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

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

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

Genetic Basis of Severe Childhood-Onset Cardiomyopathies.

BACKGROUND: Childhood cardiomyopathies are progressive and often lethal disorders, forming the most common cause of heart failure in children. Despite severe outcomes, their genetic background is still poorly characterized. OBJECTIVES: The purpose of this study was to characterize the genetics of severe childhood cardiomyopathies in a countrywide cohort. METHODS: The authors collected a countrywide cohort, KidCMP, of 66 severe childhood cardiomyopathies from the sole center in Finland performing cardiac transplantation. For genetic diagnosis, next-generation sequencing and subsequent validation using genetic, cell biology, and computational approaches were used. RESULTS: The KidCMP cohort presents remarkable early-onset and severe disorders: the median age of diagnosis was 0.33 years, and 17 patients underwent cardiac transplantation. The authors identified the pathogenic variants in 39% of patients: 46% de novo, 34% recessive, and 20% dominantly-inherited. The authors report NRAP underlying childhood dilated cardiomyopathy, as well as novel phenotypes for known heart disease genes. Some genetic diagnoses have immediate implications for treatment: CALM1 with life-threatening arrhythmias, and TAZ with good cardiac prognosis. The disease genes converge on metabolic causes (PRKAG2, MRPL44, AARS2, HADHB, DNAJC19, PPA2, TAZ, BAG3), MAPK pathways (HRAS, PTPN11, RAF1, TAB2), development (NEK8 and TBX20), calcium signaling (JPH2, CALM1, CACNA1C), and the sarcomeric contraction cycle (TNNC1, TNNI3, ACTC1, MYH7, NRAP). CONCLUSIONS: Childhood cardiomyopathies are typically caused by rare, family-specific mutations, most commonly de novo, indicating that next-generation sequencing of trios is the approach of choice in their diagnosis. Genetic diagnoses may suggest intervention strategies and predict prognosis, offering valuable tools for prioritization of patients for transplantation versus conservative treatment

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

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