The 2004 revision has done little to improve agreement on the higher ISHLT grades. An EMB grade ≥2R is not by itself sufficient as a basis for clinical decisions or as a research criterion. Steps should be taken toward greater uniformity in EMB grading, and efforts should be made to replace the ISHLT classification with diagnostic criteria--EMB based or otherwise--that correspond better with the pathophysiology of the transplanted heart.

Abstract-In earlier studies, our group has established a new "immunological" hypothesis for atherogenesis supported by experimental and clinical studies showing that inflammatory immunological reactions against heat shock protein 60 initiate the development of atherosclerosis. In the present study, we describe the discovery of a so-far-unknown network of dendritic cells in the innermost layer of arteries, the intima, but not veins of healthy humans and rabbits. The number of these dendritic cells is comparable to that of Langerhans cells in the skin, and dendritic cells show a similar phenotype (CD1a ϩ S-100 ϩ lag ϩ CD31 Ϫ CD83 Ϫ CD86 Ϫ and no staining for von Willebrand factor or smooth muscle cell myosin). These vascular-associated dendritic cells accumulate most densely in those arterial regions that are subjected to major hemodynamic stress by turbulent flow conditions and are known to be predisposed for the later development of atherosclerosis. These results open new perspectives for the activation of the immune system within the arterial wall.

ObjectivesTo evaluate the nonclinical outcomes of a proactive palliative care program funded and operated by a health system for Medicare Advantage plan beneficiaries.DesignObservational, retrospective study using propensity‐based matching.SettingA health system in southern California.ParticipantsIndividuals who received the intervention between 2007 and 2014 (n = 368) were matched with 1,075 comparison individuals within each of four disease groups: cancer, chronic obstructive pulmonary disease, heart failure, and dementia. All were known to be dead at the time of the retrospective study, were Medicare Advantage beneficiaries, and had 2 years of usage data before death. Median age at death for each disease group was older than 80.InterventionHome‐ and clinic‐based palliative care (PC) services provided by a multidisciplinary team.MeasurementsOutcomes included hospital costs, other healthcare costs, readmission rates, hospital admissions and bed days, intensive care unit use in final 30 days of life, and death within 30 days of an admission.ResultsIntervention participants in all four disease groups had less hospital use and lower hospital costs nonintervention participants, which drove lower overall healthcare costs. In the final 6 months of life, healthcare costs for the intervention groups stayed largely the same from month to month, whereas costs for comparison participants increased dramatically.ConclusionIn the context of an alternative payment model in which the provider was “at risk” of bearing the costs of care, a proactive PC program helped to avoid the escalation in hospital use and costs commonly seen in the final months of life.

AimsA non-invasive gene-expression profiling (GEP) test for rejection surveillance of heart transplant recipients originated in the USA. A European-based study, Cardiac Allograft Rejection Gene Expression Observational II Study (CARGO II), was conducted to further clinically validate the GEP test performance.Methods and resultsBlood samples for GEP testing (AlloMap®, CareDx, Brisbane, CA, USA) were collected during post-transplant surveillance. The reference standard for rejection status was based on histopathology grading of tissue from endomyocardial biopsy. The area under the receiver operating characteristic curve (AUC-ROC), negative (NPVs), and positive predictive values (PPVs) for the GEP scores (range 0–39) were computed. Considering the GEP score of 34 as a cut-off (>6 months post-transplantation), 95.5% (381/399) of GEP tests were true negatives, 4.5% (18/399) were false negatives, 10.2% (6/59) were true positives, and 89.8% (53/59) were false positives. Based on 938 paired biopsies, the GEP test score AUC-ROC for distinguishing ≥3A rejection was 0.70 and 0.69 for ≥2–6 and >6 months post-transplantation, respectively. Depending on the chosen threshold score, the NPV and PPV range from 98.1 to 100% and 2.0 to 4.7%, respectively.ConclusionFor ≥2–6 and >6 months post-transplantation, CARGO II GEP score performance (AUC-ROC = 0.70 and 0.69) is similar to the CARGO study results (AUC-ROC = 0.71 and 0.67). The low prevalence of ACR contributes to the high NPV and limited PPV of GEP testing. The choice of threshold score for practical use of GEP testing should consider overall clinical assessment of the patient's baseline risk for rejection.