This study aimed to test these hypotheses: cystathionine ␥-lyase (CSE) is expressed in a human artery, it generates hydrogen sulfide (H 2 S), and H 2 S relaxes a human artery. H 2 S is produced endogenously in rat arteries from cysteine by CSE. Endogenously produced H 2 S dilates rat resistance arteries. Although CSE is expressed in rat arteries, its presence in human blood vessels has not been described. In this study, we showed that both CSE mRNA, determined by reverse transcription-polymerase chain reaction, and CSE protein, determined by Western blotting, apparently occur in the human internal mammary artery (internal thoracic artery). Artery homogenates converted cysteine to H 2 S, and the H 2 S production was inhibited by DL-propargylglycine, an inhibitor of CSE. We also showed that H 2 S relaxes phenylephrine-precontracted human internal mammary artery at higher concentrations but produces contraction at low concentrations. The latter contractions are stronger in acetylcholine-prerelaxed arteries, suggesting inhibition of nitric oxide action. The relaxation is partially blocked by glibenclamide, an inhibitor of K ATP channels. The present results indicate that CSE protein is expressed in human arteries, that human arteries synthesize H 2 S, and that higher concentrations of H 2 S relax human arteries, in part by opening K ATP channels. Low concentrations of H 2 S contract the human internal mammary artery, possibly by reacting with nitric oxide to form an inactive nitrosothiol. The possibility that CSE, and the H 2 S it generates, together play a physiological role in regulating the diameter of arteries in humans, as has been demonstrated in rats, should be considered.
In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor prognosis, whereas EGFR and p53 mutations do not seem to have survival impact. Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the progression of NSCLC from early- to late-stage disease. WGA may be used to expand starting deoxyribonucleic acid from low-volume lung biopsies for further analysis of advanced-stage NSCLC.
Introduction: Singapore has the world’s second most efficient healthcare system
while costing less than 5% GDP. It remains unclear whether transcatheter aortic
valve implantation (TAVI) is cost-effective for treating intermediate-low risk severe
aortic stenosis (AS) patients in a highly efficient healthcare system. Materials and
Methods: A two-phase economic model combining decision tree and Markov model
was developed to assess the costs, effectiveness, and the incremental cost-effectiveness ratio (ICER) of transfemoral (TF) TAVI versus surgical aortic valve replacement (SAVR) in intermediate-low risk patients over an 8-year time horizon. Mortality and complications rates were based on PARTNER 2 trial cohort A and Singapore life table. Costs were mainly retrieved from Singapore National University Health System database. Health utility data were obtained from Singapore population
based on the EuroQol-5D (EQ-5D). A variety of sensitivity analyses were conducted.
Results: In base case scenario, the incremental effectiveness of TF-TAVI versus
SAVR was 0.19 QALYs. The ICER of TF-TAVI was S$33,833/QALY. When time
horizon was reduced to 5 years, the ICER was S$60,825/QALY; when event
rates from the propensity analysis was used, the ICER was S$21,732/QALY and
S$44,598/QALY over 8-year and 5-year time horizons, respectively. At a willingness
to pay threshold of S$73,167/QALY, TF-TAVI had a 98.19% probability of being
cost-effective after 100,000 simulations. The model was the most sensitive to the
costs of TF-TAVI procedure. Conclusion: TF-TAVI is a highly cost-effective option
compared to SAVR for intermediate-low risk severe AS patients from a Singapore
healthcare system perspective. Increased procedure experience, reduction in device
cost, and technology advance may have further increased the cost-effectiveness
of TF-TAVI per scenario analysis.
Keywords: Surgical aortic valve replacement, Quality of life, Transfemoral
TAVI, Reimbursement
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