Clinical approaches to non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)ranges from simple steatosis to nonalcoholic steatohepatitis(NASH),leading to fibrosis and potentially cirrhosis,and it is one of the most common causes of liver disease worldwide.NAFLD is associated with other medical conditions such as metabolic syndrome,obesity,cardiovascular disease and diabetes.NASH can only be diagnosed through liver biopsy,but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis,reducing the need for liver biopsy and risk to patients.Disease progression varies between individuals and is linked to a number of risk factors.Mechanisms involved in the pathogenesis are associated with diet and lifestyle,influx of free fatty acids to the liver from adipose tissue due to insulin resistance,hepatic oxidative stress,cytokines production,reduced very low-density lipoprotein secretion and intestinal microbiome.Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD.Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial.Omega 3 polyunsaturated fatty acids and statins may offer additional benefits.Bariatric surgery should be considered in morbidly obese patients.More research is needed to assess the impact of these treatments on a long-term basis.The objective of this article is to briefly review the diagnosis,management and treatment of this disease in order to aid clinicians in managing these patients.     

CASE STUDIES OF THE TREATMENT OF HYPOTHYROIDISM BY MERIDIAN THEORY OF CHINESE MEDICINE

Some patients with hypothyroidism still remain symptom after prolonged treatment with thyroxine. Alternative treatment needs to be explored. The treatment is described as overlapof acupunture, supplemented with electric acupuncture, magnetic acupuncture, ear acupuncture, herbaltreatment, and acupressure of thyroid. The result of two case studies will be discussed in the presentation.The theoretical basis for the approach will also be explored.In Chinese medicine, hypothyroidismis often defined as spleen deficiency in the early stage and can be treated with ISRQ recipes (Invigorating the Spleen and Replenishing the Qi). In the chronic stage, hypothyroidism can be seen as kidneydeficiency and can be treated with KRR (Kidney Reinforcing Regimen). Hypthyroidism symptoms aresometimes diffcult to treat. However, TCM (Traditional Chinese Medicine) diagnosis and treatmentare based on an overall analysis of the illness according to patients' condition. After successful treamentof TCM, patients can stop taking Thy     

p27 Protein and cancers of the gastrointestinal tract and liver: an overview

GOALS: The purpose of this review is to look at the evidence presented in the literature on the immunoexpression of p27 in cancers of the gastrointestinal tract and liver. BACKGROUND: Cell cycle proteins have been shown to play an important role in the oncogenesis of many tumors. Several of these proteins have been examined in concert and in isolation, and some have been put forward as putative tumor markers. p27, which is an important inhibitory protein in the cell cycle and belonging to a group of cyclin-dependent kinase inhibitors, has also been studied in several malignancies, most notably breast, lung, bladder, and prostate cancers. Considerable work has also been done on the expression of this protein in cancers occurring within the gastrointestinal tract. RESULTS: Cancers occurring in the major sites of the gastrointestinal tract (esophagus, stomach, and colorectum) and liver show a similar pattern with regard to p27 protein levels. p27 emerges as a statistically significant predictor of survival and tumor behavior. It has been suggested that p27 loss occurs early in the carcinogenesis process, with dysplastic epithelium having decreased expression. The more aggressive, metastasizing cancers tend to lack p27 expression as well. Some studies have also invoked the subcellular localization of p27 (cytoplasmic versus nuclear) as also being of prognostic value. CONCLUSION: Therefore, in gastrointestinal and hepatic cancers, low p27 expression is regarded as an important adverse prognostic factor.     

The Natural History of the Non-Nephrotic Membranous Nephropathy Patient

Background and objectives: Although early studies suggest that patients with idiopathic membranous nephropathy (MGN) and subnephrotic range proteinuria overall do well, these studies were small and follow-up was short or difficult to discern.Design, setting, participants, & measurements: Three hundred ninety-five cases of idiopathic MGN with at least 12 mo of follow-up from the Toronto Glomerulonephritis Registry were reviewed to determine the outcome of the subgroup of patients that presented with subnephrotic range proteinuria. Onset and follow-up data included mean arterial pressure (MAP) and creatinine clearance (CrCl) as determined by the Cockcroft-Gault equation. Outcome variables included the rate of progression (slope of CrCl), 50% reduction in initial CrCl, and end-stage renal disease (ESRD).Results: One hundred eight (27% of the total) patients presented with subnephrotic proteinuria and almost 40% (42 of 108) of this subgroup remained subnephrotic. Their long-term slope was −0.93 ml/min/yr. In contrast, those who subsequently developed nephrotic range proteinuria had a progression rate almost four times faster (−3.52 ml/min/yr). The majority who developed nephrotic syndrome did so within the first year of follow-up. The only distinguishing baseline feature between the two groups was a higher level of urine protein in the group that subsequently developed nephrotic syndrome (1.98 [0.3 to 3.4] versus 2.43 [0.5 to 3.4] g/d).Conclusions: Patients with MGN and sustained subnephrotic range proteinuria have an excellent prognosis. Conservative management with close monitoring is recommended given the difficulty predicting which patients will develop nephrotic range proteinuria and then progress more rapidly.Idiopathic membranous nephropathy (MGN) remains the most common cause of adult onset nephrotic syndrome. The natural history of the disease is stated to ascribe to the rule of thirds, wherein approximately one-third of the affected have a complete and spontaneous remission of their proteinuria, one-third enter a partial remission with subnephrotic range proteinuria, and a final third remain nephrotic and progress to end-stage renal disease (ESRD) (1–4). Studies utilizing multivariate analysis techniques have identified clinical predictors of poor renal survival. These include older age, male gender, and elevated serum creatinine at the time of diagnosis as well as the severity of proteinuria at the time of disease onset and during follow-up (5–10). However, despite these known predictors, the long-term outcome is variable with the 10 yr renal survival ranging from 60 to 80% (1–4). Thus, the optimal strategy for the management of patients with MGN has remained unclear with varying opinions emerging in the literature (11–13).This variation in opinion extends to the MGN patient with subnephrotic range proteinuria. Although there exists data to suggest these patients overall do well, previous natural history studies included only small numbers of this subset of patients, often with limited follow-up or inadequate details with respect to their clinical course. In particular, the time course for evolution to nephrotic range proteinuria was rarely defined (2,4,6,14–17). The largest natural history study was published in 1979 and included 116 untreated patients with MGN, of which 28 (24.2%) presented with subnephrotic range proteinuria. However, the outcome for this subgroup of patients was not described, and almost 25% of the patients were followed for less than 1 yr (2). In other studies, between 15 and 46% of patients presented with subnephrotic range proteinuria (6,14,17). In the largest of these reports, 19% entered a complete remission, 21% had persistent subnephrotic range proteinuria, and only 6% progressed to nephrotic syndrome (17). This study, along with smaller studies that included a total of only 42 patients presenting with subnephrotic range proteinuria, noted an excellent renal survival as long as proteinuria did not progress (4,14,15). Progression to nephrotic range proteinuria was noted to be rare, occurring in only four of 42 patients (10%) (4,15,16). In addition, the time course for the evolution to nephrotic range proteinuria could not be determined in these early studies, and all were published before the development of the classes of drugs that block the renin angiotensin system (RAS), which could potentially alter disease progression.We describe the long-term outcome of the largest cohort to date of patients with idiopathic MGN who present with subnephrotic proteinuria. This cohort was followed prospectively, allowing for the long-term assessment of these patients, including those that evolved to nephrotic range proteinuria, and compares these patients to the classic MGN patient who presents with nephrotic syndrome. Based on these data, a management strategy is suggested for this cohort.     

Resource utilization and cost of influenza requiring hospitalization in Canadian adults: A study from the serious outcomes surveillance network of the Canadian Immunization Research Network

Background

Consideration of cost determinants is crucial to inform delivery of public vaccination programs.

Objectives

To estimate the average total cost of laboratory‐confirmed influenza requiring hospitalization in Canadians prior to, during, and 30 days following discharge. To analyze effects of patient/disease characteristics, treatment, and regional differences in costs.

Methods

Study utilized previously recorded clinical characteristics, resource use, and outcomes of laboratory‐confirmed influenza patients admitted to hospitals in the Serious Outcomes Surveillance (SOS), Canadian Immunization Research Network (CIRN), from 2010/11 to 2012/13. Unit costs including hospital overheads were linked to inpatient/outpatient resource utilization before and after admissions.

Results

Dataset included 2943 adult admissions to 17 SOS Network hospitals and 24 Toronto Invasive Bacterial Disease Network hospitals. Mean age was 69.5 years. Average hospital stay was 10.8 days (95% CI: 10.3, 11.3), general ward stays were 9.4 days (95% CI: 9.0, 9.8), and ICU stays were 9.8 days (95% CI: 8.6, 11.1) for the 14% of patients admitted to the ICU. Average cost per case was $14 612 CAD (95% CI: $13 852, $15 372) including $133 (95% CI: $116, $150) for medical care prior to admission, $14 031 (95% CI: $13 295, $14 768) during initial hospital stay, $447 (95% CI: $271, $624) post‐discharge, including readmission within 30 days.

Conclusion

The cost of laboratory‐confirmed influenza was higher than previous estimates, driven mostly by length of stay and analyzing only laboratory‐confirmed influenza cases. The true per‐patient cost of influenza‐related hospitalization has been underestimated, and prevention programs should be evaluated in this context.     

阿尔茨海默病APPswe/PS1dE9双转基因小鼠的病理生化和行为学研究(英文)

目的阿尔茨海默病(Alzheimer’sdisease,AD)APPswe/PS1dE9双转基因小鼠已被广泛运用于各种实验研究。AD小鼠脑内产生过量的β淀粉样蛋白(Aβ),后者会影响突触功能和中枢神经系统的发育。然而,该转基因小鼠模型的生化和行为学特征却未见报道。本研究旨在对该小鼠模型的病理从生化和行为学角度进行检测。方法对6月和12月龄转基因和野生型小鼠取血约100μL,1200g离心后,分离血清。在小鼠6月和12月龄时,进行为期15天的辐射状六臂水迷宫实验。ELISA法检测血清和大脑中Aβ1-40和Aβ1-42的含量,以及血清中8-羟基脱氧鸟苷的含量。比较转基因和野生型小鼠大脑不同部位中α-,β-和γ-分泌酶活性的差异。结果在6月龄之前,APP-swe/PS1dE9双转基因小鼠的死亡率约为35%,这些死亡的小鼠脑内Aβ1-40和Aβ1-42水平较高,两者比例约为1:10。在6月和12月龄时,转基因小鼠血清中Aβ1-40水平均显著高于Aβ1-42水平,Aβ1-40与Aβ1-42比例为2.37:1。在12月龄时,转基因小鼠大脑中Aβ1-42水平显著高于Aβ1-40水平,两者比例约为2.17:1,并且在不同脑区...