Hypermethylation of TMEM240 predicts poor hormone therapy response and disease progression in breast cancer.

BACKGROUND: Approximately 25% of patients with early-stage breast cancer experience cancer progression throughout the disease course. Alterations in TMEM240 in breast cancer were identified and investigated to monitor treatment response and disease progression. METHODS: Circulating methylated TMEM240 in the plasma of breast cancer patients was used to monitor treatment response and disease progression. The Cancer Genome Atlas (TCGA) data in Western countries and Illumina methylation arrays in Taiwanese breast cancer patients were used to identify novel hypermethylated CpG sites and genes related to poor hormone therapy response. Quantitative methylation-specific PCR (QMSP), real-time reverse transcription PCR, and immunohistochemical analyses were performed to measure DNA methylation and mRNA and protein expression levels in 394 samples from Taiwanese and Korean breast cancer patients. TMEM240 gene manipulation, viability, migration assays, RNA-seq, and MetaCore were performed to determine its biological functions and relationship to hormone drug treatment response in breast cancer cells. RESULTS: Aberrant methylated TMEM240 was identified in breast cancer patients with poor hormone therapy response using genome-wide methylation analysis in the Taiwan and TCGA breast cancer cohorts. A cell model showed that TMEM240, which is localized to the cell membrane and cytoplasm, represses breast cancer cell proliferation and migration and regulates the expression levels of enzymes involved in estrone and estradiol metabolism. TMEM240 protein expression was observed in normal breast tissues but was not detected in 88.2% (67/76) of breast tumors and in 90.0% (9/10) of metastatic tumors from breast cancer patients. QMSP revealed that in 54.5% (55/101) of Taiwanese breast cancer patients, the methylation level of TMEM240 was at least twofold higher in tumor tissues than in matched normal breast tissues. Patients with hypermethylation of TMEM240 had poor 10-year overall survival (p = 0.003) and poor treatment response, especially hormone therapy response (p < 0.001). Circulating methylated TMEM240 dramatically and gradually decreased and then diminished in patients without disease progression, whereas it returned and its levels in plasma rose again in patients with disease progression. Prediction of disease progression based on circulating methylated TMEM240 was found to have 87.5% sensitivity, 93.1% specificity, and 90.2% accuracy. CONCLUSIONS: Hypermethylation of TMEM240 is a potential biomarker for treatment response and disease progression monitoring in breast cancer.

Multicenter Study of Device-Associated Infection Rates, Bacterial Resistance, Length of Stay, and Mortality in Intensive Care Units of 2 Cities of Vietnam: International Nosocomial Infection Control Consortium Findings.

OBJECTIVE: The aim of the study was to report the results of the International Nosocomial Infection Control Consortium (INICC) study conducted from May 2008 to March 2015. METHODS: A device-associated healthcare-acquired infection surveillance study in three adult intensive care units (ICUs) and 1 neonatal ICU from 4 hospitals in Vietnam using U.S. the Centers for Disease Control and Prevention's National Healthcare Safety Network (CDC/NHSN) definitions and criteria as well as INICC methods. RESULTS: We followed 1592 adult ICU patients for 12,580 bed-days and 845 neonatal ICU patients for 4907 bed-days. Central line-associated bloodstream infection (CLABSI) per 1000 central line-days rate was 9.8 in medical/surgical UCIs and 1.5 in the medical ICU. Ventilator-associated pneumonia (VAP) rate per 1000 mechanical ventilator-days was 13.4 in medical/surgical ICUs and 23.7 in the medical ICU. Catheter-associated urinary tract infection (CAUTI) rate per 1000 urinary catheter-days was 0.0 in medical/surgical ICUs and 5.3 in the medical ICU. While most device-associated healthcare-acquired infection rates were similar to INICC international rates (4.9 [CLABSI]; 16.5 [VAP]; 5.3 [CAUTI]), they were higher than CDC/NHSN rates (0.8 [CLABSI], 1.1 [VAP], and 1.3 [CAUTI]) for medical/surgical ICUs, with the exception of CAUTI rate for medical/surgical ICU and CLABSI rate for the medical ICU. Because of limited resources of our Vietnamese ICUs, cultures could not be taken as required by the CDC/NHSN criteria, and therefore, there was underreporting of CLABSI and CAUTI, influencing their rates. Most device utilization ratios and bacterial resistance percentages were higher than INICC and CDC/NHSN rates. CONCLUSIONS: Device-associated healthcare-acquired infection rates found in the ICUs of our study were higher than CDC/NHSN US rates, but similar to INICC international rates. It is necessary to build more capacity to conduct surveillance and prevention strategies.

Cost-effectiveness of a hand hygiene program on health care-associated infections in intensive care patients at a tertiary care hospital in Vietnam.

BACKGROUND: The cost-effectiveness of a hand hygiene (HH) program in low- and middle-income countries (LMICs) is largely unknown. We assessed the cost-effectiveness of a HH program in a large tertiary Vietnamese hospital. METHODS: This was a before and after study of a hand hygiene program where HH compliance, incidence of hospital-acquired infections (HAIs), and costs were analyzed.The HH program was implemented in 2 intensive care and 15 critical care units. The program included upgrading HH facilities, providing alcohol-based handrub at point of care, HH campaigns, and continuous HH education. RESULTS: The HH compliance rate increased from 25.7% to 57.5% (P < .001). The incidence of patients with HAI decreased from 31.7% to 20.3% (P < .001) after the intervention. The mean cost for patients with HAI was $1,908, which was 2.5 times higher than the costs for patients without an HAI. The mean attributable cost of an HAI was $1,131. The total cost of the HH program was $12,570, which equates to a per-patient cost of $6.5. The cost-effectiveness was estimated at -$1,074 or $1,074 saved per HAI prevented. The intervention remained cost savings under various scenarios with lower HAI rates. CONCLUSION: The HH program is an effective strategy in reducing the incidence of HAIs in intensive care units and is cost-effective in Vietnam. HH programs need to be encouraged across Vietnam and other LMICs.