The prevalence of pre-operative anaemia and an examination of its effect on transfusion practice between sexes: A multicentre retrospective study.

Pre-operative anaemia affects one third of patients presenting for surgery and is associated with increased peri-operative morbidity and mortality. Most studies on this subject make a distinction in acceptable haemoglobin level between sexes. We analysed data for patients undergoing major elective surgery, with pre-operative anaemia defined as haemoglobin <13 g/dL. Data was collected for 1074 patients, of whom 411 (38.3%) had pre-operative anaemia. The odds of red cell transfusion were significantly higher in patients with pre-operative anaemia, OR = 4.35 [95%CI OR: 3.0- 6.2]. Additional binary logistic regression results identified haemoglobin level, male gender and increasing age as independent predictors for red cell transfusion. The length of post-operative stay was also significantly higher in anaemic patients, those with lower haemoglobin, males and older patients. Women were twice as likely to have a haemoglobin < 13 g/dl as men. Women were also 3.55 times more likely not to be transfused despite being anaemic. This suggests differences in clinician's attitudes to transfusion limits in women, despite Blaudszun et al. 2018 showing that women with borderline anaemia (Hb 12-12.9 g/dL) are: more likely to be transfused; to be transfused more units of red cells; and to have longer lengths of hospital stay than non- anaemic women. A change in attitude to acceptable haemoglobin in women is needed. Increased clinician awareness of the associated morbidity of even a mild reduction in haemoglobin in women is required to result in more pro-active anaemia management pre-operatively and less allogenic red cell transfusion, shorter lengths of hospital stay and overall decreased morbidity.

Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a disease of an accumulation of mature B cells that are highly dependent on the microenvironment for maintenance and expansion. However, little is known regarding the mechanisms whereby CLL cells create their favorable microenvironment for survival. High-mobility group protein B-1 (HMGB1) is a highly conserved nuclear protein that can be actively secreted by innate immune cells and passively released by injured or dying cells. We found significantly increased HMGB1 levels in the plasma of CLL patients compared with healthy controls, and HMGB1 concentration is associated with absolute lymphocyte count. We therefore sought to determine potential roles of HMGB1 in modulating the CLL microenvironment. CLL cells passively released HMGB1, and the timing and concentrations of HMGB1 in the medium were associated with differentiation of nurse-like cells (NLCs). Higher CD68 expression in CLL lymph nodes, one of the markers for NLCs, was associated with shorter overall survival of CLL patients. HMGB1-mediated NLC differentiation involved internalization of both receptor for advanced glycation end products (RAGE) and Toll-like receptor-9 (TLR9). Differentiation of NLCs can be prevented by blocking the HMGB1-RAGE-TLR9 pathway. In conclusion, this study demonstrates for the first time that CLL cells might modulate their microenvironment by releasing HMGB1.

Water, Walls, and Bicycles: Wealth Index Composition Using Census Microdata.

In this study, we produce a valid and consistent variable for socioeconomic status at the household level with census microdata from ten developing countries available from the Integrated Public Use Microdata Series - International (IPUMS-I), the world's largest census database. We use principal components analysis to compute a wealth index based on asset ownership, utilities, and dwelling characteristics. We validate the index by verifying socioeconomic gradients on school enrollment and educational attainment. Given that the availability of socioeconomic indicators varies considerably across samples of census microdata, we implement a stepwise elimination procedure on the wealth index to identify the conditions that produce an internally consistent index. Using the results of the stepwise methodology, we propose which indicators are most important in measuring household socioeconomic status. The development of the asset index for such a large archive of international census microdata is a very useful public resource for researchers.

Dysregulation of autophagy in human follicular lymphoma is independent of overexpression of BCL-2.

Overexpression of the anti-apoptotic protein BCL-2 is characteristic of human follicular lymphoma (FL) and some cases of diffuse large B cell lymphoma (DLBCL). We aimed to determine autophagy status in primary FL and DLBCL samples and the BCL-2+/BCL-2- lymphoma cell lines using both autophagy PCR array and tissue microarray (TMA). A greater number of autophagy machinery genes were up-regulated in the BCL-2+ Su-DHL4 cell line compared with BCL-2- Su-DHL8 cells, at both the basal level and in response to autophagic stress. The autophagy-related gene expression profiles were determined in purified and unpurified malignant human lymph node biopsies. Seven autophagy machinery genes were up-regulated in purified FL B-cells compared with reactive B-cells. Only 2 autophagy machinery genes were up-regulated in DLBCL B-cells. In unpurified tissue biopsies, 20 of 46 genes in FL and 2 of 5 genes in DLBCL with increased expression were autophagy machinery genes. Expression of autophagy substrates p62 and LC3 were determined by TMAs. FL samples showed significantly decreased levels of both p62 and LC3 compared with reactive and DLBCL, indicative of an increased autophagy activity in FL. In summary, these results demonstrate that FL showed increased basal autophagy activity, regardless of overexpression of BCL-2 in this disease.