Molecular mechanisms of phytoconstituents from selected Egyptian plants against non-small cell lung cancer using integrated in vitro network pharmacology and molecular docking approach

Non-small cell lung cancer (NSCLC) is a widespread highly malignant type of lung cancer. Conventional chemotherapeutic drugs may be accompanied by both drug resistance and serious side effects in patients. Therefore, safer and more effective medications are urgently needed for the treatment of NSCLC. This study investigates the mode of action of 21 phytoconstituents previously isolated from the Amaryllidaceous plants Crinum bulbispermum (Burm.f.), Pancratium maritimum L., and Hippeastrum vittatum Herbert alongside the Asteraceous plant Centaurea scoparia Sieb. for therapy of NSCLC via in vitro cytotoxic, network pharmacology, and molecular docking analyses. Despite the in vitro and in vivo cytotoxic studies carried out on phytoconstituents from these plants in treating numerous cancer types, scarce information documenting their cytotoxic activity towards NSCLC cells is available. First, the compounds were tested for their in vitro cytotoxic activities and selectivity on human non-small cell lung cancer cells using disk diffusion assay. Compounds having significant potencies were promoted for network pharmacology analysis. Pharm mapper, Genecards, STRING, and KEGG databases were utilized for surfing target genes and pathways for these compounds, while for construction of compound-target-pathway (C-T-P) network, Cytoscape 3.7.1. freeware was used. Molecular docking and dynamics simulation were run for the top hit constituents against the most enriched molecular targets followed by in silico ADMET studies using Schrodinger(®) suite and Gromacs. In vitro cytotoxicity testing demonstrated that crinamine was the most potent compound followed by lycorine, hemanthidine, and haemanthamine. The network pharmacology approach revealed the enrichment of acetyllycoramine, pluviine, 5-hydroxy-7-methoxy-2-methylchromone, and ismine. Whereas, androgen receptor (AR), epidermal growth factor receptor (EGFR), and estrogen-sensitive receptor alpha (ESR1) were the most enriched target genes. Pathway analysis revealed that central carbon metabolism, EGFR tyrosine kinase inhibitor endocrine resistance, and non-small cell lung cancer were the most enriched cancer-related pathways. Ismine possessed the most stable ligand-protein interactions when docked to the three proteins, with MD simulations further confirming its strong and consistent binding to AR, moderate stability with ESR-1, and lower stability with EGFR over the 100 ns trajectory. ADMET study conducted on the above compounds confirmed their excellent drug-likeness properties, oral bioavailability, and safety profiles highlighting the need for some structural modifications to pluviine to enhance its oral bioavailability. These integrated approaches showed that some constituents from the investigated plants interact synergistically against non-small cell lung cancer-related genes and pathways

Outpatient chemotherapy drug costs and expensive chemotherapy drug use in 340B and Non-340B hospitals: an observational study

BACKGROUND: The 340B Drug Pricing Program has been controversial since its inception in 1992, a major criticism being that 340B hospitals use more outpatient drugs, and more expensive drugs, because of financial incentives to make money through the program. The goal of this study was to determine whether characteristics of patients treated at 340B hospitals, and affiliation of hospitals with NCI-designated cancer centers, would explain higher Part B drug costs and use of more expensive chemotherapy drugs. METHODS: This is an observational study using data from SEER-Medicare and 340B entity database. Fee-for-service Medicare beneficiaries who were first diagnosed with cancer between 1/1/2013 and 12/31/2015 were included. Hospital, patient, and cancer/clinical characteristics were used as predictors of both overall Part B drug costs and use of expensive chemotherapy drugs. Patient characteristics and cancer conditions were compared between those who were treated at 340B and non-340B hospitals, and between those who used and who did not use any expensive chemotherapy treatment. Independent relationships between overall Part B drug costs and patients\u27 340B status, and between patients\u27 use of expensive chemotherapy drug and patients\u27 340B status were evaluated in multivariate analyses, using a stepwise generalized estimating equation modeling approach. RESULTS: We found that patients at 340B hospitals had a somewhat higher chance of using one of the ten expensive chemotherapy drugs, and somewhat higher overall drug costs, but these relationships became non-significant when patient, cancer/clinical factors, and cancer center status were considered. Compared to the reference patients, patients who were treated in an NCI-designated cancer center or a hospital affiliated with such center, who had certain types of cancers (e.g., B-cell), or had advanced-stage disease had a higher chance to use expensive chemotherapy treatment; patients who were older, survived the first 12 months upon diagnosis, had advanced-stage disease, or had more drug claims had higher drug costs. CONCLUSIONS: Hospital 340B status was not significantly associated with use of more expensive cancer drugs or drug costs once other relevant factors (e.g., cancer center status, advanced-stage disease) were taken into account

Transforming Transplantation Access: A Federal Directive for Comprehensive Pre-Waitlisting Data Collection

There is substantial variation in access to transplantation across the United States that is not entirely explained by the availability of donor organs. Barriers to transplantation and variation in care among patients with end-stage organ disease exist prior to patients\u27 placement on a transplant waiting list as well as following waitlist placement. However, there are currently no national data available to examine rates and variations in key care processes related to pre-listing, including transplant referral, evaluation, or candidate selection. In February of 2024, the Health Resources and Services Administration (HRSA) released a directive and, in November 2024, released for public comment the proposed expansion of the Organ Procurement and Transplantation Network (OPTN) data collection to include pre-waitlist data for all solid organ transplant patients to promote transparency across the transplant continuum. While data elements and details have not been finalized, the purpose of this article is to detail the rationale and anticipated details for pre-waitlisting data collection to inform the transplant community. These data aim to examine care processes and barriers to care for patients with end-stage organ disease in the United States

Surgical options for advanced renal cell carcinoma

Detection of advanced renal cell carcinoma (RCC) is not uncommon, although there has been a stage migration due to frequent use of abdominal imaging allowing early detection of renal masses. Since open IVC thrombectomy was introduced in 1972, minimally invasive approaches such as laparoscopic approach, hand-assisted approach and robotic approach have been adopted. While robotic surgery has potential benefits to improve perioperative outcomes, and our experience with robotic surgery has grown significantly over the last decade, open surgery at an academic center remains the standard of care in this setting. In the setting of metastatic RCC, cytoreductive nephrectomies have been discussed for many years but their indications are unclearly defined, although cytoreductive nephrectomy can be considered in patients with disease largely limited to the kidney or on-going or impending symptomatic disease. Significant advances have been made in systematic therapy for RCC which will eventually lead to the evolution of neoadjuvant and adjuvant therapy in patients with advanced RCC. The surgical management of advanced RCC is a major and complex undertaking but has shown to be feasible and effective

Barriers to orthodox medical care of prostate cancer in Ghana

Traditional medicine is widely used in sub-Saharan Africa, particularly in Ghana, where it is commonly integrated with modern orthodox medicine. This study examines the barriers that delay the pursuit of orthodox medical care for prostate cancer (PCa) in Ghana\u27s Central region, where a blend of traditional and modern orthodox medicine exists. The preference for indigenous traditional medicine often results in late-stage presentations of PCa, adversely affecting patient outcomes. This prospective cross-sectional study was conducted from July to December 2022 at the Cape Coast Teaching Hospital (CCTH) and in four local communities. We investigated why men prefer traditional over orthodox medicine and identified cultural beliefs, attitudes, and gaps in health awareness that contribute to delays in diagnosing and treating PCa. The study involved administering questionnaires, providing education on PCa, and conducting free prostate-specific antigen (PSA) screening. Ethical approval was obtained from the Ethics Research Committee of the Ghana Health Service. A total of 282 patients participated, including 268 men from the communities and 14 diagnosed with PCa at CCTH after initially consulting traditional healers. Of the community-recruited patients who underwent PSA testing, 26% had elevated PSA levels and underwent further diagnostic procedures. Ultimately, nine of 268 community patients were confirmed to have PCa. Most patients (57.4%) had limited education, which correlated with late presentations and various misconceptions about PCa. The study highlights significant cultural and economic barriers that lead to the late-stage presentation of PCa among men in Ghana\u27s Central region. There is a critical need for a culturally sensitive, multi-pronged strategy that enhances public education about the benefits of early diagnosis and fosters collaboration between traditional healers and orthodox healthcare providers to improve prostate cancer outcomes in Ghana

Development and Implementation of Oral Anticancer Agent Tools for a Thematic Quality Improvement Program: A Collaboration Between Hematology Oncology Pharmacist Association and ASCO Quality Training Program

PURPOSE: The Hematology Oncology Pharmacist Association Oral Chemotherapy Collaborative (HOPA OCC) developed practice-based tools to use in program development and improvement for the management of patients receiving oral anticancer agents (OAAs). METHODS: These tools include a baseline OAA program assessment, clinical OAA adherence tool, and OAA dashboard. HOPA OCC distributed these tools to teams participating in the 6-month HOPA ASCO Quality Training Programs (QTPs). Barriers in the delivery of OAA services across practice sites were determined through the use of baseline assessments, and the following domains were evaluated: (1) side-effect monitoring, (2) adherence monitoring, (3) use of patient-reported outcomes, (4) social determinants of health, and (5) collaborative practice agreements for oncology pharmacists. The OAA adherence tool offers clinical patient adherence questions and guidance for supporting adherence in practice. Finally, the dashboard includes multiple metrics that may be helpful for practices to measure their program outcomes. HOPA OCC used the Consolidated Framework for Implementation Research to assess tool usefulness by the QTP participants. RESULTS: Barriers to implementation include deficits in information technology, resources, and competing priorities. CONCLUSION: Standardized OAA tools can inform and support quality improvement initiatives and improve the care of patients receiving OAAs

Impact of Subsequent Fellowship on Urology Chief Resident Case Log Volumes

OBJECTIVE: To characterize the impact of subsequent fellowship on the case log experience of trainees throughout their residency and specifically their chief resident year. MATERIALS AND METHODS: Urology resident case logs from 2010 to 2022 were obtained from 13 institutions for total residency and chief years. Five categorized index procedures were included for analysis: General Urology; Endourology; Reconstructive Urology; Urologic Oncology; and Pediatric Urology. Subsequent fellowship data (yes/no and type) were available for 338. Regression models analyzed the interactions of case log volumes and subsequent fellowship. RESULTS: Of the 338 residents, 141 (42%) went onto practice and 197 (58%) completed a fellowship including 53 in oncology, 44 in reconstruction, 43 in endourology, 29 in pediatric, and 28 in another nonindexed domain. A total of 419,353 cases were logged during training, including 125,319 (30%) during the chief resident year. The median number of total cases completed per resident increased irrespective of subsequent fellowship. Conversely, the median number of total cases completed during chief year declined with the slope of decline being significant in those residents not completing a fellowship [slope = -2.44, CI: (-4.66, -0.23), p-value = 0.031]. Temporal trends demonstrated that absence of subsequent fellowship was associated with decrease in chief resident cases across all index domains (p for all \u3c 0.001). The specific type of fellowship, however, had no association with chief year trends. CONCLUSIONS: The median number of chief resident cases has declined, most significantly in those trainees not pursuing a fellowship, possibly reflecting a focus on urology encounters which are not captured in ACGME logs

Relationship between Neighborhood-Level Social Risk Factor Measures and Presenting Glaucoma Severity Utilizing Multilevel Modeling

PURPOSE: The neighborhood and built environment social determinant of health domain has several social risk factors (SRFs) that are modifiable through policy efforts. We investigated the impact of neighborhood-level SRFs on presenting glaucoma severity at a tertiary eye care center. DESIGN: A cross-sectional study from August 2012 to May 2022 in the University of Michigan electronic health record (EHR). PARTICIPANTS: Patients with a diagnosis of any open-angle glaucoma with ≥1 eye care visit at the University of Michigan Kellogg Eye Center and ≥1 reliable visual field (VF). METHODS: Participants who met inclusion criteria were identified by International Classification of Diseases ninth and tenth revision codes (365.x/H40.x). Data extracted from the EHR included patient demographics, address, presenting mean deviation (MD), and VF reliability. Addresses were mapped to SRF measures at the census tract, block group, and county levels. Multilevel linear regression models were used to estimate the fixed effects of each SRF on MD, after adjusting for patient-level demographic factors and a random effect for neighborhood. Interactions between each SRF measure with patient-level race and Medicaid status were tested for an additive effect on MD. MAIN OUTCOME MEASURES: The main outcome measure was the effect of SRF on presenting MD. RESULTS: In total, 4428 patients were included in the analysis who were, on average, 70.3 years old (standard deviation = 11.9), 52.6% self-identified as female, 75.8% self-identified as White race, and 8.9% had Medicaid. The median value of presenting MD was −4.94 decibels (dB) (interquartile range = −11.45 to −2.07 dB). Neighborhood differences accounted for 4.4% of the variability in presenting MD. Neighborhood-level measures, including worse area deprivation (estimate, β = −0.31 per 1-unit increase; P \u3c 0.001), increased segregation (β = −0.92 per 0.1-unit increase in Theil\u27s H index; P \u3c 0.001), and increased neighborhood Medicaid (β = −0.68; P \u3c 0.001) were associated with worse presenting MD. Significant interaction effects with race and Medicaid status were found in several neighborhood-level SRF measures. CONCLUSIONS: Although patients\u27 neighborhood SRF measures accounted for a minority of the variability in presenting MD, most neighborhood-level SRFs are modifiable and were associated with clinically meaningful differences in presenting MD. Policies that aim to reduce neighborhood inequities by addressing allocation of resources could have lasting impacts on vision outcomes. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article