Molecular biology of cholangiocarcinoma and its implications for targeted therapy in patient management.

Cholangiocarcinoma (CCA) remains a devastating malignancy and a significant challenge to treat. The majority of CCA patients are diagnosed at an advanced stage, making the disease incurable in most cases. The advent of high-throughput genetic sequencing has significantly improved our understanding of the molecular biology underpinning cancer.

The importance of preclinical models in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an adenocarcinoma of the hepatobiliary system with a grim prognosis. Incidence is rising globally and surgery is currently the only curative treatment, but is only available for patients who are fit and diagnosed in an early-stage of disease progression. Great importance has been placed on developing preclinical models to help further our understanding of CCA and potential treatments to improve therapeutic outcomes.

Impacts of an Acute Care Telenursing Program on Discharge, Patient Experience, and Nursing Experience: Retrospective Cohort Comparison Study.

Background: Despite widespread growth of televisits and telemedicine, it is unclear how telenursing could be applied to augment nurse labor and support nursing.

Objective: This study evaluated a large-scale acute care telenurse (ACTN) program to support web-based admission and discharge processes for hospitalized patients.

Methods: A retrospective, observational cohort comparison was performed in a large academic hospital system (approximately 2100 beds) in Houston, Texas, comparing patients in our pilot units for the ACTN program (telenursing cohort) between June 15, 2022, and December 31, 2022, with patients who did not participate (nontelenursing cohort) in the same units and timeframe.

Utilizing Telenursing to Supplement Acute Care Nursing in an Era of Workforce Shortages: A Feasibility Pilot.

Hospitals are experiencing a nursing shortage crisis that is expected to worsen over the next decade. Acute care settings, which manage the care of very complex patients, need innovations that lessen nurses' workload burden while ensuring safe patient care and outcomes. Thus, a pilot study was conducted to evaluate the feasibility of implementing a large-scale acute care telenurse program, where a hospital-employed telenurse would complete admission and discharge processes for hospitalized patients virtually.

Predicting physiologically-relevant oxygen concentrations in precision-cut liver slices using mathematical modelling.

Precision cut liver slices represent an encouraging ex vivo method to understand the pathogenesis of liver disease alongside drug induced liver injury. Despite being more physiologically relevant compared to in vitro models, precision cut liver slices are limited by the availability of healthy human tissue and experimental variability. Internal oxygen concentration and media composition govern the longevity and viability of the slices during the culture period and as such, a variety of approaches have been taken to maximise the appropriateness of the internal oxygen concentrations across the slice.

Acupuncture and Reflexology for Patients Undergoing Chemotherapy: A Cohort Study.

Purpose: Around three quarters of individuals undergoing chemotherapy self-report multiple symptoms. There is clinical trial evidence of effectiveness for acupuncture for commonly experienced symptoms, and emerging evidence for reflexology, but little is known about the effects of these therapies on multiple symptoms when implemented in a real world setting during active chemotherapy treatment.

Methods: This was a cohort study of participants receiving reflexology and/or acupuncture while attending chemotherapy.

The Factors for Success and Lack of Success in the Breast Cancer Patient Care Pathway: A Qualitative Study From the Health Care Staff Perspective.

Objective: To produce information about factors related to successful and unsuccessful breast cancer care pathways from the health care staff perspective.

Materials And Methods: An electronic qualitative survey was used to collect data simultaneously from hospitals located in four different countries, focusing on four professional groups: diagnostic radiographers; radiation therapists; breast cancer nurses; and biomedical laboratory scientists (n = 23). The hospitals participating in the study treat breast cancer patients and research permits were applied from all of them.

Dual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion.

Unlabelled: Perfusate lactate clearance (LC) is considered one of the useful indicators of liver viability assessment during normothermic machine perfusion (NMP); however, the applicable scope and potential mechanisms of LC remain poorly defined in the setting of liver donation after circulatory death.

Methods: The ex situ NMP of end-ischemic human livers was performed using the OrganOx Metra device. We further studied the extracellular signal-regulated kinases (phospho-extracellular signal-regulated kinase1/2 [pERK1/2]) pathway and several clinical parameters of these livers with successful LC (sLC, n = 5) compared with non-sLC (nLC, n = 5) in the perfusate (<2.

Pilot study of a noninvasive real-time optical backscatter probe in liver transplantation.

Transplantation of severely steatotic donor livers is associated with early allograft dysfunction and poorer graft survival. Histology remains the gold standard diagnostic of donor steatosis despite the lack of consensus definition and its subjective nature. In this prospective observational study of liver transplant patients, we demonstrate the feasibility of using a handheld optical backscatter probe to assess the degree of hepatic steatosis and correlate the backscatter readings with clinical outcomes.

Cold Pulsatile Machine Perfusion Versus Static Cold Storage for Kidneys Donated After Circulatory Death: A Multicenter Randomized Controlled Trial.

Background: The benefits of cold pulsatile machine perfusion (MP) for the storage and transportation of kidneys donated after circulatory death are disputed. We conducted a UK-based multicenter, randomized controlled trial to compare outcomes of kidneys stored with MP versus static cold storage (CS).

Methods: Fifty-one pairs of kidneys donated after circulatory death were randomly allocated to receive static CS or cold pulsatile MP.

In situ normothermic perfusion of livers in controlled circulatory death donation may prevent ischemic cholangiopathy and improve graft survival.

Livers from controlled donation after circulatory death (DCD) donors suffer a higher incidence of nonfunction, poor function, and ischemic cholangiopathy. In situ normothermic regional perfusion (NRP) restores a blood supply to the abdominal organs after death using an extracorporeal circulation for a limited period before organ recovery. We undertook a retrospective analysis to evaluate whether NRP was associated with improved outcomes of livers from DCD donors.

Modelling the impact of changes in the extracellular environment on the cytosolic free NAD+/NADH ratio during cell culture.

Cancer cells depend on glucose metabolism via glycolysis as a primary energy source, despite the presence of oxygen and fully functioning mitochondria, in order to promote growth, proliferation and longevity. Glycolysis relies upon NAD+ to accept electrons in the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) reaction, linking the redox state of the cytosolic NAD+ pool to glycolytic rate. The free cytosolic NAD+/NADH ratio is involved in over 700 oxidoreductive enzymatic reactions and as such, the NAD+/NADH ratio is regarded as a metabolic readout of overall cellular redox state.

Observations on the ex situ perfusion of livers for transplantation.

Normothermic ex situ liver perfusion might allow viability assessment of livers before transplantation. Perfusion characteristics were studied in 47 liver perfusions, of which 22 resulted in transplants. Hepatocellular damage was reflected in the perfusate transaminase concentrations, which correlated with posttransplant peak transaminase levels.

Normothermic Perfusion in the Assessment and Preservation of Declined Livers Before Transplantation: Hyperoxia and Vasoplegia-Important Lessons From the First 12 Cases.

Background: A program of normothermic ex situ liver perfusion (NESLiP) was developed to facilitate better assessment and use of marginal livers, while minimizing cold ischemia.

Methods: Declined marginal livers and those offered for research were evaluated. Normothermic ex situ liver perfusion was performed using an erythrocyte-based perfusate.

Modulation of Antimalarial Activity at a Putative Bisquinoline Receptor In Vivo Using Fluorinated Bisquinolines.

Antimalarials can interact with heme covalently, by π⋅⋅⋅π interactions or by hydrogen bonding. Consequently, the prototropy of 4-aminoquinolines and quinoline methanols was investigated by using quantum mechanics. Calculations showed mefloquine protonated preferentially at the piperidine and was impeded at the endocyclic nitrogen because of electronic rather than steric factors.

Preimplant Normothermic Liver Perfusion of a Suboptimal Liver Donated After Circulatory Death.

Livers retrieved after circulatory death are associated with an increased incidence of primary nonfunction, early allograft dysfunction, and biliary strictures. The authors report a case of preimplant normothermic perfusion of a suboptimal liver from a 57-year-old donor after circulatory death who had been hospitalized for 9 days; predonation alanine transaminase level was 63 IU/L, and the period from withdrawal of life-supporting treatment to circulatory arrest was 150 minutes. After 5 hours of static cold storage, the liver was subject to normothermic machine perfusion with a plasma-free red cell-based perfusate.

Analysis of ischemia/reperfusion injury in time-zero biopsies predicts liver allograft outcomes.

Ischemia/reperfusion injury (IRI) that develops after liver implantation may prejudice long-term graft survival, but it remains poorly understood. Here we correlate the severity of IRIs that were determined by histological grading of time-zero biopsies sampled after graft revascularization with patient and graft outcomes. Time-zero biopsies of 476 liver transplants performed at our center between 2000 and 2010 were graded as follows: nil (10.

In situ normothermic regional perfusion for controlled donation after circulatory death--the United Kingdom experience.

Organs recovered from donors after circulatory death (DCD) suffer warm ischemia before cold storage which may prejudice graft survival and result in a greater risk of complications after transplant. A period of normothermic regional perfusion (NRP) in the donor may reverse these effects and improve organ function. Twenty-one NRP retrievals from Maastricht category III DCD donors were performed at three UK centers.

Sildenafil citrate in a donation after circulatory death experimental model of renal ischemia-reperfusion injury.

Introduction: Phosphodiesterase-5 inhibitors prevent the breakdown of cyclic guanosine 3',5'-monophosphate (cGMP) and therefore may be useful in reducing the detrimental effects of ischemia-reperfusion (I/R) injury. The aim of this study was to assess the effects of the phosphodiesterase-5 inhibitor sildenafil, on I/R injury in a porcine model of donation after circulatory death kidney transplantation.

Methods: Kidneys were subjected to 20 min warm ischemia followed by 2 or 18 hr of cold storage (n=6 kidneys per group).

Normothermic regional perfusion for donation after circulatory death without prior heparinization.

Background: Over 40% of deceased donors in the UK donate after circulatory death (DCD). Normothermic regional perfusion has been reported to improve outcomes in such donors in Europe and the United States. Unlike the United States, legal and professional requirements in the UK prevent cannulation and heparinization before verification of death, which must be a minimum of 5 min after circulatory arrest.

Functional characterization of late outgrowth endothelial progenitor cells in patients with end-stage renal failure.

Renal transplantation is potentially curative in renal failure, but long-term efficacy is limited by untreatable chronic rejection. Endothelial damage contributes to chronic rejection and is potentially repairable by circulating endothelial progenitor cells (EPC). The frequency and function of EPC are variably influenced by end-stage renal failure (ESRF).