Since the approval of sorafenib for patients with advanced hepatocellular carcinoma (HCC) in 2007, many drugs have failed in the first and second-line setting. Fortunately, during the recent 2 years, between 2017 and 2018, four drugs (regorafenib, lenvatinib, cabozantinib, and ramucirumab) were found to be effective and tolerable for patients with HCC as the first- or second-line therapy. Regorafenib, a multi-kinase inhibitor, has a similar structure to sorafenib, and was shown to improve the survival of patients who progressed after sorafenib treatment compared to the placebo control. According to the phase III trial of regorafenib, it became the first approved systemic therapy for patients with progression after sorafenib. Lenvatinib is also a tyrosine kinase inhibitor (TKI), and in a phase III trial comparing sorafenib and lenvatinib, the primary end-point of non-inferior survival was met. Based on the trial results, lenvatinb has become another systemic therapy for treatment-naïve patients with advanced HCC. Cabozantinib is a dual inhibitor of Mesenchymal-Epithelial Transition factor/Vascular Endothelial Growth Factor Receptor2, and was shown to prolong the overall survival in patients who progressed after sorafenib compared to the placebo. Ramucirumab is a monoclonal antibody to inhibit a single target of VEGFR2. First, this drug failed to improve the survival of patients who progressed after sorafenib failure. On the other hand, it was effective in patients with baseline AFP ≥400 ng/mL. In a subsequent clinical trial that enrolled only patients with AFP ≥400 ng/mL, ramucirumab was also found to improve the overall survival compared to placebo. Thus, ramucirumab became the first biomarker-driven systemic treatment. Another category of drugs that are attracting considerable interest are immune checkpoint inhibitors, such as anti-programmed cell death protein (PD) 1 or anti-PD-ligand 1. This review provides a synopsis of new systemic therapies, including TKI, monoclonal antibody, and immune-oncology drugs.
Carcinoma, Hepatocellular* ; Cell Death ; Endothelial Growth Factors ; Hand ; Humans ; Protein-Tyrosine Kinases

PURPOSE: We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC). MATERIALS AND METHODS: A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS. RESULTS: There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs. 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea. CONCLUSION: Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.
Arm ; Breast Neoplasms* ; Breast* ; Capecitabine* ; Diarrhea ; Disease-Free Survival ; Epidermal Growth Factor ; Global Health ; Hand-Foot Syndrome ; Humans ; Neutropenia ; Quality of Life ; Triple Negative Breast Neoplasms ; Weights and Measures

BACKGROUND: This study purposed to compare the difference on medical utilization and health expenditure of baby boomer generation by depression between gender. METHODS: Korea Welfare Panel Survey 2016, provided by the Korea Institute for Health and Social Affairs, was used for the analysis. For the research, we used the two-part model, yes or no of use (part 1), and frequency of use (part 2) for medical utilization. The dependent variables are the whether or not to use of hospitalization services, outpatient services, length of stay, outpatient service visits, and health expenditure. And the independent variables are used as the predisposing (education, spouse presence), enabling (insurance type, private insurance, economic activity, income), and need (chronic disease, self-rated health, disability) factors in the Andersen behavior model. Depression was used as intervening variables. Structural equation model and multiple group analysis by gender were used. RESULTS: There were differences in the medical care usage and cost between men and women in baby boomer. For men, mediating effects of depression were present at the hospitalization (yes/no), length of stay, and health expenditure. On the other hand, for women, the mediating effect of depression was found only at the outpatient visits. Specially, depression was working at the medical services by the different way between gender. The size of effect (multiple group analysis) was affected by significant differences between men and women. CONCLUSION: This study found that the mediating effect of depression is increased medical usage and health expenditure and the effect factors are different by gender. Therefore, it is necessary to establish a medical care policy considering the socio-economic characteristics of baby boomers.
Depression ; Female ; Hand ; Health Expenditures ; Hospitalization ; Humans ; Insurance ; Korea ; Length of Stay ; Male ; Negotiating ; Outpatients ; Population Growth ; Sex Characteristics ; Spouses

SHORT syndrome is an extremely rare congenital condition due to a chromosomal mutation of the PIK3R1 gene found at 5q13.1. SHORT is a mnemonic representing six manifestations of the syndrome: (S) short stature, (H) hyperextensibility of joints and/or inguinal hernia, (O) ocular depression, (R) Rieger anomaly, and (T) teething delay. Other key aspects of this syndrome not found in the mnemonic include lipodystrophy, triangular face with dimpled chin (progeroid facies, commonly referred to as facial gestalt), hearing loss, vision loss, insulin resistance, and intrauterine growth restriction (IUGR). 3q duplication syndrome is rare syndrome that occurs due to a gain of function mutation found at 3q25.31-33 that presents with a wide array of manifestations including internal organ defects, genitourinary malformations, hand and foot deformities, and mental disability. We present a case of a 2 year and 3 month old male with SHORT syndrome and concurrent 3q duplication syndrome. The patient presented at birth with many of the common manifestations of SHORT syndrome such as bossing of frontal bone of skull, triangular shaped face, lipodystrophy, micrognathia, sunken eyes, and thin, wrinkled skin (progeroid appearance). Additionally, he presented with findings associated with 3q duplication syndrome such as cleft palate and cryptorchidism. Although there is no specific treatment for these conditions, pediatricians should focus on referring patients to various specialists in order to treat each individual manifestation.
Chin ; Cleft Palate ; Cryptorchidism ; Depression ; Facies ; Fetal Growth Retardation ; Foot Deformities ; Frontal Bone ; Hand ; Hearing Loss ; Hernia, Inguinal ; Humans ; Insulin Resistance ; Joints ; Lipodystrophy ; Male ; Micrognathism ; Parturition ; Skin ; Skull ; Specialization ; Tooth ; Tooth Eruption

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive disorder caused by a defect in the immunoglobulin mu binding protein 2 (IGHMBP2) gene, leading to motor neuron degeneration. We identified an infant with SMARD1 by targeted exome sequencing from a consanguineous Syrian family having a history of recurrent infant deaths. The patient initially presented intrauterine growth retardation, poor sucking, failure to thrive, and respiratory failure at the age of two months, and an inborn error of metabolism was suspected at first. Over a period of one month, the infant showed rapid progression of distal muscular weakness with hand and foot contractures, which were suggestive of neuromuscular disease. Using targeted exome sequencing, the mutation in IGHMBP2 was confirmed, although the first report was normal. Targeted exome sequencing enabled identification of the genetic cause of recurrent mysterious deaths in the consanguineous family. Additionally, it is suggested that a detailed phenotypic description and communication between bioinformaticians and clinicians is important to reduce false negative results in exome sequencing.
Carrier Proteins ; Contracture ; Exome ; Failure to Thrive ; Fetal Growth Retardation ; Foot ; Hand ; Humans ; Immunoglobulins ; Infant Death ; Infant ; Metabolism ; Motor Neurons ; Muscle Weakness ; Muscular Atrophy, Spinal ; Neuromuscular Diseases ; Respiratory Insufficiency

OBJECTIVE: To determine the socio-demographic, psychologic, hematologic, or other relevant factors associated with hand grip strength in Korean farmers. METHODS: A total of 528 healthy Korean farmers were enrolled. Hand grip strength was measured in both hands using a hydraulic dynamometer. Socio-demographic characteristics were assessed and anthropometric measurements were obtained. Psycho-cognitive measurements such as sleep quality (Pittsburgh Sleep Quality Index) and Go/No-Go test response time were conducted. In addition to physical measurements, serologic parameters including insulin-like growth factor 1 were measured. The factors associated with hand grip strength were analyzed using multiple linear regression analysis after adjusting for age, height, and weight. RESULTS: The mean hand grip strength was associated with the Pittsburgh Sleep Quality Index total score (β=-0.12, p=0.01), the Go/No-Go test response time (β=-0.18, p=0.001), vitamin D (β=0.12, p=0.02), and insulin-like growth factor 1 levels (β=0.1, p=0.045). In female farmers, hand grip strength was only associated with the Pittsburgh Sleep Quality Index total score (β=-0.32, p < 0.001). CONCLUSION: The results of this study demonstrate that hand grip strength was associated with sleep quality and attention in Korean farmers.
Agriculture* ; Farmers ; Female ; Hand Strength* ; Hand* ; Humans ; Insulin-Like Growth Factor I ; Linear Models ; Reaction Time ; Vitamin D

This paper intends to examine the realities of modern hygiene and medical institutions making their appearance in the rural Honam Plain (often called the “rice basket”) of colonial Korea in terms of organizing local units and spreading colonial ‘sanitary discipline’ throughout the region. In the Honam area, modern medical staff and facilities tended to concentrate on the cities in plain region (Kunsan, Jeonju, and Iri), while in the counties in mountainous region they were placed in the township where head office of each county was located. The case of Iksan County in plain region represented this pattern, which was closely associated with the behavior pattern of local Japanese immigrants as well as population growth (i.e., urbanization). The colonial city of Iri in Iksan County with burgeoning population of Japanese immigrants witnessed an early case of hygiene association right after Japan's annexation of Korea in 1910. The Iri hygiene association was a product of organizational restructuring of the preannexation Japanese resident association into the school association after the annexation, under which it was subordinated. It stands as an interesting contrast to the Jeonju hygiene association organized ‘autonomously’ under the official (police) auspices in the mid-1930s, which did not undergo the stage of school association. Yet, both cases represented the urban ‘autonomous’ (civil) organizations' effort to transplant colonial ‘sanitary discipline’ into the colonial local societies without recourse to the hygiene police apparatus. On the other hand, the sanitary project in rural areas was carried out on the basis of model hygiene village, with the identical purpose of raising awareness of hygiene and prohibiting epidemics just as the hygiene association in cities. However, considering the low level of epidemic inspection of Korean patients, the effect of the Japanese colonial sanitary project in Korean local societies was disappointing. There was an ever-widening gap in the colonial hygiene and medical services between Koreans and their colonizers as well as between urban and rural areas.
Asian Continental Ancestry Group ; Colon ; Emigrants and Immigrants ; Hand ; Head ; Humans ; Hygiene* ; Jeollabuk-do ; Korea* ; Medical Staff ; Police ; Population Growth

PURPOSE: The purpose of this study was to develop parent coaching domains for the health management of childhood leukemia survivors. METHODS: In this study, we conducted a literature review and in-depth interviews with 6 parents of childhood leukemia survivors who were identified using convenience sampling. We identified areas of parent coaching through the 4 stages of the GROW model, which are: goal setting, realistic grasp, confirmation of realization, and search for alternatives. RESULTS: Nine domains and 27 subcategories emerged from the study. The 9 parent coaching domains for the health management of childhood leukemia survivors were routine life management, education and information provision, emotional support for the surviving children, social support for the surviving children, follow-up management, family support, school life management, symptom management, and improvement of growth and development. CONCLUSION: This research developed 9 parent coaching domains for the health management of children surviving leukemia. The results of this study are expected to contribute to the efficient health management of childhood leukemia survivors by enabling practitioners to continuously identify new coaching domains as needed for their health management. Researchers should improve the health management of childhood leukemia survivors by developing nursing interventions for these new coaching areas.
Child ; Delivery of Health Care ; Education ; Follow-Up Studies ; Growth and Development ; Hand Strength ; Humans ; Leukemia ; Nursing ; Parents ; Survivors

BACKGROUND: Hemoglobin concentration reportedly is positively associated with muscle strength, for example, handgrip strength. However, hemoglobin cannot repair muscle directly, but is beneficial only in a supportive role. Since hepatocyte growth factor (HGF) regulates muscle satellite cell production and differentiation, which is stimulated by organ injury, the supportive effect of hemoglobin should thus be stronger for participants with high HGF than for those with low HGF. However, the association between hemoglobin concentration and handgrip strength in relation to HGF levels remains unknown. METHODS: We conducted a cross-sectional study of 255 Japanese elderly men aged 60-69 years who participated in annual health check-ups in 2014-2015. The study population was categorized on the basis of a median value of HGF of 300.6 pg/mL. RESULTS: Among present study population, 128 participants showed low HGF. For participants with low HGF, hemoglobin concentration showed no significant association with handgrip strength (standardized parameter estimate (β) = 0.03, p = 0.767), but for those with high HGF, hemoglobin concentration was significantly positively associated with handgrip strength (β = 0.23, p = 0.014). CONCLUSIONS A significant positive association between hemoglobin level and handgrip strength was established for elderly Japanese men aged 60-69 years with high HGF but not for participants with low HGF. Our finding indicates that HGF levels could determine the relationship of hemoglobin concentration with handgrip strength in elderly Japanese men aged 60-69 years. This result can be expected to serve as an effective tool for the clarification of the roles played by HGF and hemoglobin concentration in maintenance of muscle strength.
Aged ; Cross-Sectional Studies ; Hand Strength ; physiology ; Hemoglobins ; metabolism ; Hepatocyte Growth Factor ; genetics ; metabolism ; Humans ; Japan ; Male ; Middle Aged

Streptococcus pneumoniae, pneumococcus, is the most common cause of community-acquired pneumonia (CAP). CAP is an important infectious disease with high morbidity and mortality, and it is still one of the leading causes of death worldwide. Many genetic factors of the host and various environmental factors surrounding it have been studied as important determinants of the pathophysiology and outcomes of pneumococcal infections. Various cytokines, including transforming growth factor (TGF)-β1, are involved in different stages of the progression of pneumococcal infection. TGF-β1 is a cytokine that regulates a wide range of cellular and physiological functions, including immune and inflammatory responses. This cytokine has long been known as an anti-inflammatory cytokine that is critical to preventing the progression of an acute infection to a chronic condition. On the other hand, recent studies have unveiled the diverse roles of TGF-β1 on different stages of pneumococcal infections other than mitigating inflammation. This review summarizes the recent findings of the role of TGF-β1 on the pathophysiology of pneumococcal infections, which is fundamental to developing novel therapeutic strategies for such infections in immune-compromised patients.
Cause of Death ; Communicable Diseases ; Cytokines ; Fibrosis ; Hand ; Humans ; Inflammation ; Mortality ; Pneumococcal Infections* ; Pneumonia ; Streptococcus pneumoniae ; Transforming Growth Factor beta1 ; Transforming Growth Factors*