Heart transplant waiting list implications of increased ventricular assist device use as a bridge strategy: A national analysis.

The use of ventricular assist devices (VADs) as a bridge to heart transplant (HT) is increasing, while HT volume remains stagnant. This may portend longer waiting times and an otherwise more competitive environment for all patients on the HT waiting list. A retrospective analysis of patients who were listed for HT in the United Network for Organ Sharing (UNOS) database from 2000 to 2015 was conducted. Mean waiting time, proportion of HT reception (%HT), proportion of death (%death), and proportion of waiting list removal (%removal) were calculated across three eras: Era 1 (2000-2007), Era 2 (2008-2011), and Era 3 (2012-2015). During the study period, 29 728 patients successfully underwent HT. 19 127 (64.3%) were directly transplanted (direct HT); 4491 (15.1%) received VADs prior to listing as a bridge to decision (BTD); and 4593 (15.5%) received VADs after listing as a bridge to transplant (BTT). Across the three eras, the average number of registrants per year grew. Among all groups, waiting time increased across the eras. %HT generally decreased in the BTD and BTT groups but remained constant in the direct HT group. %removal increased, while %death decreased in all group across the eras. Waiting time for HT increased from 2000 to 2015. Patients with VADs as a bridge strategy experienced decreasing %HT and increasing %removal but stable survival. Improvements in VAD safety and durability will ensure their success as part of a bridge strategy to HT under the new UNOS allocation policy.

IL-1R signaling enables bystander cells to overcome bacterial blockade of host protein synthesis.

The innate immune system is critical for host defense against microbial pathogens, yet many pathogens express virulence factors that impair immune function. Here, we used the bacterial pathogen Legionella pneumophila to understand how the immune system successfully overcomes pathogen subversion mechanisms. L. pneumophila replicates within macrophages by using a type IV secretion system to translocate bacterial effectors into the host cell cytosol. As a consequence of effector delivery, host protein synthesis is blocked at several steps, including translation initiation and elongation. Despite this translation block, infected cells robustly produce proinflammatory cytokines, but the basis for this is poorly understood. By using a reporter system that specifically discriminates between infected and uninfected cells within a population, we demonstrate here that infected macrophages produced IL-1α and IL-1ß, but were poor producers of IL-6, TNF, and IL-12, which are critical mediators of host protection. Uninfected bystander cells robustly produced IL-6, TNF, and IL-12, and this bystander response required IL-1 receptor (IL-1R) signaling during early pulmonary infection. Our data demonstrate functional heterogeneity in production of critical protective cytokines and suggest that collaboration between infected and uninfected cells enables the immune system to bypass pathogen-mediated translation inhibition to generate an effective immune response.

Alveolar macrophages and neutrophils are the primary reservoirs for Legionella pneumophila and mediate cytosolic surveillance of type IV secretion.

Legionella pneumophila, an intracellular pathogen responsible for the severe pneumonia Legionnaires' disease, uses its dot/icm-encoded type IV secretion system (T4SS) to translocate effector proteins that promote its survival and replication into the host cell cytosol. However, by introducing bacterial products into the host cytosol, L. pneumophila also activates cytosolic immunosurveillance pathways, thereby triggering robust proinflammatory responses that mediate the control of infection. Thus, the pulmonary cell types that L. pneumophila infects not only may act as an intracellular niche that facilitates its pathogenesis but also may contribute to the immune response against L. pneumophila. The identity of these host cells remains poorly understood. Here, we developed a strain of L. pneumophila producing a fusion protein consisting of ß-lactamase fused to the T4SS-translocated effector RalF, which allowed us to track cells injected by the T4SS. Our data reveal that alveolar macrophages and neutrophils both are the primary recipients of T4SS-translocated effectors and harbor viable L. pneumophila during pulmonary infection of mice. Moreover, both alveolar macrophages and neutrophils from infected mice produced tumor necrosis factor and interleukin-1α in response to T4SS-sufficient, but not T4SS-deficient, L. pneumophila. Collectively, our data suggest that alveolar macrophages and neutrophils are both an intracellular reservoir for L. pneumophila and a source of proinflammatory cytokines that contribute to the host immune response against L. pneumophila during pulmonary infection.

Association Among Surgeon Experience, Patient Risk, and Outcomes in Coronary Artery Bypass Grafting.

BACKGROUND: There is an association between surgeon experience and outcomes after cardiac surgery. However, this association is not well studied in the context of patient risk. The purpose of this single-center, retrospective, observational study was to describe how surgeon experience relates to patient risk in isolated coronary artery bypass grafting (CABG) surgery and how this impacts patient outcomes. METHODS: Surgeon experience was defined as time between the surgeon finishing fellowship and date of the patient's surgery. Society of Thoracic Surgeons (STS) Predicted Risk of Mortality (PROM) was used to define patient risk. The Kaplan-Meier method was used to calculate long-term survival, and multivariable Cox proportional hazards regression was used to determine the effect of surgeon experience on survival. RESULTS: Between 2002 and 2018, 7652 patients underwent isolated CABG. STS PROM was 1.35% (interquartile range [IQR], 0.70%-2.80%), 1.55% (IQR, 0.79%-3.34%), 1.78% (IQR, 0.84%-3.84%), and 1.19% (IQR, 0.62%-2.41%) in surgeon experience quartiles 1 (0.01-6.05 years), 2 (6.05-11.5 years), 3 (11.5-16.6 years), and 4 (16.6-32.1 years), respectively (P < .001). For patients in the lowest PROM quartile, Kaplan-Meier survival was similar across surgeon experience groups (P = .66). For patients in the highest PROM quartile, increasing surgeon experience was associated with better survival (P < .001). Cox regression identified surgeon experience as a protective factor (hazard ratio, 0.99, P = .027). In the least experienced surgeon group, increased ejection fraction was a protective factor for long-term survival (hazard ratio, 0.97; 95% confidence interval, 0.95-0.99). CONCLUSIONS: Increasing surgeon experience is associated with higher-risk patients, but the most experienced surgeons take on lower-risk patients. Greater experience correlates with improved outcomes, especially with higher-risk cases.