Management and treatment of hepatocellular carcinoma with immunotherapy: A review of current and future options

With mortality rates of liver cancer doubling in the last 20 years, this disease is on the rise and has become the fifth most common cancer in men and the seventh most common cancer in women. Hepatocellular carcinoma (HCC) represents approximately 90% of all primary liver cancers and is a major global health concern. Patients with HCC can be managed curatively with surgical resection or with liver transplantation, if they are diagnosed at an early stage. Unfortunately, most patients with HCC present with advanced stages of the disease and have underlying liver dysfunction, which allows only 15% of patients to be eligible for curative treatment. Several different treatment modalities are available, including locoregional therapy radiofrequency ablation, microwave ablation, percutaneous ethanol injection, trans-arterial chemoembolization, transarterial radio-embolization, cryoablation, radiation therapy, stereotactic radiotherapy, systemic chemotherapy, molecularly targeted therapies, and immunotherapy. Immunotherapy has recently become a promising method for inhibiting HCC tumor progression, recurrence, and metastasis. The term “Immunotherapy” is a catch-all, encompassing a wide range of applications and targets, including HCC vaccines, adoptive cell therapy, immune checkpoint inhibitors, and use of oncolytic viruses to treat HCC. Immunotherapy in HCC is a relatively safe option for treating patients with advanced disease in the USA who are either unable to receive or failed sorafenib/lenvatinib therapy and thus may offer an additional survival benefit for these patients. The purpose of this review is to elaborate on some of the most recent advancements in immunotherapy

Geriatric Hepatology: The Hepatic Diseases of the Elderly and Liver Transplant

Introduction: With the aging US population, chronic liver diseases are becoming more commonly diagnosed in the geriatric population. Advanced age leads to changes in liver blood flow, volume, morphology and normal physiology. This predisposes elderly patients to develop certain chronic liver diseases. Also, the clinical course and management differ in an older patient when compared to a younger patient. Some causes of chronic liver disease in the geriatric population include Hepatitis A, B, C, Non-Alcoholic Fatty liver disease, prolonged alcohol use and inflammation. Many chronic liver diseases are characterized by a slow, indolent course of progression with non-specific symptoms and thus may lead to diagnosis at a later age. The presence of an advanced liver disease, cirrhosis, and hepatocellular carcinoma are becoming more frequent in older patients and often the first clinical presentation. Aim: The aim of this study is to highlight hepatic diseases in the geriatric population to better understand the scope of the clinical management including liver transplantation. Method: PubMed, MEDLINE, EMBASE, and EMBASE classic were searched to research published articles, case reports, cross-sectional and case-control studies reporting regarding aging and the liver diseases. Result: Decreases in the functioning of the liver and other organs, as well as, alterations in immune functions should be taken into consideration in the management of the liver diseases. Aging has been shown to not only enhance vulnerability to acute liver injury but also increase the susceptibility of the fibrotic response. Aging has a significant impact on the risk and poor prognosis of various liver diseases including NAFLD, ALD, HCV, and liver transplantation. The diagnosis of advanced liver disease is important to make in the elderly population since many of the condition’s features are treatable and can lead to improved quality of life and, most importantly, decrease the likelihood of acute care hospitalization, which carries a high risk of nosocomial infections and therapeutic mishaps in the aged population. Conclusion: Geriatric patients show various changes in the liver, which play a role in the clinical characteristics of liver diseases in these patients. Geriatric patients with risk factors for hepatitis should be screened for liver disease, along with those that have a family history of liver diseases, or a history of long-term or heavy alcohol consumption. Age cannot be a single exclusion criterion from the liver transplantation, and an individualization strategy, which takes into consideration all risk factors of a recipient, needs to be considered. We suggest geriatric patients should be a candidate for liver transplant, and the healthcare team treating our elderly generation to collaborate for these patients for them to have a smoother transition both in pre-transplant phase and post-transplant phase

Osteological characteristics of Turkmenian stone loach, Paraschistura cristata (Cypriniformes: Nemacheilidae)

Formerly the Turkmenian stone loach was the only member of the genus Metaschistura based on osteological characters. But recently, it is placed in the genus Paraschistura based on mtDNA COI data. To provide a detailed description of the osteological characteristics of Paraschistura cristata (Berg 1898), ten specimens of P. cristata were collected from the Hari River basin in Iran and their osteological characteristics were examined. According to the results, P. cristata is osteologically characterized by a foramen in the ventral part of the exoccipital, two extra urohyals, sesamoid ossifications, trapezoid-shaped prevomer, three basibranchials, five hypural, lack of bony bridge between the parietal and pterotic, having over 20 procurrent rays supporting the adipose crest. The detailed skeletal description of P. cristata showed that this species can be easily distinguished from the related genera. Despite the mtDNA COI result, the osteological data of this species showed some features to describe it as a distinctive genus, but this needs the osteological data of the all other Paraschistura species to be compared

Agreement Between Swept-source Optical Coherence Tomography and Rotating Scheimpflug Camera in Measurement of Corneal Parameters in Normal and Keratoconic Eyes

Purpose: This study aimed to assess the agreement between topographic indices of healthy subjects and keratoconus (KCN) patients using a swept-source optical coherence tomography (SS-OCT CASIA2) versus a Scheimpflug camera (Pentacam). Methods: 40 eyes of 23 patients with KCN and 40 eyes of 20 healthy subjects were included and evaluated with the CASIA2, followed by the Pentacam. Two consecutive modalities were obtained for one eye of each patient. Corneal parameters, including anterior keratometry at steep (Ks) and flat meridians (Kf), anterior astigmatism, anterior and posterior corneal elevation values, thinnest corneal thickness, and apex corneal thickness, were evaluated. Results: CASIA2 and Pentacam showed perfect agreement (95% limits of agreement (LoA): -0.22 to 0.68, 95% LoA: -1.5 to 1.44 D) and good correlation (Intraclass correlation (ICC):0.986, ICC:0.987; to 0.68, 95% LoA: -1.5 to 1.44 D) and good correlation (Intraclass correlation (ICC):0.986, ICC:0.987; P <0.01) for anterior (Ks) in normal and ectatic corneas, respectively. The cylinder amount had moderate agreement and correlation (95% LoA: -0.55 to 0.47D, ICC: 0.797, P <0.01) in normal, and moderate to strong agreement and correlation (95% LoA: -1.57 to 0.87D, ICC=0.911, P <0.01) in Keratoconic eyes. There was a fair agreement for anterior and posterior corneal elevation values in normal subjects (95% LoA: -3.09 to 4.59, 95% LoA: -6.91 to 7.31D). The thinnest corneal thickness amount had an excellent agreement in normal and KCN patients (ICC: 0.983, 0.953; respectively). Conclusions: Although the devices had different mean indices values, they had a good agreement based on the Bland–Altman plots. Since Pentacam is accepted as the standard tool for diagnosing ectatic cornea, pentacam CASIA2 is also helpful for early diagnosis of KCN

Effect of attachment-based therapy training on intimacy and alexithymia in parents of children with intellectual disabilities

Parents of children with Intellectual Disabilities obviously and undeniably experience the same love and joy for their children, but they also have an increased risk of encountering stressors (e.g., high medical costs), anxiety, and depression. The present study was conducted with the aim of investigating the effect of attachment-based therapy training on increasing intimacy and alexithymia of the parents of intellectual disabilities children. 30 parents were randomly selected. They were then randomly divided into two groups. The experimental group participated in 8 sessions of attachment-based therapy and control group received no intervention. The research design was quasi-experimental. The research findings revealed a significant difference between the experimental group and the control group concerning the degree of intimacy. However, no significant contrast was found in terms of the Alexithymia. With respect to findings of the current study, it can be concluded that training based upon the attachment style can lead to intimacy increase among parents of mentally retarded children

Nanostructured Lipid Carrier for Topical Application of N-Acetyl Glucosamine

Purpose: Hyperpigmentation occurs when melanin is overproduced in certain spots on the skin and is one of the most challenging skin conditions to treat. Although it is usually harmless, for cosmetic reasons, it is dreadfully bothersome to those who undergo it. It was reported that N-acetyl-glucosamine (NAGA) prevents melanin synthesis and alters the expression of numerous genes related to pigmentation. In spite of these advantages, NAGA cannot be employed in topical formulations due to its extremely polar characteristics. Nanoparticles, especially lipid-based ones, have been introduced as an efficient carrier for dermal drug delivery. Methods: The aim of the present study was to load adequate hydrophilic NAGA to the lipophilic nanostructured lipid carriers (NLCs) for potential dermal application. Methods: NAGA-loaded NLCs were formulated, using hot homogenization technique, and the characteristics of the optimized formulation were analyzed by laser light scattering, X-ray diffraction, and scanning electron microscopy methods. Loading capacity percentage and in vitro release study were carried out by applying a validated HPLC method. The optimum formulation was utilized for the in vivo skin lightening evaluations in healthy volunteers. Results: NAGA-loaded NLCs demonstrated promising results (the size of 190 nm, narrow size distribution, loading capacity of 9%, and appropriate NAGA release profile) suitable for dermal delivery. XRD results exhibited a dramatic reduction in the crystalline structure of encapsulated NAGA. Dermoscopy images indicated a considerable decline in melanin distribution pattern in the majority of the cases treated with NAGA-loaded NLCs. Conclusion: Thus, this study has opened new horizons for the potential use of lipid based nanoparticles in the managing of hyperpigmentation

VEGF gene polymorphism interactions with dietary trace elements intake in determining the risk of metabolic syndrome

There is a complex interaction between genetic, metabolic, and environmental factors in determining the risk of Metabolic Syndrome (MetS). The aim of this study was to investigate the interaction between the dietary intake of iron, copper, zinc, manganese, selenium and iodine (assessed by 24 recall) with vascular endothelial growth factor variants (rs6921438, rs4416670, rs6993770, and rs10738760), on the risk of metabolic syndrome. Two hundred and forty eight individuals with MetS and 100 individuals without MetS recruited. Dietary intake and the daily average of energy and nutrients intake were obtained by questionnaire and quantified using Diet Plan 6 software. DNA was extracted from EDTA anticoagulated whole blood. The SNPs were assessed using using a Sequenom iPLEX Gold assay. Data analysis was undertaken using the Student’s t-test, χ2 test and logistic regression using SPSS 11.5 software. There was a significant interaction between low dietary iron intake with rs6993770 (β= 0.10, p<0.05), and a low dietary zinc and a high manganese intake with rs6921438 in relation to the presence of metabolic syndrome (β= -0.17, p<0.05, β= -0.30, p<0.05, respectively). Our data showed the association of rs6993770 with iron intake and rs6921438 with zinc and manganese intake, indicating further investigating in a larger population to evaluate their values

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. Methods We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. Findings In 2017, cirrhosis caused more than 1.32 million (95% UI 1.27-1.45) deaths (440000 [416 000-518 000; 33.3%] in females and 883 000 [838 000-967 000; 66.7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2.4% (2.3-2.6) of total deaths globally in 2017 compared with 1.9% (1.8-2.0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21.0 (19.2-22.3) per 100 000 population in 1990 to 16.5 (15.8-18-1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32.2 [25.8-38.6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10.1 [9.8-10-5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3.7 [3.3-4.0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103.3 [64.4-133.4] per 100 000 in 2017). There were 10.6 million (10.3-10.9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33.2% for compensated cirrhosis and 54.8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases snore than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI. Interpretation Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.Peer reviewe

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks