Background & Aims: Non‐alcoholic fatty liver disease (NAFLD) is a risk factor for development of type 2 diabetes mellitus (T2DM). We aimed to evaluate whether conventional histological grading of steatosis and accurate quantification of fat content in liver biopsies using stereological point counting (SPC) can predict mortality and future development of T2DM in NAFLD patients.Methods: 129 patients with biopsy proven NAFLD, enrolled between 1988 and 1992, were re‐evaluated on two occasions, after 13.7 (±1.5) and 23.2 (±6.8) years. In patients accepting to undergo the procedure, repeat liver biopsies were performed on each follow‐up and were evaluated with conventional histopathological methodology and SPC.Results: Of the 106 patients without T2DM at baseline, 66 (62%) developed T2DM during a mean follow‐up of 23.2 (± 6.8) years. Steatosis grade and liver fat measured with SPC independently (adjusted for age, BMI, fibrosis stage) predicted development of T2DM with an aHR of 1.60 per grade and 1.03 for each SPC percentage increase respectively. Overall mortality and development of T2DM was more common in patients with grade 3 steatosis compared to lower grades of steatosis. Liver fat measured with SPC was significant for overall mortality (aHR 1.04). In patients that underwent repeat biopsy, reduction in liver fat measured with SPC was associated with decreased risk of developing T2DM (aHR 0.91 for each SPC percentage decrease).Conclusion: Steatosis grade and liver fat measured with SPC predict mortality and the risk of developing T2DM in NAFLD. Reduction in liver fat decreases the risk of developing T2DM.

NOTCH1 PEST domain mutations in chronic lymphocytic leukemia have recently been shown to be of prognostic relevance. Both NOTCH1 and NOTCH2 are constitutively activated in B-cell CLL but not expressed in normal B cells and may be involved in survival and resistance to apoptosis in CLL. We screened for mutations in different parts of both NOTCH1 and NOTCH2 genes and related the changes to survival and other known risk factors. In a cohort of 209 CLL patients, we used single strand conformation analysis to determine which of the samples carrying the NOTCH mutations and direct dideoxy sequencing was used to determine the exact nucleotide changes. Kaplan-Meier curves and log rank test were used to determine overall survival for NOTCH1 mutated cases and Cox regression analysis was used to calculate hazardous ratios. In the present study, we found NOTCH1 PEST domain mutations in 6.7% of the cases. A shorter overall survival was found in patients with NOTCH1 mutations compared to wildtype (p = 0.049). Further, we also examined the extracellular and the heterodimerisation domains of the NOTCH1 gene and the PEST domain and heterodimerisation domain of the NOTCH2 gene, but no mutations were found in these regions. NOTCH1 mutations were most commonly observed in patients with unmutated IGHV gene (10/14), and associated with a more aggressive disease course. In addition, NOTCH1 mutations were almost mutually exclusive with TP53 mutations. In the combined group of NOTCH1 (6.7%) or TP53 (6.2%) mutations, a significant difference in overall survival compared to the wildtype NOTCH1 and TP53 was found (p = 0.002). Both NOTCH1 and TP53 mutations seem to be independent predictive markers for worse outcome in CLL-patients and this study emphasizes the contention that NOTCH1 mutations is a novel risk marker.

New and clinically useful markers of cardiovascular risk are of essence in type 2 diabetes since ischemic heart disease is a major cause of death in these patients. We analyzed baseline data from 476 men and 244 women who participated in “Cardiovascular Risk factors in Patients with Diabetes -a Prospective study in Primary care” study. All participants had type 2 diabetes and were 55-66 years old at recruitment during year 2005 to 2008. Except for established traditional risk markers for vascular disease, we also estimated vascular complications non-invasively by performance of carotid-femoral pulse-wave velocity (PWV, with applanation-tonometry) and intima-media thickness of carotid arteries (IMT, with B-mode ultrasound). Patients were followed for incidence of ischemic heart disease mortality and morbidity until end of the year 2012, using the national Swedish Cause of Death and Hospitalization Registries. During the follow-up period of a median of 6 years 47 men and 10 women died or were hospitalized for ischemic heart disease including myocardial infarction. Leptin levels were positively related to the hazard ratio (HR) in men (HR for each log 10 unit 4.9, CI 1.99 to 11.8) and women (HR 11.5, CI 1.47 to 89.7). Leptin predicted ischemic heart disease independently of age, HbA1c, BMI, systolic blood pressure and LDL-cholesterol/HDL-cholesterol ratio (men: HR 12.9 CI 3.2-53, women: HR 19.9, CI 1.2-327) This finding of increased risk related to high leptin levels was also statistically significant when carotid-femoral PWV and IMT were both added to the equations in men (hazard ratio 9.2 CI 2.1-41). Our data support the use of serum leptin in type 2 diabetes to add independent prognostic information in terms of ischemic heart disease when compared with traditional cardiovascular risk factors. In the men of the cohort this prognostic information was in addition also to data on IMT and PWV, two non-invasive measurements of the extent of vascular disease. The power to detect a similar relationship in women was less strong due to lower incidence of cardiovascular disease. ClinicalTrials.gov: NCT01049737 .

Background: Although repositioning is considered an important intervention to prevent pressure ulcers, tissue response during loading in different lying positions has not been adequately explored. Aim: To compare the effects of different lying positions on interface pressure, skin temperature, and tissue blood flow in nursing home residents. Method: From May 2011 to August 2012, interface pressure, skin temperature, and blood flow at three tissue depths were measured for 1 hr over the sacrum in 30° supine tilt and 0° supine positions and over the trochanter major in 30° lateral and 90° lateral positions in 25 residents aged 65 years or older. Measurement of interface pressure was accomplished using a pneumatic pressure transmitter connected to a digital manometer, skin temperature using a temperature sensor, and blood flow using photoplethysmography and laser Doppler flowmetry. Results: Interface pressure was significantly higher in the 0° supine and 90° lateral positions than in 30° supine tilt and 30° lateral positions. The mean skin temperature increased from baseline in all positions. Blood flow was significantly higher in the 30° supine tilt position compared to the other positions. A hyperemic response in the post pressure period was seen at almost all tissue depths and positions. Conclusion: The 30° supine tilt position generated less interface pressure and allowed greater tissue perfusion, suggesting that this position is the most beneficial.