Mark Niven

Background Vascular diseases are a major cause of morbidity and mortality, particularly in diabetic patients. Stem/progenitor cell treatments with bone marrow‐derived cells show safety and promising outcomes, albeit not without some preprocedural adverse events related to cell collection and mobilization. We describe a novel technology for generating a therapeutic population (BGC101) of enriched endothelial progenitor cells (EPCs) from non‐mobilized blood, using dendritic cells to specifically direct stem/progenitor cell activity in vitro. Methods and results Selected immature plasmacytoid and myeloid dendritic cells from 24 healthy and two diabetic donors were activated with anti‐inflammatory and pro‐angiogenic molecules to induce specific activation signals. Co‐culturing of activated dendritic cells with stem/progenitor cells for 12–66 h generated 83.7 ± 7.4 × 10⁶ BGC101 cells with 97% viability from 250 mL of blood. BGC101, comprising 52.4 ± 2.5% EPCs (expressing Ulex‐lectin, AcLDL uptake, Tie2, vascular endothelial growth factor receptor 1 and 2, and CD31), 16.1 ± 1.9% stem/progenitor cells (expressing CD34 and CD184) and residual B and T helper cells, demonstrated angiogenic and stemness potential and secretion of interleukin‐8, interleukin‐10, vascular endothelial growth factor and osteopontin. When administered to immunodeficient mice with limb ischemia (n = 40), BGC101 yielded a high safety profile and significantly increased blood perfusion, capillary density and leg function after 21 days. Cell tracking and biodistribution showed that engraftment was restricted to the ischemic leg. Conclusions These observations provide preliminary evidence that alternatively activated dendritic cells can promote the generation of EPC‐enriched stem/progenitor cells within a 1‐day culture. The resulting product BGC101 has the potential for treatment of various vascular conditions such as coronary heart disease, stroke and peripheral ischemia. Copyright © 2014 John Wiley & Sons, Ltd.

Urinary catheterization has risks and its use should be limited because it is the main cause of healthcare-associated urinary tract infection. Other risks are the potential for urethral injuries and the possibility that the catheter will be left in permanently. Rates of urinary catheterization in internal medicine departments generally range from 8% to 20%, with higher rates in older adult...

The aim of the study was to determine whether intravenous gamma globulin (IVIG) treatment is effective in patients with West Nile Virus (WNV) neuroinvasive disease. We contacted hospital based infectious disease experts in Israeli hospitals to identify patients with WNV neuroinvasive disease who were treated with IVIG. The main outcome measure was neurological response after treatment. There were 12 patients who received IVIG and four improved within 48 h. Three patients died, 6 had partial recovery, and 3 recovered completely. Eleven of the 12 patients were infected with Israeli genotypes that are highly homologous to Europe/Africa viruses. The rapid response in some patients suggests that IVIG is effective, and might be used to treat patients with WNV neuroinvasive disease with IVIG.

Pandemic influenza A/H1N1 carries a relatively high morbidity, particularly in young people. Early identification would enable prompt initiation of therapy, thereby improving outcomes. To describe the epidemiological, clinical and laboratory characteristics of children admitted to hospital with the clinical diagnosis of influenza with reference to pandemic influenza A/H1N1. We conducted a prospective study of all children aged 16 years or less admitted to the pediatric department with the clinical diagnosis of influenza-like illness from July to October 2009. The presence of A/H1N1 virus was confirmed using real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis of nasopharyngeal secretions. Positive cases were compared with negative cases concerning epidemiological data, risk factors, clinical presentation and laboratory parameters, with emphasis on changes in the differential blood count. Of the 106 study patients, 53 were positive to influenza A/H1N1 and 53 were negative. In both groups nearly all patients had fever at presentation and approximately two-thirds had both fever and cough. All patients had a mild clinical course, no patient needed to be admitted to the intensive care unit and no mortalities were recorded. Hyperactive airway disease was more common in the A/H1N1-positive group. Pneumonia occurred in 30% of children in both groups. Laboratory findings included early lymphopenia and later neutropenia in theA/H1N1-infected patients. Leukopenia consisting of lymphopenia and later neutropenia was common in patients with A/H1N1 infection but was not correlated with disease severity or clinical course, which were similar in both groups. However, reduced leukocyte count can be used as an additional criterion for diagnosing A/H1N1 infection until RT-PCR results are available.

Objective To determine whether a sentinel clinic network or an emergency department (ED) was more timely in identifying the 2009 influenza A (H1N1) pandemic. Methods All reasons for presenting to the adult regional medical ED were coded online by admission secretaries, without the aid of medical personnel. Increased influenza activity defined by weekly chief complaints of fever was compared with activity defined by the Israel Center for Disease Control (viral surveillance as well as a large sentinel clinic network). Results Influenza activity during the pandemic increased in the ED 2 weeks before outpatient sentinel clinics. During the pandemic, maximal ED activity was much higher than in previous seasons. Maximal activity during the past 5 years correlated with the timeliness of the chief complaint of fever in identifying the onset of epidemics. Conclusion Chief complaint of fever in the ED can be a sensitive marker of increased influenza activity and might replace the use of sentinel clinics.

To determine if feeds high in fiber continuously administered might minimize diarrhea. The addition of soluble fiber to enteral feedings has not consistently decreased diarrhea in controlled clinical trials, and the effect of the use of intermittent or continuous infusions on the rate of diarrhea is similarly controversial. We studied 148 of 160 selected elderly well-nourished patients with acute disease prohibiting oral intake in a controlled clinical trial in the setting of an internal medicine departments in a regional hospital who were divided into 4 groups and fed according to combinations of intermittent or continuous systems, with fiber-free or fiber rich formulas. The 5-day rate of diarrhea was defined as 2 liquid stools or 3 or more semisolid or liquid bowel movements during a 24-hour period. Other outcome variables included mortality, hospital days, prolonged hospitalization (over 20 d), fever, and stools positive for Clostridium difficile cytotoxin A/B. The increased relative risk of the continuous/fiber-free, intermittent/fiber, and intermittent/fiber-free groups compared with the continuous/fiber group was 2.8 [95% confidence interval (CI)=1.0-8.1], 2.5 (95% CI=0.9-7.1), and 5.0 (95% CI=1.9-13.2), respectively. These findings were independent of age (>80 y), female sex, being treated with antibiotics for respiratory or urinary infections, receiving respiratory support, or being fully conscious. There were no significant differences in the other outcomes. We conclude that in elderly well-nourished hospitalized patients with acute diseases prohibiting oral intake, continuous and closed enteral feedings with the addition of fiber is effective in reducing the rate of diarrhea.