Severe COVID-19 infection results in significant immune dysregulation resulting from excessive recruitment and activation of neutrophils. The aim of this study was to confirm feasibility, initial ...safety and detect signal of efficacy of a non-propriety device delivered using an intermittent extra-corporeal system (LMOD) allowing leucocytes modulation in the setting of Severe COVID-19 infection. Twelve patients were recruited. Inclusion criteria were > 18 years age, confirmed COVID-19, acute respiratory distress syndrome requiring mechanical support and hypotension requiring vasopressor support. Primary end point was vasopressor requirements (expressed as epinephrine dose equivalents) and principle secondary endpoints related to safety, ability to deliver the therapy and markers of inflammation assessed over five days after treatment initiation. LMOD treatment appeared safe, defined by hemodynamic stability and no evidence of white cell number depletion from blood. We demonstrated a significant decrease in vasopressor doses (-37%, p = 0.02) in patients receiving LMOD therapy (despite these patients having to tolerate an additional extracorporeal intermittent therapy). Vasopressor requirements unchanged/increasing in control group (+ 10%, p = 0.48). Although much about the use of this therapy in the setting of severe COVID-19 infection remains to be defined (e.g. optimal dose and duration), this preliminary study supports the further evaluation of this novel extracorporeal approach.
Background
Sodium-23 magnetic resonance imaging (
23
Na MRI) allows non-invasive assessment of tissue sodium concentration (Na
+
). Age and chronic kidney disease (CKD) are associated with increased ...tissue Na
+
in adults, but limited information is available pertaining to children and adolescents. We hypothesized that pediatric CKD is associated with altered tissue Na
+
compared to healthy controls.
Methods
This was a case–control exploratory study on healthy children and adults and pediatric CKD patients. Study participants underwent an investigational visit, blood/urine biochemistry, and leg
23
Na MRI for tissue Na
+
quantification (whole leg, skin, soleus muscle). CKD was stratified by etiology and patients’ tissue Na
+
was compared against healthy controls by computing individual Z-scores. An absolute Z-score > 1.96 was deemed to deviate significantly from the mean of healthy controls. Pearson correlation was used to compute the associations between tissue Na
+
and kidney function.
Results
A total of 36 pediatric participants (17 healthy, 19 CKD) and 19 healthy adults completed the study. Healthy adults had significantly higher tissue Na
+
compared with pediatric groups; conversely, no significant differences were found between healthy children/adolescents and CKD patients. Four patients with glomerular disease and one kidney transplant recipient due to atypical hemolytic-uremic syndrome had elevated whole-leg Na
+
Z-scores. Reduced whole-leg Na
+
Z-scores were found in two patients with tubular disorders (Fanconi syndrome, proximal–distal renal tubular acidosis). All tissue Na
+
measures were significantly associated with proteinuria and hypoalbuminemia.
Conclusions
Depending on etiology, pediatric CKD was associated with either increased (glomerular disease) or reduced (tubular disorders) tissue Na
+
compared with healthy controls.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
.
Aims
To investigate high‐risk sociodemographic and environmental determinants of health (SEDH) potentially associated with adult obesity in counties in the United States using machine‐learning ...techniques.
Materials and Methods
We performed a cross‐sectional analysis of county‐level adult obesity prevalence (body mass index ≥30 kg/m2) in the United States using data from the Diabetes Surveillance System 2017. We harvested 49 county‐level SEDH factors that were used in a classification and regression trees (CART) model to identify county‐level clusters. The CART model was validated using a ‘hold‐out’ set of counties and variable importance was evaluated using Random Forest.
Results
Overall, we analysed 2752 counties in the United States, identifying a national median (interquartile range) obesity prevalence of 34.1% (30.2%, 37.7%). The CART method identified 11 clusters with a 60.8% relative increase in prevalence across the spectrum. Additionally, seven key SEDH variables were identified by CART to guide the categorization of clusters, including Physically Inactive (%), Diabetes (%), Severe Housing Problems (%), Food Insecurity (%), Uninsured (%), Population over 65 years (%) and Non‐Hispanic Black (%).
Conclusion
There is significant county‐level geographical variation in obesity prevalence in the United States, which can in part be explained by complex SEDH factors. The use of machine‐learning techniques to analyse these factors can provide valuable insights into the importance of these upstream determinants of obesity and, therefore, aid in the development of geo‐specific strategic interventions and optimize resource allocation to help battle the obesity pandemic.
Preclinical data suggest sodium deposited (without water) in tissues may lead to aberrant remodeling and systemic inflammation, independently of fluid overload in patients with heart failure (HF). ...Tissue salt storage can be measured noninvasively and quantitatively with
Na-magnetic resonance imaging. We aimed to investigate the possibility that patients with HF complicated by renal dysfunction are subject to higher tissue sodium concentration exposure than patients with chronic kidney disease alone.
We conducted an exploratory study including 18 patients with HF, 34 hemodialysis patients (with no meaningful renal clearance of sodium), and 31 patients with chronic kidney disease, with glomerular filtration rate matched to the patients with HF. Every patient underwent
Na-magnetic resonance imaging of the calf, to quantify tissue sodium and allow comparison among the 3 patient groups.
There were no differences in age, sex, and body mass index between groups. Median (interquartile range) skin sodium content in HF (31 23-37 mmol/L) was very high and indistinguishable from skin sodium content in hemodialysis patients (30 22-35 mmol/L),
=0.6. Patients with HF exhibited significantly higher skin sodium content than matched estimated glomerular filtration rate chronic kidney disease patients (22 19-26 mmol/L),
=0.005. Median muscle sodium content in patients with HF was significantly higher than in patients with chronic kidney disease,
=0.002. There was no relationship with estimated glomerular filtration rate in patients with HF. We report a significant correlation between skin sodium and urinary sodium (
=0.04) but no correlation with muscle sodium. Patients who were assessed as being volume depleted (sodium excretion fraction <1%) had lower skin sodium content than patients with sodium excretion fraction >1% (
=0.03).
We have demonstrated that patients with HF characteristically have very high levels of skin sodium storage, comparable to well-characterized extreme levels seen in patients with end-stage kidney disease requiring hemodialysis.
Na-magnetic resonance imaging may allow precision medicine in the management of this challenging group of patients with HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03004547.
Summary
Secretory immunoglobulin A (SIgA) antibodies play an important role in protecting the mucosal surfaces against pathogens and maintaining homeostasis with the commensal microbiota. Because a ...substantial portion of the gut microbiota is coated with SIgA, we hypothesized that microbiota–SIgA complexes are important for the maintenance of gut homeostasis. Here we investigated the relationship between microbiota–SIgA complexes and inflammatory epithelial cell responses. We used a multi‐cellular three‐dimensional (3D) organotypical model of the human intestinal mucosa composed of an intestinal epithelial cell line and primary human lymphocytes/monocytes, endothelial cells and fibroblasts. We also used human SIgA from human colostrum, and a prominent bacterial member of the first colonizers, Escherichia coli, as a surrogate commensal. We found that free and microbiota‐complexed SIgA triggered different epithelial responses. While free SIgA up‐regulated mucus production, expression of polymeric immunoglobulin receptor (pIgR) and secretion of interleukin‐8 and tumoir necrosis factor‐α, microbiota‐complexed SIgA mitigated these responses. These results suggest that free and complexed SIgA have different functions as immunoregulatory agents in the gut and that an imbalance between the two may affect gut homeostasis.
ABSTRACT
Background
Sodium-23 magnetic resonance imaging (23Na MRI) allows the measurement of skin sodium concentration (Na+). In patients requiring dialysis, no data are available relating to the ...clinical outcomes associated with skin sodium accumulation or the determinants of increasing deposition.
Methods
This was an exploratory, observational study of adult hemodialysis (HD) and peritoneal dialysis (PD) patients. Participants underwent skin Na+ quantification with leg 23Na MRI at the study’s beginning. Outcomes of interest were all-cause mortality and composite all-cause mortality plus major adverse cardiovascular events. Cumulative total and event-free survival were assessed using the Kaplan–Meier survival function after stratification into skin Na+ quartiles. Cox proportional hazards regression was used to model the association between skin Na+ and outcomes of interest. Multiple linear regression was used to model the predictors of skin Na+.
Results
A total of 52 participants (42 HD and 10 PD) underwent the study procedures. The median follow-up was 529 days (interquartile range: 353–602). Increasing skin Na+ quartiles were associated with significantly shorter overall and event-free survival (log-rank χ2(1) = 3.926, log-rank χ2(1) = 5.685; P for trend <0.05 in both instances). Skin Na+ was associated with all-cause mortality {hazard ratio (HR) 4.013, 95% confidence interval (95% CI) 1.988–8.101; P < 0.001} and composite events HR 2.332 (95% CI 1.378–3.945); P < 0.01, independently of age, sex, serum Na+ and albumin. In multiple regression models, dialysate Na+, serum albumin and congestive heart failure were significantly associated with skin Na+ in HD patients (R2adj = 0.62).
Conclusions
Higher skin Na+ was associated with worse clinical outcomes in dialysis patients and may represent a direct therapeutic target.
Graphical Abstract
Graphical Abstract
Fine particulate matter <2.5 microns (PM2.5) is the most studied air pollutant. Both short- and long-term exposure to PM2.5 have been linked to cardiovascular disease (CVD). Studies evaluating air ...pollution in South America are scarce. Therefore, the impact of exposure to PM2.5, household air pollution (HAP), and ambient air pollution (AAP) on CVD mortality and CVD disability-adjusted life years (DALYs) in South American countries from 1990 to 2019 was explored.
The Global Burden of Disease initiative exposure-response function was used to analyze the total PM2.5, ambient PM2.5, and household PM2.5-related CVD deaths and DALYs rates, per 100,000 individuals, in 12 South American countries between 1990 and 2019. The relative change in burden was also assessed by comparing the 1990–1994 to 2015–2019 periods.
In 2019, 70,668 deaths and 1,736,414 DALYs due to CVD were attributed to total PM2.5 exposure in South America. Substantial regional heterogeneity was observed concerning the absolute change in PM2.5 concentration levels comparing 1990 to 2019. All South American countries observed a relative decline in CVD deaths and DALYs comparing the 1990–1994 to 2015–2019 periods. No country was able to reach the current World Health Organization 5 μg/m3 recommended limit in 2019. Predominantly, AAP was the greatest contributor to the CVD burden.
Air pollution substantially impacted CVD in South America; however, this impact was heterogenous, and the relative reduction of HAP and AAP burden was also not uniform. Recognizing PM2.5 importance is key for developing target population and individual-level interventions, which could ultimately alleviate its burden.
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We conducted a survey to investigate to what extent the fear of COVID-19 has influenced the patients decision to undergo or to cancel endoscopic procedures. We collected data from 847 patients from ...13 centres. The main indication for endoscopy was anemia, followed by pain and unexplained weight loss. The percentage of not presenters progressively increased throughout the three weeks of study, from 15.1% at the beginning to 48.2% at the end. 37 (34.2%) upper GI endoscopies and 112 (56.3 %) colonoscopies showed an organic cause explaining the symptoms presented by the patients, respectively; 5 cases of gastric cancer (4.6%) and 16 cases of colorectal cancer (CRC) (6.0%), respectively, were detected; during the second week the percentage of organic diseases found at upper endoscopy was 19 (33.3%) with 5 cancer (8.7%), and 61 (49.1% ) at colonoscopy, with 2 CRC (1.6%); finally, during the third week the corresponding figures were 19 (48.7%) for upper GI examinations, with 3 gastric cancers (7.7%), and 43 (60.5%) with 4 (6.5%) CRC cases found.We conclude that patients weighted the fear of having a clinically relevant disease with the fear of becoming infected by coronavirus, and a relevant percentage of them (29.4%) decided not to attend the endoscopy suites at the scheduled date.
Abnormalities in cognitive function are almost universal in patients receiving hemodialysis (HD) and are associated with worse quality of life, impaired decision making, increased healthcare ...utilization and mortality. While cognitive impairment in the HD population is increasingly recognized, it is unclear how quickly it develops after starting HD.
This was a cross-sectional study of a cohort of low dialysis vintage HD patients (<12 months). We used the validated Cambridge Brain Science (CBS) battery of web-based tests to evaluate cognition compared to age- and sex matched controls across three cognitive domains: verbal processing, reasoning and short-term memory.
Forty-nine HD patients were included in this study; 43 completed the full battery of tests. The average scores for HD patients were consistently below the age and sex-matched controls. Fifty-five percent of HD patients had cognitive impairment in verbal skills, 43% in reasoning and 18% in short-term memory.
There is a high prevalence of CI evident early after starting HD, with the largest deficits seen in reasoning and verbal processing. These deficits may be attributable to the HD treatment itself. Further studies are needed to characterize the natural history of CI in this patient population and to test interventions aimed at preventing or slowing its progression.
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