Day 1 :
Keynote Forum
Yury Marakhouski
Belarussian Medical Academy of Postgraduate Education, Belarus
Keynote: New possibilities for detecting liver metabolic dysfunction and non-pharmacological effects on it
Time : 12:00-12:30
Biography:
Yury Marakhouski approved as Professor of Clinical Medicine in 2005 year by the Higher Certification Commission of the Council of Ministers of the Republic of Belarus. He is head of the Department Gastroenterology and Nutrition of the Belarussian Medical Academy of Postgraduate Education. He has published more than 30 papers in reputed journals and is serving as a member of the editorial board of several reputed journals (predominantly in Russia and Belarus). His Current Position is Head of Department of Gastroenterology and Nutrition, Belarussian Medical Academy of Postgraduate Education (BelMAPE). He is principal investigator on numerous clinical (18) and preclinical (6) studies and has been involved in the study of many medication including mesalazine, amino acids, anti-TNF drugs.
Abstract:
The criteria for liver metabolic dysfunction remain highly controversial. At the same time, metabolic liver dysfunction is directly related to metabolic flexibility.
Aim: To determine the possibility of alternative liver ketogenesis induction and assess the effect of a special variant of drinking water on this process.
Methods:
Part 1: Search and analysis of publications on ketogenic amino acids (AA) for conducting a clinical study confirming the ketogenic effect of the selected AA.
Part 2: Drinking water with special properties (effect on the body metabolically active components) and their confirmation in preclinical and clinical studies.
Part 3: Selective induction of hepatic ketosis before and after 14 days of water intake.
Results:
Part 1: L-lysine is predominantly indicated as a ketogenic AA, but the ketogenic effect of lysine was not described in humans. Clinical study showed: Area Under Curve (AUC) at lysine doses 1,0 g and 2,0 g was 1155 and 5070, maximum ketones (breath test) on 120 min in both doses was 16 ppm at 1,0 g and 46 ppm at 2,0g. Ketosis index gave the following results in ppm/minute: in 30% cases – 1, 0 and more (fast inductors), 0, 1 - 0, 4 (medium inductors) and with the absence of ketosis - slow inductors.
Part 2: We selected the drinking water (DWP) after special processing (details are not disclosed, patent is being filed). In groups of animals (rats) that received DWP, the survival rate after radiation exposure (dose of 5 Gy) increased by 30%, compared with the control group (water with same composition). Results in animals with DWP showed an improvement in the whole series of metabolic parameters.
Clinical study: The total response to the DWP intake in terms of active cell mass (ACM), intracellular fluid (ICF) and phase angle impedance characterized that water as having a stabilizing effect on the ACM of the body, ICF and cell membranes hydration. The incidence of altered blood glucose values (above 5.5 mmol/l) significantly decreased on the 28-day course of DWP intake. The same results were obtained in the incidence of altered liver biomarkers.
Part 3: Selective induction of hepatic ketosis before and after 14 days of DWP intake. We calculated a ketosis coefficient (KC): the intensity of ketosis multiplied by 100 and divided by the active cells body mass (bioimpedance detected) in kg. The median KC was 2, 8 (25/75 Quartiles = 2, 1 – 5, 9). It was determined, that the patients with a KC 2.0 and lower had liver pathology – MAFLD. According to the results, the L-lysine ketosis induction test is valuable in the liver metabolic flexibility assessment, and DWP drinking increases the liver metabolic flexibility.
Conclusion: A simple and non-invasive method has been developed for liver metabolic status evaluation. The liver metabolic potential can be improved by the regular intake of a special drinking water.
Keynote Forum
Bene Ekine-Afolabi
ZEAB Therapeutic LTD, UK
Keynote: Exploring & exploiting the homeostasis network orchestration & biomarkers in human health: Disease prevention
Time : 14:20-14:50
Biography:
Bene Ekine-Afolabi is a graduate of River State University of Science & Technology in Applied Biology (Medical Microbiology option); with an MRes degree at University of East London, United Kingdom. She had her PhD study & worked at the Department of Natural Sciences, Middlesex University, UK. She trained in practical approach to toxicology in drug development (American College of Toxicology/British Toxicology Society). Bene does research in Microbiology, Molecular Biology and Cancer: Her current focus of research (which has yielded eight designed models), is on the Investigation of molecular mechanism of colorectal cancer and due to the current pandemic, has been involved in drug development for COVID-19. Bene had Harvard University part-sponsored training in therapeutic research in Cancer Biology & Therapeutic. Bene has been involved in three published peer reviewed article, two manuscript awaiting publication, among which one is on COVID-19 and was submitted to the Chief Medical Officer of United Kingdom to assist in response to the pandemic.
Abstract:
Background: The implications of disease in human are mostly addressed from the progression stage. For instance, colorectal cancer is mostly diagnosed at age 50 years and above for non-hereditary colorectal cancer. Insufficient attention has been focused on understanding the early progression of diseases, particularly colorectal cancer, prior to the age in which most diagnosis occurs. Homeostasis biomarkers have not been given enough attention. Importantly, one of the key elements in homeostasis, glutathione, and its associated operating genes, has not been well elucidated in disease initiation, promotion, and progression. Additionally, the interplay the glutathione pathway has with other physiological functions and how they orchestrate in homeostasis is yet to be fully elucidated.
Methods: Targeted quantitative analysis was performed on 41 samples of colon cancer and normal cell lines using capillary electrophoresis mass spectrometry (CE-TOFMS and CE-QqQMS) in the cation and anion analysis modes for analysing cationic and anionic metabolites, respectively. A total of 116 metabolites (54 and 62 metabolites in the cation and anion mode, respectively) involved in glycolysis, pentose phosphate pathway, tricarboxylic acid (TCA) cycle, urea cycle, and polyamine, creatine, purine, glutathione, nicotinamide, choline, and amino acid metabolisms were annotated based on the HMT metabolite database.
Results: In both colon cancer cell lines, HCT-116 and HT-29, there were treatment effects from the addition of fiber and bile acids. Bile acid-A alone appeared to increase oxidative stress, osmotic stress, drive ATP demand and increase NAD+/NADH ratio consistent with a tumor promoter role. Bile acid-B alone decreased levels of oxidative and osmotic stress and energy demand. Bile acid-B magnified decrease levels of oxidative and osmotic stress and energy demand when Bile acid-A and/or Fiber was added. The effects were similar between HCT-116 and HT-29, but not duplicative, as these are two different cancer cell lines.
Conclusion: HCT-116 and HT-29 are colon cancer cell lines that exhibit proliferation in culture. Metabolomics profiling exhibits osmotic, energy and oxidative stress in these cell lines compared to normal colon cells. With different combinations of bile acids and fibres, it has been demonstrated that cellular stress in the colon cancer cells can be reduced to more normal levels.
- Gastroenterology | Gastrointestinal Cancer | Gallbladder and Biliary Tract Diseases | Clinical Advances in Liver Diseases | Esophageal Disease
Session Introduction
Piyush Mathur
Santokba Durlabhji Memorial Hospital, India
Title: The spectrum and outcome of acute pancreatitis patients with acute kidney injury
Time : 10:00-10:30
Biography:
Piyush Mathur is presently working as Senior Consultant Nephrologist at Santokba Durlabhji Memorial Hospital, Jaipur, India which is a 550 bedded multispecialty hospital and teaching institute. He has nearly 25 years of experience after MBBS, working at various institutes and organizations and at various positions including general practice, teaching, specialty, and super specialty training. He is Faculty for CRRT and AKI. He has many publications in national and international journals. He was an author of chapters on Continuous Renal Replacement Therapies and Acute Kidney Injury in many textbooks of Nephrology Principal/sub-investigator in many clinical trials.
Abstract:
Statement of the Problem: Acute Pancreatitis (AP) results in 100,000 hospitalizations per year and the incidence of acute pancreatitis ranges from 13 to 45 per 100,000 population-years. Eighty percent of cases of AP are interstitial and mild; the remaining 20% to 30% are necrotizing and severe with hospital mortality rates of 15%. Acute kidney injury (AKI) is a common serious complication of AP and an important marker of morbidity and mortality in critically ill patients. The prognosis of AP patients with AKI is extremely poor with mortality rates ranging between 25-75%. Purpose of the study: To study the disease spectrum and outcome in patients of AP with AKI. Study type: Prospective, longitudinal, and observational.
Methodology & Theoretical Orientation:
Study design: Cross sectional study: The main source of data for the study was collected from patients with AP admitted in Department of General Medicine and Gastroenterology department of Santokba Durlabhji Memorial Hospital, Jaipur.
Findings: AKI was found in 27 out of total 144 study subject resulting in an incidence of 18.75% in our study. Mean age of patients who developed AKI was 50.48 ± 20.45 which was significantly higher when compared to patients without AKI (40.97 ±16.13) with a P value of 0.009. BMI of AP patients, who developed AKI, was higher (24.56 ± 3.08kg/m2) when compared to patients without AKI (22.90 ± 2.36kg/m2) with p value 0.002. Patients who had higher SOFA score at admission had greater chance of developing AKI. Patients of AP with AKI had average hospital stay of 12.22 ± 8.60 days v/s 8.41 ± 5.87 in non AKI patients. ICU stay in AKI group (8.07 ± 8.99) was also longer when compared to non AKI group (1.74 ± 4.31). AP patients who developed AKI had significantly high mortality (48.15% Vs 1.71%) as compared to patients of AP without AKI. Patients of AP with AKI had very high mortality 48.15% (13 out of 27) as compared to total of 117 patient of AP without AKI where mortality was 1.71%.
Conclusion & Significance: From current study we can conclude that, AKI is a serious complication of AP and leads to a poor outcome.
Lucia Moletta
University of Padova, Italy
Title: Treatment of esophageal perforations: The role of the Pittsburgh Severity Score to guide the therapeutic approach
Time : 11:30-12:00
Biography:
Lucia Moletta graduated at the University of Padua Medical School in 2008, and finished his Residency in General Surgery (2015) at the same University. Since 2017, she had been working as research associate at the Department of Surgical, Oncological and Gastroenterological Sciences (DISCOG), Clinica Chirurgica 3, University and Hospital of Padua. She attended in 2015 as a visiting physician the Hepatobiliary and Pancreatic Surgical Unit at the Academisch Medisch Centrum (Amsterdam). Her main interest lies in the oncologic diseases of the pancreas, as far as both the diagnosis and surgical treatment are concerned and in the oncologic diseases of the esophagus and stomach. She is Author and Co-Author of 42 papers dealing with oncologic surgery.
Abstract:
Esophageal perforation (EP) is characterized by high morbidity and mortality. The Pittsburgh Severity Score (PSS) is a scoring system based on clinical factors at the time of EP presentation, intended to guide treatment. The aim of the study is to verify PSS usefulness in stratifying EP severity and in guiding clinical decisions. All patients referred to our Unit for EP between January 2005 and January 2020 was enrolled. Patients were stratified according to their PSS into 3 groups (PSS 2; 3-5 and & gt; 5) the postoperative outcomes were compared. The predictive value of the PSS was evaluated by simple linear and logistic regression for the following outcomes: need for surgery, complications, in-hospital mortality, ICU and hospital stay, and time to refeeding and need for reintervention.
Seventy-three patients were referred for EP (M/F: 46/27). Perforations were more frequently iatrogenic (41.1%) or spontaneous (38.3 %). The median PSS was 4 (IQR 2-6). Surgery was required in 60.3% of cases. PSS was associated with ICU admission, hospital stay, need for surgery and reintervention, post- perforation complications and mortality. After regression analysis, PSS was significantly predictive of post perforation complications (p & lt; 0.01); in-hospital mortality (p=0.01); ICU admission (p & lt; 0.01); need for surgical treatment (p & lt; 0.01) and need for reintervention (p=0.02).
Conclusion: PSS is useful in stratifying patients in risk groups with different morbidity and mortality. It is also useful in guiding the therapeutic conduct, selecting patients for non-operative management. Prospective studies are needed to confirm the role of the PSS in the treatment of esophageal perforation.
Karim Chafee
Alexandria University, Egypt
Title: Effect of extracellular matrix in the process of intestinal anastomosis in the murine model
Biography:
Abstract:
The extracellular matrix (ECM) is a non-cellular, three-dimensional network that provides structural and biochemical support to surrounding cells. Resident cells secrete ECM components intracellularly via exocytosis. This process produces an interlocking web of fibrous proteins and glycosaminoglycans (GAGs). These polymers attach to ECM proteins to form negatively charged proteoglycans which attract sodium ions and water.
This process hydrates the ECM. Examples of GAGs are heparan sulfate and chondroitin sulfate. Heparan sulfate regulates angiogenesis, blood coagulation, and tumor metastasis while chondroitin sulfates help cartilage, tendons, ligaments, and aorta walls to maintain tensile strength. Furthermore, the most prevalent protein in the ECM is collagen, which provides structural support to the cell. Elastins are synthesized by fibroblasts, and in smooth muscle cells provide tissue elasticity. Attachment proteins, such as fibrin and fibronectin, link the ECM through binding to cell surface integrin receptors.
The ECM undergoes constant remodeling during normal and pathological states which is driven by various matrix-degrading enzymes. These enzymes are vital for maintaining normal homeostasis. Growth factors up regulate the expression of integrin receptors in fibroblasts, making cell-matrix interactions easier. Variations in the composition of the ECM affect cytokine control of fibroblast responses. After cytokine stimulation of fibroblasts, the expression of matrix-degrading enzymes, such as MMPs, is elevated. Then TGF- inhibits collagenolytic MMP-1, which is caused by IL- Activating plasminogen.
This results in matrix degradation and facilitates cell migration. Modulation of these processes opens up new avenues for controlling the cell-matrix interaction during wound healing. In intestinal anastomosis, the ECM has been used to improve adherence and prevent dehiscence in the murine model. The use of ECM as an adjuvant in intestinal anastomosis improves the outcome and is an option to enhance surgical anastomosis significantly.
Lem Edith Abongwa
University of Bamenda, Cameroon
Title: Development of hepatotoxicity in individuals harbouring different HIV subtypes and drugresistant variants in Cameroon
Time : 13:50-14:20
Biography:
Lem is a lecturer in the University of Bamenda-Cameroon. She was awarded her Ph.D. in Medical Microbiology in 2019 from Kenyatta University. Her Ph.D. work focused on hepatotoxicity, genetic diversity, and drug-resistant mutation among HIV patients. Her research focus is exploring parasite strain diversity and it impact on disease progression, diagnosis, response to treatment, associated side effects, and the identification of drug resistance mutation. She has a keen interest in the identification and assessment of risk factors that expose communities to infections and possible solutions to prevention and control. She has co-authored several research papers and is also a reviewer in some peer journals. She is currently a Visiting Research Fellow in the African Center of Excellence for Genomics and Infectious Diseases (ACEGID) at Redeemer’s University in Nigeria. She perceives that life is a process of conscious evolution as female researchers and mentors in science.
Abstract:
The advent of antiretroviral therapy (ART) has significantly reduced the morbidity and mortality rates in HIV infected patients. However, hepatotoxicity has been reported across all families of ART and is one of the leading causes of morbidity and mortality. Nowadays with increased ART treatment coverage, drug resistance-associated mutations (DRM) are expected to increase. Furthermore, Genetic diversity remains one of the major hindrances to the eradication of HIV and has shown to influence disease progression, therapy success and vaccine design. This study aim to determine the effect of HIV-1 genetic variants and DRM on the development of hepatotoxicity, this was a longitudinal study of 81 newly diagnosed HIV-infected individuals in five HIV Treatment clinics in the Northwest Region of Cameroon.
Eighty-one antiretroviral drug-naïve patients were recruited into the study and followed-up for 6 months. Blood samples were collected prior to ART initiation and 180 days (D180) later. Serum levels of aminotransferases were analysed by enzymatic methods. The HIV-1 protease and reverse transcriptase sequences were obtained using an in-house protocol and DRMs were identified using the Stanford HIVDR interpretation program, and HIV-1 subtypes by phylogeny.
Results: The mean age of the study participants was 36.5 years. Of these, 37(45.7%) patients showed hepatotoxicity at D180. There were four pure subtypes and five recombinant types with CRF02_AG (74.1%) being the predominant genetic variants. The prevalence of hepatotoxicity was highest among individuals infected with HIV-1 CRF02_AG (70.3%). The prevalence of DRM was 11.1% (9/81). Hepatotoxicity was significantly (p =0.04) higher 77.8% (7/9) among patients with resistant virus.
Conclusion: Data from this study reveals a high level of hepatotoxicity among patients with DRM probably as a result of persistent viral replication. These findings highlight the need to conduct routinely DRM surveillance among patients with hepatotoxicity in order to improve patient management and care.
Efren Mireles Sandoval
Autonomous University of Zacatecas, Mexico
Title: Effect of extracellular matrix in the process of intestinal anastomosis in the murine model
Time : 14:50-15:20
Biography:
Efren has completed his MD from the Autonomous University of Zacatecas and is now part of the first generation of a select group of doctors to carry out the Professional Master in Medical Consultation of Excellence by Harvard University. He was also a participant of the Professional Master in Neoconcepts in Endocrine Metabolism with the Japanese Medical Institute. He has done multiple internships in general, maxillofacial and plastic surgery in Italy and Mexico. Currently has homologated his title in Spain and in the process of the United States Medical Licensing to continue post graduate studies and a fellowship in surgery. Recently with the pandemic he forms part of a medical network that provides distance consultation to patients in need of assistance in Mexico.
Abstract:
The extracellular matrix (ECM) is a non-cellular, three-dimensional network that provides structural and biochemical support to surrounding cells. Resident cells secrete ECM components intracellularly via exocytosis. This process produces an interlocking web of fibrous proteins and glycosaminoglycans (GAGs). These polymers attach to ECM proteins to form negatively charged proteoglycans which attract sodium ions and water.
This process hydrates the ECM. Examples of GAGs are heparan sulfate and chondroitin sulfate. Heparan sulfate regulates angiogenesis, blood coagulation, and tumor metastasis while chondroitin sulfates help cartilage, tendons, ligaments, and aorta walls to maintain tensile strength. Furthermore, the most prevalent protein in the ECM is collagen, which provides structural support to the cell. Elastins are synthesized by fibroblasts, and in smooth muscle cells provide tissue elasticity. Attachment proteins, such as fibrin and fibronectin, link the ECM through binding to cell surface integrin receptors.
The ECM undergoes constant remodeling during normal and pathological states which is driven by various matrix-degrading enzymes. These enzymes are vital for maintaining normal homeostasis. Growth factors up regulate the expression of integrin receptors in fibroblasts, making cell-matrix interactions easier. Variations in the composition of the ECM affect cytokine control of fibroblast responses. After cytokine stimulation of fibroblasts, the expression of matrix-degrading enzymes, such as MMPs, is elevated. Then TGF- inhibits collagenolytic MMP-1, which is caused by IL- Activating plasminogen.
This results in matrix degradation and facilitates cell migration. Modulation of these processes opens up new avenues for controlling the cell-matrix interaction during wound healing. In intestinal anastomosis, the ECM has been used to improve adherence and prevent dehiscence in the murine model. The use of ECM as an adjuvant in intestinal anastomosis improves the outcome and is an option to enhance surgical anastomosis significantly.