Unlocking Synergistic Potential: Enhancing Regorafenib Efficacy in Hepatocellular Carcinoma Through Combination Therapy With 18ß-Glycyrrhetinic Acid.

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is a primary liver cancer with limited treatment options and poor prognosis. Regorafenib, a multi-kinase inhibitor, has shown promise in HCC treatment; however, its efficacy can be enhanced by combining it with other agents. 18ß-glycyrrhetinic acid (18ß-gly) is a natural compound with potential anti-cancer properties. MATERIALS AND METHODS: The toxicity and mechanism of regorafenib and 18ß-gly was assessed on Hep3B cells, Huh7 cells, and Hep3B bearing animal model. RESULTS: The combination of regorafenib and 18ß-gly exhibited synergistic toxicity in HCC cells and animal model. Importantly, no significant differences in body weight or major tissue damage were observed after treatment with the combination of two drugs. Furthermore, the combination treatment modulated apoptosis-related markers and the mTOR signaling pathway. CONCLUSION: The study provides evidence for the synergistic effect of 18ß-gly and regorafenib in a HCC model. The combination treatment modulated apoptosis-related markers and the mTOR signaling pathway, highlighting potential mechanisms underlying its therapeutic efficacy.

DNA damage and NF-κB inactivation implicate glycyrrhizic acid-induced G1 phase arrest in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most frequently occurring liver malignancy in Asia. Glycyrrhizic acid is known to reduce the risk of HCC formation in patients with chronic hepatitis C. To identify whether glycyrrhizic acid may play a role in anti-HCC therapy as an adjuvant is important. However, the inhibitory effect of glycyrrhizic acid on cell cycle progression in HCC cells and the mechanism of such have not been fully elucidated. This study used the comet assay, cell cycle analysis, immunofluorescence staining, the TUNEL assay, and Western blotting to identify the anti-HCC role of glycyrrhizic acid. Glycyrrhizic acid may induce DNA damage, apoptosis, activation of ATM, and expression of p21, and p27 in HCC cells. In addition, glycyrrhizic acid may also induce G1 phase arrest and suppress NF-κB-mediated Cyclin D1 expression. DNA damage and NF-κB inactivation may be associated with glycyrrhizic acid-induced G1 phase arrest in HCC cells.

Prognostic value of postoperative serum carcinoembryonic antigen levels in colorectal cancer patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) can increase serum carcinoembryonic antigen (CEA) levels. We thus aimed to evaluate the impact of CKD on CEA prognostic accuracy in colorectal cancer. METHODS: Altogether, 429 patients who underwent curative resection for stages I-III colorectal adenocarcinoma were grouped according to postoperative CEA levels and history of CKD. RESULTS: Three-year disease-free survival (DFS) was higher in patients with normal postoperative CEA (group A, 83.4%) than in those with elevated postoperative CEA (group B, 64.3%) (p < 0.001). CKD patients had higher postoperative CEA levels than non-CKD patients (odds ratio 3.27, 95% confidence interval 1.78-5.99, p < 0.001). In multivariable analysis, postoperative CEA level was an independent prognostic factor for DFS in non-CKD, but not CKD, patients. CONCLUSIONS: CKD can increase postoperative CEA levels in colorectal cancer patients. Elevated postoperative CEA levels were associated with shorter DFS in non-CKD, but not CKD, patients.

Postoperative serum carcinoembryonic antigen levels cannot predict survival in colorectal cancer patients with type II diabetes.

BACKGROUND: Most clinical guidelines recommend measuring postoperative carcinoembryonic antigen (CEA) levels to predict the prognosis of colorectal cancer. However, type II diabetes can increase serum CEA levels which may bias the prognosis. Thus, we aimed to evaluate the impact of type II diabetes on CEA prognostic accuracy in colorectal cancer. METHODS: This retrospective cohort study included 407 patients who underwent curative resection for stage I to III colorectal adenocarcinoma in a single institution between January 2010 and June 2018. The patients were categorized into two groups according to their postoperative serum CEA levels: group A <5.0 ng/mL (n = 341) and group B ≥5.0 ng/mL (n = 66). Patients were also categorized into two subgroups according to their history of type II diabetes: patients with type II diabetes mellitus (n = 112) and patients without type II diabetes (n = 295). RESULTS: The 3-year disease-free survival (DFS) rates were significantly higher in patients with normal postoperative CEA (group A, 83.8%) than in patients with elevated preoperative and postoperative CEA (group B, 63.6%) (p < 0.001). However, although patients with type II diabetes mellitus had higher postoperative CEA levels than those without type II diabetes mellitus (3.1 vs 2.5 ng/mL, p < 0.001), group B patients with type II diabetes mellitus had a significantly higher 3-year DFS rate than those without type II diabetes mellitus (80.0% vs 55.6%, p = 0.003). CONCLUSION: Type II diabetes was associated with higher preoperative and postoperative CEA levels in patients with colorectal cancer. Consequently, elevated postoperative CEA level was not associated with shorter 3-year DFS in patients with type II diabetes, as opposed to patients without type II diabetes. Therefore, colorectal cancer patients with type II diabetes may need alternative tumor markers to be used during the surveillance strategy after curative surgery.

Prognostic value of postoperative serum carcinoembryonic antigen levels in colorectal cancer patients who smoke.

Serum carcinoembryonic antigen (CEA) levels can help predict the prognosis of colorectal cancer patients. Accordingly, high preoperative CEA levels that is not restored after surgery are indicative of a worse outcome. On the other hand, smoking can increase serum CEA levels independently of the disease status. Thus, we aimed to evaluate the impact of smoking on the prognostic value of serum CEA levels. This retrospective cohort study included 273 patients who underwent curative resection for stage I-III colorectal adenocarcinoma at a single institution, between January 2010 and December 2017. Patients were grouped as follows: group A, normal preoperative and postoperative CEA levels (n = 152); group B, elevated preoperative CEA levels that returned to reference values after surgery (n = 69); and group C, elevated postoperative serum CEA levels (n = 52). Patients were also grouped according to their smoking history: group S (current smokers, n = 79) and group NS (never and former smokers, n = 194). Group A showed a higher 3-year disease-free survival (DFS) rate (84.9%) than groups B (75.4%) and C (62.0%) (p < 0.001). Postoperative serum CEA levels were significantly higher in the S group than in the NS group (2.6 vs. 3.1 ng/mL, p = 0.009), whereas preoperative levels were similar (3.8 vs. 4.1, p = 0.182). Further, smokers showed higher 3 year-DFS rates than nonsmokers in group C (83.3% vs. 43.9%, p = 0.029). This suggests that while elevated postoperative CEA levels are associated with lower DFS rates in never and former smokers, they are not associated with lower DFS rates in current smokers. We conclude that persistent smoking alters the prognostic value of postoperative serum CEA levels in colorectal cancer patients and that, consequently, alternative surveillance strategies need to be developed for colon cancer patients with smoking habits.

Induction of apoptosis through extrinsic/intrinsic pathways and suppression of ERK/NF-κB signalling participate in anti-glioblastoma of imipramine.

Glioblastomas are the most aggressive type of brain tumour, with poor prognosis even after standard treatment such as surgical resection, temozolomide and radiation therapy. The overexpression of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in glioblastomas is recognized as an important treatment target. Thus, an urgent need regarding glioblastomas is the development of a new, suitable agent that may show potential for the inhibition of extracellular signal-regulated kinase (ERK)/NF-κB-mediated glioblastoma progression. Imipramine, a tricyclic antidepressant, has anti-inflammatory actions against inflamed glial cells; additionally, imipramine can induce glioblastoma toxicity via the activation of autophagy. However, whether imipramine can suppress glioblastoma progression via the induction of apoptosis and blockage of ERK/NF-κB signalling remains unclear. The main purpose of this study was to investigate the effects of imipramine on apoptotic signalling and ERK/NF-κB-mediated glioblastoma progression by using cell proliferation (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide [MTT] assay), flow cytometry, Western blotting, and cell invasion/migration assay analysis in vitro. The ERK and NF-κB inhibitory capacity of imipramine is detected by NF-κB reporter gene assay and Western blotting. Additionally, a glioblastoma-bearing animal model was used to validate the therapeutic efficacy and general toxicity of imipramine. Our results demonstrated that imipramine successfully triggered apoptosis through extrinsic/intrinsic pathways and suppressed the invasion/migration ability of glioblastoma cells. Furthermore, imipramine effectively suppressed glioblastoma progression in vivo via the inhibition of the ERK/NF-κB pathway. In summary, imipramine is a potential anti-glioblastoma drug which induces apoptosis and has the capacity to inhibit ERK/NF-κB signalling.

The Impact of Hemodialysis on Terminal Cancer Patients in Hospices: A Nationwide Retrospective Study in Taiwan.

OBJECTIVE: Hemodialysis (HD) is the most common renal replacement therapy for patients with end-stage renal disease in Taiwan. The use of HD in hospice care and its impact on terminal cancer patients remains unclear. METHODS: Using claim data from the Taiwan National Health Insurance Research Database, all patients who died from cancer and claim data of their terminal admissions in hospice from 2007 to 2010. Those with a comorbid diagnosis of renal failure or who had health insurance claims data for HD were enrolled. RESULTS: A total of 5482 subjects were identified, of whom 4484 received HD and 998 did not. The HD group was significantly correlated with a younger age and high costs of terminal hospice admission. After adjusting for age and gender, the HD group was positively associated with a long hospice stay, in-hospice death, bone/connective tissue/breast cancers, and secondary/metastatic cancers, but negatively associated with genitourinary cancer. Compared with Department of Health/municipal hospitals, patients at both national and private university-affiliated hospitals were less likely to undergo HD. CONCLUSIONS: For terminal cancer patients under hospice care, HD was associated with a younger age, long terminal hospice stay, and high medical costs. Some types of cancers were associated with HD. University-affiliated hospitals played significant roles in non-HD renal supportive care. In-hospice HD is still common in Taiwan. Dialysis withdrawal and alternative care have space to promoting in hospice care.

Magnolol Induces Apoptosis and Inhibits ERK-modulated Metastatic Potential in Hepatocellular Carcinoma Cells.

BACKGROUND/AIM: The aim of the present study was to evaluate the anti-cancer effect of magnolol in hepatocellular carcinoma (HCC) cells in vitro. MATERIALS AND METHODS: HCC SK-Hep1 cells were treated with different concentrations of magnolol or PD98059 [extracellular-signal-regulated kinase (ERK) inhibitor] for 48 h, and then cell viability, apoptosis, signal transduction, expression of anti-apoptotic and metastasis-related proteins, and cell invasion were investigated by [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, flow cytometry, nuclear factor kappa B (NF-ĸB) reporter gene, western blotting, and cell invasion assays. RESULTS: Magnolol significantly induced accumulation of sub-G1 phase and caspase-3 activation and inhibited NF-ĸB activation, cell invasion, expression of phosphorylated ERK (pERK), anti-apoptotic and metastatic-related proteins. ERK inactivation was required for magnolol-induced inhibition of metastatic potential of SK-Hep1 cells. CONCLUSION: Taken together, these results indicated that magnolol not only induced apoptosis, but also inhibited ERK-modulated metastatic potential of HCC SK-Hep1 cells.

Reduction in the incidence of pneumonia in elderly patients after hip fracture surgery: An inpatient pulmonary rehabilitation program.

Hip fracture is an important health care issue in the elderly. Postoperative pulmonary complications occur in 4% of patients after hip fracture surgery. However, previous research is limited regarding pulmonary rehabilitation in this group. In this study, we present clinical evidence regarding the impact of a comprehensive pulmonary rehabilitation program in elderly hip fracture patients after hip surgery.We designed a nonrandomized, Quasi-experimental study, comparing 2 sequential time periods in the same center. Elderly patients (≥65 years) with a new hip fracture from February 1, 2014 to December 31, 2015 and who were willing to undergo a postoperative pulmonary rehabilitation program were enrolled. The pulmonary rehabilitation program started on January 1, 2015. Patients who refused rehabilitation or did not receive a surgical intervention were excluded. Patients received either standard care (standard care group) or standard care plus the postoperative rehabilitation program (intervention group).A total of 240 patients (163 women and 77 men) were enrolled, including 138 in the standard care group and 102 in the intervention group. The intervention group had a significantly lower incidence of pneumonia (6 patients, 5.9%) compared to the standard care group (19 patients, 13.9%). An age >80 years, cancer status, and not undergoing the postoperative pulmonary rehabilitation program were factors associated with a higher risk of pneumonia. In multivariate analysis, age >80 years, history of stroke/cancer, thrombocytopenia, and hyperglycemia (>200 mg/dL) were identified as risk factors for pneumonia.The incidence of pneumonia was lower in the elderly patients with hip fractures who received the postoperative pulmonary rehabilitation program after surgery. This is the first trial to demonstrate the effect of a postoperative pulmonary rehabilitation program in hip surgery patients.

CBX3/heterochromatin protein 1 gamma is significantly upregulated in patients with non-small cell lung cancer.

AIM: Lung cancer is typically categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC comprises of the majority of lung cancer with a poor prognosis in advanced cases. Transcriptional profiling studies, including microarrays and RNA-sequencing studies, have significantly enriched our knowledge of gene expression patterns in NSCLC. A recent transcriptional profiling study identified high prevalence of CBX3/HP1-gamma upregulation in human NSCLC samples. CBX3/HP1-gamma is an isoform of the heterochromatin protein 1 family, which plays a role in heterochromatin formation and is linked to cancer. METHODS: We examined lung cancer samples from our hospital using immunohistochemistry for CBX3/HP1-gamma staining. We also analyzed publicly available databases of NSCLC transcriptional profiling to validate our results. RESULTS: We identified a high prevalence (77.2%) of samples with positive CBX3/HP1-gamma staining by immunohistochemistry in NSCLC patient samples. Independently, we queried a publicly available dataset (GSE40419) containing RNA-seq data from 77 patients. Upregulation of CBX3/HP1-gamma in tumor samples was present in 60.2% of the patients. A similar correlation was also observed in the The Cancer Genome Atlas (TCGA) database. Interestingly, we discovered a highly significant association between positive CBX3/HP1-gamma staining and EGFR mutation in our patient samples (40 of 42 patients, P < 0.001). Treatment of EGFR mutant NSCLC cell lines with the EGFR inhibitor gefitinib failed to yield a change in CBX/HP1-gamma expression, suggesting that CBX/HP1-gamma expression may be independent of EGFR downstream signaling. CONCLUSION: We report a significant upregulation of CBX3/HP1-gamma in NSCLC patients, and also a possible relationship between CBX3/HP1-gamma expression and EGFR mutation.

Regorafenib Induces Apoptosis and Inhibits Metastatic Potential of Human Bladder Carcinoma Cells.

The aim of the present study was to verify the effects of regorafenib on apoptosis and metastatic potential in TSGH 8301 human bladder carcinoma cells in vitro. Cells were treated with different concentration of regorafenib for different periods of time. Effects of regorafenib on cell viability, apoptosis pathways, metastatic potential, and expression of metastatic and anti-apoptotic proteins were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, flow cytometry, cell migration and invasion assay, and western blotting. We found regorafenib significantly reduced cell viability, cell migration and invasion, and expression of metastatic and anti-apoptotic proteins. In addition, regorafenib significantly induced accumulation of sub-G1 phase cells, loss of mitochondrial membrane potential, and expression of active caspase-3 and caspase-8. These results show that regorafenib not only induces apoptosis, but also inhibits metastatic potential in bladder cancer TSGH 8301 cells in vitro.

Regorafenib diminishes the expression and secretion of angiogenesis and metastasis associated proteins and inhibits cell invasion via NF-κB inactivation in SK-Hep1 cells.

The aim of the present study was to investigate the effects of regorafenib on the nuclear factor κ-light-chain-enhancer of activated B cells (NF)-κB-modulated expression of angiogenesis- and metastasis-associated proteins and cell invasion in human hepatocellular carcinoma SK-Hep1 cells. The SK-Hep1 cells were treated with different concentrations of NF-κB inhibitor 4-N-[2-(4-phenoxyphenyl) ethyl] quinazoline-4,6-diamine (QNZ) or regorafenib for 24 or 48 h. The effects of QNZ and regorafenib on cell viability, NF-κB activation, expression and secretion levels of angiogenesis- and metastasis-associated proteins and cell invasion were evaluated with MTT assays, western blotting, ELISA, gelatin zymography and cell invasion assays. The results demonstrated that QNZ and regorafenib significantly reduced the expression and secretion levels of the angiogenesis- and metastasis-associated proteins vascular endothelial growth factor, tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, matrix metalloproteinase (MMP)-2 and MMP-9, NF-κB activation and cell invasion. In conclusion, the inhibition of NF-κB activation induces anti-angiogenic and antimetastatic effects in SK-Hep1 cells. Regorafenib reduces the level of expression and secretion of angiogenesis- and metastasis-associated proteins and cell invasion through the suppression of NF-κB activation in SK-Hep1 cells.

Implementation and outcomes of an antimicrobial stewardship program: Effectiveness of education.

BACKGROUND: Unnecessary use of antibiotics is a common occurrence in hospitals. Implementation of antibiotic stewardship programs (ASPs) has been shown to reduce both unnecessary antibiotic use and drug-resistant bacteria. Education is a fundamental component of an ASP. However, the effectiveness of proper uses of antibiotics education has not been clearly analyzed. METHODS: In a 520-bed university hospital located in northeastern Taiwan, a significantly increasing prescription of carbapenems, specifically imipenem and meropenem, was observed. An educational program highlighting the judicious use of carbapenems was started, beginning in October 2013. A multidisciplinary ASP was implemented starting in January 2014. The consumption of antibiotics, measured by defined daily dose per 1000 occupied bed-days, was compared among the pre-educational, posteducational, and post-ASP periods. RESULTS: Compared with the pre-educational period, there was a significant reduction in antibiotics consumption of 13% total inpatient antibiotics (p = 0.008), 29.8% carbapenems (p = 0.001), 34.9% imipenem and meropenem (p < 0.001), and 27% glycopeptides (p = 0.015), in the posteducational and post-ASP periods. The major reduction emerged during the posteducational period and was sustained after the ASP. The percentage of inpatients prescribed with antibiotics was significantly decreased (16.2%; p < 0.001). The rate of carbapenem-resistant Acinetobacter baumannii decreased from 70.8% to 29.6% within 7 months. CONCLUSION: A focused educational program is effective in controlling the prescription of specific antibiotic classes in the early phase of a multidisciplinary ASP.

Place of death for hospice-cared terminal patients with cancer: A nationwide retrospective study in Taiwan.

BACKGROUND: Hospice care has been part of the Taiwan health-care system for 20 years. Detailed information on the place of death for terminal cancer patients is lacking. Impending death discharge (IDD) is unique in Taiwan, and our study aims to compare IDD with in-hospice death among terminal cancer patients under hospice care. METHODS: This retrospective study used claims data of decedents of cancer from the National Health Insurance Research Database of Taiwan from 2007 to 2010. RESULTS: Of the 22,720 cancer decedents enrolled, 6316 had claims data marked with IDD and 16,404 with in-hospice death. Those with IDD were older; had a shorter hospice stay; and higher rates of gastrointestinal, peritoneal, and pulmonary cancers. The mean daily health-care expenditure was higher in those with IDD, however, the total expenditure of terminal hospice admission was lower than those dying in hospices. Patients who were treated at public hospitals had a higher rate of in-hospice death than those treated at private hospitals. Patients with IDD were positively correlated with increasing age and shorter hospice stay. Patients with IDD were positively correlated with private hospitals, especially religious corporation-based hospitals. Male sex, oropharyngeal cancer, bone/connective/breast cancers, and secondary/metastatic cancers were negatively correlated with IDD. CONCLUSION: Patients with IDD have characteristics distinct from those dying in hospices. Advanced age and short hospice stays were common in those with IDD, and in-depth investigations were needed. As a unique predying process in Taiwan, relevant health-care issues regarding IDD are warranted for further investigations.

Hyperforin Inhibits Cell Growth by Inducing Intrinsic and Extrinsic Apoptotic Pathways in Hepatocellular Carcinoma Cells.

The aim of the present study was to investigate the antitumor effect and mechanism of action of hyperforin in hepatocellular carcinoma (HCC) SK-Hep1 cells in vitro. Cells were treated with different concentrations of hyperforin for different periods of time. Effects of hyperforin on cell viability, apoptosis signaling, and expression of anti-apoptotic and proliferative proteins [cellular FLICE-like inhibitory protein (c-FLIP), X-linked inhibitor of apoptosis protein (XIAP), myeloid cell leukemia 1(MCL1), and cyclin-D1] were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and western blotting. Hyperforin significantly inhibited cell viability and expression of anti-apoptotic and proliferative proteins. We also found that hyperforin significantly induced accumulation of cells in sub-G1 phase, loss of mitochondrial membrane potential, and increased levels of active caspase-3, and caspase-8. Taken together, our findings indicate that hyperforin triggers inhibition of tumor cell growth by inducing intrinsic and extrinsic apoptotic pathways in HCC SK-Hep1 cells.

Video-assisted thoracoscopic surgical decortication in the elderly with thoracic empyema: Five years' experience.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) with decortication is a major treatment for thoracic empyema in the fibropurulent stage. Compared to open thoracotomy, VATS decortication has similar efficacy but fewer postoperative complications in the treatment of thoracic empyema. The role of VATS decortication in the elderly had rarely been investigated. METHODS: From January 2006 to August 2011, we retrospectively enrolled 33 patients older than 65 years diagnosed as thoracic empyema and treated with VATS decortication. We analyzed the outcomes of this geriatric population, including surgical effectiveness, postoperative morbidity, and mortality. RESULTS: A total of 33 patients with mean age of 73.6 ± 7.1 years received VATS decortication for their empyema. Twenty-one (63.6%) patients were male. Only one patient died of progressive sepsis, due to pulmonary infection 9 days after VATS decortication. The 30-day mortality was 3% after the surgery. The major etiology (87.9%) of thoracic empyema was pneumonia. The main causes of postoperation morbidity included respiratory failure requiring mechanical ventilation for >7 days (15.2%) and septic shock (15.2%), followed by persistent air leakage for >7 days (9.1%). Twenty-four (75%) of 32 patients had good re-expansion of the affected lung 3 months after VATS decortication. CONCLUSION: We concluded that VATS decortication in the treatment of thoracic empyema is effective in elderly patients. The major concerns of postoperative complications are respiratory failure and sepsis.

Curcumin alters gene expression-associated DNA damage, cell cycle, cell survival and cell migration and invasion in NCI-H460 human lung cancer cells in vitro.

Lung cancer is the most common cause of cancer mortality and new cases are on the increase worldwide. However, the treatment of lung cancer remains unsatisfactory. Curcumin has been shown to induce cell death in many human cancer cells, including human lung cancer cells. However, the effects of curcumin on genetic mechanisms associated with these actions remain unclear. Curcumin (2 µM) was added to NCI-H460 human lung cancer cells and the cells were incubated for 24 h. Total RNA was extracted from isolated cells for cDNA synthesis, labeling, microarray hybridization and flour­labeled cDNA hybridized on chip. Localized concentrations of fluorescent molecules were detected and quantified using Expression Console software (Affymetrix) with default RMA parameters. GeneGo software was used for the key genes involved and their possible interaction pathways. The results showed that ~170 genes were significantly upregulated and 577 genes were significantly downregulated in curcumin­treated cells. Specifically, the up­ and downregulated genes included CCNE2, associated with DNA damage; ID3, associated with cell survival and 146 genes with a >2- to 3-fold change including the TP53INP1 gene, associated with DNA damage; CDC6, CDCA5, TAKMIP2, CDK14, CDK5, CDCA76, CDC25A, CDC5L and SKP2, associated with cell cycle; the CARD6, ID1 and ID2 genes, associated with cell survival and the BRMS1L, associated with cell migration and invasion. Additionally, 59 downregulated genes exhibited a >4-fold change, including the DDIT3 gene, associated with DNA damage; while 97 genes had a >3- to 4-fold change including the DDIT4 gene, associated with DNA damage; the CCPG1 gene, associated with cell cycle and 321 genes with a >2- to 3-fold including the GADD45A and CGREF1 genes, associated with DNA damage; the CCPG1 gene, associated with cell cycle, the TNFRSF10B, GAS5, TSSC1 and TNFRSF11B gene, associated with cell survival and the ARHAP29 and CADM2 genes, associated with cell migration and invasion. In conclusion, gene alterations provide information regarding the cytotoxic mechanism of curcumin at the genetic level and provide additional biomarkers or targets for the treatment of human lung cancer.

Systemic sclerosis and the risk of tuberculosis.

OBJECTIVE: Pulmonary involvement is common in patients with systemic sclerosis (SSc), and this condition causes substantial morbidity and mortality. Disrupted immunity from the disease or associated medication may render such patients subject to tuberculosis (TB) infection. However, the relationship between SSc and TB has not yet been investigated. METHODS: Using the Taiwan National Health Insurance Research Database, 838 patients with SSc diagnosed in Taiwan during 2000-2006 were identified and followed for emergence of TB infection. Incidence rate ratios (IRR) of TB compared to 8380 randomly selected age-, sex-, and comorbidity-matched controls without SSc were calculated. The Cox proportional hazards model was used for multivariate adjustment to identify independent risk factors for TB infection. RESULTS: The risk of TB infection was higher in the SSc cohort than in controls (IRR 2.81, 95% CI 1.36-5.37; p = 0.004), particularly for pulmonary TB (IRR 2.53, 95% CI 1.08-5.30; p = 0.022). Other independent risk factors for TB infection in patients with SSc were age ≥ 60 years [hazard ratio (HR) 3.52, 95% CI 1.10-11.33; p = 0.035] and pulmonary hypertension (PH; HR 6.06, 95% CI 1.59-23.17; p = 0.008). Mortality did not differ for SSc patients with or without TB. CONCLUSION: In this nationwide study, the incidence of TB infection was significantly higher among patients with SSc than in controls without SSc. Special care should be taken in managing patients with SSc who are at high risk for TB, especially those aged ≥ 60 years or who also have PH.

Incidence and renal survival of ESRD in the young Taiwanese population.

BACKGROUND AND OBJECTIVES: ESRD in the young represents a heavy burden to patients, families, and health care systems. This nationwide retrospective study characterized the incidence of ESRD and analyzed diagnoses associated with renal survival in the young population in Taiwan. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Through use of Taiwan's National Health Insurance Research Database, the population of young patients (age<30 years, including children and young adults) with ESRD between January 1998 and December 2009 were enrolled. The medical claims were used to derive the date when the cause of ESRD was first determined. The medical data were reviewed and the renal survival time (time from first diagnosis of the cause to the start of ESRD) was calculated by experts, including clinical physicians and a large-database specialist. RESULTS: The incidence rate of ESRD in the young population was high compared with the worldwide rate at 21.1 per million person-years, whereas the incidence in the pediatric group was still similar to that in other countries at 10.3 per million person-years. A total of 2304 patients with new-onset ESRD and identified renal diseases during the study period were enrolled. All preschool-age patients (100%) began receiving peritoneal dialysis as their initial treatment for ESRD. The leading causes, which varied by sex and onset age, were glomerulonephropathy followed by hypertension for the young adult group and glomerulonephropathy followed by congenital anomalies of the kidney and urinary tract (CAKUT) for the pediatric group. Renal survival was cause-dependent. The median overall renal survival duration was 0.8 year (interquartile range [IQR], 0.7-3.5 years). CAKUT-related ESRD had the longest progression time (median renal survival, 16.0 years; IQR, 10.7-23.5 years); glomerulonephropathy progressed more rapidly into ESRD and had the shortest median renal survival of 0.5 year (IQR, 0.1-2.7 years). CONCLUSIONS: The incidence and causes of ESRD greatly differ between pediatric patients and young adults. Moreover, renal survival in the young population markedly varies depending on the cause of renal disease.

Investigations of the pediatric hospice care in Taiwan: 2005 to 2010.

BACKGROUND: The utilization of pediatric hospice care remains unclear in Taiwan. METHODS: Data were analyzed from the claims of hospice admissions in patients aged 18 years or younger using the National Health Insurance Research Database from 2005 to 2010. RESULTS: A total of 91 patients and 136 admissions were enrolled (male-female = 50:41; mean 11.6 years old). In all, 62 patients were admitted once, including 47 patients who died. All the patients had cancer, with brain cancer (40.7%) accounting the most . Among acute comorbidities, neurological complications (16.2%) were mostly accounted. Family physicians provided most (64.7%) of the hospice services. Hospice stay ≤3 days correlated positively with death in hospices (odds ratio = 2.922, 95% confidence interval = 1.268-6.730). CONCLUSIONS: Pediatric hospice care revealed characteristics different from adults. Underlying late referrals were prevalent. There is space to promote the utilization of hospices for terminally ill pediatric patients.