Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (9)

Search Parameters:
Authors = Eduard Tilkiyan

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
12 pages, 302 KiB  
Article
The Impact of a 10-Month Synbiotic Intake on eGFR, Uremic Toxins, Oxidative Stress, and Inflammatory Markers in Non-Dialysis Chronic Kidney Disease Patients: A Prospective, Non-Randomized, Placebo-Controlled Study
by Teodor Kuskunov, Eduard Tilkiyan, Irina Zdravkova, Siyana Valova, Krasimir Boyanov and Anelia Bivolarska
Medicina 2025, 61(7), 1199; https://doi.org/10.3390/medicina61071199 - 30 Jun 2025
Viewed by 354
Abstract
Background and Objectives: The worldwide prevalence of chronic kidney disease (CKD) continues to increase, representing a major concern for public health systems. CKD is associated with gut microbiota dysbiosis, which may exacerbate disease progression by increasing the levels of uremic toxins, systemic [...] Read more.
Background and Objectives: The worldwide prevalence of chronic kidney disease (CKD) continues to increase, representing a major concern for public health systems. CKD is associated with gut microbiota dysbiosis, which may exacerbate disease progression by increasing the levels of uremic toxins, systemic inflammation, and oxidative stress. Modulation of the gut microbiota through biotic supplementation has been proposed as a potential therapeutic strategy to slow CKD progression and mitigate its complications. This study aimed to evaluate the effect of 10-month synbiotic supplementation on estimated glomerular filtration rate (eGFR), circulating concentrations of indoxyl sulfate (IS), p-cresyl sulfate (p-CS), interleukin-6 (IL-6), and malondialdehyde (MDA) in patients with stage IV–V CKD not receiving dialysis, in comparison to placebo. Materials and Methods: Fifty non-dialysis CKD IV–V patients were assigned (n = 25 each) via matched, non-randomized allocation (age, sex, and primary disease) to synbiotic or placebo. This single-blind, placebo-controlled trial blinded participants and laboratory personnel. The synbiotic group received daily capsules containing Lactobacillus acidophilus La-14 (2 × 1011 CFU/g) + fructooligosaccharides; controls received identical placebo. Adherence was monitored monthly (pill counts, diaries), with < 80% over two visits resulting in withdrawal. The eGFR, IS, p-CS, IL-6, and MDA were measured at baseline and month 10. Results: Forty-two patients (21/arm) completed the study; eight withdrew (4 per arm). At 10 months, the change in eGFR was −1.2 ± 2.5 mL/min/1.73 m2 (synbiotic) vs. −3.5 ± 3.0 mL/min/1.73 m2 (placebo); between-group difference in change was 2.3 mL/min/1.73 m2 (95% CI: 0.5–4.1; p = 0.014; adjusted p = 0.07). IS decreased by −15.4 ± 8.2 ng/L vs. −3.1 ± 6.5 ng/L; between-group difference in change was −12.3 ng/L (95% CI: −17.8 to −6.8; p < 0.001; adjusted p = 0.005). No significant differences were observed for p-CS, IL-6, or MDA after correction. Conclusions: Synbiotic supplementation over a 10-month period resulted in a trend toward decreased serum IS levels in patients with advanced CKD, suggesting potential benefits of microbiota-targeted therapies. However, no significant effects were observed on renal function, inflammatory, or oxidative stress markers. Further large-scale studies are warranted to confirm these findings and explore the long-term impact of synbiotics in CKD management. Full article
(This article belongs to the Section Urology & Nephrology)
17 pages, 2543 KiB  
Case Report
Acute Kidney Injury and Chronic Kidney Disease Associated with a Genetic Defect: A Report of Two Cases
by Irina Zdravkova, Eduard Tilkiyan, Hristo Ivanov, Atanas Lambrev, Violeta Dzhongarova, Gergana Kraleva and Boris Kirilov
Int. J. Mol. Sci. 2025, 26(10), 4681; https://doi.org/10.3390/ijms26104681 - 14 May 2025
Viewed by 723
Abstract
Rhabdomyolysis is one of the leading causes of acute kidney injury (AKI) and is infrequently associated with chronic kidney disease (CKD). CKD appears in diabetes mellitus and arterial hypertension, as a result of other systemic diseases and glomerulonephritis. In this study, we present [...] Read more.
Rhabdomyolysis is one of the leading causes of acute kidney injury (AKI) and is infrequently associated with chronic kidney disease (CKD). CKD appears in diabetes mellitus and arterial hypertension, as a result of other systemic diseases and glomerulonephritis. In this study, we present two cases (one with CKD and one with AKI) that are caused by a genetic defect. A genetic examination was performed in both patients, proving that the patient with CKD has a genetic defect in the RYR1 gene, which is observed in patients with malignant hyperthermia. Meanwhile, the patient with AKI has a homozygous pathogenic variant in SLC2A9, which is associated with urinary urate wasting and is characterized by asymptomatic hypouricemia and AKI after exercise. The first case is chronic rhabdomyolysis, as the patient is an athlete and performs heavy daily exercise. The second case is AKI without prior kidney damage or symptoms. Both patients did not undergo a kidney biopsy. In the first case, changes in daily routine without extreme physical exercise led to the recovery of normal kidney function. The second patient recovered from AKI without sequelae. These two cases are an example of “thinking outside the box” with respect to how genetic diseases and defects can cause kidney damage, both chronic and acute. Full article
Show Figures

Graphical abstract

18 pages, 5008 KiB  
Hypothesis
Hypothetical Pathogenetic Model of Membranous Nephropathy
by Irina Zdravkova, Eduard Tilkiyan, Desislava Bozhkova, Teodor Kuskunov, Yovko Ronchev and Boris Kirilov
Int. J. Mol. Sci. 2025, 26(5), 2206; https://doi.org/10.3390/ijms26052206 - 28 Feb 2025
Viewed by 816
Abstract
Membranous nephropathy (MN) is a disease with an etiology and pathogenesis that are still not fully understood, and it represents a great challenge. It is characterized by a variable course, spontaneous remissions and relapses. The inability to rely entirely on antibodies and the [...] Read more.
Membranous nephropathy (MN) is a disease with an etiology and pathogenesis that are still not fully understood, and it represents a great challenge. It is characterized by a variable course, spontaneous remissions and relapses. The inability to rely entirely on antibodies and the continuous threat of a malignant disease make the differentiation of MN types extremely difficult. Data of twelve patients with membranous nephropathy, ranging in age between 28 and 67 years, are presented; in total, seven men and five women were observed for a period of 2 to 10 years. In all patients, the diagnosis was confirmed through kidney biopsy and laboratory tests, including immunological, histopathological, and immunohistochemical tests. Histopathological and immunohistochemical tests were applied on available material from the thyroid gland in two patients and the gallbladder in two patients with MN. Data of 102 patients with MN and their comorbidities are evaluated in order to establish correlations. These and other data are used to build a hypothetical pathogenetic model that explains the etiology and the likely pattern of disease occurrence. We found a connection between chronic cholecystitis, thyroiditis, hepatitis, and other diseases in the occurrence of MN and disease course. From our practice and cases, we drew the conclusion that chronic inflammation in sites that express PLA2R leads to the formation of antibodies against PLA2R. These antibodies occur as a preformed immune complex or separately and are deposited in the subepithelial space, leading to MN appearance. Full article
Show Figures

Figure 1

15 pages, 258 KiB  
Review
Artificial Intelligence Algorithms and Their Current Role in the Identification and Comparison of Gleason Patterns in Prostate Cancer Histopathology: A Comprehensive Review
by Usman Khalid, Jasmin Gurung, Mladen Doykov, Gancho Kostov, Bozhidar Hristov, Petar Uchikov, Maria Kraeva, Krasimir Kraev, Daniel Doykov, Katya Doykova, Siyana Valova, Lyubomir Chervenkov, Eduard Tilkiyan and Krasimira Eneva
Diagnostics 2024, 14(19), 2127; https://doi.org/10.3390/diagnostics14192127 - 25 Sep 2024
Cited by 1 | Viewed by 1840
Abstract
The development of the Gleason grading system has proven to be an irreplaceable tool in prostate cancer diagnostics within urology. Despite the advancements and developments in diagnostics, there remains a discrepancy in the grading process among even the most experienced pathologists. AI algorithms [...] Read more.
The development of the Gleason grading system has proven to be an irreplaceable tool in prostate cancer diagnostics within urology. Despite the advancements and developments in diagnostics, there remains a discrepancy in the grading process among even the most experienced pathologists. AI algorithms have demonstrated potential in detecting cancer and assigning Gleason grades, offering a solution to the issue of significant variability among pathologists’ evaluations. Our paper explores the evolving role of AI in prostate cancer histopathology, with a key focus on outcomes and the reliability of various AI algorithms for Gleason pattern assessment. We conducted a non-systematic review of the published literature to examine the role of artificial intelligence in Gleason pattern diagnostics. The PubMed and Google Scholar databases were searched to gather pertinent information about recent advancements in artificial intelligence and their impact on Gleason patterns. We found that AI algorithms are increasingly being used to identify Gleason patterns in prostate cancer, with recent studies showing promising advancements that surpass traditional diagnostic methods. These findings highlight AI’s potential to be integrated into clinical practice, enhancing pathologists’ workflows and improving patient outcomes. The inter-observer variability in Gleason grading has seen an improvement in efficiency with the implementation of AI. Pathologists using AI have reported successful outcomes, demonstrating its effectiveness as a supplementary tool. While some refinements are still needed before AI can be fully implemented in clinical practice, its positive impact is anticipated soon. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
14 pages, 12506 KiB  
Article
Mannose-Binding Lectin Deposition in Membranous Nephropathy and Differentiation of Primary from Secondary Forms
by Irina Zdravkova, Eduard Tilkiyan and Desislava Bozhkova
Int. J. Mol. Sci. 2024, 25(14), 7659; https://doi.org/10.3390/ijms25147659 - 12 Jul 2024
Viewed by 1261
Abstract
The differentiation between primary and secondary forms of membranous nephropathy (MN) is a cornerstone that is necessary for adequate decision making regarding the treatment options and behavior of each specific case. Kidney biopsy and antibody results can be controversial, and a unique biomarker [...] Read more.
The differentiation between primary and secondary forms of membranous nephropathy (MN) is a cornerstone that is necessary for adequate decision making regarding the treatment options and behavior of each specific case. Kidney biopsy and antibody results can be controversial, and a unique biomarker has still not been found. Background and Objectives: We investigated the lack of mannose-binding lectin (MBL) deposition in patients with secondary MNs (sMNs) with the presence of IgG4 deposition in relation to the presence of MBL deposition in patients with primary MNs (pMNs). We also established a connection between the stage of MN and MBL deposition. Materials and Methods: Materials from 72 renal biopsies with proven MN were used for immunohistochemistry staining (IHC) for the phospholipase A2 receptor (PLA2R), immunoglobulin subtype IgG4, and MBL. Patients were separated into one of the following three groups: primary MN (pMN), idiopathic MN (iMN), and secondary MN (sMN). Serum antibodies for PLA2R and thrombospondin type-I-domain-containing 7A (THSD7A) were also used for the precise evaluation of the type of MN, as well as for detecting positivity for PLA2R using IHC. Which stage of MN was present in relation to the deposition of MBL was evaluated. Results: In total, 50 patients were positive for IgG4, 34 with pMN, 12 with iMN, and 4 with sMN. A total of 20 patients were positive for MBL, 14 with pMN and 6 with iMN; no MBL deposits were found in patients with sMN. MBL positivity was predominantly present in the first two stages of MN, with a gradual reduction in the later stages. Conclusions: The activation of the lectin–complement pathway occurs in the early stages of the disease and is associated with the deposition of IgG4; IgG4 deposition is present in sMN, but there is no MBL deposition. IgG4 cannot be used for the differentiation of primary from secondary MNs, but the lack of MBL can be used as a marker for sMN in the early stages of the disease. Full article
Show Figures

Figure 1

12 pages, 2833 KiB  
Case Report
Hepatico-Duodenal Fistula Following Iatrogenic Strasberg Type E4 Bile Duct Injury: A Case Report
by Bozhidar Hristov, Daniel Doykov, Desislav Stanchev, Krasimir Kraev, Petar Uchikov, Gancho Kostov, Siyana Valova, Eduard Tilkiyan, Katya Doykova and Mladen Doykov
Medicina 2023, 59(9), 1621; https://doi.org/10.3390/medicina59091621 - 7 Sep 2023
Cited by 3 | Viewed by 2506
Abstract
Introduction: Gallstone disease (GSD) is among the most common disorders worldwide. Gallstones are established in up to 15% of the general population. Laparoscopic cholecystectomy (LC) has become the “gold standard” for treatment of GSD but is associated with a higher rate of certain [...] Read more.
Introduction: Gallstone disease (GSD) is among the most common disorders worldwide. Gallstones are established in up to 15% of the general population. Laparoscopic cholecystectomy (LC) has become the “gold standard” for treatment of GSD but is associated with a higher rate of certain complications, namely, bile duct injury (BDI). Biliary fistulas (BF) are a common presentation of BDI (44.1% of all patients); however, they are mainly external. Post-cholecystectomy internal BF are exceedingly rare. Case report: a 33-year Caucasian female was admitted with suspected BDI after LC. Strasberg type E4 BDI was established on endoscopic retrograde cholangiopancreatography (ERCP). Urgent laparotomy established biliary peritonitis. Delayed surgical reconstruction was planned and temporary external biliary drains were positioned in the right and left hepatic ducts. During follow-up, displacement of the drains occurred with subsequent evacuation of bile through the external fistula, which resolved spontaneously, without clinical and biochemical evidence of biliary obstruction or cholangitis. ERCP established bilio-duodenal fistula between the left hepatic duct (LHD) and duodenum, with a stricture at the level of the LHD. Endoscopic management was chosen with staged dilation and stenting of the fistulous tract over 18 months until fistula maturation and stricture resolution. One year after stent extraction, the patient remains symptom free. Discussion: Management of post-cholecystectomy BDI is challenging. The optimal approach is determined by the level and extent of ductal lesion defined according to different classifications (Strasberg, Bismuth, Hannover). Type E BDI are managed mainly surgically with a delayed surgical approach generally deemed preferable. Only three cases of choledocho-duodenal fistulas following LC BDI currently exist in the literature. Management is controversial, with expectant approach, surgical treatment (biliary reconstruction), or liver transplantation being described. Endoscopic treatment has not been described; however, in the current paper, it proved to be successful. More reports or larger case series are needed to confirm its applicability and effectiveness, especially in the long term. Full article
(This article belongs to the Special Issue Advances in Cholecystitis and Cholecystectomy)
Show Figures

Figure 1

12 pages, 8070 KiB  
Article
The Effect of Synbiotic Supplementation on Uremic Toxins, Oxidative Stress, and Inflammation in Hemodialysis Patients—Results of an Uncontrolled Prospective Single-Arm Study
by Teodor Kuskunov, Eduard Tilkiyan, Daniel Doykov, Krasimir Boyanov, Anelia Bivolarska and Bozhidar Hristov
Medicina 2023, 59(8), 1383; https://doi.org/10.3390/medicina59081383 - 28 Jul 2023
Cited by 10 | Viewed by 2537
Abstract
Introduction: Numerous studies to date have shown that the development of dysbiotic gut microbiota is a characteristic finding in chronic kidney disease (CKD). A number of uremic toxins progressively accumulate in the course of CKD, some of them generated by the intestinal [...] Read more.
Introduction: Numerous studies to date have shown that the development of dysbiotic gut microbiota is a characteristic finding in chronic kidney disease (CKD). A number of uremic toxins progressively accumulate in the course of CKD, some of them generated by the intestinal microbiome, such as indoxyl sulfate (IS) and p-cresyl sulfate (p-CS). They are found to be involved in the pathogenesis of certain complications of uremic syndrome, including low-grade chronic inflammation and oxidative stress. The aim of the present study is to research the serum concentration of IS and p-CS in end stage renal disease (ESRD) patients undergoing conventional hemodialysis, as well as to study the possibilities of influencing some markers of inflammation and oxidative stress after taking a synbiotic. Materials and Methods: Thirty patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment who were taking a synbiotic in the form of Lactobacillus acidophilus La-14 2 × 1011 (CFU)/g and prebiotic fructooligosaccharides were included in the study. Serum levels of total IS, total p-CS, Interleukin-6 (IL-6), and Malondialdehyde (MDA) were measured at baseline and after 8 weeks. Results. The baseline values of the four investigated indicators in the patients were significantly higher—p-CS (29.26 ± 58.32 pg/mL), IS (212.89 ± 208.59 ng/mL), IL-6 (13.84 ± 2.02 pg/mL), and MDA (1430.33 ± 583.42 pg/mL), compared to the results obtained after 8 weeks of intake, as we found a significant decrease in the parameters compared to the baseline—p-CS (6.40 ± 0.79 pg/mL, p = 0.041), IS (47.08 ± 3.24 ng/mL, p < 0.001), IL-6 (9.14 ± 1.67 pg/mL, p < 0.001), and MDA (1003.47 ± 518.37 pg/mL, p < 0.001). Conclusions: The current study found that the restoration of the intestinal microbiota in patients with CKD significantly decreases the level of certain uremic toxins. It is likely that this favorably affects certain aspects of CKD, such as persistent low-grade inflammation and oxidative stress. Full article
(This article belongs to the Section Urology & Nephrology)
Show Figures

Figure 1

10 pages, 1143 KiB  
Case Report
Cholangioscopy-Assisted Laser Lithotripsy for Treatment of Postcholecystectomy Mirizzi Syndrome: Case Series
by Bozhidar Hristov, Daniel Doykov, Vladimir Andonov, Deyan Radev, Krasimir Kraev, Petar Uchikov, Gancho Kostov, Siyana Valova, Eduard Tilkiyan and Katya Doykova
Gastroenterol. Insights 2023, 14(1), 121-130; https://doi.org/10.3390/gastroent14010009 - 6 Mar 2023
Cited by 1 | Viewed by 6355
Abstract
Introduction. Mirizzi syndrome (MS) represents a rare clinical entity caused by impaction of one or multiple stones in the infundibulum of the gall bladder or the cystic duct resulting in partial or complete obstruction of the common hepatic or common bile duct (CBD). [...] Read more.
Introduction. Mirizzi syndrome (MS) represents a rare clinical entity caused by impaction of one or multiple stones in the infundibulum of the gall bladder or the cystic duct resulting in partial or complete obstruction of the common hepatic or common bile duct (CBD). Though described more than a century ago, MS is still one of the most challenging diseases in the spectrum of biliary pathology. In recent years, endoscopic treatment has become an increasingly popular treatment modality. Patients and methods. Three consecutive patients subjected to cholangioscopy-assisted laser lithotripsy (CA-LL) for postocholecystectomy MS (pMS) were retrospectively evaluated. Case reports. Successful clearance of the cystic duct was achieved in all patients in one or two sessions. One complication in the form of mild cholangitis was observed. Clinical success was 100%. Discussion. According to current research, CA-LL achieves a high rate of ductal clearance and acceptable complication rate in patients with pMS. A 250 µm laser fiber seems to be the optimal choice for CA-LL. Our results suggest that procedure duration is closely associated to the stone size and possibly to the operator experience. In our opinion, upon obtainment of successful ductal clearance and drainage, prophylactic stenting does not improve clinical outcome. Conclusions. Our results demonstrate that CA-LL is a safe and effective treatment for pMS. Full article
(This article belongs to the Section Biliary Content)
Show Figures

Figure 1

9 pages, 3047 KiB  
Case Report
Clinical Outcomes of EUS-Guided Choledochoduodenostomy for Biliary Drainage in Unresectable Pancreatic Cancer: A Case Series
by Bozhidar Hristov, Deyan Radev, Petar Uchikov, Gancho Kostov, Mladen Doykov, Siyana Valova and Eduard Tilkiyan
Medicina 2023, 59(2), 351; https://doi.org/10.3390/medicina59020351 - 13 Feb 2023
Cited by 6 | Viewed by 3129
Abstract
Introduction. Pancreatic ductal adenocarcinoma (PDA) is associated with poor prognosis and 98% loss-of-life expectancy. 80% of patients with PDA are unfit for radical surgery. In those cases, emphasis is set on management of cancer-related symptoms, among which obstructive jaundice is most common. Endoscopic [...] Read more.
Introduction. Pancreatic ductal adenocarcinoma (PDA) is associated with poor prognosis and 98% loss-of-life expectancy. 80% of patients with PDA are unfit for radical surgery. In those cases, emphasis is set on management of cancer-related symptoms, among which obstructive jaundice is most common. Endoscopic ultrasound-guided biliary drainage (EUS-BD) emerges as a valid alternative to the well-accepted methods for treatment of biliary obstruction. Patient Selection. Five consecutive patients with unresectable pancreatic malignancy, were subjected to EUS-BD, particularly EUS-guided choledochoduodenostomy (EUS-CDS). Ethics. Oral and written informed consent was obtained in all cases prior procedure. Technique. EUS-guided puncture of the common bile duct was performed, followed by advancement of a guidewire to the intrahepatic bile ducts. After dilation of the fistulous tract with a cystotome, a fully covered self-expandable metal stent was inserted below the hepatic confluence and extending at least 3 cm in the duodenum. Technical and clinical success was achieved in four patients without adverse events. In one patient procedure failed due to dislocation of the guidewire, with consequent biliary leakage requiring urgent surgery. Recovery was uneventful with no further clinical sequelae and there was no mortality associated with procedure. Discussion. Introduced in 2001, EUS-guided biliary drainage has become an accepted option for treatment of obstructive jaundice. According to recent guidelines published by European Society of Gastrointestinal Endoscopy (ESGE) in 2022, EUS-CDS is a preferred modality to percutaneous transhepatic biliary drainage (PTBD) and surgery in patients with failed ERCP, with comparable efficiency and better safety profile, which is supported by our experience with the procedure. Conclusions. Our case series suggests that EUS-CDS is an excellent option for palliative management of malignant distal biliary obstruction, emphasizes on the importance of adequate technique and experience for the technical success, and urges the need for future research on establishing the best choice for guidewire and dilation device. Full article
(This article belongs to the Special Issue Acute and Chronic Pancreatitis, Pancreatic Malignancies)
Show Figures

Figure 1

Back to TopTop