ABSTRACT
Kinetochore associated 1 (KNTC1) encodes a kinetochore component in Rod-Zwilch-ZW10 (RZZ) complex which is essential for the segregation of sister chromatids during mitosis and participates in the spindle checkpoint. Recent research demonstrated that kinetochore proteins may be potential biomarkers and may contribute to the development of human malignancies. Our immunohistochemistry experiment showed that KNTC1 was highly expressed in hepatocellular carcinoma (HCC) tissues and correlated with terrible prognosis, indicating that KNTC1 acts a pivotal role in HCC development. Furthermore, lentivirus delivered short hairpin RNA (shRNA) KNTC1 (Lv-shKNTC1) was applied to infect BEL-7404 and SK-HEP-1 to identify roles of KNTC1 on HCC. Lv-shKNTC1 cells showed reduced proliferation ability, increased apoptosis and decreased migration ability. In vivo experiments suggested that xenografts grow significantly slower upon the silencing of KNTC1. Mechanistically, the protein levels of PIK3CA, p-Akt, CCND1, CDK6 are all down-regulated in Lv-KNTC1 cells and the Lv-shKNTC1 tumor tissues of nude mice. Therefore, KNTC1 may affect the biological activity of HCC cells through PI3K/Akt signaling pathway. Further studies revealed that ZW10 is a pivotal protein that participates in KNTC1-induced regulation of PI3K/Akt signaling pathway. In summary, the key finding of this report highlighted the significance of KNTC1 in tumor regression of HCC, demonstrating KNTC1 as an innovative target for adjuvant treatment of HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Mice , Animals , Humans , Carcinoma, Hepatocellular/pathology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Liver Neoplasms/pathology , Mice, Nude , Cell Proliferation/genetics , Apoptosis/genetics , RNA, Small Interfering/genetics , Cell Line, Tumor , Microtubule-Associated Proteins , Cell Cycle Proteins/geneticsABSTRACT
Present guidelines recommend a multidisciplinary team (MDT) approach to diabetic foot ulcer (DFU) care, but relevant data from Asia are lacking. We aim to evaluate the clinical and economic outcomes of an MDT approach in a lower extremity amputation prevention programme (LEAPP) for DFU care in an Asian population. We performed a case-control study of 84 patients with DFU between January 2017 and October 2017 (retrospective control) vs 117 patients with DFU between December 2017 and July 2018 (prospective LEAPP cohort). Comparing the clinical outcomes between the retrospective cohort and the LEAPP cohort, there was a significant decrease in mean time from referral to index clinic visit (38.6 vs 9.5 days, P < .001), increase in outpatient podiatry follow-up (33% vs 76%, P < .001), decrease in 1-year minor amputation rate (14% vs 3%, P = .007), and decrease in 1-year major amputation rate (9% vs 3%, P = .05). Simulation of cost avoidance demonstrated an annualised cost avoidance of USD $1.86m (SGD $2.5m) for patients within the LEAPP cohort. In conclusion, similar to the data from Western societies, an MDT approach in an Asian population, via a LEAPP for patients with DFU, demonstrated a significant reduction in minor and major amputation rates, with annualised cost avoidance of USD $1.86m.
Subject(s)
Diabetes Mellitus , Diabetic Foot , Foot Ulcer , Amputation, Surgical , Case-Control Studies , Diabetic Foot/prevention & control , Diabetic Foot/surgery , Humans , Lower Extremity , Patient Care Team , Prospective Studies , Retrospective StudiesABSTRACT
INTRODUCTION: A poor prognosis owing to cancer invasion and metastasis, hepatocellular carcinoma (HCC) is one of the leading causes of malignancy deaths worldwide. A dominant epithelial-to-mesenchymal transition or EMT function in tumour metastasis is substantially evidenced. Prior reports identified a likely correlation of the nuclear hormone receptor NR1D2 with HCC progression, but the underlying molecular mechanisms and role of invasion and metastasis are still to be adequately documented. METHODS: We carried out PROGgeneV2 platform database analysis and compared NR1D2 expression in HCC tissues with that in adjacent noncancerous tissues by Western blotting. Cell proliferation, invasion, and migration were also assessed using a lentivirus system. Moreover, the relevant signalling proteins were evaluated. RESULTS: The PROGgeneV2 platform database analysis suggested an upregulated NR1D2 expression related to poor overall survival, or OS, in HCC, with higher levels in HCC, compared to the adjoining non-cancerous tissue. Depleting NR1D2 decreased HCC cell proliferation, migration and invasion in vitro, whilst in vivo downregulation revealed fewer metastatic nodules in the lungs. Furthermore, NR1D2 knockdown amplified epithelial marker, namely E-cadherin expressions, and decreased mesenchymal markers, ie, N-cadherin and vimentin expressions, with ß-catenin overexpression. CONCLUSION: NR1D2 is shown to accelerate HCC progression via driving EMT.
ABSTRACT
Long noncoding RNAs play vital roles in several biological processes, including cell growth and embryonic development. We showed that MACC1-AS1 was overexpressed in hepatocellular carcinoma (HCC) cells and tissues. The MACC1-AS1 expression level was dramatically upregulated in HCC samples compared to adjacent normal samples, and 77.5% (31 of 40) of HCC samples showed overexpression of MACC1-AS1. Ectopic MACC1-AS1 expression enhanced cell proliferation and cyclin D1 expression in both SMMC7721 and MHCC-97H cells. Ectopic expression of MACC1-AS1 promoted vimentin, N-cadherin and snail expression and decreased E-cadherin expression in both SMMC7721 and MHCC-97H cells. MACC1-AS1 overexpression also induced cell invasion in the same two cell lines. Furthermore, MACC1-AS1 overexpression enhanced PAX8 expression in HCC cells. The PAX8 level was dramatically increased in HCC samples compared to adjacent normal samples, and 75% (30 of 40) of HCC samples showed overexpression of PAX8. PAX8 expression was positively correlated with MACC1-AS1 expression in HCC samples. MACC1-AS1 overexpression promoted HCC cell proliferation, EMT and invasion through regulating PAX8. These results suggest that MACC1-AS1 acts as an oncogene in the development of HCC.
Subject(s)
Carcinoma, Hepatocellular/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , PAX8 Transcription Factor/genetics , RNA Interference , RNA, Antisense/genetics , Trans-Activators/genetics , Biomarkers, Tumor , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement/genetics , Ectopic Gene Expression , Epithelial-Mesenchymal Transition/genetics , Humans , RNA, Long Noncoding/geneticsABSTRACT
Liver cancer is one of the most common cancer types globally. However, the acquisition of drug resistance limits the effectiveness of chemotherapy and commonly results in metastasis. Therefore, an effective therapeutic approach to target chemoresistance-associated cellular molecules is imperative. Claudin-1 (CLDN1) has previously been reported to be associated with the development of drug resistance. The present study investigated the effect of CLDN1 on the sensitivity of 5-fluorouracil (5-FU)-resistant liver cancer cells. Firstly, a 5-FU-resistant HepG2 liver cancer cell line (Hep/5FU) was developed by continuous 5-FU treatment. MTT proliferation, Transwell and Matrigel assays indicated that Hep/5FU cells were significantly resistant to 5-FU, and demonstrated increased migration and invasion abilities, compared with parental HepG2 cells. Furthermore, reverse transcription-quantitative polymerase chain reaction and western blot analysis indicated that mRNA and protein expression levels of CLDN1 were significantly increased in Hep/5FU cells, compared with HepG2 cells. CLDN1 was knocked down by transfection with small interference RNA. MTT and Annexin V-fluorescein isothiocyanate/propidium iodide assays demonstrated that CLDN1 silencing significantly inhibits proliferation and enhances apoptosis induced by 5-FU treatment in Hep/5FU cells, compared with non-silenced Hep/5FU cells. Additionally, CLDN1 silencing attenuated the migration and invasion capabilities of Hep/5FU cells. In addition, it was identified that CLDN1 silencing decreased drug resistance by inhibiting autophagy, which was associated with a decrease in the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I and upregulation of P62. A cell proliferation assay revealed that the addition of autophagy inhibitor 3-methyladenine decreased drug resistance of Hep/5FU cells. By contrast, incubation with the autophagy agonist Rapamycin elevated drug resistance of CLDN1-silenced Hep/5FU cells. In summary, these data indicate that CLDN1 may be a potential target for resensitizing resistant liver cancer HepG2 cells to 5-FU by regulating cell autophagy.
ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of death by malignancy worldwide. HCC has a poor prognosis due to tumor invasiveness and metastasis. There is substantial evidence that the epithelial-to-mesenchymal transition (EMT) plays a central role in cancer metastasis. In a previous study, a possible association between integrator complex 8 (INTS8) and the progression and development of HCC was discovered. However, its role and the molecular mechanisms in HCC are poorly understood. METHODS: The PROGgeneV2 platform database and Kaplan-Meier plotter analysis were used to analyze the potential effects of INTS8 in HCC. Moreover, we performed migration, transwell, and metastasis assays to investigate the effects of INTS8 on HCC cells. In addition, relevant signaling pathways were examined by western blot and RT-qPCR assays. RESULTS: We used the PROGgeneV2 platform database and Kaplan-Meier plotter analysis, which indicated that increased expression of INTS8 is associated with poor overall survival of HCC. Moreover, INTS8 expression was higher in HCC tissues than in adjacent noncancerous tissues. INTS8 depletion reduced the invasion and migration of HCC cell lines. Downregulation of INTS8 in vivo resulted in fewer observed metastatic nodules in lungs. Moreover, INTS8 knockdown also increased the expression of epithelial markers (E-cadherin) and decreased the expression of mesenchymal markers (N-cadherin and vimentin) following the downregulation of SMAD4. In addition, pretreatment with TGF-ß1 could partly prevent the decrease in the expression of SMAD4 and EMT markers induced by INTS8 knockdown. CONCLUSION: Overall, these findings suggest that INTS8 accelerates the EMT in HCC by upregulating the TGF-ß signaling pathway.
ABSTRACT
INTRODUCTION: Comorbidity is common in elderly patients and it imposes heavy burden on both individual and the whole healthcare system. This study aims to gain insights of comorbidity development by simulating the lifetime trajectory of disease progression from single chronic disease to comorbidity. METHODS: Eight health states spanning from no chronic condition to comorbidity are considered in this study. Disease progression network is constructed based on the seven-year retrospective data of around 700,000 residents living in Singapore central region. Microsimulation is applied to simulate the process of aging and disease progression of a synthetic new-born cohort for the entire lifetime. RESULTS: Among the 40 unique trajectories observed from the simulation, the top 10 trajectories covers 60% of the cohort. Timespan of most trajectories from birth to death is 80â¯years. Most people progress to at risk at late 30â¯s, develop the first chronic condition at 50â¯s or 60â¯s, and then progress to complications at 70â¯s. It is also observed that the earlier one person develops chronic conditions, the more life-year-lost is incurred. DISCUSSION: The lifetime disease progression trajectory constructed for each person in the cohort describes how a person starts healthy, becomes at risk, then progresses to one or more chronic conditions, and finally deteriorates to various complications over the years. This study may help us have a better understanding of chronic disease progression and comorbidity development, hence add values to chronic disease prevention and management.
Subject(s)
Chronic Disease , Comorbidity , Disease Progression , Medical Informatics/methods , Adolescent , Adult , Aged , Aged, 80 and over , Body Mass Index , Child , Child, Preschool , Computer Simulation , Databases, Factual , Diabetes Complications/diagnosis , Diabetes Mellitus/diagnosis , Female , Humans , Hypertension/complications , Hypertension/diagnosis , Infant , Infant, Newborn , Male , Middle Aged , Overweight , Registries , Research Design , Retrospective Studies , Risk , Singapore/epidemiology , Young AdultABSTRACT
INTRODUCTION: With population health management being a priority in the Singapore, this paper aims to provide a data-driven perspective of the population health management initiatives to aid program planning and serves as a baseline for evaluation of future implemented programs. METHODS: A database with information on patient demographics, health services utilization, cost, diagnoses and chronic disease information from 2008 to 2013 for three regional health systems in Singapore was used for analysis. Patients with three or more inpatient admissions were considered as "Frequent Admitters." Health service utilization was quantified, and cross utilization of services was studied. One-year readmission rate for inpatients was studied, and a predictive model for readmission or death was developed. RESULTS: There were a total of 2.8 M patients in the database. Frequent admitters accounted for 0.9% of all patients with an average cost per patient of S$29 547. Of these, 89% had chronic diseases. Cross utilization of health services showed that 8.2% of the patients utilized services from more than one hospital with 19.6% utilizing hospital and polyclinic services in 2013. The highest risk of readmission or death was for those patients who had five or more inpatient episodes in each of the preceding 2 years. CONCLUSION: By understanding the profile of the patients and their utilization patterns in the three regional health systems, our study will help clinicians and decision makers design appropriate integrated care programs for patients with the aim of covering the healthcare needs for the enitre population across the healthcare spectrum in Singapore. Copyright © 2015 John Wiley & Sons, Ltd.
Subject(s)
Health Services/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Databases, Factual , Female , Health Services/economics , Humans , Male , Middle Aged , Patient Readmission , Singapore , Young AdultABSTRACT
Immunosuppressive agents used postoperatively after liver transplantation (LT) for hepatocellular carcinoma (HCC) favor recurrence and metastasis. Therefore, new effective immunosuppressants are needed. This retrospective study assessed combined sirolimus and metformin on survival of HCC patients after LT. In 2001-2013, 133 HCC patients with LT were divided into four groups: sirolimus and metformin combination (Sir+Met), sirolimus monotherapy (Sir), other immunosuppressants in diabetes mellitus (DM) patients without metformin (No Sir with DM), and other immunosuppressants in patients without DM (No Sir without DM). Kaplan-Meier and Log-rank tests were used to assess survival. Cell proliferation and tumor xenograft assays were performed to disclose the mechanisms underlying the sirolimus and metformin effects. The Sir+Met group showed significantly prolonged survival compared to the other groups. The most significant cytotoxicity was seen in the Sir+Met group, with significantly decreased levels of phosphorylated PI3K, AKT, AMPK, mTOR, 4EBP1 and S6K, compared with the other groups. In agreement, Sir+Met had the highest suppressive effect on tumor growth among all groups (P<0.01). In summary, Sir+Met treatment significantly prolonged survival, likely by suppressing cell proliferation. Therefore, this combination could represent a potential routine-regimen for patients post LT.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Hepatitis B/drug therapy , Liver Cirrhosis/drug therapy , Liver Neoplasms/drug therapy , Metformin/administration & dosage , Sirolimus/administration & dosage , Adult , Animals , Carcinoma, Hepatocellular/complications , Cell Line, Tumor , Cell Proliferation , Cell Survival , Drug Synergism , Female , Hep G2 Cells , Hepatitis B virus , Humans , Immunosuppressive Agents/therapeutic use , Liver Cirrhosis/complications , Liver Cirrhosis/virology , Liver Neoplasms/complications , Liver Transplantation , Male , Mice , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neoplasm Transplantation , Phosphorylation , Treatment OutcomeABSTRACT
Despite progress in the diagnostics and treatment of hepatocellular carcinoma (HCC), its prognosis remains poor. In this study, we globally assessed long noncoding RNAs (lncRNA) for contributions to HCC using publicly available microarray data, in vitro and in vivo assays. Here, we report that ZFAS1, encoding a lncRNA that is frequently amplified in HCC, is associated with intrahepatic and extrahepatic metastasis and poor prognosis of HCC. ZFAS1 functions as an oncogene in HCC progression by binding miR-150 and abrogating its tumor-suppressive function in this setting. miR-150 repressed HCC cell invasion by inhibiting ZEB1 and the matrix metalloproteinases MMP14 and MMP16. Conversely, ZFAS1 activated ZEB1, MMP14, and MMP16 expression, inhibiting these effects of miR-150. Our results establish a function for ZFAS1 in metastatic progression and suggest its candidacy as a new prognostic biomarker and target for clinical management of HCC.
Subject(s)
Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Animals , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/genetics , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Matrix Metalloproteinase 14/genetics , Matrix Metalloproteinase 16/genetics , Mice, Inbred BALB C , Prognosis , Transcription Factors/genetics , Xenograft Model Antitumor Assays , Zinc Finger E-box-Binding Homeobox 1ABSTRACT
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Despite progress in diagnostics and treatment of HCC, its prognosis remains poor because the molecular mechanisms underlying hepatocarcinogenesis are not well understood. In the study, we focused on identifying the role of miRNAs in HCC progression. miRNA microarray was used to analyze the differentially expressed miRNAs, and the results were validated by qPCR. We found that the miR-150-5p expression is down-regulated in HCC tissues compared with pair non-tumor tissues. miR-150-5p expression is also decreased in metastatic cancer tissues compared with pair primary tissues, indicating that miR-150-5p may be involved in HCC metastasis. Functionally, miR-150-5p inhibition significantly promotes hepatoma cell migration and invasion, whereas miR-150-5p overexpression suppresses cancer cell migration and invasion in vitro. The matrix metalloproteinase 14 (MMP14) is identified as a new target gene of miR-150-5p. miR-150-5p markedly inhibits MMP14 expression in hepatoma cells, and miR-150-5p expression is negative correlation with MMP14 expression in vivo. More important, re-expression of MMP14 in hepatoma cells partially reverses the effect of miR-150-5p in inhibiting cell invasion.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Cell Movement , Liver Neoplasms/metabolism , Matrix Metalloproteinase 14/biosynthesis , MicroRNAs/biosynthesis , Neoplasm Proteins/biosynthesis , RNA, Neoplasm/biosynthesis , Adult , Aged , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Matrix Metalloproteinase 14/genetics , MicroRNAs/genetics , Middle Aged , Neoplasm Invasiveness , Neoplasm Proteins/genetics , RNA, Neoplasm/geneticsABSTRACT
BACKGROUND: Cholangiocarcinoma (CCA) is becoming a common fatal hepatic tumor. Early detection of CCA is hampered by the absence of a sufficiently accurate and noninvasive diagnostic test. Proteomic analysis would be a powerful tool to identify potential biomarkers of this cancer. AIMS: This study aims to identify new protein markers that are specific for CCA using proteomic approaches and to evaluate the performance of S100 calcium-binding protein A9 (S100A9) and chaperonin-containing TCR1, subunit 3 (CCTγ) as diagnostic markers for screening test of CCA. METHODS: Two-dimensional differential gel electrophoresis (2-D DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were used to analyze and screen biomarker candidates in the proteomes of five human CCA samples and five healthy control samples. Subsequently, two potential biomarkers, S100A9 and CCTγ, were chosen for validation and analysis by immunohistochemical methods using CCA tissue microarrays. RESULTS: Twenty protein spots were significantly elevated and five protein spots were downregulated in all patients (p < 0.05). The positive rate was significantly higher in patients with CCA (48 ± 35%) compared with the normal liver control group (5 ± 10%, p < 0.001), the hepatocellular carcinoma group (15 ± 20%, p < 0.001), and the cirrhosis group (12 ± 16%, p < 0.001). A greater proportion of patients with CCA were positive for CCTγ (72 ± 18%) compared with the normal liver control group (43 ± 22%, p < 0.001), the hepatocellular carcinoma group (45 ± 20%, p < 0.001), and the cirrhosis group (39 ± 25%, p < 0.001). CONCLUSIONS: Combined comparative proteomic analysis using 2-D DIGE and MALDI-TOF is an effective method for identifying differentially expressed proteins in CCA tissues. The expression of S100A9 and CCTγ showed promise as novel diagnostic markers for CCA.
Subject(s)
Bile Duct Neoplasms/diagnosis , Bile Ducts, Intrahepatic , Biomarkers, Tumor/metabolism , Calgranulin B/metabolism , Chaperonin Containing TCP-1/metabolism , Cholangiocarcinoma/diagnosis , Proteomics , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/metabolism , Case-Control Studies , Cholangiocarcinoma/genetics , Cholangiocarcinoma/metabolism , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Humans , Liver/metabolism , Male , Middle Aged , Prospective Studies , ROC Curve , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tissue Array Analysis , Two-Dimensional Difference Gel Electrophoresis , Up-RegulationABSTRACT
Pancreatic cancer is characterized as a type of gastrointestinal tumor with a poor prognosis and high degree of malignancy. CIITA gene was found highly methylated in pancreatic carcinoma cell line PANC-1 and responsible for the low expression of major histocompatability complex II (MHC-II) that may lead to immune evasion. Here, we prepared pancreatic cancer vaccine with PANC-1 cells via epigenetic modification to enhance the MHC-II expression. Then the vaccine was injected into C57BL/6J mice and the effect was examined. Our study found that the vaccine could promote the proliferation of antigen-specific T cells, enhance the killing activity of cytotoxic T lymphocytes (CTLs), promote Th1-type cell-mediated secretion of cytokines IFN-γ and IL-2 while inhibiting Th2-type cell-mediated secretion of IL-4, and inhibit the secretion of TGF-ß. Generally, the epigenetically modified vaccine could enhance the body's antitumor immune response, providing feasibility research on cancer vaccine for therapy of pancreatic cancer.
Subject(s)
Cancer Vaccines/immunology , Epigenesis, Genetic , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/immunology , Animals , Antigens/immunology , Cancer Vaccines/administration & dosage , Cell Line, Tumor , Cell Proliferation , Coculture Techniques , Cytokines/biosynthesis , Cytotoxicity, Immunologic , DNA Methylation , Disease Models, Animal , Gene Expression Regulation, Neoplastic , Humans , Lymphocyte Activation/immunology , Mice , Nuclear Proteins/genetics , Pancreatic Neoplasms/therapy , T-Cell Antigen Receptor Specificity , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Trans-Activators/genetics , Xenograft Model Antitumor AssaysABSTRACT
Mycophenolate Mofetil (MMF) is widely used in preventing acute rejection in liver transplantation. Only free MPA (fMPA) can exert the pharmacological effect. In this study, we aimed to develop the new model which could be best fit to predict the fMPA area under the plasma concentration-time curve (AUC) by limited sampling strategy (LSS) in Chinese liver transplant patients. Fifty patients received MMF with the combination of tacrolimus. Free MPA concentrations were determined around day 7. Optimal subset regression analysis was used to establish the models for estimated fMPA AUC(0-12h). Three excellent better models were validated by Bootstrap analysis. Twenty-four models including four blood time point samplings were established. For the selected four models, 100% were successful and were not significantly different from the original dataset by Bootstrap analysis. The best model for prediction of fMPA AUC(0-12h) was by using C(1h), C(2h), C(4h) and C(6h). This model showed the minimal mean prediction error and the minimal mean absolute prediction error. In conclusion, the models for estimation of the fMPA AUC(0-12h) were established in liver transplant recipients and the best model for prediction of fMPA AUC was: estimated fMPA AUC=34.2+1.12C(1h)+1.29C(2h)+2.28C(4h)+3.95C(6h).
Subject(s)
Liver Transplantation , Mycophenolic Acid/pharmacokinetics , Area Under Curve , Drug Therapy, Combination/methods , Female , Graft Rejection/metabolism , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/pharmacokinetics , Male , Middle Aged , Mycophenolic Acid/blood , Tacrolimus/therapeutic useABSTRACT
PURPOSE: The intensive care unit (ICU) in a hospital caters for critically ill patients. The number of the ICU beds has a direct impact on many aspects of hospital performance. Lack of the ICU beds may cause ambulance diversion and surgery cancellation, while an excess of ICU beds may cause a waste of resources. This paper aims to develop a discrete event simulation (DES) model to help the healthcare service providers determine the proper ICU bed capacity which strikes the balance between service level and cost effectiveness. DESIGN/METHODOLOGY/APPROACH: The DES model is developed to reflect the complex patient flow of the ICU system. Actual operational data, including emergency arrivals, elective arrivals and length of stay, are directly fed into the DES model to capture the variations in the system. The DES model is validated by open box test and black box test. The validated model is used to test two what-if scenarios which the healthcare service providers are interested in: the proper number of the ICU beds in service to meet the target rejection rate and the extra ICU beds in service needed to meet the demand growth. FINDINGS: A 12-month period of actual operational data was collected from an ICU department with 13 ICU beds in service. Comparison between the simulation results and the actual situation shows that the DES model accurately captures the variations in the system, and the DES model is flexible to simulate various what-if scenarios. ORIGINALITY/VALUE: DES helps the healthcare service providers describe the current situation, and simulate the what-if scenarios for future planning.
Subject(s)
Hospital Bed Capacity/statistics & numerical data , Intensive Care Units/statistics & numerical data , Computer Simulation , Elective Surgical Procedures/statistics & numerical data , Emergency Service, Hospital/statistics & numerical data , Humans , Length of Stay/statistics & numerical data , Models, StatisticalABSTRACT
BACKGROUND: Our purpose was to assess the clinicopathological features and surgical outcomes of combined hepatocellular-cholangiocarcinoma (HCC-CC) in an Asian center. METHODS: Between 1998 and 2009, 27 patients were diagnosed with combined HCC-CC at our hospital. Their medical records were reviewed and clinicopathological data retrospectively analyzed. RESULTS: The 27 patients included 24 (88.9%) males and 3 (11.1%) females with a mean age of 58.26 ± 11.18 years. Cirrhosis was present in 10 patients (37.0%), and 12 patients had hepatitis C or hepatitis B virus infection. Serum alpha fetoprotein was >20 ng/ml in 7 of the 19 patients in whom it was measured (36.8%). Twenty-five patients underwent hepatic resections and 2 received liver transplantations. Five (18.5%) patients had separate HCC and CC within the same liver (type I), 21 (77.8%) had tumors with mixed components (type II), and 1 patient had a type III tumor (3.7%). Of 22 patients with immunohistochemical data, 19 (86.4%) were cytokeratin (CK) 7-positive, 20 (90.9%) were CK19-positive, and 4 (18.2%) were CK20-positive. Mean follow-up was 25.8 months. The 1- and 2-year survival rates were 72.5 and 49.4%, respectively. The 1- and 2-year disease-free survival rates were 54.2 and 41.3%, respectively. Symptoms at the time of diagnosis, and regional lymph node metastases, were associated with higher mortality and recurrence. CONCLUSIONS: Lymph node metastasis and positive resection margins are important factors affecting HCC-CC surgical outcomes.
Subject(s)
Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Neoplasms, Multiple Primary/pathology , Adult , Aged , Bile Duct Neoplasms , Bile Ducts, Intrahepatic , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Cholangiocarcinoma , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Keratins/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Lymphatic Metastasis , Male , Middle Aged , Neoplasms, Multiple Primary/metabolism , Neoplasms, Multiple Primary/mortality , Neoplasms, Multiple Primary/surgery , Prognosis , Retrospective StudiesABSTRACT
This paper is focused on the factors causing long patient waiting time/clinic overtime in outpatient clinics and how to mitigate them using discrete event simulation. A two-week period of data collection is conducted in an outpatient clinic of a Singapore government hospital. Detailed time study from patient arrival to patient departure is conducted, and the possible factors causing long patient waiting time/clinic overtime are discussed. A discrete simulation model is constructed to illustrate how to improve the clinic performance by mitigating the detected factors. Simulation and implementation results show that significant improvement is achieved if the factors are well addressed.
Subject(s)
Ambulatory Care Facilities/organization & administration , Computer Simulation , Outpatient Clinics, Hospital/organization & administration , Waiting Lists , Ambulatory Care Facilities/statistics & numerical data , Appointments and Schedules , Efficiency, Organizational , Humans , Outpatient Clinics, Hospital/statistics & numerical data , Personnel Staffing and Scheduling , Singapore , Time Factors , Workflow , WorkloadABSTRACT
Beds are one of the most important resources in a healthcare system. How to manage beds efficiently is an important indicator of the efficiency of the healthcare system. Bed management is challenging to many healthcare service providers in many aspects. In recent years, population growth and aging society impose extra pressure on bed requirement. There are usually two key performance indicators of a bed management system: bed occupancy rate and bed waiting time. In this paper, different discharge patterns and their impacts on the bed occupancy rate and bed waiting time are studied. A discrete event simulation model is constructed to evaluate the existing discharge pattern in a Singapore regional hospital using actual hospital admission and discharge transaction data. Then different discharge patterns are tested in the same context. Simulation results show that a proper discharge pattern significantly smoothes the fluctuation of bed occupancy rate and reduce the bed waiting time.
Subject(s)
Bed Occupancy , Models, Theoretical , Patient Admission , Patient Discharge , Computer Simulation , Hospitals , Humans , Singapore , Time FactorsABSTRACT
OBJECTIVE: To summarize the initial experience of simultaneous pancreas kidney transplantation (SPK) with portal venous and enteric drainage. METHODS: Between Jane 2001 and Jane 2003, SPK were performed in 5 patients. Systemic venous-enteric drainage (SED) was used in the first 2 patients and portal venous-enteric drainage (PED) in the last 3 cases. All patient were immunosuppressed with quadruple therapy, which included anti-CD25 mAb (Zenapax/Simulect) induction therapy, FK506, mycophenolate mofetil (MMF), and prednisone baseline therapy. The complications were analyzed. RESULTS: Serum glucose and renal function of the 5 cases were normal and no further insulin was needed within 7 days post-operation. No technique complications such as duodenal fistula and thrombosis were observed, One episode of acute rejection of kidney allograft occurred in one patient with SED, and resolved with a bolus corticosteroids. One case with SED and one with PED were died of sepsis and FK506 toxicity 4 weeks after transplantation. The death occurred with functioning pancreas graft. No latter complications were observed in the 3 survived patients with excellent graft functions. CONCLUSIONS: Both methods of SED and PED can be performed successfully and with no latter complications. But with its potential physiologic and immunologic advantages, PED might be a standard procedure for SPK.