5-Fluorouracil Induced Hypertriglyceridemia During the Colorectal Cancer Treatment in a Patient With Multifactorial Chylomicronemia Syndrome: A Case Report.

PURPOSE: The case of a 47-year-old female patient who underwent sigmoidectomy for metastatic colorectal cancer is reported. Treatment with capecitabine and 5-fluorouracil induced severe hypertriglyceridemia repeatedly. METHODS: Based on laboratory tests and clinical evaluations, treatment was suggested by specialists. FINDINGS: After treatment with capecitabine, the patient's triglycerides increased from 19.7 mmol/L to 42 mmol/L. It was proposed that the patient had multifactorial chylomicronemia syndrome triggered by secondary factors. Statins, fenofibrate, ezetimib, and metformin were added to the therapy. After metastases appeared, FOLFIRI (leucovorin calcium [folinic acid], 5-fluorouracil, and irinotecan hydrochloride) chemotherapy and biological treatment (cetuximab) followed and triglycerides increased to 55.3 mmol/L. IMPLICATIONS: Monitoring triglyceride levels before and during therapy is suggested.

The Effect of Adjuvant Therapy with Molecular Hydrogen on Endogenous Coenzyme Q10 Levels and Platelet Mitochondrial Bioenergetics in Patients with Non-Alcoholic Fatty Liver Disease.

Molecular hydrogen (H2) has been recognized as a novel medical gas with antioxidant and anti-inflammatory effects. Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increased fat accumulation in liver tissue caused by factors other than alcohol consumption. Platelet mitochondrial function is considered to reflect systemic mitochondrial health. We studied the effect of adjuvant therapy with hydrogen-rich water (HRW) on coenzyme Q10 (CoQ10) content and platelet mitochondrial bioenergetics in patients with NAFLD. A total of 30 patients with NAFLD and 15 healthy volunteers were included in this clinical trial. A total of 17 patients (H2 group) drank water three × 330 mL/day with tablets producing HRW (>4 mg/L H2) for 8 weeks, and 13 patients (P group) drank water with placebo tablets producing CO2. The concentration of CoQ10-TOTAL was determined by the HPLC method, the parameter of oxidative stress, thiobarbituric acid reactive substances (TBARS), by the spectrophotometric method, and mitochondrial bioenergetics in platelets isolated from whole blood by high-resolution respirometry. The patients with NAFLD had lower concentrations of CoQ10-TOTAL in the blood, plasma, and platelets vs. the control group. Mitochondrial CI-linked LEAK respiration was higher, and CI-linked oxidative phosphorylation (OXPHOS) and CII-linked electron transfer (ET) capacities were lower vs. the control group. Plasma TBARS concentrations were higher in the H2 group. After 8 weeks of adjuvant therapy with HRW, the concentration of CoQ10 in platelets increased, plasma TBARS decreased, and the efficiency of OXPHOS improved, while in the P group, the changes were non-significant. Long-term supplementation with HRW could be a promising strategy for the acceleration of health recovery in patients with NAFLD. The application of H2 appears to be a new treatment strategy for targeted therapy of mitochondrial disorders. Additional and longer-term studies are needed to confirm and elucidate the exact mechanisms of the mitochondria-targeted effects of H2 therapy in patients with NAFLD.

Difference in alcohol consumption in central and eastern Slovakia during a coronavirus pandemic (COVID-19).

INTRODUCTION: The COVID-19 pandemic has caused several negative changes. Increased alcohol consumption has been reported in some studies. This study aimed to compare the level of alcohol consumption among college students in the central and eastern regions of Slovakia. MATERIALS AND METHODS: This cross-sectional study was conducted during the COVID-19 pandemic. Three Slovak universities were included in the study. The Alcohol Use Disorders Identification Test (AUDIT) was used to determine alcohol consumption. RESULTS: The total number of college students was 3,647. The overall AUDIT score was significantly higher in the eastern region (p 0.05). During a typical drinking day, more alcohol was consumed in the eastern region compared to the central region of Slovakia in men (p < 0.028). Excess drinking by men has been reported in the eastern region compared to the central region (p 0.05). Inability to remember what happened on a night of drinking was a significant difference in eastern men (p = 0.047). CONCLUSION: Alcohol consumption is a significant problem in Slovakia. The number of students with a high AUDIT score from the eastern region is higher than the number of students with a high AUDIT score from the central region. More significant differences were found between men compared to women from eastern and central Slovakia (Tab. 5, Fig. 2, Ref. 34). Text in PDF www.elis.sk Keywords: alcohol consumption, AUDIT, pandemic, COVID-19, Slovakia.

Molecular mechanisms in the pathogenesis of metabolically associated fatty liver disease.

Inflammation is a common feature of all chronic liver diseases and atherosclerosis. The article discusses the participation of cytokines and inflammasomes in the process of development of metabolically associated fatty liver disease (MAFLD) and the ways of their activation under the influence of inductive stimuli (toxins, alcohol, fat, viruses, etc.), most often in the case of disruption of intestinal permeability through toll-like receptors with an imbalance in the composition of intestinal microflora and bile acids. Inflammasomes and cytokines are the sources of sterile inflammation in the liver in obesity and metabolic syndrome with subsequent lipotoxicity which is followed by fibrogenesis. The prospects for therapeutic modulation of diseases with the participation of inflammasomes are therefore sought precisely at the level of influencing the mentioned molecular mechanisms. The article emphasizes the importance of the liver-intestinal axis and modulation of microbiome, as well as calls attention to the influence of the circadian rhythm of the 12-hour pacemaker on gene production in NASH (non-alcoholic steatohepatitis) developing (Fig. 4, Ref. 56). Keywords: NASH, MAFLD, microbiome, lipotoxicity, bile acids, inflammasomes.

Biological Effects of Hydrogen Water on Subjects with NAFLD: A Randomized, Placebo-Controlled Trial.

Non-alcoholic fatty liver disease (NAFLD) is a liver pathology affecting around 25% of the population worldwide. Excess oxidative stress, inflammation and aberrant cellular signaling can lead to this hepatic dysfunction and eventual carcinoma. Molecular hydrogen has been recognized for its selective antioxidant properties and ability to attenuate inflammation and regulate cellular function. We administered hydrogen-rich water (HRW) to 30 subjects with NAFLD in a randomized, double-blinded, placebo-controlled manner for eight weeks. Phenotypically, we observed beneficial trends (p > 0.05) in decreased weight (≈1 kg) and body mass index in the HRW group. HRW was well-tolerated, with no significant changes in liver enzymes and a trend of improved lipid profile and reduced lactate dehydrogenase levels. HRW tended to non-significantly decrease levels of nuclear factor kappa B, heat shock protein 70 and matrix metalloproteinase-9. Interestingly, there was a mild, albeit non-significant, tendency of increased levels of 8-hydroxy-2'-deoxyguanosine and malondialdehyde in the HRW group. This mild increase may be indicative of the hormetic effects of molecular hydrogen that occurred prior to the significant clinical improvements reported in previous longer-term studies. The favorable trends in this study in conjunction with previous animal and clinical findings suggest that HRW may serve as an important adjuvant therapy for promoting and maintaining optimal health and wellness. Longer term studies focused on prevention, maintenance, or treatment of NAFLD and early stages of NASH are warranted.

Relationship between alcohol consumption and adverse childhood experiences in college students-A cross-sectional study.

Background: Alcohol consumption is an important issue. Adverse childhood experiences (ACEs) can affect alcohol consumption later in life. Therefore, the main objective of this study was to test the association between ACE and the alcohol consumption in college students. Materials and methods: A cross-sectional study on college students was conducted during December 2021 and January 2022, Through the school web system, students received a standard questionnaire on alcohol consumption (AUDIT) and ACEs. The study involved 4,044 participants from three universities in Slovakia. Result: Compared to men, the incidence of emotional abuse by a parent, physical abuse by a parent, and sexual abuse was significantly higher in women (p < 0.001). Furthermore, women reported greater emotional and physical neglect (p < 0.001). The incidence of a high or very high AUDIT score in college students with ACE-0, ACE-1, ACE-2, ACE-3, and ACE-4+ was 3.8, 4.7, 4.1, 6.4, and 9.3%, respectively. Conclusion: More adverse childhood experiences were associated with increased alcohol consumption in both male and female university students. Baseline drinking was higher in male students, but increased drinking in relation to an increase in ACEs was higher in female students. These results point to gender-specific driving forces and targets for intervention.

Questionnaire for risk factors of alcoholic and nonalcoholic fatty liver disease.

OBJECTIVES: Non-communicable diseases are estimated to account for 90 % of total deaths and 19 % of premature deaths in Slovakia. Major preventable risk factors of premature mortality are overweight, obesity and alcohol consumption. BACKGROUND: Screening of risk factors related to alcoholic and nonalcoholic fatty liver diseases (AFLD and NAFLD, respectively) in Slovak outpatients with liver disease. METHODS: A total group of 923 patients, aged 19-91 years were included in the study. Self-administered anonymous questionnaires (Q) were filled in by them. Twelve questions were included relating to age, gender, education, BMI, intake of vegetable, fruit, fish, alcohol, and coffee, as well as to smoking and physical exercise. RESULTS: Overweight/obesity was detected in 59 % of patients, insufficient fiber intake in 87 % of patients, insufficient fish intake in 85 % of patients, and insufficient physical exercise in 68 % of patients. BMI over 25 together with the risk of alcohol consumption was present in 68 % of patients. Smoking was present in 19 % of patients and insufficient coffee intake (from its hepatoprotective point of view) was in 35 % of patients. A total proportion of 75 % of patients were at risk for NAFLD. The risk of alcohol consumption was present in 64 % of patients. CONCLUSIONS: An anonymous questionnaire is a useful screening tool for searching for the risks of NAFLD and AFLD in general practice. Recommendation of a screening schedule for general practitioners is implemented (Tab. 2, Fig. 4, Ref. 36).

Advanced heart failure and cardiac arrhythmia in a young adult survivor of childhood cancer.

The goal of this case report is to describe the young childhood cancer survivor who was treated for nonHodgkin lymphoma with chemotherapy containing anthracycline doxorubicin and who developed symptoms of serious cardiovascular damage 27 years after diagnosis of cancer. The patient is in longterm complete remission of the lymphoma. He started guideline medical therapies for chronic heart failure and had a cardioverter defibrillator implanted for primary prevention of sudden cardiac death. He is currently a candidate for heart transplantation.

Fatal coincidence of inapparent SARS-CoV-2 infection and drug toxicity in the field of immunosuppression in a 33-year old woman.

The COVID-19 pandemic represents a wide-ranging form of involvement from asymptomatic through mild respiratory form to bilateral bronchopneumonia with acute respiratory and multiorgan fatal failure. Patients with comorbidities (obesity, cardiovascular diseases, diabetes mellitus) are particularly at risk of a more severe course of infection. We present a 33-year old lean patient with a medical history of ulcerative colitis on immunosuppressive treatment with Azathioprine, after unsuccessful in vitro fertilization one week before the onset of symptoms, admitted to hospital for two-week-long cough with sore throat with fever ap to 40°C. CT confirmed bilateral bronchopneumonia without etiological detection of the infectious agent. Three PCR tests (two of nasopharyngeal swabs and one of bronchoalveolar lavage (BAL)) were negative for COVID-19, including antigen and antibody tests. Complex parenteral ATB treatment with high-flow nasal oxygen therapy was ineffective, and artificial lung ventilation was indicated for acute respiratory failure. After 4 days antifungal treatment of Fluconazole, condition of patient progressed to hepatic and multiorgan failure and the patient died on day 14 of hospitalization. Post-mortem histological examination revealed the presence of coronavirus in the cells of lung parenchyma. The case recalls that even young patients with immunosuppressive treatment are at risk for the critical course of COVID-19 disease. The negativity of the tests was due to the capture of the patient only after the second week of infection, at the time of the diagnostic window between the positive PCR test and the formation of antibodies. The persistent effect of immunosuppression was most likely the reason for the lack of antibody response.

Glucose Metabolism Changes in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals.

Background and Aims: Chronic hepatitis C is a systemic disease and type 2 diabetes mellitus (T2DM) belongs to more common extrahepatic. The aim of this study was to (i) explore the prevalence of impaired fasting glucose (IFG) and T2DM in patients with chronic hepatitis C, (ii) explore the effect of direct acting antivirals (DAA) treatment on the glycemia, and (iii) explore the factors that modulate the effect of DAA treatment on glycemia in patients with chronic hepatitis C. Methods: We performed a longitudinal retrospective observational study focused on the patients undergoing DAA treatment of chronic hepatitis C. Data about glycemia, history of diabetes, hepatitis C virus, treatment, and liver status, including elastography, were obtained at baseline (before treatment start), at the end of treatment and 12 weeks after the end of treatment. Patients were treated with various regimens of direct acting antivirals. Results: We included 370 patients; 45.9% had F4 fibrosis. At baseline, the prevalence of T2DM increased with the degree of fibrosis (F0-F2 14.4%, F3 21.3%, and F4 31.8%, p=0.004). Fasting glycemia also increased with the degree of fibrosis (F0-F2 5.75±0.18 F3 5.84±0.17, and F4 6.69±0.2 mmol/L, p=0.001). We saw significant decrease of glycemia after treatment in all patients, but patients without T2DM or IFG from 6.21±0.12 to 6.08±0.15 mmol/L (p=0.002). The decrease was also visible in treatment experienced patients and patients with Child-Pugh A cirrhosis. Conclusion: We confirmed that the prevalence of either T2DM or IFG increases in chronic hepatitis C patients with the degree of fibrosis. The predictive factors for T2DM were, besides F4, fibrosis also higher age and BMI. Significant decrease of fasting glycemia after the DAA treatment was observed in the whole cohort and in subgroups of patients with T2DM, IFG, cirrhotic, and treatment experienced patients.

[Drug and herbal hepatotoxicity: an overview of clinical classifications]. / Lieková a herbálna hepatotoxicita: prehlad klinických klasifikácií.

Drug induced liver injury (DILI) is often underdiagnosed disease with increasing incidence. In developed countries it belongs to the leading causes of acute liver failure. Risk groups are women and persons older than 60 years. The work summarizes the up to date information on diagnosis and mostly used classifications on DILI. It is quite often and serious complication of medicament therapy. DILI belongs to the most often cause of acute hepatic failure in the old age in developed countries. Diagnostic procedure includes medical history (time correlation with drug intake), clinical symptoms and blood tests. Laboratory tests may be helpful to specify immunopathogenetic origin, but negative results does not exclude diagnosis. The exclusion of other possible etiological factors is the crucial condition of diagnosis statement. Key words: DILI/drug induced liver toxicity - DILIn network - RUCAM classification.

[Coffee as hepatoprotective factor]. / Káva ako hepatoprotektívny faktor.

The mind about the coffee did change upon the recent studies and metaanalysis of the last years. Consensual protective effect of coffee on the progression of chronic liver diseases (NASH, viral hepatitis, liver cirrhosis, hepatocelullar carcinoma) was detected in experimental, clinical and large population studies together with decrease of mortality. Antioxidant, antifibrotic, insulinsensitizing and anticarcinogenic effect of coffee were detected. Modulation of genetic expression of key enzymes of fatty acid synthesis, modulation of mRNA included in autophagia, reduction of stress of endoplasmatic reticulum together with decrease of proinflammatory cytokines and decrease of fibrogenesis are main mechanisms. Chlorogenic acids, diterpens (cafestol, kahweol), caffein, polyfenols and melanoidins are key protective components of coffee. Inverse dose-dependent correlation of coffee consumption with liver diseases was found in clinical and population studies. Coffee is non-pharmacological tool of primary and secondary prevention of chronic liver diseases. Review of published data together with supposed mechanisms of hepatoprotection are given.Key words: coffee - hepatoprotective effect - metaanalysis.

[Uncorrected Tetralogy of Fallot--a case report of a 69-year-old patient]. / Nekorigovaná Fallotova tetralógia u 69-rocného pacienta.

Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart defect. The actual treatment relies on cardio-surgery--complete correction within the infant age. Without surgery only 10% of subjects survived 3rd decade and only 3-5% of subjects were able to survive until their 40th. This particular paper is dedicated to case of a 69-years old male subject with positive history of uncorrected ToF due to his refusal of surgery, ischemic cardiac disease NYHA III-IV and chronic kidney failure. This subject was hospitalized within the department of internal medicine due to several days of chest pain connected with lower extremities oedemas and dyspnoeic syndrome after minimal physical load. Provided echocardiography revealed pulmonary artery stenosis, severe tricuspid insufficiency, concentric hypertrophy of ventricles, ventricular septal defect, dextroposition of aorta and severe pericardial effusion. Chest X-ray proved massive pleura effussion. The actual conditions of subject improved significantly after onset of diuretics, antiarrhytmics and providing of pleural punction. Subject has been discharged. Cases of ToF presented within available sources in older population were associated with left ventricular hypertrophy and hypoplastic pulmonary artery and slow subpulmonal obstruction development which also presented within our subject. Left ventricular hypertrophy has a potential to develop continuously and therefore its benefits can be visible within adult age.