Comparative effectiveness of first-line systemic treatments for metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.

OBJECTIVES: No head-to-head trials had been performed to estimate the relative effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) and androgen receptor signaling inhibitor (ARSi) in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). We aimed to perform a systematic review and network meta-analysis to evaluate the comparative effectiveness of various systemic treatment agents for patients with mCRPC. METHODS: A comprehensive literature search was conducted for abstracts and full-text articles from the database's inception through April 27, 2023. The study concentrated on assessing radiographic progression-free survival (rPFS) for both overall and homologous recombination repair mutation (HRRm) population, with overall survival (OS) as the secondary measure. Under the Bayesian framework, the overall effect was pooled using the fixed-effects model in base case analysis. Scenario analysis using restricted mean survival time (RMST) methods was performed to test the robustness of the results. RESULTS: Nine studies with 6,830 patients and 8 unique treatment options were included. Network meta-analysis demonstrated that talazoparib in combination with enzalutamide (TALA + ENZA; overall population, hazard ratio [HR], 0.20; 95% credible interval [CrI]: 0.16-0.26; RMST, 3.51; 95% confidence interval [CI] 2.46-4.60; HRRm population, HR, 0.15; 95% CrI: 0.09-0.23; RMST, 4.14; 95% CI 2.84-5.39) was superior to other treatments in the first-line setting in terms of rPFS. The results of Bayesian framework and RMST models showed consistent efficacy ranks. When extrapolated to overall survival benefit, within the Bayesian framework, olaparib plus abiraterone acetate and prednisone (OLAP + AAP) achieved the highest OS benefit for the overall population, which was not statistically significant when compared to TALA + ENZA. However, TALA + ENZA achieved the highest OS benefit at 3 years by applying RMST. CONCLUSIONS: We suggest that talazoparib in combination with enzalutamide is probably a preferred treatment agent for the overall population and HRRm patients with mCRPC. Given the limitations of network framework and the modeling assumptions undertaken to finalize the analyses, results should be cautiously interpreted.

Predictive Value of 5-Methoxytryptophan on Long-Term Clinical Outcome after PCI in Patients with Acute Myocardial Infarction-a Prospective Cohort Study.

BACKGROUND: In recent years, 5-Methoxytryptophan (5-MTP) has been identified as an endothelial factor with vaso-protective and anti-inflammatory properties. METHODS: In this prospective cohort study, a total of 407 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) successfully were enrolled. A 1-year follow-up Kaplan-Meier survival analysis was used for evaluating the correlation between 5-MTP and major adverse cardiovascular event (MACE) while Cox proportional-hazards regression was used to identify predictive values of 5-MTP on MACE after AMI. RESULTS: Increased 5-MTP level led to a significant downtrend in the incidence of MACE (All Log-rank p < 0.05). Thus, a high baseline 5-MTP could reduce the 1-year incidence of MACE (HR = 0.33, 95%Cl 0.17-0.64, p = 0.001) and heart failure (HF) (HR = 0.28, 95% Cl 0.13-0.62, p = 0.002). Subgroup analysis indicated the predictive value of 5-MTP was more significant in patients aged ≤ 65 years and those with higher baseline NT-proBNP, T2DM, STEMI, and baseline HF with preserved LVEF (HFpEF) characteristics. CONCLUSIONS: Plasma 5-MTP is an independent and protective early biomarker for 1-year MACE and HF events in patients with AMI, especially in younger patients and those with T2DM, STEMI, and baseline HFpEF characteristics.

Normobaric hyperoxia therapy in acute ischemic stroke: A literature review.

Background: Ischemic stroke is one of the most severe cerebrovascular diseases that leads to disability and death and seriously endangers health and quality of life. Insufficient oxygen supply is a critical factor leading to ischemic brain injury. However, effective therapies for ischemic stroke are lacking. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve prognosis after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBHO) has been shown to have neuroprotective effects during ischemic stroke and is considered an appropriate neuroprotective therapy for ischemic stroke. Evidence indicates that NBHO plays a neuroprotective role through different mechanisms in acute ischemic stroke. Recent studies have also reported that combinations with other drug therapies can enhance the efficacy of NBHO in ischemic stroke. Here, we aimed to provide a summary of the potential mechanisms underlying the use of NBHO in ischemic stroke and an overview of the benefits of NBHO in ischemic stroke. Methods: We screened 83 articles on PubMed and other websites. A quick review was conducted, including clinical trials, animal trials, and reviews of studies in the field of NBHO treatment published before July 1, 2023. The results were described and synthesized, and the bias risk and evidence quality of all included studies were assessed. Results: The results were divided into four categories: the mechanism of NBHO, animal and clinical trials of NBHO, the clinical application and prospects of NBHO, and adverse reactions of NBHO. Conclusion: NBHO is a simple, non-invasive therapy that may be delivered early after stroke onset, with promising potential for the treatment of acute ischemic stroke. However, the optimal therapeutic regimen remains uncertain. Further studies are needed to confirm its efficacy and safety.

Cost-Effectiveness Analysis of Risk Factor-Based Lung Cancer Screening Program by Low-Dose Computer Tomography in Current Smokers in China.

Although the effectiveness of lung cancer screening by low-dose computed tomography (LDCT) could be shown in China, there could be variation in the evidence concerning the economic impact. Our study explores the cost-effectiveness of lung cancer screening and optimizes the best definition of a high-risk population. A Markov model consisting of the natural history and post-diagnosis states was constructed to estimate the costs and quality-adjusted life years (QALYs) of LDCT screening compared with no screening. A total of 36 distinct risk factor-based screening strategies were assessed by incorporating starting ages of 40, 45, 50, 55, 60 and 65 years, stopping ages of 69, 74 and 79 years as well as smoking eligibility criteria. Screening data came from community-based mass screening with LDCT for lung cancer in Guangzhou. Compared with no screening, all screening scenarios led to incremental costs and QALYs. When the willingness-to-pay (WTP) threshold was USD37,653, three times the gross domestic product (GDP) per capita in China, six of nine strategies on the efficiency frontier may be cost-effective. Annual screening between 55 and 79 years of age for those who smoked more than 20 pack-years, which yielded an incremental cost-effectiveness ratio (ICER) of USD35,000.00 per QALY gained, was considered optimal. In sensitivity analyses, the result was stable in most cases. The trends of the results are roughly the same in scenario analyses. According to the WTP threshold of different regions, the optimal screening strategies were annual screening for those who smoked more than 20 pack-years, between 50 and 79 years of age in Zhejiang province, 55-79 years in Guangdong province and 65-74 years in Yunnan province. However, annual screening was unlikely to be cost-effective in Heilongjiang province under our modelling assumptions, indicating that tailored screening policies should be made regionally according to the local epidemiological and economic situation.

Lipidomic profile in patients with a very high risk of atherosclerotic cardiovascular disease on PCSK9 inhibitor therapy.

We evaluated the lipidomic profile of patients with very high-risk atherosclerotic cardiovascular disease (ASCVD) by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-MS). A total of 64 patients with a very high risk of ASCVD were recruited and randomLy divided into the atorvastatin group (20 mg, every night, 4 weeks) or the combined group (evolocumab, 140 mg, once every 2 weeks on top of atorvastatin (20 mg per day)). The level of serum lipids was detected before and after treatment for 4 weeks. The lipid classes of triacylglycerols, cholesteryl esters, and sphingomyelins were analyzed using an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry system. There were 32 patients in each group. After 4 weeks of treatment, the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in both groups and the level of lipoprotein-a (Lp-a) in the combined group were lower. In the combined treatment group, the levels of TC, LDL-C, and Lp-a decreased significantly (P < 0.05) after 4 weeks of treatment. Most of the lipid classes in plasma decreased in the combined group at 4 weeks, especially sphingolipids. Only 1 patient had an adverse event (a rash) in the combined group, which improved after anti-allergic treatment. PCSK9 inhibitors can rapidly and effectively reduce most lipid classes in patients with very-high-risk ASCVD.

Ultrasonic-assisted top-down preparation of NbSe2 micro/nanoparticles and hybrid material as solid lubricant for sliding electrical contact.

2H-NbSe2 single crystal flake (ca. 2 × 2 × 0.5 mm in size) by chemical vapor transport is employed as the precursor for a top-down preparation of NbSe2 micro/nanoparticles by two kinds of processes, i.e. (1) mechanical exfoliation; (2) ultrasonic-assisted exfoliation in ethanol without ageing and with ageing for 210 days. NbSe2 micro/nanoparticles are applied on top of a Cu disk by a drop-casting process and the tribological property in sliding against a Cu pin under sliding electrical contact is investigated at room temperature. Mechanical exfoliation produces NbSe2 microplatets with typical sizes of 1 µm to 30 µ m with a thickness less than 2 µm. Ultrasonic-assisted exfoliation without aging facilitates the formation of NbSe2 micro/nanoplatets with sizes of 0.1 µm to 25 µm and nano-whiskers with 100 nm in diameter and 1 ~ 3 µm in length, but Nb2O5 and Se are also found on the basis of XPS results. Prolonged aging of the suspensions modifies the morphology by converting platets and whiskers into corrugated floccules (hybrid material), which are composed of Nb2O5, Se, NbSe2, and graphene. Notably, NbSe2 micro/nanoparticles by ultrasonic-assisted exfoliation without ageing exhibit an excellent lubricating property with low friction coefficient (0.3), mild wear, and longer wear lifetime (120 min) than that of mechanical exfoliated NbSe2 microplatets (10 min). The wear lifetime for the aged NbSe2 micro/nanoparticles can be as long as 504 min and are 4.2 times of the sample without aging, which can be a good solid lubricant for sliding electrical contact.

Electrochemical analysis of trifluralin using a nanostructuring electrode with multi-walled carbon nanotubes.

The electroanalytical behaviors of the endocrine-disrupting chemical trifluralin have been studied at a nanostructuring electrode. The nanostructuring electrode was fabricated by coating a uniform multi-wall carbon nanotubes/dihexadecyl hydrogen phosphate (MWNTs/DHP) film on glassy carbon electrode (GCE). The reduction peak currents of trifluralin increased remarkably and the reduction peak potential shifted positively at the nanostructuring electrode, compared with that at a bare GCE. The results showed that this nanostructuring electrode exhibited excellent enhancement effects on the electrochemical reduction of trifluralin. Consequently, a simple and sensitive electroanalytical method was developed for the determination of trifluralin. Under optimal conditions, a linear response of trifluralin was obtained in the range from 5.0 x 10(-9) to 6.0 x 10(-6) mol L(-1) (r=0.998) and with a limit of detect (LOD) of 2.0 x 10(-9) mol L(-1). The proposed procedure was successfully applied to determine trifluralin in soil samples with satisfactory results.