Preliminary experience of CT imaging of the ischaemic brain penumbra through spectral processing of multiphasic CTA datasets.

To assess ischaemic penumbra through the post-processing of the spectral multiphasic CT Angiography (mCTA) data in acute ischaemic stroke (AIS) patients. Thirty one consecutive patients strongly suspected of severe Middle Cerebral Artery AIS presenting less than 6 h after onset of symptoms or with unknown time of onset of symptoms underwent a standardized CT protocol in spectral mode including Non Contrast CT, mCTA, and Perfusion CT (CTP) on a dual-layer MDCT system. Areas disclosing delayed enhancement on iodine density (ID) maps were highlighted by subtraction of the serial mCTA datasets. Two neuroradiologists independently rated the correspondence between delayed enhancing areas at mCTA and the penumbral/infarcted areas delineated by two validated CTP applications using a 5-levels scoring scale. Interobserver agreement between observers was evaluated by kappa statistics. Dose delivery was recorded for each acquisition. Averaged correspondence score between penumbra delineation using subtracted mCTA-derived ID maps and CTP ones was 2.76 for one application and 2.9 for the other with best interobserver agreement kappa value at 0.59. All 6 stroke mimics out of the 31 patients' cohort were correctly identified. Average dose delivery was 7.55 mSv for the whole procedure of which CTP accounted for 39.7%. Post-processing of spectral mCTA data could allow clinically relevant assessment of the presence or absence of ischaemic penumbra in AIS-suspected patients if results of this proof-of-concept study should be confirmed in larger patients'series.

Localised childhood vulvar pemphigoid: a rare case study.

In this case report we present a young patient with localised childhood vulvar pemphigoid. It is a rare variant of bullous pemphigoid with mostly a favourable prognosis and prompt response to potent topical corticosteroids. She presented with relapsing vulvar pain and lesions. Our case enlightens the recognition of this unusual subtype and the importance of performing a cutaneous biopsy.

A multifunctional matching algorithm for sample design in agricultural plots.

Collection of accurate and representative data from agricultural fields is required for efficient crop management. Since growers have limited available resources, there is a need for advanced methods to select representative points within a field in order to best satisfy sampling or sensing objectives. The main purpose of this work was to develop a data-driven method for selecting locations across an agricultural field given observations of some covariates at every point in the field. These chosen locations should be representative of the distribution of the covariates in the entire population and represent the spatial variability in the field. They can then be used to sample an unknown target feature whose sampling is expensive and cannot be realistically done at the population scale. An algorithm for determining these optimal sampling locations, namely the multifunctional matching (MFM) criterion, was based on matching of moments (functionals) between sample and population. The selected functionals in this study were standard deviation, mean, and Kendall's tau. An additional algorithm defined the minimal number of observations that could represent the population according to a desired level of accuracy. The MFM was applied to datasets from two agricultural plots: a vineyard and a peach orchard. The data from the plots included measured values of slope, topographic wetness index, normalized difference vegetation index, and apparent soil electrical conductivity. The MFM algorithm selected the number of sampling points according to a representation accuracy of 90% and determined the optimal location of these points. The algorithm was validated against values of vine or tree water status measured as crop water stress index (CWSI). Algorithm performance was then compared to two other sampling methods: the conditioned Latin hypercube sampling (cLHS) model and a uniform random sample with spatial constraints. Comparison among sampling methods was based on measures of similarity between the target variable population distribution and the distribution of the selected sample. MFM represented CWSI distribution better than the cLHS and the uniform random sampling, and the selected locations showed smaller deviations from the mean and standard deviation of the entire population. The MFM functioned better in the vineyard, where spatial variability was larger than in the orchard. In both plots, the spatial pattern of the selected samples captured the spatial variability of CWSI. MFM can be adjusted and applied using other moments/functionals and may be adopted by other disciplines, particularly in cases where small sample sizes are desired.

Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study.

BACKGROUND AND OBJECTIVE: We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS-International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies. METHODS: We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014-2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST. RESULTS: Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44-47), 46.0% (42-50), 38% (35-41) and 37% (35-41), respectively; death was 19.2% (19-21), 15.3% (12.7-18.4), 29.2% (27-32) and 28.6% (27-31); and SICH was 3.6% (3-4), 4.4% (3.0-6.4), 5.8% (4.7-7.1) and not available. CONCLUSION: Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.

Breath analysis for the detection of digestive tract malignancies: systematic review.

BACKGROUND: In recent decades there has been growing interest in the use of volatile organic compounds (VOCs) in exhaled breath as biomarkers for the diagnosis of multiple variants of cancer. This review aimed to evaluate the diagnostic accuracy and current status of VOC analysis in exhaled breath for the detection of cancer in the digestive tract. METHODS: PubMed and the Cochrane Library database were searched for VOC analysis studies, in which exhaled air was used to detect gastro-oesophageal, liver, pancreatic, and intestinal cancer in humans, Quality assessment was performed using the QUADAS-2 criteria. Data on diagnostic performance, VOCs with discriminative power, and methodological information were extracted from the included articles. RESULTS: Twenty-three articles were included (gastro-oesophageal cancer n = 14, liver cancer n = 1, pancreatic cancer n = 2, colorectal cancer n = 6). Methodological issues included different modalities of patient preparation and sampling and platform used. The sensitivity and specificity of VOC analysis ranged from 66.7 to 100 per cent and from 48.1 to 97.9 per cent respectively. Owing to heterogeneity of the studies, no pooling of the results could be performed. Of the VOCs found, 32 were identified in more than one study. Nineteen were reported as cancer type-specific, whereas 13 were found in different cancer types. Overall, decanal, nonanal, and acetone were the most frequently identified. CONCLUSION: The literature on VOC analysis has documented a lack of standardization in study designs. Heterogeneity between the studies and insufficient validation of the results make interpretation of the outcomes challenging. To reach clinical applicability, future studies on breath analysis should provide an accurate description of the methodology and validate their findings.

Disrupted regulation of serpinB9 in circulating T cells is associated with an increased risk for post-transplant skin cancer.

Cutaneous squamous cell carcinoma (cSCC) is a serious complication after organ transplantation and patients benefit from an early risk assessment. We hypothesized that functional differences in circulating T cells may represent risk factors for post-transplant cSCC development. Here, we analysed genome-wide DNA methylation of circulating T cells of kidney transplant recipients before the clinical onset of cSCC, to identify differences associated with post-transplant cSCC development. This analysis identified higher DNA methylation of SERPINB9, which is an intracellular inhibitor of granzyme B, a protein that induces apoptosis in target cells. High DNA methylation of SERPINB9 in circulating T cells was confirmed in a second patient cohort during recurrent cSCC, indicating that high SERPINB9 methylation represents a persistent risk factor for cSCC development. At the functional level, the inverse correlation between DNA methylation and messenger RNA expression present in non-cSCC patients was absent in the cSCC patients. Also, a significant difference in serpinB9 protein expression between cSCC patients and non-cSCC patients was observed. It was concluded that disturbed regulation of serpinB9 in circulating T cells represents a novel risk factor for post-transplant cSCC in kidney transplant recipients.

Intravenous thrombolysis in stroke mimics: results from the SITS International Stroke Thrombolysis Register.

BACKGROUND AND PURPOSE: Patients with stroke mimics (SM), i.e. conditions with stroke-like symptoms, may risk harm if treated with intravenous thrombolysis (IVT). Current guidelines state low risk of intracerebral hemorrhage based on studies comprising a total of <400 SM cases. We aimed to compare safety and outcomes following IVT between patients with acute ischaemic stroke and mimicking conditions. METHODS: We included IVT-treated ischaemic stroke patients in the SITS International Stroke Thrombolysis Register 2003-2017, examined with magnetic resonance imaging 22-36 h after treatment. Outcomes were parenchymal hematoma (PH) after treatment, symptomatic intracerebral hemorrhage (SICH) per Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST), Second European Co-operative Stroke Study (ECASS II) and National Institutes of Neurological Disorders and Stroke Study (NINDS) criteria, death and modified Rankin Scale score (mRS) at 3 months. RESULTS: Of 10 436 patients, 429 mimics (4.1%) were identified. The most common types were functional (30.8%), migraine (17.5%) and seizure (14.2%). Patients with mimics had fewer cerebrovascular risk factors and lower median National Institutes of Health Stroke Scale score [7 (interquartile range, 5-10) vs. 8 (5-14), P < 0.001]. Among mimics versus stroke patients, PH was seen in 1.2% vs. 5.1% (P < 0.001), SICH NINDS in 0.5% vs. 3.9% (P < 0.001), SICH ECASS II in 0.2% vs. 2.1% (P = 0.007) and SICH SITS-MOST in 0% vs. 0.5% (P = 0.28). Modified Rankin Scale score 0-1 at 3 months was present in 84.1% vs. 57.7% (P < 0.001) and death within 3 months in 2.6% vs. 5.4% (P = 0.028) of mimics and stroke patients, respectively. CONCLUSIONS: This large observational study indicated that PH and SICH following IVT in patients with SM are uncommon.

WHO-5 and BDI-II are acceptable screening instruments for depression in people with diabetes.

AIMS: To investigate the acceptability of two questionnaires, the five item WHO Well-being Index (WHO-5) and the Beck Depression Inventory II (BDI-II), which differ in length and focus, by comparing three screening groups: (1) WHO-5, (2) BDI-II and (3) WHO-5 and BDI-II. METHODS: A total of 699 individuals with diabetes were approached to participate in the study, of whom 95 completed the WHO-5, 254 completed the BDI-II and 350 completed both the WHO-5 and the BDI-II questionnaires. Five facets of acceptability were compared, including objective aspects (response rate and completion level) and subjective aspects (appreciation, agreeableness and accuracy of the screening questionnaire). Data were analysed using logistic regression analysis and (multivariate) analysis of covariance. RESULTS: The overall response rate was 65% (453 out of 699). No differences between the three groups were found with respect to the response rate (WHO-5: 66%; BDI-II: 63%; WHO-5 and BDI-II: 66%; P ≥ 0.19) and completion level (WHO-5: 99.5%; BDI-II: 97.8%; WHO-5 and BDI-II: 98.7%; P=0.45). The three groups did differ significantly in their scores on two of the three subjective indicators (P<0.03), i.e. appreciation (P=0.002) and agreeableness (P=0.035), with those completing only the WHO-5 reporting greater appreciation and agreeableness. CONCLUSIONS: A brief well-being questionnaire, such as the WHO-5, results in greater appreciation of mood screening and appreciation of completing the questionnaire, but this does not result in a better response rate and higher questionnaire completion. Given these results, either or both questionnaires can be used to screen for depressive symptoms in people with diabetes in clinical practice.

Safety and immunogenicity of HBAI20 Hepatitis B vaccine in healthy naïve and nonresponding adults.

Approximately 5% of the healthy adult population respond inadequately to the commercial recombinant hepatitis B vaccines. As the recombinant vaccines all have an aluminium-based adjuvant, we tried to enhance the immune response by adding a cytokine-based adjuvant. This new adjuvant AI20, containing 20 µg recombinant human IL-2 attached to 20 µg aluminium hydroxide, was added to HBVaxPro©-10 µg (HBAI20). In a double-blind randomized controlled trial (RCT), 24 naïve subjects were randomized to receive either HBAI20 or commercial HBVaxPro©-10 µg vaccine. In an open-label study, 10 nonresponders received HBAI20 vaccine. All participants received 3 vaccinations (0, 1 and 6 months). In the RCT, the occurrence of any adverse events or severe events was similar between the trial arms. At month 7, all naïve participants were seroprotected; moreover, 92% in the HBAI20 group had protective antibodies 10 days after the second vaccination vs 58% in the HBVaxPro©-10 µg group, P = .16. In the open-label study, no serious adverse events were noted. The HBAI20 vaccine was able to elicit protective anti-HBs titres in 90% of nonresponders, 1 month after the third vaccination. According to these results, the new HBAI20 vaccine seems safe, well-tolerated and may promote more rapid protection against hepatitis B infection.

How to influence the obesity landscape using health policies.

There is widespread acceptance that a significant and sustained impact on the growing global obesity burden requires implementation of a range of health policies to influence the obesity landscape. This acceptance is underpinned by the understanding that the obesity landscape is a complex interaction between the many factors that influence an individual's dietary intake and physical activity levels. Over the past decade we have seen increasing convergence in national and international recommendations on how to best improve this obesity landscape. In the past few years this has led to a noticeable increase in the implementation of these recommended national, state and local government policies. Here, we argue that to maximise the impact of population-level policies intended to improve diet and activity environments we need to see progress in a number of key areas, namely: broadening the range of environments that can be empowered to implement policy; improving our understanding of how best to combine multiple policies and interventions; and improving our understanding of the equity impact of these policies. We also argue that a key goal moving forward should be better capture and communication of the existing activities in order to more rapidly spread the uptake of these policies globally and at scale.

Does intentional weight loss improve daytime sleepiness? A systematic review and meta-analysis.

Obesity is associated with excessive daytime sleepiness, but its causality remains unclear. We aimed to assess the extent to which intentional weight loss affects daytime sleepiness. Electronic databases were searched through 24 October 2016. Studies involving overweight or obese adults, a weight loss intervention and repeated valid measures of daytime sleepiness were included in the review. Two independent reviewers extracted data on study characteristics, main outcome (change in daytime sleepiness score standardized by standard deviation of baseline sleepiness scores), potential mediators (e.g. amount of weight loss and change in apnoea-hypopnoea index) and other co-factors (e.g. baseline demographics). Forty-two studies were included in the review. Fifteen before-and-after studies on surgical weight loss interventions showed large improvements in daytime sleepiness, with a standardized effect size of -0.97 (95% confidence interval [CI] -1.21 to -0.72). Twenty-seven studies on non-surgical weight loss interventions showed small-to-moderate improvement in daytime sleepiness, with a standardized effect size of -0.40 (95%CI -0.52 to -0.27), with no difference between controlled and before-and-after studies. We found a nonlinear association between amount of weight loss and change in daytime sleepiness. This review suggests that weight loss interventions improve daytime sleepiness, with a clear dose-response relationship. This supports the previously hypothesized causal effect of obesity on daytime sleepiness. It is important to assess and manage daytime sleepiness in obese patients.

Obesity in older adults and life expectancy with and without cardiovascular disease.

BACKGROUND: The prevalence of overweight and obesity is increasing globally and is an established risk factor for cardiovascular disease (CVD). Our objective was to evaluate the impact of overweight and obesity on life expectancy and years lived with and without CVD in older adults. METHODS: The study included 6636 individuals (3750 women) aged 55 years and older from the population-based Rotterdam Study. We developed multistate life tables by using prevalence, incidence rate and hazard ratios (HR) for three transitions (free-of-CVD-to-CVD, free-of-CVD-to-death and CVD-to-death), stratifying by the categories of body mass index (BMI) at baseline and adjusting for confounders. RESULTS: During 12 years of follow-up, we observed 1035 incident CVD events and 1902 overall deaths. Obesity was associated with an increased risk of CVD among men (HR 1.57 (95% confidence interval (CI) 1.17, 2.11)) and women (HR 1.49 (95% CI 1.19, 1.86)), compared with normal weight individuals. Overweight and obesity were not associated with mortality in men and women without CVD. Among men with CVD, obesity compared with normal weight, was associated with a lower risk of mortality (HR 0.67 (95% CI 0.49, 0.90)). Overweight and obesity did not influence total life expectancy. However, obesity was associated with 2.6 fewer years (95% CI -4.8, -0.4) lived free from CVD in men and 1.9 (95% CI -3.3, -0.9) in women. Moreover, men and women with obesity lived 2.9 (95% CI 1.1, 4.8) and 1.7 (95% CI 0.6, 2.8) more years suffering from CVD compared with normal weight counterparts. CONCLUSIONS: Obesity had no effect on total life expectancy in older individuals, but increased the risk of having CVD earlier in life and consequently extended the number of years lived with CVD. Owing to increasing prevalence of obesity and improved treatment of CVD, we might expect more individuals living with CVD and for a longer period of time.

Discarded Human Thymus Is a Novel Source of Stable and Long-Lived Therapeutic Regulatory T Cells.

Regulatory T cell (Treg)-based therapy is a promising approach to treat many immune-mediated disorders such as autoimmune diseases, organ transplant rejection, and graft-versus-host disease (GVHD). Challenges to successful clinical implementation of adoptive Treg therapy include difficulties isolating homogeneous cell populations and developing expansion protocols that result in adequate numbers of cells that remain stable, even under inflammatory conditions. We investigated the potential of discarded human thymuses, routinely removed during pediatric cardiac surgery, to be used as a novel source of therapeutic Tregs. Here, we show that large numbers of FOXP3(+) Tregs can be isolated and expanded from a single thymus. Expanded thymic Tregs had stable FOXP3 expression and long telomeres, and suppressed proliferation and cytokine production of activated allogeneic T cells in vitro. Moreover, expanded thymic Tregs delayed development of xenogeneic GVHD in vivo more effectively than expanded Tregs isolated based on CD25 expression from peripheral blood. Importantly, in contrast to expanded blood Tregs, expanded thymic Tregs remained stable under inflammatory conditions. Our results demonstrate that discarded pediatric thymuses are an excellent source of therapeutic Tregs, having the potential to overcome limitations currently hindering the use of Tregs derived from peripheral or cord blood.

Changing guards: time to move beyond body mass index for population monitoring of excess adiposity.

With the obesity epidemic, and the effects of aging populations, human phenotypes have changed over two generations, possibly more dramatically than in other species previously. As obesity is an important and growing hazard for population health, we recommend a systematic evaluation of the optimal measure(s) for population-level excess body fat. Ideal measure(s) for monitoring body composition and obesity should be simple, as accurate and sensitive as possible, and provide good categorization of related health risks. Combinations of anthropometric markers or predictive equations may facilitate better use of anthropometric data than single measures to estimate body composition for populations. Here, we provide new evidence that increasing proportions of aging populations are at high health-risk according to waist circumference, but not body mass index (BMI), so continued use of BMI as the principal population-level measure substantially underestimates the health-burden from excess adiposity.

Trends in child and adolescent obesity prevalence in economically advanced countries according to socioeconomic position: a systematic review.

Recent obesity trends in children and adolescents suggest a plateau. However, it is unclear whether such trends have been experienced across socioeconomic groups. We analysed whether recent trends in child and adolescent overweight and obesity differ by socioeconomic position (SEP) across economically advanced countries. Eligible studies reported overweight and obesity prevalence in children and/or adolescents (2-18 years), for at least two time points since 1990, stratified by SEP. Socioeconomic differences in trends in child and adolescent overweight and obesity over time were analysed. Differences in trends between SEP groups were observed across a majority of studies. Over half the studies indicated increasing prevalence among low SEP children and adolescents compared to a third of studies among children and adolescents with a high SEP. Around half the studies indicated widening socioeconomic inequalities in overweight and obesity. Since 2000 a majority of studies demonstrated no change or a decrease in prevalence among both high and low SEP groups. However around 40% of studies indicated widening of socioeconomic inequalities post-2000. While our study provides grounds for optimism, socioeconomic inequalities in overweight and obesity continue to widen. These findings highlight the need for greater consideration of different population groups when implementing obesity interventions.