Follow-up Blood Samples Research Articles

Recruitment and retention of pediatric participants for pandemic preparedness research: Experience from the PREMISE EV-D68 Pilot Study

Recruitment and retention are challenges for prospective pediatric cohort studies, particularly those involving serial venipunctures. We investigated factors underlying enrollment and retention in the Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) Enterovirus D68 (EV-D68) Pilot Study, a multicenter prospective longitudinal cohort study assessing the utility of immunologic surveillance for pandemic preparedness. This study enrolls children ≤10 years for two blood draws, pre- and post-EV-D68 season, separated by 6–18 months. Overall, 174 children were enrolled in Cohort 1 of the study and 120 (69 %) of children completed the study, with follow-up blood samples obtained from 101 (58 %) of participants. Families were primarily motivated to participate by a desire to help other children, advance science, and better prepare for the next pandemic. Adding research blood draws to clinically indicated blood draws improved enrollment, and multiple study touch points facilitated retention. These findings can be applied to improve recruitment and retention in future pandemic preparedness efforts and longitudinal pediatric cohort studies.

Controlled Hypoxia Acutely Prevents Physical Inactivity-Induced Peripheral BDNF Decline.

Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. A total of 25 healthy adults (25.8 ± 3.3 years, 15 female) were analyzed in a randomized controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO2] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO2 were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. NH decreased SpO2 (p < 0.001, ηp2 = 0.747) and increased heart rate (p = 0.006, ηp2 = 0.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p < 0.001, ηp2 = 0.581) and plasma (p < 0.001, ηp2 = 0.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p = 0.018) in serum and after 30 min (p = 0.040) and 90 min (p = 0.005) in plasma. There was no significant BDNF decline under NH. A 24 h follow-up examination showed a significant decline in serum BDNF, both after NH and NOR. Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

Integrating deep learning network and liquid biopsy for the evaluation and prediction of response in patients with advanced non-small cell lung cancer: Initial results from the RATIONALE prospective study.

e20036 Background: Lung cancerstill represents one of the most common and lethal diseases worldwide. There remains an unmet clinical need for the discovery of biomarkers to refine the management of patients with advanced non-small cell lung cancer (NSCLC). The combined evaluation of circulating cell-free DNA (cfDNA) and deep learning-based radiomic methods remains to be validated in the clinical setting. Methods: The RATIONALE study is a retro-prospective observational clinical trial consecutively enrolling treatment-naïve patients with advanced NSCLC who received standard first-line systemic treatments at Paolo Giaccone University Hospital, Palermo (Italy). Baseline and follow-up blood samples were collected according to computed tomography (CT) examinations performed using the same equipment (Siemens SOMATOM 128 slices), the same acquisition protocol, and the same contrast medium (Iomeron 400) every twelve weeks. All primary lung tumor internal regions of interest (ROIs) were segmented. Radiomic feature extraction was performed on the ROIs using Pyradiomics, an extension of the 3DSlicer. Circulating cfDNA was extracted from 1 ml of plasma using a QIAamp Circulating Nucleic Acid Kit (Qiagen) and quantified in terms of ng/μL using a QubitTM dsDNA HS Assay Kit (ThermoFisher Scientific). The diagnostic performance was evaluated using receiver operating characteristic (ROC) curves. Results: Between June 2021 and November 2023, fifty-five patients were included. Here we present the first results from the cohort of twenty patients undergoing first-line pembrolizumab-based treatments. Among the thirteen features extracted, the feature 'original_glcm_Id' evaluating the local image homogeneity emerged as statistically significant for differentiating adenocarcinoma and squamous cell carcinoma (sensitivity of 83.7%, specificity of 81.0%, accuracy of 82.8%; p &lt; 0.001). When correlating cfDNA dynamics and radiologic response, out of the eight features examined, the feature 'first order_mean' measuring the average intensity of gray levels proved to be statistically significant (sensitivity of 86.0%, specificity of 87.7%, accuracy of 86.9%; p &lt; 0.006). Finally, the feature 'size zone non-uniformity' measuring the variability of volumes in different gray level zones within the image showed a good performance in predicting overall survival (sensitivity of 65.8%, specificity of 100.0%, accuracy of 77.8%; p &lt; 0.001). Conclusions: The preliminary results of this ongoing study suggest the combined evaluation of liquid biopsy and radiomic features for obtaining minimally invasive and cost-effective biomarkers in the first-line clinical setting of NSCLC undergoing first-line pembrolizumab.

Effects of Chinese heart-healthy diet on blood lipids, glucose, and estimated 10-y cardiovascular disease risk among Chinese adults: results on secondary outcomes of a randomized controlled trial

BackgroundHealthy diet is essential for cardiovascular disease risk management, but its effects among Chinese patients, whose diets differ from Western diets, remain largely unknown. MethodsIn this multicenter, patient- and outcome assessor-blind, randomized controlled feeding trial, 265 Chinese adults with baseline systolic blood pressure 130 to 159 mmHg were randomly assigned into Chinese heart-healthy (CHH) diet or usual diet for a 28-d intervention after a 7-d run-in period on usual diet. Blood lipids and glucose were measured from overnight fasting blood samples before and after the intervention. Ten-year cardiovascular disease risk was estimated using models previously developed and validated in Chinese. The changes in secondary outcomes of serum total cholesterol (TC), blood glucose, and 10-y cardiovascular disease risk over the intervention period were compared between intervention groups, adjusting for center, among participants with baseline and follow-up blood samples available. Sensitivity analyses were done with further adjustment for baseline values and covariables; missing data imputed; and among per-protocol population. ResultsAmong 256 eligible participants (130 on CHH diet, 126 on control diet), 42% had hypercholesterolemia and 15% had diabetes at baseline. In the control group, TC and 10-y cardiovascular disease risk decreased after the intervention by 0.16 mmol/L and 0.91%, respectively, but blood glucose increased by 0.25 mmol/L. Compared with usual diet, the CHH diet lowered TC (−0.14 mmol/L, P = 0.017) and 10-y cardiovascular disease risk (−1.24%, P = 0.001) further. No effect on blood glucose was found. All sensitivity analyses confirmed the results on TC and 10-y cardiovascular disease risk, and analysis with multiple variables adjusted showed a borderline significant effect on blood glucose (−0.17 mmol/L, P = 0.051). The differences in intake of nutrients and food groups between intervention groups explained the results. ConclusionsThe CHH diet reduced TC and 10-y cardiovascular disease risk and was likely to reduce blood glucose among Chinese adults with mild hypertension. Further studies with longer terms are warranted.This trial was registered at clinicaltrials.gov as NCT03882645.

Inflammatory biomarkers and long-term outcome in young stable patients 3 months after a first myocardial infarction

Abstract Background Inflammation is an important driver of coronary artery disease (CAD). Several circulating inflammatory biomarkers have been associated with outcome, both before and after established CAD. However, studies in established CAD have often been limited by short follow-up period or blood sampling in the acute phase of a coronary event, which introduces a bias from the inflammatory response activated during a myocardial infarction (MI). Purpose This study aimed to compare the predictive value of several inflammatory biomarkers in a population of young stable patients 3 months after a first time MI. Methods 382 men and women ≤60 years of age with a first time MI were included from three Swedish hospitals between 1996 and 2000. 383 age- and sex-matched healthy controls were recruited from the general population. Individuals with previous MI, chronic inflammatory disease, kidney disease (creatinine &amp;gt;200 µmol/L), diabetes mellitus type 1, drug addiction or psychiatric disease were excluded. Three months after the acute index event, 15 biomarkers known to be involved in atherosclerosis were analysed; C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-18, interferon-gamma (IFN-γ), tumor necrosis factor-alfa (TNF-α), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase (MMP)-1, MMP-3 and MMP-9. The Swedish population register and national patient register were used to analyse cardiovascular outcome including all-cause mortality, recurrent MI and heart failure (HF) during 20 years of follow-up. A variable importance analysis and a Cox regression model were used. Biomarkers were divided in tertiles and compared with the lowest tertile as a reference. Results At inclusion, 82% of cases were men with a mean age of 52 years. 19% were smokers, 34% had a diagnosis of hypertension and 11% had diabetes mellitus. The level of each biomarker in cases and controls is shown in Table. When biomarkers were compared, IL-6 was identified as the most important biomarker to predict outcome. In cases, IL-6 was associated with a composite outcome of all-cause mortality, non-fatal MI and non-fatal HF in a model adjusted for age, sex and cardiovascular risk factors (HR 1.96, 95% CI 1.37-2.80) (Figure). IL-6 also was associated with all-cause mortality (HR 2.42, 95% CI 1.45-4.04) and HF (HR 2.58, 95% CI 1.54-4.33). Conclusions When 15 inflammatory markers involved in atherosclerosis were analysed, IL-6 was the most important biomarker to predict long-term cardiovascular outcome. This study is unique considering the extended follow-up period of 20 years in young individuals with blood sampled in a convalescent phase after a first myocardial infarction. IL-6 is a promising biomarker to predict long-term prognosis and a possible treatment target.Table.Medians for all 15 biomarkersOutcome in relation to IL-6 level

Concordance of circulating and solid tumor DNA through comprehensive genomic profiling in a large integrated cancer network.

3059 Background: Comprehensive Genomic Profiling (CGP) of solid tumors is crucial in diagnosing and treating cancer patients. Circulating Tumor DNA (ctDNA) is a potential biomarker for detecting mutations when tissue samples are limited or unavailable. However, the sensitivity of ctDNA tests vary greatly, making concordance studies with tissue samples critical to validate clinical use. This study presents results of CGP in paired tumor tissue and plasma samples from representative cancer patients treated in a community-based, Integrated Network Cancer Program. Methods: Over 2000 cancer patients have provided solid tumor and/or blood samples to date including serial follow-up blood samples. To optimize ctDNA integrity, we collected blood using a membrane stabilizer (Streck), ensured courier transport in ≤ 72 hours, separated plasma via differential centrifugation x 3, extracted cell free DNA with magnetic beads, and performed Next Generation Sequencing (NGS) using the ct-TSO500 assay (Illumina). In cases where patients provided both a solid tumor and concurrent blood sample, st-TSO500 NGS results from the solid tumor were compared to the ctDNA results for these matching specimens. Clinical actionability of variants was determined using the OncoKB database at levels 1, 2, and R1. Results: 146 matched blood and solid tumor specimens were analyzed to date. CGP studies revealed 1179 ± 102 unique variants across 20 different cancer types. Coding mutations from these specimens averaged 183 ± 25 variants. The ctDNA contained 96.5% of initial variants (1088 ± 95) and 95.1% of coding mutations (163 ± 20) found in the respective matched solid tumor. 76 patients had one or more oncogenic mutations detected only in the ctDNA and 28 (36.8%) of these included an actionable anticancer pharmacotherapy. Concordance by selective tumor type for clinical oncogenic variants was 95.8% (prostate), 95.0% (pancreas), 92.8% (lung and ovarian), 90.0% (endometrium), 84.3% (colon) and 82.4% for breast cancer. There was no difference in concordance between stage IV (91.0%) and stage I-III (86.5%) tumors (p = 0.14). An average of 6.2 ± 2.5 oncogenic variants were detected in both ctDNA and tissue. 99.3% of all patients contained an oncogenic biomarker in both ctDNA and tissue assays. Conclusions: We developed a prospective tissue and plasma repository of patients across a large integrated cancer network. These data demonstrate high concordance between circulating and solid tumor DNA using an “in-house” CGP assay. With no loss of concordance across cancer stages, ctDNA can identify actionable mutations not found in solid tumor analysis. This study is an important step toward incorporating “in-house” ctDNA CGP into routine cancer care. Future goals are to utilize these data for development of novel prognostic and predictive classifiers for use in a community-based hospital system across various disease sites.

Tumor-informed patient-specific MRD monitoring analysis in colorectal cancer.

48 Background: Growing studies have suggested that personalized tumor-informed circulating tumor DNA (ctDNA) based minimal residual disease (MRD) detection can precisely predict recurrence in resectable patients (pts) with colorectal cancer (CRC). We developed an improved approach, a Tumor-Informed Patient-specific panel integrating with a tiny tumor-specific Core panel (TIPC) to monitor MRD by ultra-deep sequencing of plasma samples. The combination with a core panel confers TIPC overcoming the tumor temporal and spatial heterogeneity to some extent and providing more comprehensive information to guide individualized management. Here, we investigated the clinical utility of this assay and performed a head-to-head comparison with a Tumor-Informed Off-the-shelf panel approach (TIO). Methods: The retrospective study enrolled 34 I-IV CRC patients undergoing curative intent surgery from multiple centers and a median follow-up of 482 days. Tissue samples were collected at surgery. Peripheral blood samples collected postoperative and before relapse were analyzed. For all patients, at least one sample was available within 6 months before progression, defined as surveillance time point. TIPC is a whole exome sequencing (WES) based approach to identify somatic mutations from tissue samples, followed by customizing a patient-specific capture panel covering up to 50 top-ranked variants, and then combined with a CRC universal core panel containing 10 actionable or high prevalence cancer-related genes to conduct ultra-deep sequencing above 100,000X of follow-up blood samples. TIO assay was performed in serial plasma samples by using an off-the-shelf 338 gene panel at a sequencing depth of 30,000X. Results: As of August 31, 2022, 25 pts had confirmed recurrence. For the surveillance time point, 24/25 (96.0%) disease recurrence pts were detected MRD positive with TIPC assay, meanwhile, all disease-free pts were MRD negative (100%, 9/9). MRD detection preceded radiographic progression (median 5.6 months). TIO approach showed the same MRD detection specificity performance as TIPC, whereas the sensitivity was 88.0% (22/25). The ctDNA fraction of these two TIO undetectable pts was quantified using TIPC were 0.0168% and 0.0177%, while the positive mutations were beyond the 338 gene panel. The detectable postoperative ctDNA was associated with a poor prognosis for patients by either TIPC or TIO assay, with hazard ratios 20.8 (p＜0.0001) and 7.8 (p＜0.0001) respectively. To further verify TIPC may possess higher sensitivity, another cohort of 4 radiographic progressed CRC pts with TIO longitudinal undetectable MRD was analyzed, 3/4 (75.0%) was detectable by TIPC (ctDNA fraction range 0.0006%-0.0075%). Conclusions: WES-based patient-specific MRD detection assay demonstrated encouraging recurrence risk stratification value in CRC pts and may pave the way for the management of individual treatment.

Changing Smoking Behavior and Epigenetics: A Longitudinal Study of 4,432 Individuals From the General Population

Hypomethylation of the aryl hydrocarbon receptor repressor (AHRR) gene indicates long-term smoking exposure and might therefore be a monitor for smoking-induced disease risk. However, studies of individual longitudinal changes in AHRR methylation are sparse. How does the recovery of AHRR methylation depend on change in smoking behaviors and demographic variables? This study included 4,432 individuals from the Copenhagen City Heart Study, with baseline and follow-up blood samples and smoking information collected approximately 10 years apart. AHRR methylation at the cg05575921 site was measured in bisulfite-treated leukocyte DNA. Four smoking groups were defined: participants who never smoked (Never-Never), participants who formerly smoked (Former-Former), participants who quit during the study period (Current-Former), and individuals who smoked at both baseline and follow-up (Current-Current). Methylation recovery was defined as the increase in AHRR methylation between baseline and follow-up examination. Methylation recovery was highest among participants who quit, with a median methylation recovery of 5.58%(interquartile range, 1.79; 9.15) vs1.64%(interquartile range, -1.88; 4.96) in the Current-Current group (P< .0001). In individuals who quit smoking, older age was associated with lower methylation recovery (P< .0001). In participants who quit aged > 65 years, methylation recovery was 5.9%at 5.6 years after quitting; methylation recovery was 8.5%after 2.8 years for participants who quit aged< 55 years. AHRR methylation recovered after individuals quit smoking, and recovery was more pronounced and occurred faster in younger compared with older interim quitters.

Neurofilament light chains in serum as biomarkers of axonal damage in early MS lesions: a histological–serological correlative study

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease associated with axonal injury, and neurofilament light chains in serum (sNfL) are considered a biomarker for this damage. We aimed to investigate the relationship between sNfL and the axonal damage in early MS lesions in a special cohort of biopsied patients. sNfL from 106 biopsied patients with 26 follow-up samples were analyzed using single-molecule array (SiMoA) technology. Findings were correlated with clinical parameters and histological findings of acute axonal damage (APP-positive spheroids) and axonal loss in different lesion stages. A median of 59 pg/ml sNfL was found (range 8–3101 pg/ml). sNfL levels correlated with APP-positive spheroids in early active demyelinating lesions that represent the earliest lesion stages (p < 0.01). A significant negative correlation between sNfL levels in follow-up blood samples and axonal density in normal-appearing white matter was also observed (p = 0.02). sNfL levels correlated with the Expanded Disability Status Score at biopsy (p < 0.01, r = 0.49) and at last clinical follow-up (p < 0.01, r = 0.66). In conclusion, sNfL likely represent a compound measure of recent and ongoing neuroaxonal damage. We found that sNfL in biopsied MS patients correlate with acute axonal damage in the earliest MS lesion stages. Determination of sNfL levels thus allows insight into brain pathology and underlines the relevance of relapse-associated lesional pathology. Axonal loss in normal-appearing white matter contributes to sNfL levels independent of relapses. Since sNfL levels correlate with clinical disability, they may predict the future disability of patients and help with individual treatment decisions.

An evaluation into the use of procalcitonin levels as a biomarker of bacterial sepsis to aid the management of intrapartum pyrexia and chorioamnionitis

BACKGROUNDProcalcitonin is an established biomarker for bacterial sepsis in the nonpregnant population with better diagnostic and prognostic value for bacterial infections.OBJECTIVEThis study aimed to evaluate whether procalcitonin levels could be used in the diagnosis and management of intrapartum sepsis in women and their neonates suspected of intrapartum bacterial sepsis.STUDY DESIGNA prospective observational cohort study was conducted at the University Hospitals of Bristol and Weston NHS Foundation Trust. Overall, 117 women and their neonates managed for suspected intrapartum sepsis from June 2020 to October 2020 were included. Procalcitonin levels were measured in addition to routine biomarkers white cell count and C-reactive protein in women and their neonates during the initial septic screen and follow-up blood samples. The placentas underwent detailed histopathology. Maternal and neonatal parameters were used to categorize cases into “high-suspicion bacterial sepsis,” “equivocal bacterial sepsis,” and “low-suspicion bacterial sepsis.” The Kruskal-Wallis test was used to compare categories with biomarker values and placental histology scores.RESULTSProcalcitonin level was increased in 6 women in the initial septic screen sample, compared with 100 women with an increased C-reactive protein level. There was a significant difference in maternal postnatal procalcitonin results between “high-suspicion bacterial sepsis” and “low-suspicion bacterial sepsis” categories (P=.004). Moreover, 71.2% of placentas showed varying degrees of chorioamnionitis.CONCLUSIONIn our cohort of women, 94.6% had normal procalcitonin levels while in labor at the time of the septic screen, consistent with the low number of confirmed bacteremia. The result provided a basis that procalcitonin may complement clinical judgment and interpretation of already used prognostic and diagnostic tests, improving patient care in the management of intrapartum sepsis.

PD58-04 A COMPREHENSIVE LIQUID BIOPSY TO DETECT PRIMARY UPPER TRACT UROTHELIAL CARCINOMA: A PILOT STUDY

You have accessJournal of UrologyCME1 May 2022PD58-04 A COMPREHENSIVE LIQUID BIOPSY TO DETECT PRIMARY UPPER TRACT UROTHELIAL CARCINOMA: A PILOT STUDY Alireza Ghoreifi, Stephanie Shishido, Jeremy Mason, George Courcoubetis, Manju Aron, Inderbir Gill, Monish Aron, Mihir Desai, Siamak Daneshmand, Peter Kuhn, and Hooman Djaladat Alireza GhoreifiAlireza Ghoreifi More articles by this author , Stephanie ShishidoStephanie Shishido More articles by this author , Jeremy MasonJeremy Mason More articles by this author , George CourcoubetisGeorge Courcoubetis More articles by this author , Manju AronManju Aron More articles by this author , Inderbir GillInderbir Gill More articles by this author , Monish AronMonish Aron More articles by this author , Mihir DesaiMihir Desai More articles by this author , Siamak DaneshmandSiamak Daneshmand More articles by this author , Peter KuhnPeter Kuhn More articles by this author , and Hooman DjaladatHooman Djaladat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002643.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Diagnosis and preoperative risk stratification of patients with upper tract urothelial carcinoma (UTUC) present distinct challenges given the limitations of current available diagnostic tools, such as imaging and endoscopic biopsy. Blood-based liquid biopsy has emerged as a novel diagnostic and prognostic biomarker in cancer patients, yet the possibility of this test in UTUC patients is unknown. The aim of this study is to explore the feasibility of a liquid biopsy to detect UTUC. METHODS: Under an IRB-approved protocol, blood samples were collected from primary UTUC patients before radical nephroureterectomy between May and October 2021. Patients with concomitant bladder cancer or those with positive bladder biopsies within the past 3 months were excluded. The samples were analyzed using third generation of comprehensive high-definition single cell assay (HDSCA3.0) to detect single cell circulatory tumor cells (CTCs). The findings were compared to the blood samples of normal blood donors (NBDs) who had no known pathology. RESULTS: A total of 5 UTUC patients and 5 NBDs were included in the pilot analysis. Demographic and pathological features of the UTUC patients are shown in Table 1. All patients showed papillary UTUC with no variant histology. HDSCA3.0 analysis indicated that rare cells are detectable in the peripheral blood collected from UTUC patients with high heterogeneity (Figure 1-A). The total rare cell count detected in UTUC patient samples was significantly higher than that from the NBDs (p-value = 0.009). Similar trend was seen in total CK+ cells (p=0.009), DAPI|CK (p=0.009), DAPI|Vim (0.028), DAPI|CK|Vim|CD45/CD31 (p=0.009), and DAPI only (p=0.009) (Figure 1-B). CONCLUSIONS: In this pilot study, the proposed liquid biopsy is feasible in UTUC patients. UTUC samples showed significantly higher rare cell count compared to the normal blood donors. A larger sample size study, including follow-up blood samples, to validate the accuracy of this test is the next step. Source of Funding: USC Urology Pilot Research Program © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1012 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alireza Ghoreifi More articles by this author Stephanie Shishido More articles by this author Jeremy Mason More articles by this author George Courcoubetis More articles by this author Manju Aron More articles by this author Inderbir Gill More articles by this author Monish Aron More articles by this author Mihir Desai More articles by this author Siamak Daneshmand More articles by this author Peter Kuhn More articles by this author Hooman Djaladat More articles by this author Expand All Advertisement PDF DownloadLoading ...

Fatty liver index for hyperuricemia diagnosis: a community-based cohort study

BackgroundStudies have demonstrated the relationship between the fatty liver index (FLI) and metabolism, while few research reported its relationship with hyperuricemia (HUA). This study aimed to predict HUA by determining the relationship between the baseline FLI and HUA events and by validating the FLI–HUA correlation through follow-up.MethodsThis study was a community-based cohort study involving 8851 adults in China. We performed anthropometric assessments and analyzed baseline and follow-up blood samples. HUA was defined as a uric acid level of > 420 µmol/L (7 mg/dL).ResultsPatients with HUA had a higher prevalence of diabetes mellitus, lipid metabolism disorders, and hypertension and higher FLI values than those with normal uric acid levels (P < 0.001). Serum uric acid was positively correlated with the FLI (r = 0.41, P < 0.001); the diagnostic cut-off value of FLI for the diagnosis of HUA was 27.15, with a specificity of 70.9% and sensitivity of 79.6%. FLI was an independent risk factor for HUA, with a 1.72-, 2.74-, and 4.80-fold increase in the risk of developing HUA with increasing FLI quartile levels compared with the FLI at quartile level 1 (P < 0.001). After a mean follow-up of 4 years, as the FLI values increased compared with the FLI at quartile level 1, the risk of new-onset HUA increased by 3.10-, 4.89-, and 6.97-fold (P < 0.001).ConclusionThere is a higher incidence of metabolic abnormalities in HUA populations, and FLI is an independent factor that may contribute to HUA development. Therefore, FLI is a potential tool to predict the risk of developing HUA.

Safety Evaluation of a Medical Congress Held During the COVID-19 Pandemic-A Prospective Cohort.

Objectives: During the COVID-19 pandemic, few scientific congresses have been held on-site. We prospectively evaluated the safety concept of the congress of the Swiss Societies of Infectious Diseases and Hospital Hygiene. Methods: The congress was held in Geneva (Switzerland) while local COVID-19 incidence (with SARS-CoV-2 wild type circulating) was 65/100,000 population (September 2020). A rigorous safety concept was implemented. Congress attendees filled out a questionnaire to assess risk perception, exposures, symptoms and diagnoses of SARS-CoV-2 before, during and after the congress. Dried blood spots were taken on-site and 4 weeks later to detect SARS-CoV-2 seroconversions. Results: Of 365 congress attendees, 196 (54%) either answered the questionnaire (N = 150) or provided baseline and follow-up blood samples (N = 168). None of the participants reported a positive PCR in the 2 weeks after the congress. Five of 168 (3%) participants were seropositive at follow-up, all of which had already been positive at baseline. Conclusion: Findings indicate that congresses with a rigorous safety concept may take place, even in areas with moderately-high COVID-19 activity. Whether this holds true in vaccinated populations and with more transmissible viral variants circulating remains unclear.

Effectiveness of COVID-19 Vaccines in Patients Under Maintenance Hemodialysis.

BackgroundSeveral published data on the dialysis population showed that antibody levels decreased after COVID-19 vaccinations in comparison to the overall population. We aimed to illustrate the persistence of humoral response after receiving second dose of the Pfizer or AstraZeneca vaccines in patients under maintenance hemodialysis (HD).MethodsA total of 119 adult patients on HD who were recruited from a single hemodialysis center in Madinah, Saudi Arabia. An enzyme-linked immunosorbent assay (ELISA) was utilized to measure the specific antibody response to the spike protein in the serum samples.ResultsMean age of patients was 48.5 ± 13.5 years, while mean time since starting the renal dialysis was 5.09 ± 5.29 years. Blood samples were collected after 89.2 ± 25.7 days of receiving the second dose of the vaccines. A very high positive correlation between anti-S IgG antibodies in pre- and post-dialysis was found (rs= 0.93, p < 0.001). Additionally, there was a high positive correlation between anti-S IgG antibody collected at baseline and follow-up blood samples (30 days apart) (rs= 0.82, p < 0.001). Moreover, patients who received Pfizer had significantly higher mean change in anti-S IgG antibodies compared to patients who received AstraZeneca (0.41 ± 0.94 vs 0.03 ± 0.30, respectively, p = 0.026).ConclusionThe majority of the patients included in this study were able to yield an immune response to the vaccine after receiving the two doses. Persistence of IgG antibodies in the majority of the patients on HD in response to COVID-19 vaccines is encouraging in terms of continuing to vaccinate this category of patients in addition to monitoring them.

Patients with checkpoint inhibitor-induced inflammatory arthritis do not become seropositive for anti-cyclic citrullinated peptide when followed over time.

Patients with checkpoint inhibitor-induced inflammatory arthritis do not become seropositive for anti-cyclic citrullinated peptide when followed over time.

Breast Cancer-related Biomarkers And Weight Regain Following An Exercise Intervention In Postmenopausal Women

PURPOSE: To assess the strength of the associations between breast cancer-related biomarkers and weight regain following exercise-induced weight loss in postmenopausal women. METHODS: The Breast Cancer and Exercise Trial in Alberta (BETA) included 400 participants that were randomized to either 150 or 300 minutes/week of aerobic exercise over 12 months with follow-up measurements at 24 months. During the follow-up period, no exercise intervention was prescribed. For these secondary analyses, we included participants who lost weight during the intervention and who had follow-up blood samples, body composition and covariate measurements (n = 214). Outcomes were measured at baseline, 12 months and 24 months. Linear regression models were used to explore associations between changes in body weight during follow-up, with changes in serum levels of breast-cancer related biomarkers: estradiol, free estradiol, estrone, sex hormone-binding globulin (SHBG), insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), and C-reactive protein (CRP). RESULTS: Weight regain during follow-up was significantly associated with increases in estradiol (treatment effect ratio (TER) = 1.03, 95% CI: 1.01, 1.04), estrone (TER = 1.02, 95% CI: 1.01, 1.03), free estradiol (TER = 1.04, 95% CI: 1.02, 1.05), HOMA-IR (TER = 1.03, 95% CI: 1.02, 1.05), insulin (TER = 1.03, 95% CI: 1.01, 1.04), and decreases in SHBG (TER = 0.98, 95% CI: 0.97, 0.99) levels. Non-statistically significant associations were found for glucose and CRP. Furthermore, categorical results revealed increases in estradiol, free estradiol, insulin, HOMA-IR and CRP for participants who regained any amount of weight compared with those who continued to lose or maintained weight loss during follow-up. CONCLUSION: Weight regain after an exercise intervention is associated with increases in estradiol, free estradiol, estrone, insulin, and decreases in SHBG in postmenopausal women. Future studies should analyze other blood biomarkers and tissue-specific markers that increase breast cancer risk, and their associations with weight regain following exercise-induced weight loss. Sources of funding: Research Grant No. 24404 from the Alberta Cancer Foundation and No. 2011-701000 by the Canadian Cancer Society.

Alternative Complement Pathway Is Activated and Associated with Galactose-Deficient IgA1 Antibody in IgA Nephropathy Patients.

BackgroundGalactose-deficient IgA1 (Gd-IgA1) and alternative complement pathway activation are considered to be involved in the pathogenesis of IgA nephropathy (IgAN). Nevertheless, the relationships between alternative pathway activation and disease activity or Gd-IgA1 level remains unclear.MethodsNinety-eight biopsy-diagnosed IgAN, twenty-five primary focal segmental sclerosis (FSGS) patients and forty-two healthy individuals were recruited in this study. Among them, fifty IgAN patients received immunosuppression. Follow-up blood samples at 1 and 3~6 months after immunosuppression were collected. Plasma levels of complement C5a, factor Ba and Gd-IgA1 were measured and analyzed. Immunostaining for complement was performed in twenty-five IgAN and FSGS patients.ResultsAt baseline, IgAN patients had higher levels of plasma C5a, factor Ba and Gd-IgA1 than control subjects. Gd-IgA1 levels positively correlated with plasma C5a and factor Ba. In addition, levels of factor Ba and Gd-IgA1 were positively associated with proteinuria and negatively associated with renal function. Immunostaining revealed positive staining for factor Bb and C3c in glomeruli in IgAN patients, but not in FSGS patients. At baseline, patients receiving immunosuppression had more severe proteinuria and higher factor Ba. After 6 months, eGFR declined and proteinuria persisted in patients without immunosuppression. In contrast, patients who received immunosuppression exhibited decreased plasma levels of C5a, factor Ba, and Gd-IgA1 as early as 1 month after treatment. Proteinuria decreased and renal function also remained stable 6 months after immunosuppression.ConclusionsOur results indicate a close relationship between alternative complement pathway activation, Gd-IgA1 concentration and clinical severity of IgAN. Level of complement factor B may be a potential marker for disease activity and therapeutic target in IgAN patients.

Vitamin A–fortified rice increases total body vitamin A stores in lactating Thai women measured by retinol isotope dilution: a double-blind, randomized, controlled trial

Lactating women are at increased risk for vitamin A (VA) deficiency due to demands for breast milk content and limited hepatic stores for women in some countries. Previously, consumption of triple-fortified rice, which included VA, iron, and zinc, successfully improved the VA status of Thai children in whom their total body VA stores (TBSs) were doubled in 2 mo. This study assessed the efficacy of consuming VA-fortified rice, which delivered 500 µg retinol activity equivalents (RAEs)/d, on TBSs and estimated total liver VA reserves (TLRs) in Thai lactating women using the retinol isotope dilution (RID) test. A randomized controlled trial was conducted with 70 lactating women (n=35/group) who received either VA-fortified rice (500 µg RAEs/d) or unfortified rice for 14 wk on weekdays only. Serum retinol concentrations (SRs), C-reactive protein, and TBSs were assessed before and after the intervention. The paired 13C-RID test was used to measure TBSs. After a baseline blood sample, 2.0 µmol [14,15]-13C2-retinyl acetate was administered orally. A follow-up blood sample was drawn 14 d later. The RID test was repeated after the intervention. TBSs increased significantly (P<0.05) in the intervention group from 240 (182, 316) to 331 (251, 447) [geometric means (95% CIs)] µmol retinol, and this change in TBSs was significantly higher (P<0.05) than that in the control group [+52.9 (-74, 453) compared with -4.3 (-106, 275) µmol retinol]. Estimated TLRs indicated a high prevalence of VA deficiency among these lactating women. Initial and final SRs did not differ by group and did not change over the course of the intervention. VA-fortified rice improved the VA status of lactating women by increasing TBSs. A targeted approach to disseminate VA interventions among vulnerable groups should be considered in some contexts. This trial was registered at clinicaltrials.gov as NCT03056625.

Diagnostic performance of anti-Zika virus IgM, IgAM and IgG ELISAs during co-circulation of Zika, dengue, and chikungunya viruses in Brazil and Venezuela.

BackgroundSerological diagnosis of Zika virus (ZIKV) infection is challenging because of the antibody cross-reactivity among flaviviruses. At the same time, the role of Nucleic Acid Testing (NAT) is limited by the low proportion of symptomatic infections and the low average viral load. Here, we compared the diagnostic performance of commercially available IgM, IgAM, and IgG ELISAs in sequential samples during the ZIKV and chikungunya (CHIKV) epidemics and co-circulation of dengue virus (DENV) in Brazil and Venezuela.Methodology/Principal findingsAcute (day of illness 1–5) and follow-up (day of illness ≥ 6) blood samples were collected from nine hundred and seven symptomatic patients enrolled in a prospective multicenter study between June 2012 and August 2016. Acute samples were tested by RT-PCR for ZIKV, DENV, and CHIKV. Acute and follow-up samples were tested for IgM, IgAM, and IgG antibodies to ZIKV using commercially available ELISAs. Among follow-up samples with a RT-PCR confirmed ZIKV infection, anti-ZIKV IgAM sensitivity was 93.5% (43/46), while IgM and IgG exhibited sensitivities of 30.3% (10/33) and 72% (18/25), respectively. An additional 24% (26/109) of ZIKV infections were detected via IgAM seroconversion in ZIKV/DENV/CHIKV RT-PCR negative patients. The specificity of anti-ZIKV IgM was estimated at 93% and that of IgAM at 85%.Conclusions/SignificanceOur findings exemplify the challenges of the assessment of test performance for ZIKV serological tests in the real-world setting, during co-circulation of DENV, ZIKV, and CHIKV. However, we can also demonstrate that the IgAM immunoassay exhibits superior sensitivity to detect ZIKV RT-PCR confirmed infections compared to IgG and IgM immunoassays. The IgAM assay also proves to be promising for detection of anti-ZIKV seroconversions in sequential samples, both in ZIKV PCR-positive as well as PCR-negative patients, making this a candidate assay for serological monitoring of pregnant women in future ZIKV outbreaks.

Weight Regain and Breast Cancer-Related Biomarkers Following an Exercise Intervention in Postmenopausal Women.

Epidemiologic studies have reported associations between weight fluctuations and postmenopausal breast cancer risk; however, the biological markers involved in this association are unknown. This study aimed to explore the associations between breast cancer-related biomarkers and weight regain following exercise-induced weight loss. From the 400 participants included in the Breast Cancer and Exercise Trial in Alberta, a total of 214 lost weight during the intervention and had follow-up blood samples, body composition, and covariate measurements. Outcomes were measured at baseline, 12 months (end of the study), and 24 months (follow-up). During follow-up, weight regain was 1.80 kg [95% confidence interval (CI): -0.40-3.90], and was significantly associated with increases in estradiol [treatment effect ratio (TER) = 1.03; 95% CI, 1.01-1.04], estrone (TER = 1.02; 95% CI, 1.01-1.03), free estradiol (TER = 1.04; 95% CI, 1.02-1.05), the homeostatic model assessment for insulin resistance (TER = 1.03; 95% CI, 1.02-1.05), and insulin (TER = 1.03; 95% CI, 1.01-1.04), and decreases in sex hormone-binding globulin (SHBG; TER = 0.98; 95% CI, 0.97-0.99) levels. Nonstatistically significant associations were found for glucose and C-reactive protein. Furthermore, a statistically significant linear trend of increasing levels for all biomarkers, and decreasing SHBG, across weight regain categories was found. These results suggest that weight regain following exercise-induced weight loss is associated with breast cancer-related biomarker changes in postmenopausal women. These findings provide evidence to support the importance of developing effective strategies to prevent weight regain and, consequently, decrease postmenopausal breast cancer risk via changes in adiposity-related biomarkers.