Publications by authors named "Tsvetelina Velikova"

63 Publications

Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Bulgaria: an internet-based survey.

Dig Dis 2022 Aug 16. Epub 2022 Aug 16.

Background: The global pooled prevalence of gastroesophageal reflux disease (GORD) is approximately 14% and varies significantly according to the country. More population-based studies are needed in regions lacking epidemiological data on the prevalence of GORD, such as Eastern Europe, particularly Bulgaria. This current study aimed to evaluate the prevalence of GORD in Bulgaria and assess the risk factors associated with this disorder.

Methods: An internet-based health survey was sent to Bulgarian adults. Individuals were invited to complete an online questionnaire on general and gastrointestinal (GI) health. The aim of the study was not explicitly stated. The survey collected data on socio-demographic and behavioral characteristics, validated questions to assess GORD, diagnostic questions based on Rome IV criteria to assess irritable bowel syndrome (IBS) and functional dyspepsia (FD), and questions about antisecretory drugs usage.

Results: Data was collected from 1896 individuals (mean age = 35.5 years, SD = 11.7, 73.1% females). The prevalence of GORD in the study population was 27.5%, while 57.29% of all GORD patients taking PPIs had PPI-refractory GORD. Age (p=0.02), BMI (p<0.001), marital status (p=0.03), occupation (p<0.001), sexual problems (p<0.001), FD (p<0.001), and IBS (p<0.001) were significantly associated with GORD prevalence. Patients with FD (p<0.001; OR 5.38), IBS (p=0.03; OR 1.07), and with higher BMI (p<0.001, OR 1.05) were at an increased risk of having GORD.

Conclusions: The first data on GORD prevalence in the adult population in Bulgaria has been reported. Disorders of gut-brain interaction have a significant impact on the prevalence of GORD.
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http://dx.doi.org/10.1159/000526355DOI Listing
August 2022

COVAD survey 2 long-term outcomes: unmet need and protocol.

Rheumatol Int 2022 Aug 14. Epub 2022 Aug 14.

Department of Medicine and Therapeutics, College of Health Sciences, University of Ghana School of Medicine and Dentistry, Korle-Bu, Accra, Ghana.

Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups.
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http://dx.doi.org/10.1007/s00296-022-05157-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376047PMC
August 2022

Impaired physical function in patients with idiopathic inflammatory myopathies: results from the multicentre COVAD patient-reported e-survey.

Rheumatology (Oxford) 2022 Aug 3. Epub 2022 Aug 3.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Objectives: The assessment of physical function is fundamental in the management of patients with idiopathic inflammatory myopathies (IIMs). We aimed to investigate the physical function of patients with IIMs compared with those with non-IIM autoimmune rheumatic diseases (AIRDs) utilizing Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) data obtained in the COVAD study, an international self-reported e-survey assessing the safety of COVID-19 vaccines in AIRDs.

Methods: Demographics, AIRD diagnosis, disease activity, and PROMIS PF short form-10a data were extracted from the COVAD database. PROMIS PF-10a scores were compared between disease categories and stratified by disease activity. Factors affecting PROMIS PF-10a scores other than disease activity were identified by multivariable regression analysis in patients with inactive disease.

Results: 1057 IIM patients, 3635 non-IIM AIRD patients, and 3981 healthy controls (HCs) responded to the COVAD e-survey from April to August 2021. Using a binomial regression model, the predicted mean of PROMIS PF-10a scores was significantly lower in IIM patients compared with non-IIM AIRD patients or HCs (36.3 [95% confidence interval (CI) 35.5-37.1] vs 41.3 [95%CI 40.2-42.5] vs 46.2 [95%CI 45.8-46.6], P < 0.001), irrespective of disease activity. The independent factors for lower PROMIS PF-10a scores in patients with inactive disease were older age, female, longer disease duration, and a diagnosis of inclusion body myositis or polymyositis.

Conclusion: Physical function is significantly impaired in IIMs compared with non-IIM AIRDs or HCs, even in patients with inactive disease. Our study highlights a critical need for better strategies to minimize functional disability in patients with IIMs.
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http://dx.doi.org/10.1093/rheumatology/keac441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384667PMC
August 2022

COVID-19 Vaccination In Autoimmune Diseases (COVAD) Study: Vaccine Safety In Idiopathic Inflammatory Myopathies.

Muscle Nerve 2022 Jul 23. Epub 2022 Jul 23.

Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Introduction/aims: We studied COVID-19 vaccination-related adverse events (ADEs) 7-days post-vaccination in patients with idiopathic inflammatory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders (SAIDs).

Methods: 7-day vaccine ADEs were collected in an international patient self-reported e-survey. Descriptive statistics and multivariable regression were performed.

Results: 10,900 respondents [1227 IIMs; 4640 SAIDs; 5033 healthy controls (HCs), median age 42 (IQR 30-55) years, 74% female, 45% Caucasian, 69% completely vaccinated] were analysed. 76.3% IIMs patients reported minor and 4.6% major ADEs. Patients with active IIMs reported more frequent major [OR 2.7 (1.04-7.3)] and minor [OR 1.5 (1.1-2.2)] ADEs than inactive IIMs. Rashes were more frequent in IIMs [OR-2.3(1.2-4.2)] than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/subcutaneous immunoglobulins were associated with a higher risk of minor ADEs [OR 1.9 (1.1-3.3), OR 2.2 (1.1-4.3)]. Overall, ADEs were less frequent in inclusion body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients DISCUSSION: 7-day post-vaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rashes in IIMs. Patients with DM, active disease may be at higher risk, and IBM patients at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID-19 through vaccination likely outweighs the risk of vaccine-related ADEs Our results may inform future guidelines regarding COVID-19 vaccination in patients with SAIDs, and specifically in IIMs. Studies to evaluate long-term outcomes and disease flares are needed to shed more light on developing future COVID-19 vaccination guidelines. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/mus.27681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349921PMC
July 2022

COVID-19 vaccination-related adverse events among autoimmune disease patients: results from the COVAD study.

Rheumatology (Oxford) 2022 Jun 17. Epub 2022 Jun 17.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Objectives: COVID-19 vaccines have been proven to be safe in the healthy population. However, gaps remain in the evidence of their safety in patients with systemic autoimmune and inflammatory disorders (SAIDs). COVID-19 vaccination related adverse events (ADEs) in patients with SAIDs and healthy controls (HC) seven days post-vaccination were assessed in the COVAD study, a patient self-reported cross-sectional survey.

Methods: The survey was circulated in early 2021 by > 110 collaborators (94 countries) to collect SAID details, COVID-19 vaccination details, and 7-day vaccine ADEs, irrespective of respondent vaccination status. Analysis was performed based on data distribution and variable type.

Results: 10900 respondents [42 (30-55) years, 74% females and 45% Caucasians] were analyzed. 5,867 patients (54%) with SAIDs were compared with 5033 HCs.79% had minor and only 3% had major vaccine ADEs requiring urgent medical attention (but not hospital admission) overall. Headache [SAIDs=26%, HCs=24%; OR = 1.1 (1.03-1.3); p = 0.014], abdominal pain [SAIDs=2.6%, HCs=1.4%; OR = 1.5 (1.1-2.3); p = 0.011], and dizziness [SAIDs=6%, HCs=4%; OR = 1.3 (1.07-1.6); p = 0.011], were slightly more frequent in SAIDs. Overall, major ADEs [SAIDs=4%, HCs=2%; OR = 1.9 (1.6-2.2); p < 0.001] and, specifically, throat closure [SAIDs=0.5%, HCs=0.3%; OR = 5.7 (2.9-11); p = 0.010] were more frequent in SAIDs though absolute risk was small (0-4%). Major ADEs and hospitalizations (less than 2%) were comparable across vaccine types in SAIDs.

Conclusion: Vaccination against COVID-19 is relatively safe in SAID patients. SAIDs were at a higher risk of major ADEs than HCs, though absolute risk was small. There are small differences in minor ADEs between vaccine types in SAID patients.
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http://dx.doi.org/10.1093/rheumatology/keac305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214139PMC
June 2022

Nutritional Management of Thyroiditis of Hashimoto.

Int J Mol Sci 2022 May 5;23(9). Epub 2022 May 5.

Department of Cell and Developmental Biology, Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tsankov Blvd., 1164 Sofia, Bulgaria.

Since the thyroid gland is one of the organs most affected by autoimmune processes, many patients with thyroiditis of Hashimoto (TH) seek medical advice on lifestyle variance and dietary modifications to improve and maintain their hyroid function. In this review, we aim to present and discuss some challenges associated with the nutritional management of TH, focusing on environmental and dietary deficits, inflammatory and toxic nutrients, cyanotoxins, etc. We discuss the relationships among different diets, chronic inflammation, and microbiota, and their impact on the development and exacerbation of TH in detail. We share some novel insights into the role of vitamin D and melatonin for preserving thyroid function during chronic inflammation in autoimmune predisposed subjects. A comprehensive overview is provided on anti-inflammatory nutrients and ecological diets, including foods for cleansing and detoxification, which represent strategies to prevent relapses and achieve overall improvement of life quality. In conclusion, data from biomedical and clinical studies provide evidence that an appropriate dietary and lighting regimen could significantly improve the function of the thyroid gland and reduce the reactivity of autoantibodies in TH. Compliance with nutritional guidelines may help TH patients to reduce the need for medicines.
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http://dx.doi.org/10.3390/ijms23095144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101513PMC
May 2022

Cellular, Antibody and Cytokine Pathways in Children with Acute SARS-CoV-2 Infection and MIS-C-Can We Match the Puzzle?

Antibodies (Basel) 2022 Apr 1;11(2). Epub 2022 Apr 1.

Department of Clinical Immunology, University Hospital Lozenetz, Sofia University St. Kliment Ohridski, Kozyak 1 Str., 1407 Sofia, Bulgaria.

The newly identified strain of the Coronaviridae family called severe acute respiratory syndrome (SARS-CoV-2) recently became the most significant health threat for adults and children. Some main predictors of severe clinical course in patients with SARS-CoV-2 infection are age and concomitant health conditions. Therefore, the proper evaluation of SARS-CoV-2-specific immunity is urgently required to understand and predict the spectrum of possible clinical phenotypes and recommend vaccination options and regimens in children. Furthermore, it is critical to characterize the nature of SARS-CoV-2-specific immune responses in children following asymptomatic infection and COVID-19 and other related conditions such as multisystem inflammatory syndrome (MIS-C), para-infectious and late postinfectious consequences. Recent studies involving children revealed a variety of cytokines, T cells and antibody responses in the pathogenesis of the disease. Moreover, different clinical scenarios in children were observed-asymptomatic seroprevalence, acute SARS-CoV-2 infection, and rarely severe COVID-19 with typical cytokine storm, MIS-C, long COVID-19, etc. Therefore, to gain a better clinical view, adequate diagnostic criteria and treatment algorithms, it is essential to create a realistic picture of the immunological puzzle of SARS-CoV-2 infection in different age groups. Finally, it was demonstrated that children may exert a potent and prolonged adaptive anti-SARS-CoV-2 immune response, with significant cross-reactions against other human Corona Viruses, that might contribute to disease sparing effect in this age range. However, the immunopathology of the virus has to be elucidated first.
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http://dx.doi.org/10.3390/antib11020025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036295PMC
April 2022

Specific Immunoglobulin E and G to Common Food Antigens and Increased Serum Zonulin in IBS Patients: A Single-Center Bulgarian Study.

Antibodies (Basel) 2022 Mar 29;11(2). Epub 2022 Mar 29.

Laboratory of Clinical Immunology, University Hospital Lozenetz, Sofia University St. Kliment Ohridski, 1407 Sofia, Bulgaria.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder whose pathogenesis is considered multifactorial, including abnormal gut motility, visceral hyperreactivity, psychological factors, disturbances in the brain-gut axis, leaky gut, oxidative stress, etc. We aimed to investigate serum levels of specific immunoglobulin E and G to common food antigens and zonulin and to assess their use in clinical practice for patients with IBS.

Material And Methods: We included 23 participants, 15 with IBS (diagnosed according to the Rome IV criteria) and 8 healthy controls. We investigated serum levels of specific IgG antibodies to 24 food antigens, specific IgE antibodies to 20 food antigens, anti-celiac antibodies, fecal calprotectin and serum zonulin by ELISA.

Results: Food-specific positive IgG antibodies were significantly higher in patients with IBS than in controls ( = 0.007). IgE-mediated allergic reactions were found in five patients with IBS; no one had anti-TG antibodies. One-third of IBS patients demonstrated a low degree of chronic inflammation (positive fecal calprotectin test > 50 ng/mL) without specific bacterial infection. Serum levels of zonulin in IBS patients were higher than in healthy controls (0.378 ± 0.13 vs. 0.250 ± 0.14 ng/mL, = 0.0315). However, no correlations between clinical symptoms and zonulin levels were found.

Conclusion: The mechanisms of IgG hypersensitivity and low degree inflammation in IBS and elevated zonulin may contribute to multifactor pathogenesis in IBS.
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http://dx.doi.org/10.3390/antib11020023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036216PMC
March 2022

COVID-19 Delta Wave Caused Early Overburden of Hospital Capacity in the Bulgarian Healthcare System in 2021.

Healthcare (Basel) 2022 Mar 22;10(4). Epub 2022 Mar 22.

Department of Clinical Immunology, University Hospital Lozenetz, Sofia University St. Kliment Ohridski, 1407 Sofia, Bulgaria.

We develop and apply our methodology to estimate the overburdening of hospitals in Bulgaria during the upcoming delta surge. We base our estimations on an exponential risk model from the UK. Still, the methodology is generally applicable to all risk models, depending on age. Our hypothesis is that during the delta wave in Bulgaria, the system experienced a burden from late August due to decreased capacity. This will explain most of the excess mortality during the wave. We estimate the number of people from the active cases in need of hospitalization and intensive care.
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http://dx.doi.org/10.3390/healthcare10040600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031990PMC
March 2022

MMEF may predict significant BDR and future risk of exacerbations in asthmatic children with normal baseline FEV.

Int J Physiol Pathophysiol Pharmacol 2022 15;14(1):33-47. Epub 2022 Feb 15.

University Hospital Lozenetz, Sofia University - Medical Faculty 1 Kozyak Street, 1407 Sofia, Bulgaria.

(1) Background: Several recent studies on the clinical value of spirometry indexes demonstrated high sensitivity of FEF as a marker of bronchial obstruction in asthmatics with normal baseline spirometry. Our study aims to evaluate the clinical value of maximal mid-expiratory flow in children with asthma. (2) Methods: For two years, 257 children were included - 211 with asthma and 46 healthy controls. Pre- and post-bronchodilator spirometry, atopic status determination and asthma control assessment were performed. (3) Results: The small airway obstruction (SAO) group (FEV≥80%, ММEF<65%) demonstrated significantly lower values for FEV, FEV/FVC, PEFR, МMMF and a significant higher bronchodilator response (BDR, ΔFEV% init. ≥12%) compared to normal baseline spirometry group (FEV>80%, MMEF≥65%) (Р<0.0001). In addition, we found a statistically significant difference in FEF/FVC median between asthmatics and healthy controls (Р<0.0001) regardless of the FEV value. Children with SAO have a 2.338-fold higher risk of poor asthma outcome (OR 95% CI [1.077-5.294]) and a 6.171-fold (OR 95% CI [2.523-15.096]) greater probability of demonstrating positive BDR, compared to children with normal baseline spirometry. MMEF was found to be a good predictor for positive BDR with AUC 0.843 (CI 0.781-0.845) and a best cut-off value of 58.1% (77.8% sensitivity and 78.8% specificity). (4) Conclusion: Our results confirmed that a small but substantial group of asthmatic children with normal baseline FEV and low MMEF are at higher risk for poor asthma outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918602PMC
February 2022

Elevated levels of interleukin-18 are associated with several indices of general and visceral adiposity and insulin resistance in women with polycystic ovary syndrome.

Arch Endocrinol Metab 2022 Mar;66(1):3-11

Clinic of Endocrinology, University Hospital "Alexandrovska", Department of Internal Medicine, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.

Objective: Our aim was to analyze levels of proinflammatory biomarker interleukin-18 (IL-18) in healthy controls and patients with polycystic ovary syndrome (PCOS) focusing on its association with obesity, clinical, hormonal, and metabolic characteristics.

Methods: Fifty-eight patients with PCOS were enrolled in the study fulfilling the Rotterdam criteria and were matched for age, body mass index (BMI), and ethnicity with 30 healthy controls. Detailed anthropometric measurements, clinical investigations, hormonal and biochemical tests were obtained between the 3 and 5 day of a menstrual cycle. A subanalysis of the PCOS group was performed separating patients into several groups according to a waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum IL-18 levels were measured using the ELISA method.

Results: Levels of IL-18 were similar between PCOS patients and controls. IL-18 was higher in overweight/obese women compared to normal-weight women when analyzing all participants together and separately PCOS or controls group (p < 0.001, p < 0.001, p = 0.01, respectively). Additionally, IL-18 levels were higher in high-WHtR and IR subgroups compared to low-WHtR (p < 0.001) and non-IR PCOS women (p < 0.001). PCOS women with high FAI had greater serum IL-18 levels than normal-FAI patients (p = 0.002). Levels of IL-18 correlated positively with most of the anthropometric and metabolic parameters. In multiple linear regression, age, waist circumference, and fasting insulin were independently related factors with IL-18.

Conclusion: Elevated levels of IL-18 were related to several indices of general and visceral adiposity and insulin resistance in PCOS.
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http://dx.doi.org/10.20945/2359-3997000000442DOI Listing
March 2022

Anandamide is associated with waist-to-hip ratio but not with body mass index in women with polycystic ovary syndrome.

Minerva Endocrinol (Torino) 2022 Feb 23. Epub 2022 Feb 23.

Department of Internal Medicine, Clinic of Endocrinology, University Hospital Alexandrovska, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.

Background: The endocannabinoid system is involved in the regulation of energy balance and ovarian function and may be implicated in the pathogenesis of polycystic ovary syndrome (PCOS). The purpose of the present study is to determine anandamide (AEA) levels in PCOS patients and controls and to analyze its association with metabolic and hormonal disturbances in women with PCOS.

Methods: The study included 88 women - 58 patients with PCOS (25.9±5.2 years) and 30 healthy controls (27.6±5.2 years). Further, patients were divided into two subgroups according to their waist-to-hip ratio (WHR): android type PCOS (WHR≥0.85; n=26) and gynoid type PCOS (WHR<0.85; n=32). Detailed anthropometric measurements, hormonal and biochemical tests and pelvic ultrasound were obtained between the 3rd and 5th day of a menstrual cycle. AEA was examined by ELISA kits.

Results: Patients with PCOS and healthy controls did not differ in anthropometric, metabolic parameters, AEA, and sex hormone-binding globulin (SHBG) levels. The PCOS group had increased total testosterone, FAI, DHEAS, androstenedione, and 17-OHprogesterone levels (p<0.001) and elevated LH/FSH ratio (p=0.023). A negative correlation between AEA levels was found with glycaemia at 120 minutes (r=-0.304, p=0.020) and WHR (r=-0.266, p=0.044). In the subanalysis of patients, the gynoid type group had significantly higher levels of AEA than the android type PCOS (5.4 [2.3;8.8] vs. 2.5 [1.8;5.1]; p=0.020).

Conclusions: AEA did not differ between healthy women and patients, but a significant difference in its levels was found in PCOS patients divided according to their body constitution type.
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http://dx.doi.org/10.23736/S2724-6507.21.03336-4DOI Listing
February 2022

Liver dysfunction as a cytokine storm manifestation and prognostic factor for severe COVID-19.

World J Hepatol 2021 Dec;13(12):2005-2012

Department of Clinical Immunology, University Hospital Lozenetz, Sofia 1407, Bulgaria.

Liver damage in severe acute respiratory coronavirus 2 infection occurs in patients with or without preexisting liver disorders, posing a significant complication and mortality risk. During coronavirus disease 2019 (COVID-19), abnormal liver function is typically observed. However, liver injury may occur because of the treatment as well. Ischemia, cytokine storm, and hypoxia were identified as the three major factors contributing to liver damage during COVID-19. Indeed, raised liver enzymes during hospitalizations may be attributed to medications used, as well as sepsis and shock. As a result, the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14% to 53%. Aminotransferases and bilirubin are found most often elevated. Usually, increased gamma-glutamyltransferase, alkaline phosphatase, and decreased serum albumin levels are demonstrated. Additionally, although there is no specific treatment for COVID-19, many of the drugs used to treat the infection are hepatotoxic. In this mini-review, we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm. Furthermore, data show that liver injury can be an independent predictor of severe COVID-19, the need for hospitalization, and death.
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http://dx.doi.org/10.4254/wjh.v13.i12.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727206PMC
December 2021

Interferon-gamma release assays outcomes in healthy subjects following BNT162b2 mRNA COVID-19 vaccination.

Rheumatol Int 2022 03 20;42(3):449-456. Epub 2022 Jan 20.

Laboratory of Clinical Immunology, Unversity Hospital "St. Ivan Rilski", Akad. Ivan Geshov Blvd 15, 1431, Sofia, Bulgaria.

The pathogenesis of COVID-19 involves both humoral and cellular immunological responses, with cell-mediated immunity being discussed as the primary and most effective immune response to viral infection. It is supposed that COVID-19 vaccines also elicited effective cell immune response, and specifically IFNγ secreted by SARS-CoV-2-specific T-helper 1 and Tcytotoxic cells. Using an interferon-gamma release assay (IGRA) test, we aimed to monitor cellular post-vaccination immunity in healthy subjects vaccinated with BNT162b2 mRNA COVID-19 vaccine (Comirnaty). We tested 37 healthcare workers (mean age 54.3 years, range 28-72, 22 females, 15 males) following COVID-19 mRNA COVID-19 vaccine and 15 healthy unvaccinated native persons as control subjects using QuantiFERON SARS-CoV-2 RUO test, performed approximately 1 month after vaccination. We also measured virus-neutralizing antibodies. Thirty-one out of 37 tested subjects had significantly raised levels of SARS-CoV-2 specific IFNγ against SARS-CoV-2 Ag1 and Ag2 1 month following COVID-19 vaccination. In addition, we found a significant difference between the IFNγ levels in fully vaccinated subjects and the control group (p < 0.01).We also found a substantial correlation (r = 0.9; p < 0.01) between virus-neutralizing antibodies titers and IFNγ concentrations released by T cells. We believe that IGRA tests are an excellent tool to assess the development of a post-vaccination immune response when immunized against SARS-CoV-2. However, IGRA-based tests should be performed within a few weeks following vaccination. Therefore, we can speculate that the application of these tests to assess long-term immune response is debatable.
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http://dx.doi.org/10.1007/s00296-022-05091-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775149PMC
March 2022

Omentin-1 and diabetic foot.

Int J Low Extrem Wounds 2022 Jan 5:15347346211069813. Epub 2022 Jan 5.

Clinic of Endocrinology, University Hospital Alexandrovska, Department of Internal Medicine, 58789Medical University-Sofia, Sofia, Bulgaria.

Diabetic foot disease is an advanced complication of diabetes mellitus, which is associated with severe invalidization and high mortality rate among affected people. Many factors are involved in its pathogenesis but not all of them are fully elucidated. Adipose tissue and its hormones - adipokines, are related to diabetic complications and metabolic disorders. Until now, there are limited data on their role in diabetic foot. The aim of this cross-sectional study is to determine the levels of the adipokine omentin-1 in people with and without diabetic foot disease and to look for its potential involvement in this complication. Eighty patients with type 2 diabetes and mean age of 60.8±10.5 years were included in this study. They were divided into two groups: with (n=36) and without (n=44) diabetic foot disease. Standard antrometric, clinical and laboratory tests were made. Body composition was analyzed by bioelectrical impedance based device. Serum omentin-1 was measured using ELISA method. Levels of omentin-1 were significantly higher among people with diabetic foot disease (700.2±345.1 ng/ml), compared to the other group (560.2±176.7 ng/ml). This difference remained significant even after adjusting for potential confounders. In a regression model omentin-1 proved its predictive value for development of diabetic foot. Adipokines, and particularly omentin-1, might be included in the pathogenesis of diabetic foot disease.
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http://dx.doi.org/10.1177/15347346211069813DOI Listing
January 2022

Genetic variation of as a protective genotype for the development of colorectal cancer in men.

World J Gastrointest Oncol 2021 Nov;13(11):1766-1780

Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Stara Zagora 6000, Bulgaria.

Background: The role of transforming growth factor beta (TGF-β) signaling, including both the cytokine and their receptors, in the etiology of colorectal cancer (CRC) has been of particular interest lately.

Aim: To investigate the association between promoter polymorphism in TGF-β receptor 2 TGF-ΒR2GA with a CRC risk in a cohort of Bulgarian patients using a case-control gene association study approach, as well as the protein levels of TGF-β1 in the peripheral blood.

Methods: A cohort of 184 CRC patients and 307 sex and age-matched healthy subjects were recruited in the study. A genotyping of the TGF-ΒR2GA (rs3087465) polymorphism was performed by primer-introduced restriction analyses-polymerase chain reaction approaches.

Results: The frequency of TGF-ΒR2GA genotype was decreased in male patients with CRC than in healthy men (31.3% 44.8%; = 0.058). Among males, the TGF-ΒR2GG genotype was related to a significantly increased risk of CRC development (OR = 1.820, 95%CI: 0.985-3.362, = 0.055) than the GA + AA genotype. Also, TGF-ΒR2*A-allele itself was rarer in men with CRC than healthy men (19.1% 26.9%, = 0.086) and was associated with a protective effect (OR = 0.644; 95%CI: 0.389-1.066; = 0.086). Regarding the genotypes, we found that TGF-β1 serum levels were higher in GG genotype in healthy persons above 50 years than the CRC patients [36.3 ng/mL interquartile range (IQR) 19.9-56.5 22.4 ng/mL IQR 14.8-29.7, = 0.014]. We found significant differences between higher levels of TGF-β1 serum levels in healthy controls above 50 years (GG genotype) and CRC patients (GG genotype) at the early stage (36.3 ng/mL IQR 19.9-56.5 22.8 ng/mL IQR 14.6-28.6, = 0.037) and advanced CRC (36.3 ng/mL IQR 19.9-56.5 21.6 ng/mL IQR 15.9-33.9, = 0.039).

Conclusion: In summary, our results demonstrated that TGF-ΒR2 AG and AA genotypes were associated with a reduced risk of CRC, as well as circulating levels of TGF-β could prevent CRC development in a gender-specific manner. Notably, male carriers of TGF-ΒR2 -875A allele genotypes had a lower risk of CRC development and progression, suggesting that TGF-ΒR2 -875A/G polymorphism significantly affects the protective biological factors that also impact the risk of colon and rectal carcinogenesis.
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http://dx.doi.org/10.4251/wjgo.v13.i11.1766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8603459PMC
November 2021

COVID-19 vaccination in autoimmune disease (COVAD) survey protocol.

Rheumatol Int 2022 01 15;42(1):23-29. Epub 2021 Nov 15.

Division of Rheumatology and Clinical Immunology, Department of Medicine, UPMC Arthritis and Autoimmunity Center, School of Medicine, University of Pittsburgh, 3601 Fifth Ave., Suite 2B, Pittsburgh, PA, 15213, USA.

The coronavirus disease-2019 (COVID-19) pandemic continues to be a cause of unprecedented global morbidity and mortality. Whilst COVID-19 vaccination has emerged as the only tangible solution to reducing poor clinical outcomes, vaccine hesitancy continues to be an obstacle to achieving high levels of vaccine uptake. This represents particular risk to patients with autoimmune diseases, a group already at increased risk of hospitalization and poor clinical outcomes related to COVID-19 infection. Whilst there is a paucity of long-term safety and efficacy data of COVID-19 vaccination in patients with autoimmune diseases, the current evidence strongly suggests that the benefits of vaccination outweigh the risks of adverse effects and disease flares. Herein, we report the protocol of the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an ongoing international collaborative study involving 29 countries and over 110 investigators.
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http://dx.doi.org/10.1007/s00296-021-05046-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591970PMC
January 2022

Liver Involvement in Children with COVID-19 and Multisystem Inflammatory Syndrome: A Single-Center Bulgarian Observational Study.

Microorganisms 2021 Sep 15;9(9). Epub 2021 Sep 15.

Department of Clinical Immunology, Medical Faculty, University Hospital Lozenetz, Sofia University, St. Kliment Ohridski, Kozyak 1 Str., 1407 Sofia, Bulgaria.

SARS-CoV-2 infection may precede and cause various autoimmune and inflammatory diseases, including multisystem inflammatory syndrome in children (MIS-C). Therefore, we aimed to observe the clinical presentation and laboratory, instrumental and other constellations in children with MIS-C, including liver involvement. We present the outcomes from a single-center prospective observational study in which 89 children was included (60 with proven COVID-19, 10 symptomatic with confirmed COVID-19 contact and 19 diagnosed with MIS-C). Laboratory, instrumental, immunological, and clinical investigations were performed. Only 12% ( = 4) from the COVID-19 group (except the ICU cases), we found elevated AST and/or ALT (up to 100). All of the children with elevated transaminase were overweight or obese, presenting along with moderate COVID-19 pneumonia. The majority of children with MIS-C showed typical laboratory constellations with higher levels of IL-6 (120.36 ± 35.56 ng/mL). About half of the children in the MIS-C group (52%, = 11) showed elevated transaminases. Eleven children (57.9%) presented with abdominal pain, eight (42.1%) with ascites, two (10.5%) with hepatosplenomegaly, and four (21.1%) with symptoms such as diarrhea. Mesenteric lymphadenitis was observed more often in patients with elevated LDH (327.83 ± 159.39, = 0.077). Ascites was associated with lymphopenia (0.86 ± 0.80, = 0.029) and elevated LDH. Hepato-splenomegaly was also more frequent in children with lymphopenia (0.5 ± 0.14, = 0.039), higher troponin (402.00 ± 101.23, = 0.004) and low ESR. Diarrhea was more frequent in patients with lower CRP (9.00 ± 3.44 vs. 22.25 ± 2.58, = 0.04), and higher AST and ALT (469.00 ± 349.59 vs. and 286.67 ± 174.91, respectively, = 0.010), and D-dimer (4516.66 ± 715.83, = 0.001). Our data suggest that the liver can also be involved in MIS-C, presenting with typical laboratory and instrumental outcomes.
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http://dx.doi.org/10.3390/microorganisms9091958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467138PMC
September 2021

Targeting Inflammatory Cytokines to Improve Type 2 Diabetes Control.

Biomed Res Int 2021 13;2021:7297419. Epub 2021 Sep 13.

Clinic of Rheumatology, University Hospital "St. Marina, " First Department of Internal Medicine, Medical Faculty, Medical University-Varna, Varna 9010, Bulgaria.

Type 2 diabetes (T2D) is one of the most common chronic metabolic disorders in adulthood worldwide, whose pathophysiology includes an abnormal immune response accompanied by cytokine dysregulation and inflammation. As the T2D-related inflammation and its progression were associated with the balance between pro and anti-inflammatory cytokines, anticytokine treatments might represent an additional therapeutic option for T2D patients. This review focuses on existing evidence for antihyperglycemic properties of disease-modifying antirheumatic drugs (DMARDs) and anticytokine agents (anti-TNF-, anti-interleukin-(IL-) 6, -IL-1, -IL-17, -IL-23, etc.). Emphasis is placed on their molecular mechanisms and on the biological rationale for clinical use. Finally, we briefly summarize the results from experimental model studies and promising clinical trials about the potential of anticytokine therapies in T2D, discussing the effects of these drugs on systemic and islet inflammation, beta-cell function, insulin secretion, and insulin sensitivity.
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http://dx.doi.org/10.1155/2021/7297419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455209PMC
January 2022

Surgical complications in COVID-19 patients in the setting of moderate to severe disease.

World J Gastrointest Surg 2021 Aug;13(8):788-795

Department of Clinical Immunology, University Hospital Lozenetz, Sofia 1407, Bulgaria.

The coronavirus disease 2019 (COVID-19) pandemic has had a considerable impact on the work of physicians and surgeons. The connection between the patient and the surgeon cannot be replaced by telemedicine. For example, the surgical staff faces more serious difficulties compared to non-surgical specialists during the COVID-19 pandemic. The primary concerns include the safest solutions for protecting healthcare staff and patients and the ability to provide adequate surgical care. Additionally, the adverse effects of any surgery delays and the financial consequences complicate the picture. Therefore, patients' admission during the COVID-19 pandemic should be taken into consideration, as well as preoperative measures. The COVID-19 situation brings particular risk to patients during surgery, where preoperative morbidity and mortality rise in either asymptomatic or symptomatic COVID-19 patients. This review discusses the recent factors associated with surgical complications, mortality rates, outcomes, and experience in COVID-19 surgical patients.
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http://dx.doi.org/10.4240/wjgs.v13.i8.788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394377PMC
August 2021

Gastrointestinal mucosal immunity and COVID-19.

World J Gastroenterol 2021 Aug;27(30):5047-5059

Clinic of Gastroenterology, Tsaritsa Joanna University Hospital, Medical University of Sofia, Sofia 1527, Bulgaria.

As the gastrointestinal tract may also be a crucial entry or interaction site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the role of the gut mucosal immune system as a first-line physical and immunological defense is critical. Furthermore, gastrointestinal involvement and symptoms in coronavirus disease 2019 (COVID-19) patients have been linked to worse clinical outcomes. This review discusses recent data on the interactions between the virus and the immune cells and molecules in the mucosa during the infection. By carrying out appropriate investigations, the mucosal immune system role in SARS-CoV-2 infection in therapy and prevention can be established. In line with this, COVID-19 vaccines that stimulate mucosal immunity against the virus may have more advantages than the others.
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http://dx.doi.org/10.3748/wjg.v27.i30.5047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384742PMC
August 2021

Factors affecting complications development and mortality after single lung transplant.

World J Transplant 2021 Aug;11(8):320-334

Department of Clinical Immunology, University Hospital Lozenetz, Sofia 1407, Bulgaria.

Lung transplantation (LT) is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung disease. Furthermore, as a therapeutic option for high-risk candidates, single LT (SLT) can be feasible because the immediate morbidity and mortality after transplantation are lower compared to sequential single (double) LT (SSLTx). Still, the long-term overall survival is, in general, better for SSLTx. Despite the great success over the years, the early post-SLT period remains a perilous time for these patients. Patients who undergo SLT are predisposed to evolving early or late postoperative complications. This review emphasizes factors leading to post-SLT complications in the early and late periods including primary graft dysfunction and chronic lung allograft dysfunction, native lung complications, anastomosis complications, infections, cardiovascular, gastrointestinal, renal, and metabolite complications, and their association with morbidity and mortality in these patients. Furthermore, we discuss the incidence of malignancy after SLT and their correlation with immunosuppression therapy.
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http://dx.doi.org/10.5500/wjt.v11.i8.320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371496PMC
August 2021

Hypotheses and facts for genetic factors related to severe COVID-19.

World J Virol 2021 Jul;10(4):137-155

Department of Clinical Immunology, University Hospital Lozenetz, Sofia 1407, Bulgaria.

Genome-wide association analysis allows the identification of potential candidate genes involved in the development of severe coronavirus disease 2019 (COVID-19). Hence, it seems that genetics matters here, as well. Nevertheless, the virus's nature, including its RNA structure, determines the rate of mutations leading to new viral strains with all epidemiological and clinical consequences. Given these observations, we herein comment on the current hypotheses about the possible role of the genes in association with COVID-19 severity. We discuss some of the major candidate genes that have been identified as potential genetic factors associated with the COVID-19 severity and infection susceptibility: , Further study of genes and genetic variants will be of great benefit for the prevention and assessment of the individual risk and disease severity in different populations. These scientific data will serve as a basis for the development of clinically applicable diagnostic and prognostic tests for patients at high risk of COVID-19.
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http://dx.doi.org/10.5501/wjv.v10.i4.137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316875PMC
July 2021

Biomarkers in Irritable Bowel Syndrome: Biological Rationale and Diagnostic Value.

Dig Dis 2022 22;40(1):23-32. Epub 2021 Mar 22.

Department of Clinical Immunology, University Hospital Lozenetz, Sofia University St. Kliment Ohridski, Sofia, Bulgaria.

Background: Patients with irritable bowel syndrome (IBS) usually suffer from nonspecific and overlapping signs that hamper the diagnostic process. In line with this, biomarkers specific for IBS could be of great benefit for diagnosing and managing patients. In IBS, the need is for apparent distinguishing features linked to the disease that improve diagnosis, differentiate from other organic diseases, and discriminate between IBS subtypes.

Summary: Some biomarkers are associated with a possible pathophysiologic mechanism of IBS; others are used for differentiating IBS from non-IBS patients. Implementation of IBS biomarkers in everyday clinical practice is critical for early diagnosis and treatment. However, our knowledge about their efficient use is still scarce. Key Messages: This review discusses the biomarkers implemented for IBS diagnosis and management, such as blood (serum), fecal, immunological, related to the microbiome, microRNAs, and some promising novel biomarkers associated with imaging and psychological features of the disease. We focus on the most commonly studied and validated biomarkers and their biological rationale, diagnostic, and clinical value.
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http://dx.doi.org/10.1159/000516027DOI Listing
January 2022

Neopterin in the Evolution from Obesity to Prediabetes and Newly Diagnosed Type 2 Diabetes.

Metab Syndr Relat Disord 2021 05 16;19(4):249-255. Epub 2021 Feb 16.

Clinic of Endocrinology, Department of Internal Medicine, Medical University of Sofia, University Hospital "Alexandrovska," Sofia, Bulgaria.

Neopterin, marker of cellular immunity and oxidative stress, is mainly produced by activated macrophages. It could play a crucial role in the development of insulin resistance (IR) and type 2 diabetes (T2D). The aim of this study was to investigate the circulating levels of neopterin in different stages of glucose dysregulation from obesity through prediabetes to newly diagnosed diabetes. Neopterin levels were determined using a commercially available human enzyme-linked immunosorbent assay kit. The homeostasis model assessment of IR was used as an index to assess IR. The sample consisted of 163 subjects with mean age 52.5 ± 11.3 years, divided in three age- and body mass index (BMI)-matched groups-obesity, prediabetes, and diabetes. The control group consisted of 42 healthy individuals. Neopterin levels were significantly higher in patients with obesity and/or prediabetes and newly diagnosed diabetes than those in the control group, respectively (4.14 ± 2.51; 4.04 ± 2.80 and 2.17 ± 1.93 vs. 0.87 ± 0.84;  < 0.05). Correlation analysis showed that the level of neopterin positively correlated with BMI, waist, waist-to-stature ratio, waist-to-hip ratio, fasting glucose, and triglycerides. Receiver operating characteristic analysis established neopterin suitable for distinguishing subjects with obesity [area under the curve (AUC) = 0.83;  < 0.001] and carbohydrate disturbances (AUC = 0.59;  < 0.05) from those without these conditions. Neopterin ≥0.47 ng/mL have an odds ratio (OR) of 2.71 for development of dysglycemia, whereas threshold value of neopterin ≥0.56 ng/mL shows an OR of 5.94 for development of obesity. The levels of neopterin were increased in patients with obesity and carbohydrate disturbances. Further studies will elucidate the role of the biomarker in development of T2D and its complications.
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http://dx.doi.org/10.1089/met.2020.0144DOI Listing
May 2021

Antibiotic-Related Changes in Microbiome: The Hidden Villain behind Colorectal Carcinoma Immunotherapy Failure.

Int J Mol Sci 2021 Feb 10;22(4). Epub 2021 Feb 10.

Department of Gastroenterology, University Hospital Lozenetz, Sofia University St. Kliment Ohridski, Kozyak 1 Str., 1407 Sofia, Bulgaria.

The interplay between drugs and microbiota is critical for successful treatment. An accumulating amount of evidence has identified the significant impact of intestinal microbiota composition on cancer treatment response, particularly immunotherapy. The possible molecular pathways of the interaction between immune checkpoint inhibitors (ICIs) and the microbiome can be used to reverse immunotherapy tolerance in cancer by using various kinds of interventions on the intestinal bacteria. This paper aimed to review the data available on how the antibiotic-related changes in human microbiota during colorectal cancer (CRC) treatment can affect and determine ICI treatment outcomes. We also covered the data that support the potential intimate mechanisms of both local and systemic immune responses induced by changes in the intestinal microbiota. However, further better-powered studies are needed to thoroughly assess the clinical significance of antibiotic-induced alteration of the gut microbiota and its impact on CRC treatment by direct observations of patients receiving antibiotic treatment.
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http://dx.doi.org/10.3390/ijms22041754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916407PMC
February 2021

SARS-CoV-2 vaccines and autoimmune diseases amidst the COVID-19 crisis.

Rheumatol Int 2021 03 30;41(3):509-518. Epub 2021 Jan 30.

First Department of Internal Medicine, Faculty of Medicine, Medical University-Varna, 55 Marin Drinov Str., Varna, 9002, Bulgaria.

Coronavirus disease 2019 (COVID-19) pandemic has become challenging even for the most durable healthcare systems. It seems that vaccination, one of the most effective public-health interventions, presents a ray of hope to end the pandemic by achieving herd immunity. In this review, we aimed to cover aspects of the current knowledge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and vaccine candidates in the light of autoimmune inflammatory diseases (AIIDs) and to analyze their potential in terms of safety and effectiveness in patients with AIIDs. Therefore, a focused narrative review was carried out to predict the possible implications of different types of SARS-CoV-2 vaccines which confer distinct immune mechanisms to establish immune response and protection against COVID-19: whole virus (inactivated or weakened), viral vector (replicating and non-replicating), nucleic acid (RNA, DNA), and protein-based (protein subunit, virus-like particle). Still, there is uncertainty among patients with AIIDs and clinicians about the effectiveness and safety of the new vaccines. There are a variety of approaches towards building a protective immunity against SARS-CoV-2. Only high-quality clinical trials would clarify the underlying immunological mechanisms of the newly implemented vaccines/adjuvants in patients living with AIIDs.
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http://dx.doi.org/10.1007/s00296-021-04792-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846902PMC
March 2021

Current concept for tertiary lymphoid structures in urothelial carcinoma of the bladder: a literature review and our experience.

Am J Clin Exp Immunol 2020 15;9(5):64-72. Epub 2020 Dec 15.

Department of Clinical Immunology, Medical University of Sofia, Bulgaria/University Hospital Lozenetz Sofia, Bulgaria.

Bladder carcinoma (BC) is one of the most common malignancies of the urinary system in developed countries, with a high number of recurrences. The secondary lymphoid organs (SLO) are crucial for initiating the adaptive immune response. They are developed as a part of a genetically preprogrammed process during embryogenesis. However, SLO's organogenesis can be reduplicated de novo in other tissues by a process termed lymphoid neo-genesis, giving rise to tertiary lymphoid structures (TLS). These well-organized lymphoid structures in cancer are essential modulators of cancer immunologic response, and the histological examination of TLS gave a new strategy for cancer immunotherapy. This review explores the biological and histological characteristics of TLS in muscle non-invasive and invasive BC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811926PMC
December 2020

Concentrations of Interleukin-1ß in Gingival Crevicular Fluid and Saliva - a Potential Diagnostic Biomarker of Periodontal Diseases.

Folia Med (Plovdiv) 2020 Dec;62(4):825-830

Medical University of Sofia, Sofia, Bulgaria.

Introduction: Bacterial challenge in periodontal diseases activates both local and systemic immune responses of a macroorganism by increasing multiple proinflammatory factors that can be discovered in gingival crevicular fluid (GCF) and in saliva. We tested the hypothesis that IL-1β concentration in GCF and saliva correlates with periodontal health and diseases. Materials and methods: The study included 62 people (mean age 36±14 yrs), divided into three groups - patients with periodontitis (24 people), patients with gingivitis (19 people) and periodontally healthy people (19 people). Saliva and GCF samples were taken from all participants and the levels of IL-1β in all samples were determined by ELISA.

Results: IL-1β concentrations in GCF of healthy individuals were significantly lower than the IL-1β concentration in GCF of patients with gingivitis (p=0.009) and with periodontitis (p.
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http://dx.doi.org/10.3897/folmed.62.e49872DOI Listing
December 2020

What could microRNA expression tell us more about colorectal serrated pathway carcinogenesis?

World J Gastroenterol 2020 Nov;26(42):6556-6571

Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria.

In the last two decades, the vision of a unique carcinogenesis model for colorectal carcinoma (CRC) has completely changed. In addition to the adenoma to carcinoma transition, colorectal carcinogenesis can also occur the serrated pathway. Small non-coding RNA, known as microRNAs (miRNAs), were also shown to be involved in progression towards malignancy. Furthermore, increased expression of certain miRNAs in premalignant sessile serrated lesions (SSLs) was found, emphasizing their role in the serrated pathway progression towards colon cancer. Since miRNAs function as post-transcriptional gene regulators, they have enormous potential to be used as useful biomarkers for CRC and screening in patients with SSLs particularly. In this review, we have summarized the most relevant information about the specific role of miRNAs and their relevant signaling pathways among different serrated lesions and polyps as well as in serrated adenocarcinoma. Additional focus is put on the correlation between gut immunity and miRNA expression in the serrated pathway, which remains unstudied.
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http://dx.doi.org/10.3748/wjg.v26.i42.6556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673963PMC
November 2020
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