for primary prevention of AD, but biomarkers are needed to guide cost-effective targeted therapy for high-risk individuals. In established early-onset AD, secondary preventive strategies are needed to attenuate progression to other allergic disorders such as food allergy, asthma, and allergic rhinitis (the atopic march). This review aims to describe the mechanisms underpinning the development of epicutaneous sensitization to food allergens and progression to clinical food allergy; summarize current evidence for interventions to halt the progression from AD to food sensitization and clinical food allergy; and highlight unmet needs and directions for future research.     

《轻度认知损害临床研究指导原则(草案)》编制说明

本文评述了近几年来有关轻度认知损害（mildcognitiveimpairment,MCI）的诊断、分型、纳入标准和排除标准、评价量表、疗效性指标设计以及证候诊断量表等方面的研究文献,为首都医学发展基金（CapitalFoundationofMedicalDevelopments,CFMD）MCI联合攻关组编制的《轻度认知损害临床研究指导原则（草案）》提供证据支持。文章指出欧洲MCI诊断标准及其诊断程序更加符合MCI综合征的异质性特征。MCI患者诊断标准有赖于各种分级筛选量表得分,临床痴呆分级量表（ClinicalDementiaRating,CDR）、整体衰退量表（G10balDeteriorationScale,GDS）、AD评价量表认知（Alzheimer＇sDiseaseAssessmentScale—cognitivesubscale,ADAS—cog）和工具性日常生活活动（InstrumentalActivitiesofDailyLiving,IADL）在确定MCI患者中非常有用,但不能代替MCI诊断标准。强调MCI患者的认知损害对日常生活没有较大影响,但在复杂的日常生活活动方面,患者可能会有非常轻微的损害。经过作者前期临床研究验证,在MCI病例筛选中值得推崇的神经心理学量表主要是简易精神状态检查（MiniMentalStateExamination,MMSE）、延迟故事回忆（DelayedStoryRecall,DSR）、画钟测验（ClockDrawTest,CDT）和言语分类流畅性测验生物学检测和海马体积或内侧颞叶体积缩小等对MCI诊断的贡献也给予了简要说明。     

Mild cognitive impairment (MCI) in medical practice: a critical review of the concept and new diagnostic procedure. Report of the MCI Working Group of the European Consortium on Alzheimer's Disease

Mild cognitive impairment (MCI) was proposed as a nosological entity referring to elderly people with mild cognitive deficit but no dementia. MCI is a heterogeneous clinical entity with multiple sources of heterogeneity. The concept of MCI was reviewed and a diagnostic procedure with three different stages was proposed by the European Consortium on Alzheimer's Disease Working Group on MCI. Firstly, MCI should correspond to cognitive complaints coming from the patients or their families; the reporting of a relative decline in cognitive functioning during the past year by a patient or informant; cognitive disorders as evidenced by clinical evaluation; absence of major repercussions on daily life; and absence of dementia. These criteria, similar to those defined during an international workshop in Stockholm, make it possible to identify an MCI syndrome, which is the first stage of the diagnostic procedure. Secondly, subtypes of MCI had to be recognised. Finally, the aetiopathogenic subtype could be identified. Identifying patients at a high risk for progression to dementia and establishing more specific and adapted therapeutic strategies at an early stage, together with more structured overall management, is made possible by the diagnostic procedure proposed.     

Participation in clinical studies among patients infected with HIV-1 in a single treatment centre over 12 years

Objective To examine a complete population of clinic attenders in order to compare the demographics of patients who participated in a clinical study with those who had not. These were subdivided into trials of antivirals, trials for drugs used in opportunistic infections or symptomatic HIV and epidemiological studies. The setting was an established London teaching hospital. All patients diagnosed HIV-positive and attending between July 1983 and 1 January 1999 with one measured CD4 count and at least one follow-up visit were included. Methods The demographics of those participating in a clinical study were compared to those not enrolling using χ² tests and Wilcoxon tests. Cox models were used to determine factors related to participation in clinical studies. Results Data from 2703 patients representing 5342.7 person-years' follow-up were assessed. Median time of follow-up was 23.6 months. Six hundred and eighty-seven (33%) patients had ever participated in a clinical study. After adjustment for demographic factors in multivariate analysis using Cox models, homosexuals were more likely to participate compared with heterosexuals or injecting drug users (IDU) (P = 0.0035 and P = 0.0001, respectively). Women were more likely to enter a study (P = 0.02) and there was no difference between Caucasians and black Africans (P = 0.35). Between the three types of studies few differences were seen. Conclusion High rates of participation in clinical trials and epidemiological studies were seen in this cohort. In keeping with other studies, homosexual men were well represented but IDU were under-represented. However, women and black African patients showed good uptake of all clinical studies. Hence in this population there is some success in targeting representative groups to participate in clinical studies, but more effort needs to be made with IDU.