Background:Modern systemic anti-cancer therapies have resulted in an improved prognosis for lung cancer patients. However, their complex toxicities require close monitoring. An existing e-Health platform called eRAPID (Electronic patient self-Reporting of Adverse events: Patient Information and aDvice), enables patients to report symptoms and receive automatic severity-dependent advice to self-manage or contact the hospital. Symptom data is available in real-time for clinicians in the patients' electronic patient record (EPR). The feasibility study aimed to implement eRAPID for symptom/toxicity monitoring of lung cancer patients during and after systemic therapy. Primary outcomes were recruitment and consent rates, attrition rates and adherence to symptom reporting. Secondary outcomes were: (I) type, frequency, and severity of self-reported symptoms; (II) activated clinical algorithms for patient advice; and (III) patient and staff acceptance and views. Methods:Consecutive patients starting systemic therapy were recruited and followed up for 12-months. Participants joined Cohort 1 (online access, reporting weekly from home) or Cohort 2 (no online access, completing before appointments every 4-6 weeks with assistance). Patients completed symptom reports, designed with the lung clinicians, plus 3 monthly quality-of-life questionnaires (EuroQol-5 dimensions). Descriptive analysis was employed for the quantitative outcomes. Semi-structured interviews and online feedback gathered views from a subset of patients and clinicians, using thematic framework analysis. Study project registration number: NCT04324437. Results:Between August 2020 and July 2022, eighty-five patients were eligible, 43 (50.6%) consented, 33 Cohort 1, 10 Cohort 2. The attrition rate was 65.1% (28/43) primarily due to disease progression. For all patients, a total of 841 symptom reports were generated. For Cohort 1, the mean weekly adherence for symptom reporting was 68.9% (range, 50-70%). The most reported symptoms were fatigue (77%), physical limitations (76%), pain (60%) and shortness of breath (59%), but they were mainly mild. The clinical algorithm generated 56 notifications to the clinical team for severe symptoms (6.7%, 56/841), with physical limitations and rash most common. Three-monthly adherence to quality-of-life questionnaires was 60-90%. Patient and staff feedback (n=14 and n=9) revealed reassurance and confidence from patients in self-managing side-effects. Although clinicians did not always discuss the reported symptoms, patients felt more connected to their healthcare team. Clinicians valued eRAPID for tracking symptoms, planning consultations, making timely clinical decisions and improving patient relations. Conclusions:The eRAPID approach was accepted by half of the patients who were eligible to take part. There was good adherence over time, and willingness to complete 3-monthly quality of life measures. Clinicians and patients supported the intervention for routine practice but required further investment and support from the hospital to make the symptom monitoring sustainable.

BACKGROUND:Adverse event monitoring is essential to monitor safety for oncology patients on early-phase clinical trials. Previous research considers that electronic patient-reported adverse events reporting is feasible and complementary to traditional clinician-led recording. An electronic patient-reported adverse event system was developed to explore the feasibility of this in early trials patients. METHODS:A prospective single-arm feasibility study was undertaken at two recruiting hospitals. Participants were adult oncology patients who had recently (<1 month) started receiving a novel anticancer treatment on an academic early-phase trial and had access to the Internet. For a 12-week period, weekly reminders were sent to participants to complete an electronic patient-reported adverse event questionnaire remotely covering symptoms identified as relevant to the recruiting trials. The primary outcome was compliance (proportion of completed questionnaires/expected completions). Secondary outcomes included recruitment rates, attrition, electronic patient-reported outcome versus clinician-recorded adverse events, number of notifications, issues recorded, and patient acceptability. RESULTS:Twenty-three participants consented (76.7% consent rate), 18 remained on study at 12 weeks (4 were withdrawn due to toxicity and 1 patient choice). Compliance with weekly electronic patient-reported adverse event was high, with a cumulative of 85.1% across the 12 weeks. Comparison with clinician-recorded adverse events showed electronic patient-reported adverse event resulted in wider coverage of adverse events: three times as many symptoms reported on electronic patient-reported adverse event (n = 174 last assessment) than recorded in the medical charts (n = 50 last record). End-of-study feedback indicated most patients reflected positively on their time on the study. CONCLUSIONS:Remote electronic patient-reported adverse event reporting by patients in early-phase trials is feasible and acceptable. The study highlights some logistical challenges that require consideration in future electronic patient-reported outcome work to ensure adverse events are fully captured and recorded. TRIAL REGISTRATION:ClinicalTrials.gov ID: NCT03461939 (first registered: 05/03/2018).

PURPOSE A randomized controlled trial of online symptom monitoring during chemotherapy with electronic patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) system found improved symptom control and patient self-efficacy, without increasing hospital admissions and visits. The aim of this study was to evaluate the cost-effectiveness of the eRAPID eHealth intervention compared with usual care for patients receiving systemic treatment for colorectal, breast, or gynecologic cancers in the United Kingdom. METHODS An embedded economic evaluation was conducted alongside the trial evaluating the effectiveness of eRAPID from health care provider and societal perspectives. Costs and quality-adjusted life-years (QALYs) of patients were compared over 18 weeks of the trial. Incremental cost-effectiveness ratios (ICERs) were estimated and compared with the National Institute for Health and Care Excellence cost-effectiveness threshold. Uncertainty around the ICER was explored using nonparametric bootstrapping and sensitivity analyses. Follow-up data were collected 12-months after random assignment for a subset of the study sample to conduct exploratory analysis of potential longer-term effects. RESULTS Patients in the eRAPID group had the highest QALY gain and lowest costs over 18 weeks. Although differences were small and not statistically significant, eRAPID had a 55%-58% probability of being more cost-effective than usual care. Patient out-of-pocket costs were lower in the eRAPID group, indicating eRAPID may help patients access support needed within the National Health Service. Exploratory 12-months analysis showed small differences in costs and QALYs, with higher QALY gains in the eRAPID group but also higher costs. Exploratory subgroup analysis by disease status indicated that the eRAPID intervention was cost-effective for patients with early-stage cancers but not for patients with metastatic disease. CONCLUSION Despite small differences in QALYs and costs, the analyses show potential cost-effectiveness of online symptom monitoring, when added to usual care, particularly during adjuvant systemic treatment for early-stage cancers.

Soil contamination is an environmental issue due to increasing anthropogenic activities. Existing processes for soil remediation suffer from long treatment time and lack generality because of different sources, occurrences, and properties of pollutants. Here, we report a high-temperature electrothermal process for rapid, water-free remediation of multiple pollutants in soil. The temperature of contaminated soil with carbon additives ramps up to 1000 to 3000 °C as needed within seconds via pulsed direct current input, enabling the vaporization of heavy metals like Cd, Hg, Pb, Co, Ni, and Cu, and graphitization of persistent organic pollutants like polycyclic aromatic hydrocarbons. The rapid treatment retains soil mineral constituents while increases infiltration rate and exchangeable nutrient supply, leading to soil fertilization and improved germination rates. We propose strategies for upscaling and field applications. Techno-economic analysis indicates the process holds the potential for being more energy-efficient and cost-effective compared to soil washing or thermal desorption.

Development of cementitious materials with low carbon footprint is critical for greenhouse gas mitigation. Coal fly ash (CFA) is an attractive diluent additive in cement due to its widespread availability and ultralow cost, but the heavy metals in CFA could leach out over time. Traditional acid washing processes for heavy metal removal suffer from high chemical consumption and high-volume wastewater streams. Here, we report a rapid and water-free process based on flash Joule heating (FJH) for heavy metals removal from CFA. The FJH process ramps the temperature to ~3000 °C within one second by an electric pulse, enabling the evaporative removal of heavy metals with efficiencies of 70–90% for arsenic, cadmium, cobalt, nickel, and lead. The purified CFA is partially substituted in Portland cement, showing enhanced strength and less heavy metal leakage under acid leaching. Techno-economic analysis shows that the process is energy-efficient with the cost of ~$21 ton −1 in electrical energy. Life cycle analysis reveals the reuse of CFA in cement reduces greenhouse gas emissions by ~30% and heavy metal emissions by ~41%, while the energy consumption is balanced, when compared to landfilling. The FJH strategy also works for decontamination of other industrial wastes such as bauxite residue.

Heteroatom doping can effectively tailor the local structures and electronic states of intrinsic two-dimensional materials, and endow them with modified optical, electrical, and mechanical properties. Recent studies have shown the feasibility of preparing doped graphene from graphene oxide and its derivatives via some post-treatments, including solid-state and solvothermal methods, but they require reactive and harsh reagents. However, direct synthesis of various heteroatom-doped graphene in larger quantities and high purity through bottom-up methods remains challenging. Here, we report catalyst-free and solvent-free direct synthesis of graphene doped with various heteroatoms in bulk via flash Joule heating (FJH). Seven types of heteroatom-doped flash graphene (FG) are synthesized through millisecond flashing, including single-element-doped FG (boron, nitrogen, oxygen, phosphorus, sulfur), two-element-co-doped FG (boron and nitrogen), as well as three-element-co-doped FG (boron, nitrogen, and sulfur). A variety of low-cost dopants, such as elements, oxides, and organic compounds are used. The graphene quality of heteroatom-doped FG is high, and similar to intrinsic FG, the material exhibits turbostraticity, increased interlayer spacing, and superior dispersibility. Electrochemical oxygen reduction reaction of different heteroatom-doped FG is tested, and sulfur-doped FG shows the best performance. Lithium metal battery tests demonstrate that nitrogen-doped FG exhibits a smaller nucleation overpotential compared to Cu or undoped FG. The electrical energy cost for the synthesis of heteroatom-doped FG synthesis is only 1.2 to 10.7 kJ g-1, which could render the FJH method suitable for low-cost mass production of heteroatom-doped graphene.

Rare earth elements (REEs) are critical materials in electronics and clean technologies. With the diminishing of easily accessible minerals for mining, the REE recovery from waste is an alternative toward a circular economy. Present methods for REE recovery suffer from lengthy purifications, low extractability, and high wastewater streams. Here, we report an ultrafast electrothermal process (~3000°C, ~1 s) based on flash Joule heating (FJH) for activating wastes to improve REE extractability. FJH thermally degrades or reduces the hard-to-dissolve REE species to components with high thermodynamic solubility, leading to ~2× increase in leachability and high recovery yields using diluted acid (e.g., 0.1 M HCl). The activation strategy is feasible for various wastes including coal fly ash, bauxite residue, and electronic waste. The rapid FJH process is energy-efficient with a low electrical energy consumption of 600 kWh ton−1. The potential for this route to be rapidly scaled is outlined.

Background: Cancer is treated using multiple modalities (e.g. surgery, radiotherapy and systemic therapies) and is frequently associated with adverse events that affect treatment delivery and quality of life. Regular adverse event reporting could improve care and safety through timely detection and management. Information technology provides a feasible monitoring model, but applied research is needed. This research programme developed and evaluated an electronic system, called eRAPID, for cancer patients to remotely self-report adverse events. Objectives: The objectives were to address the following research questions: is it feasible to collect adverse event data from patients’ homes and in clinics during cancer treatment? Can eRAPID be implemented in different hospitals and treatment settings? Will oncology health-care professionals review eRAPID reports for decision-making? When added to usual care, will the eRAPID intervention (i.e. self-reporting with tailored advice) lead to clinical benefits (e.g. better adverse event control, improved patient safety and experiences)? Will eRAPID be cost-effective? Design: Five mixed-methods work packages were conducted, incorporating co-design with patients and health-care professionals: work package 1 – development and implementation of the electronic platform across hospital centres; work package 2 – development of patient-reported adverse event items and advice (systematic and scoping reviews, patient interviews, Delphi exercise); work package 3 – mapping health-care professionals and care pathways; work package 4 – feasibility pilot studies to assess patient and clinician acceptability; and work package 5 – a single-centre randomised controlled trial of systemic treatment with a full health economic assessment. Setting: The setting was three UK cancer centres (in Leeds, Manchester and Bristol). Participants: The intervention was developed and evaluated with patients and clinicians. The systemic randomised controlled trial included 508 participants who were starting treatment for breast, colorectal or gynaecological cancer and 55 health-care professionals. The radiotherapy feasibility pilot recruited 167 patients undergoing treatment for pelvic cancers. The surgical feasibility pilot included 40 gastrointestinal cancer patients. Intervention: eRAPID is an online system that allows patients to complete adverse event/symptom reports from home or hospital. The system provides immediate severity-graded advice based on clinical algorithms to guide self-management or hospital contact. Adverse event data are transferred to electronic patient records for review by clinical teams. Patients complete an online symptom report every week and whenever they experience symptoms. Main outcome measures: In systemic treatment, the primary outcome was Functional Assessment of Cancer Therapy – General, Physical Well-Being score assessed at 6, 12 and 18 weeks (primary end point). Secondary outcomes included cost-effectiveness assessed through the comparison of health-care costs and quality-adjusted life-years. Patient self-efficacy was measured (using the Self-Efficacy for Managing Chronic Diseases 6-item Scale). The radiotherapy pilot studied feasibility (recruitment and attrition rates) and selection of outcome measures. The surgical pilot examined symptom report completeness, system actions, barriers to using eRAPID and technical performance. Results: eRAPID was successfully developed and introduced across the treatments and centres. The systemic randomised controlled trial found no statistically significant effect of eRAPID on the primary end point at 18 weeks. There was a significant effect at 6 weeks (adjusted difference least square means 1.08, 95% confidence interval 0.12 to 2.05; p = 0.028) and 12 weeks (adjusted difference least square means 1.01, 95% confidence interval 0.05 to 1.98; p = 0.0395). No between-arm differences were found for admissions or calls/visits to acute oncology or chemotherapy delivery. Health economic analyses over 18 weeks indicated no statistically significant difference between the cost of the eRAPID information technology system and the cost of usual care (£12.28, 95% confidence interval –£1240.91 to £1167.69; p > 0.05). Mean differences were small, with eRAPID having a 55% probability of being cost-effective at the National Institute for Health and Care Excellence-recommended cost-effectiveness threshold of £20,000 per quality-adjusted life-year gained. Patient self-efficacy was greater in the intervention arm (0.48, 95% confidence interval 0.13 to 0.83; p = 0.0073). Qualitative interviews indicated that many participants found eRAPID useful for support and guidance. Patient adherence to adverse-event symptom reporting was good (median compliance 72.2%). In the radiotherapy pilot, high levels of consent (73.2%) and low attrition rates (10%) were observed. Patient quality-of-life outcomes indicated a potential intervention benefit in chemoradiotherapy arms. In the surgical pilot, 40 out of 91 approached patients (44%) consented. Symptom report completion rates were high. Across the studies, clinician intervention engagement was varied. Both patient and staff feedback on the value of eRAPID was positive. Limitations: The randomised controlled trial methodology led to small numbers of patients simultaneously using the intervention, thus reducing overall clinician exposure to and engagement with eRAPID. Furthermore, staff saw patients across both arms, introducing a contamination bias and potentially reducing the intervention effect. The health economic results were limited by numbers of missing data (e.g. for use of resources and EuroQol-5 Dimensions). Conclusions: This research provides evidence that online symptom monitoring with inbuilt patient advice is acceptable to patients and clinical teams. Evidence of patient benefit was found, particularly during the early phases of treatment and in relation to self-efficacy. The findings will help improve the intervention and guide future trial designs. Future work: Definitive trials in radiotherapy and surgical settings are suggested. Future research during systemic treatments could study self-report online interventions to replace elements of traditional follow-up care in the curative setting. Further research during modern targeted treatments (e.g. immunotherapy and small-molecule oral therapy) and in metastatic disease is recommended. Trial registration: The systemic randomised controlled trial is registered as ISRCTN88520246. The radiotherapy trial is registered as ClinicalTrials.gov NCT02747264. Funding: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 10, No. 1. See the NIHR Journals Library website for further project information.

Source data for "High-surface-area corundum nanoparticles by resistive hotspot-induced phase transformation".

Nanoscale carbides enhance ultra-strong ceramics and show activity as high-performance catalysts. Traditional lengthy carburization methods for carbide syntheses usually result in coked surface, large particle size, and uncontrolled phase. Here, a flash Joule heating process is developed for ultrafast synthesis of carbide nanocrystals within 1 s. Various interstitial transition metal carbides (TiC, ZrC, HfC, VC, NbC, TaC, Cr 2 C 3 , MoC, and W 2 C) and covalent carbides (B 4 C and SiC) are produced using low-cost precursors. By controlling pulse voltages, phase-pure molybdenum carbides including β-Mo 2 C and metastable α-MoC 1-x and η-MoC 1-x are selectively synthesized, demonstrating the excellent phase engineering ability of the flash Joule heating by broadly tunable energy input that can exceed 3000 K coupled with kinetically controlled ultrafast cooling (>10 4 K s −1 ). Theoretical calculation reveals carbon vacancies as the driving factor for topotactic transition of carbide phases. The phase-dependent hydrogen evolution capability of molybdenum carbides is investigated with β-Mo 2 C showing the best performance.

High-surface-area α-Al 2 O 3 nanoparticles are used in high-strength ceramics and stable catalyst supports. The production of α-Al 2 O 3 by phase transformation from γ-Al 2 O 3 is hampered by a high activation energy barrier, which usually requires extended high-temperature annealing (~1500 K, > 10 h) and suffers from aggregation. Here, we report the synthesis of dehydrated α-Al 2 O 3 nanoparticles (phase purity ~100%, particle size ~23 nm, surface area ~65 m 2 g −1 ) by a pulsed direct current Joule heating of γ-Al 2 O 3 . The phase transformation is completed at a reduced bulk temperature and duration (~573 K, < 1 s) via an intermediate δʹ-Al 2 O 3 phase. Numerical simulations reveal the resistive hotspot-induced local heating in the pulsed current process enables the rapid transformation. Theoretical calculations show the topotactic transition (from γ- to δʹ- to α-Al 2 O 3 ) is driven by their surface energy differences. The α-Al 2 O 3 nanoparticles are sintered to nanograined ceramics with hardness superior to commercial alumina and approaching that of sapphire.

Improvements in whole genome amplification (WGA) would enable new types of basic and applied biomedical research, including studies of intratissue genetic diversity that require more accurate single-cell genotyping. Here, we present primary template-directed amplification (PTA), an isothermal WGA method that reproducibly captures >95% of the genomes of single cells in a more uniform and accurate manner than existing approaches, resulting in significantly improved variant calling sensitivity and precision. To illustrate the types of studies that are enabled by PTA, we developed direct measurement of environmental mutagenicity (DMEM), a tool for mapping genome-wide interactions of mutagens with single living human cells at base-pair resolution. In addition, we utilized PTA for genome-wide off-target indel and structural variant detection in cells that had undergone CRISPR-mediated genome editing, establishing the feasibility for performing single-cell evaluations of biopsies from edited tissues. The improved precision and accuracy of variant detection with PTA overcomes the current limitations of accurate WGA, which is the major obstacle to studying genetic diversity and evolution at cellular resolution.

Electrochemical oxygen reduction to hydrogen peroxide is now being studied as a promising renewable and localized alternative for the traditional complex anthraquinone process. Catalysts for this two-electron reduction pathway with high selectivity are required to achieve industrialization. Here, we disclose an inexpensive metal-free catalyst that is synthesized from commercial carbon black (CB) with a one-step plasma method for the affordable electrochemical generation of hydrogen peroxide in 100% Faradaic efficiency. This catalyst shows a high onset potential (0.1 mA cm(-2) at 0.80 V vs reversible hydrogen electrode (RHE)) and the highest mass activity (300 A g(-1) at 0.60 V vs reversible hydrogen electrode) among state-of-the-art catalysts. The performance could be maintained after the removal of oxygen-containing groups. Microscopic and spectroscopic characterizations as well as density functional theory (DFT) calculations indicate that the performance comes from the defective structure after plasma treatment.

Streptococcus pneumoniae (pneumococcus) is one of the primary bacterial pathogens that complicates influenza virus infections. These bacterial coinfections increase influenza-associated morbidity and mortality through a number of immunological and viral-mediated mechanisms, but the specific bacterial genes that contribute to postinfluenza pathogenicity are not known. Here, we used genome-wide transposon mutagenesis (Tn-Seq) to reveal bacterial genes that confer improved fitness in influenza virus-infected hosts. The majority of the 32 genes identified are involved in bacterial metabolism, including nucleotide biosynthesis, amino acid biosynthesis, protein translation, and membrane transport. We generated mutants with single-gene deletions (SGD) of five of the genes identified, SPD1414, SPD2047 (cbiO1), SPD0058 (purD), SPD1098, and SPD0822 (proB), to investigate their effects on in vivo fitness, disease severity, and host immune responses. The growth of the SGD mutants was slightly attenuated in vitro and in vivo, but each still grew to high titers in the lungs of mock- and influenza virus-infected hosts. Despite high bacterial loads, mortality was significantly reduced or delayed with all SGD mutants. Time-dependent reductions in pulmonary neutrophils, inflammatory macrophages, and select proinflammatory cytokines and chemokines were also observed. Immunohistochemical staining further revealed altered neutrophil distribution with reduced degeneration in the lungs of influenza virus-SGD mutant-coinfected animals. These studies demonstrate a critical role for specific bacterial genes and for bacterial metabolism in driving virulence and modulating immune function during influenza-associated bacterial pneumonia.

PURPOSE:Electronic patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) is an online eHealth system for patients to self-report symptoms during cancer treatment. It provides automated severity-dependent patient advice guiding self-management or medical contact and displays the reports in electronic patient records. This trial evaluated the impact of eRAPID on symptom control, healthcare use, patient self-efficacy, and quality of life (QOL) in a patient population treated predominantly with curative intent. METHODS:Patients with colorectal, breast, or gynecological cancers commencing chemotherapy were randomly assigned to usual care (UC) or the addition of eRAPID (weekly online symptom reporting for 18 weeks). Primary outcome was symptom control (Functional Assessment of Cancer Therapy-General, Physical Well-Being subscale [FACT-PWB]) assessed at 6, 12, and 18 weeks. Secondary outcomes were processes of care (admissions or chemotherapy delivery), patient self-efficacy, and global quality of life (Functional Assessment of Cancer Therapy-General, EQ5D-VAS, and EORTC QLQ-C30 summary score). Multivariable mixed-effects repeated-measures models were used for analyses. Trial registration: ISRCTN88520246. RESULTS:Participants were 508 consenting patients (73.6% of 690 eligible) and 55 health professionals. eRAPID compared to UC showed improved physical well-being at 6 (P = .028) and 12 (P = .039) weeks and no difference at 18 weeks (primary end point) (P = .69). Fewer eRAPID patients (47%) had clinically meaningful physical well-being deterioration than UC (56%) at 12 weeks. Subgroup analysis found benefit in the nonmetastatic group at 6 weeks (P = .0426), but not in metastatic disease. There were no differences for admissions or chemotherapy delivery. At 18 weeks, patients using eRAPID reported better self-efficacy (P = .007) and better health on EQ5D-VAS (P = .009). Average patient compliance with weekly symptom reporting was 64.7%. Patient adherence was associated with clinician's data use and improved FACT-PWB at 12 weeks. CONCLUSION:Real-time monitoring with electronic patient-reported outcomes improved physical well-being (6 and 12 weeks) and self-efficacy (18 weeks) in a patient population predominantly treated with curative intent, without increasing hospital workload.

Identification of genomic and epigenomic determinants of drug resistance provides important insights for improving cancer treatment. Using agnostic genome-wide interrogation of messenger RNA and microRNA (miRNA) expression, DNA methylation, single-nucleotide polymorphisms, copy number alterations and single-nucleotide variants/indels in primary human acute lymphoblastic leukemia cells, we identified 463 genomic features associated with glucocorticoid resistance. Gene-level aggregation identified 118 overlapping genes, 15 of which were confirmed by genome-wide CRISPR screen. Collectively, this identified 30 of 38 (79%) known glucocorticoid-resistance genes/miRNAs and all 38 known resistance pathways, while revealing 14 genes not previously associated with glucocorticoid resistance. Single-cell RNA-sequencing and network-based transcriptomic modeling corroborated the top previously undiscovered gene, CELSR2 . Manipulation of CELSR2 recapitulated glucocorticoid resistance in human leukemia cell lines and revealed a synergistic drug combination (prednisolone and venetoclax) that mitigated resistance in mouse xenograft models. These findings illustrate the power of an integrative genomic strategy for elucidating genes and pathways conferring drug resistance in cancer cells.

BACKGROUNDHypotensive resuscitation to raise systolic pressure to 80–90 mm Hg is the standard of care on the battlefield for hemorrhaging Soldiers, and is maintained until the casualty is transported to a surgical unit usually within one hour of injury. Prompt evacuations may not be possible in future conflicts, and hypotension will be required for longer periods of time. This study determined the long‐term effects of prolonged hypotension (PH) held for 0, 1, 2 and 3 hours on kidney, liver and muscle damage up to 21 days after PH, and tested the hypothesis that longer duration of hypotension after hemorrhage will result in greater organ damage.METHODSMale baboons were anesthetized and hemorrhaged until systolic blood pressure was 70 mmHg for 10 min. Systolic blood pressure of greater than 80 mm Hg with autologous blood was maintained for 1 hour (1hr PH; n=5), 2 hours (2hr PH; n=5), or 3 hours (3hr PH; n=5) hours. After the PH period, the hemorrhage volume of whole blood was replaced, and the animal was recovered and monitored for 21 days. Control animals were anesthetized, hemorrhaged and immediately resuscitated with hemorrhaged blood (0hr PH, n=3). Blood samples were obtained before and 1, 3, 7, 14 and 21 days after PH, and analyzed for blood chemistry profile. Data were analyzed with 2 way repeated measures ANOVA and Holm‐Sidak test, and expressed as Mean ± Standard Deviation.RESULTSPlasma creatinine and blood urea nitrogen were unaffected by PH and remained within normal limits in all PH groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH) values were significantly elevated after PH (time effect; P<0.001; PH group effect; P=0.3). Maximum ALT levels were observed on Day 1 after PH in 0hr PH (140 ± 56 U/L), 1hr PH (170 ± 130 U/L), 2hr PH (322 ± 241 U/L), and 3hr PH (387 ± 167 U/L). Maximum AST levels were observed on Day 1 after PH in 0hr PH (218 ± 44 U/L), 1hr PH (354 ± 219 U/L), 2hr PH (515 ± 424 U/L), and 3hr PH (711 ± 278U/L). Maximum CPK values were observed on Day 1 after PH in 0hr PH (7834 ± 3681 U/L), 1hr PH (24336 ± 22268 U/L), 2hr PH (50494 ± 67653 U/L), and 3hr PH (59857 ± 32408 U/L). Maximum LDH values were observed on Day 1 after PH in 0hr PH (890 ± 396 U/L), 1hr PH (2055 ± 1520 U/L), 2hr PH (3992 ± 4895 U/L), and 3hr PH (4771 ± 1884 U/L). Max levels of ALT, AST, CPK, and LDH were positively correlated with the duration of PH (P<0.05). All values returned to pre‐PH levels by 21 days after PH.CONCLUSIONSThese results indicate that PH up to 3 hours in duration results in transient liver and muscle damage that is correlated with the duration of PH in male baboons. PH of any duration produced minimal effects on the kidney. More studies are needed to determine if longer periods of PH result in permanent and more extensive organ damage.Support or Funding InformationThis study was funded by the United States Army, Medical Research and Materiel CommandThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.