Ethical Considerations Surrounding Survival Benefit-Based Liver Allocation

poster abstractThe disparity between the demand for and supply of donor livers has continued to grow over the last two decades, placing greater weight on the need for efficient and effective allocation. Although the use of extended criteria donors (ECD) has shown greater potential, it remains unregulated. Schaubel et al. have recently proposed a survival benefit model which balances waitlist survival and potential transplantation benefit for a given quality of donor liver. The OPTN/UNOS Liver and Intestinal Organ Transplantation Committee considered this and other models in a recent report, concluding that the current allocation method does not require modification. In order to further evaluate the survival benefit model, the various ethical concerns shaping organ allocation were discussed and used to identify strengths and shortcomings associated with the proposed model. Compared to the current MELD/PELD system, the survival benefit model incorporates a greater number of ethical principles, uses a sophisticated statistical model to increase efficiency and reduce waste, minimizes bias, and parallels developments in the allocation of other organs. Conversely, the model fails to address quality of life concerns, prioritization for younger patients, its less promising posttransplant prediction accuracy, and potential issues regarding informed consent and economic burdens. To remedy these issues, we suggested incorporating various improvements based on recent literature. Although limitations exist, the survival benefit model now exists as a better means of improving allocation. We support the model proposed by Schaubel et al., with the amendments we suggested, and urge the OPTN/UNOS Liver and Intestinal Organ Transplantation Committee and the transplant community to strongly consider this model as another step toward better liver allocation

Opiate Written Behavioral Agreements: A Case for Abandonment

Written behavioral agreements (WBAs) are gaining popularity as part of the effort to manage the alarming increase in prescription drug abuse. The rationale for increased use of WBAs in managing patients with chronic pain is that they are believed to increase adherence to agreed-upon behaviors, reduce addiction to or diversion of prescription drugs, and satisfy informed consent requirements. However, there are no high-quality data to support their widespread use in any of these areas. The evidence used to support the use of WBAs is insufficient to justify their unfairness and the high risk of harm they pose to the doctor-patient relationship. Instead, we contend that WBAs are being used to provide leverage for severing relationships with some of our most challenging patients. We propose that physicians treating patients for chronic pain abandon the use of WBAs. Alternatives include open communication, detailed informed consent processes, carefully documented discussions, and most important, commitment to ongoing relationships even with difficult patients

032: Thirty months outcomes after PCI of unprotected left main coronary artery according to the SYNTAX score

AimsTo assess middle term outcomes according to SYNTAX score and rates of delayed surgical/bleeding events after unprotected left main (LM) coronary artery (ULMCA) PCI in an unselected patients population.MethodsConsecutive patients treated by PCI for ULMCA were included among a single center 3508 PCI database within 36 months. Syntax scores were calculated, post discharge extracardiac surgery or hemorrhage were recorded during follow-up as clinical outcomes (Death, TVR, MACCE=cardiovascular death+MI+stroke+TLR).Results102 (3.6%) patients underwent PCI of the LM, including 21 protected LM. Among the 81 patients with PCI of ULMCA, mean age was 65±13, 27% had urgent PCI for AMI or cardiogenic shock, 61% had DES.SYNTAX score was 28±14 in mean and ≤22 in 30 (37%), 23 to 32 in 22 (27%) and ≥33 in 29 (36%) patients.At 30±11 months follow up (98% of the patients), death occurred in 24 patients (30%), TVR in 16 (20%) and MACCE in 35 (43%). Clinical events according to the SYNTAX score are shown in figure. No cardiovascular death occurred in patients with syntax ≤22. MACCE rates were significantly lower when DES were used (24% vs. 64%, p<0.05) and in case of non-urgent PCI (36% vs. 71%, p<0.05).During follow-up, 20 (25%) and 12 (15%) patients underwent unplanned extracardiac surgery and/or hemorrhage, leading to antiplatelet withdrawal in 31% of the cases.ConclusionsIn unselected patients treated by PCI of ULMCA with Syntax score ≤22, outcomes were found to be excellent with no cardiovascular death observed at 30 months. DES and non-urgent PCI were associated with a better prognosis. One patient out of three underwent unplanned extracardiac surgery or hemorrhage during follow up.Figure: 30-months outcomes according to SYNTAX scor

Mafb lineage tracing to distinguish macrophages from other immune lineages reveals dual identity of Langerhans cells

Current systems for conditional gene deletion within mouse macrophage lineages are limited by ectopic activity or low efficiency. In this study, we generated a Mafb-driven Cre strain to determine whether any dendritic cells (DCs) identified by Zbtb46-GFP expression originate from a Mafb-expressing population. Lineage tracing distinguished macrophages from classical DCs, neutrophils, and B cells in all organs examined. At steady state, Langerhans cells (LCs) were lineage traced but also expressed Zbtb46-GFP, a phenotype not observed in any other population. After exposure to house dust mite antigen, Zbtb46-negative CD64(+) inflammatory cells infiltrating the lung were substantially lineage traced, but Zbtb46-positive CD64(−) cells were not. These results provide new evidence for the unique identity of LCs and challenge the notion that some inflammatory cells are a population of monocyte-derived DCs

Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation

BACKGROUND: Coronary atherosclerosis and its thrombotic complications are the major cause of mortality and morbidity throughout the industrialized world. Thrombosis on disrupted atherosclerotic plaques plays a key role in the onset of acute coronary syndromes. Macrophages density is one of the most critical compositions of plaque in both plaque vulnerability and thrombogenicity upon rupture. It has been shown that macrophages have a high uptake of (18)F-FDG (FDG). We studied the correlation of FDG uptake with histopathological macrophage accumulation in atherosclerotic plaques in a rabbit model. METHODS: Atherosclerosis was induced in rabbits (n = 6) by a combination of atherogenic diet and balloon denudation of the aorta. PET imaging was performed at baseline and 2 months after atherogenic diet and coregistered with magnetic resonance (MR) imaging. Normal (n = 3) rabbits served as controls. FDG uptake by the thoracic aorta was expressed as concentration (μCi/ml) and the ratio of aortic uptake-to-blood radioactivity. FDG uptake and RAM-11 antibody positive areas were analyzed in descending aorta. RESULTS: Atherosclerotic aortas showed significantly higher uptake of FDG than normal aortas. The correlation of aortic FDG uptake with macrophage areas assessed by histopathology was statistically significant although it was not high (r = 0.48, p < 0.0001). When uptake was expressed as the ratio of aortic uptake-to-blood activity, it correlated better (r = 0.80, p < 0.0001) with the macrophage areas, due to the correction for residual blood FDG activity. CONCLUSION: PET FDG activity correlated with macrophage content within aortic atherosclerosis. This imaging approach might serve as a useful non-invasive imaging technique and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion

Prediction of All-Cause Mortality Following Percutaneous Coronary Intervention in Bifurcation Lesions Using Machine Learning Algorithms

Stratifying prognosis following coronary bifurcation percutaneous coronary intervention (PCI) is an unmet clinical need that may be fulfilled through the adoption of machine learning (ML) algorithms to refine outcome predictions. We sought to develop an ML-based risk stratification model built on clinical, anatomical, and procedural features to predict all-cause mortality following contemporary bifurcation PCI. Multiple ML models to predict all-cause mortality were tested on a cohort of 2393 patients (training, n = 1795; internal validation, n = 598) undergoing bifurcation PCI with contemporary stents from the real-world RAIN registry. Twenty-five commonly available patient-/lesion-related features were selected to train ML models. The best model was validated in an external cohort of 1701 patients undergoing bifurcation PCI from the DUTCH PEERS and BIO-RESORT trial cohorts. At ROC curves, the AUC for the prediction of 2-year mortality was 0.79 (0.74–0.83) in the overall population, 0.74 (0.62–0.85) at internal validation and 0.71 (0.62–0.79) at external validation. Performance at risk ranking analysis, k-center cross-validation, and continual learning confirmed the generalizability of the models, also available as an online interface. The RAIN-ML prediction model represents the first tool combining clinical, anatomical, and procedural features to predict all-cause mortality among patients undergoing contemporary bifurcation PCI with reliable performance

Acceptance and commitment therapy for fatigue interference in advanced gastrointestinal cancer and caregiver burden: protocol of a pilot randomized controlled trial

Background: Fatigue interference with activities, mood, and cognition is one of the most prevalent and bothersome concerns of advanced gastrointestinal (GI) cancer patients. As fatigue interferes with patient functioning, family caregivers often report feeling burdened by increasing responsibilities. Evidence-based interventions jointly addressing cancer patient fatigue interference and caregiver burden are lacking. In pilot studies, acceptance and commitment therapy (ACT) has shown promise for addressing symptom-related suffering in cancer patients. The current pilot trial seeks to test a novel, dyadic ACT intervention for both advanced GI cancer patients with moderate-to-severe fatigue interference and their family caregivers with significant caregiving burden or distress. Methods: A minimum of 40 patient-caregiver dyads will be randomly assigned to either the ACT intervention or an education/support control condition. Dyads in both conditions attend six weekly 50-min telephone sessions. Outcomes are assessed at baseline as well as 2 weeks and 3 months post-intervention. We will evaluate the feasibility, acceptability, and preliminary efficacy of ACT for improving patient fatigue interference and caregiver burden. Secondary outcomes include patient sleep interference and patient and caregiver engagement in daily activities, psychological flexibility, and quality of life. We will also explore the effects of ACT on patient and caregiver physical and mental health service use. Discussion: Findings will inform a large-scale trial of intervention efficacy. Results will also lay the groundwork for further novel applications of ACT to symptom interference with functioning and caregiver burden in advanced cancer

Duration of Dual Antiplatelet Therapy Following Drug-Eluting Stent Implantation in Diabetic and Non-Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Diabetic patients account for an increasing number of patients undergoing percutaneous coronary intervention (PCI). However, diabetes mellitus (DM) is associated with increased residual platelet activity during dual antiplatelet treatment (DAPT) and DM patients have worse clinical outcomes after PCI as compared to non DM