Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling

Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation - measured as β-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2-negative controls. The higher β-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-methyl-d-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neurotoxic properties. Mechanistically, β-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC

25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients

BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients.METHODS: We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and =15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type.RESULTS: Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04).CONCLUSIONS: Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor

Low documentation of chronic kidney disease among high-risk patients in a managed care population: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Early detection of chronic kidney disease (CKD) is sub-optimal among the general population and among high risk patients. The prevalence and impact of major CKD risk factors, diabetes (DM) and hypertension (HTN), on CKD documentation among managed care populations have not been previously reported. We examined this issue in a Kaiser Permanente Georgia (KPG) CKD cohort.</p> <p>Methods</p> <p>KPG enrollees were included in the CKD cohort if they had eGFRs between 60 and 365 days apart that were <90 ml/min during 1999-2006. The current analysis is restricted to participants with eGFR 10-59 ml/min/1.73 m². CKD documentation was defined as a presenting diagnosis of CKD by a primary care physician or nephrologist using ICD-9 event codes. The association between CKD documentation and DM and HTN were assessed with multivariate logistic regression models.</p> <p>Results</p> <p>Of the 50,438 subjects within the overall KPG CKD cohort, 20% (N = 10,266) were eligible for inclusion in the current analysis. Overall, CKD diagnosis documentation was low; only 14.4% of subjects had an event-based CKD diagnosis at baseline. Gender and types 2 diabetes interacted on CKD documentation. The prevalence of CKD documentation increased with the presence of hypertension and/or type 2 diabetes, but type 2 diabetes had a lower effect on CKD documentation. In multivariate analysis, significant predictors of CKD documentation were eGFR, hypertension, type 2 diabetes, congestive heart failure, peripheral artery disease, statin use, age and gender. CKD documentation was lower among women than similarly affected men.</p> <p>Conclusion</p> <p>Among patients with an eGFR 10-59, documentation of CKD diagnosis by primary and subspecialty providers is low within a managed care patient cohort. Gender disparities in CKD documentation observed in the general population were also present among KPG CKD enrollees.</p

25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients

BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients.METHODS: We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (&lt;15 ng/ml and =15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type.RESULTS: Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (&lt;15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04).CONCLUSIONS: Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor

Novel classification of proximal forearm perforator vein in the planning and creation of percutaneous and surgical Gracz-type arteriovenous fistulae

Background: The perforator vein determines whether it is feasible to create a percutaneous (pAVF) or surgical Gracz-type arteriovenous fistula (sAVF). Creating a standard anatomic classification of the antecubital region is beneficial to both the selection of the appropriate device and/or procedure and technical outcomes. Accordingly, an analysis of a large cohort of patients undergoing pAVF/sAVF was performed, focusing on perforator vein anatomical suitability, and a novel anatomical classification of the antecubital region was developed and proposed. Methods: Between August 2018 and July 2022, chronic or end-stage kidney disease patients as well as patients anticipated an initiation of apheresis, who were referred for vascular access planning, underwent a standardized evaluation of upper extremities. A vessel mapping summary detailing the vasculature and the access creation plan was completed, indicating the anatomical suitability for sAVF and pAVF (Ellipsys and WavelinQ) techniques. Results: Of 524 patients, 36.5% were female (average age 65 years). 53.2% were on dialysis, 41.6% had diabetes, and 13.2% had a previously failed permanent dialysis access. The anatomy for successful pAVF creation was judged to be suitable in 54% of patients for an Ellipsys-pAVF, and 29.8% for WavelinQ-pAVF. Of the WavelinQ group, 54.4% had suitable anatomy for ulnar, 26.9% for radial, and 18.6% for both ulnar/radial anastomoses. Additionally, 60.7% had suitable anatomy for pAVF creation with at least one of the systems, while 22.5% were suited for both types of pAVF-systems. 80.3% were candidates for creation of a Gracz-AVF. Conclusion: Overall, we found that about 60% of patients are likely candidates for a pAVF, with 80% being candidates for creation of a Gracz-AVF. Male patients have significantly higher suitability for most types of AVF creation, and younger patients are more suitable for Ellipsys-pAVF and RCAVFs. Most importantly, a universal classification of perforator vein was developed, which is indispensable in modern vascular access planning

25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients.

Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients. We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and ≥15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type. Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04). Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor