Investigating Recovery After Subarachnoid Hemorrhage With the Imaging, Cognition and Outcome of Neuropsychological Functioning After Subarachnoid Hemorrhage (ICONS) Study:Protocol for a Longitudinal, Prospective Cohort Study

Background: A subarachnoid hemorrhage is a hemorrhage in the subarachnoid space that is often caused by the rupture of an aneurysm. Patients who survive a subarachnoid hemorrhage have a high risk of complications and a negative long-term outcome. Objective: The aim of the Imaging, Cognition and Outcome of Neuropsychological functioning after Subarachnoid hemorrhage (ICONS) study is to investigate whether and to what extent deficits exist in multiple domains after subarachnoid hemorrhage, including cognition, emotion and behavior, and to investigate whether brain damage can be detected in patients with subarachnoid hemorrhage. We aim to determine which early measures of cognition, emotion and behavior, and brain damage in the subacute stage play a role in long-term recovery after subarachnoid hemorrhage. Recovery is defined as functioning at a societal participation level, with a focus on resuming and maintaining work, leisure activities, and social relationships over the long term. Methods: The ICONS study is an observational, prospective, single-center cohort study. The study includes patients with subarachnoid hemorrhage admitted to the Neurosurgery Unit of the University Medical Centre Groningen in the Netherlands. The inclusion criteria include diagnosis of an aneurysmal subarachnoid hemorrhage or an angiographically negative subarachnoid hemorrhage, sufficient ability in the Dutch language, and age older than 18 years. Patients will undergo neuropsychological assessment and magnetic resonance imaging 6 months after the subarachnoid hemorrhage. Furthermore, patients will be asked to fill in questionnaires on multiple psychosocial measures and undergo a structured interview at 6 months, 1 year, and 2 years after the subarachnoid hemorrhage. The primary outcome measure of the ICONS study is societal participation 1 year after the subarachnoid hemorrhage, measured with the Dutch version of the Impact on Participation and Autonomy questionnaire. Results: The study was launched in December 2019 and recruitment is expected to continue until June 2023. At the time of the acceptance of this paper, 76 patients and 69 healthy controls have been included. The first results are expected in early 2023. Conclusions: The ICONS study is the first to collect and combine data after subarachnoid hemorrhage in a variety of domains, including cognition, emotion and behavior, and brain damage. The results will contribute to a more comprehensive understanding of the consequences of both aneurysmal subarachnoid hemorrhage and angiographically negative subarachnoid hemorrhage, which may ultimately optimize timely treatment for this patient group by setting realistic and attainable goals to improve daily functioning

Automated multiclass segmentation, quantification, and visualization of the diseased aorta on hybrid PET/CT–SEQUOIA

Background Cardiovascular disease is the most common cause of death worldwide, including infection and inflammation related conditions. Multiple studies have demonstrated potential advantages of hybrid positron emission tomography combined with computed tomography (PET/CT) as an adjunct to current clinical inflammatory and infectious biochemical markers. To quantitatively analyze vascular diseases at PET/CT, robust segmentation of the aorta is necessary. However, manual segmentation is extremely time-consuming and labor-intensive. Purpose To investigate the feasibility and accuracy of an automated tool to segment and quantify multiple parts of the diseased aorta on unenhanced low-dose computed tomography (LDCT) as an anatomical reference for PET-assessed vascular disease. Methods A software pipeline was developed including automated segmentation using a 3D U-Net, calcium scoring, PET uptake quantification, background measurement, radiomics feature extraction, and 2D surface visualization of vessel wall calcium and tracer uptake distribution. To train the 3D U-Net, 352 non-contrast LDCTs from (2-[18F]FDG and Na[18F]F) PET/CTs performed in patients with various vascular pathologies with manual segmentation of the ascending aorta, aortic arch, descending aorta, and abdominal aorta were used. The last 22 consecutive scans were used as a hold-out internal test set. The remaining dataset was randomly split into training (n = 264; 80%) and validation (n = 66; 20%) sets. Further evaluation was performed on an external test set of 49 PET/CTs. The dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to assess segmentation performance. Automatically obtained calcium scores and uptake values were compared with manual scoring obtained using clinical softwares (syngo.via and Affinity Viewer) in six patient images. intraclass correlation coefficients (ICC) were calculated to validate calcium and uptake values. Results Fully automated segmentation of the aorta using a 3D U-Net was feasible in LDCT obtained from PET/CT scans. The external test set yielded a DSC of 0.867 ± 0.030 and HD of 1.0 [0.6–1.4] mm, similar to an open-source model with a DSC of 0.864 ± 0.023 and HD of 1.4 [1.0–1.8] mm. Quantification of calcium and uptake values were in excellent agreement with clinical software (ICC: 1.00 [1.00–1.00] and 0.99 [0.93–1.00] for calcium and uptake values, respectively). Conclusions We present an automated pipeline to segment the ascending aorta, aortic arch, descending aorta, and abdominal aorta on LDCT from PET/CT and to accurately provide uptake values, calcium scores, background measurement, radiomics features, and a 2D visualization. We call this algorithm SEQUOIA (SEgmentation, QUantification, and visualizatiOn of the dIseased Aorta) and is available at https://github.com/UMCG-CVI/SEQUOIA. This model could augment the utility of aortic evaluation at PET/CT studies tremendously, irrespective of the tracer, and potentially provide fast and reliable quantification of cardiovascular diseases in clinical practice, both for primary diagnosis and disease monitoring

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Spectral tuning of white light allows for strong reduction in melatonin suppression without changing illumination level or color temperature

Studies with monochromatic light stimuli have shown that the action spectrum for melatonin suppression exhibits its highest sensitivity at short wavelengths, around 460 to 480 nm. Other studies have demonstrated that filtering out the short wavelengths from white light reduces melatonin suppression. However, this filtering of short wavelengths was generally confounded with reduced light intensity and/or changes in color temperature. Moreover, it changed the appearance from white light to yellow/orange, rendering it unusable for many practical applications. Here, we show that selectively tuning a polychromatic white light spectrum, compensating for the reduction in spectral power between 450 and 500 nm by enhancing power at even shorter wavelengths, can produce greatly different effects on melatonin production, without changes in illuminance or color temperature. On different evenings, 15 participants were exposed to 3 h of white light with either low or high power between 450 and 500 nm, and the effects on salivary melatonin levels and alertness were compared with those during a dim light baseline. Exposure to the spectrum with low power between 450 and 500 nm, but high power at even shorter wavelengths, did not suppress melatonin compared with dim light, despite a large difference in illuminance (175 vs. <5 lux). In contrast, exposure to the spectrum with high power between 450 and 500 nm (also 175 lux) resulted in almost 50% melatonin suppression. For alertness, no significant differences between the 3 conditions were observed. These results open up new opportunities for lighting applications that allow for the use of electrical lighting without disturbance of melatonin production

Higher Free Fatty Acid Uptake in Visceral Than in Abdominal Subcutaneous Fat Tissue in Men

Visceral adipose tissue has been shown to have high lipolytic activity. The aim of this study was to examine whether free fatty acid (FFA) uptake into visceral adipose tissue is enhanced compared to abdominal subcutaneous tissue in vivo. Abdominal adipose tissue FFA uptake was measured using positron emission tomography (PET) and [F-18]-labeled 6-thia-hepta-decanoic acid ([F-18]FTHA) and fat masses using magnetic resonance imaging (MRI) in 18 healthy young adult males. We found that FFA uptake was 30% higher in visceral compared to subcutaneous adipose tissue (0.0025 +/- 0.0018 vs. 0.0020 +/- 0.0016 mu mol/g/min, P = 0.005). Visceral and subcutaneous adipose tissue FFA uptakes were strongly associated with each other (P <0.001). When tissue FFA uptake per gram of fat was multiplied by the total tissue mass, total FFA uptake was almost 1.5 times higher in abdominal subcutaneous than in visceral adipose tissue. In conclusion, we observed enhanced FFA uptake in visceral compared to abdominal subcutaneous adipose tissue and, simultaneously, these metabolic rates were strongly associated with each other. The higher total tissue FFA uptake in subcutaneous than in visceral adipose tissue indicates that although visceral fat is active in extracting FFA, its overall contribution to systemic metabolism is limited in healthy lean males. Our results indicate that subcutaneous, rather than visceral fat storage plays a more direct role in systemic FFA availability. The recognized relationship between abdominal visceral fat mass and metabolic complications may be explained by direct effects of visceral fat on the liver