Quantifying genome-specific carbon fixation in a 750-meter deep subsurface hydrothermal microbial community.

Dissolved inorganic carbon has been hypothesized to stimulate microbial chemoautotrophic activity as a biological sink in the carbon cycle of deep subsurface environments. Here, we tested this hypothesis using quantitative DNA stable isotope probing of metagenome-assembled genomes (MAGs) at multiple 13C-labeled bicarbonate concentrations in hydrothermal fluids from a 750-m deep subsurface aquifer in the Biga Peninsula (Turkey). The diversity of microbial populations assimilating 13C-labeled bicarbonate was significantly different at higher bicarbonate concentrations, and could be linked to four separate carbon-fixation pathways encoded within 13C-labeled MAGs. Microbial populations encoding the Calvin-Benson-Bassham cycle had the highest contribution to carbon fixation across all bicarbonate concentrations tested, spanning 1-10 mM. However, out of all the active carbon-fixation pathways detected, MAGs affiliated with the phylum Aquificae encoding the reverse tricarboxylic acid (rTCA) pathway were the only microbial populations that exhibited an increased 13C-bicarbonate assimilation under increasing bicarbonate concentrations. Our study provides the first experimental data supporting predictions that increased bicarbonate concentrations may promote chemoautotrophy via the rTCA cycle and its biological sink for deep subsurface inorganic carbon.

Carbon metabolism and biogeography of candidate phylum "Candidatus Bipolaricaulota" in geothermal environments of Biga Peninsula, Turkey.

Terrestrial hydrothermal springs and aquifers are excellent sites to study microbial biogeography because of their high physicochemical heterogeneity across relatively limited geographic regions. In this study, we performed 16S rRNA gene sequencing and metagenomic analyses of the microbial diversity of 11 different geothermal aquifers and springs across the tectonically active Biga Peninsula (Turkey). Across geothermal settings ranging in temperature from 43 to 79°C, one of the most highly represented groups in both 16S rRNA gene and metagenomic datasets was affiliated with the uncultivated phylum "Candidatus Bipolaricaulota" (former "Ca. Acetothermia" and OP1 division). The highest relative abundance of "Ca. Bipolaricaulota" was observed in a 68°C geothermal brine sediment, where it dominated the microbial community, representing 91% of all detectable 16S rRNA genes. Correlation analysis of "Ca. Bipolaricaulota" operational taxonomic units (OTUs) with physicochemical parameters indicated that salinity was the strongest environmental factor measured associated with the distribution of this novel group in geothermal fluids. Correspondingly, analysis of 23 metagenome-assembled genomes (MAGs) revealed two distinct groups of "Ca. Bipolaricaulota" MAGs based on the differences in carbon metabolism: one group encoding the bacterial Wood-Ljungdahl pathway (WLP) for H2 dependent CO2 fixation is selected for at lower salinities, and a second heterotrophic clade that lacks the WLP that was selected for under hypersaline conditions in the geothermal brine sediment. In conclusion, our results highlight that the biogeography of "Ca. Bipolaricaulota" taxa is strongly correlated with salinity in hydrothermal ecosystems, which coincides with key differences in carbon acquisition strategies. The exceptionally high relative abundance of apparently heterotrophic representatives of this novel candidate Phylum in geothermal brine sediment observed here may help to guide future enrichment experiments to obtain representatives in pure culture.

A system-wide extracorporeal membrane oxygenation quality collaborative improves patient outcomes.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) use in adult patient populations has grown rapidly with wide variation in practices and outcomes. We evaluated the impact on patient outcomes, resource use, and costs of an initiative to coordinate and standardize best practices across ECMO programs within a large integrated health care system. METHODS: The ECMO Collaborative Project brought clinicians and service-line leaders from 4 programs within a single health care system together with operational subject matter experts tasked with developing and implementing standardized guidelines, order sets, and an internal database to support an automated quarterly report card. Patient outcomes, resource use, and financial measures were compared for the 16 months before (January 2017 to April 2018; "precollaborative," n = 185) versus the 14 months after (November 2018 to December 2019, "postcollaborative," n = 243) a 6-month implementation and blanking period. Subset analyses were performed for venoarterial ECMO, venovenous ECMO, and extracorporeal cardiopulmonary resuscitation. RESULTS: Survival to discharge/transfer increased significantly (in-hospital mortality hazard ratio, 0.75; 95% confidence interval [95% CI], 0.58-0.99) for the postcollaborative versus the precollaborative period (107/185, 57.8% vs 113/243, 46.5%, P = .03), predominantly due to improvement among patients receiving venoarterial ECMO (hazard ratio, 0.61; 95% CI, 0.41-0.91). The percentage of patients successfully weaned from ECMO increased from 58.9% (109/185) to 70% (170/243), P = .02. Complication rates decreased by 40% (incidence rate ratio, 0.60; 95% CI, 0.49-0.72). No significant changes were observed in ECMO duration, intensive care unit or hospital length of stay, or cost-per-case; payment-per-case and contribution-margin-per-case both decreased significantly. CONCLUSIONS: The ECMO Collaborative Project improved survival to discharge/transfer, weaning rates and complications, without additional costs, through coordination and standardization across ECMO programs within a health care system.

Carbon assimilating fungi from surface ocean to subseafloor revealed by coupled phylogenetic and stable isotope analysis.

Fungi are ubiquitous in the ocean and hypothesized to be important members of marine ecosystems, but their roles in the marine carbon cycle are poorly understood. Here, we use 13C DNA stable isotope probing coupled with phylogenetic analyses to investigate carbon assimilation within diverse communities of planktonic and benthic fungi in the Benguela Upwelling System (Namibia). Across the redox stratified water column and in the underlying sediments, assimilation of 13C-labeled carbon from diatom extracellular polymeric substances (13C-dEPS) by fungi correlated with the expression of fungal genes encoding carbohydrate-active enzymes. Phylogenetic analysis of genes from 13C-labeled metagenomes revealed saprotrophic lineages related to the facultative yeast Malassezia were the main fungal foragers of pelagic dEPS. In contrast, fungi living in the underlying sulfidic sediments assimilated more 13C-labeled carbon from chemosynthetic bacteria compared to dEPS. This coincided with a unique seafloor fungal community and dissolved organic matter composition compared to the water column, and a 100-fold increased fungal abundance within the subseafloor sulfide-nitrate transition zone. The subseafloor fungi feeding on 13C-labeled chemolithoautotrophs under anoxic conditions were affiliated with Chytridiomycota and Mucoromycota that encode cellulolytic and proteolytic enzymes, revealing polysaccharide and protein-degrading fungi that can anaerobically decompose chemosynthetic necromass. These subseafloor fungi, therefore, appear to be specialized in organic matter that is produced in the sediments. Our findings reveal that the phylogenetic diversity of fungi across redox stratified marine ecosystems translates into functionally relevant mechanisms helping to structure carbon flow from primary producers in marine microbiomes from the surface ocean to the subseafloor.

Validación de la PDMS-2 en población española. Evaluación de la intervención de fisioterapia y la participación de los padres en el tratamiento de niños con trastornos del neurodesarrollo / Validation of the PDMS-2 scale in the Spanish population. Evaluation of physiotherapy intervention and parental involvement in the treatment of children with neurodevelopmental disorders

Objetivo: Adaptar transculturalmente la escala del desarrollo motor de Peabody, segunda edición (PDMS-2), del español mexicano al español de España y evaluar su validez. Determinar la eficacia del tratamiento fisioterápico (número de sesiones de fisioterapia y actividades propuestas por el fisioterape uta y realizadas por los padres) en niños con trastornos del neurodesarrollo de 0 a 3 años.Sujetos y métodos: Un primer estudio descriptivo prospectivo de validación de la PDMS-2, que incluyó a 74 sujetos con trastorno del neurodesarrollo con edades comprendidas entre 0 y 3 años. Un segundo ensayo clínico aleatorio para evaluar la intervención de fisioterapia (concepto Bobath) en el grupo experimental (n = 37), que recibió sesiones únicas de 30 minutos semanales durante ocho semanas frente al grupo de control (n = 37), que no recibió fisioterapia y utilizó la PDMS-2 para su evaluación. Resultados: Se encontró una adecuada confiabilidad interagente (coeficiente de correlación intraclase = 0,76). La escala mostró también una muy buena consistencia interna (alfa = 0,99). Hubo diferencias significativas entre ambos grupos a las ocho semanas. El grupo experimental obtuvo mejores puntuaciones en el postest después de administrar el tratamiento de fisioterapia (p < 0,001). Se encontraron coeficientes de correlación moderados y significativos entre el número de sesiones de fisioterapia y el cociente motor total (r = 0,38; p < 0,05) y las actividades realizadas en casa con el cociente motor total (r = 0,46; p = 0,005). Conclusiones: La PDMS-2 es un instrumento válido y fiable para medir el desarrollo motor grueso y fino en niños con trastorno del neurodesarrollo de 0 a 3 años. La fisioterapia es útil en la mejoría en niños con retraso del neurodesarrollo...(AU)

Aim: Cross-culturally adapt the PDMS-2 scale from Spanish-Mexican to Spanish-Spanish and evaluate its validity. To determine the efficacy of physiotherapy treatment (number of physiotherapy sessions and activities proposed by the physiotherapist and performed by the parents) in children with neurodevelopmental disorders between the ages of 0 and 3 years. Subjects and methods: A first prospective descriptive study of validation of the PDMS-2 scale including 74 subjects with neurodevelopmental disorder with aged from 0 and 3 years old. A second randomized clinical trial to evaluate the physiotherapy (Bobath concept) intervention in the experimental group (EG) (n = 37) who received unique 30-minute weekly sessions for 8 weeks against the control group (CG) (n = 37) that did not receive physiotherapy using the PDMS-2 scale for evaluation. Results: An adequate inter-rater reliablity was found (ICC = 0.76). The scale showed also a very good internal consistency (alpha = 0,99). Significant differences between both groups at 8 weeks. EG obtained better scores in the postest after administrating the physiotherapy treatment (p < 0.001) Moderate and significant correlation coefficients were found between the number of physiotherapy sessions and Total Motor Quotient (TMQ) (r = 0.38; p < 0.05) and the home actitvities with TMQ (r = 0.46; p = 0.005). Conclusions: The Peabody PDMS-2 scale is a valid and reliable instrument to measure gross and fine motor development in children with neurodevelopmental disorder aged from 0 and 3 years old. Physiotherapy is useful for helping children with delayed neurodevelopment improve. The number of physiotherapy sessions and the activities proposed by the physiotherapist and performed at home by the parents show a direct and positive relationship with the results obtained in motor development.(AU)

Validation of the PDMS-2 scale in the Spanish population. Evaluation of physiotherapy intervention and parental involvement in the treatment of children with neurodevelopmental disorders. / Validación de la PDMS-2 en población española. Evaluación de la intervención de fisioterapia y la participación de los padres en el tratamiento de niños con trastornos del neurodesarrollo.

AIM: Cross-culturally adapt the PDMS-2 scale from Spanish-Mexican to Spanish-Spanish and evaluate its validity. To determine the efficacy of physiotherapy treatment (number of physiotherapy sessions and activities proposed by the physiotherapist and performed by the parents) in children with neurodevelopmental disorders between the ages of 0 and 3 years. SUBJECTS AND METHODS: A first prospective descriptive study of validation of the PDMS-2 scale including 74 subjects with neurodevelopmental disorder with aged from 0 and 3 years old. A second randomized clinical trial to evaluate the physiotherapy (Bobath concept) intervention in the experimental group (EG) (n = 37) who received unique 30-minute weekly sessions for 8 weeks against the control group (CG) (n = 37) that did not receive physiotherapy using the PDMS-2 scale for evaluation. RESULTS: An adequate inter-rater reliablity was found (ICC = 0.76). The scale showed also a very good internal consistency (alpha = 0,99). Significant differences between both groups at 8 weeks. EG obtained better scores in the postest after administrating the physiotherapy treatment (p < 0.001) Moderate and significant correlation coefficients were found between the number of physiotherapy sessions and Total Motor Quotient (TMQ) (r = 0.38; p < 0.05) and the home actitvities with TMQ (r = 0.46; p = 0.005). CONCLUSIONS: The Peabody PDMS-2 scale is a valid and reliable instrument to measure gross and fine motor development in children with neurodevelopmental disorder aged from 0 and 3 years old. Physiotherapy is useful for helping children with delayed neurodevelopment improve. The number of physiotherapy sessions and the activities proposed by the physiotherapist and performed at home by the parents show a direct and positive relationship with the results obtained in motor development.

TITLE: Validación de la PDMS-2 en población española. Evaluación de la intervención de fisioterapia y la participación de los padres en el tratamiento de niños con trastornos del neurodesarrollo.Objetivo. Adaptar transculturalmente la escala del desarrollo motor de Peabody, segunda edición (PDMS-2), del español mexicano al español de España y evaluar su validez. Determinar la eficacia del tratamiento fisioterápico (número de sesiones de fisioterapia y actividades propuestas por el fisioterapeuta y realizadas por los padres) en niños con trastornos del neurodesarrollo de 0 a 3 años. Sujetos y métodos. Un primer estudio descriptivo prospectivo de validación de la PDMS-2, que incluyó a 74 sujetos con trastorno del neurodesarrollo con edades comprendidas entre 0 y 3 años. Un segundo ensayo clínico aleatorio para evaluar la intervención de fisioterapia (concepto Bobath) en el grupo experimental (n = 37), que recibió sesiones únicas de 30 minutos semanales durante ocho semanas frente al grupo de control (n = 37), que no recibió fisioterapia y utilizó la PDMS-2 para su evaluación. Resultados. Se encontró una adecuada confiabilidad interagente (coeficiente de correlación intraclase = 0,76). La escala mostró también una muy buena consistencia interna (alfa = 0,99). Hubo diferencias significativas entre ambos grupos a las ocho semanas. El grupo experimental obtuvo mejores puntuaciones en el postest después de administrar el tratamiento de fisioterapia (p menor de 0,001). Se encontraron coeficientes de correlación moderados y significativos entre el número de sesiones de fisioterapia y el cociente motor total (r = 0,38; p menor de 0,05) y las actividades realizadas en casa con el cociente motor total (r = 0,46; p = 0,005). Conclusiones. La PDMS-2 es un instrumento válido y fiable para medir el desarrollo motor grueso y fino en niños con trastorno del neurodesarrollo de 0 a 3 años. La fisioterapia es útil en la mejoría en niños con retraso del neurodesarrollo. El número de sesiones de fisioterapia y las actividades propuestas por el fisioterapeuta y realizadas en casa por los padres muestran una relación directa y positiva con los resultados obtenidos en el desarrollo motor.

Sulfurization of dissolved organic matter in the anoxic water column of the Black Sea.

Today's oceans store as much dissolved organic carbon (DOC) in the water column as there is CO2 in the atmosphere, and as such dissolved organic matter (DOM) is an important component of the global carbon cycle. It was shown that in anoxic marine sediments, reduced sulfur species (e.g., H2S) abiotically react with organic matter, contributing to carbon preservation. It is not known whether such processes also contribute to preserving DOM in ocean waters. Here, we show DOM sulfurization within the sulfidic waters of the Black Sea, by combining elemental, isotopic, and molecular analyses. Dissolved organic sulfur (DOS) is formed largely in the water column and not derived from sediments or allochthonous nonmarine sources. Our findings suggest that during large-scale anoxic events, DOM may accumulate through abiotic reactions with reduced sulfur species, having long-lasting effects on global climate by enhancing organic carbon sequestration.

Versatile cyanobacteria control the timing and extent of sulfide production in a Proterozoic analog microbial mat.

Cyanobacterial mats were hotspots of biogeochemical cycling during the Precambrian. However, mechanisms that controlled O2 release by these ecosystems are poorly understood. In an analog to Proterozoic coastal ecosystems, the Frasassi sulfidic springs mats, we studied the regulation of oxygenic and sulfide-driven anoxygenic photosynthesis (OP and AP) in versatile cyanobacteria, and interactions with sulfur reducing bacteria (SRB). Using microsensors and stable isotope probing we found that dissolved organic carbon (DOC) released by OP fuels sulfide production, likely by a specialized SRB population. Increased sulfide fluxes were only stimulated after the cyanobacteria switched from AP to OP. O2 production triggered migration of large sulfur-oxidizing bacteria from the surface to underneath the cyanobacterial layer. The resultant sulfide shield tempered AP and allowed OP to occur for a longer duration over a diel cycle. The lack of cyanobacterial DOC supply to SRB during AP therefore maximized O2 export. This mechanism is unique to benthic ecosystems because transitions between metabolisms occur on the same time scale as solute transport to functionally distinct layers, with the rearrangement of the system by migration of microorganisms exaggerating the effect. Overall, cyanobacterial versatility disrupts the synergistic relationship between sulfide production and AP, and thus enhances diel O2 production.

Author Correction: Metabolic activity analyses demonstrate that Lokiarchaeon exhibits homoacetogenesis in sulfidic marine sediments.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

High-quality cardiac surgery through teamwork.

The high-quality cardiothoracic surgery program is primed for mindful effective surgery. The challenge lies in attaining mindful skills and efficiency. Herein is one journey toward high departmental quality over two decades.

Metabolic activity analyses demonstrate that Lokiarchaeon exhibits homoacetogenesis in sulfidic marine sediments.

The genomes of the Asgard superphylum of Archaea hold clues pertaining to the nature of the host cell that acquired the mitochondrion at the origin of eukaryotes1-4. Representatives of the Asgard candidate phylum Candidatus Lokiarchaeota (Lokiarchaeon) have the capacity for acetogenesis and fermentation5-7, but how their metabolic activity responds to environmental conditions is poorly understood. Here, we show that in anoxic Namibian shelf sediments, Lokiarchaeon gene expression levels are higher than those of bacterial phyla and increase with depth below the seafloor. Lokiarchaeon gene expression was significantly different across a hypoxic-sulfidic redox gradient, whereby genes involved in growth, fermentation and H2-dependent carbon fixation had the highest expression under the most reducing (sulfidic) conditions. Quantitative stable isotope probing revealed that anaerobic utilization of CO2 and diatomaceous extracellular polymeric substances by Lokiarchaeon was higher than the bacterial average, consistent with higher expression of Lokiarchaeon genes, including those involved in transport and fermentation of sugars and amino acids. The quantitative stable isotope probing and gene expression data demonstrate homoacetogenic activity of Candidatus Lokiarchaeota, whereby fermentative H2 production from organic substrates is coupled with the Wood-Ljungdahl carbon fixation pathway8. The high energetic efficiency provided by homoacetogenesis8 helps to explain the elevated metabolic activity of Lokiarchaeon in this anoxic, energy-limited setting.

Outcomes of orthotopic heart transplantation and left ventricular assist device in patients aged 65 years or more with end-stage heart failure.

Age has traditionally been a limiting factor for advanced heart failure (HF) therapies. Orthotopic heart transplantation (OHT) age guidelines have become less restrictive, and left ventricular assist devices (LVADs) are increasingly utilized as destination therapy for patients ≥65 years. Although indications differ, we assessed outcomes for both modalities in this older population. We reviewed charts of consecutive advanced HF therapy recipients aged ≥65 years at our center from 2012 to 2016. Of 118 patients evaluated, 46 (39%) received an LVAD and 72 (61%) received OHT. Gender, body mass index, and rate of prior sternotomy were similar between groups; OHT recipients were younger, less likely to have diabetes mellitus, and more likely to have HF due to ischemic etiology. Forty-six percent of patients receiving LVADs were urgent need (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] profile 1-2), compared to 29% of patients receiving OHT (United Network for Organ Sharing 1A criteria; P = 0.068). OHT recipients had shorter lengths of stay and better 1-year survival compared to LVAD recipients. Although many centers do not offer advanced HF therapy to patients aged ≥65 years, our results indicate that age alone should not be prohibitive for advanced HF therapy, particularly OHT.

Extracorporeal membrane oxygenation as a salvage therapy for patients with severe primary graft dysfunction after heart transplant.

BACKGROUND: Severe primary graft dysfunction (PGD) is the leading cause of early death after heart transplant. AIM: To examine the outcomes of heart transplant recipients who received venoarterial extracorporeal membrane oxygenation (VA-ECMO) for severe PGD. METHODS: We reviewed electronic health records of adult patients who underwent heart transplant from November 2005 through June 2015. We defined severe PGD according to International Society for Heart and Lung Transplantation consensus statements. RESULTS: Of 1030 heart transplant patients, 31 (3%) had severe PGD and required VA-ECMO. The mean (range) age was 59 (43-69) years. Fifteen patients (48%) underwent prior sternotomy and 10 (32%) received a left ventricular assist device as a bridge to transplant. Severe PGD manifested as failure to wean from cardiopulmonary bypass in 20 patients (65%) and as severe hemodynamic instability in the immediate postoperative period in 10 (32%), including cardiac arrest in 3 (10%). Twenty-five patients (81%) were successfully weaned from VA-ECMO, and 19 (61%) were discharged; the other 12 (39%) died. CONCLUSIONS: Although VA-ECMO is a common method for providing mechanical circulatory support to patients with PGD, multicenter studies are needed to assess factors associated with successful outcomes and improved survival of these patients.

Outcomes of Moderate-to-Severe Acute Kidney Injury following Left Ventricular Assist Device Implantation.

BACKGROUND: Although acute kidney injury (AKI) is a common complication following cardiac surgery, less is known about the occurrence and consequences of moderate/severe AKI following left ventricular assist device (LVAD) implantation. METHODS: All patients who had an LVAD implanted at our center from 2008 to 2016 were reviewed to determine the incidence of, and risk factors for, moderate/severe (stage 2/3) AKI and to compare postoperative complications and mortality rates between those with and those without moderate/severe AKI. RESULTS: Of 246 patients, 68 (28%) developed moderate/severe AKI. A multivariable logistic regression comprising body mass index and prior sternotomy had fair predictive ability (area under the curve = 0.71). A 1-unit increase in body mass index increased the risk of moderate/severe AKI by 7% (odds ratio = 1.07; 95% confidence interval: 1.03-1.11); a prior sternotomy increased the risk more than 3-fold (odds ratio = 3.4; 95% confidence interval: 1.84-6.43). The group of patients with moderate/severe AKI had higher rates of respiratory failure and death than the group of patients with mild/no AKI. Patients with moderate/severe AKI were at 3.2 (95% confidence interval: 1.2-8.2) times the risk of 30-day mortality compared to those without. Even after adjusting for age and Interagency Registry for Mechanically Assisted Circulatory Support profile, those with moderate/severe AKI had 1.75 (95% confidence interval: 1.03-3.0) times the risk of 1-year mortality compared to those without. DISCUSSION: Risk-stratifying patients prior to LVAD placement in regard to AKI development may be a step toward improving surgical outcomes.

Durable left ventricular assist device implantation in extremely obese heart failure patients.

Left ventricular assist devices (LVADs) have improved clinical outcomes and quality of life for those with end-stage heart failure. However, the costs and risks associated with these devices necessitate appropriate patient selection. LVAD candidates are becoming increasingly more obese and there are conflicting reports regarding obesity's effect on outcomes. Hence, we sought to evaluate the impact of extreme obesity on clinical outcomes after LVAD placement. Consecutive LVAD implantation patients at our center from June 2008 to May 2016 were studied retrospectively. We compared patients with a body mass index (BMI) ≥40 kg/m2 (extremely obese) to those with BMI < 40 kg/m2 with respect to patient characteristics and surgical outcomes, including survival. 252 patients were included in this analysis, 30 (11.9%) of whom met the definition of extreme obesity. We found that patients with extreme obesity were significantly younger (47[33, 57] vs. 60[52, 67] years, P < 0.001) with fewer prior sternotomies (16.7% vs. 36.0%, P = 0.04). They had higher rates of pump thrombosis (30% vs. 9.0%, P = 0.003) and stage 2/3 acute kidney injury (46.7% vs. 27.0%, P = 0.003), but there were no differences in 30-day or 1-year survival, even after adjusting for age and clinical factors. Extreme obesity does not appear to place LVAD implantation patients at a higher risk for mortality compared to those who are not extremely obese; however, extreme obesity was associated with an increased risk of pump thrombosis, suggesting that these patients may require additional care to reduce the need for urgent device exchange.

Relation of Vasoplegia in the Absence of Primary Graft Dysfunction to Mortality Following Cardiac Transplantation.

Vasoplegia following cardiac transplantation is associated with increased morbidity and mortality. Previous studies have not accounted for primary graft dysfunction (PGD). The definition of vasoplegia is based on pressor requirement at 48 hours, many PGD parameters may have normalized after the initial 24 hours on inotropes. We surmised that the purported negative effects of vasoplegia following transplantation may in part be driven by PGD. We reviewed 240 consecutive adult cardiac transplants at our center between 2012 and 2016. The severity of vasoplegia was evaluated as a risk factor for 1-year survival, and the analysis was repeated for the subgroup of 177 patients who did not develop PGD. Overall, 63 (26%) of patients developed mild, moderate, or severe PGD. In those without PGD, vasoplegia was associated with length of stay but not with short- or long-term mortality. Moderate and/or severe vasoplegia occurred in 35 (15%) patients and was associated with higher short-term mortality, length of stay, and PGD. Multivariate logistic regression identified body mass index ≥35 kg/m2, left ventricular assist device before transplantation, and use of extracorporeal membrane oxygenation as joint risk factors for vasoplegia. In patients without PGD, only left ventricular assist device before transplantation was associated with vasoplegia. In conclusion, our results show that, in the sizeable subgroup of patients with no signs of PGD, vasoplegia had a much more modest impact on post-transplant morbidity and no significant effect on 1- and 3-year survival. This suggests that PGD may be a confounder when assessing vasoplegia as a risk factor for adverse outcomes.

Longitudinal Modeling of Lung Function Trajectories in Smokers with and without Chronic Obstructive Pulmonary Disease.

RATIONALE: The relationship between longitudinal lung function trajectories, chest computed tomography (CT) imaging, and genetic predisposition to chronic obstructive pulmonary disease (COPD) has not been explored. OBJECTIVES: 1) To model trajectories using a data-driven approach applied to longitudinal data spanning adulthood in the Normative Aging Study (NAS), and 2) to apply these models to demographically similar subjects in the COPDGene (Genetic Epidemiology of COPD) Study with detailed phenotypic characterization including chest CT. METHODS: We modeled lung function trajectories in 1,060 subjects in NAS with a median follow-up time of 29 years. We assigned 3,546 non-Hispanic white males in COPDGene to these trajectories for further analysis. We assessed phenotypic and genetic differences between trajectories and across age strata. MEASUREMENTS AND MAIN RESULTS: We identified four trajectories in NAS with differing levels of maximum lung function and rate of decline. In COPDGene, 617 subjects (17%) were assigned to the lowest trajectory and had the greatest radiologic burden of disease (P < 0.01); 1,283 subjects (36%) were assigned to a low trajectory with evidence of airway disease preceding emphysema on CT; 1,411 subjects (40%) and 237 subjects (7%) were assigned to the remaining two trajectories and tended to have preserved lung function and negligible emphysema. The genetic contribution to these trajectories was as high as 83% (P = 0.02), and membership in lower lung function trajectories was associated with greater parental histories of COPD, decreased exercise capacity, greater dyspnea, and more frequent COPD exacerbations. CONCLUSIONS: Data-driven analysis identifies four lung function trajectories. Trajectory membership has a genetic basis and is associated with distinct lung structural abnormalities.

Donor predicted heart mass as predictor of primary graft dysfunction.

BACKGROUND: Concern over the hazards associated with undersized donor hearts has impeded the utilization of otherwise viable allografts for transplantation. Previous studies have indicated predicted heart mass (PHM) may provide better size matching in cardiac transplantation than total body weight (TBW). We investigated whether size-matching donor hearts by PHM is a better predictor of primary graft dysfunction (PGD) than matching by TBW. METHODS: Records of consecutive adult cardiac transplants performed between 2012 and 2016 at a single-center academic hospital were reviewed. We compared patients implanted with hearts undersized by ≥30% with those implanted with donor hearts matched for size (within 30%), and performed the analysis both for undersizing by PHM and for undersizing by TBW. The primary outcome was moderate/severe PGD within 24 hours, according to the 2014 International Society for Heart and Lung Transplantation consensus. Secondary outcome was 1-year survival. RESULTS: Of 253 patients, 21 (8%) and 30 (12%) received hearts undersized by TBW and PHM, respectively. The overall rate of moderate/severe PGD was 13% (33 patients). PGD was associated with undersizing if performed by PHM (p = 0.007), but not if performed by TBW (p = 0.49). One-year survival was not different between groups (log-rank, p > 0.8). Multivariate analysis confirmed that undersizing donor hearts by PHM, but not by TBW, was predictive of moderate/severe PGD (OR 3.3, 95% CI 1.3 to 8.6). CONCLUSIONS: Undersized donor hearts by ≥30% by PHM may increase rates of PGD after transplantation, confirming that PHM provides more clinically appropriate size matching than TBW. Better size matching may ultimately allow for expanding the donor pool.

Reoperative sternotomy is associated with primary graft dysfunction following heart transplantation.

OBJECTIVES: Prior sternotomy is associated with increased morbidity and mortality following heart transplantation. However, its effect on primary graft dysfunction (PGD), a major contributor to early mortality, is unknown. Herein, this effect is studied using the International Society for Heart and Lung Transplantation consensus definition for PGD. METHODS: Medical records of consecutive adult cardiac transplants between 2012 and 2016 were reviewed. Baseline characteristics, postoperative findings and 1-year survival were compared between patients with and without prior sternotomy. RESULTS: Among 255 total patients included, 139 (55%) had undergone prior sternotomy; these recipients were older, more often male, had higher body mass index, higher frequencies of united network for organ sharing (UNOS) 1A status and ischaemic cardiomyopathy and experienced longer waitlist times when compared with those without prior sternotomy (all P < 0.018). Postoperatively, the prior sternotomy group exhibited higher rates of mild to severe PGD (32% vs 18%; P = 0.015) and higher short-term mortality (P = 0.017) and 1-year mortality (P = 0.047). They required more blood transfusions, had more postoperative pneumonia, wound infection and longer hospital stays. A stepwise multivariable regression model identified prior sternotomy as a predictor of PGD (odds ratio 2.7). Multiple prior sternotomies was associated with even more UNOS 1A status, ischaemic cardiomyopathy and pneumonia. However, logistic modelling did not show a difference in the rate of PGD between those with 1 or ≥2 prior sternotomies. CONCLUSIONS: Our data suggest that prior sternotomy is a risk factor for PGD. Consistent with previous reports, prior sternotomy is associated with increased morbidity, blood product utilization and 1-year mortality following cardiac transplantation.

Major Adverse Renal and Cardiac Events After Coronary Angiography and Cardiac Surgery.

BACKGROUND: Patients at high risk for having postprocedural complications may receive iodixanol, an iso-osmolar contrast, during coronary angiography to minimize the risk of renal toxicity. For those who also require cardiac surgery, the wait time between angiography and surgery may be a modifiable factor capable of mitigating poor surgical outcomes; however, there have been inconsistent reports regarding the optimal wait time. We sought to determine the effects of wait time between angiography and cardiac surgery, as well as contrast-induced acute kidney injury on the development of major adverse renal and cardiac events (MARCE). METHODS: We merged datasets to identify adults who underwent coronary angiography with iodixanol and subsequent cardiac surgery. RESULTS: Of 965 patients, 126 (13.1%) had contrast-induced acute kidney injury; 133 (13.8%) had MARCE within 30 days and 253 (26.2%) within 1 year of surgery. After adjusting for contrast-induced acute kidney injury, age, and Thakar acute renal failure score, the effect of wait time lost significance for the full cohort, but remained for the subgroup of 654 who had coronary artery bypass graft surgery. Patients undergoing coronary artery bypass graft surgery within 1 day of coronary angiography had an approximate twofold increase in risk of MARCE (30-day hazard ratio 2.13, 95% confidence interval: 1.16 to 3.88, p = 0.014; 1-year hazard ratio 2.07, 95% confidence interval: 1.32 to 3.23, p = 0.002) compared with patients who waited 5 or more days. CONCLUSIONS: Patients who had contrast-induced acute kidney injury and had cardiac surgery within 1 day of angiography had an increased risk of MARCE.