Report on the seventh meeting of national control laboratories for vaccines and biologicals of the WHO Western Pacific and South-East Asia member states.

The Biregional Network of National Control Laboratories (NCLs) of the WHO Western Pacific and South-East Asia Regions has been meeting annually since 2018 to enhance NCLs' voluntary participation capacity. Its seventh meeting was hosted by the Korea National Institute of Food and Drug Safety Evaluation (NIFDS) of the Ministry of Food and Drug Safety (MFDS), in conjunction with the Global Bio Conference, in Seoul on September 6, 2022. Over 60 participants from seven countries, (India, Indonesia, Japan, Korea, Malaysia, the Philippines, and Vietnam) attended the meeting on-site and online. The theme of this meeting was 'Quality Control Issues and International Trends for Biologicals including Vaccines and Plasma-Derived Medicinal Products.' Three special speeches were presented on sharing the quality control system for biologicals, including NCLs' considerations in preparing the WHO Listed Authorities and sharing MFDS experiences. Furthermore, the participating NCLs shared country-specific issues related to national lot releases during the COVID-19 pandemic and acknowledged the meeting's crucial role in response preparedness for pandemic emergencies and enhancing regulatory capacity through coalitions and information exchange among NCLs. The NIFDS will cooperate closely with other Asian NCLs to enhance biological product quality control, aiming to establish regional standards and standardize test methods through collaboration.

Does Computer-Aided Diagnosis Permit Differentiation of Angiomyolipoma Without Visible Fat From Renal Cell Carcinoma on MDCT?

OBJECTIVE: The purpose of this study was to evaluate the diagnostic value of computer-aided diagnosis (CADx) in differentiating angiomyolipoma without visible fat from renal cell carcinoma (RCC) on MDCT. MATERIALS AND METHODS: The study included 406 patients who had 47 angiomyolipomas without visible fat and 359 RCCs smaller than 4 cm, all of which were diagnosed on the basis of findings from nephrectomy or percutaneous biopsy performed at our institution between 2000 and 2011. MDCT (slice thickness, 2.5 mm for corticomedullary phase image or 5 mm for the other phase images) and clinical findings were blindly reviewed by two radiologists in a single session. At the time the study was performed, radiologist 1 had 8 years of experience, and radiologist 2 had 18 years of experience. On the basis of the MDCT and clinical findings, CADx classified renal tumors as angiomyolipoma and RCC, and each radiologist independently recorded the probability score (0-5) for angiomyolipoma. The accuracy of CADx versus radiologists in diagnosing angiomyolipoma was compared using ROC analysis. Interobserver agreement between the two radiologists was evaluated. RESULTS: CADx yielded an area under the curve (Az) value of 0.949, which was greater than the Az values yielded by radiologists 1 and 2 (0.872 and 0.782, respectively; p < 0.05). In addition, the Az value for radiologist 1 was greater than that for radiologist 2 (p = 0.01). CADx with a threshold of -1.0085 showed greater sensitivity than radiologist 1 and greater sensitivity, specificity, and accuracy than radiologist 2 (p < 0.05). The interobserver agreement for the differentiation was fair (κ = 0.289). CONCLUSION: CAD can improve diagnostic performance in differentiating angiomyolipoma from RCC. The diagnostic performance of radiologists is variable according to the clinical experience and physical and emotional states of the radiologists.

Analysis of Removal Torque of Injection Molded Zirconia Implants; An Experimental Study on Beagles.

This study compared the removal torque between injection molded zirconia implants and titanium implants with resorbable blast media (RBM) surfaces in beagle humeri. Fifteen screw-shaped implants were classified into 3 groups; titanium implant with RBM surface (Group RT), injection molded zirconia implant (Group Zr) and injection molded zirconia implant with sand-blasted surface (Group ZrS). Implants were inserted into beagle humeri. After 12 weeks, removal torque values were measured. The Zr group has a slightly higher removal torque value than the RT and ZrS groups but there were no significant differences among groups. Zirconia implants shows a similar removal torque to RBM titanium implants. This in vivo study showed injection molded zirconia implants could be an alternative to RBM titanium implants in terms of removal torque.

Arterial stiffness, fatty liver and the presence of coronary artery calcium in a large population cohort.

BACKGROUND: We tested whether fatty liver, brachial-ankle pulse wave velocity (baPWV) and conventional cardiovascular risk factors were associated with a coronary artery calcium (CAC) score > 0 (as a marker of the presence of early atherosclerosis) in a cohort of healthy Korean adults. METHOD: The study population consisted of individuals who underwent a comprehensive health examination in 2010 at Kangbuk Samsung Hospital, College of Medicine, Sungkyunkwan University in South Korea. The 6009 subjects of total 7371 participants who had an assigned CAC score following coronary computed tomography (CT) scanning and baPWV were analyzed. RESULTS: Among the study subjects, 39.2% of the population had evidence of fatty liver by ultrasound and 4.6% of the population had evidence of CAC score > 0. Among individuals with a CAC score = 0, 38% of the individuals had fatty liver compared with 58% of the individuals with a CAC score > 0. The individuals with a CAC score > 0 also had higher blood pressure and had more metabolic abnormalities. The prevalence of CAC score > 0 was increased according to baPWV quartiles and was higher in the fatty liver group in comparison with those without fatty liver. The odds ratio for CAC score > 0, after adjusting for clinical risk factors, showed a significant elevation with increasing quartiles of baPWV and the presence of fatty liver. CONCLUSION: We showed that both fatty liver and baPWV are independently associated with the presence of CAC, a marker of preclinical atherosclerosis. These associations are independent of conventional risk factors and medical history.

Prospective Associations between Cumulative Average Intake of Flavonoids and Hypertension Risk in the CArdioVascular Disease Association Study (CAVAS).

In this study, we aimed to investigate the prospective associations and their shapes between the dietary intake of total flavonoids and their seven subclasses and hypertension risk in a prospective cohort, the KoGES_CArdioVascular disease Association Study (CAVAS), and to consider obesity status as an additional factor. A total of 10,325 adults aged 40 years and older were enrolled at baseline, and 2159 patients were newly diagnosed with hypertension during a median follow-up of 4.95 years. Cumulative dietary intake was estimated using a repeated food frequency questionnaire. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were estimated using modified Poisson models with a robust error estimator. We observed nonlinear inverse associations between total and seven subclasses of flavonoids and hypertension risk, although there was no significant association between total flavonoids and flavones with hypertension risk in the highest quartile. For men, these inverse associations tended to be pronounced in the high BMI group, particularly for anthocyanins and proanthocyanidins [IRR (95% CI) in overweight/obese men: 0.53 (0.42-0.67) for anthocyanins; 0.55 (0.42-0.71) for proanthocyanidins]. Our results suggested that consumption of dietary flavonoids may not be dose-responsive but is inversely associated with hypertension risk, particularly among overweight/obese men.

Asthma and increased risk of myocardial infarction and mortality among hypertensive Korean patients.

This study aimed to evaluate the effects of asthma on cardiovascular disease incidence in patients with hypertension. A total of 639,784 patients with hypertension from the Korea National Health Insurance Service database were included, of whom 62,517 had history of asthma after propensity score matching. The risks of all-cause mortality, myocardial infarction (MI), stroke, and end-stage renal disease (ESRD) were assessed according to the presence of asthma, long-acting ß2-agonist (LABA) inhaler usage, and/or systemic corticosteroid usage for up to 11 years. In addition, whether these risks were modified by average blood pressure (BP) levels during the follow-up period was examined. Asthma was associated with an increased risk of all-cause mortality (hazard ratio [HR], 1.203; 95% confidence interval [CI], 1.165-1.241) and MI (HR, 1.244; 95% CI, 1.182-1.310) but not the risk of stroke or ESRD. LABA inhaler usage was associated with a higher risk of all-cause mortality and MI, and systemic corticosteroids usage showed a higher risk of ESRD as well as all-cause mortality and MI among hypertensive patients with asthma. Compared to patients without asthma, there was a graded increase in the risk of all-cause mortality and MI in those with asthma without LABA inhaler/systemic corticosteroid usage and in those with asthma with LABA inhaler/systemic corticosteroid usage. These associations were not significantly modified by BP levels. This nationwide population-based study supports that asthma may be a clinical factor that increases the risk of poor outcomes in patients with hypertension.

Korean guidelines for the management of gout.

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.

Korean guidelines for the management of gout.

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.

The major determinants of arterial stiffness in Korean patients with rheumatoid arthritis are age and systolic blood pressure, not disease-related factors.

Patients with rheumatoid arthritis are at increased risk of cardiovascular morbidity and mortality. This study was undertaken to investigate the prevalence of peripheral arterial disease, and to identify factors, especially those related to rheumatoid arthritis, influencing arterial stiffness in Korean patients with rheumatoid arthritis. A total of 262 patients with rheumatoid arthritis managed in a tertiary clinic were included. Ankle-brachial index and brachial-ankle pulse wave velocity were measured. Rheumatoid arthritis-related factors were determined, as well as the traditional cardiovascular risk factors. The prevalence of peripheral arterial disease was only 1.5%. Mean pulse wave velocity was 1,559 ± 354 cm/s. Age, body mass index, blood pressure, lipid profile, and glucose, not rheumatoid arthritis-related factors such as disease duration, seropositivity and disease activity, were significantly correlated with pulse wave velocity. Moreover, stepwise multiple regression analysis revealed that only age over 65 (OR = 9.1, 95% CI 4.3-19.1, P < 0.001), systolic blood pressure over 140 mmHg (OR = 15.7, 95% CI 7.4-33.1, P < 0.001), and corticosteroid use (OR = 2.1, 95% CI 1.03-4.3, P = 0.04) were independent risk factors for high pulse wave velocity. The prevalence of peripheral arterial disease in Korean patients with rheumatoid arthritis is very low. Among the many factors related to arterial stiffness, only old age, high systolic blood pressure, and, to a certain extent, corticosteroid use appear to be major determinants, especially in clinical setting with relatively well controlled patients with rheumatoid arthritis.

Role of ambulatory blood pressure monitoring in elderly hypertensive patients.

BACKGROUND: Arterial hypertension is facing some changes in the last years. Its prevalence is increasing in elderly subjects. This growing prevalence is due to longer survival of the population worldwide, among other factors. On the other hand, recent guidelines have insisted in the relevance of out of office blood pressure measurements, to improve diagnostic and management of hypertension. Therefore, elderly subjects with hypertension could benefit from out of office blood pressure measurements, like ambulatory blood pressure measurements; nevertheless, there are very few or no specific recommendations regarding this. AIM: In this review, we will gather the most important information about this subject. RESULTS: As hypertension in the elderly has some specific characteristics related to aging of the cardiovascular system, the most important aspect could be that these characteristics make ambulatory blood pressure measurement suitable for its use in elderly. Among those a higher prevalence of white coat hypertension, white coat phenomenon, and a higher nocturnal blood pressure and higher prevalence of nondipper and riser pattern, represent aspects that should be considered for better diagnostic and an improved management. CONCLUSION: As the prevalence of hypertension will grow in the next years, more studies specifically directed to this subject are needed.

Evaluating Prediction Models of Sleep Apnea From Smartphone-Recorded Sleep Breathing Sounds.

Importance: Breathing sounds during sleep are an important characteristic feature of obstructive sleep apnea (OSA) and have been regarded as a potential biomarker. Breathing sounds during sleep can be easily recorded using a microphone, which is found in most smartphone devices. Therefore, it may be easy to implement an evaluation tool for prescreening purposes. Objective: To evaluate OSA prediction models using smartphone-recorded sounds and identify optimal settings with regard to noise processing and sound feature selection. Design, Setting, and Participants: A cross-sectional study was performed among patients who visited the sleep center of Seoul National University Bundang Hospital for snoring or sleep apnea from August 2015 to August 2019. Audio recordings during sleep were performed using a smartphone during routine, full-night, in-laboratory polysomnography. Using a random forest algorithm, binary classifications were separately conducted for 3 different threshold criteria according to an apnea hypopnea index (AHI) threshold of 5, 15, or 30 events/h. Four regression models were created according to noise reduction and feature selection from the input sound to predict actual AHI: (1) noise reduction without feature selection, (2) noise reduction with feature selection, (3) neither noise reduction nor feature selection, and (4) feature selection without noise reduction. Clinical and polysomnographic parameters that may have been associated with errors were assessed. Data were analyzed from September 2019 to September 2020. Main Outcomes and Measures: Accuracy of OSA prediction models. Results: A total of 423 patients (mean [SD] age, 48.1 [12.8] years; 356 [84.1%] male) were analyzed. Data were split into training (n = 256 [60.5%]) and test data sets (n = 167 [39.5%]). Accuracies were 88.2%, 82.3%, and 81.7%, and the areas under curve were 0.90, 0.89, and 0.90 for an AHI threshold of 5, 15, and 30 events/h, respectively. In the regression analysis, using recorded sounds that had not been denoised and had only selected attributes resulted in the highest correlation coefficient (r = 0.78; 95% CI, 0.69-0.88). The AHI (ß = 0.33; 95% CI, 0.24-0.42) and sleep efficiency (ß = -0.20; 95% CI, -0.35 to -0.05) were found to be associated with estimation error. Conclusions and Relevance: In this cross-sectional study, recorded sleep breathing sounds using a smartphone were used to create reasonably accurate OSA prediction models. Future research should focus on real-life recordings using various smartphone devices.

[Colonic Mass Secondary to Sevelamer-associated Rectal Ulcer].

The phosphorous balance is clinically important in increasing the long-term outcomes and preventing complications of end-stage renal disease. Sevelamer is a phosphate binder used widely to regulate hyperphosphatemia. On the other hand, gastrointestinal side effects increase with increasing sevelamer intake. A 29-year-old male with end-stage renal disease of IgA nephropathy on maintenance hemodialysis was admitted for diffuse alveolar bleeding and pneumonia. He presented with a low-grade fever and watery diarrhea tinged with blood. Initially, a Clostridioides difficile-associated diarrhea treatment was started with positive findings of Clostridioides difficile toxin and culture. Despite this, there was no improvement in the symptoms even with the appropriate antibiotic treatment. Computed tomography of the abdomen and pelvis revealed an occlusive mass in the rectum and secondary obstructive changes in the sigmoid colon. The initial suspicion was a malignancy or fungal infection. Sigmoidoscopy with a biopsy identified the mass as a lump of mucous material with the entire lumen covered with exudate. The subsequent histopathology examination revealed a colonic mucosal injury and characteristic "fish scale"-like sevelamer crystals in the exudate. The diagnosis of a sevelamer-induced rectal ulcer was made. We report this case of a sevelamer-associated rectal ulcer of the sigmoid.

Protective effect of controlled blood pressure on risk of dementia in low-risk, grade 1 hypertension.

OBJECTIVE: High blood pressure (BP) increases the risk of dementia; however, few studies have reported on the risk of dementia in patients with low-risk, early-grade hypertension. We investigated the protective effect of controlled BP on risk of dementia in treated, low-risk, grade 1 hypertensive patients from the entire National Health Insurance Service National Health Examinee cohort. METHODS: We selected grade 1 hypertension (140-159/90-99 mmHg) patients with low risk, diagnosed in 2005-2006. All patients (N = 128 665) were classified into controlled (average BP < 140/90 mmHg during the follow-up) and uncontrolled (average BP ≥ 140/90 mmHg) BP groups and followed up until 2015. The risk of dementia was estimated using Cox proportional hazard model after adjustments for propensity score. RESULTS: Average BP was 131/81 mmHg in the controlled group (N = 49 408) and 144/87 mmHg in the uncontrolled group (N = 99 257). Overall dementia incidence rates in controlled and uncontrolled groups were 4.9 and 8.1 per 1000 person-year, respectively. The controlled group showed lower risk of overall dementia, Alzheimer's disease, and vascular dementia than the uncontrolled group. The controlled group had a low risk of vascular dementia at all ages, especially in the younger group (age <60). The optimal BP level associated with the lowest risk of dementia was 130 to less than 140 mmHg for SBP and 70 to less than 80 mmHg for DBP. CONCLUSION: We concluded that among even low-risk and grade 1 hypertension patients, controlled BP significantly reduced the risk of dementia, including Alzheimer's disease and vascular dementia.

A randomized, double-blind clinical trial to evaluate the efficacy and safety of a fixed-dose combination of amlodipine/rosuvastatin in patients with dyslipidemia and hypertension.

This multicenter, randomized, double-blind, parallel-group phase III clinical trial aimed to investigate the efficacy and safety of a rosuvastatin + amlodipine combination compared with that of rosuvastatin or amlodipine monotherapy in hypertensive patients with dyslipidemia. A total of 106 patients of 15 institutions in Korea were randomly assigned to 1 of 3 treatment groups: rosuvastatin 20 mg + amlodipine 10 mg, amlodipine 10 mg, or rosuvastatin 20 mg. After 8 weeks of treatment, the mean ± SD of change in mean sitting systolic blood pressure (msSBP) was -22.82 ± 12.99 mm Hg in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. The percentage of patients whose msSBP decreased ≥20 mm Hg or msDBP decreased ≥10 mm Hg was also highest in this group (74.29%). The mean ± SD percentage change in low-density lipoprotein cholesterol (LDL-C) level from baseline after 8 weeks was -52.53% ± 11.21% in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. More patients in the rosuvastatin + amlodipine group achieved their target LDL-C goal at 8 weeks, compared with the other treatment groups (97.14%). No serious adverse events or adverse drug reactions were observed in all groups. In hypertensive patients with dyslipidemia, combination treatment with rosuvastatin 20 mg + amlodipine 10 mg effectively reduced blood pressure and LDL-C levels while maintaining safety.

Efficacy and safety of co-administered telmisartan/amlodipine and rosuvastatin in subjects with hypertension and dyslipidemia.

Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low-density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow-up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least-Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were -19.3 (2.68) mm Hg and -6.69 (2.76) mm Hg. The difference between the two groups was significant (-12.60 (2.77) mm Hg, 95% CI -18.06 to -7.14, P < .0001). The LS Mean for the percent changes from baseline in LDL cholesterol in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg) groups were -52.45 (3.23) % and 2.68 (3.15) %. The difference between the two groups was significant (-55.13 (3.20) %, 95% CI -61.45 to -48.81, P < .0001). There were no adverse events leading to discontinuation or death. Combined administration of telmisartan/amlodipine 80/5 mg and rosuvastatin 20 mg for the treatment of hypertensive patients with dyslipidemia significantly reduces blood pressure and improves lipid control. ClinicalTrials.gov identifier: NCT03067688.

Efficacy and Safety of a Fixed-Dose Combination of Candesartan and Rosuvastatin on Blood Pressure and Cholesterol in Patients With Hypertension and Hypercholesterolemia: A Multicenter, Randomized, Double-Blind, Parallel Phase III Clinical Study.

PURPOSE: The aim of this study was to evaluate the blood pressure-lowering and cholesterol-lowering effects of a fixed-dose combination therapy using candesartan (CND)/rosuvastatin (RSV) compared with CND or RSV monotherapy in patients with hypertension and hypercholesterolemia. METHODS: This study was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 394 patients were screened. After a 4-week run-in period, 219 of these patients with hypertension and primary hypercholesterolemia were randomized. Patients received 1 of 3 regimens for 8 weeks: (1) CND 32 mg/RSV 20 mg, (2) RSV 20 mg, or (3) CND 32 mg. The primary outcome variables were changes in the systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the percentage changes in LDL-C from baseline to the drug treatment at 8 weeks. The secondary outcome variables were percentage changes of total cholesterol, triglycerides, HDL-C, non-HDL-C, apolipoprotein B, apolipoprotein A-I, high-sensitivity C-reactive protein, and glucose metabolic indices, including percentage changes of the homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and hemoglobin A1c. Tolerability of combination therapy was compared with other monotherapy groups. FINDINGS: The percentage changes of LDL-C were -48.6% (from 157.2 to 80.1 mg/dL) in the RSV group and -49.8% (from 160.2 to 78.9 mg/dL) in the CND/RSV group from baseline to the end of 8 weeks of treatment. Mean SBP and DBP were significantly decreased in the CND/RSV and CND groups after 8 weeks (P < 0.001 for all); however, no significant differences were found between the 2 groups. Total cholesterol levels, triglycerides, non-HDL-C, and apolipoprotein B were significantly reduced in the CND/RSV and RSV groups, with no significant differences between the groups compared with the CND group (P < 0.001 for all). The percentage changes of HOMA-IR, adiponectin, and hemoglobin A1c had no significant differences between the combination groups and monotherapy groups. However, in a 2-sample t test, HOMA-IR was significantly decreased in the CND/RSV group compared with the RSV group in nondiabetic patients (mean [SD] percentage change of HOMA-IR, -8.7% [37.6%] vs 17.1% [53.1%]; P = 0.048). There were no significant differences in metabolic indices between the diabetic groups. Adverse events in the CND/RSV group were similar to those in the monotherapy group. IMPLICATIONS: Once-daily fixed-dose combination therapy with CND/RSV is an effective, tolerable, convenient treatment option for patients with essential hypertension and hypercholesteremia. ClinicalTrials.gov identifier: NCT02770261.

C-reactive Protein Overexpression in the Background Liver of Hepatitis B Virus-Associated Hepatocellular Carcinoma Is a Prognostic Biomarker.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Peripheral blood C-reactive protein (CRP) concentration and CRP overexpression in HCC cells are proven to be prognostic markers for HCC, but the significance of CRP expression in non-neoplastic hepatocytes, which are the primary origin of CRP, has not been studied. This study was conducted to determine the clinicopathologic significance of CRP immunoreactivity in the background liver of HBV-associated HCC. METHODS: CRP immunostaining was done on tissue microarrays of non-neoplastic liver tissues obtained from surgically resected, treatment-naïve HBV-associated HCCs (n = 156). The relationship between CRP immunoreactivity and other clinicopathologic parameters including cancer-specific survival was analyzed. CRP immunoreactivity was determined using a 4-tier grading system: grades 0, 1, 2, and 3. RESULTS: CRP was positive in 139 of 156 cases (89.1%) of non-neoplastic liver in patients with HCCs: grade 1 in 83 cases (53.2%); grade 2 in 50 cases (32.1%); and grade 3 in six cases (3.8%). The patients with diffuse CRP immunoreactivity (grade 3) had decreased cancer-specific survival (p = .031) and a tendency for shorter interval before early recurrence (p = .050). The degree of CRP immunoreactivity correlated with serum CRP concentration (p < .001). CONCLUSIONS: CRP immunoreactivity in non-neoplastic liver is a novel biomarker for poor cancer-specific survival of HBV-associated HCC and correlates with serum CRP concentration.

Stress distribution in premolars restored with inlays or onlays: 3D finite element analysis.

PURPOSE: To analyze stress distribution in premolars restored with inlays or onlays using various materials. MATERIALS AND METHODS: Three-dimensional maxillary premolar models of abutments were designed to include the following: 1) inlay with O cavity (O group), 2) inlay with MO cavity (MO group), 3) inlay with MOD cavity (MOD group), and 4) onlay (ONLAY group). A restoration of each inlay or onlay cavity was simulated using gold alloy, e.max ceramic, or composite resin for restoration. To simulate masticatory forces, a total of 140 N static axial force was applied onto the tooth at the occlusal contact areas. A finite element analysis was performed to predict the magnitude and pattern of stresses generated by occlusal loading. RESULTS: Maximum von Mises stress values generated in the abutment teeth of the ONLAY group were ranged from 26.1 to 26.8 MPa, which were significantly lower than those of inlay groups (O group: 260.3-260.7 MPa; MO group: 252.1-262.4 MPa; MOD group: 281.4-298.8 MPa). Maximum von Mises stresses generated with ceramic, gold, and composite restorations were 280.1, 269.9, and 286.6 MPa, respectively, in the MOD group. They were 252.2, 248.0, 255.1 MPa, respectively, in the ONLAY group. CONCLUSION: The onlay design (ONLAY group) protected tooth structures more effectively than inlay designs (O, MO, and MOD groups). However, stress magnitudes in restorations with various dental materials exhibited no significant difference among groups (O, MO, MOD, ONLAY).

Clinical Benefit of Treatment of Stage-1, Low-Risk Hypertension.

Evidence about the benefits of treating uncomplicated, low-risk, stage-1 hypertension is lacking. The study aimed to investigate the association between mean blood pressure (BP) and clinical outcomes, and to determine optimal BPs in treated, low-risk, stage-1 hypertension. From the National Health Insurance Service Health Examination Database, patients with stage-1 hypertension between 2005 and 2006 were selected. They had a systolic BP of 140 to 159 mm Hg or diastolic BP of 90 to 99 mm Hg. Patients were grouped as controlled (mean BP <140/90 mm Hg; n=99 301) and uncontrolled (mean BP ≥140/90 mm Hg; n=49 460) according to their mean BP recorded during the follow-up health examination. All-cause mortality and cardiovascular outcomes were examined. Mean BPs in the controlled and uncontrolled groups were 131.1/80.9 and 144.6/86.8 mm Hg, respectively. Controlled BP was associated with significantly lower risks of all-cause mortality, all stroke, hemorrhagic stroke, ischemic stroke, and end-stage renal disease. Subgroup analysis demonstrated benefits of controlled BP in hypertensive patients aged <50 years for all-cause mortality, all stroke, hemorrhagic stroke, ischemic stroke, and end-stage renal disease, with no significant interaction according to age. The BP associated with the lowest risk of all-cause mortality was 120 to <130 mm Hg (systolic BP) and 70 to <80 mm Hg (diastolic BP). There was an increased risk of myocardial infarction in patients with mean systolic BP <120 mm Hg and diastolic BP <80 mm Hg. BP <140/90 mm Hg was associated with a significant reduction in the risk of mortality, stroke, and end-stage renal disease, with the lowest mortality risk at BP ranges of 120 to <130 and 70 to <80 mm Hg.