Heart transplantation from donation after circulatory death: Impact on waitlist time and transplant rate.

The effect of using donation after circulatory death (DCD) hearts on waitlist outcomes has not been substantiated. We retrospectively analyzed 184 heart transplant (HT) candidates at our institution from 2019 to 2021. Patients were stratified into 2 observation periods centered on September 12, 2020, when the adult DCD HT program officially began. The primary outcome was a comparison of transplant rate between period 1 (pre-DCD) and period 2 (post-DCD). Secondary outcomes included waitlist time-to-transplant, waitlist mortality rate, independent predictors of incidence of HT, and posttransplant outcomes. A total of 165 HTs (n = 92 in period 1 and n = 73 in period 2) were performed. The median waitlist time-to-transplant decreased from 47.5 to 19 days in periods 1 and 2, respectively (P = .004). The transplant rate increased from 181 per 100 patient-years in period 1 to 579 per 100 patient-years in period 2 (incidence rate ratio, 1.87; 95% CI, 1.04-3.38; P = .038). There were no statistical differences in waitlist mortality rate (P = .566) and 1-year survival (P = .699) between the 2 periods. DCD HTs (n = 36) contributed to 49.3% of overall HT activity in period 2. We concluded that utilization of DCD hearts significantly reduced waitlist time and increased transplant rate. Short-term posttransplant outcomes were comparable between the pre-DCD and post-DCD periods.

Heart-liver-kidney transplantation for AL amyloidosis using normothermic recovery and storage from a donor following circulatory death: Short-term outcome in a first-in-world experience.

AL amyloidosis is a rare condition characterized by the overproduction of an unstable free light chain, protein misfolding and aggregation, and extracellular deposition that can progress to multiorgan involvement and failure. To our knowledge, this is the first worldwide report to describe triple organ transplantation for AL amyloidosis and triple organ transplantation using thoracoabdominal normothermic regional perfusion recovery with a donation from a circulatory death (DCD) donor. The recipient was a 40-year-old man with multiorgan AL amyloidosis with a terminal prognosis without multiorgan transplantation. An appropriate DCD donor was selected for sequential heart, liver, and kidney transplants via our center's thoracoabdominal normothermic regional perfusion pathway. The liver was additionally placed on an ex vivo normothermic machine perfusion, and the kidney was maintained on hypothermic machine perfusion while awaiting implantation. The heart transplant was completed first (cold ischemic time [CIT]: 131 minutes), followed by the liver transplant (CIT: 87 minutes, normothermic machine perfusion: 301 minutes). Kidney transplantation was performed the following day (CIT: 1833 minutes). He is 8 months posttransplant without evidence of heart, liver, or kidney graft dysfunction or rejection. This case highlights the feasibility of normothermic recovery and storage modalities for DCD donors, which can expand transplant opportunities for allografts previously not considered for multiorgan transplantations.

Pulmonary complications of eating disorders: a literature review.

The medical complications of eating disorders (EDs) have been described in the literature; however, the pulmonary system has historically been described as relatively spared from the ravages of eating disorders and thus neglected in the literature. Here we review the pulmonary complications that have been described in the literature, including the effects of starvation on the lungs of nutritionally deprived animals and patients with anorexia nervosa. There is clear evidence of weakness of respiratory muscles with starvation in both groups. However, there is discordance in the literature as to whether starvation results in "nutritional emphysema," and if so, by what mechanism and at what degree of malnutrition it develops. We also explore the growing concern for the risk of non-tuberculosis mycobacterium infection as well as risk for pneumomediastinum and pneumothorax in patients with restrictive EDs. From the limited literature, it is clear the lungs, in fact, are not spared and that further research is needed to fully understand the full extent of pulmonary complications instigated by EDs.

Eating disorders have many medical complications, however, historically the lungs have been described as spared from these complications. The authors review the available scientific literature and conclude that eating disorders do not spare the lungs as previously described and in fact may place patients at risk for weakness of the muscles that help us breath, changes to the structure of the lung, rare lung infections and potentially life-threatening collapse of the lung.

A Case-Based Critical Care Curriculum for Internal Medicine Residents Addressing Social Determinants of Health.

Introduction: Graduate medical education on social determinants of health (SDOH) is limited. Residents often directly care for vulnerable populations at safety-net hospitals, yet curricula thus far are based in the ambulatory setting. Methods: We developed a case-based curriculum integrating SDOH with critical care topics to standardize knowledge and improve skills and attitudes of internal medicine residents working with these patients. We conducted a needs assessment, identified systematic social risk domains, and modified a published curriculum to develop the content. Case-based discussions were conducted weekly in the medical intensive care unit, while knowledge, attitudes, and skills were assessed daily during multidisciplinary rounds. A 360-degree assessment was completed with pre- and postcurriculum surveys and self-reflection. Results: Eleven residents completed postcurriculum surveys. Both pre- and postcurriculum, residents reported confidence in identifying and describing how SDOH affect care. After the curriculum, residents could name more resources for patients experiencing health disparities due to substance abuse (pre: 47%, post: 73%) and financial constraints (pre: 50%, post:64%). This curriculum was recognized as the first training many residents received (pre: 31%, post: 91%) with formal feedback (pre: 16%, post: 64%). Discussion: Implementing a curriculum of social risk assessment in critically ill patients was difficult due to competition with clinical care. Participating residents said they "loved the open dialogue" to reflect on their experiences; this became an avenue to "debrief on specific patient encounters and [how] SDOH brought [patients] to the ICU." Future directions include qualitative analysis of reflections and assessment of curricular impact on trainee resiliency.

Experiences of Latinx Individuals Hospitalized for COVID-19: A Qualitative Study.

Importance: Latinx individuals, particularly immigrants, are at higher risk than non-Latinx White individuals of contracting and dying from coronavirus disease 2019 (COVID-19). Little is known about Latinx experiences with COVID-19 infection and treatment. Objective: To describe the experiences of Latinx individuals who were hospitalized with and survived COVID-19. Design, Setting, and Participants: The qualitative study used semistructured phone interviews of 60 Latinx adults who survived a COVID-19 hospitalization in public hospitals in San Francisco, California, and Denver, Colorado, from March 2020 to July 2020. Transcripts were analyzed using qualitative thematic analysis. Data analysis was conducted from May 2020 to September 2020. Main Outcomes and Measures: Themes and subthemes that reflected patient experiences. Results: Sixty people (24 women and 36 men; mean [SD] age, 48 [12] years) participated. All lived in low-income areas, 47 participants (78%) had more than 4 people in the home, and most (44 participants [73%]) were essential workers. Four participants (9%) could work from home, 12 (20%) had paid sick leave, and 21 (35%) lost their job because of COVID-19. We identified 5 themes (and subthemes) with public health and clinical care implications: COVID-19 was a distant and secondary threat (invincibility, misinformation and disbelief, ingrained social norms); COVID-19 was a compounder of disadvantage (fear of unemployment and eviction, lack of safeguards for undocumented immigrants, inability to protect self from COVID-19, and high-density housing); reluctance to seek medical care (worry about health care costs, concerned about ability to access care if uninsured or undocumented, undocumented immigrants fear deportation); health care system interactions (social isolation and change in hospital procedures, appreciation for clinicians and language access, and discharge with insufficient resources or clinical information); and faith and community resiliency (spirituality, Latinx COVID-19 advocates). Conclusions and Relevance: In interviews, Latinx patients with COVID-19 who survived hospitalization described initial disease misinformation and economic and immigration fears as having driven exposure and delays in presentation. To confront COVID-19 as a compounder of social disadvantage, public health authorities should mitigate COVID-19-related misinformation, immigration fears, and challenges to health care access, as well as create policies that provide work protection and address economic disadvantages.

Safety and Outcomes of Prolonged Usual Care Prone Position Mechanical Ventilation to Treat Acute Coronavirus Disease 2019 Hypoxemic Respiratory Failure.

OBJECTIVES: Prone position ventilation is a potentially life-saving ancillary intervention but is not widely adopted for coronavirus disease 2019 or acute respiratory distress syndrome from other causes. Implementation of lung-protective ventilation including prone positioning for coronavirus disease 2019 acute respiratory distress syndrome is limited by isolation precautions and personal protective equipment scarcity. We sought to determine the safety and associated clinical outcomes for coronavirus disease 2019 acute respiratory distress syndrome treated with prolonged prone position ventilation without daily repositioning. DESIGN: Retrospective single-center study. SETTING: Community academic medical ICU. PATIENTS: Sequential mechanically ventilated patients with coronavirus disease 2019 acute respiratory distress syndrome. INTERVENTIONS: Lung-protective ventilation and prolonged protocolized prone position ventilation without daily supine repositioning. Supine repositioning was performed only when Fio2 less than 60% with positive end-expiratory pressure less than 10 cm H2O for greater than or equal to 4 hours. MEASUREMENTS AND MAIN RESULTS: Primary safety outcome: proportion with pressure wounds by Grades (0-4). Secondary outcomes: hospital survival, length of stay, rates of facial and limb edema, hospital-acquired infections, device displacement, and measures of lung mechanics and oxygenation. Eighty-seven coronavirus disease 2019 patients were mechanically ventilated. Sixty-one were treated with prone position ventilation, whereas 26 did not meet criteria. Forty-two survived (68.9%). Median (interquartile range) time from intubation to prone position ventilation was 0.28 d (0.11-0.80 d). Total prone position ventilation duration was 4.87 d (2.08-9.97 d). Prone position ventilation was applied for 30.3% (18.2-42.2%) of the first 28 days. Pao2:Fio2 diverged significantly by day 3 between survivors 147 (108-164) and nonsurvivors 107 (85-146), mean difference -9.632 (95% CI, -48.3 to 0.0; p = 0·05). Age, driving pressure, day 1, and day 3 Pao2:Fio2 were predictive of time to death. Thirty-eight (71.7%) developed ventral pressure wounds that were associated with prone position ventilation duration and day 3 Sequential Organ Failure Assessment. Limb weakness occurred in 58 (95.1%) with brachial plexus palsies in five (8.2%). Hospital-acquired infections other than central line-associated blood stream infections were infrequent. CONCLUSIONS: Prolonged prone position ventilation was feasible and relatively safe with implications for wider adoption in treating critically ill coronavirus disease 2019 patients and acute respiratory distress syndrome of other etiologies.

Oligonucleotide-based Preconditioning of DCD Cardiac Donors and Its Impact on Cardiac Viability.

BACKGROUND: While clinical donation after circulatory death (DCD) cardiac transplantation is being implemented with increasing frequency to address the supply/demand mismatch of donor grafts, no research to date has examined a strategy of donor preconditioning to optimize the viability of DCD hearts for transplantation. In our rat model of the DCD protocol, we investigate the impact of pretreating donors with phosphorothioate-linked cytosine and guanine rich oligodeoxynucleotides (CpG ODN) and their effects on cardiac function, injury, and a novel left ventricular (LV) mRNA biomarker panel. METHODS: DCD rats were subjected to a withdrawal protocol, followed by 20 minutes of warm acirculatory standoff, representing a group of severely injured hearts as previously demonstrated. Beating heart controls and DCD rats were pretreated with vehicle or stimulatory CpG ODN (beating heart control and DCD stimulated with CpG ODN, BST and DST). Hearts were harvested for ex situ heart perfusion (ESHP), where LV function, histochemical injury, and differences in gene expression were characterized between groups. RESULTS: Donor pretreatment with CpG ODN doubled the number of functional DCD hearts at ESHP. Pretreatment was associated with improved systolic and diastolic LV function, a reduction in histological injury, and markedly reduced elaboration of cardiac troponin-I in coronary effluent during ESHP. Pretreatment was also associated with a reduction in mRNA biomarkers associated with myocardial injury. CONCLUSIONS: A single dose of CpG ODN was associated with reduced biomarkers of cardiac injury and a 100% increase in cardiac viability in this rodent model of marginal DCD cardiac donation.

Recycling of polymeric fraction of cable waste by rotational moulding.

This study focuses on the mechanical recycling of polymeric waste that is produced in considerable amount from the cable industry. Every year large amounts of cables become waste; wires recycling has traditionally focused on metal recovery, while the polymer cover has just been considered as a residue, being landfilled or incinerated. Nowadays, increasingly restrictive regulations and concern about environment make necessary to reduce landfilling as much as possible. Main novelty of the study is that the material used in the research is a post-consumer material and the entire residual material is used, without a previous purification, in contrast with similar studies. Characterization of this residue was performed by thermal analysis, showing that the material is mainly made up of a heavy fraction (84% of the residue), which is not able to melt, fact what makes recycling more difficult. Once characterized, the material was ground, blended with virgin polyethylene and reprocessed by rotational moulding. The influence of the amount of residue and parts structure (1, 2 and 3 layers) was assessed, studying the mechanical behaviour of obtained parts (tensile, flexural and impact properties). It has been found that although mechanical properties get reduced with the increased amount of residue, up to a 35% of residue can be used without an important decrease in mechanical properties. On the other hand, the use of multiple layers in the mouldings allowed obtaining a better external appearance without compromising the mechanical properties.

Tamponade: Hemodynamic and Echocardiographic Diagnosis.

Cardiac tamponade is a medical emergency that can be readily reversed with timely recognition and appropriate intervention. The clinical diagnosis of cardiac tamponade requires synthesis of a constellation of otherwise nonspecific features based on an understanding of the underlying pathophysiological characteristics. Although echocardiographic examination is a central component of diagnosis, alone it is insufficient to establish the physiological diagnosis of hemodynamically significant cardiac tamponade. The hemodynamic diagnosis of cardiac tamponade requires clinical evidence of low cardiac output and stroke volume in the setting of elevated cardiac filling pressures, with evidence of increased sympathetic tone (eg, tachycardia, peripheral vasoconstriction), and exclusion of other causes of shock as the primary problem (particularly cardiogenic shock). The hemodynamic features of tamponade are revealed by considering the effects of pericardial constraint. Pulsus paradoxus and loss of the normal "y" descent of a jugular venous pressure waveform may be appreciated on clinical examination. When a pulmonary artery catheter is placed, equalization of diastolic pressures across all chambers is observed. Echocardiographic examination confirms the size, location, and other characteristics of the causal pericardial collection. Several echocardiographic features support the hemodynamic diagnosis of tamponade, including early diastolic collapse of the right ventricle, late diastolic collapse of the right atrium, respiratory variation in mitral valve inflow (akin to pulsus paradoxus), and decreased early filling (E wave) of mitral valve inflow (related to loss of the y descent). Echocardiographic examination then supports decisions about the early treatment and drainage of the tamponading effusion.

A Rodent Model of Cardiac Donation After Circulatory Death and Novel Biomarkers of Cardiac Viability During Ex Vivo Heart Perfusion.

BACKGROUND: Organ donation after circulatory death (DCD) is increasingly being used as a means of addressing the organ supply/demand mismatch in solid organ transplantation. There is reluctance to use DCD hearts, due to an inability to precisely identify hearts that have suffered irreversible injury. We investigated novel biomarkers and clinically relevant endpoints across a spectrum of warm ischemic times, before and during ex vivo heart perfusion (EVHP), to identify features associated with a nonviable cardiac phenotype. METHODS: Donor rats sustained a hypoxic cardiac arrest, followed by variable acirculatory standoff periods (DCD groups). Left ventricular function, histochemical injury, and differences in left ventricular gene expression were studied before, and during, EVHP. RESULTS: As warm ischemic time exposure increased in DCD groups, fewer hearts were functional during EVHP, and ventricular function was increasingly impaired. Histochemical assessment identified severely injured hearts during EVHP. A novel gene expression signature identified severely injured hearts during EVHP (upregulation of c-Jun, 3.19 (2.84-3.60); P = 0.0014; HMOX-1, 3.87 (2.72-5.50); P = 0.0037; and Hsp90, 7.66 (6.32-9.27); P < 0.0001 in DCD20), and may be useful in identifying high-risk hearts at the point of harvest (Hsp90). CONCLUSIONS: We demonstrate that our preclinical model recapitulates the cardio-respiratory decompensation observed in humans, and that EVHP appears necessary to unmask distinguishing features of severely injured DCD hearts. Furthermore, we outline a clinically relevant multimodal approach to assessing candidate DCD hearts. Novel mRNA signatures correlated with elevations in cardiac Troponin-I in severely injured hearts during EVHP, and may also detect injury at the point of harvest.

The Causal Role of IL-4 and IL-13 in Schistosoma mansoni Pulmonary Hypertension.

RATIONALE: The etiology of schistosomiasis-associated pulmonary arterial hypertension (PAH), a major cause of PAH worldwide, is poorly understood. Schistosoma mansoni exposure results in prototypical type-2 inflammation. Furthermore, transforming growth factor (TGF)-ß signaling is required for experimental pulmonary hypertension (PH) caused by Schistosoma exposure. OBJECTIVES: We hypothesized type-2 inflammation driven by IL-4 and IL-13 is necessary for Schistosoma-induced TGF-ß-dependent vascular remodeling. METHODS: Wild-type, IL-4(-/-), IL-13(-/-), and IL-4(-/-)IL-13(-/-) mice (C57BL6/J background) were intraperitoneally sensitized and intravenously challenged with S. mansoni eggs to induce experimental PH. Right ventricular catheterization was then performed, followed by quantitative analysis of the lung tissue. Lung tissue from patients with schistosomiasis-associated and connective tissue disease-associated PAH was also systematically analyzed. MEASUREMENTS AND MAIN RESULTS: Mice with experimental Schistosoma-induced PH had evidence of increased IL-4 and IL-13 signaling. IL-4(-/-)IL-13(-/-) mice, but not single knockout IL-4(-/-) or IL-13(-/-) mice, were protected from Schistosoma-induced PH, with decreased right ventricular pressures, pulmonary vascular remodeling, and right ventricular hypertrophy. IL-4(-/-)IL-13(-/-) mice had less pulmonary vascular phospho-signal transducer and activator of transcription 6 (STAT6) and phospho-Smad2/3 activity, potentially caused by decreased TGF-ß activation by macrophages. In vivo treatment with a STAT6 inhibitor and IL-4(-/-)IL-13(-/-) bone marrow transplantation also protected against Schistosoma-PH. Lung tissue from patients with schistosomiasis-associated and connective tissue disease-associated PAH had evidence of type-2 inflammation. CONCLUSIONS: Combined IL-4 and IL-13 deficiency is required for protection against TGF-ß-induced pulmonary vascular disease after Schistosoma exposure, and targeted inhibition of this pathway is a potential novel therapeutic approach for patients with schistosomiasis-associated PAH.

Rat Heterotopic Abdominal Heart/Single-lung Transplantation in a Volume-loaded Configuration.

Herein, we describe a novel technique for heterotopic abdominal heart-lung transplantation (HAHLT) in rats. The configuration of the transplant graft involves anastomosis of donor inferior vena cava (IVC) to recipient IVC, and donor ascending aorta (Ao) to recipient abdominal Ao. The right upper and middle lung lobes are preserved and function as conduits for blood flow from right heart to left heart. There are several advantages to using this technique, and it lends itself to a broad range of applications. Because the graft is transplanted in a configuration that allows for dyamic volume-loading, cardiac function may be directly assessed in vivo. The use of pressure-volume conductance catheters permits characterization of load-dependent and load-independent hemodynamic parameters. The graft may be converted to a loaded configuration by applying a clamp to the recipient's infra-hepatic IVC. We describe modified surgical techniques for both donor and recipient operations, and an ideal myocardial protection strategy. Depending on the experimental aim, this model may be adapted for use in both acute and chronic studies of graft function, immunologic status, and variable ventricular loading conditions. The conducting airways to the transplanted lung are preserved, and allow for acute lung re-ventilation. This facilitates analysis of the effects of the mixed venous and arterial blood providing coronary perfusion to the graft. A limitation of this model is its technical complexity. There is a significant learning curve for new operators, who should ideally be mentored in the technique. A surgical training background is advantageous for those wishing to apply this model. Despite its complexity, we aim to present the model in a clear and easily applicable format. Because of the physiologic similarity of this model to orthotopic transplantation, and its broad range of study applications, the effort invested in learning the technique is likely to be worthwhile.

Escherichia coli persister cells suppress translation by selectively disassembling and degrading their ribosomes.

Bacterial persisters are rare, phenotypically distinct cells that survive exposure to multiple antibiotics. Previous studies indicated that formation and maintenance of the persister phenotype are regulated by suppressing translation. To examine the mechanism of this translational suppression, we developed novel methodology to rapidly purify ribosome complexes from persister cells. We purified His-tagged ribosomes from Escherichia coli cells that over-expressed HipA protein, which induces persister formation, and were treated with ampicillin to remove antibiotic-sensitive cells. We profiled ribosome complexes and analyzed the ribosomal RNA and protein components from these persister cells. Our results show that (i) ribosomes in persisters exist largely as inactive ribosomal subunits, (ii) rRNAs and tRNAs are mostly degraded and (iii) a small fraction of the ribosomes remain mostly intact, except for reduced amounts of seven ribosomal proteins. Our findings explain the basis for translational suppression in persisters and suggest how persisters survive exposure to multiple antibiotics.

Kinetics of the angiogenic response in lung endothelium following acute inflammatory injury with bleomycin.

PURPOSE/AIM: Angiogenesis is a central component of normal wound healing but it has not been fully characterized in lung repair following acute inflammatory injury. The current literature lacks vital information pertaining to the extent, timing, and location of this process. This information is necessary for examining mechanisms that drive normal lung repair in resolving acute inflammatory injury. The goal of our study was to formally characterize lung angiogenesis over a time course of bleomycin-induced lung injury. MATERIALS AND METHODS: Female C57BL/6 mice age 8-12 weeks were treated with a single dose of intratracheal bleomycin. Total lung endothelial cells were quantified with flow cytometry 0, 7, 14, 21, and 28 days following bleomycin administration, and endothelial cell replication was assessed using bromodeoxyuridine (BrdU) incorporation. RESULTS: Endothelial cell replication was maximal 14 days after bleomycin administration, while total lung endothelial cells peaked at day 21. Tissue analysis with stereology was performed to measure total lung vascular surface area in bleomycin at day 21 relative to controls and demonstrated a trend toward increased vasculature in the bleomycin group. CONCLUSIONS: Angiogenesis begins shortly after injury in the bleomycin model and leads to an expansion in the lung endothelial cell population that peaks at day 21. This study offers the first longitudinal examination of angiogenesis following acute inflammatory lung injury induced by bleomycin. Information provided in this study will be vital for further investigating mechanisms of angiogenesis in both normal and abnormal lung repair.

Fas ligand-expressing lymphocytes enhance alveolar macrophage apoptosis in the resolution of acute pulmonary inflammation.

Apoptosis of alveolar macrophages and their subsequent clearance by neighboring phagocytes are necessary steps in the resolution of acute pulmonary inflammation. We have recently identified that activation of the Fas death receptor on the cell surface of macrophages drives macrophage apoptosis. However, the source of the cognate ligand for Fas (FasL) responsible for induction of alveolar macrophage apoptosis is not defined. Given their known role in the resolution of inflammation and ability to induce macrophage apoptosis ex vivo, we hypothesized that T lymphocytes represented a critical source of FasL. To address this hypothesis, C57BL/6J and lymphocyte-deficient (Rag-1(-/-)) mice were exposed to intratracheal lipopolysaccharide to induce pulmonary inflammation. Furthermore, utilizing mice expressing nonfunctional FasL, we adoptively transferred donor lymphocytes into inflamed lymphocyte-deficient mice to characterize the effect of lymphocyte-derived FasL on alveolar macrophage apoptosis in the resolution of inflammation. Herein, evidence is presented that lymphocytes expressing FasL enhance alveolar macrophage apoptosis during the resolution of LPS-induced inflammation. Moreover, lymphocyte induction of alveolar macrophage apoptosis results in contraction of the alveolar macrophage pool, which occurs in a FasL-dependent manner. Specifically, FasL-expressing CD8(+) T lymphocytes potently induce alveolar macrophage apoptosis and contraction of the alveolar macrophage pool. Together, these studies identify a novel role for CD8(+) T lymphocytes in the resolution of acute pulmonary inflammation.

Circulating hematopoietic progenitor cells are decreased in COPD.

RATIONALE: Bone marrow derived progenitor cells participate in the repair of injured vessels. The lungs of individuals with emphysema have reduced alveolar capillary density and increased endothelial apoptosis. We hypothesized that circulating levels of endothelial and hematopoietic progenitor cells would be reduced in this group of patients. OBJECTIVES: The goal of this study was to measure circulating levels of endothelial progenitor cells (EPCs) and hematopoietic progenitor cells (HPCs) in subjects with COPD and to determine if progenitor levels correlated with disease severity and the presence of emphysema. METHODS: Peripheral blood mononuclear cells were isolated from 61 patients with COPD and 32 control subjects. Levels of EPCs (CD45(dim) CD34+) and HPCs (CD45(+) CD34(+) VEGF-R2(+)) were quantified using multi-parameter flow cytometry. Progenitor cell function was assessed using cell culture assays. All subjects were evaluated with spirometry and CT scanning. MEASUREMENTS AND MAIN RESULTS: HPC levels were reduced in subjects with COPD compared to controls, whereas circulating EPC levels were similar between the two groups. HPC levels correlated with severity of obstruction and were lowest in subjects with severe emphysema. These associations remained after correction for factors known to affect progenitor cell levels including age, smoking status, the use of statin medications and the presence of coronary artery disease. The ability of mononuclear cells to form endothelial cell colony forming units (EC-CFU) was also reduced in subjects with COPD. CONCLUSIONS: HPC levels are reduced in subjects with COPD and correlate with emphysema phenotype and severity of obstruction. Reduction of HPCs may disrupt maintenance of the capillary endothelium, thereby contributing to the pathogenesis of COPD.

Prophylactic magnesium does not prevent atrial fibrillation after cardiac surgery: a meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is a common complication after cardiac surgery. Previous meta-analyses have concluded prophylactic magnesium (Mg) prevents postoperative AF, although with a significant degree of heterogeneity among included studies. Recently, the largest randomized, controlled trial published to date (but not included in prior published meta-analyses) concluded that Mg sulfate is not protective against AF after cardiac surgery. The objective of this study was to conduct a new meta-analysis including the results of new Mg trials not included in previous meta-analyses, and to investigate the potential causes and effects of significant heterogeneity observed in previously published meta-analyses. METHODS: The MEDLINE, EMBASE, and CENTRAL databases were searched for relevant studies published up to March 31, 2012. Pooled odds ratios of occurrence of AF were calculated using random-effects models. Heterogeneity was assessed as significant using the I(2) statistic. RESULTS: Egger's and funnel plots demonstrated biases toward stronger and more positive effects of Mg in smaller studies. When the analysis was restricted to the five double-blind, intention-to-treat studies in which AF was the primary outcome (Mg arm, n = 710; control arm, n = 713), Mg did not prevent postoperative AF (odds ratio, 0.94; p = 0.77), and heterogeneity was no longer significant (I(2) = 40%; p = 0.15). CONCLUSIONS: This meta-analysis, restricted to well-conducted trials, does not support the prophylactic use of Mg to prevent AF after cardiac surgery. Prior meta-analyses have drawn conclusions from simple random-effects models with significant heterogeneity. However, this approach leaves important residual heterogeneity and overemphasizes the strongly positive effects of smaller studies.

Vascular endothelial growth factor enhances macrophage clearance of apoptotic cells.

Efficient clearance of apoptotic cells from the lung by alveolar macrophages is important for the maintenance of tissue structure and function. Lung tissue from humans with emphysema contains increased numbers of apoptotic cells and decreased levels of vascular endothelial growth factor (VEGF). Mice treated with VEGF receptor inhibitors have increased numbers of apoptotic cells and develop emphysema. We hypothesized that VEGF regulates apoptotic cell clearance by alveolar macrophages (AM) via its interaction with VEGF receptor 1 (VEGF R1). Our data show that the uptake of apoptotic cells by murine AMs and human monocyte-derived macrophages is inhibited by depletion of VEGF and that VEGF activates Rac1. Antibody blockade or pharmacological inhibition of VEGF R1 activity also decreased apoptotic cell uptake ex vivo. Conversely, overexpression of VEGF significantly enhanced apoptotic cell uptake by AMs in vivo. These results indicate that VEGF serves a positive regulatory role via its interaction with VEGF R1 to activate Rac1 and enhance AM apoptotic cell clearance.

Thrombosis and failure of a HeartMate II device in the absence of alarms.

Next-generation left ventricular assist devices such as the HeartMate II (Thoratec Corporation, Pleasanton, CA) have significantly improved patient outcomes. In particular, the incidence of thromboembolic events appears to be significantly reduced. Pump thrombosis has occurred, however, and is well reported in the literature. The thromboses reported with next-generation devices have generally been partial thromboses associated with significant abnormalities in the system performance data as displayed on the system monitor. We describe a case of complete thrombosis of a HeartMate II axial-flow pump resulting in cardiac arrest but in the absence of alarms or significant aberrations in the performance data.

Successful weaning and explantation of the Heartmate II left ventricular assist device.

BACKGROUND: Ventricular assist devices (VADs) are used in cases of heart failure refractory to medical therapy. Most VADs are used as a bridge to heart transplantation; however, in certain cases, myocardial function recovers and VADs can be explanted after the patient is weaned. The objectives of this study were to describe patients who required Heartmate II VAD insertion, followed by myocardial recovery and explanation in a quaternary heart centre. METHODS: Patients who had a VAD explanted were identified in the mechanical support institutional database and their outcomes were analyzed. Clinical examinations, biochemical markers, and serial echocardiograms were used to demonstrate myocardial recovery. RESULTS: Seventeen patients had a Heartmate II VAD inserted between 2008 and 2010. Four patients underwent successful weaning and subsequent VAD explantation. Etiology of decompensated heart failure was idiopathic dilated cardiomyopathy (n = 1), ischemic (n = 1), or myocarditis (n = 2). Mean age was 35.3 years. Patients were supported for 213 days (range 70-293 days) and were in New York Heart Association class I in the community before explantation. The devices were explanted via a minimally invasive approach, without cardiopulmonary bypass. All patients survived explantation and were discharged alive from hospital after an average of 5.7 ± 1.5 days post pump explantation. No adverse events were reported after explantation. Only one patient required allogenic blood transfusion after the procedure. CONCLUSIONS: Patients requiring VAD support for myocardial failure can undergo significant reverse remodelling. Explantation can lead to optimal outcome with minimal morbidity. Methods for assessment of reverse remodelling, weaning protocol, and optimal timing of explantation remain under evaluation.