Comparison of two high dose rate brachytherapy regimes

Background: Two HDR brachytherapy regimes were compared, 9.5 Gray per fraction for two fractions and 7.5 Gray per fraction for three fractions. Materials and Methods: A total of 80 patients with histologically evident squamous cell carcinoma cervix were taken in the current research after randomization. Radiotherapy dose delivered was 50 Gray/25#/5 weeks with concomitant chemotherapy with weekly cisplatin 35 mg/m2. Following external chemoradiation, patients were randomized into two arms. In Arm A, 40 patients were given high dose rate (HDR) brachytherapy of weekly 7.5 Gray in three fractions over 3 weeks. In Arm B, 40 patients were given high dose rate (HDR) brachytherapy of weekly 9.5 Gray in two fractions over 2 weeks. BED and LQED had been calculated, and the evaluation of response and consequences was examined. Results: In Arm A, BED to point A was 99.38 ± 0.00 and EQD2 to point A was 82.81 ± 0.00. In Arm B, BED to point A was 97.05 ± 0.00 and EQD2 to point A was 80.89 ± 0.00. With respect to rectum in Arm A, BED rectum was 108.66 ± 11.43 and EQD2 rectum was 65.07 ± 6.84. In Arm B, BED rectum was 107 ± 10.83 and EQD2 rectum was 64.21 ± 6.49. Similarly in Arm A, BED bladder was 107.86 ± 10.23 and EQD2 bladder was 64.59 ± 6.13. In arm B, BED bladder was 104.14 ± 10.79 and EQD2 bladder was 62.36 ± 6.46. Conclusion: In a follow-up of 6 months, no statistical significance in terms of local control as well as complications rates in both the arms. Our research demonstrates that two fractions of HDR are comparable with three fractions of HDR

Integration of the social determinants of health into quality indicators for colorectal cancer surgery: a scoping review protocol

Introduction Quality monitoring is a critical component of high-performing cancer care systems. Quality indicators (QIs) are standardised, evidence-based measures of healthcare quality that allow healthcare systems to track performance, identify gaps in healthcare delivery and inform areas of priority for strategic planning. Social structures and economic systems that allow for unequal access to power and resources that shape health and health inequities can be described through the social determinants of health (SDoH) framework. Therefore, granular analysis of healthcare quality through SDoH frameworks is required to identify patient subgroups who may experience health inequity. Given the high burden of disease of colorectal cancer (CRC) and well-defined cancer care pathways, CRC is often the first disease site targeted by health systems for quality improvement. The objective of this review is to examine how SDoH have been integrated into QIs for CRC surgery. This review aims to address three primary questions: (1) Have SDoH been integrated into the development, reporting and assessment of CRC surgery QIs? (2) When integrated, what measures and statistical methods have been applied? (3) In which direction do individual SDoH influence QIs outputs?Methods This review will follow Arksey and O’Malley frameworks for scoping reviews. We will search MEDLINE, EMBASE, HealthSTAR databases for papers that examine QIs for CRC surgery applicable to healthcare systems from database inception until January 2023. Interventional trials, prospective and retrospective observational studies, reviews, case series and qualitative study designs will be included. Two authors will independently review all titles, abstracts and full texts to determine which studies meet the inclusion criteria.Ethics & dissemination No ethics approval is required for this review. Results will be disseminated through scientific presentation and relevant conferences targeted for researchers examining healthcare quality and equity in cancer care.Registration details osf.io/vfzd3-Open Science Framework

Four-Dimensional Characterization of Thrombosis in a Live-Cell, Shear-Flow Assay: Development and Application to Xenotransplantation

<div><p>Background</p><p>Porcine xenografts are a promising source of scarce transplantable organs, but stimulate intense thrombosis of human blood despite targeted genetic and pharmacologic interventions. Current experimental models do not enable study of the blood/endothelial interface to investigate adhesive interactions and thrombosis at the cellular level under physiologic conditions. The purpose of this study was to develop and validate a live-cell, shear-flow based thrombosis assay relevant to general thrombosis research, and demonstrate its potential in xenotransplantation applications.</p><p>Methodology/Principal Findings</p><p>Confluent wild-type (WT, n = 48) and Gal transferase knock-out (GalTKO, which resist hyperacute rejection; n = 11) porcine endothelia were cultured in microfluidic channels. To mimic microcirculatory flow, channels were perfused at 5 dynes/cm² and 37°C with human blood stained to fluorescently label platelets. Serial fluorescent imaging visualized percent surface area coverage (SA, for adhesion of labeled cells) and total fluorescence (a metric of clot volume). Aggregation was calculated by the fluorescence/SA ratio (FR). WT endothelia stimulated diffuse platelet adhesion (SA 65 ± 2%) and aggregation (FR 120 ± 1 a.u.), indicating high-grade thrombosis consistent with the rapid platelet activation and consumption seen in whole-organ lung xenotransplantation models. Experiments with antibody blockade of platelet aggregation, and perfusion of syngeneic and allo-incompatible endothelium was used to verify the biologic specificity and validity of the assay. Finally, with GalTKO endothelia thrombus volume decreased by 60%, due primarily to a 58% reduction in adhesion (P < 0.0001 each); importantly, aggregation was only marginally affected (11% reduction, P < 0.0001).</p><p>Conclusions/Significance</p><p>This novel, high-throughput assay enabled dynamic modeling of whole-blood thrombosis on intact endothelium under physiologic conditions, and allowed mechanistic characterization of endothelial and platelet interactions. Applied to xenogeneic thrombosis, it enables future studies regarding the effect of modifying the porcine genotype on sheer-stress-dependent events that characterize xenograft injury. This in-vitro platform is likely to prove broadly useful to study thrombosis and endothelial interactions under dynamic physiologic conditions.</p></div

Results from perfusing porcine endothelia with syngeneic and allo-incompatible porcine blood.

<p>*All experiments were performed with heparinized blood. a.u., arbitrary units; TV, thrombus volume; Δ, relative change; SA, percent surface area coverage; FR, fluorescence ratio; T₅₀, time to 50% maximal surface area coverage. All Δ & <i>P</i> values are versus WT controls, and are expressed as mean ± SEM.</p><p>Results from perfusing porcine endothelia with syngeneic and allo-incompatible porcine blood.</p

Mortality and Complication Rates in Adult Trauma Patients Receiving Tranexamic Acid: A Single-center Experience in the Post-CRASH-2 Era.

OBJECTIVES:The CRASH-2 trial demonstrated that tranexamic acid (TXA) in adults with significant traumatic hemorrhage safely reduces mortality. Given that the CRASH-2 trial did not include U.S. sites, our objective was to evaluate patient characteristics, TXA dosing strategies, and the incidence of mortality and adverse events in adult trauma patients receiving TXA at a U.S. Level I trauma center in the post-CRASH-2 era. METHODS:We conducted a retrospective study that included patients aged 18&nbsp;years or older who received TXA after an acute injury from July 2014 to June 2017. We excluded patients who received TXA orally, patients who received TXA for elective surgical procedures or nontrauma indications, patients who received it 8&nbsp;hours or longer after the time of injury, and patients with cardiac arrest at time of emergency department arrival. Trained abstractors collected data from the trauma registry and hospital electronic medical records. Our primary outcome measures were in-hospital death and acute thromboembolic events within 28&nbsp;days from injury. RESULTS:We included 273 patients with a mean (±SD) age of 43.8 (±18.7) &nbsp;years. The mean (±SD) time of administration of TXA from time of injury was 1.55 (±1.2) &nbsp;hours with 229 patients (83.9%) receiving TXA within 3&nbsp;hours. The overall mortality within 28&nbsp;days from injury was 12.8% (95% confidence interval [CI]&nbsp;=&nbsp;8.9% to 16.7%), which was similar compared to that in the CRASH-2 trial (14.5%, 95% CI&nbsp;=&nbsp;13.9% to 15.2%). The incidence of acute thromboembolic events was 6.6% (95% CI&nbsp;=&nbsp;3.7% to 9.5%), which was higher than that in the CRASH-2 trial (2.0%, 95% CI&nbsp;=&nbsp;1.73% to 2.27%). Patients in our cohort also received surgery (64.8% vs. 47.9%) and blood transfusions (74.0% vs. 50.4%) more frequently than those in the CRASH-2 cohort. CONCLUSIONS:Adult trauma patients receiving TXA had similar incidences of death but higher incidences of thromboembolic events compared to the CRASH-2 trial. Variation in patient characteristics, injury severity, TXA dosing, and surgery and transfusion rates could explain these observed differences. Further research is necessary to provide additional insight into the incidence and risk factors of thromboembolic events in TXA use

A—C. Representative volumetric thrombus models.

<p>3D surface renderings of end-perfusion images (<i>t</i> = 50 minutes) for WT and GalTKO endothelia perfused with heparinized human blood (A & B, respectively) and WT endothelium perfused with heparinized human blood treated with 0.5 μg/mL abciximab (C). Panel A demonstrates significant adhesion and aggregation. In Panel B adhesion is reduced but aggregation is mostly intact, while in Panel C aggregation is ablated. Source images were taken at 100x magnification using a 100-millisecond exposure and rendered using ImageJ.</p

Mortality and Complication Rates in Adult Trauma Patients Receiving Tranexamic Acid: A Single-center Experience in the Post-CRASH-2 Era.

OBJECTIVES:The CRASH-2 trial demonstrated that tranexamic acid (TXA) in adults with significant traumatic hemorrhage safely reduces mortality. Given that the CRASH-2 trial did not include U.S. sites, our objective was to evaluate patient characteristics, TXA dosing strategies, and the incidence of mortality and adverse events in adult trauma patients receiving TXA at a U.S. Level I trauma center in the post-CRASH-2 era. METHODS:We conducted a retrospective study that included patients aged 18&nbsp;years or older who received TXA after an acute injury from July 2014 to June 2017. We excluded patients who received TXA orally, patients who received TXA for elective surgical procedures or nontrauma indications, patients who received it 8&nbsp;hours or longer after the time of injury, and patients with cardiac arrest at time of emergency department arrival. Trained abstractors collected data from the trauma registry and hospital electronic medical records. Our primary outcome measures were in-hospital death and acute thromboembolic events within 28&nbsp;days from injury. RESULTS:We included 273 patients with a mean (±SD) age of 43.8 (±18.7) &nbsp;years. The mean (±SD) time of administration of TXA from time of injury was 1.55 (±1.2) &nbsp;hours with 229 patients (83.9%) receiving TXA within 3&nbsp;hours. The overall mortality within 28&nbsp;days from injury was 12.8% (95% confidence interval [CI]&nbsp;=&nbsp;8.9% to 16.7%), which was similar compared to that in the CRASH-2 trial (14.5%, 95% CI&nbsp;=&nbsp;13.9% to 15.2%). The incidence of acute thromboembolic events was 6.6% (95% CI&nbsp;=&nbsp;3.7% to 9.5%), which was higher than that in the CRASH-2 trial (2.0%, 95% CI&nbsp;=&nbsp;1.73% to 2.27%). Patients in our cohort also received surgery (64.8% vs. 47.9%) and blood transfusions (74.0% vs. 50.4%) more frequently than those in the CRASH-2 cohort. CONCLUSIONS:Adult trauma patients receiving TXA had similar incidences of death but higher incidences of thromboembolic events compared to the CRASH-2 trial. Variation in patient characteristics, injury severity, TXA dosing, and surgery and transfusion rates could explain these observed differences. Further research is necessary to provide additional insight into the incidence and risk factors of thromboembolic events in TXA use

Thrombus generation curves for primary wild type and GalTKO endothelia.

<p>Summary of thrombus volume for primary WT versus GalTKO.hCD46 endothelia perfused with heparinized human blood. a.u., arbitrary units. Values are corrected for streak artifact (presumed embolization events) and photo-bleaching, and are expressed as mean ± SEM.</p

Results from xenoperfusion of porcine endothelia with human blood.

<p>*All experiments were performed with heparinized blood. a.u., arbitrary units; TV, thrombus volume; Δ, relative change; SA, percent surface area coverage; FR, fluorescence ratio; T₅₀, time to 50% maximal surface area coverage. All Δ & <i>P</i> values are versus WT controls, and are expressed as mean ± SEM.</p><p>Results from xenoperfusion of porcine endothelia with human blood.</p