Organ preservation solutions: linking pharmacology to survival for the donor organ pathway

PURPOSE OF REVIEW: To provide an understanding of the scientific principles, which underpinned the development of organ preservation solutions, and to bring into context new strategies and challenges for solution development against the background of changing preservation technologies and expanded criteria donor access. RECENT FINDINGS: Improvements in organ preservation solutions continue to be made with new pharmacological approaches. New solutions have been developed for dynamic perfusion preservation and are now in clinical application. Principles defining organ preservation solution pharmacology are being applied for cold chain logistics in tissue engineering and regenerative medicine. SUMMARY: Organ preservation solutions support the donor organ pathway. The solution compositions allow additives and pharmacological agents to be delivered direct to the target organ to mitigate preservation injury. Changing preservation strategies provide further challenges and opportunities to improve organ preservation solutions

Pesticide Consumption in Greenhouses; a Case Study of Kashan Region

Aims: In regard to increasing greenhouse area in Iran followed by increased use of pesticides and contaminated crops, this study aimed to determine the frequency and types of consumed pesticides in Kashan region, Iran, greenhouses. Instrument & Methods: In this descriptive study in 2011-2012, samples was entered by census method. At the first step, a list of greenhouses was obtained from agricultural organization, 39 active greenhouses were detected, thereafter the questionnaires have been completed in detail by direct interview; obtained data were analyzed in SPSS 23 by descriptive statistics. Findings: 87.1 of greenhouses used chemical methods for controlling pest and diseases of products and 43.5 used non-chemical methods. The most frequent used chemical pesticides were Deltamethrin (37.9) and Permethrin (28.3) as pyrethroid insecticides, Diazinon (23.1) as an organophosphate insecticide and Carbendazim (23.2) as a fungicides. Conclusion: 87.1 of the greenhouses’ owners of Kashan region, Iran, use chemical pesticide for pest control

The integration of rapid qualitative research in clinical trials: reflections from the ward-based goal-directed fluid therapy (GDFT) in acute pancreatitis feasibility trial

Background: There has been an increase in the integration of qualitative studies in randomised controlled trials. The purpose of this article is to reflect on our experience of carrying out a rapid qualitative study during a feasibility trial of goal-directed fluid therapy (GDFT) in patients with acute pancreatitis, including our sharing of emerging findings and the use of these findings by the trial team. / Methods: The study was designed as a rapid feedback evaluation and combined interviews with staff and patients who took part in the trial. / Findings: The rapid qualitative study pointed to common problems in trial recruitment among multiple sites, where lack of engagement of clinical teams across sites might impact negatively on patient recruitment. The article describes how the use of rapid feedback loops can be used as the trial is ongoing to inform changes in implementation. It also covers the potential challenges of working rapidly and collaborative with the trial team. / Conclusions: Rapid feedback evaluations can be used to generate findings across all stages of trial design and delivery. Additional research is required to explore the implementation of this research design in other settings and trial designs

Ward-based Goal-Directed Fluid Therapy (GDFT) in Acute Pancreatitis (GAP) trial: study protocol for a feasibility randomised controlled trial

IntroductionAcute pancreatitis is an inflammatory disease of the pancreas with high risk of developing multiorgan failure and death. There are no effective pharmacological interventions used in current clinical practice. Maintaining fluid and electrolyte balance is the mainstay of supportive management. Goal-directed fluid therapy (GDFT) has been shown to decrease morbidity and mortality in surgical conditions with systemic inflammatory response. There is currently no randomised controlled trial (RCT) investigating the role of GDFT based on cardiac output parameters in patients with acute pancreatitis in the ward setting. A feasibility trial was designed to determine patient and clinician support for recruitment into an RCT of ward-based GDFT in acute pancreatitis, adherence to a GDFT protocol, safety, participant withdrawal, and to determine appropriate endpoints for a subsequent larger trial to evaluate efficacy.Methods and analysisThe GDFT in Acute Pancreatitis trial is a prospective two-centre feasibility RCT. Eligible adults admitted with new onset of acute pancreatitis will be enrolled and randomised into ward-based GDFT (n=25) or standard fluid therapy (n=25) within 6 hours from the diagnosis and continuing for the following 48 hours. Cardiac output parameters will be monitored with a non-invasive device (Cheetah NICOM; Cheetah Medical). The intervention group will consist of a protocolised GDFT approach consisting of stroke volume optimisation with crystalloid fluid boluses, while the control group will receive standard care fluid therapy as advised by the clinical team. The primary endpoint is feasibility. Secondary endpoints will include safety of the intervention, complications, mortality, admission to intensive care unit, cost and quality of life.Ethics and disseminationEthics approval was granted by the London Central Research Ethics Committee (17/LO/1235, project ID: 221872). The results of this trial will be presented to international conference with interest in general surgery and acute care and published in a peer-reviewed journal.Trial registration numberISRCTN36077283.</jats:sec

Human liver memory CD8(+) T cells use autophagy for tissue residence

Tissue-resident memory T cells have critical roles in long-term pathogen and tumor immune surveillance in the liver. We investigate the role of autophagy in equipping human memory T cells to acquire tissue residence and maintain functionality in the immunosuppressive liver environment. By performing ex vivo staining of freshly isolated cells from human liver tissue, we find that an increased rate of basal autophagy is a hallmark of intrahepatic lymphocytes, particularly liver-resident CD8(+) T cells. CD8(+) T cells with increased autophagy are those best able to proliferate and mediate cytotoxicity and cytokine production. Conversely, blocking autophagy induction results in the accumulation of depolarized mitochondria, a feature of exhausted T cells. Primary hepatic stellate cells or the prototypic hepatic cytokine interleukin (IL)-15 induce autophagy in parallel with tissue-homing/retention markers. Inhibition of T cell autophagy abrogates tissue-residence programming. Thus, upregulation of autophagy adapts CD8(+) T cells to combat mitochondrial depolarization, optimize functionality, and acquire tissue residence

P-P06 Ward based goal directed fluid therapy (GDFT) in acute pancreatitis (GAP) trial: a feasibility randomised controlled trial [ISRCTN 36077283]

Abstract Background Goal directed fluid therapy (GDFT) based on cardiac output assessment has been shown to reduce complications and improve survival for people undergoing major general surgery. There are no reports of cardiac output evaluation being used to optimise the fluid administration for patients with acute pancreatitis who are in a general surgery admission ward. Methods The trial protocol has been published. 50 patients with acute pancreatitis were recruited, consented and randomly allocated to either ward-based GDFT with intravenous (IV) fluids administered based on stroke volume optimisation or standard ward care but with blinded cardiac output evaluation for 48 hours following hospital admission. Results Over a period of 20 months 50 of 142 screened patients were recruited demonstrating that it was feasible to recruit into a randomised trial of this nature in ward patients with acute pancreatitis. 36 (72%) completed the allocated 48 hours of goal directed fluids with 10 (20%) discharged within 48 hours and 4 withdrawals (3 GDFT and 1 SC).  Baseline characteristics of the groups were similar with only 3 participants having severe disease (6%, 1 GDFT, 2 SC). Similar volumes of IV fluids were administered in both groups (GDFT 5465 (1839) ml, SC 5211 (1745) ml). GDFT group had a lower heart rate, blood pressure and respiratory rate and improved oxygen saturations. GDFT was not associated with any harms. Complications of AP appear to be similar as was duration of stay in intensive care. Length of hospital stay was 5 (2.9) in GDFT and 6.3 (7.6) in SC groups. Conclusions Ward GDFT is feasible and shows a signal of possible efficacy in acute pancreatitis in this early-stage study. A larger multi-site RCT is required to confirm clinical and cost effectiveness. </jats:sec

Ward based goal directed fluid therapy (GDFT) in acute pancreatitis (GAP) trial: a feasibility randomised controlled trial [ISRCTN 36077283]

File replaced (incorrect version) on 9/8/22 by KT (LDS).Background: Goal-directed fluid therapy (GDFT) reduces complications in patients undergoing major general surgery. There are no reports of cardiac output evaluation being used to optimise the fluid administration for patients with acute pancreatitis (AP) in a general surgery ward. Method: 50 patients with AP were randomised to either ward-based GDFT (n=25) with intravenous (IV) fluids administered based on stroke volume optimisation protocol or standard care (SC) (n=25), but with blinded cardiac output evaluation, for 48-hours following hospital admission. Primary outcome was feasibility. Results: 50 of 116 eligible patients (43.1%) were recruited over 20 months demonstrating feasibility. 36 (72%) completed the 48-hours of GDFT; 10 (20%) discharged within 48-hours and 4 withdrawals (3 GDFT, 1 SC). Baseline characteristics were similar with only 3 participants having severe disease (6%, 1 GDFT, 2 SC). Similar volumes of IV fluids were administered in both groups (GDFT 5465 (1839) ml, SC 5211 (1745) ml). GDFT group had a lower heart rate, blood pressure and respiratory rate and improved oxygen saturations. GDFT was not associated with any harms. There was no evidence of difference in complications of AP (GDFT 24%, SC 32%) or in the duration of stay in intensive care (GDFT 0 (0), SC 0.7 (3) days). Length of hospital stay was 5 (2.9) days in GDFT and 6.3 (7.6) in SC groups. Conclusion: Ward-based GDFT is feasible and shows a signal of possible efficacy in AP in this early-stage study. A larger multi-site RCT is required to confirm clinical and cost effectiveness