The association between ambient air pollution exposure and connective tissue sarcoma risk: a nested case-control study using a nationwide population-based database.

A nationwide population-based database was utilized in a nested case-control study to explore the association between ambient air pollution exposure and the likelihood of developing connective tissue sarcoma. The study examined 280 cases of connective tissue sarcoma diagnosed between 2000 and 2012. A random sample of 1120 control subjects was selected from a subpopulation of claim records without a connective tissue sarcoma diagnosis in a 1:4 ratio. The control subjects were selected based on similar characteristics as the connective tissue sarcoma patients, including gender, birth year, and the year of diagnosis of the case group with medical records. Risk factors for connective tissue sarcoma were collected for analysis. Our data on exposure to air pollutants was collected from Taiwan's Air Quality Monitoring Network, which has been gathering air quality data from a growing network of sampling stations (now 76) throughout the country since 1997. It was discovered that the risk of connective tissue sarcoma was significantly increased by the Charlson comorbidity index (CCI), elevated levels of specific air pollution indices (e.g., total hydrocarbons (THC), fine particulate matter (PM2.5), and O3_8 (the annual mean of the daily maximum 8-h average concentration of O3), the High Pollutant Standards Index (hPSI) (the percentage of days in a given year in Taiwan where the PSI exceeds 100), and an insurable monthly wage over US$1100. Further investigation is needed to explore the involvement of these air pollutants in the formation of connective tissue sarcoma.

Tumor subtypes and signature model construction based on chromatin regulators for better prediction of prognosis in uveal melanoma.

Background: Uveal Melanoma (UM) is the most prevalent primary intraocular malignancy in adults. This study assessed the importance of chromatin regulators (CRs) in UM and developed a model to predict UM prognosis. Methods: Gene expression data and clinical information for UM were obtained from public databases. Samples were typed according to the gene expression of CRs associated with UM prognosis. The prognostic key genes were further screened by the protein interaction network, and the risk model was to predict UM prognosis using the least absolute shrinkage and selection operator (LASSO) regression analysis and performed a test of the risk mode. In addition, we performed gene set variation analysis, tumor microenvironment, and tumor immune analysis between subtypes and risk groups to explore the mechanisms influencing the development of UM. Results: We constructed a signature model consisting of three CRs (RUVBL1, SIRT3, and SMARCD3), which was shown to be accurate, and valid for predicting prognostic outcomes in UM. Higher immune cell infiltration in poor prognostic subtypes and risk groups. The Tumor immune analysis and Tumor Immune Dysfunction and Exclusion (TIDE) score provided a basis for clinical immunotherapy in UM. Conclusion: The risk model has prognostic value for UM survival and provides new insights into the treatment of UM.

Quality of care in the course of subcutaneous versus intravenous trastuzumab administration in patients with breast cancer: an integrated time-motion study with mixed-methods research.

OBJECTIVES: This study aimed to compare the time required and concerns raised by various perspectives of participants regarding administering subcutaneous and intravenous trastuzumab for patients with breast cancer (BC). DESIGN: This observational time-motion study design with mixed-methods research (cross-sectional surveys and semistructured interviews) was conducted. The time spent on preparing or administering trastuzumab by different healthcare professionals (HCPs) was recorded. The data were analysed by descriptive/inferential statistical analyses, followed by thematic analyses. SETTING: Outpatient and inpatient administration units of a single medical centre in Taiwan. PARTICIPANTS: The study included patients with early-stage BC who received subcutaneous or intravenous trastuzumab (n=93), and HCPs including two attending physicians, a nurse practitioner, two pharmacists and two nurses. RESULT: Based on the perspectives of patients and HCPs, the subcutaneous form of trastuzumab was more efficient, less expensive and produced less discomfort in outpatient units than inpatient units. More participants preferred the subcutaneous form over the intravenous form in both outpatient and inpatient units. Pharmacists and nurse practitioners spent threefold more time on patients when preparing and administering the intravenous form in both outpatient and inpatient units. The concerns raised by patients and HCPs varied in certain aspects, including the injection skills, speed, mental distress (eg, needle phobia) and pain associated with the subcutaneous form. Almost all patients preferred receiving the subcutaneous form in outpatient units after the initial COVID-19 outbreak. CONCLUSION: Patients with early-stage BC preferred receiving subcutaneous trastuzumab in outpatient units rather than inpatient units or the intravenous form before and after the COVID-19 outbreak. Such findings may serve as real-world evidence to facilitate better quality of care regarding administration of subcutaneous or intravenous trastuzumab in medical settings, and its feasible resolutions to balance the quality, concerns and efficiency of anticancer administration during the COVID-19 pandemic.

Luteolin Suppresses Three Angiogenesis Modes and Cell Interaction in Uveal Melanoma in Vitro.

PURPOSE: Uveal melanoma is a high-vascularized tumor that lacks effective systemic therapies. Most anti-angiogenesis drug therapies only target endothelial cell-dependent angiogenesis but not vasculogenic mimicry (VM), which supplies blood to tumors independent of endothelial cells. Thus, we aimed to explore the inhibitory effects of luteolin on proliferation, migration, invasiveness, angiogenesis, and VM activity of uveal melanoma. We further explored the signaling pathway underlying the mechanism of action of luteolin. METHODS: Monocultures of uveal melanoma C918 cells, human umbilical vein endothelial cells (HUVECs), and co-cultures of these two cell lines were established. Angiogenesis of HUVECs, VM formation of C918 cells, and the mosaic vessels formed by both cell types were observed under an inverted microscope. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU), wound scratch, Transwell cell migration, and invasion assays were performed. VEGF levels were detected by ELISA. Western blotting was used to detect the expression of PI3K, p-PI3K P85, Akt, and p-Akt Ser473 proteins. RESULTS: Luteolin inhibited all three modes of angiogenesis observed in uveal melanoma in vitro. Luteolin effectively inhibited the proliferation, migration, and invasion of C918 cells and proliferation and migration of HUVECs. Furthermore, luteolin could inhibit the interaction between the endothelial cells and C918 cells. VEGF secretion in C918 cells and HUVECs treated with luteolin was inhibited. Luteolin decreased the levels of phosphorylated Akt kinase. CONCLUSION: We demonstrated the anti-angiogenic effects of luteolin, including against the VM type, in addition to suppressing tumor cell proliferation and migration in vitro. Furthermore, luteolin likely exerts its inhibitory effects via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Luteolin might be an effective therapeutic candidate for treating highly vascularized uveal melanoma tumors.

Luteolin inhibits the proliferation, adhesion, migration and invasion of choroidal melanoma cells in vitro.

Choroidal melanoma is a devastating disease that causes visual loss and a high mortality rate due to metastasis. Luteolin, a potential anticancer compound, is widely found in natural plants. The aim of this study was to evaluate the antiproliferative, antiadhesive, antimigratory and anti-invasive effects of luteolin on choroidal melanoma cells in vitro and to explore its potential mechanism. Cell counting kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) assays, Cell adhesion, migration, and invasion assays were performed to examine the inhibitory effects of luteolin on cell cell viability, proliferation, adhesion, migration and invasion capacities, respectively. Considering the correlation between Matrix metalloenzymes and tumor metastasis, Enzyme-linked immunosorbent assays (ELISAs) were used to assess matrix metalloproteases MMP-2 and MMP-9 secretion. Western blotting was performed to detect p-PI3K P85, Akt, and p-Akt protein expression. The cytoskeletal proteins vimentin were observed with cell immunofluorescence staining. Luteolin can inhibit OCM-1 cell proliferation, migration, invasion and adhesion and C918 cell proliferation, migration, and invasion through the PI3K/Akt signaling pathway. Therefore, Luteolin may have potential as a therapeutic medication for Choroidal melanoma.

Effect of luteolin on apoptosis and vascular endothelial growth factor in human choroidal melanoma cells.

AIM: To investigate the effects of luteolin on apoptosis, the cell cycle, and the expression and secretion of vascular endothelial growth factor (VEGF) in human choroidal melanoma cells (C918 and OCM-1). METHODS: C918 and OCM-1 cells cultured in vitro were treated with various concentrations of luteolin (0, 5, 10, 15 µmol/L). Cell growth was observed with an inverted microscope, and cell cycle arrest was detected by propidium iodide (PI) staining using flow cytometry. Apoptosis was detected by Hoechst33342 staining, and apoptosis rate was determined by Annexin V-FITC/PI experiments using flow cytometry. The expression of apoptosis-related proteins Bcl-2, Bax and VEGF was analyzed using Western blots. The levels of VEGF secreted by the cells into the supernatant was analyzed using ELISA. RESULTS: After treating with 5 to 15 µmol/L luteolin for 48h, the fusion degree of C918 and OCM-1 cells decreased, and more floating apoptotic cells appeared. Luteolin treatment increased the G0-G1 phase ratio of the C918 and OCM-1 cells, blocked cell cycle progression, and increased the apoptosis rate of the C918 and OCM-1 cells. Western blot showed that luteolin decreased the expression of Bcl-2 and VEGF in the C918 and OCM-1 cells and increased the expression of Bax protein. The ELISA results showed that 10 to 15 µmol/L luteolin decreased the cell secretion of VEGF. CONCLUSION: Luteolin may induce apoptosis by regulating the levels of apoptosis-related proteins in C918 and OCM-1 cells. Luteolin can induce cell cycle arrest, decrease the expression of VEGF.

Copper(I)-Catalyzed Nitrile-Addition/N-Arylation Ring-Closure Cascade: Synthesis of 5,11-Dihydro-6H-indolo[3,2-c]quinolin-6-ones as Potent Topoisomerase-I Inhibitors.

In this paper, we present a copper(I)-catalyzed nitrile-addition/N-arylation ring-closure cascade for the synthesis of 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones from 2-(2-bromophenyl)-N-(2-cyanophenyl)acetamides. Using CuBr and t-BuONa in dimethylformamide (DMF) as the optimal reaction conditions, the cascade reaction gave the target products, in high yields, with a good substrate scope. Application of the cascade reaction was demonstrated on the concise total syntheses of alkaloid isocryptolepine. Further optimization of the products from the cascade reaction led to 3-chloro-5,12-bis[2-(dimethylamino)ethyl]-5,12-dihydro-6H-[1,3]dioxolo[4',5':5,6]indolo[3,2-c]quinolin-6-one (2k), which exhibited the characteristic DNA topoisomerase-I inhibitory mechanism of action with potent in vitro anticancer activity. Compound 2k actively inhibited ARC-111- and SN-38-resistant HCT-116 cells and showed in vivo activity in mice bearing human HCT-116 and SJCRH30 xenografts. The interaction of 2k with the Top-DNA cleavable complex was revealed by docking simulations to guide the future optimization of 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones as topoisomerase-I inhibitors.

Nasogastric tube decompression is unnecessary in patients undergoing laparoscopic nephroureterectomy for localized upper tract urothelial carcinoma.

BACKGROUND/PURPOSE: This study investigates the safety and feasibility to perform laparoscopic nephroureterectomy (LNU) for upper tract urothelial carcinoma (UTUC) without routine nasogastric tube (NGT) decompression. METHODS: The hospital-based samples comprised of 100 consecutive UTUC patients receiving elective LNU performed by two experienced surgeons. The nationwide data was based on LHID2005 composed of one million beneficiaries randomly selected from the Taiwan National Health Insurance Research Database to identify patients with the diagnoses of UTUCs receiving LNUs. We then compared baseline characteristics, peri-operative data, convalescence parameters and complications between two groups stratified by use of NGT tube. RESULTS: The hospital-based samples composed of 50 subjects with NGT and 50 without. There were no significant differences in baseline characteristics between two groups. Peri-operative and convalescence parameters were similar when comparing no NGT versus NGT: blood loss of 206 vs. 165 mL; operative time of 180.5 vs.181.1 min; days to intake was 2.1 vs.1.7 days; and hospital stay of 7.8 vs. 7.5 days (all p > 0.05). The nationwide study samples comprised 140 subjects, of which 72 were with NGT and 68 were with no NGT. The baseline data, complications and length of hospital stay were similar between two groups. CONCLUSION: Surgery-naïve patients with localized UTUC received LNU without peri-operative NGT is safe and feasible.

Phantom validation of quantitative susceptibility and dynamic contrast-enhanced permeability MR sequences across instruments and sites.

BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative permeability (DCEQP) on magnetic resonance (MR) have been shown to correlate with neurovascular disease progression as markers of vascular leakage and hemosiderin deposition. Applying these techniques as monitoring biomarkers in clinical trials will be necessary; however, their validation across multiple MR platforms and institutions has not been rigorously verified. PURPOSE: To validate quantitative measurement of MR biomarkers on multiple instruments at different institutions. STUDY TYPE: Phantom validation between platforms and institutions. PHANTOM MODEL: T1 /susceptibility phantom, two-compartment dynamic flow phantom. FIELD STRENGTH/SEQUENCE: 3T/QSM, T1 mapping, dynamic 2D SPGR. ASSESSMENT: Philips Ingenia, Siemens Prisma, and Siemens Skyra at three different institutions were assessed. A QSM phantom with concentrations of gadolinium, corresponding to magnetic susceptibilities of 0, 0.1, 0.2, 0.4, and 0.8 ppm was assayed. DCEQP was assessed by measuring a MultiHance bolus as the consistency of the width ratio of the curves at the input and outputs over a range of flow ratios between outputs. STATISTICAL TESTS: Each biomarker was assessed by measures of accuracy (Pearson correlation), precision (paired t-test between repeated measurements), and reproducibility (analysis of covariance [ANCOVA] between instruments). RESULTS: QSM accuracy of r2 > 0.997 on all three platforms was measured. Precision (P = 0.66 Achieva, P = 0.76 Prisma, P = 0.69 Skyra) and reproducibility (P = 0.89) were good. T1 mapping of accuracy was r2 > 0.98. No significant difference between width ratio regression slopes at site 2 (P = 0.669) or site 3 (P = 0.305), and no significant difference between width ratio regression slopes between sites was detected by ANCOVA (P = 0.48). DATA CONCLUSION: The phantom performed as expected and determined that MR measures of QSM and DCEQP are accurate and consistent across repeated measurements and between platforms. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1192-1199.

Trends in the use of antimuscarinics and alpha-adrenergic blockers in women with lower urinary tract symptoms in Taiwan: A nationwide, population-based study, 2007-2012.

BACKGROUND: We aim to examine the trend in the use of antimuscarinics and off-label alpha-adrenergic blockers for treatment of lower urinary tract symptoms (LUTS) in a Taiwanese Women Cohort between 2007 and 2012. METHODS: This population-based National Health Insurance Research Database (NHIRD) was used to examine the trends in the use of antimuscarinics or off-label alpha-adrenergic blockers in Taiwan. A sample of 1,000,000 individuals randomly drawn from the whole population of 23 million individuals who were registered in the NHI in 2005. From 2007 through 2012, women aged over 18 years whose claim record contained prescriptions of either of the two drugs for treatment of any of the LUTS-related diagnoses were identified and analyzed. The annual usage of the two drug classes were calculated by defined daily dose (DDD). RESULTS: From 2007-2012, there was a 0.80 fold (69676.8 to 125104.3) increase in DDD of antimuscarinics in our cohort. The overall healthcare seeking prevalence of LUTS was 7.33% in 2007 and 12.38% in 2012, in a rising trend. The prevalence of antimuscarinics-treated LUTS in our cohort increased from 2.53 in 2007 to 3.41 per 1000 women in 2012. The prevalence of LUTS treated by antimuscarinics increased especially for those older than 60 years during the study period. CONCLUSIONS: This 6-year observational study provided the epidemiologic information of clinically significant LUTS of Asian female population. Moreover, there was a rising trend in the use of antimuscarinics and off-label alpha-adrenergic blockers in the population-based cohort.

Factors associated with reoperation in hypospadias surgery - A nationwide, population-based study.

BACKGROUND/OBJECTIVE: To analyze the preoperative factors associated with the need for secondary surgery following primary urethroplasty. METHODS: This study utilized a subset of the National Health Insurance Research Database, which includes the data on all paid medical benefit claims from 1997 to 2007, for 1 million beneficiaries in 2005. We analyzed the claims data for all patients with hypospadias who had undergone primary urethroplasty. The characteristics of the patients, surgeons, and hospitals associated with surgical outcomes were analyzed to investigate possible associations with the need for secondary surgery. RESULTS: Among 52,705 live male newborn babies, 218 were diagnosed with hypospadias, of whom 89 received repair surgery. A total of 75 (84.3%) male newborn babies received single hypospadias surgery, and 14 (15.7%) underwent more than two surgical procedures. Univariate analysis demonstrated that the type of hypospadias and the surgeon caseload volume were significantly associated with the need for additional hypospadias surgery (p = 0.02 and p = 0.03, respectively). In multivariate analysis, the type of hypospadias (distal vs. proximal, odds ratio, 0.25; p = 0.03) and the surgeon caseload volume (high vs. low, odds ratio, 0.04; p = 0.05) were significantly correlated with secondary operation. CONCLUSION: The type of hypospadias and the surgeon caseload volume were significantly associated with the need for secondary hypospadias surgery. The findings of this study provide important information on the outcomes of hypospadias repair for parents and specialists.

Identification of SPHK1 as a therapeutic target and marker of poor prognosis in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is characterized by a uniquely aggressive behavior and lack of effective targeted therapies. After analyzing the gene expression profiles of seven paired intrahepatic CCA microarrays, a novel sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P) pathway and a novel target gene, SPHK1, were identified. We hypothesized that therapeutic targeting of this pathway can be used to kill intrahepatic cholangiocarcinoma (CCA) cells. High levels of SPHK1 protein expression, which was evaluated by immunohistochemical staining of samples from 96 patients with intrahepatic CCA, correlated with poor overall survival. The SPHK1 inhibitor SK1-I demonstrated potent antiproliferative activity in vitro and in vivo. SK1-I modulated the balance of ceramide-sphinogosine-S1P and induced CCA apoptosis. Furthermore, SK1-I combined with JTE013, an antagonist of the predominant S1P receptor S1PR2, inhibited the AKT and ERK signaling pathways in CCA cells. Our preclinical data suggest SPHK1/S1P pathway targeting may be an effective treatment option for patients with CCA.

Muscle-fat MRI: 1.5 Tesla and 3.0 Tesla versus histology.

INTRODUCTION: We evaluated muscle/fat fraction (MFF) accuracy and reliability measured with an MR imaging technique at 1.5 Tesla (T) and 3.0T scanner strengths, using biopsy as reference. METHODS: MRI was performed on muscle samples from pig and rabbit species (n = 8) at 1.5T and 3.0T. A chemical shift based 2-point Dixon method was used, collecting in-phase and out-of-phase data for fat/water of muscle samples. Values were compared with MFFs calculated from histology. RESULTS: No significant difference was found between 1.5T and 3.0T (P values = 0.41-0.96), or between histology and imaging (P = 0.83) for any muscle tested. CONCLUSIONS: RESULTS suggest that a 2-point Dixon fat/water separation MRI technique may provide reliable quantification of MFFs at varying field strengths across different animal species, and consistency was established with biopsy. The results set a foundation for larger scale investigation of quantifying muscle fat in neuromuscular disorders.

Factors related to the time to cryptorchidism surgery--a nationwide, population-based study in Taiwan.

BACKGROUND/PURPOSE: Current guidelines recommend that the optimal timing for cryptorchidism surgery is by the age of 12 months. This study investigated the trend of surgical timing and examined the factors associated with time to surgery for cryptorchidism in Taiwan by using a nationwide, population-based database. METHODS: The present study utilized the Longitudinal Health Insurance Database 2005, a subset of the National Health Insurance Research Database, which contains data on all paid medical benefit claims over the period 1997-2007 for a subset of 1 million beneficiaries randomly drawn from 22.72 million individuals enrolled in the National Health Insurance program in 2005. We analyzed the timing of surgery in boys younger than 18 years with diagnosis of cryptorchidism. RESULTS: We identified 547 boys who underwent surgery under 18 years of age. Approximately 79.2% of study participants received surgery after the age of 12 months. A multivariate analysis showed that several factors were significantly associated with time to surgery: age of the physician making the diagnosis, age of the surgeon performing the surgery, age of the patient at the first diagnosis of cryptorchidism, and number of previous clinic visits with the diagnosis of cryptorchidism and urbanization level of the patient's residence. CONCLUSION: A surprisingly high rate (79.2%) of all study participants underwent surgery beyond the optimal timing. Certain doctor and patient factors were associated with time to cryptorchidism surgery. Improving the alertness and education of parents and specialists may lead to earlier surgeries.

Epidemiology of upper urinary tract stone disease in a Taiwanese population: a nationwide, population based study.

PURPOSE: We investigated the epidemiology of upper urinary tract stone disease in Taiwan using a nationwide, population based database. MATERIALS AND METHODS: This study was based on the National Health Insurance Research Database of Taiwan, which contains data on all medical beneficiary claims from 22.72 million enrollees, accounting for almost 99% of the Taiwanese population. The Longitudinal Health Insurance Database 2005, a subset of the National Health Insurance Research Database, contains data on all medical benefit claims from 1997 through 2010 for a subset of 1 million beneficiaries randomly sampled from the 2005 enrollment file. For epidemiological analysis we selected subjects whose claims records included the diagnosis of upper urinary tract urolithiasis. RESULTS: The age adjusted rate of medical care visits for upper urinary tract urolithiasis decreased by 6.5% from 1,367/100,000 subjects in 1998 to 1,278/100,000 in 2010. There was a significantly decreasing trend during the 13-year period in visits from female and all subjects (r(2) = 0.86, p = 0.001 and r(2) = 0.52, p = 0.005, respectively). In contrast, an increasing trend was noted for male subjects (r(2) = 0.45, p = 0.012). The age adjusted prevalence in 2010 was 9.01%, 5.79% and 7.38% in male, female and all subjects, respectively. The overall recurrence rate at 1 and 5 years was 6.12% and 34.71%, respectively. Male subjects had a higher recurrence rate than female subjects. CONCLUSIONS: Our study provides important information on the epidemiology of upper urinary tract stone disease in Taiwan, helping to quantify the burden of urolithiasis and establish strategies to decrease the risk of urolithiasis.

Factors associated with delayed pediatric hypospadias surgery in Taiwan: a population-based, nationwide analysis.

BACKGROUND/PURPOSE: Current guidelines recommend that hypospadias repair should be performed before age 18 months. This study aims to investigate the trends of surgical timing and to determine what factors are associated with age at surgery. METHODS: The present study utilized a subset of the National Health Insurance Research Database, known as Longitudinal Health Insurance Database 2005, which contains the data of all paid medical benefit claims over the period from 1997 to 2007 for a subset of one million beneficiaries randomly drawn from the population of 22.72 million individuals in NHI program during any part of calendar year 2005. We analyzed claims data for all subjects with the diagnoses of hypospadias. RESULTS: Among 52,705 live male newborns, 218 were diagnosed with hypospadias and thus were included as subjects in our study. Among them, 89 received repair surgery. Approximately 60.6% of the study subjects received repair after the age of 18 months. Multivariate analysis showed that several factors were significantly associated with age at hypospadias surgery: specialty of clinics where first diagnosis was made; specialty of physician making the first diagnosis, age of physician making the first diagnosis; specialty of surgeon performing the surgery; number of years since surgeon's board certification; urbanization level of subject's residence; modality of surgery; concomitant cryptorchidism; concomitant prematurity and low birth weight; age at diagnosis; and number of well-baby clinic visits. CONCLUSION: This study addresses an important issue of delayed hypospadias surgery in Taiwan, which provides a potential opportunity for improvement in quality of care.

Epidemiology of hypospadias and treatment trends in Taiwan: a nationwide study.

PURPOSE: We investigated the rate of diagnosis and treatment trends of hypospadias in Taiwan within the first 3 years of life. MATERIALS AND METHODS: We used a subset of the Taiwan National Health Insurance Research Database, which contains data on all inpatient and outpatient medical benefit claims, for the period 1997 through 2008 for a sample of 1 million individuals randomly drawn from the population of 25.68 million who held membership in the National Health Insurance program during any part of the calendar year 2005. We analyzed claims data for all subjects who were diagnosed with hypospadias through age 3 years. RESULTS: Among 52,705 newborns (individuals whose claims included live birth) 178 were diagnosed with hypospadias within 3 years of birth. Thus, mean incidence was 33.8 per 10,000 live male births. The hypospadias repair rate was 14.3 per 10,000 live male births. There was no significant tendency toward increase or decrease in rates of diagnoses or repairs, or proportion of severe hypospadias. There were significant associations between rates of hypospadias diagnoses and urbanization level of the community where the diagnosis was made. Approximately 54% of patients who underwent surgical repair did so after age 18 months. CONCLUSIONS: The nationwide incidence of hypospadias in children younger than 3 years in Taiwan is similar to that reported in previous studies. Delayed diagnosis and treatment of hypospadias are important clinical concerns that warrant further investigation.