Chronic obstructive pulmonary disease hospitalisations and mortality in Victoria: analysis of variations by socioeconomic status

Objective: This paper analysed chronic obstructive pulmonary disease (COPD) hospitalisations, unplanned readmissions and deaths in Victoria to identify associations with socioeconomic status (SES). Methods: The data was taken from the Victorian Admitted Episodes Dataset, the Victorian Health Information Surveillance System, the Victorian Burden of Disease Study and the Australian Bureau of Statistics’ Index of Relative Socioeconomic Disadvantage. Results: COPD separations have a greater variation by SES than all separations. The average age‐standardised separation rate (10.43) for the top percentile Local Government Areas (LGA) was 5.8 times that of the bottom percentile LGAs (1.80). The top percentile group was the lowest SES group (effect size = 0.93). There were significant negative correlations between the age‐standardised COPD separation rates and SES across LGAs (r = ?0.60) and Regions (r = ?0.89). Analysis of readmissions (r = ?0.49), mortality data (r = ?0.51) and the burden of disease data (r = ?0.39) also showed significant inverse associations between COPD and SES. Conclusions and implications: Victorians living in the most disadvantaged areas have a greater burden from COPD, highlighting a need to prioritise public health services interventions to improve outcomes.     

早产儿喂养不耐受肠道菌群多样性研究

目的：采用变性梯度凝胶电泳聚合酶链反应（ PCR－DGGE）技术从微生物生态学的角度分析比较喂养不耐受（ FI）与健康早产儿肠道细菌群落结构的多样性及相似性。方法以2013年11月至2014年9月在第四军医大学附属唐都医院儿科新生儿病房诊断为FI的早产儿为FI组。选择与FI组胎龄、日龄、出生体重相匹配的非FI早产儿作为对照组。采集出现FI时和同时间段对照组的粪便标本,进行16SrDNAV3区扩增和变性梯度凝胶电泳（DGGE）,从而分析比较两组间肠道菌群多样性指数及相似性。结果细菌多样性检测显示FI组的肠道菌群多样性指数香农－维纳指数（H）、丰度（S）、均衡度指数（E）和辛普森多样性指数（D）均低于对照组（均P＜0．05）;相似性矩阵图及聚类分析结果显示组内菌群相似性较组间高（P＜0．05）;PCA结果同聚类分析一致。结论肠道微生物群落多样性的改变及群落结构紊乱可能是引起早产儿FI的重要因素。     

Journey of a patient with chronic thromboembolic pulmonary hypertension

Right ventricle (RV) dysfunction is a key outcome determinant and a leading cause of death for patients with chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we followed the 5-year clinical journey of a patient with CTEPH. The tricuspid pressure gradient was significantly increased in the early phase of CTEPH and “normalized” at the late phase of this patient’s clinical journey, but this “normalized” gradient is not a positive treatment response but rather an ominous sign of advancing right heart failure owing to an exhaustion of RV contractile function. Thus, appropriate interpretation of the tricuspid pressure gradient change is of importance for assessing RV dysfunction and treatment outcome during follow-up in patients with CTEPH. Besides systolic pulmonary artery pressure (SPAP), other RV functional parameters such as tricuspid annular plane systolic excursion, RV fractional area change, and RV longitudinal strain, together with clinical markers, may provide additional guidance regarding functional improvement or progression in patients with CTEPH.     

Transient elastography-derived liver stiffness measurements were found to be useful for predicting liver infiltration in a case of mature T-cell neoplasm involving liver dysfunction

Transient elastography (TE) is a novel, non-invasive imaging technique for measuring liver stiffness (LS). It is considered to be useful for predicting the severity of fibrosis and the risk of cirrhosis or hepatocellular carcinoma. However, the association between the presence of diffuse regions of increased cell density in the liver and elevated LS values has not been assessed. We experienced a case in which a mature T-cell neoplasm had invaded the liver, but the infiltrating lesion was not detected by contrast-enhanced computed tomography (CT) or fluorodeoxyglucose positron emission tomography/CT scans. Instead, the tumor’s presence was indicated by the change in the patient’s TE-derived LS values after chemotherapy. At diagnosis liver dysfunction was detected in a biochemical examination, and mean LS value was as high as 25.4 kPa [interquartile range (IQR): 0.3, success rate (SR):100%]. After chemotherapy, the patient’s mean LS value fell to 4.3 kPa (IQR: 0.8, SR:100%). A follow-up pathological investigation demonstrated that proliferating abnormal T-cells were no longer present in the patient’s liver. This is the first report to describe the use of LS data to support a diagnosis of liver infiltration by tumor cells exhibiting a portal and sinusoidal distribution pattern rather than a focal pattern. Elevated TE-derived LS values should lead to hepatic tumor infiltration being considered during initial examinations or a suspicion of recurrence during follow-up examination of lymphoma patients who achieve complete remission, even when radiological investigations do not detect abnormalities in the liver.     

AGE‐modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

Biomechanical strain imposed by age‐related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end‐product (AGE)‐dependent non‐enzymatic crosslinking of its major components, collagen IV and laminin. We used this model to demonstrate that antibody targeted blockade of CTLD2, the second of eight C‐type lectin‐like domains in Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) that can recognize glycosylated collagens, reversed actinomyosin‐based contractility [myosin‐light chain‐2 (MLC2) phosphorylation], loss of cell polarity, loss of cell–cell junctions, luminal infiltration and basal invasion induced by AGE‐modified basal lamina matrix in PEC acini. Our in vitro results were concordant with luminal occlusion of acini in the prostate glands of adult Endo180^{ΔEx2–6/ΔEx2–6} mice, with constitutively exposed CTLD2 and decreased survival of men with early (non‐invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE‐dependent modification of the basal lamina induces invasive behaviour in non‐transformed PECs via a molecular mechanism linked to cancer progression. This study provides a rationale for targeting CTLD2 in Endo180 in prostate cancer and other pathologies in which increased basal lamina thickness and tissue stiffness are driving factors. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The factors associated with longitudinal changes in liver stiffness in patients with chronic hepatitis B

Background/Aims

Liver stiffness (LS) as assessed by transient elastography (TE) can change longitudinally in patients with chronic hepatitis B (CHB). The aim of this study was to identify the factors that improve LS.

Methods

Between April 2007 and December 2012, 151 patients with CHB who underwent two TE procedures with an interval of about 2 years were enrolled. Ninety-six of the 151 patients were treated with nucleos(t)ide analogues [the antiviral therapy (+) group], while the remaining 55 patients were not [the antiviral therapy (-) group]. The two groups of patients were stratified according to whether they exhibited an improvement or a deterioration in LS during the study period (defined as an LS change of ≤0 or >0 kPa, respectively, over a 1-year period), and their data were compared.

Results

No differences were observed between the antiviral therapy (+) and (-) groups with respect to either their clinical characteristics or their initial LS. The observed LS improvement was significantly greater in the antiviral therapy (+) group than in the antiviral therapy (-) group (-3.0 vs. 0.98 kPa, P=0.011). In the antiviral therapy (+) group, the initial LS was higher in the LS improvement group (n=63) than in the LS deterioration group (n=33; 7.9 vs. 4.8 kPa, P<0.001). However, there were no differences in any other clinical characteristic. In the antiviral therapy (-) group, the initial LS was also higher in the LS improvement group (n=29) than in the LS deterioration group (n=26; 8.3 vs. 6.5 kPa, P=0.021), with no differences in any other clinical characteristic.

Conclusions

A higher initial LS was the only factor associated with LS improvement in patients with CHB in this study.     

In Vivo Measures of Shear Wave Speed as a Predictor of Tendon Elasticity and Strength

The purpose of this study was to assess the potential for ultrasound shear wave elastography (SWE) to measure tissue elasticity and ultimate stress in both intact and healing tendons. The lateral gastrocnemius (Achilles) tendons of 41 New Zealand white rabbits were surgically severed and repaired with growth factor coated sutures. SWE imaging was used to measure shear wave speed (SWS) in both the medial and lateral tendons pre-surgery, and at 2 and 4 wk post-surgery. Rabbits were euthanized at 4 wk, and both medial and lateral tendons underwent mechanical testing to failure. SWS significantly (p < 0.001) decreased an average of 17% between the intact and post-surgical state across all tendons. SWS was significantly (p < 0.001) correlated with both the tendon elastic modulus (r = 0.52) and ultimate stress (r = 0.58). Thus, ultrasound SWE is a potentially promising non-invasive technology for quantitatively assessing the mechanical integrity of pre-operative and post-operative tendons.     

High systemic HCO 3 − and topical 16,16-dimethyl-PGE2 protect gastric mucosa against luminal acid by enhancing its preepithelial buffer capacity

Systemic metabolic alkalosis and topical prostaglandins protect the gastric mucosa against luminal acid. This study investigates whether this protection is mediated by increased epithelial HCO ₃ ^– secretion with resultant alkalization of the preepithelial mucus-HCO ₃ ^– buffer layer. Surface pH of chamberedex vivo rat gastric epithelium was measured with liquid sensor pH microelectrodes during luminal perfusion of increasing acidities (0, 10, 30, 50, 100 mM HCl). The experimental groups were: (1) control, (2) topical 16,16-dimethyl-PGE₂ treatment, (3) high-HCO ₃ ^– metabolic alkalosis, and (4) low-HCO ₃ ^– respiratory alkalosis. The gastric mucosa of PGE₂-treated and high-HCO ₃ ^– alkalotic rats tolerated significantly better luminal acid than that of controls, but the tolerance of low-HCO ₃ ^– alkalotic rats was significantly impaired. There was a significant correlation between arterial HCO ₃ ^– concentration (but not arterial pH) and surface pH (r=0.81,P<0.01). This suggests that the protective actions of systemic high-HCO ₃ ^– alkalosis and topical-PGE₂ treatment in the gastric mucosa against luminal acid are, at least in part, mediated by enhanced buffer capacity of the preepithelial mucus-HCO ₃ ^– layer.This study is supported by grants from the Medical Research Council of the Academy of Finland and Sigrid Juselius Foundation, Helsinki, Finland and Orion Research Council, Espoo, Finland.