Highlights d 3F3-FMA is identified in a screen as a selective ferroptosisimmunostaining reagent d The antigen of 3F3-FMA is identified as the transferrin receptor 1 protein (TfR1) d Anti-TfR1 antibodies can detect ferroptosis by immunofluorescence and flow cytometry d Anti-TfR1 and anti-MDA antibodies detect ferroptosis in xenograft cancer models

Migraine is a disabling neurological disease that affects 14.7 % of Europeans. Studies evaluating the economic impact of migraine are complex to conduct adequately and with time become outdated as healthcare systems evolve. This study sought to quantify and compare direct medical costs of chronic migraine (CM) and episodic migraine (EM) in five European countries. Cross-sectional data collected via a web-based survey were screened for migraine and classified as CM (≥15 headache days/month) or EM (<15 headache days/month), and included sociodemographics, resource use data and medication use. Unit cost data, gathered using publicly available sources, were analyzed for each type of service, stratified by migraine status. Univariate and multivariate log-normal regression models were used to examine the relationship between various factors and their impact on total healthcare costs. This economic analysis included data from respondents with migraine in the UK, France, Germany, Italy, and Spain. CM participants had higher level of disability and more prevalent psychiatric disorders compared to EM. CM participants had more provider visits, emergency department/hospital visits, and diagnostic tests; the medical costs were three times higher for CM than EM. Per patient annual costs were highest in the UK and Spain and lower in France and Germany. CM was associated with higher medical resource use and total costs compared to EM in all study countries, suggesting that treatments that reduce headache frequency could decrease the clinical and economic burden of migraine in Europe. Comparing patterns of care and outcomes among countries may facilitate the development of more cost-effective care, and bring greater recognition to patients affected by migraine.

Chronic migraine was associated with higher medical resource use and total costs compared to episodic migraine. Therapies that reduce headache frequency could become important approaches for containing or reducing headache-related medical costs.

BackgroundInadequate surgical hemostasis may lead to transfusion and/or other bleeding-related complications. This study examines the incidence and costs of bleeding-related complications and/or blood product transfusions occurring as a consequence of surgery in various inpatient surgical cohorts.MethodsA retrospective analysis was conducted using Premier's Perspective™ hospital database. Patients who had an inpatient procedure within a specialty of interest (cardiac, vascular, non-cardiac thoracic, solid organ, general, reproductive organ, knee/hip replacement, or spinal surgery) during 2006-2007 were identified. For each specialty, the rate of bleeding-related complications (including bleeding event, intervention to control for bleeding, and blood product transfusions) was examined, and hospital costs and length of stay (LOS) were compared between surgeries with and without bleeding-related complications. Incremental costs and ratios of average total hospital costs for patients with bleeding-related complications vs. those without complications were estimated using ordinary least squares (OLS) regression, adjusting for demographics, hospital characteristics, and other baseline characteristics. Models using generalized estimating equations (GEE) were also used to measure the impact of bleeding-related complications on costs while accounting for the effects related to the clustering of patients receiving care from the same hospitals.ResultsA total of 103,829 cardiac, 216,199 vascular, 142,562 non-cardiac thoracic, 45,687 solid organ, 362,512 general, 384,132 reproductive organ, 246,815 knee/hip replacement, and 107,187 spinal surgeries were identified. Overall, the rate of bleeding-related complications was 29.9% and ranged from 7.5% to 47.4% for reproductive organ and cardiac, respectively. Overall, incremental LOS associated with bleeding-related complications or transfusions (unadjusted for covariates) was 6.0 days and ranged from 1.3 to 9.6 days for knee/hip replacement and non-cardiac thoracic, respectively. The incremental cost per hospitalization associated with bleeding-related complications and adjusted for covariates was highest for spinal surgery ($17,279) followed by vascular ($15,123), solid organ ($13,210), non-cardiac thoracic ($13,473), cardiac ($10,279), general ($4,354), knee/hip replacement ($3,005), and reproductive organ ($2,805).ConclusionsThis study characterizes the increased hospital LOS and cost associated with bleeding-related complications and/or transfusions occurring as a consequence of surgery, and supports implementation of blood-conservation strategies.

SUMMARY Design of small molecules that disrupt protein-protein interactions, including the interaction of RAS proteins and their effectors, have potential use as chemical probes and therapeutic agents. We describe here the synthesis and testing of potential small molecule pan-RAS ligands, which were designed to interact with adjacent sites on the surface of oncogenic KRAS. One compound, termed 3144, was found to bind to RAS proteins using microscale thermophoresis, nuclear magnetic resonance spectroscopy and isothermal titration calorimetry, and to exhibit lethality in cells partially dependent on expression of RAS proteins. This compound was metabolically stable in liver microsomes and displayed anti-tumor activity in xenograft mouse cancer models. These findings suggest that pan-RAS inhibition may be an effective therapeutic strategy for some cancers, and that structure-based design of small molecules targeting multiple adjacent sites to create multivalent inhibitors may be effective for some proteins.