Notes

Antitumor task involving fucoidan versus calm big T mobile lymphoma within vitro along with vivo.
Primary sclerosing cholangitis (PSC) is a progressive liver disease characterised by fluctuating liver biochemistries and highly variable disease progression. The Enhanced Liver Fibrosis (ELF®) test and liver stiffness measurements (LSMs) reflect fibrosis and predict clinical outcomes in PSC; however, longitudinal assessments are missing. We aimed to characterise the systematic change in ELF and LSM over time in a prospective cohort of patients with PSC, along with their longitudinal relationship to alkaline phosphatase (ALP) and bilirubin.

We included 113 non-transplant PSC patients (86 males [76.1%]; mean age 43.3 ± 15.7 years) with annual study visits between 2013 and 2019 at 2 Norwegian centres. ELF test, LSM, clinical data, liver biochemistries, and revised Mayo risk score were measured. We used linear mixed-effects models to estimate change over time, intraclass correlations (ICCs), and their relationship with ALP and bilirubin.

At baseline, the median (range) ELF test was 9.3 (7.5-12.9) and mediaect differing abilities to discriminate risk.
Primary sclerosing cholangitis (PSC) is characterised by substantial disease variability between patients and fluctuating liver biochemistries. Hence, new biomarkers are needed to identify individuals with an increased risk of developing end-stage liver disease. We explore the change over time of 2 putative prognostic biomarkers in PSC, the serum Enhanced Liver Fibrosis (ELF®) test and LSMs by ultrasound, demonstrating differences that may reflect differing abilities to discriminate risk.
Socioeconomic status and ethnicity are not incorporated as predictors in country-level cardiovascular risk charts on mainland Europe. Epacadostat IDO inhibitor The aim of this study was to quantify the sex-specific cardiovascular death rates stratified by ethnicity and socioeconomic factors in an urban population in a universal healthcare system.

Age-standardized death rates (ASDR) were estimated in a dynamic population, aged 45-75 in the city of The Hague, the Netherlands, over the period 2007-2018, using data of Statistics Netherlands. Results were stratified by sex, ethnicity (country of birth) and socioeconomic status (prosperity) and compared with a European cut-off for high-risk countries (ASDR men 225/100,000 and women 175/100,000).

In total, 3073 CVD deaths occurred during 1·76 million person years follow-up. Estimated ASDRs (selected countries of birth) ranged from 126 (95%CI 89-174) in Moroccan men to 379 (95%CI 272-518) in Antillean men, and from 86 (95%CI 50-138) in Moroccan women to 170 (95%CI 142-202) in Surinamese women. ASDRs in the highest and lowest prosperity quintiles were 94 (95%CI 90-98) and 343 (95%CI 334-351) for men, and 43 (95%CI 41-46) and 140 (95%CI 135-145), for women, respectively.

In a diverse urban population, large health disparities in cardiovascular ASDRs exists across ethnic and socioeconomic subgroups. Identifying these high-risk subgroups followed by targeted preventive efforts, might provide a basis for improving cardiovascular health equity within communities. Instead of classifying countries as high-risk or low-risk, a shift towards focusing on these subgroups within countries might be needed.

Leiden University Medical Center and Leiden University.
Leiden University Medical Center and Leiden University.
Psychological complications are frequent in type 1 diabetes (T1D) but they might be difficult to distinguish one from the other in clinical practice. Our objective was to study the distinguishing characteristics, overlaps and their use in the literature between three concepts of T1D depression, diabetes distress (DD) and diabetes burnout (DB).

A scoping review (PRISMA guidelines) performed in three databases (PubMed/MEDLINE, PsycInfo, Web of Science) with the keywords T1D, depression, diabetes and burnout, from January 1990 to June 2021. We selected original studies with participants with T1D, which reported depression, DD, or DB. We extracted information about the concepts, their sub-concepts and screening tools.

Of the 4763 studies identified, 201 studies were included in the study. Seventy-three percent, 57% and 45% of sub-concepts do not overlap in depression, DD, and DB, respectively. We observed overlap between depression (27%)/DD (27%) and between DD (20%)/DB (50%).

A number of sub-concepts distinguish depression and DD. Overlaps between concepts suggest that a more precise definition is still lacking. DB is still a relatively new concept and more research is needed to better understand how it can present itself differently, in order to personalize care in comparison to those having DD.
A number of sub-concepts distinguish depression and DD. Overlaps between concepts suggest that a more precise definition is still lacking. DB is still a relatively new concept and more research is needed to better understand how it can present itself differently, in order to personalize care in comparison to those having DD.
Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia.

We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients.

Of 94 clinical features tested, 46 were retained for clustering. Cluster 1 patients (
=498; 92% labeled MIS-C) were mostly previously healthy (71%), with mean age 7·2±0·4 years, predominant cardiovascular (77%) and/or mucocutaneous (82%) involvement, high inflammatory biomarkers, and mostly SARS-CoV-2 PCR negative (60%). Cluster 2 patients (
=445; 27% labeled MIS-C) frequently had pre-existing conditions (79%, with 39%severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C.
Chagas disease (caused by
infection) evolves to chronic chagasic cardiomyopathy (CCC) affecting 1.8 million people worldwide. This is the first randomized, placebo-controlled, double-blinded, clinical trial designed to estimate efficacy and safety of selenium (Se) treatment in CCC.

66 patients with CCC stages B1 (left ventricular ejection fraction [LVEF] > 45% and no heart failure;
=54) or B2 (LVEF < 45% and no heart failure;
=12) were randomly assigned to receive 100 mcg/day sodium selenite (
=32) or placebo (
=34) for one year (study period May 2014-September 2018). LVEF changes over time and adverse effects were investigated. Trial registration number NCT00875173 (clinicaltrials.gov).

No significant differences between the two groups were observed for the primary outcome mean LVEF after 6 (β
+1.1
=0.51 for
) and 12 months (β
+2.1;
=0.23). In a subgroup analysis, statistically significant longitudinal changes were observed for mean LVEF in the stage B2 subgroup (β= +10.1;
=0.02 for
[
=4]
[
=8]). Se treatment was safe for CCC patients, and the few adverse effects observed were similarly distributed across the two groups.

Se treatment did not improve cardiac function (evaluated from LVEF) in CCC. However, in the subgroup of patients at B2 stage, a potential beneficial influence of Se was observed. Complementary studies are necessary to explore diverse Se dose and/or associations in different CCC stages (B2 and C), as well as in A and B1 stages with longer follow-up.

Brazilian Ministry of Health, Fiocruz, CNPq, FAPERJ.
Brazilian Ministry of Health, Fiocruz, CNPq, FAPERJ.
Visually impaired older adults have a greater risk of falling, making them particularly susceptible to fall-related health consequences and restricted physical activity. Unclear however, is the relationship between having falls and longitudinal changes in daily patterns of objectively measured physical activity in older adults with visual impairments.

We created a three-year prospective cohort study (Falls in Glaucoma Study) of older adults with primary or suspected glaucoma at the Johns Hopkins Wilmer Eye Institute from 2013 to 2015. Cumulative incidence of falls was determined through self-reported fall calendars over 12 months. Participants were then classified into one of three groups multiple fallers (≥2 falls), single fallers (1 fall), and non-fallers (0). Daily physical activity was measured over 1 week using a waist-bound accelerometer during baseline and three-year follow-ups. Activity fragmentation was defined as the reciprocal of the mean activity bout length, with higher fragmentation reflectin with visual impairment, multiple falls over 12 months were associated with more transient and fragmented activity over a subsequent three-year period, and activity declines during evening hours, compared to non-fallers. These findings suggest that multiple fallers with visual impairment may be at high risk for a decline in physical capacity and endurance, warranting clinical interventions.

The research was supported in part by National Institutes of Health Grant EY022976.
The research was supported in part by National Institutes of Health Grant EY022976.
Real-world clinical data to support the use of casirivimab-imdevimab for the treatment of outpatients with mild to moderate coronavirus disease-19 (COVID-19) is needed. This study aimed to assess the outcomes of casirivimab-imdevimab treatment of mild to moderate COVID-19.

A retrospective cohort of 696 patients who received casirivimab-imdevimab between December 4, 2020 and April 9, 2021 was compared to a propensity-matched control of 696 untreated patients with mild to moderate COVID-19 at Mayo Clinic sites in Arizona, Florida, Minnesota, and Wisconsin. Primary outcome was rate of hospitalization at days 14, 21 and 28 after infusion.

The median age of the antibody-treated cohort was 63 years (interquartile range, 52-71); 45·5% were ≥65 years old; 51.4% were female. High-risk characteristics were hypertension (52.4%), body mass index ≥35 (31.0%), diabetes mellitus (24.6%), chronic lung disease (22.1%), chronic renal disease (11.4%), congestive heart failure (6.6%), and compromised immune function (6.7%). Compared to the propensity-matched untreated control, patients who received casirivimab-imdevimab had significantly lower all-cause hospitalization rates at day 14 (1.3% vs 3.3%; Absolute Difference 2.0%; 95% confidence interval (CI) 0.5-3.7%), day 21 (1.3% vs 4.2%; Absolute Difference 2.9%; 95% CI 1.2-4.7%), and day 28 (1.6% vs 4.8%; Absolute Difference 3.2%; 95% CI 1.4-5.1%). Rates of intensive care unit admission and mortality at days 14, 21 and 28 were similarly low for antibody-treated and untreated groups.

Among high-risk patients with mild to moderate COVID-19, casirivimab-imdevimab treatment was associated with a significantly lower rate of hospitalization.

Mayo Clinic.
Mayo Clinic.At the initial stage of carcinogenesis, cell competition often occurs between newly emerging transformed cells and the neighboring normal cells, leading to the elimination of transformed cells from the epithelial layer. For instance, when RasV12-transformed cells are surrounded by normal cells, RasV12 cells are apically extruded from the epithelium. However, the underlying mechanisms of this tumor-suppressive process still remain enigmatic. We first show by electron microscopic analysis that characteristic finger-like membrane protrusions are projected from both normal and RasV12 cells at their interface. In addition, FBP17, a member of the F-BAR proteins, accumulates in RasV12 cells, as well as surrounding normal cells, which plays a positive role in the formation of finger-like protrusions and apical elimination of RasV12 cells. Furthermore, cdc42 acts upstream of these processes. These results suggest that the cdc42/FBP17 pathway is a crucial trigger of cell competition, inducing "protrusion to protrusion response" between normal and RasV12-transformed cells.
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