Paediatric nodal marginal zone B‐cell lymphadenopathy of the neck: a Haemophilus influenzae‐driven immune disorder?

Many hyperplasias and lymphomas of marginal zone B‐cells are associated with infection. We identified six children and one adolescent with cervical lymphadenopathy showing prominent polyclonal nodal marginal zone hyperplasia (pNMZH) and four adolescents with monoclonal paediatric nodal marginal zone lymphoma (pNMZL). The clonality status was assessed using BIOMED‐2‐IG PCR analysis. Haemophilus influenzae was identified in all six cases of pNMZH that could be tested by direct culture (N = 3) or a very sensitive PCR for the H. influenzae gyrase gene in frozen materials (N = 5). H. influenzae was not detected in three pNMZLs and 28 non‐specific reactive cervical lymph nodes of age‐matched controls, except for a single control node that was obtained during oropharyngeal surgery for a cleft palate showing very low copy numbers of H. influenzae. pNMZH patients were younger than pNMZL patients (median age 12 versus 21 years). pNMZH showed a prominent nodular appearance with variable fibrosis without acute inflammation. Within the nodules, the expanded germinal centres and variably sized marginal zones were colonized by activated B‐cells with weak expression of IgD and lack of CD10 and/or BCL6 expression. Some areas showed skewed light chain expression in plasma cells (4/5 cases lambda). In four cases tested, this was confirmed by flow cytometry for surface Ig (3/4 cases lambda). In contrast, pNMZL showed more extensive expansion of marginal zones by centrocytoid cells and often expression of BCL2 protein. Several H. influenzae strains are known to interact with the constant part of IgD on human B‐cells, leading to their polyclonal proliferation and activation. We speculate that in vivo stimulation of IgD+ marginal zone B‐cells by this bacterium may be implicated in this particular lymphadenopathy that should be distinguished from monoclonal pNMZL. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

PATENT FORAMEN OVALE IN ELDERLY STROKE PATIENTS

The aim of this study was to determine the incidence of echocardiographically detectable patent foramen ovale (PFO) in elderly patients who have strokes from cerebral infarction, as well as to assess the association between PFOs and other risk factors for stroke disease. Forty-three patients aged ≥65 years admitted consecutively with cerebral infarction shown on computerised tomography of the brain were assessed using transoesophageal echocardiography. A PFO was present in 8 (19%) of the 43 patients. Four patients (50%) in this PFO group had stroke risk factors. Two were in atrial fibrillation and, of the six patients in sinus rhythm, a risk factor was present in two, both of whom had diabetes mellitus. A PFO was not detected in 35 patients. Twenty-nine (83%) of the patients in this group had risk factors, with 18 having two or more. Seven patients were in atrial fibrillation. Of the 28 patients in sinus rhythm, risk factors were present in 22 (78%).     

Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion

Myocardial ischemic disease is the major cause of death worldwide. After myocardial infarction, reperfusion of infracted heart has been an important objective of strategies to improve outcomes. However, cardiac ischemia/reperfusion (I/R) is characterized by inflammation, arrhythmias, cardiomyocyte damage, and, at the cellular level, disturbance in Ca(2+) and redox homeostasis. In this study, we sought to determine how acute inflammatory response contributes to reperfusion injury and Ca(2+) homeostasis disturbance after acute ischemia. Using a rat model of I/R, we show that circulating levels of TNF-α and cardiac caspase-8 activity were increased within 6 h of reperfusion, leading to myocardial nitric oxide and mitochondrial ROS production. At 1 and 15 d after reperfusion, caspase-8 activation resulted in S-nitrosylation of the RyR2 and depletion of calstabin2 from the RyR2 complex, resulting in diastolic sarcoplasmic reticulum (SR) Ca(2+) leak. Pharmacological inhibition of caspase-8 before reperfusion with Q-LETD-OPh or prevention of calstabin2 depletion from the RyR2 complex with the Ca(2+) channel stabilizer S107 ("rycal") inhibited the SR Ca(2+) leak, reduced ventricular arrhythmias, infarct size, and left ventricular remodeling after 15 d of reperfusion. TNF-α-induced caspase-8 activation leads to leaky RyR2 channels that contribute to myocardial remodeling after I/R. Thus, early prevention of SR Ca(2+) leak trough normalization of RyR2 function is cardioprotective.     

Validation of a model to predict all-cause in-hospital mortality in vascular surgical patients

Objective

To develop and validate a pre- and postoperative model of all-cause in-hospital mortality in South African vascular surgical patients.

Methods

We carried out a retrospective cohort study. A multivariate analysis using binary logistic regression was conducted on a derivation cohort using clinical, physiological and surgical data. Interaction and colinearity between covariates were investigated. The models were validated using the Homer-Lemeshow goodness-of-fit test.

Results

Independent predictors of in-hospital mortality in the pre-operative model were: (1) age (per one-year increase) [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.0–1.06), (2) creatinine > 180 μmol.l^-1 (OR 6.43, 95% CI: 3.482–11.86), (3) chronic beta-blocker therapy (OR 2.48, 95% CI: 1.38–4.48), and (4) absence of chronic statin therapy (OR 2.81, 95% CI: 1.15–6.83). Independent predictors of mortality in the postoperative model were: (1) age (per oneyear increase) (OR 1.05, 95% CI: 1.02–1.09), (2) creatinine > 180 μmol.l^-1 (OR 5.08, 95% CI: 2.50–10.31), (3) surgery out of hours without statin therapy (OR 8.27, 95% CI: 3.36–20.38), (4) mean daily postoperative heart rate (HR) (OR 1.02, 95% CI: 1.0–1.04), (5) mean daily postoperative HR in the presence of a mean daily systolic blood pressure of less than 100 beats per minute or above 179 mmHg (OR 1.02, 95% CI: 1.01–1.03) and (6) mean daily postoperative HR associated with withdrawal of chronic beta-blockade (OR 1.02, 95% CI: 1.01–1.03). Both models were validated.

Conclusion

The pre-operative model may predict the risk of in-hospital mortality associated with vascular surgery. The postoperative model may identify patients whose risk increases as a result of surgical or physiological factors.     

多培沙明,非诺多泮和丙卡特罗对心肌缺血时电生理变化影响的比较

新型多巴胺受体激动剂多培沙明(DPX)能显著减轻缺氧和缺血豚鼠心室乳头肌静息电位,动作电位幅度和O相除极速度的降低程度及动作电位时程的缩短程度,其减轻作用明显大于非诺多泮(FODA)和丙卡特罗(PCTR)。DPX能使缺氧时缩短的有效不应期(ERP)延长,而使缺血时延长的ERP缩短,其程度明显大于FODA与PCTR。提示DPX抗缺血性心律失常的作用优于其他类型的多巴胺激动剂。     

ADA与EASD对2型糖尿病高血糖处理：治疗启动与评定的新共识方案

在不到一年时间由同一批专家代表ADA和EASD先后起草和发布了两次关于“2型糖尿病高血糖处理的共识声明”同时发表在2008年1月和12月的《DiabetesCare》和《Diabetologia》上。第一次共识声明内容主要围绕TZDs药物的安全性,本刊作了摘译转载（参阅《中国糖尿病杂志22008年第7期）。第二次修订的共识声明,关注点为降糖药的新分级,论据及观点比较清晰,故仍摘译供读者参考。