Efficacy and safety of drug-eluting stents in elderly patients: A meta-analysis of randomized trials

Background: Current guidelines recommend newer generation drug-eluting stents (DES) over bare-metal stents (BMS) in patients with ischemic heart disease. However, there is no age-specific recommendation in elderly patients.Methods: Meta-analysis was performed of 6 randomized studies enrolling 5,042 elderly patients who underwent percutaneous coronary intervention (PCI) with stent implantation (DES, n = 2,579; BMS, n = 2,463).Results: Combined data indicated a significant reduction in major adverse cardiovascular events (MACEs) with use of DES (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.44–0.71, p < 0.001). Moreover, use of DES was associated with a significantly lower incidence of myocardial infarction (OR 0.54, 95% CI 0.36–0.81, p = 0.003) and repeat revascularization (OR 0.44, 95% CI 0.31–0.62, p < 0.001), was compared to that with the use of BMS. Stent thrombosis and bleeding complication rates were not significantly different between groups. In a subgroup meta-analysis, short duration (1 or 6 months) dual antiplatelet therapy (DAPT) was associated with a significantly lower MACE rate (OR 0.49, 95% CI 0.34–0.80; p = 0.003) in elderly patients who underwent PCI with everolimuseluting stent implantation, compared with that using long duration DAPT.Conclusions: This meta-analysis provides clinically relevant evidence that DES rather than BMS should be selected for elderly patients

An Allosteric Inhibitor of KRas Identified Using a Barcoded Rapid Assay Microchip Platform

Protein catalyzed capture agents (PCCs) are synthetic antibody surrogates that can target a wide variety of biologically relevant proteins. As a step toward developing a high-throughput PCC pipeline, we report on the preparation of a barcoded rapid assay platform for the analysis of hits from PCC library screens. The platform is constructed by first surface patterning a micrometer scale barcode composed of orthogonal ssDNA strands onto a glass slide. The slide is then partitioned into microwells, each of which contains multiple copies of the full barcode. Biotinylated candidate PCCs from a click screen are assembled onto the barcode stripes using a complementary ssDNA-encoded cysteine-modified streptavidin library. This platform was employed to evaluate candidate PCC ligands identified from an epitope targeted in situ click screen against the two conserved allosteric switch regions of the Kirsten rat sarcoma (KRas) protein. A single microchip was utilized for the simultaneous evaluation of 15 PCC candidate fractions under more than a dozen different assay conditions. The platform also permitted more than a 10-fold savings in time and a more than 100-fold reduction in biological and chemical reagents relative to traditional multiwell plate assays. The best ligand was shown to exhibit an in vitro inhibition constant (IC_(50)) of ∼24 μM

An Allosteric Inhibitor of KRas Identified Using a Barcoded Rapid Assay Microchip Platform

Protein catalyzed capture agents (PCCs) are synthetic antibody surrogates that can target a wide variety of biologically relevant proteins. As a step toward developing a high-throughput PCC pipeline, we report on the preparation of a barcoded rapid assay platform for the analysis of hits from PCC library screens. The platform is constructed by first surface patterning a micrometer scale barcode composed of orthogonal ssDNA strands onto a glass slide. The slide is then partitioned into microwells, each of which contains multiple copies of the full barcode. Biotinylated candidate PCCs from a click screen are assembled onto the barcode stripes using a complementary ssDNA-encoded cysteine-modified streptavidin library. This platform was employed to evaluate candidate PCC ligands identified from an epitope targeted in situ click screen against the two conserved allosteric switch regions of the Kirsten rat sarcoma (KRas) protein. A single microchip was utilized for the simultaneous evaluation of 15 PCC candidate fractions under more than a dozen different assay conditions. The platform also permitted more than a 10-fold savings in time and a more than 100-fold reduction in biological and chemical reagents relative to traditional multiwell plate assays. The best ligand was shown to exhibit an in vitro inhibition constant (IC_(50)) of ∼24 μM

Inhibition of heme sequestration of histidine-rich protein 2 using multiple epitope-targeted peptides

Plasmodium falciparum is the most lethal species of malaria. In infected human red blood cells, P. falciparum digests hemoglobin as a nutrient source, liberating cytotoxic free heme in the process. Sequestration and subsequent conversion of this byproduct into hemozoin, an inert biocrystalline heme aggregate, plays a key role in parasite survival. Hemozoin has been a longstanding target of antimalarials such as chloroquine (CQ), which inhibit the biocrystallization of free heme. In this study, we explore heme‐binding interactions with histidine‐rich‐protein 2 (HRP2), a known malarial biomarker and purported player in free heme sequestration. HRP2 is notoriously challenging to target due to its highly repetitious sequence and irregular secondary structure. We started with three protein‐catalyzed capture agents (PCCs) developed against epitopes of HRP2, inclusive of heme‐binding motifs, and explored their ability to inhibit heme:HRP2 complex formation. Cocktails of the individual PCCs exhibit an inhibitory potency similar to CQ, while a covalently linked structure built from two separate PCCs provided considerably increased inhibition relative to CQ. Epitope‐targeted disruption of heme:HRP2 binding is a novel approach towards disrupting P. falciparum‐related hemozoin formation

Inhibition of heme sequestration of histidine-rich protein 2 using multiple epitope-targeted peptides

Plasmodium falciparum is the most lethal species of malaria. In infected human red blood cells, P. falciparum digests hemoglobin as a nutrient source, liberating cytotoxic free heme in the process. Sequestration and subsequent conversion of this byproduct into hemozoin, an inert biocrystalline heme aggregate, plays a key role in parasite survival. Hemozoin has been a longstanding target of antimalarials such as chloroquine (CQ), which inhibit the biocrystallization of free heme. In this study, we explore heme‐binding interactions with histidine‐rich‐protein 2 (HRP2), a known malarial biomarker and purported player in free heme sequestration. HRP2 is notoriously challenging to target due to its highly repetitious sequence and irregular secondary structure. We started with three protein‐catalyzed capture agents (PCCs) developed against epitopes of HRP2, inclusive of heme‐binding motifs, and explored their ability to inhibit heme:HRP2 complex formation. Cocktails of the individual PCCs exhibit an inhibitory potency similar to CQ, while a covalently linked structure built from two separate PCCs provided considerably increased inhibition relative to CQ. Epitope‐targeted disruption of heme:HRP2 binding is a novel approach towards disrupting P. falciparum‐related hemozoin formation

Association between Sarcopenia and Physical Function among Preoperative Lung Cancer Patients

We aimed to investigate the prevalence of sarcopenia using new diagnostic criteria and association of sarcopenia with cardiopulmonary function and physical activity (PA) in preoperative lung cancer patients. The data of 614 patients were obtained from the CATCH-LUNG cohort study. Patients were classified into three groups—normal (n = 520), pre-sarcopenia (n = 60, low skeletal muscle mass index only), and sarcopenia (n = 34, low SMI and strength). Cardiopulmonary function was measured using the 6-min walk test (6MWT), and PA was objectively measured using a wearable device. The adjusted odds ratio (aOR) for a <400-m distance in 6MWT was 3.52 (95% confidence interval (CI) 1.34–9.21) and 6.63 (95% CI 2.25–19.60) in the pre-sarcopenia and sarcopenia groups, respectively, compared to that in the normal group. The aOR (95% CI) for <5000 steps/day was 1.64 (0.65–4.16) and 4.20 (1.55–11.38) in the pre-sarcopenia and sarcopenia groups, respectively, compared to that in the normal group. In conclusion, the prevalence of pre-sarcopenia and sarcopenia was 9.8% and 5.5%, respectively, among preoperative lung cancer patients. Cardiopulmonary function and physical activity were significantly lower in the pre-sarcopenia and sarcopenia groups than in the normal group. Patients with sarcopenia had more robust findings, suggesting the importance of muscle strength and mass