Prevalence and drivers of nurse and physician distress in cardiovascular and oncology programmes at a Canadian quaternary hospital network during the COVID-19 pandemic: a quality improvement initiative.

OBJECTIVES: To assess the prevalence and drivers of distress, a composite of burnout, decreased meaning in work, severe fatigue, poor work-life integration and quality of life, and suicidal ideation, among nurses and physicians during the COVID-19 pandemic. DESIGN: Cross-sectional design to evaluate distress levels of nurses and physicians during the COVID-19 pandemic between June and August 2021. SETTING: Cardiovascular and oncology care settings at a Canadian quaternary hospital network. PARTICIPANTS: 261 nurses and 167 physicians working in cardiovascular or oncology care. Response rate was 29% (428 of 1480). OUTCOME MEASURES: Survey tool to measure clinician distress using the Well-Being Index (WBI) and additional questions about workplace-related and COVID-19 pandemic-related factors. RESULTS: Among 428 respondents, nurses (82%, 214 of 261) and physicians (62%, 104 of 167) reported high distress on the WBI survey. Higher WBI scores (≥2) in nurses were associated with perceived inadequate staffing (174 (86%) vs 28 (64%), p=0.003), unfair treatment, (105 (52%) vs 11 (25%), p=0.005), and pandemic-related impact at work (162 (80%) vs 22 (50%), p<0.001) and in their personal life (135 (67%) vs 11 (25%), p<0.001), interfering with job performance. Higher WBI scores (≥3) in physicians were associated with perceived inadequate staffing (81 (79%) vs 32 (52%), p=0.001), unfair treatment (44 (43%) vs 13 (21%), p=0.02), professional dissatisfaction (29 (28%) vs 5 (8%), p=0.008), and pandemic-related impact at work (84 (82%) vs 35 (56%), p=0.001) and in their personal life (56 (54%) vs 24 (39%), p=0.014), interfering with job performance. CONCLUSION: High distress was common among nurses and physicians working in cardiovascular and oncology care settings during the pandemic and linked to factors within and beyond the workplace. These results underscore the complex and contextual aspects of clinician distress, and the need to develop targeted approaches to effectively address this problem.

Colony stimulating factor-1 producing endothelial cells and mesenchymal stromal cells maintain monocytes within a perivascular bone marrow niche.

Macrophage colony stimulating factor-1 (CSF-1) plays a critical role in maintaining myeloid lineage cells. However, congenital global deficiency of CSF-1 (Csf1op/op) causes severe musculoskeletal defects that may indirectly affect hematopoiesis. Indeed, we show here that osteolineage-derived Csf1 prevented developmental abnormalities but had no effect on monopoiesis in adulthood. However, ubiquitous deletion of Csf1 conditionally in adulthood decreased monocyte survival, differentiation, and migration, independent of its effects on bone development. Bone histology revealed that monocytes reside near sinusoidal endothelial cells (ECs) and leptin receptor (Lepr)-expressing perivascular mesenchymal stromal cells (MSCs). Targeted deletion of Csf1 from sinusoidal ECs selectively reduced Ly6C- monocytes, whereas combined depletion of Csf1 from ECs and MSCs further decreased Ly6Chi cells. Moreover, EC-derived CSF-1 facilitated recovery of Ly6C- monocytes and protected mice from weight loss following induction of polymicrobial sepsis. Thus, monocytes are supported by distinct cellular sources of CSF-1 within a perivascular BM niche.

Ethical decision making during a healthcare crisis: a resource allocation framework and tool.

The COVID-19 pandemic has strained healthcare resources the world over, requiring healthcare providers to make resource allocation decisions under extraordinary pressures. A year later, our understanding of COVID-19 has advanced, but our process for making ethical decisions surrounding resource allocation has not. During the first wave of the pandemic, our institution uniformly ramped-down clinical activity to accommodate the anticipated demands of COVID-19, resulting in resource waste and inefficiency. In preparation for the second wave, we sought to make such ramp down decisions more prudently and ethically. We report the development of a tool that can be used to make fair and ethical decisions in times of resource scarcity. We formed an interprofessional team to develop and use this tool to ensure that a diverse range of stakeholder perspectives were represented in this development process. This team, called the clinical activity recovery team, established institutional objectives that were combined with well-established procedural values, substantive ethical principles and decision-making criteria by using a variation on the well-known accountability for reasonableness ethical framework. The result of this is a stepwise, semiquantitative, ethical decision tool that can be applied to resource allocation challenges in order to reach fair and ethically defensible decisions. This ethical decision tool can be applied in various contexts and may prove useful at both the institutional and the departmental level; indeed this is how it is applied at our centre. As the second wave of COVID-19 strains healthcare resources, this tool can help clinical leaders to make fair decisions.

Long-term mortality risk stratification of liver transplant recipients: real-time application of deep learning algorithms on longitudinal data.

BACKGROUND: Survival of liver transplant recipients beyond 1 year since transplantation is compromised by an increased risk of cancer, cardiovascular events, infection, and graft failure. Few clinical tools are available to identify patients at risk of these complications, which would flag them for screening tests and potentially life-saving interventions. In this retrospective analysis, we aimed to assess the ability of deep learning algorithms of longitudinal data from two prospective cohorts to predict complications resulting in death after liver transplantation over multiple timeframes, compared with logistic regression models. METHODS: In this machine learning analysis, model development was done on a set of 42 146 liver transplant recipients (mean age 48·6 years [SD 17·3]; 17 196 [40·8%] women) from the Scientific Registry of Transplant Recipients (SRTR) in the USA. Transferability of the model was further evaluated by fine-tuning on a dataset from the University Health Network (UHN) in Canada (n=3269; mean age 52·5 years [11·1]; 1079 [33·0%] women). The primary outcome was cause of death, as recorded in the databases, due to cardiovascular causes, infection, graft failure, or cancer, within 1 year and 5 years of each follow-up examination after transplantation. We compared the performance of four deep learning models against logistic regression, assessing performance using the area under the receiver operating characteristic curve (AUROC). FINDINGS: In both datasets, deep learning models outperformed logistic regression, with the Transformer model achieving the highest AUROCs in both datasets (p<0·0001). The AUROC for the Transformer model across all outcomes in the SRTR dataset was 0·804 (99% CI 0·795-0·854) for 1-year predictions and 0·733 (0·729-0·769) for 5-year predictions. In the UHN dataset, the AUROC for the top-performing deep learning model was 0·807 (0·795-0·842) for 1-year predictions and 0·722 (0·705-0·764) for 5-year predictions. AUROCs ranged from 0·695 (0·680-0·713) for prediction of death from infection within 5 years to 0·859 (0·847-0·871) for prediction of death by graft failure within 1 year. INTERPRETATION: Deep learning algorithms can incorporate longitudinal information to continuously predict long-term outcomes after liver transplantation, outperforming logistic regression models. Physicians could use these algorithms at routine follow-up visits to identify liver transplant recipients at risk for adverse outcomes and prevent these complications by modifying management based on ranked features. FUNDING: Canadian Donation and Transplant Research Program, CIFAR AI Chairs Program.

The psychological burden of waiting for procedures and patient-centred strategies that could support the mental health of wait-listed patients and caregivers during the COVID-19 pandemic: A scoping review.

BACKGROUND: Waiting for procedures delayed by COVID-19 may cause anxiety and related adverse consequences. OBJECTIVE: To synthesize research on the mental health impact of waiting and patient-centred mitigation strategies that could be applied in the COVID-19 context. METHODS: Using a scoping review approach, we searched 9 databases for studies on waiting lists and mental health and reported study characteristics, impacts and intervention attributes and outcomes. RESULTS: We included 51 studies that focussed on organ transplant (60.8%), surgery (21.6%) or cancer management (13.7%). Most patients and caregivers reported anxiety, depression and poor quality of life, which deteriorated with increasing wait time. The impact of waiting on mental health was greater among women and new immigrants, and those of younger age, lower socio-economic status, or with less-positive coping ability. Six studies evaluated educational strategies to develop coping skills: 2 reduced depression (2 did not), 1 reduced anxiety (2 did not) and 2 improved quality of life (2 did not). In contrast, patients desired acknowledgement of concerns, peer support, and periodic communication about wait-list position, prioritization criteria and anticipated procedure date. CONCLUSIONS: Findings revealed patient-centred strategies to alleviate the mental health impact of waiting for procedures. Ongoing research should explore how to optimize the impact of those strategies for diverse patients and caregivers, particularly in the COVID-19 context. PATIENT OR PUBLIC CONTRIBUTION: Six patients and four caregivers waiting for COVID-19-delayed procedures helped to establish eligibility criteria, plan data extraction and review a draft and final report.

Burnout and distress among physicians in a cardiovascular centre of a quaternary hospital network: a cross-sectional survey.

BACKGROUND: Burnout and distress have a negative impact on physicians and the treatment they provide. Our aim was to measure the prevalence of burnout and distress among physicians in a cardiovascular centre of a quaternary hospital network in Canada, and compare these outcomes to those for physicians at academic health science centres (AHSCs) in the United States. METHODS: We conducted a survey of physicians practising in a cardiovascular centre at 2 quaternary referral hospitals in Toronto, Ontario, between Nov. 27, 2018, and Jan. 31, 2019. The survey tool included the Well-Being Index (WBI), which measures fatigue, depression, burnout, anxiety or stress, mental and physical quality of life, work-life integration, meaning in work and distress; a score of 3 or higher indicated high distress. We also evaluated physicians' perception of the adequacy of staffing levels and of fair treatment in the workplace, and satisfaction with the electronic health record. We carried out standard univariate statistical comparisons using the χ2, Fisher exact or Kruskal-Wallis test as appropriate to perform univariate comparisons in the sample of respondents. We assessed the relation between a WBI score of 3 or higher and demographic characteristics. We compared univariate associations among WBI data for physicians at AHSCs in the US who completed the WBI to responses from our participants. RESULTS: The response rate to the survey was 84.1% (127/151). Of the 127 respondents, 83 (65.4%) reported burnout in the previous month, and 68 (53.5%) reported emotional problems. Sixty-nine respondents (54.3%) had a WBI score of 3 or higher. Respondents were more likely to have a WBI score of 3 or higher versus a score less than 3 if they perceived insufficient staffing levels (52/69 [75%] v. 26/58 [45%], p = 0.02) or unfair treatment (23/69 [33%] v. 8/58 [14%], p = 0.03), or were anesthesiologists (26/35 [74%] v. 43/92 [47%] for other specialists, p = 0.005). Compared to 21 594 physicians in practice at AHSCs in the US, our respondents had a higher mean WBI score (2.4 v. 1.8, p = 0.004) and reported a higher prevalence of burnout (65.4% v. 56.6%, p = 0.048). INTERPRETATION: Physicians in this study had high levels of burnout and distress, driven by the perception of inadequate staffing levels and being treated unfairly in the workplace. Addressing these institutional factors may improve physicians' work experience and patient outcomes.

c-Myb Exacerbates Atherosclerosis through Regulation of Protective IgM-Producing Antibody-Secreting Cells.

Mechanisms that govern transcriptional regulation of inflammation in atherosclerosis remain largely unknown. Here, we identify the nuclear transcription factor c-Myb as an important mediator of atherosclerotic disease in mice. Atherosclerosis-prone animals fed a diet high in cholesterol exhibit increased levels of c-Myb in the bone marrow. Use of mice that either harbor a c-Myb hypomorphic allele or where c-Myb has been preferentially deleted in B cell lineages revealed that c-Myb potentiates atherosclerosis directly through its effects on B lymphocytes. Reduced c-Myb activity prevents the expansion of atherogenic B2 cells yet associates with increased numbers of IgM-producing antibody-secreting cells (IgM-ASCs) and elevated levels of atheroprotective oxidized low-density lipoprotein (OxLDL)-specific IgM antibodies. Transcriptional profiling revealed that c-Myb has a limited effect on B cell function but is integral in maintaining B cell progenitor populations in the bone marrow. Thus, targeted disruption of c-Myb beneficially modulates the complex biology of B cells in cardiovascular disease.

Comparison of cardiac surgery mortality reports using administrative and clinical data sources: a prospective cohort study.

BACKGROUND: Outcomes for coronary artery bypass surgery are of broadening interest, but the impact of data type on quality reporting has not been fully examined. We compared the performance of administrative and clinical data-based risk adjustment models at a tertiary-quaternary care hospital. METHODS: We used a prospective study design to test two risk adjustment models, one from administrative (Canadian Institute for Health Information [CIHI] Cardiac Care Quality Indicator) and one from clinical data (Society of Thoracic Surgeons), on cardiac surgical procedures performed between 2013 and 2016 (n = 1635). Our primary outcome was in-hospital mortality within 30 days of surgery. Model performance was established by comparing predicted and observed mortality, model calibration and handling of critical covariates. RESULTS: Observed mortality was 1.96%, which was the same as that predicted by the Society of Thoracic Surgeons model (1.96%), but significantly higher than that predicted by the CIHI model (1.03%). Despite both models having similar C statistics (0.756 CIHI; 0.758 Society of Thoracic Surgeons), the CIHI model showed significant underestimation of mortality among patients at higher risk. There was significant miscalibration of risk associated with 7 covariates: New York Heart Association class IV, congestive heart failure, ejection fraction less than 20%, atrial fibrillation, acute coronary insufficiency, cardiac compromise (shock, myocardial infarction < 24 h, intra-aortic balloon pump, cardiac resuscitation or preprocedure circulatory support) and creatinine concentration of 100 mg/dL or more. Together, these factors accounted for 84% of the difference in predicted mortality between the administrative and clinical models. INTERPRETATION: Risk prediction using administrative data underestimated risk of death, potentially inflating observed-to-predicted mortality ratios at hospitals with patients who are more ill. Caution is warranted when hospital reports of cardiac surgery outcomes are based on administrative data alone.

Self-renewing resident arterial macrophages arise from embryonic CX3CR1(+) precursors and circulating monocytes immediately after birth.

Resident macrophages densely populate the normal arterial wall, yet their origins and the mechanisms that sustain them are poorly understood. Here we use gene-expression profiling to show that arterial macrophages constitute a distinct population among macrophages. Using multiple fate-mapping approaches, we show that arterial macrophages arise embryonically from CX3CR1(+) precursors and postnatally from bone marrow-derived monocytes that colonize the tissue immediately after birth. In adulthood, proliferation (rather than monocyte recruitment) sustains arterial macrophages in the steady state and after severe depletion following sepsis. After infection, arterial macrophages return rapidly to functional homeostasis. Finally, survival of resident arterial macrophages depends on a CX3CR1-CX3CL1 axis within the vascular niche.

The in-hospital costs of treating high-risk patients with fenestrated and branched endografts.

OBJECTIVE: This study determined the 30-day morbidity and mortality and in-hospital costs of elective fenestrated (fEVAR) and branched (bEVAR) endovascular aneurysm repairs at a single academic institution and determined factors that influence them. METHODS: All elective fEVAR or bEVAR patients treated between November 2007 and March 2014 in a Canadian academic hospital were included. Procedural details, 30-day morbidity and mortality rates, and cost of hospitalization were analyzed. Nonparametric bootstrap analysis was used to compare means between groups and calculate confidence intervals (CIs). RESULTS: There were 84 consecutive fEVAR (n = 61) and bEVAR (n = 23) procedures. The 30-day mortality was 3.3% for fEVAR and 4.3% for bEVAR. Mean hospital stay was 7.2 ± 0.8 days for fEVAR and 12.6 ± 2.2 days for bEVAR. The mean cost of the index hospitalization was $57,000 for fEVAR and $91,000 for bEVAR. Device-related costs accounted for 55% of the total costs. The occurrence of intraoperative or postoperative events were used to further divide each of the fEVAR and bEVAR groups into "complicated hospitalization" (fEVAR, n = 10; bEVAR, n = 13) and "uncomplicated hospitalization" (fEVAR, n = 51; bEVAR, n = 10) groups. Device-related costs were not significantly different between the complicated and uncomplicated hospitalization groups (mean difference [95% CI] fEVAR: $3383 [-$3405 to $9809], P = .3; and bEVAR: $1930 [-$7892 to $11,288], P = .68). However, there were significant differences between the complicated and uncomplicated hospitalization groups in hospital length of stay (mean difference [95% CI] fEVAR: 8.1 [3.0-13.2] days, P = .001; and bEVAR: 10.8 [5.9-19.9] days, P = .002) and nondevice-related costs (mean difference [95% CI,] fEVAR: $25,843 [$11,689-$43,247], P = .001; and bEVAR; $20,326 [$9362-$36,615], P = .002). CONCLUSIONS: bEVAR and fEVAR are expensive interventions. Intraoperative adverse events and postoperative systemic complications dramatically increase costs and length of stay. Measures to minimize complications will reduce hospitalization costs and improve patient outcomes.

Pheochromocytoma in a Pregnant Woman With Prior Traumatic Aortic Injury.

BACKGROUND: Pheochromocytoma, a catecholamine-producing tumor seldom encountered in pregnancy, is often heralded by nonspecific symptoms and undue mortality with delayed diagnosis. The presence of an aortic pseudoaneurysm poses a management challenge given the risk of aortic rupture amplified by hypertensive events. CASE: A 30-year-old woman, gravida 3 para 1, presented at 23 6/7 weeks of gestation with vomiting, chest pain, and severe hypertension. Investigation revealed adrenal pheochromocytoma and pseudoaneurysm at the site of a previous aortic injury. Prazosin and phenoxybenzamine achieved α-blockade with subsequent addition of labetalol for ß-blockade. Concerns for aortic dissection led to endovascular aortic repair at 30 2/7 weeks of gestation. A female neonate was delivered by urgent cesarean delivery for persistent postprocedure fetal bradycardia. An adrenalectomy followed with near-immediate symptom resolution. Mother and neonate remain well. CONCLUSION: The case underscores the necessity of a meticulous approach to hypertension management and the pivotal role of diligent multidisciplinary collaboration to achieve a safe outcome.

Splenic metabolic activity predicts risk of future cardiovascular events: demonstration of a cardiosplenic axis in humans.

OBJECTIVES: This study sought to determine whether splenic activation after acute coronary syndrome (ACS) is linked to leukocyte proinflammatory remodeling and whether splenic activity independently predicts the risk of cardiovascular disease (CVD) events. BACKGROUND: Pre-clinical data suggest the existence of a cardiosplenic axis, wherein activation of hematopoietic tissues (notably in the spleen) results in liberation of proinflammatory leukocytes and accelerated atherosclerotic inflammation. However, it is presently unknown whether a cardiosplenic axis exists in humans and whether splenic activation relates to CVD risk. METHODS: (18)F-fluorodeoxyglucose ((18)FDG)-positron emission tomography (PET) imaging was performed in 508 individuals across 2 studies. In the first study, we performed FDG-PET imaging in 22 patients with recent ACS and 22 control subjects. FDG uptake was measured in spleen and arterial wall, whereas proinflammatory gene expression of circulating leukocytes was assessed by quantitative real-time polymerase chain reaction. In a second study, we examined the relationship between splenic tissue FDG uptake with subsequent CVD events during follow-up (median 4 years) in 464 patients who previously had undergone FDG-PET imaging. RESULTS: Splenic activity increased after ACS and was significantly associated with multiple indices of inflammation: 1) up-regulated gene expression of proinflammatory leukocytes; 2) increased C-reactive protein; and 3) increased arterial wall inflammation (FDG uptake). Moreover, in the second study, splenic activity (greater than or equal to the median) was associated with an increased risk of CVD events (hazard ratio [HR]: 3.3; 95% confidence interval [CI]: 1.5 to 7.3; p = 0.003), which remained significant after adjustment for CVD risk factors (HR: 2.26; 95% CI: 1.01 to 5.06; p = 0.04) and for arterial FDG uptake (HR: 2.68; 95% CI: 1.5 to 7.4; p = 0.02). CONCLUSIONS: Our findings demonstrate increased splenic metabolic activity after ACS and its association with proinflammatory remodeling of circulating leukocytes. Moreover, we observed that metabolic activity of the spleen independently predicted risk of subsequent CVD events. Collectively, these findings provide evidence of a cardiosplenic axis in humans similar to that shown in pre-clinical studies.

Lack of group X secreted phospholipase A2 increases survival following pandemic H1N1 influenza infection.

The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GX(-/-)) model and found that survival after infection was significantly greater in GX(-/-) mice than in GX(+/+) mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GX(-/-) mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX(-/-) mice. Based on the central role of sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza.

Management of acute limb ischemia in the pediatric population.

OBJECTIVE: Acute limb ischemia (ALI) in pediatric patients is rare but may lead to limb loss and life-long complications. This study reviewed the experience of a Canadian tertiary pediatric center with the medical and operative management of ALI. METHODS: The medical records of inpatients diagnosed with ALI of the upper or lower limb between 1999 and 2012 were reviewed. Patient demographics, arterial clot site and etiology, intervention, anticoagulation type and duration, and short-term and long-term complications were analyzed. RESULTS: A total of 151 patients (45% female) presented with signs of limb ischemia, of whom 38% were aged <30 days, 46% were between 1 and 12 months, and 16% were between 1 and 18 years. Ninety-four percent of those injuries involved the lower limbs. Ninety-one percent were due to vessel catheterization, 5% were idiopathic, 1% were congenital, and 4% traumatic. Ninety-four percent were managed nonoperatively. Patients were treated with a combination of thrombolysis, unfractionated or low-molecular-weight heparin, aspirin or warfarin, or both (duration, 1 day-13 years). All patients were monitored after discharge at our institution or at their referring hospital (average, 3.4 ± 2.8 years). Fifteen percent had complications related to ALI or anticoagulation (most commonly limb length or thigh circumference discrepancy, or intracranial hemorrhage). Nineteen percent of patients died of unrelated causes (sepsis, multiorgan dysfunction, or cardiac failure). CONCLUSIONS: In contrast with adults, ALI in children can generally be managed nonoperatively with anticoagulation, likely because of their greater ability to develop arterial collaterals. Long-term follow-up by a multidisciplinary team of pediatric and surgical specialists and allied health professionals is integral to achieving a successful outcome in children with ALI.

Innate response activator B cells aggravate atherosclerosis by stimulating T helper-1 adaptive immunity.

BACKGROUND: Atherosclerotic lesions grow via the accumulation of leukocytes and oxidized lipoproteins in the vessel wall. Leukocytes can attenuate or augment atherosclerosis through the release of cytokines, chemokines, and other mediators. Deciphering how leukocytes develop, oppose, and complement each other's function and shape the course of disease can illuminate our understanding of atherosclerosis. Innate response activator (IRA) B cells are a recently described population of granulocyte macrophage colony-stimulating factor-secreting cells of hitherto unknown function in atherosclerosis. METHODS AND RESULTS: Here, we show that IRA B cells arise during atherosclerosis in mice and humans. In response to a high-cholesterol diet, IRA B cell numbers increase preferentially in secondary lymphoid organs via Myd88-dependent signaling. Mixed chimeric mice lacking B cell-derived granulocyte macrophage colony-stimulating factor develop smaller lesions with fewer macrophages and effector T cells. Mechanistically, IRA B cells promote the expansion of classic dendritic cells, which then generate interferon γ-producing T helper-1 cells. This IRA B cell-dependent T helper-1 skewing manifests in an IgG1-to-IgG2c isotype switch in the immunoglobulin response against oxidized lipoproteins. CONCLUSIONS: Granulocyte macrophage colony-stimulating factor-producing IRA B cells alter adaptive immune processes and shift the leukocyte response toward a T helper-1-associated milieu that aggravates atherosclerosis.

Thoracic aortic endografting facilitates the resection of tumors infiltrating the aorta.

OBJECTIVES: We and others have reported the early experience with off-label use of thoracic aortic endografts to facilitate the resection of tumors infiltrating the aorta. We describe our extended experience and long-term outcome using this innovative approach. METHODS: Patients with preoperative suspected thoracic aortic infiltration who underwent endografting followed by en bloc tumor resection including the aortic wall were retrospectively reviewed and data were analyzed. RESULTS: Between 2008 and 2012, 5 patients (4 female) with a median age of 52 years (34-63 years) were included. Tumors infiltrating the aorta were non-small cell lung carcinomas (n = 3) and sarcomas (n = 2). Both patients with sarcoma had neoadjuvant radiation, whereas patients with non-small cell lung carcinomas had neoadjuvant (n = 2) or adjuvant chemoradiation (n = 1). Aortic endografting was performed 1 to 17 days before resection of the tumor. The proximal end of the stent-graft was deployed in the aortic arch (n = 2) or the descending aorta (n = 3). The tumor was resected en bloc in all patients and combined with chest wall and 2 to 3 levels of spinal resection in 4 of the 5 patients. Two patients with full-thickness aortic wall resection had additional buttressing of the defect. Cardiopulmonary bypass was never required. One patient had an empyema requiring debridements and thoracic window. After a median follow-up of 39 months (range, 9-62 months), all patients were alive and disease-free. None of them had overt endograft-related complications. CONCLUSIONS: Thoracic aortic endografting allowed safe en bloc resection of tumors invading the aortic wall. Therefore, the indication for thoracic aortic endografts could be extended to specific oncologic cases.

Myocardial infarction accelerates atherosclerosis.

During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.

Interleukin-6 is a potential biomarker for severe pandemic H1N1 influenza A infection.

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.