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Purpose@#Vibegron, a novel, potent β3 agonist, has been approved for clinical use in overactive bladder (OAB) treatment in Japan and the Unites States. We performed a bridging study to investigate the efficacy and safety of a daily 50-mg vibegron (code name JLP-2002) dose in Korean patients with OAB. @*Methods@#A multicenter, randomized, double-blind, placebo-controlled study was conducted from September 2020 to August 2021. Adult patients with OAB with a symptom duration of more than 6 months entered a 2-week placebo run-in phase. Eligibility was assessed at the end of this phase and selected patients entered a double-blind treatment phase after 1:1 randomization to either the placebo or vibegron (50 mg) group. The study drug was administered once daily for 12 weeks and follow-up visits were scheduled at weeks 4, 8, and 12. The primary endpoint was the change in mean daily micturition at the end of treatment. The secondary endpoints included changes in OAB symptoms (daily micturition, nocturia, urgency, urgency incontinence, and incontinence episodes, and mean voided volume per micturition) and safety. A constrained longitudinal data model was used for statistical analysis. @*Results@#Patients who took daily vibegron had significant improvements over the placebo group in both primary and secondary endpoints, except for daily nocturia episodes. The proportions of patients with normalized micturition and resolution of urgency incontinence and incontinence episodes were significantly higher in vibegron group than in the placebo. Vibegron also improved the patients’ quality of life with higher satisfaction rates. The incidence of adverse events in the vibegron and placebo groups was similar with no serious, unexpected adverse drug reactions. No abnormality in electrocardiographs was observed as well as no significant increase in postvoid residual volume. @*Conclusions@#Once daily vibegron (50 mg) for 12 weeks was effective, safe, and well-tolerated in Korean patients with OAB.
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Purpose@#To determine the limitations of current screening methods for lipid disorders and to suggest a new method that is effective for use in Korean adolescents. @*Methods@#Data from the 6th Korea National Health and Nutrition Examination Survey (2013–2015) were analyzed. The diagnostic validity (sensitivity and specificity) of various cardiovascular risk factors currently used for lipid disorder screening was investigated, as was the diagnostic validity of non-HDL-cholesterol ≥145 mg/dL as a screening tool. @*Results@#The prevalence of dyslipidemia and familial hypercholesterolemia (FH) among Korean adolescents was 20.4%±1.0% and 0.8%±0.3%, respectively. The current standard screening methods identified only 5.9%±1.4% and 30.3%±17.2% of the total number of dyslipidemia and FH cases, respectively. The diagnostic sensitivity and specificity of lipid profile analysis for dyslipidemia among obese adolescents were 19.5%±2.3% and 93.6%±0.8% and for FH were 30.3%±17.2% and 91.1%±0.8%, respectively. When adolescents with obesity, hypertension, or a family history of dyslipidemia or cardiocerebrovascular disease for over 3 generations were included in the screening, diagnostic sensitivity increased to 68.4%±2.8% for dyslipidemia and 83.5%±2.7% for FH. Universal screening of all adolescents based on non-HDL-cholesterol levels had sensitivities of 30.2%±2.7% and 100%, and specificities of 99.2%±0.3% and 94%±0.6% for dyslipidemia and FH, respectively. @*Conclusion@#New screening methods should be considered for early diagnosis and treatment of lipid disorders in Korean adolescents.
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Nonautoimmune hyperthyroidism is a very rare cause of congenital hyperthyroidism that is usually caused by an activating mutation in the thyroid-stimulating hormone receptor (TSHR) gene. In this report, we describe a case of nonautoimmune hyperthyroidism in a patient with TSHR mutation. Our patient was the younger of a set of twins born at 36 weeks and 6 days of gestation. The patient was noted to be more irritable than the older twin at 80 days of age, and the mother was taking methimazole for Graves’ disease that had been diagnosed 12 years prior. Therefore, a thyroid function test was conducted for the patient. The results revealed subclinical hyperthyroidism, and tests of antithyroglobulin antibody, antithyroid peroxidase antibody, and anti-thyroid-stimulating hormone (TSH) receptor antibody were all negative. During follow-up, at around 4 months of age, free T4 increased to 2.89 ng/dL, and TSH was still low at 0.01 μIU/mL; therefore, 3 mg/day of methimazole was initiated. Whole-exome sequencing showed a heterozygous variant of c.1800C>T (p.Ala627Val) in the TSHR gene. Testing in the family confirmed an identical variant in the patient's mother, leading to diagnosis of familial nonautoimmune hyperthyroidism inherited in an autosomal dominant pattern. This is the second report of A627V confirmed as a germline variant.
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Objectives@#We accessed the various clinico-histopathological factors, and their association with occult metastasis (OM) in oral tongue squamous cell carcinoma (OTSCC). @*Materials and Methods@#One hundred-nine patients with OTSCC were divided into the elective neck dissection (END) group and the watchful waiting (WW) group. Age, sex, T-stage, depth of invasion and differentiation were evaluated to determine the correlation between clinico-histopathological factors and OM. For immunohistochemical analysis, paraffin-embedded blocks of 41 OTSCC specimens were examined with antibodies (VEGF-c, c-Met, and ROR1). @*Results@#The group with tumor thickness of oral tongue cancer ≥3 mm had higher incidence of OM than those with a thickness of <3 mm. The depth of invasion was statistically correlated with OM (P=0.022). Immunohistochemical analysis showed that high expression of VEGF-c (P=0.043), c-Met (P=0.009), and ROR-1 (P=0.003) were statistically correlated with OM. @*Conclusion@#The analysis of these clinico-histopathological and immunohistochemical factors can help to determine neck dissection in clinically negative (cN0) patients.
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Familial hypophosphatemic rickets (FHR) is a disorder characterized by phosphate wasting and hypophosphatemia due to defects in renal phosphate transport regulation. There are 4 known inherited forms of FHR that differ in their molecular causes. Very few studies have been conducted that focused on the molecular analysis of FHR in Koreans. Eighteen mutations of the PHEX gene have been identified to this date in Korea. Herein, we report the clinical case of a 24-month-old boy presenting with bowed legs and short stature. The biochemical profile showed hypophosphatemia with decreased tubular reabsorption of phosphate. Several family members were identified with short stature and genu varum. Therefore, he was diagnosed with FHR. To identify the molecular causes of FHR, we performed targeted gene panel sequencing and found a novel hemizygous missense variant, c.1949T>C (p.Leu650Pro), in the PHEX gene. This variant was also detected in the boy’s mother who exhibited genu varum and short stature.
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Purpose@#To determine the limitations of current screening methods for lipid disorders and to suggest a new method that is effective for use in Korean adolescents. @*Methods@#Data from the 6th Korea National Health and Nutrition Examination Survey (2013–2015) were analyzed. The diagnostic validity (sensitivity and specificity) of various cardiovascular risk factors currently used for lipid disorder screening was investigated, as was the diagnostic validity of non-HDL-cholesterol ≥145 mg/dL as a screening tool. @*Results@#The prevalence of dyslipidemia and familial hypercholesterolemia (FH) among Korean adolescents was 20.4%±1.0% and 0.8%±0.3%, respectively. The current standard screening methods identified only 5.9%±1.4% and 30.3%±17.2% of the total number of dyslipidemia and FH cases, respectively. The diagnostic sensitivity and specificity of lipid profile analysis for dyslipidemia among obese adolescents were 19.5%±2.3% and 93.6%±0.8% and for FH were 30.3%±17.2% and 91.1%±0.8%, respectively. When adolescents with obesity, hypertension, or a family history of dyslipidemia or cardiocerebrovascular disease for over 3 generations were included in the screening, diagnostic sensitivity increased to 68.4%±2.8% for dyslipidemia and 83.5%±2.7% for FH. Universal screening of all adolescents based on non-HDL-cholesterol levels had sensitivities of 30.2%±2.7% and 100%, and specificities of 99.2%±0.3% and 94%±0.6% for dyslipidemia and FH, respectively. @*Conclusion@#New screening methods should be considered for early diagnosis and treatment of lipid disorders in Korean adolescents.
ABSTRACT
Nonautoimmune hyperthyroidism is a very rare cause of congenital hyperthyroidism that is usually caused by an activating mutation in the thyroid-stimulating hormone receptor (TSHR) gene. In this report, we describe a case of nonautoimmune hyperthyroidism in a patient with TSHR mutation. Our patient was the younger of a set of twins born at 36 weeks and 6 days of gestation. The patient was noted to be more irritable than the older twin at 80 days of age, and the mother was taking methimazole for Graves’ disease that had been diagnosed 12 years prior. Therefore, a thyroid function test was conducted for the patient. The results revealed subclinical hyperthyroidism, and tests of antithyroglobulin antibody, antithyroid peroxidase antibody, and anti-thyroid-stimulating hormone (TSH) receptor antibody were all negative. During follow-up, at around 4 months of age, free T4 increased to 2.89 ng/dL, and TSH was still low at 0.01 μIU/mL; therefore, 3 mg/day of methimazole was initiated. Whole-exome sequencing showed a heterozygous variant of c.1800C>T (p.Ala627Val) in the TSHR gene. Testing in the family confirmed an identical variant in the patient's mother, leading to diagnosis of familial nonautoimmune hyperthyroidism inherited in an autosomal dominant pattern. This is the second report of A627V confirmed as a germline variant.
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PURPOSE: To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. METHODS: To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. RESULTS: Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. CONCLUSIONS: This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.
Subject(s)
Adult , Animals , Female , Humans , Rats , Apoptosis , Bone Marrow , Cystitis , Fibrosis , Gene Expression , Human Embryonic Stem Cells , Ketamine , Mast Cells , Mesenchymal Stem Cells , Multipotent Stem Cells , Pelvic Pain , Urinary BladderABSTRACT
BACKGROUND: To report the long-term outcomes of endoscopic surgery (ES) in pediatric patients with vesicoureteral reflux in terms of success rate, urinary tract infection, and renal function. METHODS: We retrospectively reviewed the records of 73 pediatric patients (110 ureters) who underwent ES for vesicoureteral reflux. Ultrasonography was performed 1, 3, and 12 months postoperatively. Voiding cystourethrography was performed 3 months postoperatively and repeated after 1 year if vesicoureteral reflux persisted. Success was defined as the absence of reflux at the first voiding cystourethrography. Renal scans were performed at least 12 months postoperatively. Renal function deterioration was defined as a new scar or a greater than 5% decrease in function. RESULTS: The median follow-up duration was 24 (12–118) months. The overall success was 65.6%, while it was 78.9%, 87.0%, 62.5%, 37.5%, 66.7% for grades I, II, III, IV, and V, respectively. In multivariate analyses, significant predictive factors for success were vesicoureteral reflux grade (odds ratio [OR], 0.28; P < 0.001) and mound detection at the first postoperative ultrasonography (OR, 13.53; P < 0.001). Renal function deterioration was found in 8 (15.3%) ureters and was less common in those with successful surgeries than in those with failures (9.5% vs. 40.0%; P = 0.035). No significant predictive factor for renal function deterioration or urinary tract infection was found. CONCLUSION: Successful short-term outcomes of ES are expected in low-grade vesicoureteral reflux, especially when a mound is detected by postoperative ultrasonography. However, unpredictable long-term renal deterioration warrants continued follow-up.
Subject(s)
Humans , Cicatrix , Follow-Up Studies , Multivariate Analysis , Retrospective Studies , Ultrasonography , Ureter , Urinary Tract Infections , Urinary Tract , Vesico-Ureteral RefluxABSTRACT
BACKGROUND: Iron deficiency anemia (IDA) is a disease prevalent throughout the world. However, there is limited information regarding whether familial factors are associated with the risk of adolescent IDA. METHODS: This study evaluated the association between adolescent IDA and family history of IDA using data from the fifth Korea National Health Nutrition Survey (2010–2012). Data from 10-18-year-old children who underwent laboratory testing were analyzed. RESULTS: The overall prevalence of IDA was 3.1% (95% confidence interval [CI]: 2.4−4.1%), with prevalence of 0.5% among boys (95% CI: 0.2−1.3%) and 6.2% among girls (95% CI: 4.6−8.3%). The prevalence of IDA was associated with female sex (odds ratio [OR]: 13.43, 95% CI: 4.92−36.65; P < 0.001) and a family history of IDA (OR: 3.12, 95% CI: 1.11−8.76; P=0.03). Other risk factors for IDA were receiving social welfare support (OR: 3.31, 95% CI: 1.45−7.56; P=0.031), low maternal education (OR: 3.12, 95% CI: 1.39−6.99; P=0.006), receiving charitable food support (OR: 2.27: 95% CI: 0.9−5.44; P=0.04), poor body-image (OR: 2.14, 95% CI: 1.16−3.93; P=0.026), and weight-loss efforts (OR: 2.42, 95% CI: 1.27−4.61; P=0.01). Nutritional supplementation protected against IDA (OR: 0.40, 95% CI: 0.19−0.82; P=0.007), although adolescents with awareness of nutritional labels had a high IDA prevalence (OR: 8.06, 95% CI: 1.71−38.05; P < 0.001). CONCLUSION: A family history of IDA was an independent risk factor for IDA. Further studies are needed to determine whether family-level educational interventions can reduce the risk of adolescent IDA.
Subject(s)
Adolescent , Child , Female , Humans , Anemia , Anemia, Iron-Deficiency , Education , Iron , Korea , Nutrition Surveys , Prevalence , Risk Factors , Social WelfareABSTRACT
BACKGROUND: Cigarette smoking is a risk factor for cardiovascular disease (CVD) and has both beneficial and harmful effects in CVD. We hypothesized that weight gain following smoking cessation does not attenuate the CVD mortality of smoking cessation in the general Korean population. METHODS: Study subjects comprised 2.2% randomly selected patients from the Korean National Health Insurance Corporation, between 2002 and 2013. We identified 61,055 subjects who were classified as current smokers in 2003–2004. After excluding 21,956 subjects for missing data, we studied 30,004 subjects. We divided the 9,095 ex-smokers into two groups: those who gained over 2 kg (2,714), and those who did not gain over 2 kg (6,381, including weight loss), after smoking cessation. Cox proportional hazards regression models were used to estimate the association between weight gain following smoking cessation and CVD mortality. RESULTS: In the primary analysis, the hazard ratios of all-cause deaths and CVD deaths were assessed in the three groups. The CVD risk factors and Charlson comorbidity index adjusted hazard ratios (aHRs) for CVD deaths were 0.80 (95% confidence interval [CI], 0.37 to 1.75) for ex-smokers with weight gain and 0.80 (95% CI, 0.50 to 1.27) for ex-smokers with no weight gain, compared to one for sustained smokers. The associations were stronger for events other than mortality. The aHRs for CVD events were 0.69 (95% CI, 0.54 to 0.88) and 0.81 (95% CI, 0.70 to 0.94) for the ex-smokers with and without weight gain, respectively. CONCLUSION: Although smoking cessation leads to weight gain, it does not increase the risk of CVD death.
Subject(s)
Humans , Cardiovascular Diseases , Comorbidity , Mortality , National Health Programs , Risk Factors , Smoke , Smoking Cessation , Smoking , Weight GainABSTRACT
BACKGROUND: Cardiovascular disease (CVD) has become the most common cause of mortality and morbidity worldwide. Health screening is associated with higher outpatient visits for detection and treatment of CVD-related diseases (diabetes mellitus, hypertension, and dyslipidemia). We examined the association between health screening, health utilization, and economic status. METHODS: A sampled cohort database from the National Health Insurance Corporation was used. We included 306,206 participants, aged over 40 years, without CVD (myocardial infarction, stroke, and cerebral hemorrhage), CVD-related disease, cancer, and chronic renal disease. The follow-up period was from January 1, 2003 through December 31, 2005. RESULTS: Totally, 104,584 participants received at least one health screening in 2003–2004. The odds ratio of the health screening attendance rate for the five economic status categories was 1.27 (95% confidence interval [CI], 1.24 to 1.31), 1.05 (95% CI, 1.02 to 1.08), 1, 1.16 (95% CI, 1.13 to 1.19) and 1.50 (95% CI, 1.46 to 1.53), respectively. For economic status 1, 3, and 5, respectively, the diagnostic rate after health screening was as follows: diabetes mellitus: 5.94%, 5.36%, and 3.77%; hypertension: 32.75%, 30.16%, and 25.23%; and dyslipidemia: 13.43%, 12.69%, and 12.20%. The outpatient visit rate for attendees diagnosed with CVD-related disease was as follows for economic status 1, 3, and 5, respectively: diabetes mellitus: 37.69%, 37.30%, and 43.70%; hypertension: 34.44%, 30.09%, and 32.31%; and dyslipidemia: 18.83%, 20.35%, and 23.48%. CONCLUSION: Thus, higher or lower economic status groups had a higher health screening attendance rate than the middle economic status group. The lower economic status group showed lower outpatient visits after screening, although it had a higher rate of CVD diagnosis.
Subject(s)
Humans , Cardiovascular Diseases , Cohort Studies , Diabetes Mellitus , Diagnosis , Dyslipidemias , Follow-Up Studies , Hypertension , Infarction , Mass Screening , Mortality , National Health Programs , Odds Ratio , Outpatients , Renal Insufficiency, Chronic , StrokeABSTRACT
BACKGROUND: The relationship between economics and health has been of great interest throughout the years. The accumulated data is not sufficient enough to carry out long-term studies from the viewpoint of morbidity, although Korea National Health and Nutrition Examination Survey (KNHANES) was carried out yearly since 1998 in Korea. Thus, we investigated the effect of the 2008 global economic crisis on health indicators of Korea. METHODS: Health indicators were selected by paired t-test based on 2007 and 2009 KNHANES data. Age, gender, body mass index (BMI), smoking, drinking, exercise, education, income, working status, and stress were used as confounding factors, which were analyzed with logistic and probit analyses. Validation was done by comparing gross domestic product (GDP) growth rates and probit analyses results of 2007-2012 KNHANES data. RESULTS: Among several health indicators, the prevalence of hypertension and stress perception was higher after the economic crisis. Factors related with higher hypertension prevalence include older age, male gender, higher BMI, no current tobacco use, recent drinking, lower education levels, and stress perception. Factors related with more stress perception were younger age, female gender, current smoking, lower education levels, and lower income. GDP growth rates, a macroeconomic indicator, are inversely associated with hypertension prevalence with a one-year lag, and also inversely associated with stress perception without time lag. CONCLUSION: The economic crisis increased the prevalence of hypertension and stress perception. In the case of GDP growth rate change, hypertension was an inversely lagging indicator and stress perception was an inversely-related coincident indicator.
Subject(s)
Female , Humans , Male , Body Mass Index , Drinking , Economic Recession , Education , Gross Domestic Product , Guanosine Diphosphate , Hypertension , Korea , Nutrition Surveys , Prevalence , Smoke , Smoking , Tobacco UseABSTRACT
Subject(s)
Female , Humans , Male , Body Mass Index , Breast , Cervix Uteri , Chemoprevention , Early Diagnosis , Esophagus , Follow-Up Studies , Larynx , Liver , Lung , Medical Records , Mouth , Mouth Neoplasms , Neoplasms, Second Primary , Polymethacrylic Acids , Prognosis , Risk Factors , Smoke , Smoking , Stomach , Survival RateABSTRACT
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Humans , Free Tissue Flaps , Mandible , Osteogenesis , Osteolysis , Osteolysis, EssentialABSTRACT
Subject(s)
Humans , Male , Adenoma , Amylases , Dermoid Cyst , Diagnosis, Differential , Floors and Floorcoverings , Hemangioma , Lipoma , Mouth , Ranula , Skull Base , Sublingual GlandABSTRACT
BACKGROUN: Our aim was to assess the rate of flare in patients with systemic lupus erythematosus (SLE) during pregnancy, to describe fetal outcomes in lupus in Asan Medical Center and to identify clinical or serological factors that would predict pregnancy loss and poor fetal outcome. METHODS: We retrospectively studied 49 pregnancies in 47 women with SLE. Clinical and laboratory data were identified from medical record. RESULTS: Lupus flare occurred in 30 (61.2%) of the pregnancies, mostly in the second trimester. Flares presented most commonly as involvement of skin or joints, constitutional symptoms. All of the patients with flare were treated with glucocorticosteroid. There was no predictive factor for flare of lupus during pregnancy. There were 37 (75.5%) live births and 12 (24.5%) fetal losses. Of live births, 10 (20.4%) were premature babies, 5 (10.2%) intrauterine growth retardation. Of fetal losses, 5 (10.2%) were spontaneous abortion, 5 (10.2%) therapeutic abortion, 2 (4.1%) still births. Using univariate analysis, predictive factors for adverse fetal outcome include antiphospholipid antibody, renal involvement, active lupus at conception and flare of lupus during pregnancy. Using multivariate analysis, antiphospholipid antibody was the only significant predictor for fetal loss, and lupus flare during pregnancy was the only significant predictor for poor fetal outcome. CONCLUSION: There was no predictive factor for the flare of lupus during pregnancy. Most lupus pregnancies did well, but there was a higher rate of adverse fetal outcome. Antiphospholipid antibody and flare of lupus during pregnancy were the only important predictors of fetal loss and premature birth, respectively.
Subject(s)
Female , Humans , Pregnancy , Abortion, Spontaneous , Abortion, Therapeutic , Antibodies, Antiphospholipid , Fertilization , Fetal Growth Retardation , Joints , Live Birth , Lupus Erythematosus, Systemic , Medical Records , Multivariate Analysis , Parturition , Pregnancy Outcome , Pregnancy Trimester, Second , Premature Birth , Retrospective Studies , SkinABSTRACT
D-penicillamine has been used to reduce skin thickening and prevent the development of significant organ involvement in the treatment of scleroderma. This drug has a number of serious adverse reactions including glomerulonephritis with nephrotic syndrome, aplastic anemia, thrombocytopenia, and myasthenia gravis. A 44-year-old woman was admitted for weakness of the extremity muscle during repeated use. Eight months before admission, she visited dermatology department of our hospital. She was diagnosed as having scleroderma. D-penicillamine was started for the treatment of skin lesions. Based on the fluctuation of proximal muscle weakness, high titer of acetylcholine receptor antibody and definite decremental response of Jolly test, she was diagnosed as myasthenia gravis. D-penicillamine was discontinued because of the suspicion of D-penicillamine induced myasthenia gravis. Muscle weakness improved after D-penicillamine was withdrawn. The development of reversible myasthenia gravis may be regarded as a part of general predisposition for autoimmune disease related to the D-penicillamine therapy.