Search

Background: Type 1 diabetes mellitus (T1DM) is associated with adverse maternal and fetal outcomes. Continuous glucose monitoring (CGM) during pregnancy is associated with better glycemic control in women with T1DM. However, no clear benefits have been demonstrated in reducing adverse feto-maternal outcomes in pregnant women with T1DM. Design and Methods: This is a retrospective, single-center study of pregnant women with T1DM to evaluate the impact of CGM use on glycemic control and feto-maternal outcomes in pregnant women with T1DM. Results: Of 265 women with T1DM, 92 (34.7%) used CGM, and 173 (65.3%) were managed with capillary blood glucose (CBG) monitoring. The mean (SD) age and BMI at the first visit were 29.4 (4.7) years and 27.2 (5.2) kg/m2, respectively. The mean (SD) HbA1c at the first-trimester visit was 63 (1) mmol/mol, and in the last trimester was 51 (1%). There was no difference in the mean changes in HbA1c between the two groups. Women using CGM had lower insulin requirements (1.02 + 0.37 vs. 0.87 + 0.04 units/kg, p = 0.01). The two groups had no significant differences in maternal or fetal outcomes. Conclusion: CGM use in pregnant T1DM women is not associated with improved fetomaternal outcomes. [ABSTRACT FROM AUTHOR]

Background: We investigated the spectrum of infection and risk factors for invasive fungal disease due to Candida auris (CA) in Qatar. Methods: We performed structured chart reviews on individuals with any positive CA culture between May 2019 and December 2022 at three tertiary care hospitals in Qatar. Invasive CA disease (ICAD) was defined as a positive sterile site culture, or any positive culture for CA with appropriate antifungal prescription. Main outcomes included proportion of individuals who developed ICAD among those with positive cultures, and 30-day/in-hospital mortality. Results: Among 331 eligible individuals, median age was 56 years, 83.1% were male, 70.7% were non-Qataris, and 37.5% had ≥ 3 comorbidities at baseline. Overall, 86.4% were deemed to have colonization and 13.6% developed ICAD. Those with ICAD were more likely to have invasive central venous or urinary catheterization and mechanical ventilation. Individuals with ICAD had longer prior ICU stay (16 vs 26 days, P = 0.002), and longer hospital length of stay (63 vs. 43 days; P = 0.003), and higher 30-day mortality (38% vs. 14%; P<0.001). In multivariable regression analysis, only mechanical ventilation was associated with a higher risk of ICAD (OR 3.33, 95% CI 1.09–10.17). Conclusion: Invasive Candida auris Disease is associated with longer hospital stay and higher mortality. Severely ill persons on mechanical ventilation should be especially monitored for development of ICAD. [ABSTRACT FROM AUTHOR]

Background: The genetic basis of type 2 diabetes (T2D) is under-investigated in the Middle East, despite the rapidly growing disease prevalence. We aimed to define the genetic determinants of T2D in Qatar. Methods: Using whole genome sequencing of 11,436 participants (2765 T2D cases and 8671 controls) from the population-based Qatar Biobank (QBB), we conducted a genome-wide association study (GWAS) of T2D with and without body mass index (BMI) adjustment. Results: We replicated 93 known T2D-associated loci in a BMI-unadjusted model, while 96 known loci were replicated in a BMI-adjusted model. The effect sizes and allele frequencies of replicated SNPs in the Qatari population generally concurred with those from European populations. We identified a locus specific to our cohort located between the APOBEC3H and CBX7 genes in the BMI-unadjusted model. Also, we performed a transethnic meta-analysis of our cohort with a previous GWAS on T2D in multi-ancestry individuals (180,834 T2D cases and 1,159,055 controls). One locus in DYNC2H1 gene reached genome-wide significance in the meta-analysis. Assessing polygenic risk scores derived from European- and multi-ancestries in the Qatari population showed higher predictive performance of the multi-ancestry panel compared to the European panel. Conclusion: Our study provides new insights into the genetic architecture of T2D in a Middle Eastern population and identifies genes that may be explored further for their involvement in T2D pathogenesis. [ABSTRACT FROM AUTHOR]

Background: The genetic basis of type 2 diabetes (T2D) is under-investigated in the Middle East, despite the rapidly growing disease prevalence. We aimed to define the genetic determinants of T2D in Qatar. Methods: Using whole genome sequencing of 11,436 participants (2765 T2D cases and 8671 controls) from the population-based Qatar Biobank (QBB), we conducted a genome-wide association study (GWAS) of T2D with and without body mass index (BMI) adjustment. Results: We replicated 93 known T2D-associated loci in a BMI-unadjusted model, while 96 known loci were replicated in a BMI-adjusted model. The effect sizes and allele frequencies of replicated SNPs in the Qatari population generally concurred with those from European populations. We identified a locus specific to our cohort located between the APOBEC3H and CBX7 genes in the BMI-unadjusted model. Also, we performed a transethnic meta-analysis of our cohort with a previous GWAS on T2D in multi-ancestry individuals (180,834 T2D cases and 1,159,055 controls). One locus in DYNC2H1 gene reached genome-wide significance in the meta-analysis. Assessing polygenic risk scores derived from European- and multi-ancestries in the Qatari population showed higher predictive performance of the multi-ancestry panel compared to the European panel. Conclusion: Our study provides new insights into the genetic architecture of T2D in a Middle Eastern population and identifies genes that may be explored further for their involvement in T2D pathogenesis. [ABSTRACT FROM AUTHOR]

There is variability in the metabolic health status among individuals presenting with obesity; some may be metabolically healthy, while others may have developed the metabolic syndrome, a cluster including insulin resistance, hypertension, dyslipidemia, and increased risk of cardiovascular disease and type 2 diabetes. The mechanisms contributing to this metabolic heterogeneity are not fully understood. To address this question, plasma samples from 48 individuals with BMI ≥ 35 kg/m2 were examined (27 with and 21 without metabolic syndrome). Fasting plasma samples were subjected to Olink proteomics analysis for 184 cardiometabolic and inflammation-enriched proteins. Data analysis showed a clear differentiation between the two groups with distinct plasma protein expression profiles. Twenty-four proteins were differentially expressed (DEPs) between the two groups. Pathways related to immune cell migration, leukocyte chemotaxis, chemokine signaling, mucosal inflammatory response, tissue repair and remodeling were enriched in the group with metabolic syndrome. Functional analysis of DEPs revealed upregulation of 15 immunological pathways. The study identifies some of the pathways that are altered and reflect metabolic health in individuals with obesity. This provides valuable insights into some of the underlying mechanisms and can lead to identification of therapeutic targets to improve metabolic health in individuals with obesity. [ABSTRACT FROM AUTHOR]

Objectives: To examine the hypothesis that obesity complicated by the metabolic syndrome, compared to uncomplicated obesity, has distinct molecular signatures and metabolic pathways. Methods: We analyzed a cohort of 39 participants with obesity that included 21 with metabolic syndrome, age-matched to 18 without metabolic complications. We measured in whole blood samples 754 human microRNAs (miRNAs), 704 metabolites using unbiased mass spectrometry metabolomics, and 25,682 transcripts, which include both protein coding genes (PCGs) as well as non-coding transcripts. We then identified differentially expressed miRNAs, PCGs, and metabolites and integrated them using databases such as mirDIP (mapping between miRNA-PCG network), Human Metabolome Database (mapping between metabolite-PCG network) and tools like MetaboAnalyst (mapping between metabolite-metabolic pathway network) to determine dysregulated metabolic pathways in obesity with metabolic complications. Results: We identified 8 significantly enriched metabolic pathways comprising 8 metabolites, 25 protein coding genes and 9 microRNAs which are each differentially expressed between the subjects with obesity and those with obesity and metabolic syndrome. By performing unsupervised hierarchical clustering on the enrichment matrix of the 8 metabolic pathways, we could approximately segregate the uncomplicated obesity strata from that of obesity with metabolic syndrome. Conclusions: The data suggest that at least 8 metabolic pathways, along with their various dysregulated elements, identified via our integrative bioinformatics pipeline, can potentially differentiate those with obesity from those with obesity and metabolic complications. [ABSTRACT FROM AUTHOR]

Accurate determination of mortality attributable to SARS-CoV-2 vaccination is critical in allaying concerns about their safety. We reviewed every death in Qatar that occurred within 30 days of any SARS-CoV-2 vaccine administration between January 1, 2021 and June 12, 2022. Probability of association with SARS-CoV-2 vaccination was determined by four independent trained reviewers using a modified WHO algorithm. Among 6,928,359 doses administered, 138 deaths occurred within 30 days of vaccination; eight had a high probability (1.15/1,000,000 doses), 15 had intermediate probability (2.38/1,000,000 doses), and 112 had low probability or no association with vaccination. The death rate among those with high probability of relationship to SARS-CoV-2 vaccination was 0.34/100,000 unique vaccine recipients, while death rate among those with either high or intermediate probability of relationship to SARS-CoV-2 vaccination was 0.98/100,000 unique vaccine recipients. In conclusion, deaths attributable to SARS-CoV-2 vaccination are extremely rare and lower than the overall crude mortality rate in Qatar. This study assesses the probability that deaths following a COVID-19 vaccination are attributable to the vaccine. The authors review all deaths that occurred within 30 days of vaccine receipt in Qatar until June 2022 and find that deaths attributable to vaccination are extremely rare. [ABSTRACT FROM AUTHOR]

Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes mellitus. In this study, we estimated the prevalence and genetic spectrum of MODY in the Middle Eastern population of Qatar using whole-genome sequencing (WGS) of 14,364 subjects from the population-based Qatar biobank (QBB) cohort. We focused our investigations on 14 previously identified genes ascribed to the cause of MODY and two potentially novel MODY-causing genes, RFX6 and NKX6-1. Genetic variations within the 16 MODY-related genes were assessed for their pathogenicity to identify disease-causing mutations. Analysis of QBB phenotype data revealed 72 subjects (0.5%) with type 1 diabetes, 2915 subjects (20.3%) with type 2 diabetes and 11,377 (79.2%) without diabetes. We identified 22 mutations in 67 subjects that were previously reported in the Human Genetic Mutation Database (HGMD) as disease-causing (DM) or likely disease causing (DM?) for MODY. We also identified 28 potentially novel MODY-causing mutations, predicted to be among the top 1% most deleterious mutations in the human genome, which showed complete (100%) disease penetrance in 34 subjects. Overall, we estimated that MODY accounts for around 2.2–3.4% of diabetes patients in Qatar. This is the first population-based study to determine the genetic spectrum and estimate the prevalence of MODY in the Middle East. Further research to characterize the newly identified mutations is warranted. [ABSTRACT FROM AUTHOR]

Patients with end-stage kidney disease (ESKD) are at increased risk for SARS-CoV-2 infection and its complications compared with the general population. Several studies evaluated the effectiveness of COVID-19 vaccines in the dialysis population but showed mixed results. The aim of this study was to determine the effectiveness of COVID-19 mRNA vaccines against confirmed SARS-CoV-2 infection in hemodialysis (HD) patients in the State of Qatar. We included all adult ESKD patients on chronic HD who had at least one SARS-CoV-2 PCR test done after the introduction of the COVID-19 mRNA vaccines on 24 December 2020. Vaccinated patients who were only tested before receiving any dose of their COVID-19 vaccine or within 14 days after receiving the first vaccine dose were excluded from the study. We used a test-negative case–control design to determine the effectiveness of the COVID-19 vaccination. Sixty-eight patients had positive SARS-CoV-2 PCR tests (cases), while 714 patients had negative tests (controls). Ninety-one percent of patients received the COVID-19 mRNA vaccine. Compared with the controls, the cases were more likely to be older (62 ± 14 vs. 57 ± 15, p = 0.02), on dialysis for more than one year (84% vs. 72%, p = 0.03), unvaccinated (46% vs. 5%, p < 0.0001), and symptomatic (54% vs. 21%, p < 0.0001). The effectiveness of receiving two doses of COVID-19 mRNA vaccines against confirmed SARS-CoV-2 infection was 94.7% (95% CI: 89.9–97.2) in our HD population. The findings of this study support the importance of using the COVID-19 mRNA vaccine in chronic HD patients to prevent SARS-CoV-2 infection in such a high-risk population. [ABSTRACT FROM AUTHOR]

Hypoglycemia, as a complication of type 2 diabetes (T2D), causes increased morbidity and mortality but the physiological response underlying hypoglycemia has not been fully elucidated. Small noncoding microRNA (miRNA) have multiple downstream biological effects. This pilot exploratory study was undertaken to determine if induced miRNA changes would persist and contribute to effects seen 24 h post-hypoglycemia. A parallel, prospective study design was employed, involving T2D (n = 23) and control (n = 23) subjects. The subjects underwent insulin-induced hypoglycemia (2 mmol/L; 36 mg/dL); blood samples were drawn at baseline, upon the induction of hypoglycemia, and 4 h and 24 h post-hypoglycemia, with a quantitative polymerase chain reaction analysis of miRNA undertaken. The baseline miRNAs did not differ. In the controls, 15 miRNAs were downregulated and one was upregulated (FDR < 0.05) from the induction of hypoglycemia to 4 h later while, in T2D, only four miRNAs were altered (downregulated), and these were common to both cohorts (miR-191-5p; miR-143-3p; let-7b-5p; let-7g-5p), correlated with elevated glucagon levels, and all were associated with energy balance. From the induction of hypoglycemia to 24 h, 14 miRNAs were downregulated and 5 were upregulated (FDR < 0.05) in the controls; 7 miRNAs were downregulated and 7 upregulated (FDR < 0.05) in T2D; a total of 6 miRNAs were common between cohorts, 5 were downregulated (miR-93-5p, let-7b-5p, miR-191-5p, miR-185-5p, and miR-652-3p), and 1 was upregulated (miR-369-3p). An ingenuity pathway analysis indicated that many of the altered miRNAs were associated with metabolic and coagulation pathways; however, of the inflammatory proteins expressed, only miR-143-3p at 24 h correlated positively with tumor necrosis factor-α (TNFa; p < 0.05 and r = 0.46) and negatively with toll-like receptor-4 (TLR4; p < 0.05 and r = 0.43). The MiRNA levels altered by hypoglycemia reflected changes in counter-regulatory glucagon and differed between cohorts, and their expression at 24 h suggests miRNAs may potentiate and prolong the physiological response. Trial registration: ClinicalTrials.gov NCT03102801. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) has a heterogeneous etiology influencing its progression, treatment, and complications. A data driven cluster analysis in European individuals with T2D previously identified four subtypes: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild obesity-related (MOD), and mild age-related (MARD) diabetes. Here, the clustering approach was applied to individuals with T2D from the Qatar Biobank and validated in an independent set. Cluster-specific signatures of circulating metabolites and proteins were established, revealing subtype-specific molecular mechanisms, including activation of the complement system with features of autoimmune diabetes and reduced 1,5-anhydroglucitol in SIDD, impaired insulin signaling in SIRD, and elevated leptin and fatty acid binding protein levels in MOD. The MARD cluster was the healthiest with metabolomic and proteomic profiles most similar to the controls. We have translated the T2D subtypes to an Arab population and identified distinct molecular signatures to further our understanding of the etiology of these subtypes. Four T2D subtypes were previously identified: severe insulin deficient, severe insulin resistant, mild obesity-related, and mild age-related diabetes. Here, the authors show that these subtypes can be translated to an Arabic population and identify distinct subtype-specific metabolic and proteomic signatures. [ABSTRACT FROM AUTHOR]

Background: Obesity coexists with variable features of metabolic syndrome, which is associated with dysregulated metabolic pathways. We assessed potential associations between serum metabolites and features of metabolic syndrome in Arabic subjects with obesity. Methods: We analyzed a dataset of 39 subjects with obesity only (OBO, n = 18) age-matched to subjects with obesity and metabolic syndrome (OBM, n = 21). We measured 1069 serum metabolites and correlated them to clinical features. Results: A total of 83 metabolites, mostly lipids, were significantly different (p < 0.05) between the two groups. Among lipids, 22 sphingomyelins were decreased in OBM compared to OBO. Among non-lipids, quinolinate, kynurenine, and tryptophan were also decreased in OBM compared to OBO. Sphingomyelin is negatively correlated with glucose, HbA1C, insulin, and triglycerides but positively correlated with HDL, LDL, and cholesterol. Differentially enriched pathways include lysine degradation, amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, fructose and mannose metabolism, and galactose metabolism. Conclusions: Metabolites and pathways associated with chronic inflammation are differentially expressed in subjects with obesity and metabolic syndrome compared to subjects with obesity but without the clinical features of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background: The genetic factors associated with insulin resistance (IR) are not well understood. Clinical studies on first-degree relatives of type 2 diabetic (T2D) patients, which have the highest genetic predisposition to T2D, have given insights into the role of IR in T2D pathogenesis. Induced pluripotent stem cells (iPSCs) are excellent tools for disease modeling as they can retain the genetic imprint of the disease. Therefore, in this study, we aimed to investigate the genetic perturbations associated with insulin resistance (IR) in the offspring of T2D parents using patient-specific iPSCs. Methods: We generated iPSCs from IR individuals (IR-iPSCs) that were offspring of T2D parents as well as from insulin-sensitive (IS-iPSCs) individuals. We then performed transcriptomics to identify key dysregulated gene networks in the IR-iPSCs in comparison to IS-iPSCs and functionally validated them. Results: Transcriptomics on IR-iPSCs revealed dysregulated gene networks and biological processes indicating that they carry the genetic defects associated with IR that may lead to T2D. The IR-iPSCs had increased lactate secretion and a higher phosphorylation of AKT upon stimulation with insulin. IR-iPSCs have increased cellular oxidative stress indicated by a high production of reactive oxygen species and higher susceptibility to H2O2 -induced apoptosis. Conclusions: IR-iPSCs generated from offspring of diabetic patients confirm that oxidative stress and increased lactate secretion, associated with IR, are inherited in this population, and may place them at a high risk of T2D. Overall, our IR-iPSC model can be employed for T2D modeling and drug screening studies that target genetic perturbations associated with IR in individuals with a high risk for T2D. [ABSTRACT FROM AUTHOR]

In the United States (U.S.), between 2% and 10% of pregnant women have gestational diabetes mellitus (GDM). The purpose of this study is to assess the implications of GDM on pregnancy and birth outcomes as well as maternal morbidities and complications. Data from the 2019 U.S. Natality public file was analyzed on 3,423,238 singleton birth records. At the time of their pregnancy, women with GDM were more likely to be over the age of 30. Comorbidities of gestational hypertension/preeclampsia and eclampsia were substantially more common in pregnant women with GDM. Also, women with GDM were more likely to give birth via Cesarean section than those without the condition (p<.001). Newborns to mothers with GDM had a 7% higher chance of being preterm, a 29% higher chance of being low birth weight, and a 59% higher chance of being macrosomic (newborn weight =4000 grams) than newborns delivered to women without GDM. Early, targeted first-trimester screening and nutrition/exercise interventions for pregnant women at risk for GDM should be implemented to reduce adverse pregnancy and birth outcomes. [ABSTRACT FROM AUTHOR]

Short Summary Severe acute respiratory syndrome coronavirus 2 infection from the Omicron variant in children/adolescents is less severe than infection from the Delta variant. Those 6 to <18 years also have less severe disease than those <6 years old. Background There are limited data assessing coronavirus 2019 (COVID-19) disease severity in children/adolescents infected with the Omicron variant. Methods We identified children and adolescents <18 years of age with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with Delta and propensity score–matched controls with Omicron variant infection from the National COVID-19 Database in Qatar. Primary outcome was disease severity, determined by hospital admission, admission to the intensive care unit (ICU), or mechanical ventilation within 14 days of diagnosis, or death within 28 days. Results Among 1735 cases with Delta variant infection between 1 June and 6 November 2021, and 32 635 cases with Omicron variant infection between 1 January and 15 January 2022, who did not have prior infection and were not vaccinated, we identified 985 propensity score–matched pairs. Among those who were Delta infected, 84.2% had mild, 15.7% had moderate, and 0.1% had severe/critical disease. Among those who were Omicron infected, 97.8% had mild, 2.2% had moderate, and none had severe/critical disease (P  < .001). Omicron variant infection (vs Delta) was associated with significantly lower odds of moderate or severe/critical disease (adjusted odds ratio [AOR], 0.12; 95% confidence interval [CI],.07–.18). Those aged 6–11 and 12 to <18 years had lower odds of developing moderate or severe/critical disease compared with those younger than age 6 years (aOR, 0.47; 95% CI,.33–.66 for 6–11 year olds; aOR, 0.45; 95% CI,.21–.94 for 12 to <18 year olds). Conclusions Omicron variant infection in children/adolescents is associated with less severe disease than Delta variant infection as measured by hospitalization rates and need for ICU care or mechanical ventilation. Those 6 to <18 years of age also have less severe disease than those <6 years old. [ABSTRACT FROM AUTHOR]

Background: Mobile health (mHealth) is increasingly advocated for diabetes management. It is unclear if mobile applications are effective in improving glycaemic control, clinical outcomes, quality of life and overall patient satisfaction in patients with type 2 diabetes (T2DM). A new mobile application was specifically built for people with T2DM with the help of the local expertise. The objective of the study was to evaluate the effectiveness of the mobile app.Methods: The planned study is an ongoing open-label randomised controlled trial in which adults living with T2DM treated with insulin will be randomised 1:1 to the use of this diabetes application versus current standard care. The primary outcome will be the difference in mean HbA1c from baseline to 6 months. Other outcome measures include anthropometric measures, hypoglycaemic events, medication adjustments, number of clinical interactions and missed appointments and patient perceptions of their disease and diabetes self-management. The study will randomise 180 subjects for assessment of the primary outcome.Discussion: We hypothesise that the diabetes-specific mobile application will improve glycaemic control, increase patient empowerment for self-management of diabetes and improve interaction between patients and healthcare providers. If the Qatar Diabetes Mobile Application Trial (QDMAT) demonstrates this, it will inform clinical services for the future self-management of T2DM.Trial Registration: ClinicalTrials.gov Identifier: NCT03998267 . Registered on 26 June 2019. [ABSTRACT FROM AUTHOR]

Background: The complement system is pivotal in host defense mechanisms, protecting against pathogenic infection by regulating inflammation and cell immunity. Complement-related protein activation occurs through three distinct pathways: classical, alternative, and lectin-dependent pathways, which are regulated by cascades of multiple proteins. Complement activation is recognized in polycystic ovary syndrome (PCOS) to be associated with obesity and insulin sensitivity. Exercise reduces insulin resistance and may help reduce obesity, and therefore, this study was undertaken to determine the effect of exercise on the activation of complement-related proteins in PCOS and control women. Subjects and Measurements: In this study, 10 controls and 11 PCOS subjects who were age- and weight-matched underwent an 8-week supervised exercise program at 60% maximal oxygen consumption. Weight was unchanged though insulin sensitivity was increased in PCOS subjects and controls. Fasting baseline and post-exercise samples were collected and 14 complement-related proteins belonging to classical, alternative, and lectin-dependent pathways were measured. Results: Baseline levels of complement C4b and complement C3b/iC3b were higher in PCOS (P < 0.05) compared with controls. Exercise reduced complement C1q (P < 0.05), C3 (P < 0.001), C4 (P < 0.01), factor B (P < 0.01), factor H (P < 0.01), and properdin (P < 0.05) in controls, but not in PCOS women. Conclusion: Exercise induced complement changes in controls that were not seen in PCOS subjects, suggesting that these pathways remain dysregulated even in the presence of improved insulin sensitivity and not improved by moderate aerobic exercise. Clinical Trial Registration: ISRCTN registry, ISRCTN42448814. [ABSTRACT FROM AUTHOR]

Publisher's Note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. "The authors would like to thank Qatar Metabolic Institute, Medical Research Center, Translational Research Institute, Hamad Medical Corporation, Doha, Qatar for supporting the study. Keywords: complement; pregnancy; gestational diabetes; type 2 diabetes; preterm delivery EN complement pregnancy gestational diabetes type 2 diabetes preterm delivery 1 1 1 11/11/21 20211109 NES 211109 In the original article, there was an error. [Extracted from the article]

Background and objective: The risk factors for breakthrough infections among healthcare workers (HCW) after completion of a full course of vaccination are poorly understood. Our objective was to determine the risk factors for breakthrough SARS-CoV-2 infection among HCWs at a national healthcare system in Qatar. Methods: We identified all HCWs at Hamad Medical Corporation in Qatar between December 20, 2020 and May 18, 2021 with confirmed SARS-CoV-2 RT-PCR infection >14 days after the second vaccine dose. For each case thus identified, we identified one control with a negative test after December 20, 2020, matched on age, sex, nationality, job family and date of SARS-CoV-2 testing. We excluded those with a prior positive test and temporary workers. We used Cox regression analysis to determine factors associated with breakthrough infection. Results: Among 22,247 fully vaccinated HCW, we identified 164 HCW who had breakthrough infection and matched them to 164 controls to determine the factors associated with SARS-CoV-2 breakthrough infection. In the breakthrough infection group the nursing and midwifery job family constituted the largest group, spouse was identified as the most common positive contact followed by a patient. Exposure to a confirmed case, presence of symptoms and all other job families except Allied Health Professionals when compared with nursing and Midwifery staff independently predicted infection. Conclusion: Presence of symptoms and contact with a confirmed case are major risk factors for breakthrough SARS-CoV-2 infection after vaccination, and these groups should be prioritized for screening even after full vaccination. [ABSTRACT FROM AUTHOR]

Background: While many studies have reported the rate and risk of SARS-CoV-2 infection among healthcare workers (HCWs), there are scant data regarding the impact of employment type and job grades upon such risk. Methods: We determined the rate of SARS-CoV-2 infection based on a positive nasopharyngeal swab (NPS) PCR among employees of a large national healthcare system. Antibody testing was performed on those who agreed to provide a blood sample. Using logistic regression analysis, we determined the risk of infection (PCR+) associated with demographic characteristics, job family and job grade. Results: We identified 35,075 staff (30,849 full-time, 4,226 outsourced) between March 1-October 31, 2020. Among full-time employees, 78.0% had a NPS (11.8% positive). Among outsourced staff, 94.4% had a NPS (31.1% positive). Antibody testing was performed on 33.9% full-time employees (13.0% reactive), and on 39.1% of the outsourced staff (47.0% reactive). PCR-positivity was higher among outsourced staff (31.0% vs. 18.3% in non-clinical and 9.0% in clinical full-time employees) and those in the low-grade vs. mid-grade and high-grade job categories. Male sex (OR 1.88), non-clinical job family (OR 1.21), low-grade job category (OR 3.71) and being an outsourced staff (OR 2.09) were associated with a higher risk of infection. Conclusion: HCWs are a diverse population with varying risk of infection. Clinical staff are at a lower risk likely due to increased awareness and infection prevention measures. Risk is higher for those in the lower socioeconomic strata. Infection is more likely to occur in non-healthcare setting than within the healthcare facilities. [ABSTRACT FROM AUTHOR]

Aims: With the rising number of outcomes being reported following gestational diabetes (GDM), the outcomes in existing studies vary widely making it challenging to compare and contrast the effectiveness of different interventions for GDM. The purpose of this study was to develop a core outcome and measurement set (COS) for GDM treatment trials. Materials & Methods: A Delphi study with structured consultation with stakeholders and discussion within a specialist Gestational Metabolic Group (GEM) were combined with a comprehensive systematic search across different databases (PubMed, Cochrane Library, and Embase). Several Delphi rounds over 2 years were conducted culminating in this report. Results: The process resulted in a targeted set of outcomes constituting a "GEM treatment set" aligned with expert opinion. The final COS also included a measurement set for the 11 important clinical outcomes from three major domains: maternal metabolic, fetal, and pregnancy related. Conclusions: Based on the results of this study, it is recommended that future clinical trials on GDM report outcomes uniformly keeping to the recommended COS outcomes. [ABSTRACT FROM AUTHOR]

We investigated what proportion of the population acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and whether the herd immunity threshold has been reached in 10 communities in Qatar. The study included 4,970 participants during June 21-September 9, 2020. Antibodies against SARS-CoV-2 were detected by using an electrochemiluminescence immunoassay. Seropositivity ranged from 54.9% (95% CI 50.2%-59.4%) to 83.8% (95% CI 79.1%-87.7%) across communities and showed a pooled mean of 66.1% (95% CI 61.5%-70.6%). A range of other epidemiologic measures indicated that active infection is rare, with limited if any sustainable infection transmission for clusters to occur. Only 5 infections were ever severe and 1 was critical in these young communities; infection severity rate of 0.2% (95% CI 0.1%-0.4%). Specific communities in Qatar have or nearly reached herd immunity for SARS-CoV-2 infection: 65%-70% of the population has been infected. [ABSTRACT FROM AUTHOR]

Introduction: Gestational Diabetes Mellitus (GDM) development is related to underlying metabolic syndrome that is associated with elevated complement C3 and C4. Elevated C3 levels have been associated with preeclampsia and the development of macrosomia. Methods: This case-control study included 34 pregnant women with GDM and 16 non-diabetic (ND) women in their second trimester. Complement-related proteins were measured and correlated with demographic, biochemical, and pregnancy outcome data. Results: GDM women were older with a higher BMI (p<0.001); complement C3, C4 and Factor-H were significantly elevated (p=0.001, p=0.05, p=0.01, respectively). When adjusted for age and BMI, Complement C3 (p=0.04) and Factor-H (p=0.04) remained significant. Partial correlation showed significant correlation between C4 with serum alanine aminotransferase (ALT) (p<0.05) and 2nd term diastolic blood pressure (p<0.05); Factor-H and C-reactive protein (CRP; p<0.05). Pearson bivariate analysis revealed significant correlations between C3, C4, and Factor-H and CRP; p<0.05; C3 and gestational age at delivery (GA; p<0.05); C4 and ALT and second-trimester systolic blood pressure (STBP) (p=0.008 and p<0.05, respectively); Factor-H and glycated hemoglobin (HbA1c) (p<0.05). Regression analysis showed that the elevation of C3 could be accounted for by age, BMI, GA and CRP, with CRP being the most important predictor (p=0.02). C4 elevation could be accounted for by ALT, CRP and STBP. CRP predicted Factor-H elevation. Conclusion: The increased C3, C4 and Factor-H during the second trimester of pregnancy in GDM are not independently associated with GDM; inflammation and high BMI may be responsible for their elevation. The elevation of second trimester C3 in GDM is associated with earlier delivery and further work is needed to determine if this is predictive. [ABSTRACT FROM AUTHOR]

Background: The fibroblast growth factors (FGF) 19 subfamily, also referred to as endocrine FGFs, includes FGF19, FGF21, and FGF23 are metabolic hormones involved in the regulation of glucose and lipid metabolism. Fetuin-A is a hepatokine involved in the regulation of beta-cell function and insulin resistance. Endocrine FGFs and fetuin-A are dysregulated in metabolic disorders including obesity, type 2 diabetes, non-alcoholic fatty liver disease and polycystic ovary syndrome (PCOS). Our study was designed to examine the response of endocrine FGFs and fetuin-A to an acute intralipid, insulin infusion and exercise in PCOS and healthy women. Subjects and Measurements: Ten healthy and 11 PCOS subjects underwent 5-h saline infusions with a hyperinsulinemic-euglycemic clamp (HIEC) performed during the final 2 h. One week later, intralipid infusions were undertaken with a HIEC performed during the final 2 h. After an 8 week of exercise intervention the saline, intralipid, and HIEC were repeated. Plasma levels of endocrine FGFs and fetuin-A were measured. Results: Baseline fetuin-A was higher in PCOS women but FGF19, FGF21, and FGF23 did not differ and were unaffected by exercise. Insulin administration elevated FGF21 in control and PCOS, suppressed FGF19 in controls, and had no effects on FGF23 and fetuin-A. Intralipid infusion suppressed FGF19 and increased FGF21. Insulin with intralipid synergistically increased FGF21 and did not have effects on lipid-mediated suppression of FGF19 in both groups. Conclusion: Our study provides evidence for insulin and lipid regulation of endocrine FGFs in healthy and PCOS women, suggesting that FGF family members play a role in lipid and glucose metabolism. Clinical Trial Registration: www.isrctn.org, Identifier: ISRCTN42448814. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of gestational diabetes (GDM) has undergone several revisions. The broad adoption of the 2013 WHO criteria for hyperglycemia in pregnancy has increased the prevalence of GDM with no apparent benefit on pregnancy outcomes. The study aims to investigate the pregnancy outcomes in women with GDM diagnosed based on the WHO criteria compared to a control group; the impact of other confounders; and the difference in outcomes between GDM women who needed pharmacotherapy (GDM-T) and those who did not (GDM-D).Methods: This is a retrospective cohort study that included GDM women compared to normoglycemic controls between March 2015 and December 2016 in the Women's Hospital, Qatar.Results: The study included 2221 women; of which 1420 were normoglycemic, and 801 were GDM (358 GDM-D and 443 GDM-T). At conception, GDM women were older (mean age 32.5 ± 5.4 versus 29.6 ± 5.6 years, p<.001) and had higher prepregnancy BMI (mean BMI 32.2 ± 6.2 versus 28.2 ± 6.1 kg/m2, p<.01) compared to the controls, respectively. After correction for age, prepregnancy weight, and gestational weight gain (GWG); women with GDM had a higher risk of preterm labor (OR: 1.72; 95% CI: 1.32-2.23), large for gestational age (GA) (OR: 1.67; 95% CI: 1.22-2.29), neonatal ICU admission (OR: 1.57; 95% CI: 1.15-2.13), and neonatal hypoglycemia (OR: 3.22; 95% CI: 2.06-5.03). At conception, GDM-T women were older (mean age 33.3 ± 5.0 versus 31.5 ± 5.7 years, p<.001) and had higher BMI (mean BMI 32.9 ± 6.3 versus 231.2 ± 6.0 kg/m2, p=.01) compared to GDM-D, respectively. Metformin was used in 90.7% of the GDM-T women. Women in the GDM-T group had lower GWG/week compared to GDM-D (-0.01 ± 0.7 versus 0.21 ± 0.5 kg/week; p<.001). After correcting for age, prepregnancy weight and GWG; GDM-T had a higher risk of preterm labor (OR: 1.66; 95% CI: 1.20-2.22), and C-section (OR: 1.37, 95% CI: 1.02-1.85) and reduced risk of macrosomia (OR: 0.56; 95% CI: 0.32-0.96) and neonatal hypoglycemia (OR: 0.49; 95% CI: 0.28-0.82).Conclusion: In addition to hyperglycemia, the adverse effects of GDM on pregnancy outcomes are multifactorial and includes maternal age, maternal obesity, and gestational weight gain. Treatment with metformin reduces maternal weight gain, the risk of macrosomia and neonatal hypoglycemia compared to diet alone. [ABSTRACT FROM AUTHOR]

Post‐transplantation diabetes mellitus (PTDM) is a major complication in kidney transplant recipients leading to reduced allograft and patient survival. Given the high prevalence of diabetes in Qatar, which is twice the global average, we were interested in determining the incidence of PTDM, identifying risk factors, and comparing clinical outcomes in kidney transplant recipients with and without diabetes. We retrospectively followed up 191 adult kidney allograft recipients transplanted between January 1, 2012, and December 31, 2016, for a median of 41 months. A total of 76 patients (40%) had pre‐existing diabetes. A total of 39 patients developed PTDM during follow‐up; they represent 34% of patients who did not have diabetes prior to transplantation. Two thirds of PTDM occurred within 3‐6 months post‐transplantation. Prediabetes before transplant [OR = 6.07 (1.24‐29.74), P =.026] older recipient's age at the time of transplantation [OR = 1.10 (1.00‐1.20), P =.039] and average fasting blood sugar during 3‐6 months post‐transplant [OR = 1.06 (1.01‐1.11), P =.010] were independently associated with PTDM. Patient and kidney allograft survival rates exceeded 97% in all groups. The incidence of PTDM in kidney transplant recipients living in Qatar is high. Older age and prediabetes are independent risk factors for developing PTDM. [ABSTRACT FROM AUTHOR]

Background: There are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after direct-acting antiviral agent (DAA) treatment. Risk of HCC in HCV genotype-3 infected persons after DAA therapy is not well known.Methods: We prospectively studied HCV infected persons initiated on a DAA regimen between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. HCC was confirmed based on characteristic CT scan findings. Patients were followed for 12 months after the completion of therapy.Results: A total of 662 persons initiated treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic, 91% were genotype 3 and 91.9% attained SVR. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCV), 10.6%; SOF/DCV, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the 12-month period after treatment completion and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85). In Kaplan-Meier plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCV, or SOF/DCV regimens had a shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen.Conclusion: In a predominantly genotype 3 cohort, incident HCC occurred frequently and early after treatment completion, and exclusively in those with pre-treatment cirrhosis. SVR reduced the risk of HCC. Treating HCV infected persons before development of cirrhosis may reduce risk of HCC. [ABSTRACT FROM AUTHOR]

Background The effects of interferon-based therapies for hepatitis C virus (HCV) upon the risk of diabetes are controversial. The effects of newer, directly acting antiviral agents (DAA) upon this risk are unknown. We sought to determine the effects of HCV treatment upon the risk and incidence of diabetes. Methods Using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database for persons with chronic HCV infection (n = 242 680), we identified those treated with a pegylated interferon and ribavirin regimen (PEG/RBV, n = 4764) or a DAA-containing regimen (n = 21 279), after excluding those with diabetes at baseline, those with a human immunodeficiency virus or hepatitis B virus coinfection, and those treated with both PEG/RBV and DAA regimens. Age-, race-, sex-, and propensity score–matched controls (1:1) were also identified. Results Diabetes incidence rates per 1000 person-years were 20.6 (95% confidence interval [CI] 19.6–21.6) among untreated persons, 19.8 (95% CI 18.3–21.4) among those treated with PEG/RBV, and 9.89 (95% CI 8.7–11.1) among DAA-treated persons (P <.001). Among the treated, rates were 13.3 (95% CI 12.2–14.5) for those with a sustained virologic response (SVR) and 19.2 (95% CI 17.4–21.1) for those without an SVR (P <.0001). A larger reduction was observed in persons with more advanced fibrosis/cirrhosis (absolute difference 2.9 for fibrosis severity score [FIB-4] < 1.25; 5.7 for FIB-4 1.26–3.25; 9.8 for FIB-4 >3.25). DAA treatment (hazard ratio [HR] 0.53, 95% CI.46–.63) and SVR (HR 0.81, 95% CI.70–.93) were associated with a significantly reduced risk of diabetes. DAA-treated persons had longer diabetes-free survival rates, compared to untreated and PEG/RBV-treated persons. There was no significant difference in diabetes-free survival rates between untreated and PEG/RBV-treated persons. The results were similar in inverse probability of treatment and censoring weight models. Conclusions DAA therapy significantly reduces the incidence and risk of subsequent diabetes. Treatment benefits are more pronounced in persons with more advanced liver fibrosis. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Fever of unknown origin (FUO) is a diagnosis that requires a demanding workup from physicians before con- firming a diagnosis. Thyroid diseases are a rare cause of FUO. Subacute thyroiditis is an inflammatory disease that can lead to a wide spectrum of presentations. Case Report: We report a case of a previously healthy male who presented with persistent fever of 4 weeks following an upper respiratory tract infection associated with constitutional symptoms. His laboratory workup included complete blood counts (CBC), complete metabolic panel (blood urea and creatinine, liver function tests, and serum electrolytes), blood cultures, abdominal and pelvic ultrasound, and computed tomography abdomen and pelvis that were inconclusive. His thyroid function tests showed a hyperthyroid state and a thyroid scan confirmed a picture of thyroiditis. The patient was treated with Ibuprofen and then with prednisolone; he showed significant improvement over a few days and was discharged with treatment of tapering doses of prednisolone over 6 weeks. Two weeks after discharge the patient had a follow-up at an outpatient clinic and was found to be in good health with resolution of his symptoms. Conclusions: Thyroid disorders are not a common cause of FUO, and even if the clinical assessment of the patient is not suggestive of thyroid disease, we should consider it a possible cause. and thyroid function test should be performed to exclude thyroid problems. [ABSTRACT FROM AUTHOR]

Objective: Polycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder associated with mitochondrial dysfunction and insulin resistance (IR). MOTS‐c, a mitochondrial peptide, promotes insulin sensitivity (IS) through activating AKT and AMPK‐dependent pathways. The current study was designed to examine the response of MOTS‐c to lipids (intralipid) followed by insulin in PCOS and healthy subjects. Methods: All subjects underwent 5‐hour intralipid/saline infusion with a hyperinsulinemic‐euglycaemic clamp in the final 2 hours. Plasma samples were collected to measure circulating MOTS‐c using a commercial ELISA kit. Subsequently, this was repeated following an eight‐week exercise intervention. Results: Intralipid significantly increased plasma MOTS‐c both in controls and PCOS subjects, whilst the insulin infusion blunted the intralipid‐induced response seen for both lipids and MOT‐c. Intralipid elevated plasma MOTS‐c to 232 ± 124% of basal in control (P < 0.01) and to 349 ± 206% of basal in PCOS (P < 0.001) subjects. Administration of insulin suppressed intralipid‐induced MOTS‐c from 232 ± 124% to 165 ± 97% (NS) in control and from 349 ± 206% to 183 ± 177% (P < 0.05) in PCOS subjects, respectively. Following exercise, intralipid elevated plasma MOTS‐c to 305 ± 153% of basal in control (P < 0.01) and to 215 ± 103% of basal in PCOS (P < 0.01) subjects; insulin suppressed intralipid‐induced MOTS‐c only in controls. Conclusions: In conclusion, this is the first study to show increased lipid enhanced circulating MOTS‐c whilst insulin attenuated the MOTS‐c response in human. Further, eight weeks of moderate exercise training did not show any changes in circulating MOTS‐c levels in healthy controls and in women with PCOS. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial dysfunction is implicated in the pathogenesis of Type 2 diabetes (T2D) and the development of diabetes related complications such as cardiovascular disease and stroke. Mitochondria produce several small polypeptides that may influence mitochondrial function and may impact on insulin sensitivity, such as humanin (HN) and the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) that are mitochondrial derived proteins (MDP). The aim of this study was to determine MDP in normal, prediabetes and diabetes subjects. Subjects and Measurements: In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects. The relationship of serum MDP and ADP concentrations with biochemical and anthropometric measurements were performed and assessed by multilinear regression. Results: Serum HN concentrations were lower in T2D (p < 0.0001) and negatively correlated with age (p < 0.0001), HbA1c (p < 0.0001), glucose (p < 0.0001), triglycerides (p < 0.003), ALT (p < 0.004), and TG/HDL ratio (p < 0.001). Circulating HN levels were positively correlated to cholesterol (p < 0.017), LDL (p < 0.001), and HDL (p < 0.001). Linear regression analysis showed that HbA1c and ALT were two independent predictors of circulating HN. Similarly, serum MOTS-c was significantly lower in T2D subjects compared to controls (p < 0.007). Circulating MOTS-c positively correlated with BMI (p < 0.035), total cholesterol (p < 0.0001), and LDL (p < 0.001) and negatively correlated with age (p < 0.002), HbA1c (p < 0.001), and glucose (p < 0.002). Serum ADP concentrations were lower in T2D (p < 0.002) and negatively correlated with HbA1c (p < 0.001), weight (p < 0.032) TG (p < 0.0001), and ALT (p < 0.0001); and positively correlated with HDL (p < 0.0001) and HN (p < 0.003). Linear regression analysis showed that HbA1c and weight were two independent predictors of circulating ADP. Multilinear regression showed that HN and MOT-c correlated with each other, and only HN correlated with HbA1c. Conclusion: The MDPs HN and MOT-c, similar to ADP, are decreased in T2D and correlate with HbA1c. The data provide an additional evidence that mitochondrial dysfunction contributes to glycemic dysregulation and metabolic defects in T2D. [ABSTRACT FROM AUTHOR]

For persons with baseline Fibrosis-4 1.46–3.25, cirrhosis incidence/1000 patient-years was 49.3 among hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfected and 18.2 among HCV monoinfected (P =.03). Cirrhosis risk was numerically higher but statistically nonsignificant among HBV/HCV coinfected (hazards ratio [HR] 1.51; 95% confidence intervals [CI],.37–6.05) but lower among those who attained sustained virologic response (HR,.52; 95% CI,.42–.63). [ABSTRACT FROM AUTHOR]

Background: Diabetes first detected during pregnancy is currently divided into gestational diabetes mellitus (GDM) and diabetes mellitus (DM)- most of which are type 2 DM (T2DM). This study aims to define the prevalence and outcomes of diabetes first detected in pregnancy based on 75-gram oral glucose tolerance test (OGTT)using the recent WHO/IADPSG guidelines in a high-risk population. Methods: This is a retrospective study that included all patients who underwent a 75 g (OGTT) between Jan 2016 and Apr 2016 and excluded patients with known pre-conception diabetes. Results: The overall prevalence of newly detected diabetes in pregnancy among the 2000 patients who fulfilled the inclusion/exclusion criteria was 24.0% (95% CI 22.1–25.9) of which T2DM was 2.5% (95% CI 1.9–3.3), and GDM was 21.5% (95% CI 19.7–23.3). The prevalence of newly detected diabetes in pregnancy was similar among the different ethnic groups. The T2DM group was older (mean age in years was 34 ±5.7 vs 31.7±5.7 vs 29.7 ±5.7, p<0.001); and has a higher mean BMI (32.4±6.4 kg/m2 vs 31.7±6.2 kg/m2 vs 29.7± 6.2 kg/m2, p< 0.01) than the GDM and the non-DM groups, respectively. The frequency of pre-eclampsia, pre-term delivery, Caesarean-section, macrosomia, LGA and neonatal ICU admissions were significantly higher in the T2DM group compared to GDM and non-DM groups. Conclusion: Diabetes first detected in pregnancy is equally prevalent among the various ethnic groups residing in Qatar. Newly detected T2DM carries a higher risk of poor pregnancy outcomes; stressing the importance of proper classification of cases of newly detected diabetes in pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Newer direct acting antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether approval of newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. Methods: We identified HCV+ persons in ERCHIVES between October 1999 and July 2016. We excluded HIV+ and HBsAg+ and those with missing baseline HCV RNA and baseline eGFR data. We identified persons initiated on any approved DAA‐regimen through July 2016, by CKD stage. Logistic regression analyses were used to determine factors associated with treatment initiation. Results: Among 83 706 evaluable persons, 21.1% initiated treatment. Rates differed significantly by CKD stage: 22.1% for eGFR>90 mL/min/1.73 m2 and CKD stage‐2; 14.9% for CKD stage 3; and 8.0% for CKD stage‐4/5. Those with CKD stage‐3 were 33% less likely and those with CKD stage‐4/5 were 60% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90 mL/min/1.73 m2. Treatment initiation was less likely in HCV genotype 2 (OR 0.59; 95%CI 0.53,0.66) or 3 (OR 0.53; 95%CI 0.47,0.61) and those with diabetes (OR 0.87, 95% CI 0.81,0.94), cardiovascular disease (OR 0.77, 95% CI 0.70,0.84), alcohol abuse or dependence (OR 0.74, 95% CI 0.70,0.79) or cirrhosis (OR 0.86, 95% CI 0.80,0.92) at baseline. Conclusions: Persons with more advanced CKD are less likely to receive treatment for HCV despite recent data on safety and efficacy. Strategies are needed to improve treatment rates in the HCV/CKD population. [ABSTRACT FROM AUTHOR]

Background: Chronic urticaria (CU) is a common and complex disorder that occurs without any identifiable provoking factor. The mechanisms underlying CU pathogenesis are still not fully understood. The autoimmune theory of IgG autoantibodies to IgE/high-affinity receptor of IgE on mast cells and mast cell activation and autoallergy (IgE-mediated disease) might contribute to CU pathogenesis. Extracellular vesicles (EVs) are membranous vesicles released from apoptotic or activated cells of different types. Elevated circulating levels of EVs in allergic diseases were associated with inflammation and disease progression. In this study, we aimed to investigate circulating EVs as potential biomarkers in patients with CU compared with that in healthy controls. Methods: We studied 15 patients with CU and 16 healthy controls. Circulatory EVs (plasma) were characterized by the presence of externalized phosphatidylserine (annexin V staining). Endothelial cells, platelets, T and B cells, macrophages, granulocytes, PECAM 2 1, and tissue factors were investigated. An unpaired t-test was used, and P < 0.05 was considered statistically significant. Results: We did not find significant differences in the total number of EVs in patients with CU. A significant decrease in the levels of T-cells (CD3) and endothelial cells (CD146) (P < 0.05) in these patients than in controls was found. No significant differences were observed between patients with CU and healthy controls in terms of platelets, macrophages, PECAM-1, B cells, and tissue factors. Conclusion: Endothelial cells have been shown to contribute to the pathogenesis of CU and are also targeted by mediators released by mast cells and other cellular infiltrates. We identified that circulatory endothelial and T-cell EVs might play an important role in CU pathogenesis. In addition, our study highlights the importance of EVs as future therapeutic targets to be investigated. [ABSTRACT FROM AUTHOR]