Andreassencopeland1312
21 [95% CI, 1.02-1.44];
=0.03). The inferiority of PCI in 5-year composite outcome was significant in patients with CABG recommendation according to SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score II (adjusted hazard ratio 1.55 [95% CI, 1.14-2.09];
=0.005) but not evident in patients with PCI or PCI/CABG equipoise recommendation according to SYNTAX score II (adjusted hazard ratio 0.94 [95% CI, 0.75-1.17];
=0.56). A similar risk of 5-year composite outcomes was observed between CABG and PCI with residual SYNTAX score ≤8.
In this single-center retrospective study among patients with chronic total occlusion and multivessel disease, PCI was associated with higher risk of 5-year composite death, myocardial infarction, or stroke.
In this single-center retrospective study among patients with chronic total occlusion and multivessel disease, PCI was associated with higher risk of 5-year composite death, myocardial infarction, or stroke.
Coronary access (CA) after transcatheter aortic valve replacement (TAVR) with supra-annular transcatheter heart valves (THV) can be challenging. Specific Evolut R/Pro and Acurate Neo THVs orientations are associated with reduced neo-commissure overlap with coronary ostia, while SAPIEN 3 THV cannot be oriented. With the ALIGN-ACCESS study (TAVR With Commissural Alignment Followed by Coronary Access), we investigated the impact of commissural alignment on the feasibility of CA after TAVR.
We performed coronary angiography after TAVR with intra-annular SAPIEN 3, supra-annular Evolut R/Pro, and Acurate Neo THVs in 206 patients. Evolut THVs were implanted aiming for commissure alignment. SAR7334 mw Alignment of Acurate Neo was retrospectively assessed in 36, intentionally attempted in 26 cases. The primary end point was the rate of unfeasible and nonselective CA after TAVR.
Thirty-eight percent of patients received SAPIEN 3, 31.1% Evolut Pro/R, 30.1% Acurate Neo THV. Final valve orientation was favorable to commissural impaired CA after TAVR.
Commissural alignment improves the rate of selective CA after TAVR with supra-annular THVs. Nevertheless, aligned supra-annular THVs carry higher risk of unfeasible/nonselective CA than SAPIEN 3. Patients with a misaligned supra-annular THV, low sinus of Valsalva, and higher THV-sinus of Valsalva relation are at highest risk of impaired CA after TAVR.Background Epidermal growth factor receptor-tyrosine kinase (EGFR-TK) is a well-known hallmark of oral and oropharyngeal cancers, as its overexpression leads to poor prognosis and malignancy. The activating EGFR mutations (particularly T790M and L858R double mutant) are a major challenge causing drug resistance, especially in the treatment of oral cancers. Methodology This paper is an effort to exploit both structure-based and ligand-based pharmacophore modeling to discover EGFR-TK inhibitors, which show inhibition of proliferation of erlotinib-resistant FaDu and Cal27 oral cancer cells. Interestingly, the hit compound H2 also showed an effect on the downstream glucose and lactate metabolism pathways. Conclusion The results indicate the potential of H2 to be developed as an EGFR-based metabolic inhibitor for oral cancer treatment.
Adagrasib (MRTX849) is an oral, highly selective, small-molecule, covalent inhibitor of KRAS
. We report results from a phase I/IB study of adagrasib in non-small-cell lung cancer, colorectal cancer, and other solid tumors harboring the
mutation.
Patients with advanced
-mutant solid tumors were treated with adagrasib 150 mg orally once daily, 300 mg once daily, 600 mg once daily, 1,200 mg once daily, or 600 mg orally twice a day using an accelerated titration design, which transitioned to a modified toxicity probability interval design when a predefined degree of toxicity was observed or target adagrasib exposure was achieved. Safety, pharmacokinetics, and clinical activity were evaluated.
Twenty-five patients were enrolled and received at least one dose of adagrasib. The recommended phase II dose (RP2D) was 600 mg twice a day on the basis of safety, tolerability, and observed pharmacokinetics properties. No maximum tolerated dose was formally defined. After a median follow-up of 19.6 months, tion.
Calcium (Ca
) is a key regulator of energy metabolism. Impaired Ca
homeostasis damages mitochondria, causing cardiomyocyte death, pathological hypertrophy, and heart failure. This study investigates the regulation and the role of the mitochondrial Ca
uniporter (MCU) in chronic stress-induced pathological cardiac remodeling.
MCU knockout or transgenic mice were infused with isoproterenol (ISO; 10 mg/kg per day, 4 weeks). Cardiac hypertrophy and remodeling were evaluated by echocardiography and histology. Primary cultured rodent adult cardiomyocytes were treated with ISO (1 nmol/L, 48 hours). Intracellular Ca
handling and cell death pathways were monitored. Adenovirus-mediated gene manipulations were used in vitro.
Chronic administration of the β-adrenergic receptor agonist ISO increased the levels of the MCU and the MCU complex in cardiac mitochondria, raising mitochondrial Ca
concentrations, in vivo and in vitro. ISO also upregulated MCU without affecting its regulatory proteins in adult cardiouced pathological cardiac remodeling by preserving Ca
homeostasis and cardiomyocyte viability.
The β-adrenergic receptor/CaMKIIδB/CREB pathway upregulates Mcu gene expression in the heart. MCU upregulation is a compensatory mechanism that counteracts stress-induced pathological cardiac remodeling by preserving Ca2+ homeostasis and cardiomyocyte viability.
Communities with lower socioeconomic status and higher prevalence of racial/ethnic minority populations are often more exposed to environmental pollutants. Although studies have shown associations between aircraft noise and property values and various health outcomes, little is known about how aircraft noise exposures are sociodemographically patterned.
Our aim was to describe characteristics of populations exposed to aviation noise by race/ethnicity, education, and income in the United States.
Aircraft noise contours characterized as day-night average sound level (DNL) were developed for 90 U.S. airports in 2010 for DNL
≥
45
dB
(
A
)
in 1-dB(A) increments. We compared characteristics of exposed U.S. Census block groups at three thresholds (
≥
45
,
≥
55
, and
≥
65
dB
(
A
65
dB
(
A
)
compared with block groups exposed to
<
45
dB
(
A
)
. Block groups with higher proportions of residents with only a high school education had higher odds of being exposed to aircraft noise. Results were robust across multiple regression approaches; however, there was substantial heterogeneity across airports.
These results suggest that across U.S. airports, there is indication of sociodemographic disparities in noise exposures. https//doi.org/10.1289/EHP9307.
These results suggest that across U.S. airports, there is indication of sociodemographic disparities in noise exposures. https//doi.org/10.1289/EHP9307.
Diverse toxicants and mixtures that affect hormone responsive cells [endocrine disrupting chemicals (EDCs)] are highly pervasive in the environment and are directly linked to human disease. They often target the nuclear receptor family of transcription factors modulating their levels and activity. Many high-throughput assays have been developed to query such toxicants; however, single-cell analysis of EDC effects on endogenous receptors has been missing, in part due to the lack of quality control metrics to reproducibly measure cell-to-cell variability in responses.
We began by developing single-cell imaging and informatic workflows to query whether the single cell distribution of the estrogen
receptor-
α
(ER), used as a model system, can be used to measure effects of EDCs in a sensitive and reproducible manner.
We used high-throughput microscopy, coupled with image analytics to measure changes in single cell ER nuclear levels on treatment with
∼
nd the changes upon chemical challenges were remarkably stable features; and importantly, these features could be used for quality control and identification of endocrine disruptor toxicants with high sensitivity. When coupled with orthogonal assays, ER single cell distribution is a valuable resource for high-throughput screening of environmental toxicants. https//doi.org/10.1289/EHP9297.
Features of the urban physical environment may be linked to the development of high blood pressure, a leading risk factor for global burden of disease.
We examined associations of urban physical environment features with hypertension and blood pressure measures in adults across 230 Latin American cities.
In this cross-sectional study we used health, social, and built environment data from the SALud URBana en América Latina (SALURBAL) project. The individual-level outcomes were hypertension and levels of systolic and diastolic blood pressure. The exposures were city and subcity built environment features, mass transit infrastructure, and green space. Odds ratios (ORs) and mean differences and 95% confidence intervals (CIs) were estimated using multilevel logistic and linear regression models, with single- and multiple-exposure models adjusted for individual-level age, sex, education, and subcity educational attainment.
A total of 109,176 participants from 230 cities and eight countries were included ingrowing urban areas of Latin America may require attention to integrated management of urban design and transport planning. https//doi.org/10.1289/EHP7870.
Financial hardship is a growing concern for patients with cancer. Patients with head and neck cancer (HNC) are particularly vulnerable, given that a third leave the workforce following treatment. The goal of our study was to characterize financial hardship in the psychologic response (response to increased expenses) and coping behaviors (behaviors patients adopt to manage their care in the setting of increased expenses) domains in patients with HNC compared with patients with other cancers.
This was a retrospective cohort study of nationally representative public survey data from 2013 to 2018 in the National Health Interviews Survey, an annual cross-sectional household survey. We included respondents age ≥ 18 years who reported a diagnosis of cancer and identified a subset of patients with HNC. Our main outcomes were financial hardship in the psychologic response and coping behaviors domains.
Our sample included a weighted population of 357,052 patients with HNC and 21.4 million patients with other cancs, who are more often to have financial hardship. Patients with HNC have greater levels of hardship in the coping behaviors domain compared with patients with other cancers, but similar levels in the psychologic response domain.
