Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study

OBJECTIVE: Intravenous immunoglobulin as an adjunctive treatment in sepsis was regarded as promising by a Cochrane meta-analysis of smaller trials. In this phase III multicenter trial, we assessed whether intravenous immunoglobulin G (ivIgG) reduced 28-day mortality and improved morbidity in patients with score-defined severe sepsis. DESIGN: Randomized, double-blind, placebo-controlled, multicenter trial. SETTING: Twenty-three medical and surgical intensive care units in university centers and large teaching hospitals. PATIENTS: Patients (n = 653) with score-defined sepsis (sepsis score 12-27) and score-defined sepsis-induced severity of disease (Acute Physiology and Chronic Health Evaluation II score 20-35). INTERVENTIONS: Patients were assigned to receive either placebo or ivIgG (day 0, 0.6 g/kg body weight; day 1, 0.3 g/kg body weight). MEASUREMENTS AND MAIN RESULTS: The prospectively defined primary end point was death from any cause after 28 days. Prospectively defined secondary end points were 7-day all-cause mortality, short-term change in morbidity, and pulmonary function at day 4. Six hundred fifty-three patients from 23 active centers formed the intention-to-treat group, 624 patients the per-protocol group (placebo group, n = 303; ivIgG group, n = 321). The 28-day mortality rate was 37.3% in the placebo group and 39.3% in the ivIgG group and thus not significantly different (p = .6695). Seven-day mortality was not reduced, and 4-day pulmonary function was not improved. Drug-related adverse events were rare in both groups. Exploratory findings revealed a 3-day shortening of mechanical ventilation in the surviving patients and no effect of ivIgG on plasma levels of interleukin-6 and tumor necrosis factor receptors I and II. CONCLUSIONS: In patients with score-defined severe sepsis, ivIgG with a total dose of 0.9 g/kg body weight does not reduce mortality.     

Comparison of in vitro proliferative capacity of human periodontal ligament cells in juvenile and aged donors

OBJECTIVE: The aim of this study is to compare the in vitro proliferative capacity of periodontal ligament (PDL) cells from aged and juvenile donors.
MATERIALS AND METHODS: Flow-cytometric analysis of the cell cycle was used to compare the length of each cell cycle, and the ratio of the cells progressing through the cycles between four PDL cells from juvenile donors and four cells from aged donors. Then, replicative capacity of the PDL cells from three juvenile and three aged donors was compared by serial cultureS. Finally, expression of c-fos was compared between cells proliferating and cells which had reached senescent.
RESULTS: Flow-cytometric analysis of the cell cycle had revealed that although there were no differences in the length of each phase of the cell cycle, significant differences were found in the ratio of the cells entering from Gap 1 to DNA synthesis phase of the cell cycle ( P < 0.025).Replicative capacity was much longer in two cells from juvenile donors (about 20 population doublings), while all cells from aged donors showed short dividing abilities (less than eight population doublings), hence entered senescent phases shortly. Additionally, no c-fos was detected in cells which had reached senescence upon stimulation with serum.
CONCLUSIONS: It is generally believed that aged humans have an impaired wound healing ability. We believe that more fibrotic PDL tissues seen in aged humans might be the reason for this, and suggest that this phenomena might be due to the progressive accumulation of senescent cell populations.     

Prevalence and clinical relevance of the morphological substrate of ventricular arrhythmias in patients without known cardiac conditions detected by cardiovascular MR

Objective

Cardiac MR (CMR) identifies the substrate of ventricular arrhythmia (VA) in cardiomyopathies and coronary heart disease. However, little is known about the value of CMR in patients with VA without previously known cardiac disorders.

Methods

76 patients with VA (Lown ≥2) without known cardiac disease after regular diagnostic work-up were studied with CMR, and findings were correlated with electrocardiogram (ECG) and electrophysiological stimulation (EPS). Structural abnormalities matching the VA origin as defined by ECG and/or EPS, or a CMR-detected cardiac condition known to cause arrhythmia were defined as VA substrate. CMR findings were defined as clinically relevant, if resulting in a new diagnosis, change of treatment or additional diagnostic procedure.

Results

44/76 patients demonstrated pathological CMR findings. In 24/76 patients, the pathology was detected by CMR and not by echocardiography. CMR-based diagnoses of cardiac disease were established in 20/76 patients, and all were morphological substrates for VA. In seven patients, the location of the CMR finding (scar) directly matched the VA origin. CMR findings resulted in a change of treatment in 21 patients and/or additional diagnostics in 8 patients.

Conclusion

Undetected cardiac conditions are frequent causes of VA. This is the first study demonstrating the value of CMR for detection of morphological substrate and/or underlying cardiac disorders in VA patients without known cardiac disease.

Advances in knowledge

The high incidence of clinically relevant CMR findings which were not detected during initial diagnostic work-up strongly supports the use of CMR to screen VA patients for underlying heart disease.Although the value of cardiac MR (CMR) for the diagnosis of cardiac diseases such as myocarditis is undisputed, CMR is also predictive of patients at high risk for ventricular arrhythmias (VAs) with conditions such as hypertrophic cardiomyopathy (HCM) and coronary heart disease (CHD).^1–3 Recent studies have demonstrated the ability of CMR to identify the anatomical correlate of VA in those patients. This anatomical correlate has been characterized by CMR as a structural abnormality (e.g. fibrosis or peri-infarct region), which may go undetected using other non-invasive imaging modalities.^4,5 A number of studies have been undertaken, or are ongoing, to further elucidate the added value of CMR in patients with known cardiac conditions, to improve risk stratification for VA and to optimize therapy.^1,6–8 However, little is known to date regarding the added value of CMR for detection of an arrhythmogenic substrate or underlying cardiac condition in patients who present with VAs without known cardiac disease.Thus, the purpose of this study was to investigate the added value of CMR in patients with VAs for detection of underlying heart disease and an arrhythmogenic morphological substrate, and also to investigate the clinical relevance of CMR in those patients with positive findings.     

Home-based subcutaneous immunoglobulin G replacement therapy under real-life conditions in children and adults with antibody deficiency

Background

Subcutaneous immunoglobulin (SCIG) therapy is an alternative to intravenous immunoglobulin (IVIG) therapy.

Methods

We evaluated the efficacy and safety of the SCIG Vivaglobin^® (formerly known as Beriglobin^® SC) under real-life conditions in a post-marketing observational study in 82 patients with primary or secondary antibody deficiencies. Health-related quality of life (HRQoL) was evaluated in a subset of 30 patients previously treated with IVIG (including 11 children < 14 years) using the Short Form 36 (SF-36) for patients ≥ 14 years of age (adults) and the Child Health Questionnaire - Parental Form 50 (CHQ-PF50) for children < 14 years of age. Treatment preferences were assessed in adults.

Results

The mean serum immunoglobulin G (IgG) trough level during SCIG treatment (7.5 g/L) was higher than during previous IVIG treatment (6.6 g/L; p < 0.01). The investigators assessed the efficacy of SCIG therapy as "excellent" in 89% of patients. No systemic adverse drug reactions were observed. Improvements by ≥ 5 points were observed in 5 of 8 SF36 subscales and in 6 of 12 CHQ-PF50 subscales. Statistically significant improvements (p ≤ 0.05) were observed for the SF-36 subscales of bodily pain, general health perceptions, and vitality (adults), and for the CHQ-PF50 subscales of general health perceptions, parental impact - time, parental impact - emotional, and family activities (children). Patients preferred SCIG over IVIG therapy (92%) and home therapy over therapy at the clinic/physician (83%).

Conclusion

This study confirms that therapy with Vivaglobin^® at home is effective, safe, well tolerated, and improves quality of life in patients with antibody deficiency.     

Effectiveness of GPs in accident and emergency departments

Background

Many self-attending patients make inappropriate use of accident and emergency departments.

Aim

To determine whether a new care method consisting of the involvement of a GP during the day with the staff of the accident and emergency department of an academic city hospital and application of the Nederlands Triage Systeem by a practice nurse is more effective than usual care.

Design

Before and after intervention design.

Setting

Accident and emergency department in the VU University Medical Center in Amsterdam.

Method

Participants were patients (n = 1527) attending the accident and emergency department without a referral, on weekdays from 10.00–17.00 hours, from 1 November 2006 to 30 April 2007. The intervention consisted of a new care method that combined the involvement of a GP in the accident and emergency department and allocation of patients by triage to either the GP or the accident and emergency department physician. Main outcome measures were patient satisfaction, number and type of additional examinations, quality of diagnosis, process time, and treatment time.

Results

Patient satisfaction with the treatment increased significantly. Compared to the usual care method, this new care method resulted in a 13% decrease in additional examinations. The percentage of incorrect diagnoses (1 %), as a measure of quality of care, was similar with the two methods. The mean process time decreased from 93 to 69 minutes (P<0.001). The mean treatment time decreased from 60 to 35 minutes (P<0.001).

Conclusion

The new care method resulted in greater patient satisfaction and maintained the quality of care, with fewer additional examinations. It reduced both the process time and the treatment time.     

表皮生长因子含量表达与骨折愈合的关系

目的:观察骨折后表皮生长因子含量表达的变化,分析表皮生长因子浓度变化与骨折愈合之间的关系。方法:实验于2003-10在山东大学齐鲁医院动物实验室完成。选用成年雄性家兔30只,以随机数字表法分成骨折固定组、骨折组、创伤组,各10只。骨折固定组制作左第一跖骨骨折模型,然后用管型石膏将左下肢固定;骨折组造模后不给予任何固定;创伤组仅用止血钳在家兔左大腿的中部钳夹1次。在造模前、造模后24,48,96h,2,4周,分别采静脉血,采用放射免疫分析法对家兔血清表皮生长因子浓度进行测定,进行组间、组内对照,观察骨折对家兔血清表皮生长因子浓度变化的影响。并通过X射线检测骨折愈合的情况,对家兔血清表皮生长因子浓度升高是否影响骨折愈合的速度进行评估。结果:所有30只实验动物均纳入实验动物数量分析,无脱失。①骨折固定组与骨折组骨折后24h血清表皮生长因子浓度开始升高[(45.98±3.36),(43.64±3.11)μg/L];到48h达到高峰[(51.02±3.11),(49.31±2.94)μg/L];96h已开始下降[(47.18±5.08),(45.41±4.73)μg/L];2～4周可维持较正常稍高水平[(43.50±3.78),(39.15±4.20)μg/L];4周时接近正常值[(42.26±3.14),(37.64±3.93)μg/L]。②骨折后24,48,96h骨折固定组、骨折组与创伤组家兔血清表皮生长因子浓度差异均有显著性意义(P<0.05);此间骨折固定组和骨折组差异无显著性意义(P>0.05)。③X射线检查结果,4周时骨折固定组愈合5例;骨折组愈合2例。6周时骨折固定组愈合8例;骨折组愈合5例。结论:骨折可导致家兔血清表皮生长因子浓度的升高,高表皮生长因子浓度可能有利于骨折的愈合。