Low Serum Creatinine as Well as High Serum Creatinine Is Associated with Prognosis of Patients with Cancer in End-of-Life.

Background: The prognosis of end-of-life patients is challenging, and clinicians have attempted to predict survival more accurately. High serum creatinine (sCr) levels are associated with lower survival rates in patients with various cancers; however, low sCr levels are commonly expected in patients with terminal cancer because of muscle wasting and malnutrition. Therefore, we investigated the prevalence of low and high sCr levels and their association with survival duration in patients with terminal cancer in a palliative care unit. Methods: We analyzed the medical records of 280 patients admitted to a palliative care unit. Patients were divided into low (<0.5 mg/dL), normal (0.5-1.2 mg/dL), and high (>1.2 mg/dL) sCr groups. Kaplan-Meier survival curves using sCr levels were plotted and compared using the log-rank test. Using stepwise selection, a multivariable Cox proportional hazards model was used to identify the significant prognostic factors. Results: The median survival durations in the high-, low-, and normal-sCr groups were 9.57 days, 22.26 days, and 27.51 days, respectively. Multivariable Cox proportional hazard model identified that males (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.16-2.85), poor performance status (HR, 3.43; 95% CI, 1.12-10.54), total parenteral nutrition use (HR, 1.84; 95% CI, 1.09-3.1), high sCr (HR, 2.74; 95% CI, 1.52-4.94), and low sCr (HR, 1.22; 95% CI, 1.07-1.43) were significantly associated with a shorter survival time. Conclusion: Low and high serum creatinine levels were significantly associated with poor survival in patients with cancer at the end-of-life stage. Therefore, readily available and simple biomarkers may help plan advanced care in palliative care settings.

Use of thyroid transcription factor 1 and napsin A to predict local failure and survival after Gamma Knife radiosurgery in patients with brain metastases from lung adenocarcinoma.

OBJECTIVE: Stereotactic radiosurgery (SRS), combined with contemporary targeted therapies and immunotherapies, has improved the overall survival of patients with lung adenocarcinoma (ADC). Given that histological subtypes reflect prognosis in patients with primary ADC, it is important to integrate pathological biomarkers to predict clinical outcomes after SRS in patients with brain metastases from lung ADC. Therefore, the authors investigated the prognostic relevance of various biomarkers of primary lung ADC for clinical outcomes after SRS. METHODS: A total of 95 patients with 136 brain metastases (1-4 oligometastases) who were treated with Gamma Knife radiosurgery between January 2017 and December 2020 were included. The Kaplan-Meier method and univariate and multivariate analyses using Cox proportional hazard regression models were used to identify prognostic factors for local control, survival, and distant brain control. RESULTS: Multivariate analysis revealed thyroid transcription factor 1 as an independent prognostic factor for local control (HR 0.098, 95% CI 0.014-0.698, p = 0.0203) and napsin A as a significant predictor of overall survival after SRS (HR 0.080, 95% CI 0.017-0.386, p < 0.01). In a subset analysis of epidermal growth factor receptor (EGFR) mutation, patients with EGFR exon 19 mutations showed better distant brain control than those with EGFR exon 21 mutations (p < 0.01). CONCLUSIONS: Pathological biomarkers of primary cancer should be considered to predict clinical outcomes after SRS in patients with lung ADC. Use of such biomarkers may help to provide personalized treatment to each patient, improving clinical outcomes after SRS.

Ultrasonographic index for the diagnosis of non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease.

Background: Liver biopsy is a gold standard for the diagnosis of non-alcoholic steatohepatitis (NASH), but has several disadvantages including invasiveness, high cost, and sampling error. Ultrasonography (US) is a noninvasive imaging modality widely used in non-alcoholic fatty liver disease (NAFLD) patients. This study aimed: (I) to assess the feasibility of US in the prediction of NASH and (II) to develop various US indices combining US parameters and laboratory data for the detection of NASH in NAFLD patients and to compare the diagnostic performance of them. Methods: Sixty patients who underwent liver biopsy, gray-scale US [hepatorenal index (HRI) and shear-wave elastography (SWE)], and Fibroscan [controlled attenuation parameter (CAP) and transient elastography (TE)] for the evaluation of NASH were included. Patients were classified according to the NAFLD Activity Score (NAS) into the NASH (NAS ≥5) and non-NASH (NAS <5) groups. The diagnostic performance of HRI, CAP, SWE, TE, and laboratory data for grading steatosis, lobular inflammation, ballooning degeneration, and fibrosis was evaluated. After the identification of laboratory data that were independently associated with NASH through univariable and multivariable logistic regression analyses, various US indices were developed by combining US parameters with or without these laboratory data. The diagnostic performance of the US indices was assessed with obtaining area under the curve (AUC) and compared using DeLong test. Results: Twenty-five NASH and 35 non-NASH patients were included. The mean AUCs for grading steatosis were 0.871 using HRI and 0.583 using CAP. The mean AUCs for grading fibrosis and ballooning degeneration were 0.777 and 0.729 using SWE and 0.830 and 0.708 using TE, respectively. Aspartate aminotransferase (AST) was the only significant laboratory data associated with NASH (OR, 1.019; P=0.032). Using AST, the mean AUCs for grading lobular inflammation and ballooning degeneration were 0.712 and 0.775, respectively. Among various US indices, the index consisting of gray-scale US parameters (SWE and HRI) and AST showed the best diagnostic performance for the detection of NASH in NAFLD patients (AUC =0.806). Conclusions: The index combining gray-scale US parameters and AST is useful for the detection of NASH and may be used to exclude the need for liver biopsy in NAFLD patients.

Increased Risk of Type 2 Diabetes in Patients With Thyroid Cancer After Thyroidectomy: A Nationwide Cohort Study.

CONTEXT: Abnormal thyroid function after thyroidectomy and subsequent thyroid-stimulating hormone suppression can have detrimental effects on glucose homeostasis in patients with thyroid cancer. OBJECTIVE: To investigate whether thyroidectomy increases the risk of type 2 diabetes in patients with thyroid cancer and to explore the association between levothyroxine dosage and type 2 diabetes risk. METHODS: A retrospective population-based cohort study using the Korean National Health Insurance database. We included 36 377 thyroid cancer patients without known diabetes who underwent thyroidectomy between 2004 and 2013. Matched subjects with nonthyroid cancer were selected using 1:1 propensity score matching. The main outcome measure was newly developed type 2 diabetes mellitus. RESULTS: Patients with thyroid cancer who underwent thyroidectomy had a higher risk of developing type 2 diabetes mellitus than the matched controls (hazard ratio [HR] 1.43, 95% CI 1.39-1.47). Among patients with thyroid cancer, when the second quartile group (in terms of the mean levothyroxine dosage; 101-127 µg/day) was considered the reference group, the risk of type 2 diabetes mellitus increased in the first quartile (<101 µg/day; HR 1.45, 95% CI 1.36-1.54) and fourth quartile groups (≥150 µg/day; HR 1.37, 95% CI 1.29-1.45); meanwhile, the risk decreased in the third quartile group (128-149 µg/day; HR 0.91, 95% CI 0.85-0.97). CONCLUSION: Patients with thyroid cancer who underwent thyroidectomy were more likely to develop type 2 diabetes mellitus than the matched controls. There was a U-shaped dose-dependent relationship between the levothyroxine dosage and type 2 diabetes mellitus risk.

Risk of Diabetes in Patients with Long-Standing Graves' Disease: A Longitudinal Study.

BACKGROUND: The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies. METHODS: The risk of diabetes in patients with Graves' disease treated with antithyroid drugs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group. RESULTS: A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019). CONCLUSION: The risk of diabetes was significantly higher in patients with long-standing Graves' disease than in the general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.

Assessment of Additional MRI-Detected Breast Lesions Using the Quantitative Analysis of Contrast-Enhanced Ultrasound Scans and Its Comparability with Dynamic Contrast-Enhanced MRI Findings of the Breast.

Purpose: To assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) for additional MR-detected enhancing lesions and to determine whether or not kinetic pattern results comparable to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast can be obtained using the quantitative analysis of CEUS. Materials and Methods: In this single-center prospective study, a total of 71 additional MR-detected breast lesions were included. CEUS examination was performed, and lesions were categorized according to the Breast Imaging-Reporting and Data System (BI-RADS). The sensitivity, specificity, and diagnostic accuracy of CEUS were calculated by comparing the BI-RADS category to the final pathology results. The degree of agreement between CEUS and DCE-MRI kinetic patterns was evaluated using weighted kappa. Results: On CEUS, 46 lesions were assigned as BI-RADS category 4B, 4C, or 5, while 25 lesions category 3 or 4A. The diagnostic performance of CEUS for enhancing lesions on DCE-MRI was excellent, with 84.9% sensitivity, 94.4% specificity, and 97.8% positive predictive value. A total of 57/71 (80%) lesions had correlating kinetic patterns and showed good agreement (weighted kappa = 0.66) between CEUS and DCE-MRI. Benign lesions showed excellent agreement (weighted kappa = 0.84), and invasive ductal carcinoma (IDC) showed good agreement (weighted kappa = 0.69). Conclusion: The diagnostic performance of CEUS for additional MR-detected breast lesions was excellent. Accurate kinetic pattern assessment, fairly comparable to DCE-MRI, can be obtained for benign and IDC lesions using CEUS.

Fasting Plasma Glucose Variability and Gastric Cancer Risk in Individuals Without Diabetes Mellitus: A Nationwide Population-Based Cohort Study.

INTRODUCTION: Long-term glycemic variability is associated with various adverse health outcomes in patients with diabetes mellitus (DM). However, the relationship between glycemic variability and gastric cancer remains unclear. We aimed to investigate the association between glycemic variability and gastric cancer incidence in individuals without DM. METHODS: We used the Korean National Health Insurance Service data sets of claims and health checkups and included 202,562 individuals without DM. Fasting plasma glucose (FPG) variability was measured using the variability independent of the mean (VIM), coefficient of variation, SD, and average successive variability. The association between FPG variability and gastric cancer incidence was analyzed using Cox regression adjusting for age, sex, body mass index, smoking status, alcohol consumption, regular exercise, income level, family history of cancer, mean FPG level, and number/mean interval of FPG measurements. RESULTS: In total, 1,920 patients developed gastric cancer (0.95%) within a median follow-up of 5.6 (5.3, 6.4) years. The fully adjusted hazard ratio and 95% confidence interval for gastric cancer were 1.26 and 1.18-1.34, respectively, in the highest quartile of FPG variability assessed by VIM compared with that in the lowest quartile. Similar results were obtained in the normal and impaired fasting glucose groups and when using the variability indexes, including coefficient of variation, SD, and average successive variability. There was a sequential increase in the incidence of gastric cancer according to the increase in the deciles of FPG variability (P for linear trend <0.001). A 1-SD increase in FPG variability assessed by VIM was significantly associated with a 10.0% increase in gastric cancer risk in the fully adjusted model. DISCUSSION: In a DM-free population, high variability in visit-to-visit FPG levels was independently associated with an increased risk of gastric cancer.

Non-Thermal Plasma Couples Oxidative Stress to TRAIL Sensitization through DR5 Upregulation.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cells without affecting most normal cells. Despite being in clinical testing, novel strategies to induce TRAIL-mediated apoptosis are in need to overcome cancer cell unresponsiveness and resistance. Plasma-activated medium (PAM) markedly stimulates reactive oxygen/nitrogen species (ROS/RNS)-dependent apoptosis in cancer cells. We investigate the capability of PAM and TRAIL (PAM/TRAIL) combination therapy to overcome TRAIL resistance and improve the anticancer efficacy of TRAIL. The combinatorial treatment of PAM and TRAIL shows synergistic effects on growth inhibition in TRAIL-resistant cancer cells via augmented apoptosis by two attributes. DR5 (TRAIL-R2) transcription by CHOP is upregulated in a PAM-generated ROS/RNS-dependent manner, and PAM itself upregulates PTEN expression mediated by suppression of miR-425 which is involved in Akt inactivation, leading to increased apoptosis induction. Treatment of cancer cell lines with the antioxidant N-acetylcysteine reduces the extent of membrane dysfunction and the expression of both CHOP-DR5 and miR-425-PTEN axes, attenuating PAM/TRAIL-induced cancer cell apoptosis. These data suggest that PAM/TRAIL treatment is a novel approach to sensitizing cancer cells to TRAIL-induced apoptosis and overcoming TRAIL resistance. PAM is a promising candidate for further investigations as a chemotherapeutic sensitizer in the treatment of cancer.

Comparison of anthropometric indices for the screening of nonalcoholic fatty liver disease in pre- and postmenopausal women.

OBJECTIVES: Although it has been well-established that menopause causes a shift in body fat, there has been no study conducted yet to examine the best obesity parameters to predict the risk of nonalcoholic fatty liver disease (NAFLD) in this population. Thus, the aim of this study was to clarify the superiority among various obesity indices such as body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) for predicting NAFLD in pre- and postmenopausal women. METHODS: This cross-sectional analysis included 620 healthy women (318 premenopausal and 302 postmenopausal women) between 20 and 80 years of age recruited from the Health Promotion Center of Korea University Guro Hospital. NAFLD was diagnosed by abdominal ultrasonography. RESULTS: In premenopausal women, there were no statistical differences in the area under the curve values among the three obesity indices, whereas, in postmenopausal women, the area under the curve value of WHR was significantly larger than those of either BMI (difference between area: 0.102, 95% confidence interval: 0.031, 0.173) or WC (difference between area: 0.064, 95% confidence interval: 0.018-0.109). Furthermore, in postmenopausal women, the combination of WHR with BMI or WC significantly increased predictive power of NAFLD when compared to using BMI or WC alone. The optimal cutoff values for BMI, WC, and WHR for detecting NAFLD were 23.9 kg/m, 69 cm, and 0.81 in premenopausal women and 22.9 kg/m, 74 cm, and 0.86 in postmenopausal women, respectively. CONCLUSIONS: In premenopausal women, BMI, WC, and WHR hold similar potential in predicting the risk of NAFLD, whereas, in postmenopausal women, WHR is the most useful discriminative indicator for NAFLD. Women's optimal cutoff values for NAFLD were different according to menopausal status.

Association of Screening by Thyroid Ultrasonography with Mortality in Thyroid Cancer: A Case-Control Study Using Data from Two National Surveys.

Background: The incidence of thyroid cancer is increasing worldwide due to an increased detection of small well-differentiated papillary thyroid carcinomas. This study aimed to evaluate the effect of screening with ultrasonography on deaths from thyroid cancer. Materials and Methods: We conducted a matched case-control study using data from two sources representative of the adult Korean population. Cases were selected from the National Epidemiologic Survey of Thyroid Cancer database, and controls were selected from the Korean National Cancer Screening Survey database. Controls were individually matched to case patients with respect to age, sex, and area with a ratio of 10:1. The primary outcome was death from thyroid cancer. Controls were required to have been alive on the date of thyroid cancer diagnosis in the corresponding case. Results: The analysis included 120 patients who died from thyroid cancer and 1184 controls. Compared with those who had never been screened, the odds ratios for death from thyroid cancer among those who had been screened were 1.44 (95% confidence interval [CI] 0.68-3.05) if cases with missing information on screening were excluded and 1.13 [CI 0.49-2.63] if all cases were included, and missing information was imputed. Stratification by sex, year of diagnosis, and histological type did not show any statistically significant relationships between screening with ultrasonography and death from thyroid cancer, regardless of the statistical model used. Conclusions: Screening for thyroid cancer with ultrasonography does not prevent death from thyroid cancer; therefore, screening asymptomatic adults for thyroid cancer is unwarranted.

Radiation-Induced CXCL12 Upregulation via Histone Modification at the Promoter in the Tumor Microenvironment of Hepatocellular Carcinoma.

Tumor cells can vary epigenetically during ionizing irradiation (IR) treatment. These epigenetic variegations can influence IR response and shape tumor aggressiveness. However, epigenetic disturbance of histones after IR, implicating in IR responsiveness, has been elusive. Here, we investigate whether altered histone modification after IR can influence radiation responsiveness. The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and coculture of human hepatoma Huh7 and normal IMR90 cells after radiation. H3K4 methylation was also enriched and H3K9 methylation was decreased at its promoter region. Accordingly, invasiveness and the subpopulation of aggressive CD133+/CD24- cells increased after IR. Histone demethylase inhibitor IOX1 attenuated CXCL12 expression and the malignant subpopulation, suggesting that responses to IR can be partially mediated via histone modifications. Taken together, radiation-induced histone alterations at the CXCL12 promoter in hepatoma cells are linked to CXCL12 upregulation and increased aggressiveness in the tumor microenvironment.

Radiation-Induced CXCL12 Upregulation via Histone Modification at the Promoter in the Tumor Microenvironment of Hepatocellular Carcinoma.

Tumor cells can vary epigenetically during ionizing irradiation (IR) treatment. These epigenetic variegations can influence IR response and shape tumor aggressiveness. However, epigenetic disturbance of histones after IR, implicating in IR responsiveness, has been elusive. Here, we investigate whether altered histone modification after IR can influence radiation responsiveness. The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and coculture of human hepatoma Huh7 and normal IMR90 cells after radiation. H3K4 methylation was also enriched and H3K9 methylation was decreased at its promoter region. Accordingly, invasiveness and the subpopulation of aggressive CD133+/CD24- cells increased after IR. Histone demethylase inhibitor IOX1 attenuated CXCL12 expression and the malignant subpopulation, suggesting that responses to IR can be partially mediated via histone modifications. Taken together, radiation-induced histone alterations at the CXCL12 promoter in hepatoma cells are linked to CXCL12 upregulation and increased aggressiveness in the tumor microenvironment.

Defining "early" cranioplasty to achieve lower complication rates of bone flap failure: resorption and infection.

BACKGROUND: Although cranioplasty (CP) is a frequently performed and simple procedure, complications are common, particularly bone flap resorption and infection. The timing of surgery is as an important contributory factor, but the optimal timing has not been clearly determined. OBJECTIVE: We retrospectively investigated bone flap resorption and surgical site infection after CP to determine the optimal timing of surgery for reduction of complications. METHODS: The study enrolled 126 patients who underwent decompressive craniectomy (DC) and subsequent CP. Patients with bone flap resorption or surgical site infection were analyzed as the "complication" group. Receiver operating characteristic curve analysis was performed and the Youden index was used to dichotomize "early CP" and "late CP" groups. Univariate and multivariate survival analyses were performed. RESULTS: The complication group included 42 patients. The Youden index was used to identify a cutoff value for the DC-CP interval of > 44 days, and this was used to define early (< 45 days) and late (≥ 45 days) CP. Late CP was a significant risk factor in univariate and multivariate Cox regression analyses. CONCLUSION: This study showed that early CP before 45 days after DC is associated with a lower rate of bone flap resorption and surgical site infection than late CP.

Prevalence of Dizziness and Associated Factors in South Korea: A Cross-Sectional Survey From 2010 to 2012.

BACKGROUND: Dizziness is one of the most common complaints in medicine and a frequent symptom among older people. Dizziness has a considerable impact on life quality and is associated with high economic costs. The purpose of this study was to evaluate the prevalence of dizziness in the general population and to describe its clinical characteristics and associated factors. METHODS: The Korea National Health and Nutrition Examination Survey (KNHANES) is a cross-sectional survey of the civilian, non-institutionalized population of South Korea. We evaluated data for 12,653 participants (5,450 men and 7,203 women), aged 40 years and above, whom participated in the KNHANES between 2010 and 2012. RESULTS: In the age group over 40 years old, the 1-year prevalence of dizziness was 20.10%. Dizziness was more prevalent among women (25.18%) than among men (14.57%; P < 0.001) and the prevalence rate increased with age (P < 0.001). In multivariable analysis, female sex, older age, serum triglyceride level, experience of depression, limited functional status owing to visual acuity impairment, limited physical performance, smoking, alcohol consumption, and perception of stress were independently associated with dizziness. CONCLUSIONS: In our study, the prevalence of dizziness in the general population was 20.10%. There was a stronger relationship between dizziness and physical performance, chronic diseases, and health behaviors compared to that with otologic diseases. Interventions for dizziness should be approached in a multifactorial manner and an understanding of various factors is necessary for the prevention and management of this condition.

Characteristics of retinal vessels in surgically closed macular hole: an optical coherence tomography angiography study.

PURPOSE: The purpose of our study was to investigate characteristics of retinal vessels in eyes with surgically closed macular holes (MH). METHODS: We included patients who underwent surgery for idiopathic MH and a follow-up examination using optical coherence tomography angiography (OCTA). The area of the foveal avascular zone (FAZ) and retinal vascular densities of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were calculated on the postoperative OCTA images and compared with those of age-matched normal controls. RESULTS: Twenty-eight patients with MH and 28 controls were included. Mean postoperative FAZ areas of SCP and DCP (0.317 ± 0.129 mm2 and 0.500 ± 0.174 mm2) were smaller than those of normal controls (0.406 ± 0.131 mm2 and 0.687 ± 0.147 mm2) (P = 0.013 and P < 0.001, respectively). Retinal vascular densities of SCP and DCP in the MH group (32.23 ± 1.45% and 31.85 ± 1.28%) were lower than those of the control group (33.26 ± 1.71% and 33.18 ± 1.89%) (P = 0.019 and P = 0.003, respectively). The retinal vascular densities of SCP and DCP were associated with postoperative mean ganglion cell-inner plexiform layer (GC-IPL) thickness (P = 0.033 and P = 0.035, respectively). The vascular densities were horizontally asymmetric and related to asymmetric distribution of GC-IPL thickness in the MH group. CONCLUSIONS: Surgically closed MH eyes had remodeled retinal vascular patterns, which were related to morphologic changes in the inner retinal layer. The healing process after MH surgery may be involved in asymmetric change in anatomy and hemodynamics of the inner retina.

Reproducibility and diagnostic performance of shear wave elastography in evaluating breast solid mass.

Shear wave elastography (SWE) was performed independently by two radiologists in 264 solid breast masses. The images were reviewed for color overlay pattern (COP) classification by the two radiologists, double blinded to any information. The interobserver agreement of the COP was almost perfect (κ=0.908) and high in Emax (ICC=0.89). The AUC value of the COP (0.954) was significantly higher than that of Emax (0.915) (p=0.002) but not significantly different from that of Emax combined with COP (0.957) (p=0.098). The SWE color overlay pattern and Emax of breast masses were highly reproducible. The COP had better diagnostic ability than Emax, suggesting that COP may be a more reliable parameter for solid breast mass evaluation.

Peripapillary choroidal thickness after intravitreal ranibizumab injections in eyes with neovascular age-related macular degeneration.

BACKGROUND: The purpose of this study was to investigate peripapillary choroidal thickness (CT) in eyes with neovascular age-related macular degeneration (AMD) and to assess whether peripapillary CT is affected by intravitreal injection of ranibizumab (IVR) in eyes with neovascular AMD. METHODS: Peripapillary and subfoveal CT were measured in spectral domain optical coherence tomography images from 39 eyes of neovascular AMD patients and 39 eyes of age-matched controls retrospectively. The patients were treated with 0.5 mg IVR monthly for 3 months and retreated as needed. Peripapillary CT at baseline, 3 months and 6 months was measured at four locations (superior, nasal, inferior and temporal areas). RESULTS: The mean peripapillary and subfoveal baseline CTs of the eyes with neovascular AMD (153.3 ± 45.3 µm and 228.6 ± 78.6 µm) were not different from those of the controls (149.0 ± 42.3 µm and 221.4 ± 54.1 µm; P = 0.665 and P = 0.639, respectively). Subfoveal CT decreased at 3 months (213.8 ± 75.8 µm, P < 0.001) and 6 months (215.1 ± 72.8 µm, P = 0.002) following IVR treatment. Mean peripapillary CT did not show significant changes at 3 months (149.6 ± 43.8 µm, P = 0.156) or 6 months (150.0 ± 43.4 µm, P = 0.187). Subanalysis revealed that only temporal peripapillary CT decreased from baseline (167.1 ± 54.5 µm) to 3 months (159.4 ± 50.8 µm, P = 0.010) and was sustained at 6 months (160.6 ± 49.6, P = 0.026). However, superior, nasal and inferior peripapillary CT did not show significant changes after IVR. CONCLUSIONS: Changes in peripapillary CT after IVR were limited to the macular area. This result may suggest that IVR does not affect CT outside of the macula in the eyes of patients with neovascular AMD.

Comparison of intravitreal aflibercept and ranibizumab injections on subfoveal and peripapillary choroidal thickness in eyes with neovascular age-related macular degeneration.

PURPOSE: We aimed to compare changes in subfoveal and peripapillary choroidal thickness (CT) after intravitreal aflibercept or ranibizumab injections for neovascular age-related macular degeneration (AMD). METHODS: Medical records of 54 treatment-naïve, consecutive patients (54 eyes) who were diagnosed with neovascular AMD and received three monthly injections of aflibercept (21 eyes) or ranibizumab (33 eyes) were reviewed. Subfoveal and peripapillary CT were measured with images obtained using spectral domain optical coherence tomography at baseline and at three months. RESULTS: Subfoveal CT decreased from 232.2 ± 94.4 µm at baseline to 207.1 ± 89.3 µm at three months in the aflibercept group (p < 0.001) and from 231.5 ± 102.9 µm to 220.0 ± 98.0 µm in the ranibizumab group (p = 0.006). The reduction was greater in the aflibercept group than in the ranibizumab group (p = 0.024). Peripapillary CT decreased from 157.2 ± 62.2 µm at baseline to 147.4 ± 62.2 µm at three months in the aflibercept group (p < 0.001). However, the change in peripapillary CT from 154.9 ± 46.5 µm at baseline to 152.3 ± 50.0 µm at three months was not significant in the ranibizumab group (p = 0.123). CONCLUSIONS: Intravitreally injected aflibercept significantly decreased subfoveal CT more than ranibizumab. Choroidal thinning after aflibercept injection was not limited to the subfoveal area, but extended beyond the macula as well.

Effect of Cigarette Smoking and Passive Smoking on Hearing Impairment: Data from a Population-Based Study.

OBJECTIVES: In the present study, we aimed to determine the effect of both active and passive smoking on the prevalence of the hearing impairment and the hearing thresholds in different age groups through the analysis of data collected from the Korea National Health and Nutrition Examination Survey (KNHANES). STUDY DESIGN: Cross-sectional epidemiological study. METHODS: The KNHANES is an ongoing population study that started in 1998. We included a total of 12,935 participants aged ≥19 years in the KNHANES, from 2010 to 2012, in the present study. Pure-tone audiometric (PTA) testing was conducted and the frequencies tested were 0.5, 1, 2, 3, 4, and 6 kHz. Smoking status was categorized into three groups; current smoking group, passive smoking group and non-smoking group. RESULTS: In the current smoking group, the prevalence of speech-frequency bilateral hearing impairment was increased in ages of 40-69, and the rate of high frequency bilateral hearing impairment was elevated in ages of 30-79. When we investigated the impact of smoking on hearing thresholds, we found that the current smoking group had significantly increased hearing thresholds compared to the passive smoking group and non-smoking groups, across all ages in both speech-relevant and high frequencies. The passive smoking group did not have an elevated prevalence of either speech-frequency bilateral hearing impairment or high frequency bilateral hearing impairment, except in ages of 40s. However, the passive smoking group had higher hearing thresholds than the non-smoking group in the 30s and 40s age groups. CONCLUSION: Current smoking was associated with hearing impairment in both speech-relevant frequency and high frequency across all ages. However, except in the ages of 40s, passive smoking was not related to hearing impairment in either speech-relevant or high frequencies.

Circulating angiopoietin-like protein 8 (ANGPTL8) and ANGPTL3 concentrations in relation to anthropometric and metabolic profiles in Korean children: a prospective cohort study.

BACKGROUND: Previous studies have shown that angiopoietin-like protein 8 (ANGPTL8), also called as betatrophin, acts together with ANGPTL3 to regulate lipid metabolism, glucose metabolism, and energy homeostasis. Moreover, ANGPTL8 promotes proliferation of pancreatic ß-cells and induces insulin secretion. However, there are no previous longitudinal studies in humans. METHODS: We analyzed the age- and sex-matched data of 240 normal weight and overweight Korean children from the Korean Metabolic disorders and Obesity Study in Elementary School children (K-MOSES), a prospective observational cohort study. RESULTS: At baseline, ANGPTL8 concentrations were positively associated with triglycerides (TG) (r = 0.168, P = 0.010), whereas ANGPTL3 levels were associated with fasting insulin (r = 0.248, P < 0.001) and the homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.197, P = 0.002). Although both ANGPTL8 and ANGPTL3 levels did not differ between children with normal weight and children with overweight, ANGPTL8 levels were increased in males compared to females (341.2 [267.4-436.5] vs. 270.2 [213.9-378.8] pg/ml, P = 0.001). In particular, there was no significant inter-relationship between circulating ANGPTL8 and ANGPTL3 concentrations in Korean boys and girls (r = -0.073, P = 0.265). Multivariate analysis showed that baseline ANGPTL8 concentrations were independently associated with future changes of serum TG levels in Korean children after adjusting for confounding factors after a 3 year follow-up period (r = -0.165, P = 0.016). CONCLUSIONS: This longitudinal study demonstrated for the first time that baseline ANGPTL8 levels were associated with baseline and future changes in TG levels in Korean children.