Evaluation of T1 relaxation time in prostate cancer and benign prostate tissue using a Modified Look-Locker inversion recovery sequence

Purpose of this study was to evaluate the diagnostic performance of T1 relaxation time (T1) for differentiating prostate cancer (PCa) from benign tissue as well as high- from low-grade PCa. Twenty-three patients with suspicion for PCa were included in this prospective study. 3 T MRI including a Modified Look-Locker inversion recovery sequence was acquired. Subsequent targeted and systematic prostate biopsy served as a reference standard. T1 and apparent diffusion coefficient (ADC) value in PCa and reference regions without malignancy as well as high- and low-grade PCa were compared using the Mann-Whitney U test. The performance of T1, ADC value, and a combination of both to differentiate PCa and reference regions was assessed by receiver operating characteristic (ROC) analysis. T1 and ADC value were lower in PCa compared to reference regions in the peripheral and transition zone (p < 0.001). ROC analysis revealed high AUCs for T1 (0.92; 95%-CI, 0.87-0.98) and ADC value (0.97; 95%-CI, 0.94 to 1.0) when differentiating PCa and reference regions. A combination of T1 and ADC value yielded an even higher AUC. The difference was statistically significant comparing it to the AUC for ADC value alone (p = 0.02). No significant differences were found between high- and low-grade PCa for T1 (p = 0.31) and ADC value (p = 0.8). T1 relaxation time differs significantly between PCa and benign prostate tissue with lower T1 in PCa. It could represent an imaging biomarker for PCa

Carbon reservoirs in peatlands and forests in the boreal regions of Finland.

The carbon reservoir of ecosystems was estimated based on field measurements for forests and peatlands on an area in Finland covering 263 000 km2 and extending about 900 km across the boreal zone from south to north. More than two thirds of the reservoir was in peat, and less than ten per cent in trees. Forest ecosystems growing on mineral soils covering 144 000 km2 contained 10–11 kg C m–2 on an average, including both vegetation (3.4 kg C m–2) and soil (uppermost 75 cm; 7.2 kg C m–2). Mire ecosystems covering 65 000 km2 contained an average of 72 kg C m–2 as peat. For the landscape consisting of peatlands, closed and open forests, and inland water, excluding arable and built-up land, a reservoir of 24.6 kg C m–2 was observed. This includes the peat, forest soil and tree biomass. This is an underestimate of the true total reservoir, because there are additional unknown reservoirs in deep soil, lake sediments, woody debris, and ground vegetation. Geographic distributions of the reservoirs were described, analysed and discussed. The highest reservoir, 35–40 kg C m–2, was observed in sub regions in central western and north western Finland. Many estimates given for the boreal carbon reservoirs have been higher than those of ours. Either the Finnish environment contains less carbon per unit area than the rest of the boreal zone, or the global boreal reservoir has earlier been overestimated. In order to reduce uncertainties of the global estimates, statistically representative measurements are needed especially on Russian and Canadian peatlands

Carbon reservoirs in peatlands and forests in the boreal regions of Finland.

The carbon reservoir of ecosystems was estimated based on field measurements for forests and peatlands on an area in Finland covering 263 000 km2 and extending about 900 km across the boreal zone from south to north. More than two thirds of the reservoir was in peat, and less than ten per cent in trees. Forest ecosystems growing on mineral soils covering 144 000 km2 contained 10–11 kg C m–2 on an average, including both vegetation (3.4 kg C m–2) and soil (uppermost 75 cm; 7.2 kg C m–2). Mire ecosystems covering 65 000 km2 contained an average of 72 kg C m–2 as peat. For the landscape consisting of peatlands, closed and open forests, and inland water, excluding arable and built-up land, a reservoir of 24.6 kg C m–2 was observed. This includes the peat, forest soil and tree biomass. This is an underestimate of the true total reservoir, because there are additional unknown reservoirs in deep soil, lake sediments, woody debris, and ground vegetation. Geographic distributions of the reservoirs were described, analysed and discussed. The highest reservoir, 35–40 kg C m–2, was observed in sub regions in central western and north western Finland. Many estimates given for the boreal carbon reservoirs have been higher than those of ours. Either the Finnish environment contains less carbon per unit area than the rest of the boreal zone, or the global boreal reservoir has earlier been overestimated. In order to reduce uncertainties of the global estimates, statistically representative measurements are needed especially on Russian and Canadian peatlands

Contrast agent-free functional magnetic resonance imaging with matrix pencil decomposition to quantify abnormalities in lung perfusion and ventilation in patients with cystic fibrosis

BackgroundPrevious studies showed that contrast-enhanced (CE) morpho-functional magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in patients with cystic fibrosis (CF). Novel matrix pencil decomposition MRI (MP-MRI) enables quantification of lung perfusion and ventilation without intravenous contrast agent administration.ObjectivesTo compare MP-MRI with established morpho-functional MRI and spirometry in patients with CF.MethodsThirty-nine clinically stable patients with CF (mean age 21.6 ± 10.7 years, range 8–45 years) prospectively underwent morpho-functional MRI including CE perfusion MRI, MP-MRI and spirometry. Two blinded chest radiologists assessed morpho-functional MRI and MP-MRI employing the validated chest MRI score. In addition, MP-MRI data were processed by automated software calculating perfusion defect percentage (QDP) and ventilation defect percentage (VDP).ResultsMP perfusion score and QDP correlated strongly with the CE perfusion score (both r = 0.81; p &lt; 0.01). MP ventilation score and VDP showed strong inverse correlations with percent predicted FEV1 (r = −0.75 and r = −0.83; p &lt; 0.01). The comparison of visual and automated parameters showed that both MP perfusion score and QDP, and MP ventilation score and VDP were strongly correlated (r = 0.74 and r = 0.78; both p &lt; 0.01). Further, the MP perfusion score and MP ventilation score, as well as QDP and VDP were strongly correlated (r = 0.88 and r = 0.86; both p &lt; 0.01).ConclusionMP-MRI detects abnormalities in lung perfusion and ventilation in patients with CF without intravenous or inhaled contrast agent application, and correlates strongly with the well-established CE perfusion MRI score and spirometry. Automated analysis of MP-MRI may serve as quantitative noninvasive outcome measure for diagnostic monitoring and clinical trials

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI &lt;18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school&#x2;aged children and adolescents, we report thinness (BMI &lt;2 SD below the median of the WHO growth reference) and obesity (BMI &gt;2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Evaluation of possible long-term effects of repeated administration of the liver-specific contrast agent gadoxetic acid on the signal intensity in predefined brain areas on unenhanced MRI

Ziel dieser explorativen prospektiven Querschnittstudie war die MRT-gestützte Evaluierung einer möglichen langfristigen Alteration der Signalintensität (SI) in definierten Hirnregionen als Folge der wiederholten Applikation des linear ionischen gadoliniumhaltigen Kontrastmittels Dinatriumgadoxetat, das in der leberspezifischen MRT-Diagnostik Anwendung findet. Zu diesem Zweck erhielten ausgewählte Probanden einer Studiengruppe (A, n = 91) sowie einer Kontrollgruppe (B, n = 52) eine cMRT-Untersuchung in nativer T1w-SE-Sequenz (1,5 T). Die Patienten der Studiengruppe hatten Gadoxetat jeweils zwischen 1- bis 37-mal erhalten, wobei die Applikation anderer linearer oder mehr als 2 Dosen makrozyklischer MRT-Kontrastmedien in der Vergangenheit als Ausschlusskriterien galten. (Die Studienkohorte A wurde, entsprechend der Anzahl bereits erfolgter Gadoxetat-Anwendungen, in 3 annähernd gleich viele Individuen umfassende Untergruppen gegliedert: A1 10.) Die Kontrollgruppe B beschränkte sich ausschließlich auf Personen ohne jeglichen vorherigen MRT-Kontrastmittel-Kontakt. Die gewonnenen Bilddaten wurden in der Folge einer quantitativen Analyse unterzogen. Untersucht wurden die Indexregionen Nucleus dentatus (DN) und Globus pallidus (GP) in Relation zu den neutralen Referenzregionen Kleinhirnstiel (MCP), Pons (P) und Thalamus (Th). Die Erhebung der aus den Signalintensitäten dieser Areale gebildeten Quotienten (SI-Ratios) diente als Vergleichsgrundlage zwischen den Patientengruppen. Die Ergebnisse der ermittelten SI-Quotienten aus DN/MCP und DN/P zeigten signifikante Abweichungen zwischen den Probanden der Kontrollgruppe (B) und denjenigen Teilnehmern der Studiengruppe, die bereits zwischen 11 und 37 Standarddosen Gadoxetat erhalten hatten (A3). Patienten mit weniger als 5 (A1) bzw. weniger als 11 (A2) Kontrastmittel-Gaben wiesen hingegen keine statistisch bedeutsamen Unterschiede zu Testpersonen der Kontrollgruppe auf. Die Quotienten aus GP/Th waren bei der Gesamtheit der Studienpatienten im Vergleich zur Kontrollgruppe ebenfalls relevant erhöht; es ergab sich jedoch keine signifikante Assoziation dieses Parameters zur applizierten Gesamtdosis. Stattdessen ließ sich eine Altersabhängigkeit der Signalintensität des GP detektieren, die damit einen relevanten Confounder darstellte. Die erhobenen Daten lassen eine signifikante positive Korrelation zwischen der Anzahl erfolgter Gadoxetat-Applikationen und SI-Erhöhungen des Nucleus dentatus in der nativen T1w-MRT-Sequenz erkennen; dies kann, nach dem gegenwärtigen Stand der Forschung, möglicherweise mit einer längerfristigen zerebralen Gadolinium-Retention infolge der Kontrastmittel-Gabe in Zusammenhang gebracht werden. Im Vergleich zu anderen marktüblichen linearen Präparaten fällt der Effekt der T1-Verkürzung jedoch deutlich subtiler aus und wird erst nach höherer kumulativer Dosis statistisch relevant.The aim of this exploratory cross-sectional study with prospective design was the MRI-based evaluation of potential long-term alterations of signal intensity (SI) in predefined brain areas after repeated administration of the linear ionic gadolinium-based contrast agent (GBCA) gadoxetic acid, used in liver-specific MRI. Participants belonging to a study group (A, n = 91) and a control group (B, n = 52) underwent unenhanced MRI examinations of the brain using a T1-weighted Spin-Echo pulse sequence at 1.5 T. Patients in the study group had previously received from 1 to 37 doses of gadoxetic acid; exclusion criteria included past exposure to other linear MRI contrast agents or more than 2 doses of macrocyclic MRI contrast agents. (Study group A was divided into 3 subgroups according to the number of previous gadoxetic-acid enhanced examinations, each with a nearly equal number of subjects: A1 < 5, A2 5 to 10, A3 > 10.) Control group B was limited to patients who had never been given GBCA of any sort. Quantitative analysis of the image data was performed. We examined the index regions dentate nucleus (DN) and globus pallidus (GP) in relation to the neutral reference regions of the middle cerebellar peduncle (MCP), the pons (P), and the thalamus (Th). The signal intensity (SI) of each of these areas was measured, and the resulting ratios (SI ratios) served as a basis for comparison between the patient groups. SI ratios for DN/MCP and DN/P were significantly different between control subjects (B) and those patients in the study group who had previously received anywhere from 11 to 37 gadoxetic acid administrations (A3). Groups of patients with fewer than 5 (A1) or fewer than 11 (A2) gadoxetic acid administrations showed no such statistically relevant differences. GT/Th ratios differed significantly between the study group in its entirety (A) and the control group (B), whereas no significant dose dependency on gadoxetic acid was found. Instead, for the GP signal intensity we detected a significant dependency on age that might have acted as a confounding factor. Results show a significant positive correlation between the number of gadoxetic acid administrations and the increase of SI in the cerebellar region of the DN in unenhanced T1-weighted MRI images. Current research indicates that this correlation might be due to long-term gadolinium retention following the repeated application of this linear ionic contrast agent. In comparison to other commercially available linear GBCAs, however, the effect of T1 shortening is considerably subtler and becomes statistically relevant only after high cumulative doses

Cirrhosis is associated with lower serological responses to COVID-19 vaccines in patients with chronic liver disease

Background &amp; Aims: The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among patients with CLD of different aetiologies and disease stages. Methods: A total of 357 patients were recruited in clinical centres from six European countries, and 132 healthy volunteers served as controls. Serum IgG (nM), IgM (nM), and neutralising antibodies (%) against the Wuhan-Hu-1, B.1.617, and B.1.1.529 SARS-CoV-2 spike proteins were determined before vaccination (T0) and 14 days (T2) and 6 months (T3) after the second-dose vaccination. Patients fulfilling inclusion criteria at T2 (n = 212) were stratified into ‘low’ or ‘high’ responders according to IgG levels. Infection rates and severity were collected throughout the study. Results: Wuhan-Hu-1 IgG, IgM, and neutralisation levels significantly increased from T0 to T2 in patients vaccinated with BNT162b2 (70.3%), mRNA-1273 (18.9%), or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis, and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted ‘low’ humoral response, whereas viral hepatitis and antiviral therapy predicted ‘high’ humoral response. Compared with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, patients with CLD presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-CoV-2 infection rates or vaccine efficacy. Conclusions: Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease aetiology. The type of vaccine leads to different antibody responses that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. Impact and Implications: In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis, and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a ‘lower’ humoral response, whereas viral hepatitis aetiology and prior antiviral therapy predict a ‘higher’ humoral response. This differential response appears not to associate with SARS-CoV-2 infection incidence or vaccine efficacy. However, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritised for receiving booster doses and/or recently approved adapted vaccines

Cirrhosis is associated with lower serological responses to COVID-19 vaccines in patients with chronic liver disease

Background & Aims: The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among patients with CLD of different aetiologies and disease stages. Methods: A total of 357 patients were recruited in clinical centres from six European countries, and 132 healthy volunteers served as controls. Serum IgG (nM), IgM (nM), and neutralising antibodies (%) against the Wuhan-Hu-1, B.1.617, and B.1.1.529 SARS-CoV-2 spike proteins were determined before vaccination (T0) and 14 days (T2) and 6 months (T3) after the second-dose vaccination. Patients fulfilling inclusion criteria at T2 (n = 212) were stratified into ‘low’ or ‘high’ responders according to IgG levels. Infection rates and severity were collected throughout the study. Results: Wuhan-Hu-1 IgG, IgM, and neutralisation levels significantly increased from T0 to T2 in patients vaccinated with BNT162b2 (70.3%), mRNA-1273 (18.9%), or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis, and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted ‘low’ humoral response, whereas viral hepatitis and antiviral therapy predicted ‘high’ humoral response. Compared with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, patients with CLD presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-CoV-2 infection rates or vaccine efficacy. Conclusions: Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease aetiology. The type of vaccine leads to different antibody responses that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. Impact and Implications: In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis, and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a ‘lower’ humoral response, whereas viral hepatitis aetiology and prior antiviral therapy predict a ‘higher’ humoral response. This differential response appears not to associate with SARS-CoV-2 infection incidence or vaccine efficacy. However, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritised for receiving booster doses and/or recently approved adapted vaccines.SCOPUS: ar.jinfo:eu-repo/semantics/publishe