Gut microbiome composition can predict the response to nivolumab in advanced hepatocellular carcinoma patients.

BACKGROUND: Immunotherapy has revolutionized the clinical outcomes of intractable cancer patients. Little is known about the intestinal nonpathogenic bacterial composition of hepatocellular carcinoma (HCC) patients treated by immunotherapy. AIM: To determine whether there is a correlation between gut bacterial composition and prognosis in HCC patients. METHODS: From September 2019 to March 2020, we prospectively collected fecal samples and examined the gut microbiome of 8 advanced HCC patients treated with nivolumab as a second- or third-line systemic treatment. Fecal samples were collected before the start of immunotherapy. Fecal samples of patients with progression during treatment were collected at the time of progression, and fecal samples of patients who showed good response to nivolumab were collected after 5-7 mo as follow-up. Metagenomic data from 16S ribosomal RNA sequencing were analyzed using CLC Genomics Workbench. Microbiome data were analyzed according to therapeutic response. RESULTS: All 8 patients were male, of which 6 had underlying chronic hepatitis B. A higher Shannon index was found in the responders than in the non-responders after nivolumab therapy (P = 0.036). The unweighted beta diversity analysis also showed that the overall bacterial community structure and phylogenetic diversity were clearly distinguished according to therapeutic response. There was no significant difference in the diversity or composition of the patient gut microbiome according to the immunotherapy used. Several taxa specific to therapeutic response were designated as follows: Dialister pneumosintes, Escherichia coli, Lactobacillus reteri, Streptococcus mutans, Enterococcus faecium, Streptococcus gordonii, Veillonella atypica, Granulicatella sp., and Trchuris trichiura for the non-responders; Citrobacter freundii, Azospirillum sp. and Enterococcus durans for the responders. Of note, a skewed Firmicutes/Bacteroidetes ratio and a low Prevotella/Bacteroides ratio can serve as predictive markers of non-response, whereas the presence of Akkermansia species predicts a good response. CONCLUSION: The current presumptive study suggests a potential role for the gut microbiome as a prognostic marker for the response to nivolumab in treatment of HCC patients.

The value of high-sensitivity C-reactive protein in hand and knee radiographic osteoarthritis: data from the Dong-gu Study.

Due to the inconsistent association between high-sensitivity C-reactive protein (hs-CRP) and osteoarthritis (OA), we evaluated the relationship between hs-CRP and various radiographic findings in older adults with OA. This cross-sectional study recruited 2376 participants from the population-based Dong-gu cohort. The scores of radiographic features in OA on X-rays of the knees and hands were computed using a semi-quantitative grading system. The hs-CRP levels were measured using a particle-enhanced immunonephelometry assay. Correlations showing the relationship between hs-CRP and OA were calculated using multiple linear correlation analysis. The hs-CRP levels were significantly higher in older subjects (p < 0.001), those with a higher body mass index (BMI) (p < 0.001), current smokers (p < 0.001), current alcohol drinkers (p = 0.011), those who were less physically active (p = 0.002), and those with a lower level of education (p = 0.043). After adjusting for BMI and other confounders, the total OA scores (knee, p = 0.022; hand, p = 0.029) and sclerosis score (knee, p = 0.007; hand, p = 0.030) in the knees and hands were all significantly positively correlated with hs-CRP. A significant association was also observed between hs-CRP and hand erosion score (p = 0.045), hand malalignment score (p = 0.015), and tibial attrition score (p = 0.039). In this large cross-sectional study, a higher hs-CRP level was significantly associated with radiographic OA severity. Of the various types of radiographic damage, all of sclerosis, erosion, and malalignment were significantly associated with hs-CRP levels.

Association between grip strength and hand and knee radiographic osteoarthritis in Korean adults: Data from the Dong-gu study.

OBJECTIVES: We assessed whether grip strength was related to various types of radiographic damage in Korean adults with osteoarthritis (OA). METHODS: Data from 2,251 subjects enrolled in the Dong-gu study, who had no hand joint pain, were analyzed to investigate the relationship between grip strength and OA. Hand grip strength was measured using a hand-held dynamometer, and radiographs of the hand and knee were scored according to a semi-quantitative grading system. Multiple linear regressions were used to explore associations between grip strength and radiographic features of OA. RESULTS: Grip strength in men and women was negatively related to hand (both p < 0.001) and knee (men, p < 0.001; women, p = 0.010) OA after adjusting for confounders. Hand (men, p < 0.001; women, p = 0.001) and knee (both p < 0.001) joint space narrowing (JSN) showed the strongest associations with low grip strength, regardless of gender. Moreover, the severity of hand osteophytes in women (p = 0.001), and subchondral cysts (men, p < 0.001) was correlated with low grip strength in both genders. CONCLUSIONS: Among subjects without hand joint pain, low grip strength was associated significantly with hand and knee radiographic OA, regardless of gender. Among all types of OA radiographic damage, low grip strength showed the strongest association with JSN.

Public Awareness of Stroke and Its Predicting Factors in Korea: a National Public Telephone Survey, 2012 and 2014.

The aim of this study was to investigate time trends in the public awareness of stroke and its predicting factors. The target population was 9,600 community-dwelling adults, aged 19-79 years, in 16 metropolitan cities and provinces in Korea. The survey samples in 2012 and 2014 were selected separately (entirely different sets of subjects) using a proportionate quota sampling method. Information concerning knowledge of stroke and demographics was collected by trained telephone interviewers using random digit dialing. After excluding subjects with a non-response or refusal to answer any question, the analyses included 8,191 subjects in 2012 and 8,127 subjects in 2014. Respondents' awareness of stroke warning signs (numbness or weakness, difficulty speaking or understanding speech, dizziness, visual impairment, and severe headache) was highest for difficulty speaking or understanding speech (80.9% in 2012 and 86.4% in 2014). There were significant increases in the proportion of respondents understanding the appropriate action (i.e., calling an ambulance) at the time of stroke occurrence (59.6% to 67.1%), and in the proportion aware of the general need for prompt treatment (86.7% to 89.8%). In multivariable logistic regression analysis, older age, higher education level, higher household income, current non-smoking, exposure to stroke-related public relations materials, and experience of stroke education were significantly associated with both high knowledge of stroke warning signs and awareness of the need for prompt treatment. Between 2012 and 2014, the public's awareness of stroke increased significantly. More specialized interventions, including public relations materials and education, should focus on subgroups who have lower stroke knowledge.

Associations between body composition measurements of obesity and radiographic osteoarthritis in older adults: Data from the Dong-gu Study.

BACKGROUND: We examined the effects of fat deposition on radiographic osteoarthritis (OA) to determine the role of obesity in the pathogenesis of radiographic OA. METHODS: Data were taken from the Dong-gu cohort, a cross-sectional study of 2,367 subjects. Baseline characteristics, waist circumference (WC), waist-to-hip ratio (WHR), fat mass, and fat percentage were collected, along with X-rays of the knees and hands. Total knee and hand radiographic OA scores were summed using a semi-quantitative grading system, and then stratified by gender using a multiple linear regression model. RESULTS: After adjusting for confounders, weight was the only factor significantly associated with knee radiographic OA, regardless of gender (all p < 0.01). Regarding the hand, fat percentage had the largest effect on radiographic OA in males (p = 0.008), while WHR was the most significant factor in females (p = 0.001). For the knee, fat mass was the most important factor for radiographic OA in males (p = 0.001), while in females, body mass index was the most important factor (p < 0.001). Among the variables, only fat percentage was significantly related to both hand and knee radiographic OA in both genders (all p < 0.01). CONCLUSIONS: Regardless of gender, weight was significantly associated with knee radiographic OA. Otherwise, fat deposition correlated with hand and knee radiographic OA in both genders, while the distribution of fat tissue was significantly associated with hand and knee radiographic OA only in females.

Molecular Description of Macroorchis spinulosus (Digenea: Nanophyetidae) Based on ITS1 Sequences.

We performed a molecular genetic study on the sequences of 18S ribosomal RNA (ITS1 region) gene in 4-day-old adult worms of Macroorchis spinulosus recovered in mice experimentally infected with metacercariae from crayfish in Jeollanam-do Province, Korea. The metacercariae were round, 180 µm in average diameter, encysted with 2 layers of thick walls, but the stylet on the oral sucker was not clearly seen. The adult flukes were oval shape, and 760-820 µm long and 320-450 µm wide, with anterolateral location of 2 large testes. The phylogenetic tree based on ITS1 sequences of 6 M. spinulosus samples showed their distinguished position from other trematode species in GenBank. The most closely resembled group was Paragonimus spp. which also take crayfish or crabs as the second intermediate host. The present study is the first molecular characterization of M. spinulosus and provided a basis for further phylogenetic studies to compare with other trematode fauna in Korea.

The relationships between bone mineral density and radiographic features of hand or knee osteoarthritis in older adults: data from the Dong-gu Study.

OBJECTIVE: The relationship between OA and osteoporosis has exhibited contradictory features over the past four decades. The aim of this study was to determine using separate analysis of the radiographic features of OA whether various radiographic features of OA were associated differently with BMD in the Korean elderly. METHODS: Data were derived from the Dong-gu cohort; 2354 subjects were enrolled in the present cross-sectional study. Baseline characteristics, the BMDs of the lumbar spine and femoral neck measured by DXA, and X-rays of knees and hands were collected. A semi-quantitative grading system was used to estimate the severities of individual radiographic features. We adjusted for confounders using multiple linear regression modelling to analyse the relationships. RESULTS: After adjustment for confounders, hand and knee OA total scores were negatively associated with the BMDs of the lumbar spine and femoral neck, except for the total knee OA score and lumbar spine BMD. In detail, hand osteophytes and sclerosis exhibited positive relationships with the BMDs of the lumbar spine and femoral neck, except for hand osteophytes and femoral neck BMD. On the contrary, however, knee joint space narrowing (JSN), hand JSN, and hand subchondral cysts were negatively associated with the BMD of the lumbar spine and femoral neck. Knee JSN and hand subchondral cysts exerted the greatest effects on BMD. CONCLUSION: Separate analysis of the radiographic features of OA better reveals associations of OA with the BMD of the lumbar spine and femoral neck.

APOE Polymorphism Is Associated with C-reactive Protein Levels but Not with White Blood Cell Count: Dong-gu Study and Namwon Study.

We evaluated the association of the APOE polymorphism with serum C-reactive protein levels and white blood cell count in two large population-based studies in Korean. The datasets included the Dong-gu study (n = 8,893) and the Namwon Study (n = 10,032). APOE genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism. Multivariable linear regression analysis was performed to evaluate the relationship of APOE genotypes with C-reactive protein levels and white blood cell count with adjustments for age, sex, body mass index, smoking, diabetes, hypertension, and serum lipids. In the multivariate model, carriers of E3E4 or E4E4 genotype had significantly lower C-reactive protein levels compared with carriers of E3E3 genotype group (0.50 mg/L vs. 0.67 mg/L; 0.37 mg/L vs. 0.67 mg/L, respectively, for the Dong-gu Study and 0.47 mg/L vs. 0.66 mg/L; 0.45 mg/L vs. 0.66 mg/L, respectively, for the Namwon Study). However, there was no difference in white blood cell count among APOE genotypes. We found that the APOE E4 allele is associated with lower C-reactive protein levels, but not white blood cell count. Our results suggest that APOE genotype may influence C-reactive protein levels through non-inflammatory pathway.

Erratum: correction of prevalence of falls by sex in article 'risk factors for falls in older korean adults: the 2011 community health survey'.

[This corrects the article on p. 1482 in vol. 29, PMID: 25408578.].

Risk factors for falls in older Korean adults: the 2011 Community Health Survey.

Falls are a major health problem for elderly populations worldwide. We analyzed data from the 2011 Korean Community Health Survey to identify potential risk factors for falls in a representative population-based sample of community-dwelling older Korean adults. Risk factors for falls were assessed by multivariate survey logistic regression models. The prevalence of falls was 16.9% in males and 24.3% in females [Corrected]. Age and female sex were associated with a higher risk of falls. Similarly, living alone, living in an urban area, poor self-rated health, and high stress were associated with a high risk of falls. Subjects with diabetes mellitus, stroke, osteoarthritis, osteoporosis, urinary incontinence, cataracts, or depression had a high risk of falls. However, subjects with hypertension were at low risk for falls. In conclusion, age, female sex, marital status, residence location, self-rated health, stress, and several chronic conditions were significantly associated with the risk for falls in the older Korean adults. Our findings suggest that these risk factors should be addressed in public health policies for preventing falls.

Genetic variation in PSCA is associated with bladder cancer susceptibility in a Korean population.

BACKGROUND: Genetic factors play important roles in the pathogenesis of human cancer. A recent genome wide association study (GWAS) identified an association between the rs2294008 polymorphism of the prostate stem cell antigen (PSCA) gene and bladder cancer risk in Caucasians. The aim of this study was to determine whether the rs2294008 polymorphism is similarly associated with bladder cancer susceptibility in a Korean population. MATERIALS AND METHODS: We conducted a case-control study of 411 bladder cancer patients and 1,700 controls. RESULTS: The frequencies of the CC, CT, and TT genotypes of the rs2294008 polymorphism were 16.9, 54.0, and 28.8% in bladder cancer patients and 24.4, 48.1, and 27.5% in controls, respectively. We found that the combined CT/TT genotypes were associated with a significantly increased risk of bladder cancer (OR CT/TT=1.58, 95% CI=1.15-2.17), compared with the CC genotype. Smoking habits, tumor grade and tumor stage did not modify the association between rs2294008 and the risk of bladder cancer. CONCLUSIONS: Our study showed that the rs2294008 polymorphism in the PSCA gene is associated with the risk of bladder cancer in a Korean population, providing evidence that it may contribute to bladder carcinogenesis regardless of ethnicity.

Reference levels of blood mercury and association with metabolic syndrome in Korean adults.

PURPOSE: Mercury (Hg) is a nonessential and toxic metal that is widely distributed in the environment. This study was performed to estimate the representative blood Hg level, to determine the contributing factors to Hg exposure, and to analyze the association of blood Hg with metabolic syndrome in Korean adults. METHODS: Mercury exposure is assessed by total Hg concentration in blood. A total of 2,114 healthy adults who have not been exposed to Hg occupationally were sampled by the multistaged, sex-, and age-stratified probability method. Information was collected regarding the subjects' demographic characteristics, lifestyles, and past medical history. The participants then underwent physical examination and blood sampling. RESULTS: The geometric mean concentration of Hg in whole blood was 3.90 µg/L, which was significantly influenced by sex, age, smoking, alcoholic consumption, residence area, and seafood intake after adjustment for confounders. Significant increases in body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyceride were observed according to the blood Hg levels after adjustment for covariates. Also, Hg exposure was significantly associated with metabolic syndrome and their components such as obesity and increased fasting glucose. CONCLUSION: The blood Hg level in Korean adults is higher than that in USA and other Western countries, while it is similar to or lower than that in other Asian countries. The blood Hg level is influenced by sociodemographic factors and individual lifestyles including dietary habits. Furthermore, blood Hg is associated with metabolic syndrome, in which Hg exposure may play a role as a possible risk factor for cardiovascular diseases.

Arterial stiffness is associated with diabetic retinopathy in Korean type 2 diabetic patients.

OBJECTIVES: We evaluated the association between common carotid artery intima-media thickness (CCA-IMT), brachial-ankle pulse wave velocity (baPWV), carotid plaque, and peripheral arterial disease (PAD) as indicators of macroangiopathy and diabetic retinopathy as an indicator of microangiopathy in type 2 diabetic patients. METHODS: We analyzed 605 type 2 diabetic patients registered at a public health center in Korea. Following overnight fasting, venous blood and urine samples were collected and analyzed. The CCA-IMT, levels of carotid plaque, baPWV, and ankle-brachial index (ABI) of the subjects were assessed. We used non-mydriatic fundus photography to diagnose diabetic retinopathy. Multiple logistic regression analyses were used to evaluate the association between macroangiopathy and diabetic retinopathy. CCA-IMT and baPWV were divided into tertiles: CCA-IMT, 0.39 to 0.65 mm, 0.66 to 0.78 mm, and 0.79 to 1.30 mm; baPWV, 9.9 to 15.8 m/s, 15.9 to 18.9 m/s, and 19.0 to 38.0 m/s. RESULTS: The association between baPWV and diabetic retinopathy remained significant after adjustment, with an increasing odds ratio (OR) in the second tertile (OR, 2.41; 95% confidence interval [CI], 1.27 to 4.55) and the third tertile (OR, 4.63; 95% CI, 2.33 to 9.21). No significant differences were observed in carotid plaque, PAD, and each tertile of CCA-IMT. CONCLUSIONS: BaPWV was associated with diabetic retinopathy, while CCA-IMT, carotid plaque, and PAD were not. This study suggests that the association between macroangiopathy and microangiopathy may be attributable to functional processes rather than structural processes within the vascular system.

[A comparison of fasting glucose and HbA1c for the diagnosis of diabetes mellitus among Korean adults].

OBJECTIVES: The American Diabetes Association (ADA) has recently recommended the HbA1c assay as one of four options for making the diagnosis of diabetes mellitus, with a cut-point of ≥ 6.5%. We compared the HbA1c assay and the fasting plasma glucose level for making the diagnosis of diabetes among Korean adults. METHODS: We analyzed 8710 adults (age 45-74 years), who were not diagnosed as having diabetes mellitus, from the Namwon study population. A fasting plasma glucose level of ≥ 126 mg/dL and an A1c of ≥ 6.5% were used for the diagnosis of diabetes. The kappa index of agreement was calculated to measure the agreement between the diagnosis based on the fasting plasma glucose level and the HbA1c. RESULTS: The kappa index of agreement between the fasting plasma glucose level and HbA1c was 0.50. CONCLUSIONS: The agreement between the fasting plasma glucose and HbA1c for the diagnosis of diabetes was moderate for Korean adults.