HCV and HCC Tango-Deciphering the Intricate Dance of Disease: A Review Article.

Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) accounting for around one-third of all HCC cases. Prolonged inflammation in chronic hepatitis C (CHC), maintained through a variety of pro- and anti-inflammatory mediators, is one of the aspects of carcinogenesis, followed by mitochondrial dysfunction and oxidative stress. Immune response dysfunction including the innate and adaptive immunity also plays a role in the development, as well as in the recurrence of HCC after treatment. Some of the tumor suppressor genes inhibited by the HCV proteins are p53, p73, and retinoblastoma 1. Mutations in the telomerase reverse transcriptase promoter and the oncogene catenin beta 1 are two more important carcinogenic signaling pathways in HCC associated with HCV. Furthermore, in HCV-related HCC, numerous tumor suppressor and seven oncogenic genes are dysregulated by epigenetic changes. Epigenetic regulation of gene expression is considered as a lasting "epigenetic memory", suggesting that HCV-induced changes persist and are associated with liver carcinogenesis even after cure. Epigenetic changes and immune response dysfunction are recognized targets for potential therapy of HCC.

The impact of anticoagulation therapy on kidney function in patients with atrial fibrillation and chronic kidney disease.

INTRODUCTION: Atrial fibrillation (AF) and chronic kidney disease (CKD) are closely related. These diseases share common risk factors and are associated with increased risk of thromboembolic events. Choosing the appropriate oral anticoagulant therapy (OAC) in patients with AF and CKD is challenging. Deterioration of renal function is common in patients with AF treated with OACs, although not all OACs affect the kidneys equally. AREAS COVERED: In this review, we aim to summarize the current knowledge of the prevention of thromboembolic events in patients with AF and CKD, focusing on the impact of specific OAC agents on renal function. EXPERT OPINION: Consideration of OAC use is mandatory in patients with AF and CKD who are at increased risk of stroke or systemic embolism. Available evidence suggests that the use of non-vitamin K antagonist oral anticoagulants (NOACs) is associated with slower deterioration of renal function in comparison to Vitamin K antagonists (VKAs). Hence, a NOAC should be used in preference to VKAs in all NOAC-eligible patients with AF and CKD. Regarding patients with end-stage renal dysfunction and those on dialysis or renal replacement therapy, the use of NOAC should be considered in line with locally relevant formal recommendations.

Spasticity treatment in Norwegian hospitals. / Behandling av spastisitet ved norske sykehus.

BACKGROUND: Spasticity is a frequent complication of diseases of and injuries to the central nervous system. Early treatment prevents further loss of function and spasticity-related complications. Basic spasticity treatment begins in the primary healthcare service and includes physiotherapy, occupational therapy and oral spasmolytics, while treatment with botulinum toxin and baclofen pump is carried out by the specialist healthcare services. The objective of the study was to obtain an overview of the availability and organisation of these specialised forms of spasticity treatment in Norway. MATERIAL AND METHOD: We conducted a survey in which a digital questionnaire was sent to hospitals that offer spasticity treatment. RESULTS: A total of 30 of 47 hospital departments/outpatient clinics (hereafter referred to as 'hospital units') distributed across all Norwegian health regions responded to the questionnaire. Spasticity treatment with botulinum toxin and baclofen pump was available in all of the health regions. Median time from first referral was 10 weeks (interquartile range 7 weeks). A total of 14 of 30 hospital units expressed a need for more treatment days to cover the local demand. Of the 30 hospital units, 23 had interdisciplinary teams with doctors, physiotherapists, occupational therapists and/or nurses. For treatment with botulinum toxin, ultrasound was used as guidance in 22 of 26 hospital units, EMG was used in 15 units and electrical muscle stimulation was used in 11 units. INTERPRETATION: The study suggests that there may be a need for improvements to specialised spasticity treatment in Norway to ensure good patient care pathways, interdisciplinary assessments, and safe and efficient performance of the practical interventions.

Long-Term Renal Function after Catheter Ablation of Atrial Fibrillation.

Background: Atrial fibrillation (AF) is associated with the development and progression of chronic kidney disease (CKD). This study evaluated the impact of long-term rhythm outcome after catheter ablation (CA) of AF on renal function. Methods and results: The study group included 169 consecutive patients (the mean age was 59.6 ± 10.1 years, 61.5% were males) who underwent their first CA of AF. Renal function was assessed by eGFR (using the CKD-EPI and MDRD formulas), and by creatinine clearance (using the Cockcroft-Gault formula) in each patient before and 5 years after index CA procedure. During the 5-year follow-up after CA, the late recurrence of atrial arrhythmia (LRAA) was documented in 62 patients (36.7%). The mean eGFR, regardless of which formula was used, significantly decreased at 5 years following CA in patients with LRAA (all p < 0.05). In the arrhythmia-free patients, the mean eGFR at 5 years post-CA remained stable (for the CKD-EPI formula: 78.7 ± 17.3 vs. 79.4 ± 17.4, p = 0.555) or even significantly improved (for the MDRD formula: 74.1 ± 17.0 vs. 77.4 ± 19.6, p = 0.029) compared with the baseline. In the multivariable analysis, the independent risk factors for rapid CKD progression (decline in eGFR > 5 mL/min/1.73 m2 per year) were the post-ablation LRAA occurrence (hazard ratio 3.36 [95% CI: 1.25-9.06], p = 0.016), female sex (3.05 [1.13-8.20], p = 0.027), vitamin K antagonists (3.32 [1.28-8.58], p = 0.013), or mineralocorticoid receptor antagonists' use (3.28 [1.13-9.54], p = 0.029) after CA. Conclusions: LRAA after CA is associated with a significant decrease in eGFR, and it is an independent risk factor for rapid CKD progression. Conversely, eGFR in arrhythmia-free patients after CA remained stable or even improved significantly.

Sex-related differences in self-reported treatment burden in patients with atrial fibrillation.

Background: Treatment burden (TB) is defined as the patient's workload of healthcare and its impact on patient functioning and wellbeing. High TB can lead to non-adherence, a higher risk of adverse outcomes and lower quality of life (QoL). We have previously reported a higher TB in patients with atrial fibrillation (AF) vs. those with other chronic conditions. In this analysis, we explored sex-related differences in self-reported TB in AF patients. Materials and methods: A single-center, prospective study included consecutive patients with AF under drug treatment for at least 6 months before enrollment from April to June 2019. Patients were asked to voluntarily and anonymously answer the Treatment Burden Questionnaire (TBQ). All patients signed the written consent for participation. Results: Of 331 patients (mean age 65.4 ± 10.3 years, mean total AF history 6.41 ± 6.62 years), 127 (38.4%) were females. The mean TB was significantly higher in females compared to males (53.7 vs. 42.6 out of 170 points, p < 0.001), and females more frequently reported TB ≥ 59 points than males (37.8% vs. 20.6%, p = 0.001). In females, on multivariable analysis of the highest TB quartile (TB ≥ 59), non-vitamin K Antagonist Oral Anticoagulant (NOAC) use [Odds Ratio (OR) 0.319; 95% Confidence Interval (CI) 0.12-0.83, P = 0.019], while in males, catheter ablation and/or ECV of AF (OR 0.383; 95% CI 0.18-0.81, P = 0.012) were negatively associated with the highest TB quartile. Conclusion: Our study was the first to explore the sex-specific determinants of TB in AF patients. Females had significantly higher TB compared with males. Approximately 2 in 5 females and 1 in 5 males reported TB ≥ 59 points, previously shown to be an unacceptable burden of treatment for patients. Using a NOAC rather than vitamin K antagonist (VKA) in females and a rhythm control strategy in males could decrease TB to acceptable values.

Dr. Masa Zivanovic: A Pioneer in Health Care for Women and Children in Bosnia and Herzegovina.

The aim of the article is to present, primarily to the medical world and also the general public, the personality and work of Masa Zivanovic (1890-1960), a pioneer in the health care of children and mothers in Bosnia and Herzegovina (BH), a health educator and one of the leaders of the Yugoslav Women's Rights Movement in the period between the two world wars. She was born in Croatia (then part of the Austro-Hungarian Empire) as Maria Skopszynski, in a family of Polish-Czech origin. After studying at the Temporary Women's Lyceum in Zagreb and passing the matriculation exam at the boy's High School (1909), she obtained the title of Doctor of Medicine in Vienna (1916). Her activity in the Women's Rights Movement has so far generally attracted more attention from researchers than her medical work. However, this work was very important because the general and health education of women, expectant mothers and mothers, after the two World Wars was very poor in BH, and the rates of child morbidity and mortality were high. Masa Zivanovic spent almost her entire working life in Sarajevo. For 30 years, she was the head of the Dispensary for Mothers and the Children, later the Institute for Maternal and Child Health Care, into which the previous institution grew in 1931. She was among the first followers of the new concept of "comprehensive paediatrics", which included social care for children, disease prevention and treatment of the sick. She successfully connected the medical mission with the mission of a women's rights activist, also trying to act as a health educator through articles published in the Women's Movement magazine (Zenski pokret). For a time, she was the president of the Society for the Education of Woman and Protection of her Rights, i.e. the Women's Movement, and a delegate at conferences of international feminist organizations. CONCLUSION: Masa Zivanovic was a physician, a pioneer in the health care of children and mothers in BH, a long-time director of the Institute for Health Care of Mothers and Children in Sarajevo, and one of the leaders of the Yugoslav Women's Rights Movement.

Self-reported treatment burden in patients with atrial fibrillation: quantification, major determinants, and implications for integrated holistic management of the arrhythmia.

AIMS: Treatment burden (TB) refers to self-perceived cumulative work patients do to manage their health. Using validated tools, TB has been documented in several chronic conditions, but not atrial fibrillation (AF). We measured TB and analysed its determinants and impact on quality of life (QoL) in an AF cohort. METHODS AND RESULTS: A single-centre study prospectively included consecutive adult AF patients and non-AF controls managed from 1 April to 21 June 2019, who voluntarily and anonymously answered the TB questionnaire (TBQ) and 5-item EQ-5D QoL questionnaire; TB was calculated as a sum of TBQ points (maximum 170) and expressed as proportion of the maximum value. Of 514 participants, 331 (64.4%) had AF. The mean self-reported TB was 27.6% among AF patients and 24.3% among controls, P = 0.011. The mean TB was significantly higher in patients taking vitamin K antagonists (VKAs) vs. those taking non-VKA antagonist oral anticoagulants (NOAC; 29.5% vs. 24.7%, P = 0.006). The highest item-specific TB was reported for healthcare system organization-related items (e.g. visit appointment), diet, and physical activity modifications. On multivariable analyses, female sex, younger age, and permanent AF were associated with a higher TB, whereas NOACs and electrical AF cardioversion exhibited an inverse association; TB was an independent predictor of decreased QoL (all P < 0.05). CONCLUSION: Our study provided clinically relevant insights into self-perceived TB among AF patients. Approximately one in four patients with AF have a high TB. Specific AF treatments and optimization of healthcare system-required patient activities may reduce the self-perceived TB in AF patients.

Effectiveness of training with motion-controlled commercial video games on hand and arm function in young people with cerebral palsy: A systematic review and meta-analysis.

OBJECTIVE: To examine the effect of motion-controlled commercial video games compared with traditional occupational and physiotherapy methods for hand and arm function in persons of all ages with cerebral palsy. DATA SOURCES: A systematic literature search was conducted in Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, OTseeker and PEDro for randomized controlled trials involving persons with cerebral palsy using motion-controlled commercial video games as a training method for hand and arm function, compared with traditional therapy. STUDY SELECTION AND DATA EXTRACTION: Screening, data-extraction, risk of bias and quality assessment was carried out independently by 2 of the authors. The risk of bias of each study was assessed using the Cochrane Collaborations Risk of Bias Tool. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). DATA SYNTHESIS: Eight randomized controlled trials, with a total of 262 participants, were included. A random effects meta-analysis showed a statistically significant difference between the groups in favour of motion-controlled commercial video games. The quality of the evidence was, however, rated as very low. CONCLUSION: Despite a significantly greater improvement in hand and arm function in favour of motion-controlled commercial video games, the results of this review should be interpreted with caution with regards to high risk of bias and the low strength of evidence. There is a need for high-powered studies on the effectiveness of training with motion-controlled commercial video games for persons with cerebral palsy, especially in adults.

How common is Balkan endemic nephropathy among immigrants in endemic regions?

PURPOSE: In the early 1970s, a number of authors described the development of Balkan endemic nephropathy (BEN) in immigrants in endemic regions. The aim of this study was to examine whether immigrants in endemic regions are suffering from BEN today. METHODS: The study involved 193 residents of two endemic regions divided into three groups: two groups of native residents-(1) members of BEN families, (2) members of non-BEN families, and (3) immigrants, who had moved from non-affected settlements to the endemic regions of Kolubara (38 years ago) or Semberia (20 years ago). All persons were subjected to an interview, objective examination, kidney ultrasound, and laboratory analysis to detect the presence of BEN consensus diagnostic criteria. RESULTS: The number of immigrants with BEN biomarkers outside cutoff values was significantly lower than for BEN family members. Five BEN family members met diagnostic criteria for BEN and four for suspected BEN. Although five non-BEN family members had different combinations of BEN biomarkers, all of them had diseases other than BEN in which these biomarkers also occurred. None of the immigrants met the criteria for BEN. Nevertheless, one descendant of an immigrant, a 78-year-old male, whose mother was from a non-BEN family in the Kolubara district, exhibited all the criteria for BEN: alpha1-microglobulinuria, chronic renal failure, and anemia. CONCLUSION: While 30 years ago, BEN was reported equally among immigrants and natives, currently it is diagnosed in some BEN family members in the eighth decade of life, but extremely rarely in immigrants also in old age.

Are Prothrombotic Mutations a Time-to-Event Risk Factor?

BACKGROUND: Deep vein thrombosis (DVT) represents a common disorder involving genetic and acquired risk factors. It has been proposed that acquired risk factors are more important with aging than genetic factors, indicating different prevalence of prothrombotic mutations throughout the lifespan. OBJECTIVE: To determine the role of the most frequent prothrombotic genetic risk factors (Factor V [FV] Leiden and Factor II [FII] G20210A mutations) in first-time DVT etiology in patients of different ages. METHOD: This retrospective study included 701 patients living in Serbia with diagnosed DVT as a first-time thrombotic event. RESULTS: Risk assessment for mutations as age-related markers showed no statistical difference (FV Leiden mutation-OR, 1.027; 95% confidence interval [CI], .87-1.22; P = .76 and FII G20210A mutation-OR, 0.940, 95% CI, .74-1.19; P = .61). Our results show similar mutation prevalence regardless of how old the patients were at the time of the first DVT occurrence. CONCLUSION: Our results indicate that these 2 mutations cannot be used as prognostic marker for time-to-event first DVT in the Serbian population; however, further studies are required.

[Patients' diet in "Town" and "City" hospitals in Belgrade].

The roots of hospital foundation in Serbs date from the 12th century, when the hospitals in the monasteries Hilandar (1199) and Studenica (1207) were established. The "Town" Hospital of Belgrade was founded in 1841, which had the status of town and regional hospital until 1881. After that, it was transformed into a general state-owned hospital based on the Law of National Health Protection. The inhabitants of Belgrade obtained a municipal hospital again in 1935, when the "City" Hospital was founded in Zvezdara municipality, named at that period Bulbulder. By researching and observing hospital diet development of municipal hospitals in Belgrade, it was concluded that from the very beginning of the "Town" Hospital functioning there was awareness about its significance, place and role in the overall treatment of patients. Hospital diet, regardless of existing knowledge as the part of medical doctrines of particular time-periods, was often conditioned by limited hospital budgets and under the influence of different social movements and wartime periods

[The first pediatricians in Serbia].

Dr. Platon Papakostopulos (1864-1915), Dr. Milenko Materni (1875-1929), Dr. Milan Petrovic (1886-1963), Dr. Nadezda Stanojevic (1887-1979) and Dr. Dura Jovanovic (1892-1977) were founders of modern pediatrics in Serbia. They established and managed the first pediatric institutions: Hospital pediatric departments, Mother and Child Health Care Consultations and Child welfare clinics in Belgrade and Novi Sad. They also established Pediatric Section of the Serbian Medical Association and published numerous scientific and popular articles in pediatrics.

[Dr. Svetislav Sp. Barjaktarovic--30 years later]. / O Doktoru Svetislavu Sp. Barjaktarovicu--posle tridest godina.

Doctor Svetislav Sp. Barjaktarovitsh (1893-1971), full professor of University School of Medicine in Belgrade, Head of the Department of Gynaecology and Obstetrics since its foundation, Director of the University Teaching Hospital of Gynaecology and Obstetrics from 1937 to 1948, was dismissed from University for political reasons in December 1948. He was the author of classical gynaecological and obstetrics textbooks, popular books, as well as of fifty scientific papers published in domestic and foreign professional literature. While being the Director of the University Teaching Hospital of Gynaecology and Obstetrics he managed to raise money to start the building of a new hospital. He was engaged in experimental work and improved the diagnosis and therapy of genital tuberculosis, extrauterine pregnancy, adnexal inflammation, puerperal fever, etc. He was especially concerned with the determination of the child's sex before his/her birth. As a medical student he participated in the First World War working in the Company Hospital of the Morava Division. He was holder of the Albanian Commemorative Medal, The Cross of Mercy and other decorations.