A systematic review of acute kidney injury in pediatric allogeneic hematopoietic stem cell recipients

The process of allogeneic HSCT in children is associated with frequent AKI and mortality, but the epidemiology is not widely reported. The aim of this review was to summarize the available evidence on incidence, risk factors, timing, and prognosis of AKI in children following HSCT. We systematically reviewed all observational studies reporting incidence and outcomes of AKI in pediatric allogenic HSCT recipients. The minimum criteria for AKI were defined as an increase in sCr  ≥ x1.5 or urine output ≤0.5 mL/kg/min over six h. Medline and Embase were searched until March 2014. From 993 electronic records, five were eligible for inclusion (n = 571 patients). The average incidence of AKI within the first 100 days following HSCT was 21.7% (range 11–42%), and the average time of onset was 4–6 wk post‐transplant. Risk factors for AKI included cyclosporine toxicity, amphotericin B and foscarnet, SOS, and having a mismatched donor. There were conflicting reports on whether AKI was associated with the development of CKD. AKI is a common and potentially life‐threatening complication following HSCT in children. Further quality observational studies are needed to accurately determine the epidemiology and prognosis of AKI in this population.     

Prognostic value of blood pressure in ambulatory heart failure: a meta-analysis and systematic review. Ambulatory blood pressure predicts heart failure prognosis

Heart Failure Reviews - Previous primary studies have explored the association between blood pressure (BP) and mortality in ambulatory heart failure (HF) patients reporting varying and contrasting...     

Some Features of Bone Marrow Macrophages in Patients with Homozygous β-Thalassaemia

The bone marrow macrophages of patients with homozygous beta-thalassaemia were frequently situated adjacent to collagen fibres and sometimes formed intrasinusoidal cytoplasmic protrusions. They also appeared to phagocytose processes of erythroblast cytoplasm (at times containing precipitated alpha-chains) which projected into them from neighbouring erythroblasts. The cytoplasm of the macrophages included large numbers of heavily-iron-loaded secondary lysosomes of various sizes and shapes in addition to phagocytosed erythroblasts, erythrocytes and extruded erythroblast nuclei. Numerous ferritin molecules were found in the cytoplasmic matrix but there were hardly any in the mitochondria, endoplasmic reticulum or golgi saccules. A small number of ferritin molecules were present within the nucleus. Electron microscope autoradiographs of marrow fragments which had been incubated with [3H]leucine for 1 h revealed the presence of newly-synthesized protein molecules in all types of secondary lysosomes. Light microscope autoradiographs showed the [3H]thymidine labelling index of the bone marrow macrophages was less than 1% and suggested that only a very small proportion of these cells were actively preparing for division.     

Presence of bile in the oesophagus is associated with less effective oesophageal motility

BACKGROUND/AIMS: Reflux of bile to the oesophagus has been shown to be of importance in the development of gastro-oesophageal reflux disease. This study aims to assess oesophageal motility patterns in relation to acid and bile reflux to the oesophagus. METHODS: Forty-nine subjects with and without reflux disease underwent 24-hour ambulatory recordings of oesophageal pH, bile and 3-channel manometry. Gastroscopy was performed to assess severity of oesophagitis. The percentage of effective peristaltic contractions (oesophageal contractions with a peristaltic pattern and a pressure >30 mm Hg) were correlated to the degree of acid and bile reflux. Ten subjects were re-evaluated within 2 years post-fundoplication. RESULTS: Acid and bile reflux were associated with fewer effective contractions (R(2) = 0.07, p = 0.06 and R(2) = 0.21, p = 0.008, respectively). However, in a multivariate model including acid, bile, age and gender dependency, only bile could show a systematic effect on the variation in percentage of effective peristaltic contractions (R(2) = 0.22, p = 0.001). One year after laparoscopic fundoplication, 24-hour oesophageal motility was unchanged. CONCLUSION: Reflux of duodenal juice to the oesophagus is associated with less effective oesophageal motility, which in turn can perpetuate the disease by less effective oesophageal clearance of bile and acid. The reduced oesophageal motility is not reversed by fundoplication.     

Manganese superoxide dismutase is reduced in the liver of male but not female humans and rodents with non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is among the most common liver diseases. Oxidative stress is one of the pathogenic mechanisms contributing to the progression of simple fatty liver to non-alcoholic steatohepatitis (NASH). Manganese superoxide dismutase (MnSOD) is a mitochondrial antioxidative enzyme and here its expression in rodent and human NAFLD has been analyzed. MnSOD is found reduced in the liver of male mice fed a high fat diet and male ob/ob mice. Female mice fed an atherogenic diet to induce NASH have MnSOD protein levels comparable to controls. In a cohort of 30 controls, 41 patients with fatty liver and 39 NASH patients, MnSOD mRNA is significantly lower in the steatotic and NASH liver. When analyzed in both genders separately reduction of MnSOD expression is only found in males. Here, MnSOD mRNA negatively correlates with steatosis grade but not with extent of fibrosis or inflammation. MnSOD is, however, not reduced in primary human hepatocytes (PHH) treated with palmitate or oleate to increase cellular triglycerides. Lipopolysaccharide, TNF, IL-6, TGFβ and leptin which are all raised in NAFLD do not affect MnSOD in PHH. Adiponectin which attenuates oxidative stress partly by increasing MnSOD in macrophages does not induce MnSOD in PHH. In summary, current data show that hepatic MnSOD is reduced in male but not female humans and rodents with NAFLD.