Search

Abstract Obesity is a major cause of metabolic dysfunction-associated steatohepatitis (MASH) and is characterized by inflammation and insulin resistance. Interferon-γ (IFNγ) is a pro-inflammatory cytokine elevated in obesity and modulating macrophage functions. Here, we show that male mice with loss of IFNγ signaling in myeloid cells (Lyz-IFNγR2−/−) are protected from diet-induced insulin resistance despite fatty liver. Obesity-mediated liver inflammation is also attenuated with reduced interleukin (IL)−12, a cytokine primarily released by macrophages, and IL-12 treatment in vivo causes insulin resistance by impairing hepatic insulin signaling. Following MASH diets, Lyz-IFNγR2−/− mice are rescued from developing liver fibrosis, which is associated with reduced fibroblast growth factor (FGF) 21 levels. These results indicate critical roles for IFNγ signaling in macrophages and their release of IL-12 in modulating obesity-mediated insulin resistance and fatty liver progression to MASH. In this work, we identify the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and as potential therapeutic targets to treat MASH.

Objective Perioperative hypothermia can lead to various complications. Although various warming techniques have been used to prevent perioperative hypothermia, the effect of these techniques on surgical site infection (SSI) during posterior fusion surgery is unclear. The effects of warming devices on SSI rates were therefore analyzed using data complied by the Health Insurance and Review Assessment (HIRA) Service in Korea. Methods This study included 5,406 patients in the HIRA Service database who underwent posterior fusion surgery during the years 2014, 2015, and 2017. Factors related to SSI in these patients, including warming devices, antibiotics, and transfusion, were analyzed. Results The incidence of SSI was higher in patients who underwent forced air warming than in those who did not undergo active warming (odds ratio [OR], 1.73; p = 0.039), especially above 70 years old (OR, 4.11; p = 0.014). By contrast, the incidence of SSI was not significantly higher in patients who underwent device using conduction. Infection rates were higher in patients who received prophylactic antibiotics within 20 minutes before incision, than within 21 to 60 minutes (OR, 2.07; p = 0.001) and who received more blood transfusions (1 pint < volume ≤ 2 pint; OR, 1.75; p = 0.008, > 2 pint; OR, 2.73; p = 0.004). Conclusion SSI rates were higher in patients who underwent warming with forced air devices than with devices using conduction, as well as being higher in patients who older age, received blood transfusions and administered antibiotics within 20 minutes before incision. Devices using conduction have more advantages in preventing SSI than forced air warming device. In addition, the reduction of other risk factors for SSI may improve postoperative results.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Bee venom contains several bioactive components, including enzymatic and non-enzymatic proteins. There is increasing interest in the bioactive components of bee venom since they have exhibited various pharmacological effects. Recently, Apis mellifera waprin (Amwaprin) was identified as a novel protein in Apis mellifera (honeybee) venom and characterized as an antimicrobial agent. Herein, the novel biological function of Amwaprin as an antioxidant is described. In addition, the antioxidant effects of Amwaprin in mammalian cells were investigated. Amwaprin inhibited the growth of, oxidative stress-induced cytotoxicity, and inflammatory response in mammalian NIH-3T3 cells. Amwaprin decreased caspase-3 activity during oxidative stress and exhibited protective activity against oxidative stress-induced cell apoptosis in NIH-3T3 and insect Sf9 cells. The mechanism underlying the cell protective effect of Amwaprin against oxidative stress is due to its direct binding to the cell membrane. Furthermore, Amwaprin demonstrated radical-scavenging activity and protected against oxidative DNA damage. These results suggest that the antioxidant capacity of Amwaprin is attributed to the synergistic effects of its radical-scavenging action and cell shielding, indicating its novel role as an antioxidant agent.

Cardiovascular disease (CVD) is one of the most common comorbidities in breast cancer survivors. Recently, the target population and treatment period for aromatase inhibitor (AI) treatment in breast cancer patients has been expanding. However, information on adverse CVD events from the long-term use of AI is still lacking. The aim of this study was to investigate the CVD side effects of AI treatment and to evaluate the changes in lipid profile during AI treatment. A systematic search of PubMed (Medline), EMBASE, and Cochrane Library databases reporting on cardiovascular outcomes or lipid profiles change in adult female breast cancer patients (>19 years old) with AI was performed. The pooled analysis of 25 studies showed that the prevalence rate of any type of cardiovascular disease was 6.08 per 100 persons (95% CI 2.91–10.31). Angina was the most common type of heart-related cardiovascular event accounting for 3.85 per 100 persons, followed by any type of stroke (3.34) and venous thromboembolism (2.95). Ischemic stroke (OR 1.39, 95% CI 1.07–1.81) and myocardial infarction (OR 1.30, 95% CI 0.88–1.93) were more common in AI compared with tamoxifen, whereas the prevalence of venous thromboembolism (OR 0.61, 95% CI 0.37–1) was significantly lower in the AI group. In addition, treatment with AI for 6–12 months showed a decrease in HDL-cholesterol and an increase in LDL-cholesterol and total cholesterol. Various CVDs can occur when using AI, and in particular, the risk of MI and ischemic stroke increases in comparison with the adverse effect of tamoxifen. The occurrence of CVD might be related to the deterioration of the lipid profile after AI treatment. Therefore, a customized individualization strategy considering each patient’s CV risk factors is needed during AI treatment.

Background Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice. Methods In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled. Results Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of −1.05%± 1.35% (P

Previous results regarding the association between types of β-blockers and outcomes in patients on hemodialysis (HD) were inconsistent. Our study aimed to evaluate patient survival according to the type of β-blockers administered using a large sample of patients with maintenance HD. Our study included patients on maintenance HD patients from a national HD quality assessment program (n = 54,132). We divided included patients into four groups based on their use and type; Group 1 included patients without a prescription of β-blockers, Group 2 included patients with a prescription of dialyzable and cardioselective β-blockers, Group 3 included patients with a prescription of non-dialyzable and non-cardioselective β-blockers, and Group 4 included patients with prescription of non-dialyzable and cardioselective β-blockers. The number of patients in Groups 1, 2, 3, and 4 were 34,514, 2789, 15,808, and 1021, respectively. The 5-year survival rates in Groups 1, 2, 3, and 4 were 69.3%, 66.0%, 68.8%, and 69.2%, respectively. Univariate Cox regression analyses showed the hazard ratios to be 1.10 (95% CI, 1.04–1.17) in Group 2 and 1.05 (95% CI, 1.02–1.09) in Group 3 compared to Group 1. However, multivariate Cox regression analyses did not show statistical significance among the four groups. Our study showed that there was no significant difference in patient survival based on the use or types of β-blockers.

This study aimed to evaluate the effect of statin solubility on the survival of patients undergoing hemodialysis (HD). This retrospective study used laboratory and clinical data from a national HD quality assessment program and claims data (n = 53,345). The use of statins was defined as prescription ≥30 days during 6 months of each HD quality assessment period. We divided the patients into three groups based on the use and solubility of statins: No group, patients without a prescription of statins (n = 37,944); Hydro group, patients with a prescription of hydrophilic statins (n = 2823); and Lipo group, patients with a prescription of lipophilic statins (n = 12,578). The 5-year survival rates in the No, Hydro, and Lipo groups were 69.6%, 67.9%, and 67.9%, respectively (p < 0.001 for the trend). Multivariable Cox regression analyses showed that the Lipo group had better patient survival than the No group. However, multivariable analyses did not show statistical significance between the Hydro and No or Lipo groups. In all subgroups based on sex, age, presence of diabetes mellitus, and heart disease, the Lipo group had better patient survival than the No group. We identified no significant association between hydrophilic and lipophilic statins and patient survival. However, patients taking lipophilic statins had a modest survival benefit compared with those who did not receive statins.

Background Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed. Methods This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles. Results Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD. Conclusion This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

Background: Obesity is of grave concern as a comorbidity of coronavirus disease 2019 (COVID-19). We examined the factors associated with weight gain among Korean adults during the COVID-19 pandemic. Methods: We conducted an online survey of 1,000 adults (515 men and 485 women aged 20-59 years) in March 2021. Multivariable logistic regression analysis was performed to evaluate the factors associated with weight gain. The analysis was adjusted for sex, age, region, depressive mood, anxiety, eating out, late-night meals, alcohol consumption, exercise, sleep disturbance, meal pattern, subjective body image, comorbidities, marital status, living alone, and income. Results: After adjusting for confounding variables, the odds for weight gain increased in the group aged 20-34 years compared with the group aged 50-59 years (1.82; 95% confidence interval [CI], 1.01-3.32). Women were more associated with the risk of weight gain compared with men. The odds for weight gain increased in the lack of exercise group compared with the exercise group (4.89; 95% CI, 3.09-7.88). The odds for weight gain increased in the eating-out and late-night meal groups compared with that in the groups not eating out and not having late-night meals. Individuals watching a screen for 3-6 hr/day were more associated with the risk of weight gain compared with those who rarely watched a screen. The odds for weight gain increased in participants who considered themselves obese compared with those who did not consider themselves obese. Conclusion: A healthy diet and regular physical activity tend to be the best approach to reduce obesity, a risk factor for COVID-19.

Abstract Aims/Introduction We aimed to determine the hospital‐based prevalence and clinical features of fulminant type 1 diabetes mellitus in Korea. Materials and Methods We identified all patients with diabetes who regularly visited the Endocrinology outpatient clinics at eight centers for a period >1 year between January 2012 and June 2017. We investigated their medical records retrospectively. Results During this period, 76,309 patients with diabetes had been regularly followed up. Among them, 913 (1.2%) patients had type 1 diabetes mellitus . There were 462 patients with type 1 diabetes mellitus whose data at the time of the first diagnosis could be identified (359 and 103 with non‐ketosis and ketosis onset, respectively). Of these, 15 (3.2% of type 1 diabetes mellitus, 14.6% of ketosis onset diabetes) patients had fulminant type 1 diabetes mellitus. The median ages at diagnosis were 40 and 27 years in the fulminant type 1 diabetes mellitus and non‐fulminant type 1 diabetes mellitus groups, respectively. The patients with fulminant type 1 diabetes mellitus had higher body mass index, lower glycated hemoglobin and fasting/peak C‐peptide, and lower frequent glutamic acid decarboxylase antibody‐positive rate (P =0.0010) at diagnosis. Furthermore, they had lower glycated hemoglobin at the last follow‐up examination than those with non‐fulminant type 1 diabetes mellitus. Conclusions In this study, the prevalence of type 1 diabetes mellitus was 1.2% among all patients with diabetes, and that of fulminant type 1 diabetes mellitus was 3.2% among those newly diagnosed with type 1 diabetes mellitus. The glycated hemoglobin levels were lower in patients with fulminant type 1 diabetes mellitus than in those with non‐fulminant type 1 diabetes mellitus at diagnosis and at the last follow‐up examination.

Abstract Background We aimed to examine the associations between the risk of decreased renal function, obesity, and weight changes in Korean type 2 diabetic patients with normal renal function. Methods Type 2 diabetic patients (n = 1060) who visited the diabetic clinic at Soonchunhyang University Bucheon Hospital between 2001 and 2007 with follow up surveys completed in 2016 to 2017 were recruited into the study. Decreased renal function was defined as an estimated glomerular filtration rate 10% was associated with the risk of decreased renal function after adjusting for clinical variables in type 2 diabetic patients with normal renal function at baseline (OR 1.43; CI 1.11–2.00; p = 0.016). Weight loss was not associated with the risk of decreased renal function in type 2 diabetic patients with normal renal function at baseline. Conclusions Baseline obesity was associated with the increased risk of decreased renal function in Korean type 2 diabetic patients with normal renal function. Weight gain > 10% independently predicted the risk of decreased renal function. Large prospective studies are needed to clarify causal associations between obesity, weight change, and decreased renal function in patients with type 2 diabetes.

The aim of this study was to evaluate survival rates according to iron status in patients undergoing maintenance hemodialysis (HD). Thus, the National HD Quality Assessment Program dataset and claims data were used for analysis (n = 42,390). The patients were divided into four groups according to their transferrin saturation rate and serum ferritin levels: Group 1 (n = 34,539, normal iron status); Group 2 (n = 4476, absolute iron deficiency); Group 3 (n = 1719, functional iron deficiency); Group 4 (n = 1656, high iron status). Using univariate and multivariable analyses, Group 1 outperformed the three other groups in terms of patient survival. Using univariate analysis, although Group 2 showed a favorable trend in patient survival rates compared with Groups 3 and 4, the statistical significance was weak. Group 3 exhibited similar patient survival rates to Group 4. Using multivariable Cox regression analysis, Group 2 had similar patient survival rates to Group 3. Subgroup analyses according to sex, diabetic status, hemoglobin level ≥ 10 g/dL, and serum albumin levels ≥ 3.5 g/dL indicated similar trends to those of the total cohort. However, subgroup analysis based on patients with a hemoglobin level < 10 g/dL or serum albumin levels < 3.5 g/dL showed a weak statistical significant difference compared with those with hemoglobin level ≥ 10 g/dL, or serum albumin levels ≥ 3.5 g/dL. In addition, the survival difference between Group 4 and other groups was greater in old patients than in young ones. Patients with a normal iron status had the highest survival rates. Patient survival rates were similar or differed only modestly among the groups with abnormal iron status. In addition, most subgroup analyses revealed similar trends to those according to the total cohort. However, subgroup analyses based on age, hemoglobin, or serum albumin levels showed different trends.

Obesity is a prevalent and complex disease. The prevalence of obesity in Korea increased from 29.7% in 2010 to 35.7% in 2018, with the prevalence of abdominal obesity being 23.8% in 2018. Obesity contributes to medical costs and socioeconomic burden due to associated comorbidities. The treatment and management of obesity is changing based on new clinical evidence. The 2020 Korean Society for the Study of Obesity Guideline for the Management of Obesity in Korea summarizes evidence-based recommendations and treatment guidelines.

Background It is known that the painful sensation of diabetic peripheral neuropathy (DPN) results in sleep problems in type 2 diabetes mellitus (T2DM). However, it is not known that the painless DPN also is associated with poor sleep quality in T2DM. The purpose of the current study was to investigate the association between painless DPN and poor sleep quality in T2DM. Methods A total of 146 patients of T2DM who do not have any painful symptoms of DPN were recruited into the study. Among the patients, painless DPN was diagnosed by using the current perception threshold test. Sleep quality was assessed using the Pittsburgh Sleep Quality Index questionnaire. Results The percentage of painless DPN was significantly higher in the poor sleep quality group than the good sleep quality group (70.0% vs. 35.5%, P

Abstract Background This study was performed to investigate the association between the amount of alcohol consumption or binge drinking and obesity-related comorbidities in Korean men. Methods A total of 103,048 men aged 19 years or older were investigated in the 2016 Korean Community Health Survey. The participants were divided into five groups according to the standard number of alcoholic drinks consumed per week. Results Of the total participants, 20.7% were in the high alcohol consumption group, consuming more than 28 drinks per week. After adjustment for clinical factors, high alcohol consumption was significantly associated with higher odds ratios (ORs) of obesity (OR, 1.449; 95% confidence interval [CI], 1.412 to 1.591; P

To investigate the role of microRNA (miR)-155 in inflammation in an in-vitro model of Graves' orbitopathy (GO). The expression levels of miR-155 were compared between GO and non-GO orbital tissues. The effects of inflammatory stimulation of interleukin (IL)-1β and tumour necrosis factor alpha (TNF-α) on miR-155 expression on GO and non-GO orbital fibroblasts (OFs) were investigated. The effects of miR-155 mimics and inhibitors of inflammatory proteins and IL-2-inducible T-cell kinase (ITK) expression were examined, along with those related to the knockdown of ITK with siITK transfection on inflammatory proteins. We also examined how ITK inhibitors affect miR-155 expression in GO and non-GO OFs. The expression levels of miR-155 were higher in GO orbital tissues than in non-GO tissue. The overexpression of miR-155 was induced by IL-1β and TNF-α in OFs from GO and non-GO patients. IL-1β-induced IL-6 (ICAM1) protein production was significantly reduced (increased) by miR-155 mimics and inhibitors. The mRNA and protein levels of ITK were downregulated by overexpressed miR-155 via miR-155 mimics. Knockdown of ITK via siITK transfection induced a decrease in the expression levels of ITK, IL-17, IL-6, IL-1β, and TNF-α protein. The expression of miR-155 was significantly downregulated by treatment with ITK inhibitors and Bruton's tyrosine kinase (BTK)/ITK dual inhibitors in a time-dependent manner. Our results indicated a potential relationship between miR-155 and ITK in the context of GO OFs. The overexpression of miR-155 repressed ITK expression and relieved inflammation. Thus, miR-155 appears to have anti-inflammatory effects in GO OFs. This discovery provides a new concept for developing GO treatment therapeutics.

Background Few studies have examined the relationship of sarcopenia with the microcirculation. The current study investigated the relationship of sarcopenia with microcirculatory function, as assessed by skin perfusion pressure (SPP), in type 2 diabetes mellitus (T2DM) patients. Methods In total, 102 T2DM patients who underwent SPP measurements and bioelectrical impedance analysis (BIA) were enrolled in this cross-sectional study. SPP was assessed using the laser Doppler technique. Sarcopenia was defined as low height-adjusted appendicular muscle mass (men, 50 mm Hg), and an SPP below 50 mm Hg was considered to reflect impaired microcirculation. Results Fourteen patients (13.7%) were diagnosed with impaired microcirculatory function of the lower limb based on SPP. The prevalence of sarcopenia in all subjects was 11.8%, but the percentage of patients with an SPP ≤50 mm Hg who had sarcopenia was more than triple that of patients with an SPP >50 mm Hg (28.6% vs. 9.1%, P=0.036). A significant positive correlation was found between SPP and appendicular muscle mass adjusted for height (P=0.041 for right-sided SPP). Multiple logistic regression analysis showed that patients with sarcopenia had an odds ratio of 4.1 (95% confidence interval, 1.01 to 24.9) for having an SPP ≤50 mm Hg even after adjustment for confounding factors. Conclusion These results suggest that sarcopenia may be significantly associated with impaired microcirculation in patients with T2DM. Nonetheless, the small number of patients and wide CI require cautious interpretation of the results.

Obesity is a serious and growing worldwide health challenge associated with type 2 diabetes mellitus, cardiovascular disease, osteoarthritis, some cancers, sleep apnea, asthma, and nonalcoholic fatty liver. The Korean Society for the Study of Obesity recommends that pharmacotherapy should be considered when intensive lifestyle modifications fail to achieve a weight reduction in obese patients with a body mass index ≥25 kg/m². Long-term medications for obesity have traditionally fallen into two major categories: centrally acting anorexiant medications and peripherally acting medications, such as orlistat. In this paper, we provide an overview of the anti-obesity medications currently available for the long-term and individualized treatment of obesity.

Apidermins (APDs) are known as structural cuticular proteins in insects, but their additional roles are poorly understood. In this study, we characterized the honeybee, Apis mellifera, APD 2 (AmAPD 2), which displays activity suggesting antimicrobial properties. In A. mellifera worker bees, the AmAPD 2 gene is transcribed in the epidermis, hypopharyngeal glands, and fat body, and induced upon microbial ingestion. Particularly in the epidermis of A. mellifera worker bees, the AmAPD 2 gene showed high expression and responded strongly to microbial challenge. Using a recombinant AmAPD 2 peptide, which was produced in baculovirus-infected insect cells, we showed that AmAPD 2 is heat-stable and binds to live bacteria and fungi as well as carbohydrates of microbial cell wall molecules. This binding action ultimately induced structural damage to microbial cell walls, which resulted in microbicidal activity. These findings demonstrate the antimicrobial role of AmAPD 2 in honeybees.

Venoms from venomous arthropods, including bees, typically induce an immediate local inflammatory response; however, how venoms acutely elicit inflammatory response and which components induce an inflammatory response remain unknown. Moreover, the presence of superoxide dismutase (SOD3) in venom and its functional link to the acute inflammatory response has not been determined to date. Here, we confirmed that SOD3 in bee venom (bvSOD3) acts as an inducer of H2O2 production to promote acute inflammatory responses. In mouse models, exogenous bvSOD3 rapidly induced H2O2 overproduction through superoxides that are endogenously produced by melittin and phospholipase A2, which then upregulated caspase-1 activation and proinflammatory molecule secretion and promoted an acute inflammatory response. We also showed that the relatively severe noxious effect of bvSOD3 elevated a type 2 immune response and bvSOD3 immunization protected against venom-induced inflammation. Our findings provide a novel view of the mechanism underlying bee venom-induced acute inflammation and offer a new approach to therapeutic treatments for bee envenoming and bee venom preparations for venom therapy/immunotherapy.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations.

BackgroundThe objective of this study was to investigate the prevalence, management, and comorbidities of diabetes among Korean adults aged 30 years and older.MethodsThis study used 2013 to 2016 data from the Korea National Health and Nutrition Examination Survey, a nationally-representative survey of the Korean population. Diabetes was defined as fasting glucose ≥126 mg/dL, current use of antidiabetic medication, a previous history of diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%.ResultsIn 2016, 14.4% (approximately 5.02 million) of Korean adults had diabetes. The prevalence of impaired fasting glucose was 25.3% (8.71 million). From 2013 to 2016, the awareness, control, and treatment rates for diabetes were 62.6%, 56.7%, and 25.1%, respectively. People with diabetes had the following comorbidities: obesity (50.4%), abdominal obesity (47.8%), hypertension (55.3%), and hypercholesterolemia (34.9%). The 25.1%, 68.4%, and 44.2% of people with diabetes achieved HbA1c

Obesity increases the risks of diabetes, hypertension, and cardiovascular diseases, ultimately contributing to mortality. Korean Society for the Study of Obesity (KSSO) was established to improve the management of obesity through research and education; to that end, the Committee of Clinical Practice Guidelines of KSSO reviews systemic evidence using expert panels to develop clinical guidelines. The clinical practice guidelines for obesity were revised in 2018 using National Health Insurance Service Health checkup data from 2006 to 2015. Following these guidelines, we added a category, class III obesity, which includes individuals with body mass index (BMI) ≥35 kg/m². Agreeing with the International Federation for the Surgery of Obesity and Metabolic Disorders, Asian Pacific Chapter consensus, we determined that bariatric surgery is indicated for Korean patients with BMI ≥35 kg/m² and for Korean patients with BMI ≥30 kg/m² who have comorbidities. The new guidelines focus on guiding clinicians and patients to manage obesity more effectively. Our recommendations and treatment algorithms can serve as a guide for the evaluation, prevention, and management of overweight and obesity.

Honeybee vitellogenin (Vg) transports pathogen fragments from the gut to the hypopharyngeal glands and is also used by nurse bees to synthesize royal jelly (RJ), which serves as a vehicle for transferring pathogen fragments to the queen and young larvae. The proteomic profile of RJ from bacterial-challenged and control colonies was compared using mass spectrometry; however, the expression changes of major royal jelly proteins (MRJPs) in hypopharyngeal glands of the honeybee Apis mellifera in response to bacterial ingestion is not well-characterized. In this study, we investigated the expression patterns of Vg in the fat body and MRJPs 1–7 in the hypopharyngeal glands of nurse bees after feeding them live or heat-killed Paenibacillus larvae. The expression levels of MRJPs and defensin-1 in the hypopharyngeal glands were upregulated along with Vg in the fat body of nurse bees fed with live or heat-killed P. larvae over 12 h or 24 h. We observed that the expression patterns of MRJPs and defensin-1 in the hypopharyngeal glands and Vg in the fat body of nurse bees upon bacterial ingestion were differentially expressed depending on the bacterial status and the time since bacterial ingestion. In addition, the AMP genes had increased expression in young larvae fed heat-killed P. larvae. Thus, our findings indicate that bacterial ingestion upregulates the transcriptional expression of MRJPs in the hypopharyngeal glands as well as Vg in the fat body of A. mellifera nurse bees.

Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome (MetS). However, the temporal relationship between NAFLD and MetS has yet to be evaluated, especially in young adults. In this study, we investigated whether NAFLD could be a precursor for MetS in metabolically healthy young adults. Using the Korean nationwide health screening database, we analyzed subjects aged 20–39 years who were free from any component of MetS between 2009 and 2012. A total of 1,659,192 subjects without excessive alcohol consumption or concomitant liver disease were categorized into three groups according to the fatty liver index (FLI): (1) NAFLD (FLI ≥ 60); (2) borderline NAFLD (30 ≤ FLI < 60); and (3) control (FLI < 30). During the 6,699,462 person-years of follow-up, 109,239 subjects developed MetS (16.3 per 1000-person-years). The NAFLD group and the borderline NAFLD group were associated with a higher risk of MetS than the control group (incidence rate ratios, 2.9 (95% confidence interval (CI), 2.7–3.1) for the NAFLD group and 2.1 (95% CI, 2.1–2.2) for the borderline NAFLD group, respectively). In addition, all of the metabolic components were positively associated with FLI in a proportional manner. NAFLD is associated with the future onset of MetS in young adults. Therefore, active lifestyle intervention is required for young adults diagnosed with NAFLD to prevent MetS and other metabolic diseases.

BackgroundFew studies report the effects of tamoxifen intake and the occurrence of de novo fatty liver and the deterioration of existing fatty liver. The aim of this study was to investigate the effects of tamoxifen on fatty change of liver over time and also the impact of fatty liver on the prognosis of patients with breast cancer.MethodsThis was a single-center, retrospective study of patients who were diagnosed with primary breast cancer from January 2007 to July 2017. 911 consecutive patients were classified into three groups according to treatment method: tamoxifen group, aromatase inhibitor (AI) group, and control group.ResultsMedian treatment duration was 49 months (interquartile range, IQR; 32-58) and median observational period was 85 months (IQR; 50-118). Long-term use of tamoxifen significantly aggravated fatty liver status compared to AI or control groups [hazard ratio (HR): 1.598, 95% confidence interval (CI): 1.173-2.177, P = 0.003] after adjusting other factors. When analyzed separately depending on pre-existing fatty liver at baseline, tamoxifen was involved in the development of de novo fatty liver [HR: 1.519, 95% CI: 1.100-2.098, P = 0.011) and had greater effect on fatty liver worsening (HR: 2.103, 95% CI: 1.156-3.826, P = 0.015). However, the progression of fatty liver did not significantly affect the mortality of breast cancer patients.ConclusionsTamoxifen had a significant effect on the fatty liver status compared to other treatment modalities in breast cancer patients. Although fatty liver did not affect the prognosis of breast cancer, meticulous attention to cardiovascular disease or other metabolic disease should be paid when used for a long time.

BackgroundSodium-glucose cotransporter-2 inhibitors (SGLT2i) are expected to improve the liver function of patients with non-alcoholic fatty liver disease (NAFLD) combined type 2 diabetes mellitus (T2DM) by its characteristic mechanism. This study was designed to investigate the effect of dapagliflozin, one of the SGLT2i, on the liver function of T2DM with NAFLD when combined with metformin.MethodsAmong patients who received dual oral hypoglycemic agents within the 3 months of diagnosing NAFLD, patients who had abnormal alanine aminotransferase (ALT) level (>40 IU/L) were included. Patients were divided into two groups: metformin+dapagliflozin group and metformin+dipeptidyl peptidase-4 inhibitors (DPP4i) group. Demographic data, biochemical data and the clinical and treatment histories of all patients were reviewed.ResultsA total of 102 patients were included (dapagliflozin group, n=50; DPP4i group, n=52). Dapagliflozin group showed more weight loss and more ALT decline than DPP4i group (−2.9 kg vs. −0.4 kg, P=0.005; −21.1 U/L vs. −9.5 U/L, P=0.008, respectively) and the proportion of patients with ALT normalization after treatment was also significantly higher in the dapagliflozin group (80.0% vs. 61.5%, P=0.041). The effect of dapagliflozin with metformin on ALT normalization remained significant after adjustment for confounding variables including body weight loss (odds ratio, 3.489; P=0.046).ConclusionALT improvement was statistically significant in the dapagliflozin than the DPP4i when combined with metformin and the result was consistent after adjustment for confounding variables including body weight loss.

Background : Vitamin D deficiency is known to increase the incidence of metabolic syndrome. Nonalcoholic fatty liver disease is a common metabolic disease in patients with type 2 diabetes. This study evaluated nonalcoholic fatty liver disease and abdominal fat accumulation according to 25-hydroxyvitamin D status in patients with type 2 diabetes. Methods : The study comprised 302 patients with type 2 diabetes. Patients were divided into three groups based upon their 25-hydroxyvitamin D status: vitamin D deficient group (

Sperm storage in the spermathecae of honeybee (Apis mellifera) queens is vital for reproduction of honeybees. However, the molecular mechanisms whereby queens store sperm in a viable state over prolonged periods in the spermatheca are not fully understood. Here, we conducted RNA sequencing analysis of the spermathecae in both virgin and mated A. mellifera queens 24 h after mating and observed that the genes encoding transferrin (Tf) and major royal jelly proteins (MRJPs) were differentially expressed in the spermathecae of mated queens. The concentrations of Tf and antioxidant proteins such as superoxide dismutase 1, catalase, and glutathione peroxidase as well as the levels of reactive oxygen species, H2O2, and iron were higher in the spermathecal fluid of the mated queens than in virgin queens. Tf upregulation is likely to perform a protective role against the Fenton reaction occurring between iron and H2O2 in the antioxidant pathway in the mated queen’s spermathecal fluid. Furthermore, MRJPs—especially MRJP1, MRJP4, and MRJP6—were upregulated in the mated queen’s spermathecal fluid, indicating that they may serve as antimicrobial and antioxidant agents as well as an energy source for stored sperm in the spermathecal fluid of honeybee queens. Together, our findings show that Tf and MRJPs are upregulated in the spermatheca and spermathecal fluid of mated honeybee queens.

Background and Objectives: To find the differences in ocular axial length, keratometric measurements, and intraocular lens (IOL) power in patients with Graves’ disease (GD) after treatment with a thionamide antithyroid drug (ATD), methimazole. Materials and Methods: The medical charts of 28 patients (4 males and 24 females; mean age: 47.2 ± 21.2 years) were studied. Each patient was examined twice using an IOL Master Device and keratometry at the first visit (before ATD treatment) and after 1 month of ATD treatment. The IOL power was calculated for each patient using the Hoffer Q, SRK-2, and SRK/T formulas according to axial length. Results: After 1 month, the axial length increased (right and left eyes: p < 0.001 and p = 0.05, respectively). Based on keratometry, changes in the horizontal and vertical optical power [in diopters (D)] were not statistically significant. However, the IOL power changed after 1 month of ATD treatment in 64.3% of the patients. In 14 patients (50%), there was a 0.5–1.0 D IOL power decrease in single eyes; in two patients (7.1%), an IOL power decrease of 0.5–1.0 D in both eyes; and in two patients (7.1%), a 0.5 D IOL power increase in single eyes. The calculated IOL power values were lower after ATD treatment (right and left eyes, p = 0.010 and p = 0.018, respectively). Conclusions: The IOL power changed in 64.3% of GD patients after ATD treatment. Therefore, avoiding cataract surgery at the early stage of ATD treatment would be appropriate for selecting a more accurate IOL power.

An adrenal incidentaloma is an adrenal mass found in an imaging study performed for other reasons unrelated to adrenal disease and often accompanied by obesity, diabetes, or hypertension. The prevalence and incidence of adrenal incidentaloma increase with age and are also expected to rise due to the rapid development of imaging technology and frequent imaging studies. The Korean Endocrine Society is promoting an appropriate practice guideline to meet the rising incidence of adrenal incidentaloma, in cooperation with the Korean Adrenal Gland and Endocrine Hypertension Study Group. In this paper, we discuss important core issues in managing the patients with adrenal incidentaloma. After evaluating core proposition, we propose the most critical 20 recommendations from the initially organized 47 recommendations by Delphi technique.

Some clinical manifestations of obesity include nonalcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease. Calorie restriction may aid in weight loss in the short term. Exercise and physical activity are other means of weight loss. However, the efficacy of exercise and physical activity in weight reduction in obese populations is still unknown. In this review, we discuss the effects of exercise and physical activity in obese and overweight populations. We also discuss the effects of aerobic exercise and/or resistance training in weight loss and maintenance.

Purpose. To evaluate the clinical efficacy of oral hyaluronic acid (HA) in patients with dry eye disease (DED). Study Design. Prospective randomized controlled trial. Methods. This trial enrolled 54 subjects and they were randomized into the study or control group. The inclusion criteria were as follows: (1) >18 years of age; (2) distance best-corrected visual acuity ≥ 20/40 Snellen equivalent in each eye; (3) IOP ≤ 21 mmHg in both eyes; (4) ocular surface disease index (OSDI) score of ≥18 and 5 corneal spots of corneal fluorescein staining (CFS); and (7) ≤ 10 mm/5 min of the Schirmer test. All subjects were treated with a topical HA, and the study group was supplemented with oral HA. OSDI, TBUT, CFS, and the Schirmer test were evaluated for ocular surface parameters. Results. 24 patients were assigned in the study group. Significant improvement of OSDI, TBUT, and CFS was observed at 1 month and 3 months after oral HA administration in the study group. At baseline and follow-up at 1 and 3 months, OSDI scores were 61.8 ± 16.2, 47.3 ± 11.6, and 42.3 ± 9.1, respectively (P

Abstract Background Pre‐haemodialysis (HD) serum creatinine levels are reliable and inexpensive markers of muscle mass and important predictors of survival in patients with stable chronic HD. We aimed to assess whether changes in pre‐HD serum creatinine levels during a 2‐year period are linked to long‐term patient survival. Methods We retrospectively analysed patients enrolled in a periodic HD quality assessment program. Of the 21 846 participants in the fourth HD quality assessment program, 13 765 were presented in the fifth, of which 10 299 eligible patients were included in this study. We assessed the change in serum creatinine levels over 2 years. The patients were categorized into the following three groups: stable group (patients with change in serum creatinine

Damage to mitochondria induces mitophagy, a cellular process that is gaining interest for its therapeutic relevance to a variety of human diseases. However, the mechanism underlying mitochondrial depolarization and clearance in mitophagy remains poorly understood. We previously reported that mitochondria-induced cell death was caused by knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 in gastric cancer. In this study, we show that Neisseria gonorrhoeae opacity-associated-interacting protein 5 loss and gain of function modulates mitophagy induced by treatment with docetaxel, a chemotherapy drug for gastric cancer. The activation of mitophagy by Neisseria gonorrhoeae opacity-associated-interacting protein 5 overexpression promoted cell survival, preventing docetaxel-induced mitochondrial clearance. Conversely, short interfering RNA–mediated knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 accelerated docetaxel-induced apoptosis while increasing mitochondrial depolarization, reactive oxygen species, and endoplasmic reticulum stress and decreasing adenosine triphosphate production. We also found that the mitochondrial outer membrane proteins mitofusin 2 and phosphatase and tensin homolog–induced putative kinase 1 colocalized with Neisseria gonorrhoeae opacity-associated-interacting protein 5 in mitochondria and that mitofusin 2 knockdown altered Neisseria gonorrhoeae opacity-associated-interacting protein 5 expression. These findings indicate that Neisseria gonorrhoeae opacity-associated-interacting protein 5 modulates docetaxel-induced mitophagic cell death and therefore suggest that this protein comprises a potential therapeutic target for gastric cancer treatment.

BackgroundThyroid hormones can influence energy metabolism and insulin sensitivity via their interaction with adipocytokines and gut hormones. The aims of this study were to evaluate differences in serum ghrelin and leptin concentrations according to thyroid hormone levels, and to investigate the correlation of insulin resistance.MethodsA total of 154 patients (57 hyperthyroid patients, 61 euthyroid patients, and 36 hypothyroid patients; mean age, 47.9 years) were enrolled. Serum leptin, ghrelin, and insulin levels were measured and insulin resistance was calculated using the formula of the homeostasis model assessment of insulin resistance (HOMA-IR).ResultsThere were no differences in mean concentrations of ghrelin or leptin among the three groups. There were no significant differences in insulin levels between the groups (P=0.06), although hyperthyroid patients had borderline statistically significantly higher levels of insulin than did euthyroid subjects by post hoc test (26.4 µIU/mL vs. 16.1 µIU/mL, P=0.057). Regarding HOMA-IR index, the mean levels were highest in the hyperthyroid group among those of the three groups (hyperthyroid vs. euthyroid vs. hypothyroid, 6.7 vs. 3.8 vs. 4.4, P=0.068). Plasma levels of ghrelin were significantly negatively correlated with age, insulin, glucose, body mass index (BMI), and HOMA-IR. Plasma levels of leptin showed significant positive correlation with BMI and triglyceride. There were no significant correlations among thyroid hormone, thyrotropin, ghrelin, leptin, or insulin.ConclusionThe present study found that serum ghrelin, leptin, and insulin levels didn't differ according to thyroid function conditions. Further studies with larger numbers of patients are required to establish a direct relationship between plasma ghrelin, leptin, and thyroid hormone.

BackgroundThe aim of this study was to examine the clinical characteristics of adrenal incidentalomas discovered by computed tomography (CT) and to investigate metabolic features of subclinical Cushing's syndrome (SCS) in patients with adrenal incidentalomas in a tertiary hospital in Korea.MethodsThis retrospective study examined the clinical aspects of 268 patients with adrenal incidentalomas discovered by CT at Soonchunhyang University Bucheon Hospital. Clinical data and endocrine function of the patients as well as histological findings were obtained from medical records, while anatomic characteristics were analyzed by reviewing imaging studies. Hormonal tests for pheochromocytoma, Cushing's syndrome, and aldosterone-secreting adenoma were performed.ResultsMost (n=218, 81.3%) cases were nonfunctioning tumors. Of the 50 patients with functioning tumors (18.7%), 19 (7.1%) were diagnosed with SCS, nine (3.4%) with overt Cushing's syndrome, 12 (4.5%) with primary aldosteronism, and 10 (3.7%) with pheochromocytoma. Malignant tumors (both primary and metastatic) were rare (n=2, 0.7%). Body mass index, fasting glucose, hemoglobin A1c, and total cholesterol were significantly higher in patients with SCS in comparison with those with nonfunctioning tumors. The prevalence of type 2 diabetes mellitus and hypertension were significantly higher in patients with SCS compared with those with nonfunctioning tumors.ConclusionFunctioning tumors, especially those with subclinical cortisol excess, are commonly found in patients with adrenal incidentalomas, although malignancy is rare. In addition, patients with SCS in adrenal incidentalomas have adverse metabolic and cardiovascular profiles.

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

BackgroundIt is not clear whether microangiopathies are associated with subclinical atherosclerosis in type 2 diabetes mellitus (T2DM). We investigated the relation of cardiac autonomic neuropathy (CAN) and other microangiopathies with carotid atherosclerosis in T2DM.MethodsA total of 131 patients with T2DM were stratified by mean carotid intima-media thickness (CIMT) ≥ or

BackgroundThis study was performed to determine the factors associated with long-term oral hypoglycemic agent (OHA) responsiveness in Korean type 2 diabetic patients.MethodsTwo groups of patients were selected among the type 2 diabetic patients who were followed for more than two years at a university hospital diabetes clinic. The OHA responsive group consisted of 197 patients whose HbA1c levels were maintained at ≤7% with OHA for more than two years. The OHA failure group consisted of 180 patients whose HbA1c levels were >8% in spite of optimal combined OHA therapy or patients who required insulin therapy within the two years of the study.ResultsThe OHA failure group had higher baseline values of fasting and postprandial glucose, HbA1c, and lower fasting, postprandial, and delta C-peptide compared to those of the OHA responsive group. The OHA failure group also had a higher proportion of female patients, longer diabetic duration, and more family history of diabetes. There were no significant differences in body mass index (BMI) or insulin resistance index between the two groups. Multiple logistic regression analysis showed that the highest quartile of baseline fasting, postprandial glucose, and HbA1c and the lowest quartile of postprandial and delta C-peptide were associated with an increased odds ratio of OHA failure after adjustment for age, sex, body mass index, and family history of diabetes.ConclusionLower baseline values of postprandial and delta C-peptide and elevated fasting glucose and HbA1c are associated with long-term OHA responsiveness in Korean patients with type 2 diabetes mellitus.

Bone homeostasis is tightly regulated to balance bone formation and bone resorption. Many anabolic drugs are used as bone-targeted therapeutic agents for the promotion of osteoblast-mediated bone formation or inhibition of osteoclast-mediated bone resorption. Previous studies showed that ginsenoside Re has the effect of the suppression of osteoclast differentiation in mouse bone-marrow derived macrophages and zebrafish. Herein, we investigated whether ginsenoside Re affects osteoblast differentiation and mineralization in in vitro and in vivo models. Mouse osteoblast precursor MC3T3-E1 cells were used to investigate cell viability, alkaline phosphatase (ALP) activity, and mineralization. In addition, we examined osteoblastic signaling pathways. Ginsenoside Re affected ALP activity without cytotoxicity, and we also observed the stimulation of osteoblast differentiation through the activation of osteoblast markers including runt-related transcription factor 2, type 1 collagen, ALP, and osteocalcin in MC3T3-E1 cells. Moreover, Alizarin red S staining indicated that ginsenoside Re increased osteoblast mineralization in MC3T3-E1 cells and zebrafish scales compared to controls. These results suggest that ginsenoside Re promotes osteoblast differentiation as well as inhibits osteoclast differentiation, and it could be a potential therapeutic agent for bone diseases.

Purpose: The objective of this study was to assess postoperative direct medical expenses and medical utilization of elderly patients who underwent either hemiarthroplasty (HA) or internal fixation (IF) for treatment of a femoral intertrochanteric fracture and to analyze differences according to surgical methods and age groups. Materials and Methods: Data from the 2011 to 2018 Korean National Health Insurance Review & Assessment Service database were used. Risk-set matching was performed for selection of controls representing patients with the same sex, age, and year of surgery. A comparative interrupted time series analysis was performed for evaluation of differences in medical expenses and utilization between the two groups. Results: A total of 10,405 patients who underwent IF surgery and 10,405 control patients who underwent HA surgery were included. Medical expenses were 18% lower in the IF group compared to the HA group during the first year after the fracture (difference-in-difference [DID] estimate ratio 0.82, 95% confidence interval [CI] 0.77-0.87, P <0.001), and 9% lower in the second year (DID estimate ratio 0.91, 95% CI 0.85-0.99, P =0.018). Length of hospital stay was significantly shorter in the IF group compared to the HA group during the first two years after time zero in the age =80 group. Conclusion: A noticeable increase in medical expenses was observed for patients who underwent HA for treatment of intertrochanteric fractures compared to those who underwent IF over a two-year period after surgery. Therefore, consideration of such findings is critical when designing healthcare policy support for management of intertrochanteric fractures. [ABSTRACT FROM AUTHOR]

Introduction: Results on the association between the use of renin–angiotensin system blockades (RASBs) and vascular access-related outcomes are inconsistent. We aimed to compare vascular access-related outcomes according to the use of RASBs in hemodialysis patients. Methods: This study used data from a national hemodialysis quality assessment program of the Republic of Korea (n = 54,903). Group 1 was not prescribed any blood pressure-lowering drugs (n = 28,521). Group 2 was prescribed other blood pressure-lowering agents except for RASBs (n = 9571). Group 3 was prescribed RASBs (n = 16,811). Vascular access-related outcomes were classified into intervention-free survival (IFS), thrombosis-free survival (TFS), and vascular access survival (VAS). Results: No significant difference in the three access survival rates was identified among the three groups. The multivariate Cox regression analyses indicated that Group 3 had better outcomes in IFS and TFS than Group 1. The numbers of angioplasties performed were significantly greater in Group 1 than in the other two groups. The numbers of thrombectomies performed were significantly the lowest in Group 3 among all the groups. Conclusions: Our study revealed different results according to types of access survival in univariate or multivariate analyses. The association of RASBs with favorable outcomes in vascular access remains unclear. [ABSTRACT FROM AUTHOR]

Background/Aims: Sorafenib is the standard of care in the management of advanced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the characteristics, treatment patterns and outcomes of sorafenib among HCC patients in South Korea. Methods: This population-based retrospective, single-arm, observational study used the Korean National Health Insurance database to identify patients with HCC who received sorafenib between July 1, 2008, and December 31, 2014. A total of 9,923 patients were recruited in this study. Results: Among 9,923 patients, 6,669 patients (68.2%) received loco-regional therapy prior to sorafenib, and 1,565 patients (15.8%) received combination therapy with concomitant sorafenib; 2,591 patients (26.1%) received rescue therapy after sorafenib, and transarterial chemoembolization was the most common modality applied in 1,498 patients (15.1%). A total of 3,591 patients underwent rescue therapy after sorafenib, and the median overall survival was 14.5 months compared to 4.6 months in 7,332 patients who received supportive care after sorafenib. The mean duration of sorafenib administration in all patients was 105.7 days; 7,023 patients (70.8%) received an initial dose of 600 to 800 mg. The longest survival was shown in patients who received the recommended dose of 800 mg, subsequently reduced to 400 mg (15.0 months). The second longest survival was demonstrated in patients with a starting dose of 800 mg, followed by a dose reduction to 400–600 mg (9.6 months). Conclusions: Real-life data show that the efficacy of sorafenib seems similar to that observed in clinical trials, suggesting that appropriate subsequent therapy after sorafenib might prolong patient survival. [ABSTRACT FROM AUTHOR]