Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial.

IMPORTANCE Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non-small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear. OBJECTIVE To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment. DESIGN, SETTING, AND PARTICIPANTS This single-group nonrandomized clinical trial was conducted among 150 patients at the Princess Margaret Cancer Centre-University Health Network (Toronto, Ontario, Canada) between July 1, 2021, and November 30, 2022. Patients referred for investigation and diagnosis of lung cancer were eligible if they had radiologic evidence of advanced lung cancer prior to a tissue diagnosis. INTERVENTIONS Patients underwent plasma ctDNA testing with a next-generation sequencing (NGS) assay before lung cancer diagnosis. Diagnostic biopsy and tissue NGS were performed per standard of care. MAIN OUTCOME AND MEASURES The primary end point was time from referral to treatment initiation among patients with advanced nonsquamous NSCLC using ctDNA testing before diagnosis (ACCELERATE [Accelerating Lung Cancer Diagnosis Through Liquid Biopsy] cohort). This cohort was compared with a reference cohort using standard tissue genotyping after tissue diagnosis. RESULTS Of the 150 patients (median age at diagnosis, 68 years [range, 33-91 years]; 80 men [53%]) enrolled, 90 (60%) had advanced nonsquamous NSCLC. The median time to treatment was 39 days (IQR, 27-52 days) for the ACCELERATE cohort vs 62 days (IQR, 44-82 days) for the reference cohort (P < .001). Among the ACCELERATE cohort, the median turnaround time from sample collection to genotyping results was 7 days (IQR, 6-9 days) for plasma and 23 days (IQR, 18-28 days) for tissue NGS (P < .001). Of the 90 patients with advanced nonsquamous NSCLC, 21 (23%) started targeted therapy before tissue NGS results were available, and 11 (12%) had actionable alterations identified only through plasma testing. CONCLUSIONS AND RELEVANCE This nonrandomized clinical trial found that the use of plasma ctDNA genotyping before tissue diagnosis among patients with suspected advanced NSCLC was associated with accelerated time to treatment compared with a reference cohort undergoing standard tissue testing. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04863924

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

&lt;p&gt;Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.&lt;/p&gt; &lt;p&gt;Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate &#60;60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.&lt;/p&gt; &lt;p&gt;Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.&lt;/p&gt

Measurement of inelastic scattering of 0.279 MeV gamma rays from K-shell electrons of molybdenum

839-841K-shell to free electron differential Compton cross section ratio has been measured using0.279 MeV gamma rays from K-shell electrons of molybdenum at scattering angles ranging from 30 to 150 degree. Two NaI(Tl) scintillation spectrometers and a coincidence set up having 30 n sec resolving time are used for this purpose. The experimental results are compared with the available theoretical and experimental data and are found in agreement with the theoretical calculations of Shimizu et al..[Phys Rev. 140(1965)A 806]

Synthesis and characterization of sustainable inverse vulcanized copolymers from non-edible oil

Inverse vulcanization is a facile solvent-free process, which offers interesting sustainable copolymers from the reaction of sulfur with petro-based monomers or edible vegetable oils. However, sulfur reaction with the former contradicts green chemistry, whereas the latter reduces the viability of the product and can contribute to the food crisis. Herein, we report the preparation of sulfur-based polymer (SBP) by the reaction of rubber seed oil, RSO (a non-edible oil), to produce a sustainable sulfur-based copolymer for the first time. The properties of the new polymer were evaluated using different techniques such as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy coupled with energy dispersive X-rays (SEM-EDX-mapping), powdered X-ray diffractometer (p-XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The polymer was found to be soluble in tetrahydrofuran, thermally stable to 200 °C, and a low glass transition temperature (−6.41 to −7.85 °C for a polymer with 50 to 70 wt % S). The polymer morphological and DSC analysis demonstrated a uniform surface possessing a small amount of unreacted microscale sulfur particles that is lesser than similar polymers from other oils, which was confirmed by DSC. The P-XRD analysis revealed the amorphous nature of the copolymer caused by a heavily crosslinked structure. The effect of the post-polymerization treatment on the properties of the copolymers was also investigated which revealed that increasing the curing temperature or quenching medium temperature increases the glass transition temperature of the copolymer. The polymer properties were dramatically improved by reducing the amount of the unreacted sulfur by the addition of a small amount of 1,3-diisopropeynyl benzene (crosslinker), leading to 99.75 % sulfur conversion, the highest ever value achieved in such SBPs. It can be concluded that the use of RSO with sulfur enhances the sustainability of SBP and promotes their adding products