Purpose: The objective of this study was to define the learning curve required to attain satisfactory oncologic outcomes of cervical cancer patients who were undergoing open or minimally invasive surgery for radical hysterectomy, and to analyze the correlation between the learning curve and tumor size. Materials and Methods: Cervical cancer patients (stage IA-IIA) who underwent open radical hysterectomy (n=280) or minimal invasive radical hysterectomy (n=282) were retrospectively reviewed. The learning curve was evaluated using cumulative sum of 5-year recurrence rates. Survival outcomes were analyzed based on the operation period (“learning period,” P1 vs. “skilled period,” P2), operation mode, and tumor size. Results: The 5-year disease-free and overall survival rates between open and minimally invasive groups were 91.8% and 89.0% (p=0.098) and 96.1% and 97.2% (p=0.944), respectively. The number of surgeries for learning period was 30 and 60 in open and minimally invasive group, respectively. P2 had better 5-year disease-free survival than P1 after adjusting for risk factors (hazard ratio, 0.392; 95% confidence interval, 0.210 to 0.734; p=0.003). All patients with tumors < 2 cm had similar 5-year disease-free survival regardless of operation mode or learning curve. Minimally invasive group presented lower survival rates than open group when tumors ≥ 2 cm in P2. Preoperative conization improved disease-free survival in patients with tumors ≥ 2 cm, especially in minimally invasive group. Conclusion Minimally invasive radical hysterectomy required more cases than open group to achieve acceptable 5-year disease-free survival. When tumors ≥ 2 cm, the surgeon’s proficiency affected survival outcomes in both groups.

BACKGROUND AND OBJECTIVES: Oxidative stress plays an important role in the pathogenesis of coronary atherosclerosis and spasm. We investigated whether the polymorphisms in two oxidative stress-related genes, paraoxonase and p22phox, are associated with risks of coronary artery spasm and stenosis. SUBJECTS AND METHODS: The study comprised of 116 patients with variant angina, 118 patients with coronary artery stenosis and 117 control subjects, who were all classified by coronary angiography. In all three groups, the genotype frequencies of the Q192R polymorphism of the paraoxonase gene and C242T polymorphism of the p22phox gene were analyzed, and the serum thiobarbituric acid-reactive substance concentrations measured. RESULTS: The frequency of the RR genotype of the paraoxonase Q192R polymorphism was significantly higher in patients with variant angina and coronary artery stenosis than in the control subjects (40.4% in variant angina and 37.8% in coronary artery stenosis vs. 24.7% in control, p=0.020 and 0.048, respectively). From the multivariate analysis, the odds ratio of the RR genotype was 2.240 for variant angina (95% confidence interval ; 1.012-4.956), and 2.333 for coronary artery stenosis (95% confidence interval ; 1.140-4.777), in relation to the control subjects. The thiobarbituric acid-reactive substance level was significantly higher in the RR type than in the QQ+QR types (RR vs. QQ+QR : 1.106+/-0.420 nmol/mL vs. 0.949+/-0.311 nmol/mL, p=0.028). There was no significant difference in the prevalence of the C242T polymorphism of the p22phox gene between the three groups. CONCLUSION: The RR genotype of the paraoxonase gene Q192R polymorphism was found to be an independent risk factor for both coronary spasm and stenosis.
Angina Pectoris ; Aryldialkylphosphatase* ; Constriction, Pathologic ; Coronary Angiography ; Coronary Artery Disease ; Coronary Stenosis* ; Coronary Vessels* ; Genotype ; Humans ; Multivariate Analysis ; Odds Ratio ; Oxidative Stress* ; Polymorphism, Single Nucleotide ; Prevalence ; Risk Factors ; Spasm

INTRODUCTION: The rising prevalence of multiple chronic diseases is an important public health issue as it is associated with increased healthcare utilisation. This paper aimed to explore the annual per capita healthcare cost in primary care for patients with multiple chronic diseases (multimorbidity). METHODS: This was a retrospective cohort study conducted in a cluster of public primary care clinics in Singapore. De-identified data from electronic medical records were extracted from July 2015 to June 2017. Only patients with at least 1 chronic disease were included in the study. Basic demographic data and healthcare cost were extracted. A list of 20 chronic diseases was considered for multimorbidity. RESULTS: There were 254,377 patients in our study population, of whom 52.8% were female. The prevalence of multimorbidity was 62.4%. The median annual healthcare cost per capita for patients with multimorbidity was about twice the amount compared to those without multimorbidity (SGD683 versus SGD344). The greatest percentage increment in cost was when the number of chronic diseases increased from 2 to 3 (43.0%). CONCLUSION Multimorbidity is associated with higher healthcare cost in primary care. Since evidence for the optimal management of multimorbidity is still elusive, prevention or delay in the onset of multimorbidity in the general population is paramount.
Chronic Disease ; Comorbidity ; Cross-Sectional Studies ; Female ; Health Care Costs ; Humans ; Prevalence ; Primary Health Care ; Retrospective Studies ; Singapore/epidemiology*

Leptin is a peptide hormone, which has a central role in the regulation of body weight; it also exerts many potentially atherogenic effects. Ferulic acid ethyl ester (FAEE) has been approved for antioxidant properties. The aim of this study was to investigate whether FAEE can inhibit the atherogenic effects of leptin and the possible molecular mechanism of its action. Both of cell proliferation and migration were measured when the aortic smooth muscle cell (A10 cell) treated with leptin and/or FAEE. Phosphorylated p44/42MAPK, cell cycle-regulatory protein (for example, cyclin D1, p21, p27), beta-catenin and matrix metalloproteinase-9 (MMP-9) proteins levels were also measured. Results demonstrated that leptin (10, 100 ng ml-1) significantly increased the proliferation of cells and the phosphorylation of p44/42MAPK in A10 cells. The proliferative effect of leptin was significantly reduced by the pretreatment of U0126 (0.5 muM), a MEK inhibitor, in A10 cells. Meanwhile, leptin significantly increased the protein expression of cyclin D1, p21, beta-catenin and decreased the expression of p27 in A10 cells. In addition, leptin (10 ng ml-1) significantly increased the migration of A10 cells and the expression of MMP-9 protein. Above effects of leptin were significantly reduced by the pretreatment of FAEE (1 and 10 muM) in A10 cells. In conclusion, FAEE exerts multiple effects on leptin-induced cell proliferation and migration, including the inhibition of p44/42MAPK phosphorylation, cell cycle-regulatory proteins and MMP-9, thereby suggesting that FAEE may be a possible therapeutic approach to the inhibition of obese vascular disease.
Animals ; Antioxidants/*pharmacology ; Aorta/cytology/*drug effects ; Caffeic Acids/*pharmacology ; Cell Line ; Cell Movement/*drug effects ; Cell Proliferation/*drug effects ; Leptin/*metabolism ; Matrix Metalloproteinase 9/metabolism ; Muscle, Smooth, Vascular/cytology/drug effects ; Myocytes, Smooth Muscle/cytology/*drug effects ; Rats ; beta Catenin/metabolism

Abdominal Pain ; diagnosis ; Adult ; Female ; Humans ; Sports ; Superior Mesenteric Artery Syndrome ; diagnosis ; Young Adult

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is associated with considerable impairment of patients’ health-related quality of life (HRQoL). Knowledge of factors that significantly affect IBD patients’ HRQoL can contribute to better patient care. However, the HRQoL of IBD patients in non-Western countries are limited. Hence, we assessed the HRQoL of Singaporean IBD patients and identified its determinants. METHODS: A prospective, cross-sectional study was conducted at Singapore General Hospital outpatient IBD Centre. The HRQoL of IBD patients was assessed using the short IBD questionnaire (SIBDQ), Short Form-36 physical and mental component summary (SF-36 PCS/MCS) and EuroQol 5-dimensions 3-levels (EQ-5D-3L) and visual analogue scale (VAS). Independent samples t-test was used to compare HRQoL between Crohn’s disease (CD) and ulcerative colitis (UC). Determinants of HRQoL were identified through multiple linear regression. RESULTS: A total of 195 IBD patients (103 UC, 92 CD) with a mean disease duration of 11.2 years were included. There was no significant difference in HRQoL between patients with UC and CD. Factors that significantly worsened HRQoL were presence of active disease (b=−6.293 [SIBDQ], −9.409 [PCS], −9.743 [MCS], −7.254 [VAS]), corticosteroids use (b=−7.392 [SIBDQ], −10.390 [PCS], −8.827 [MCS]), poor medication adherence (b=−4.049 [SIBDQ], −1.320 [MCS], −8.961 [VAS]), presence of extraintestinal manifestations (b=−13.381 [PCS]), comorbidities (b=−4.531 [PCS]), non-employment (b=−9.738 [MCS], −0.104 [EQ-5D-3L]) and public housing (b=−8.070 [PCS], −9.207 [VAS]). CONCLUSIONS: The HRQoL is impaired in this Asian cohort of IBD. The magnitude of HRQoL impairment was similar in UC and CD. Clinical characteristics were better determinants of patients’ HRQoL than socio-demographic factors. Recognizing the factors that impact patients’ HRQoL would improve the holistic management of IBD patients.
Adrenal Cortex Hormones ; Asian Continental Ancestry Group ; Cohort Studies ; Colitis, Ulcerative ; Comorbidity ; Cross-Sectional Studies ; Hospitals, General ; Humans ; Inflammatory Bowel Diseases ; Linear Models ; Medication Adherence ; Outpatients ; Patient Care ; Prospective Studies ; Public Housing ; Quality of Life ; Singapore

PURPOSE: Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. MATERIALS AND METHODS: To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA). RESULTS: Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25,HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845). CONCLUSION: We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.
Animals ; Carboplatin ; Cause of Death ; Drug Therapy ; Exome ; Female ; Gene Expression ; Genome ; Heterografts ; Humans ; Mice ; Odds Ratio ; Ovarian Neoplasms ; Ovary ; Paclitaxel ; Recurrence ; Sequence Analysis, RNA ; Statistics as Topic

BACKGROUND AND OBJECTIVES: The 5-HT2A receptor is one of the main mediators of a serotonin-evoked coronary artery contraction. This is because vasoconstriction is selectively blocked by the 5-HT2 receptor antagonist, with the 5-HT2A receptor gene mRNA being detected in spastic coronary arteries. The relationship between the T102C polymorphism of the 5-HT2A receptor gene and the response to the 5-HT2A antagonist (clozapine) has recently been established, suggestive of a functional implication. Previous studies have observed an association between low cholesterol levels and mental disorders, but the underlying cause has not been determined. It has been established that the T102C polymorphism of the 5-HT2A serotonin receptor gene and a variety of psychological problems are related, but the relationship between the serum lipid level and this genetic polymorphism has not been reported. We investigated the influence of this polymorphism on coronary artery disease, including vasospastic angina and the clinical parameters, such as the lipid profile. SUBJECTS AND METHODS: After a diagnostic angiography was performed, the genotype was identified from the genomic DNA extracted from the peripheral blood of 646 patients without specific psychiatric diseases. RESULTS: There were no differences in the genotype frequencies between coronary artery disease, coronary artery disease with vasospasm, and the normal control groups, even from a subgroup analysis of the clinical parameters. Contrary to previous reports, the genotype distribution was not related to a myocardial infarction or hypertension. The lipid profile analysis showed significantly lower total cholesterol (193.5 vs. 202.1mg/dL, p=0.016) and HDL-cholesterol (42.7 vs. 46.2mg/dL, p=0.003) levels in the CC genotype than the other genotypes, and the frequencies of CC genotype showed a significantly decreasing trend between the HDL-cholesterol (p=0.003) and total cholesterol (p=0.003) quartiles. From a multivariate analysis, only the HDL-cholesterol level was significantly associated with a lower frequency of the CC genotype (p=0.006). CONCLUSION: The T102C polymorphism is not related to coronary artery disease, including vasospasm of the coronary artery, but the CC genotype of this polymorphism is related to low HDL-cholesterol. We identified a novel genetic polymorphism of the serotonin receptor, which affects the HDL-cholesterol level. Because previous observational studies have shown an association between low cholesterol levels and mental disorders, our data should be considered when analyzing the serum lipid levels and serotonin receptor function in humans.
Angiography ; Cholesterol ; Coronary Artery Disease* ; Coronary Vessels* ; DNA ; Genotype ; Humans ; Hypertension ; Mental Disorders ; Multivariate Analysis ; Muscle Spasticity ; Myocardial Infarction ; Polymorphism, Genetic ; Receptor, Serotonin, 5-HT2A* ; RNA, Messenger ; Serotonin ; Serotonin 5-HT2 Receptor Antagonists ; Vasoconstriction

Objectives: This study compared serum anti-Mullerian hormone (AMH) levels in endometriotic cysts (ECs) with those in non-ECs and analyzed changes thereof after single-port laparoscopic (SPL) ovarian cyst enucleation using vasopressin injection. Methods: In total, 180 patients (EC group, n = 112; non-EC group, n = 68) who underwent SPL ovarian cyst enucleation were retrospectively reviewed. Their AMH levels were checked preoperatively, on postoperative day 10 (POD10), and on postoperative month 3 (POM3). Changes in AMH levels were analyzed according to tumor type and vasopressin use. Results: The median initial and postoperative serum AMH levels in the EC group were significantly lower than those in the nonEC group (preoperation: 2.0 vs 3.8 ng/mL, P < 0.001; POD10: 1.0 vs 3.2 ng/mL, P < 0.001; POM3: 1.2 vs 3.6 ng/mL, P < 0.001). The postoperative decrease in AMH levels was higher in the EC group than the non-EC group on POD10 (0.8 vs 0.5 ng/mL, P = 0.011) but not on POM3 (0.7 vs 0.5 ng/mL, P = 0.164). Vasopressin injection during EC enucleation had no significant effect on the decrease in AMH levels on POD10 (vasopressin group vs non-vasopressin group: 1.0 vs 0.8 ng/mL, P = 0.253) and POM3 (vasopressin group vs nonvasopressin group: 1.4 vs 1.1 ng/mL, P = 0.242). Conclusions AMH levels were lower at baseline and had higher decreasing rates after SPL surgery in the EC group relative to the nonEC group. Vasopressin injection might not protect the ovary from the postoperative decrease in AMH levels.

The genus Acanthamoeba can cause severe infections such as granulomatous amebic encephalitis and amebic keratitis in humans. However, little genomic information of Acanthamoeba has been reported. Here, we constructed Acanthamoeba expressed sequence tags (EST) database (Acanthamoeba EST DB) derived from our 4 kinds of Acanthamoeba cDNA library. The Acanthamoeba EST DB contains 3,897 EST generated from amebae under various conditions of long term in vitro culture, mouse brain passage, or encystation, and downloaded data of Acanthamoeba from National Center for Biotechnology Information (NCBI) and Taxonomically Broad EST Database (TBestDB). The almost reported cDNA/genomic sequences of Acanthamoeba provide stand alone BLAST system with nucleotide (BLAST NT) and amino acid (BLAST AA) sequence database. In BLAST results, each gene links for the significant information including sequence data, gene orthology annotations, relevant references, and a BlastX result. This is the first attempt for construction of Acanthamoeba database with genes expressed in diverse conditions. These data were integrated into a database (http://www.amoeba.or.kr).
Acanthamoeba/*genetics ; Animals ; *Databases, Genetic ; *Expressed Sequence Tags