Intra-rater variability in low-grade glioma segmentation

Assessment of size and growth are key radiological factors in low-grade gliomas (LGGs), both for prognostication and treatment evaluation, but the reliability of LGG-segmentation is scarcely studied. With a diffuse and invasive growth pattern, usually without contrast enhancement, these tumors can be difficult to delineate. The aim of this study was to investigate the intra-observer variability in LGG-segmentation for a radiologist without prior segmentation experience. Pre-operative 3D FLAIR images of 23 LGGs were segmented three times in the software 3D Slicer. Tumor volumes were calculated, together with the absolute and relative difference between the segmentations. To quantify the intra-rater variability, we used the Jaccard coefficient comparing both two (J2) and three (J3) segmentations as well as the Hausdorff Distance (HD). The variability measured with J2 improved significantly between the two last segmentations compared to the two first, going from 0.87 to 0.90 (p?=?0.04). Between the last two segmentations, larger tumors showed a tendency towards smaller relative volume difference (p?=?0.07), while tumors with well-defined borders had significantly less variability measured with both J2 (p?=?0.04) and HD (p?<?0.01). We found no significant relationship between variability and histological sub-types or Apparent Diffusion Coefficients (ADC). We found that the intra-rater variability can be considerable in serial LGG-segmentation, but the variability seems to decrease with experience and higher grade of border conspicuity. Our findings highlight that some criteria defining tumor borders and progression in 3D volumetric segmentation is needed, if moving from 2D to 3D assessment of size and growth of LGGs.

     

Accidental falls,health-related quality of life and life satisfaction: A prospective study of the general elderly population

As the physical consequences of accidental falls in the elderly are well-researched, the long-term associations between falls and quality of life and related concepts are less known. The aim of this study was to prospectively examine the long-term relations between falls and health-related quality of life (HRQoL) and life satisfaction (LS) over six years in the general elderly population.     

Benefits and harms of mammography screening

Mammography screening for breast cancer is widely available in many countries. Initially praised as a universal achievement to improve women''s health and to reduce the burden of breast cancer, the benefits and harms of mammography screening have been debated heatedly in the past years. This review discusses the benefits and harms of mammography screening in light of findings from randomized trials and from more recent observational studies performed in the era of modern diagnostics and treatment. The main benefit of mammography screening is reduction of breast-cancer related death. Relative reductions vary from about 15 to 25% in randomized trials to more recent estimates of 13 to 17% in meta-analyses of observational studies. Using UK population data of 2007, for 1,000 women invited to biennial mammography screening for 20 years from age 50, 2 to 3 women are prevented from dying of breast cancer. All-cause mortality is unchanged. Overdiagnosis of breast cancer is the main harm of mammography screening. Based on recent estimates from the United States, the relative amount of overdiagnosis (including ductal carcinoma in situ and invasive cancer) is 31%. This results in 15 women overdiagnosed for every 1,000 women invited to biennial mammography screening for 20 years from age 50. Women should be unpassionately informed about the benefits and harms of mammography screening using absolute effect sizes in a comprehensible fashion. In an era of limited health care resources, screening services need to be scrutinized and compared with each other with regard to effectiveness, cost-effectiveness and harms.     

Validation of abridged mini-mental state examination scales using population-based data from Sweden and USA

The objective of this study is to validate two abridged versions of the mini-mental state examination (MMSE): one intended for use in face-to-face interviews, and the other developed for telephonic interviews, using data from Sweden and the US to validate the abridged scales against dementia diagnoses as well as to compare their performance to that of the full MMSE scale. The abridged versions were based on eight domains from the original MMSE scale. The domains included in the MMSE-SF were registration, orientation, delayed recall, attention, and visual spatial ability. In the MMSE-SF-C, the visual spatial ability item was excluded, and instead, one additional orientation item was added. There were 794 participants from the Swedish HARMONY study [mean age 81.8 (4.8); the proportion of cognitively impaired was 51 %] and 576 participants from the US ADAMS study [mean age 83.2 (5.7); the proportion of cognitively impaired was 65 %] where it was possible to compare abridged MMSE scales to dementia diagnoses and to the full MMSE scale. We estimated the sensitivity and specificity levels of the abridged tests, using clinical diagnoses as reference. Analyses with both the HARMONY and the ADAMS data indicated comparable levels of sensitivity and specificity in detecting cognitive impairment for the two abridged scales relative to the full MMSE. Receiver operating characteristic curves indicated that the two abridged scales corresponded well to those of the full MMSE. The two abridged tests have adequate validity and correspond well with the full MMSE. The abridged versions could therefore be alternatives to consider in larger population studies where interview length is restricted, and the respondent burden is high.     

Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure.

AIMS: Although cardiac sympathetic activation is associated with adverse outcome in patients with chronic heart failure (CHF), the influence of renal sympathetic activity on outcome is unknown. We assessed the hypothesis that renal noradrenaline (NA) spillover is a predictor of the combined endpoint of all-cause mortality and heart transplantation in CHF. METHODS AND RESULTS: Sixty-one patients with CHF, New York Heart Association (NYHA) I-IV (66% NYHA III-IV), and left ventricular ejection fraction (LVEF) 26+/-9% (mean+/-SD) were studied with cardiac and renal catheterizations at baseline and followed for 5.5+/-3.7 years (median 5.5 years, range 12 days to 11.6 years). Nineteen deaths and 13 cases of heart transplantation were registered. Only renal NA spillover above median, 1.19 (interquartile range 0.77-1.43) nmol/min, was independently associated with an increased relative risk (RR) of the combined endpoint (RR 3.1, 95% CI 1.2-7.6, P=0.01) in a model also including total body NA spillover, LVEF, glomerular filtration rate (GFR), renal blood flow, cardiac index, aetiology, and age. CONCLUSION: Renal noradrenergic activation has a strong negative predictive value on outcome independent of overall sympathetic activity, GFR, and LVEF. These findings suggest that treatment regimens that further reduce renal noradrenergic stimulation could be advantageous by improving survival in patients with CHF.     

Genetic and epidemiological relationships among Campylobacter isolates from humans

84 Campylobacter jejuni isolates from Swedish patients with domestic infection were characterized with pulsed-field gel electrophoresis (PFGE), and the subtype information considered in relation to epidemiological data. Based on pattern combinations from restriction cleavage with SmaI and SalI, 52 different PFGE types were identified. Types with an average pattern similarity of at least 82% and 63% were assembled in groups and clusters, respectively. The 2 largest clusters included 71% of the isolates. The distribution in time varied between different groups and clusters, where some were isolated sporadically during the whole period and others appeared more concentrated in time. Types in 1 cluster were significantly more often isolated in summer than other types in the study. Isolates from children showed lower pattern similarity to other isolates than isolates from adults. Sets of type and time related cases, possibly representing small outbreaks, were identified when indistinguishable PFGE patterns were found in isolates from temporally related cases. Our results indicate that although a large number of genotypes may be found among C. jejuni strains infecting humans, a large proportion of these may be genetically related, and that different genotypes may appear during different seasons and infect individuals of different ages.     

Simultaneous generation of cytomegalovirus-specific CD8+ and CD4+ T lymphocytes by use of dendritic cells comodified with pp65 mRNA and pp65 protein

Cytomegalovirus (CMV) disease remains a severe complication in patients who have undergone transplantation. Viremia can be prevented and treated by the adoptive transfer of donor-derived CMV-directed T cells. To ensure long-term protection against CMV disease, it is important to transfer CMV antigen-specific T cells that represent both the CD8+ and the CD4+ subsets. In the present study, we used as stimulators dendritic cells (DCs) that were electroporated with in vitro-transcribed 5'-capped polyadenylated messenger RNA (mRNA) that encoded the CMV pp65 protein (i.e., pp65 mRNA). These DCs could efficiently activate CMV-directed CD8+ T cells, as assayed by tetramer staining, interferon- gamma production, and cytolytic activity. We also used DCs that were pulsed with a recombinant pp65 protein to activate CMV-directed CD4+ T cells. When DCs were comodified with pp65 mRNA and pp65 protein, large numbers of CMV-directed CD8+ and CD4+ T cells were generated simultaneously. The approach outlined in the present study can be adapted for a clinical protocol that circumvents potential virus-related biohazards and is available to all patients independently of their human leukocyte antigen haplotype.