Evaluating the Impact of Ex Vivo Lung Perfusion on Organ Transplantation: A Retrospective Cohort Study.

BACKGROUND: Ex vivo lung perfusion (EVLP) sustains and allows advanced assessment of potentially useable donor lungs before transplantation, potentially relieving resource constraints. OBJECTIVE: We sought to characterize the effect of EVLP on organ utilization and patient outcomes. METHODS: We performed a retrospective, before-after cohort study using linked institutional data sources of adults wait-listed for lung transplant and donor organs transplanted in Ontario, Canada between 2005 and 2019. We regressed the annual number of transplants against year, EVLP use, and organ characteristics. Time-to-transplant, waitlist mortality, primary graft dysfunction, tracheostomy insertion, in-hospital mortality, and chronic lung allograft dysfunction were evaluated using propensity score-weighted regression. RESULTS: EVLP availability ( P =0.01 for interaction) and EVLP use ( P <0.001 for interaction) were both associated with steeper increases in transplantation than expected by historical trends. EVLP was associated with more donation after circulatory death and extended-criteria donors transplanted, while the numbers of standard-criteria donors remained relatively stable. Significantly faster time-to-transplant was observed after EVLP was available (hazard ratio=1.64 [1.41-1.92]; P <0.001). Fewer patients died on the waitlist after EVLP was available, but no difference in the hazard of waitlist mortality was observed (HR=1.19 [0.81-1.74]; P =0.176). We observed no difference in the likelihood of chronic lung allograft dysfunction before versus after EVLP was available. CONCLUSIONS: We observed a significant increase in organ transplantation since EVLP was introduced into practice, predominantly from increased acceptance of donation after circulatory death and extended-criteria lungs. Our findings suggest that EVLP-associated increases in organ availability meaningfully alleviated some barriers to transplant.

Queer(ing) medical spaces: queer theory as a framework for transformative social change in anesthesiology and critical care medicine.

Queer theory is a disruptive lens that can be adopted by researchers, educators, clinicians, and administrators to effect transformative social change. It offers opportunities for anesthesiologists, critical care physicians, and medical practitioners to more broadly understand what it means to think queerly and how queering anesthesiology and critical care medicine spaces improves workplace culture and patient outcomes. This article grapples with the cis-heteronormative medical gaze and queer people's apprehensions of violence in medical settings to offer new ways of thinking about structural changes needed in medicine, medical language, and the dehumanizing application of medical modes of care. Using a series of clinical vignettes, this article outlines the historical context underlying queer peoples' distrust of medicine, a primer in queer theory, and an understanding of how to begin to "queer" medical spaces using this critical framework.

RéSUMé: La théorie queer est une lentille perturbatrice qui peut être adoptée par la communauté de la recherche et de l'éducation, les personnes en clinique et les directions d'établissement pour apporter des changements sociaux transformateurs. Elle offre aux anesthésiologistes, aux intensivistes et aux médecins l'occasion de comprendre plus globalement ce que signifie le fait de penser de manière queer et comment la 'queer-icisation' des espaces d'anesthésiologie et de médecine de soins intensifs améliore la culture du milieu de travail et les devenirs des patient·es. Cet article s'attaque au regard médical cis- et hétéronormatif et aux appréhensions des personnes queer face à la violence dans les milieux médicaux afin de proposer de nouvelles façons de penser les changements structurels nécessaires en médecine, le langage médical et l'application déshumanisante des modes de soins médicaux. À l'aide d'une série de vignettes cliniques, cet article décrit le contexte historique sous-jacent à la méfiance des personnes queer à l'égard du monde médical. Il propose également une introduction à la théorie queer et une interprétation de la façon de commencer à rendre plus queer les espaces médicaux en utilisant ce cadre critique.

Determining Optimal Treatment to Correct Preoperative Anemia and Reduce Perioperative Allogeneic Blood Transfusions in Cardiac Surgery: A Retrospective Cohort Study.

OBJECTIVE: Preoperative anemia management reduces red blood cell (RBC) transfusion and adverse outcomes, but how best to optimize the patient's hemoglobin (Hgb) before cardiac surgery remains unclear. The authors sought to determine the optimal treatment of anemia using iron and epoetin alfa before cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Sunnybrook Health Sciences Centre, University of Toronto. PARTICIPANTS: The study comprised 532 consecutive patients referred to the outpatient Blood Conservation Clinic and who underwent cardiac surgery between 2008 and 2018. INTERVENTIONS: Of the 532 patients, 207 received oral iron, 84 received intravenous (IV) iron, 71 received epoetin alfa, 92 received combination therapy, and 78 received no treatment. MEASUREMENTS AND MAIN RESULTS: Multivariate linear, logistic, and Poisson regressions modelled preoperative Hgb, the change from referral to preoperative Hgb (∆Hgb), the odds of transfusion, and the number of RBC units transfused, while accounting for baseline covariates. Higher ∆Hgb was associated with IV iron >600 mg (9.80 g/L [6.17-13.42]), epoetin alfa >80,000 U (5.80 g/L [2.20-9.40]), and higher referral Hgb (1.91 g/L [1.09-2.74] per 10 g/L). Higher preoperative Hgb (odds ratio 0.76 [0.64-0.90]; count ratio 0.84 [0.77-0.93] per 10 g/L) corresponded to a lower likelihood of being transfused and transfusion of fewer RBC units. CONCLUSIONS: Preoperative IV iron >600 mg and epoetin alfa >80,000 U each was associated with significant increases in Hgb. Higher preoperative Hgb was associated with a lower likelihood of transfusion and transfusion of fewer RBC units. The authors recommend that cumulative preoperative doses of IV iron >600 mg and epoetin alfa >80,000 U be used for treatment of anemia before cardiac surgery.

A systematic review of the factors affecting choice of surgery as a career.

BACKGROUND: Interest in surgical careers among medical students has declined over the past decade. Multiple explanations have been offered for why top students are deterred or rejected from surgical programs, though no consensus has emerged. METHODS: We conducted a review of the literature to better characterize what factors affect the pursuit of a surgical career. We searched PubMed and EMBASE and performed additional reference checks. Agency for Healthcare Research and Quality (AHRQ) and Newcastle-Ottawa Education scores were used to evaluate the included data. RESULTS: Our search identified 122 full-text, primary articles. Analysis of this evidence identified 3 core concepts that impact surgical career decision-making: gender, features of surgical education, and student "fit" in the culture of surgery. CONCLUSION: Real and perceived gender discrimination has deterred female medical students from entering surgical careers. In addition, limited exposure to surgery during medical school and differences between student and surgeon personality traits and values may deter students from entering surgical careers. We suggest that deliberate and visible effort to include women and early-career medical students in surgical settings may enhance their interest in carreers in surgery.

CONTEXTE: On constate que l'intérêt pour une carrière en chirurgie a décliné chez les étudiants en médecine depuis une dizaine d'années. Plusieurs raisons ont été invoquées pour expliquer le désintérêt des étudiants talentueux à l'égard des programmes de chirurgie ou leur rejet de ces programmes, sans qu'on en arrive à un consensus. MÉTHODES: Nous avons procédé à une revue de la littérature afin de mieux cerner les facteurs qui influent sur la poursuite d'une carrière de chirurgien. Nous avons interrogé les bases de données PubMed et Embase et procédé à des vérifications additionnelles des références. Nous avons utilisé les scores de l'Agency for Healthcare Research and Quality (AHRQ) et l'échelle Newcastle-Ottawa pour l'éducation afin d'analyser les données retenues. RÉSULTATS: Notre recherche a permis de recenser 122 articles de fond en texte intégral. Leur analyse a mis au jour 3 facteurs clés qui influent sur les prises de décisions concernant une carrière en chirurgie : le sexe, les caractéristiques de la formation chirurgicale et la concordance entre le profil de l'étudiant et la culture du milieu chirurgical. CONCLUSION: La discrimination sexuelle réelle et perçue a détourné des étudiantes de la chirurgie comme perspective de carrière. De plus, l'exposition limitée à la chirurgie durant les études de médecine et les différences entre les traits de personnalité et les valeurs des étudiants et des chirurgiens peuvent dissuader les étudiants d'entreprendre une carrière en chirurgie. Selon nous, des efforts délibérés et tangibles d'intégration des femmes et des futurs médecins au domaine chirurgical contribueraient à accroître leur intérêt pour cette spécialité.

Same-day discharge after unilateral parathyroidectomy is safe.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) with intraoperative parathyroid hormone monitoring is the most common surgical approach among endocrine surgeons for primary hyperparathyroidism (PHPT). Overnight hospitalization after MIP represents a drain on resources and may be unnecessary. The aim of this study was to determine the safety of same-day discharge after MIP. METHODS: We performed a retrospective cohort study of patients treated for PHPT between August 2010 and July 2015. Patients were stratified by their length of stay in hospital and compared in terms of postoperative complications. RESULTS: During the study period 154 MIPs were performed. Of these, 101 patients were discharged on the day of their surgery (group 1) and the remaining 53 stayed 1 or more days (group 2). Three patients in group 2 required readmission within 30 days of discharge (p = 0.039). Seven patients in group 1 and 1 patient in group 2 visited the emergency department within 30 days of discharge (p = 0.72). Two patients in group 1 experienced persistent or recurrent PHPT (p = 0.55). Patients in group 2 were older than those in group 1 (69 v. 61 yr, p < 0.001) and had a higher mean American Society of Anesthesiologists classification of physical status (2.66 v. 2.24, p < 0.001). CONCLUSION: Same-day discharge after MIP is a safe practice and saves the cost of an overnight stay in hospital. Same-day discharge should be considered for all patients undergoing MIP if there are no clear indications for overnight hospitalization.

BACKGROUND: La parathyroïdectomie à effraction minimale avec surveillance peropératoire de la parathormone est la technique chirurgicale la plus employée par les chirurgiens endocriniens pour traiter l'hyperparathyroïdie primaire. L'hospitalisation d'une nuit suivant cette intervention, qui engloutit des ressources considérables, pourrait ne pas être nécessaire. La présente étude visait donc à déterminer la sécurité des chirurgies d'un jour dans ce BACKGROUND. METHODS: Nous avons mené une étude de cohorte rétrospective portant sur les patients qui avaient subi l'intervention entre août 2010 et juillet 2015. Après avoir stratifié les patients selon la durée de leur séjour à l'hôpital, nous avons comparé l'incidence de complications postopératoires. RESULTS: Au cours de la période visée, 154 parathyroïdectomies à effraction minimale ont été pratiquées. De ces 154 patients, 101 ont reçu leur congé le jour même (groupe 1), tandis que les 53 autres ont été hospitalisés 1 journée ou plus (groupe 2). Dans les 30 jours suivant leur congé, 3 patients du groupe 2 ont dû être réhospitalisés (p = 0,039), tandis que 7 patients du groupe 1 et 1 patient du groupe 2 se sont rendus à l'urgence (p = 0,72). Deux patients du groupe 1 ont continué de présenter une hyperparathyroïdie primaire persistante ou récurrente (p = 0,55). Les patients du groupe 2 étaient plus âgés que ceux du groupe 1 (69 ans contre 61 ans; p < 0,001) et appartenaient à une catégorie plus élevée du système de classification de la santé physique de l'American Society of Anesthesiologists (2,66 contre 2,24; p < 0,001). CONCLUSION: Il est donc sécuritaire de donner leur congé le jour même aux patients qui subissent une parathyroïdectomie à effraction minimale. Cette pratique, qui permet d'éviter les coûts associés à une hospitalisation, devrait être envisagée pour tous les patients, sauf en cas d'indication claire d'hospitalisation.

Crystal structure of the DdrB/ssDNA complex from Deinococcus radiodurans reveals a DNA binding surface involving higher-order oligomeric states.

The ability of Deinococcus radiodurans to recover from extensive DNA damage is due in part to its ability to efficiently repair its genome, even following severe fragmentation by hundreds of double-strand breaks. The single-strand annealing pathway plays an important role early during the recovery process, making use of a protein, DdrB, shown to greatly stimulate ssDNA annealing. Here, we report the structure of DdrB bound to ssDNA to 2.3 Å. Pentameric DdrB was found to assemble into higher-order structures that coat ssDNA. To gain further mechanistic insight into the protein's function, a number of point mutants were generated altering both DNA binding and higher order oligomerization. This work not only identifies higher-order DdrB associations but also suggests the presence of an extended DNA binding surface running along the 'top' surface of a DdrB pentamer and continuing down between two individual subunits of the ring structure. Together this work sheds new insight into possible mechanisms for DdrB function in which higher-order assemblies of DdrB pentamers assist in the pairing of complementary ssDNA using an extended DNA binding surface.

Arthroaspis n. gen., a common element of the Sirius Passet Lagerstätte (Cambrian, North Greenland), sheds light on trilobite ancestry.

BACKGROUND: Exceptionally preserved Palaeozoic faunas have yielded a plethora of trilobite-like arthropods, often referred to as lamellipedians. Among these, Artiopoda is supposed to contain taxa united by a distinctive appendage structure. This includes several well supported groups, Helmetiida, Nektaspida, and Trilobita, as well as a number of problematic taxa. Interrelationships remain unclear, and the position of the lamellipedian arthropods as a whole also remains the subject of debate. RESULTS: Arthroaspis bergstroemi n. gen. n. sp., a new arthropod from the early Cambrian Sirius Passet Lagerstätte of North Greenland shows a striking combination of both dorsal and ventral characters of Helmetiida, Nektaspida, and Trilobita. Cladistic analysis with a broad taxon sampling of predominantly early Palaeozoic arthropods yields a monophyletic Lamellipedia as sister taxon to the Crustacea or Tetraconata. Artiopoda is resolved as paraphyletic, giving rise to the Marrellomorpha. Within Lamellipedia, a clade of pygidium bearing taxa is resolved that can be shown to have a broadly helmetiid-like tergite morphology in its ground pattern. This morphology is plesiomorphically retained in Helmetiida and in Arthroaspis, which falls basally into a clade containing Trilobita. The trilobite appendages, though similar to those of other lamellipedians in gross morphology, have a unique outward rotation of the anterior trunk appendages, resulting in a 'hard wired' lateral splay, different to that observed in other Lamellipedia. CONCLUSIONS: The combination of helmetiid, trilobite, and nektaspid characters in Arthroaspis gives important hints concerning character polarisation within the trilobite-like arthropods. The distinctive tergite morphology of trilobites, with its sophisticated articulating devices, is derived from flanged edge-to-edge articulating tergites forming a shield similar to the helmetiids, previously considered autapomorphic for that group. The stereotypical lateral splay of the appendages of lamellipedians is a homoplastic character shown to be achieved by several groups independently.

Determining the impact of ex-vivo lung perfusion on hospital costs for lung transplantation: A retrospective cohort study.

INTRODUCTION: Ex-vivo lung perfusion (EVLP) has improved organ utilization for lung transplantation, but it is not yet known whether the benefits of this technology offset its additional costs. We compared the institutional costs of lung transplantation before vs after EVLP was available to identify predictors of costs and determine the health-economic impact of EVLP. METHODS: We performed a retrospective, before-after, propensity-score weighted cohort study of patients wait-listed for lung transplant at University Health Network (UHN) in Ontario, Canada, between January 2005 and December 2019 using institutional administrative data. We compared costs, in 2019 Canadian Dollars ($), between patients referred for transplant before EVLP was available (Pre-EVLP) to after (Modern EVLP). Cumulative costs were estimated using a novel application of multistate survival models. Predictors of costs were identified using weighted log-gamma generalized linear regression. RESULTS: A total of 1,199 patients met inclusion criteria (352 Pre-EVLP; 847 Modern EVLP). Mean total costs for the transplant hospitalization were $111,878 ($94,123-$130,767) in the Pre-EVLP era and $110,969 ($87,714-$136,000) in the Modern EVLP era. Cumulative five-year costs since referral were $278,777 ($82,575-$298,135) in the Pre-EVLP era and $293,680 ($252,832-$317,599) in the Modern EVLP era. We observed faster progression to transplantation when EVLP was available. EVLP availability was not a predictor of waitlist (cost ratio [CR] 1.04 [0.81-1.37]; p = 0.354) or transplant costs (CR 1.02 [0.80-1.29]; p = 0.425) but was associated with lower costs during posttransplant years 1&2 (CR 0.75 [0.58-1.06]; p = 0.05) and posttransplant years 3+ (CR 0.43 [0.26-0.74]; p = 0.001). CONCLUSIONS: At our center, EVLP availability was associated with faster progression to transplantation at no significant marginal cost.

Cost-effectiveness analysis of genetic tools to predict treatment response in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies show variable efficacy for patients with CF. Patient-derived predictive tools may identify individuals likely to respond to CFTRs, but are not in routine use. We aimed to determine the cost-utility of predictive tool-guided treatment with CFTRs as add-on to standard of care (SoC) for individuals with CF. METHODS: This economic evaluation compared two strategies using an individual level simulation: (i) Treat All, where all patients received CFTRs plus SoC and (ii) Test→Treat, where patients who tested positive on predictive tools received CFTRs plus SoC and those who tested negative received SoC only. We simulated 50,000 individuals over their lifetime, and estimated costs (2020 CAD) per quality-adjusted life year (QALY) from the healthcare payer's perspective, discounted at 1.5% annually. The model was populated using Canadian CF registry data and published literature. Probabilistic and deterministic sensitivity were conducted. RESULTS: The Treat All and Test→Treat and strategies yielded 22.41 and 21.36 QALYs, and cost $4.21 M and $3.15 M respectively. Results of probabilistic sensitivity analysis showed that Test→Treat was highly cost-effective compared to Treat All in 100% of simulations at cost-effectiveness thresholds as high as $500,000 per QALY. Test→Treat may save between $931 K to $1.1 M per QALY lost, depending on sensitivity and specificity of predictive tools. CONCLUSION: The use of predictive tools could optimize the health benefits of CFTR modulators while reducing costs. Our findings support the use of pre-treatment predictive testing and may help inform coverage and reimbursement policies for individuals with CF.

Time to extubation for lung transplant recipients represents a pragmatic end-point to guide the development of prognostic tests.

The field of transplantation would benefit from the integration of advanced precision medicine techniques. Although predictive tests for lung transplantation require a well-defined clinical end-point, there exists no consensus regarding which outcomes are optimal end-points for these purposes. While many possible candidate end-points exist, we propose that time-to-extubation is an optimal end-point for prognostic tests because of its: clinical relevance; objectiveness; stability over time; and association with healthcare expenditure. Herein, we describe the rationale for this selection and present the limitations of alternative outcomes for this purpose. Using a 72-hour cut-off, time to extubation correlated well with Primary Graft Dysfunction Grade 3, intensive care unit and hospital length of stay, and a greater than 2-fold increase in healthcare cost ratios. Given that time-to-extubation is an objective measure that is readily measured by all lung transplant centers, this metric represents a preferred primary end-point for prognostic tests developed for lung transplantation.

Standing out or fitting in: A latent projective content analysis of discrimination of women and 2SLGBTQ+ anesthesiologists and providers.

INTRODUCTION: Discrimination toward sex and gender minority anesthesiologists and anesthesia trainees exists. Potential reasons for this discrimination are unclear and incompletely characterized. This study sought to better understand what discrimination looks like for sex and gender minorities in anesthesiology and the culture within anesthesiology that allows this discrimination to occur. MATERIALS AND METHODS: With institutional research ethics board approval and informed consent, we performed a qualitative analysis of free-text responses from a previously-published internet-based cross-sectional survey distributed to Canadian anesthesiology residents, fellows, and staff. The purpose of this survey was to characterize intersections between respondent gender or sexuality with experiences of discrimination in the workplace. Separate analysis of qualitative and quantitative components of this survey was planned a priori, and the quantitative component was published elsewhere. Free-text responses were independently coded by two researchers and subsequently synthesized into emerging themes using latent projective content analysis sensitized by Butler's theory of performativity. RESULTS: Out of 490 free-text responses from 171 respondents [140 (81.9%) identifying as heterosexual], two themes emerged: i) fitting in: performativity reinforcing the status quo, and ii) standing out: performativity as a means of disruptive social change. Power structures were observed to favour individuals who "fit in" with the normative performances of gender and/or sexuality. DISCUSSION: Our study illuminates how individuals whose performances of gender and sexuality "fit in" with those expected normative performances reinforce a workplace culture that advantages them, whereas individuals whose performances of gender and sexuality "stand out" disproportionately experience discrimination. The dismantling of bias and discrimination in the anesthesiology workplace requires individuals (a) who are empowered within their workplace because they "fit in" with the majority; (b) who recognize discrimination toward communities of their peers and/or colleagues; and (c) who actively choose to "stand out".

Tidal volume during 1-lung ventilation: A systematic review and meta-analysis.

BACKGROUND: The selection of tidal volumes for 1-lung ventilation remains unclear, because there exists a trade-off between oxygenation and risk of lung injury. We conducted a systematic review and meta-analysis to determine how oxygenation, compliance, and clinical outcomes are affected by tidal volume during 1-lung ventilation. METHODS: A systematic search of MEDLINE and EMBASE was performed. A systematic review and random-effects meta-analysis was conducted. Pooled mean difference estimated arterial oxygen tension, compliance, and length of stay; pooled odds ratio was calculated for composite postoperative pulmonary complications. Risk of bias was determined using the Cochrane risk of bias and Newcastle-Ottawa tools. RESULTS: Eighteen studies were identified, comprising 3693 total patients. Low tidal volumes (5.6 [±0.9] mL/kg) were not associated with significant differences in partial pressure of oxygen (-15.64 [-88.53-57.26] mm Hg; P = .67), arterial oxygen tension to fractional intake of oxygen ratio (14.71 [-7.83-37.24]; P = .20), or compliance (2.03 [-5.22-9.27] mL/cmH2O; P = .58) versus conventional tidal volume ventilation (8.1 [±3.1] mL/kg). Low versus conventional tidal volume ventilation had no significant impact on hospital length of stay (-0.42 [-1.60-0.77] days; P = .49). Low tidal volumes are associated with significantly decreased odds of pulmonary complications (pooled odds ratio, 0.40 [0.29-0.57]; P < .0001). CONCLUSIONS: Low tidal volumes during 1-lung ventilation do not worsen oxygenation or compliance. A low tidal volume ventilation strategy during 1-lung ventilation was associated with a significant reduction in postoperative pulmonary complications.

Financial Incentives for Transcatheter Aortic Valve Implantation in Ontario, Canada: A Cost-Utility Analysis.

Background Transcatheter aortic valve implantation (TAVI) is a minimally invasive therapy for patients with severe aortic stenosis, which has become standard of care. The objective of this study was to determine the maximum cost-effective investment in TAVI care that should be made at a health system level to meet quality indicator goals. Methods and Results We performed a cost-utility analysis using probabilistic patient-level simulation of TAVI care from the Ontario, Canada, Ministry of Health perspective. Costs and health utilities were accrued over a 2-year time horizon. We created 4 hypothetical strategies that represented TAVI care meeting ≥1 quality indicator targets, (1) reduced wait times, (2) reduced hospital length of stay, (3) reduced pacemaker use, and (4) combined strategy, and compared these with current TAVI care. Per-person costs, quality-adjusted life years, and clinical outcomes were estimated by the model. Using these, incremental net monetary benefits were calculated for each strategy at different cost-effectiveness thresholds between $0 and $100 000 per quality-adjusted life year. Clinical improvements over the current practice were estimated with all comparator strategies. In Ontario, achieving quality indicator benchmarks could avoid ≈26 wait-list deaths and 200 wait-list hospitalizations annually. Compared with current TAVI care, the incremental net monetary benefit for this strategy varied from $10 765 (±$8721) and $17 221 (±$8977). This would translate to an annual investment of between ≈$14 to ≈$22 million by the Ontario Ministry of Health to incentivize these performance measures being cost-effective. Conclusions This study has quantified the modest annual investment required and substantial clinical benefit of meeting improvement goals in TAVI care.

Positive end-expiratory pressure and recruitment maneuvers during one-lung ventilation: A systematic review and meta-analysis.

BACKGROUND: It is unclear how positive end-expiratory pressure (PEEP) and recruitment maneuvers impact patients during one-lung ventilation (OLV). We conducted a systematic review and meta-analysis of the effect of lung recruitment and PEEP on ventilation and oxygenation during OLV. METHODS: A systematic review and random-effects meta-analysis were performed. Mean difference with standard deviation was calculated. Included studies were evaluated for quality and risk of bias using the Cochrane Risk of Bias tool and the modified Newcastle-Ottawa Score where appropriate. RESULTS: In total, 926 articles were identified, of which 16 were included in meta-analysis. Recruitment maneuvers increased arterial oxygen tension (PaO2) by 82 mm Hg [20, 144 mm Hg] and reduced dead-space by 5.9% [3.8, 8.0%]. PEEP increased PaO2 by 30.3 mm Hg [11.9, 48.6 mm Hg]. Subgroup analysis showed a significant increase in PaO2 (P = .0003; +35.4 mm Hg [16.2, 54.5 mm Hg]) with PEEP compared with no PEEP but no such difference in comparisons with PEEP-treated controls. No significant difference in PaO2 was observed between "high" and "low" PEEP-treated subgroups (P = .29). No significant improvement in PaO2 was observed for subgroups coadministered PEEP, lung recruitment, and low tidal volumes. PEEP was associated with a modest but statistically significant increase in compliance (P = .03; 4.33 mL/cmH2O [0.33, 8.32]). High risk of bias was identified in the majority of studies. Considerable heterogeneity was observed. CONCLUSIONS: Recruitment maneuvers and PEEP have physiologic advantages during OLV. The optimal use of PEEP is yet to be determined. The evidence is limited by heavy use of surrogate outcomes. Future studies with clinical outcomes are necessary to determine the impact of recruitment maneuvers and PEEP during OLV.

Ediacaran Doushantuo-type biota discovered in Laurentia.

The Ediacaran period (635-541 Ma) was a time of major environmental change, accompanied by a transition from a microbial world to the animal world we know today. Multicellular, macroscopic organisms preserved as casts and molds in Ediacaran siliciclastic rocks are preserved worldwide and provide snapshots of early organismal, including animal, evolution. Remarkable evolutionary advances are also witnessed by diverse cellular and subcellular phosphatized microfossils described from the Doushantuo Formation in China, the only source showing a diversified assemblage of microfossils. Here, we greatly extend the known distribution of this Doushantuo-type biota in reporting an Ediacaran Lagerstätte from Laurentia (Portfjeld Formation, North Greenland), with phosphatized animal-like eggs, embryos, acritarchs, and cyanobacteria, the age of which is constrained by the Shuram-Wonoka anomaly (c. 570-560 Ma). The discovery of these Ediacaran phosphatized microfossils from outside East Asia extends the distribution of the remarkable biota to a second palaeocontinent in the other hemisphere of the Ediacaran world, considerably expanding our understanding of the temporal and environmental distribution of organisms immediately prior to the Cambrian explosion.

Effect of synthetic agonists of toll-like receptor 9 on canine lymphocyte proliferation and cytokine production in vitro.

Synthetic agonists of TLR9 containing novel DNA structures and R'pG (wherein R=1-(2'-deoxy-beta-d-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine) motifs, referred to as immune modulatory oligonucleotides (IMOs), have been shown to stimulate T(H)-1-type-immune responses and potently reverse allergen-induced T(H)-2 responses to T(H)-1 responses in vitro and in vivo in mice. In order to investigate the immunomodulatory potential of IMOs in dogs, canine peripheral blood mononuclear cells (PBMC) from healthy dogs were stimulated with three different IMOs and a control IMO, alone or in combination with concanavalin A (ConA). Lipopolysaccharide (LPS) was used as a positive control for B lymphocyte activation. Carboxyfluorescein diacetate succinimidyl ester and phenotype staining was used to tag proliferating T and B lymphocytes (CD5(+) and CD21(+)) by flow cytometry. Real-time PCR and ELISA were processed to assay cytokine production of IFN-gamma, IL-10, TGF-beta, IL-6 and IL-10. Like LPS, IMOs alone induced neither proliferation of CD5(+) T cells nor CD21(+) B cells, but both LPS and IMO had the capacity to co-stimulate ConA and induced proliferation of B cells. In combination with ConA, one of the IMOs (IMO1) also induced proliferation of T cells. IMO1 also significantly enhanced the expression of IFN-gamma on the mRNA and protein level in canine PBMC, whereas expression of IL-10, TGF-beta and IL-4 mRNAs was not induced by any of the IMOs. These results indicate that in canine PBMC from healthy dogs, IMO1 was able to induce a T(H)-1 immune response including T- and B-cell proliferation.

Medium and long-term emergency department utilization after oesophagectomy: a population-based analysis.

OBJECTIVES: Oesophagectomy is a complex operation with the potential for prolonged recovery. The aim of this study was to evaluate healthcare resource utilization, specifically emergency department (ED) visits within 1 year of oesophagectomy, and to identify risk factors for ED visits and frequent ED use (FEDU). METHODS: A retrospective cohort study of consecutive oesophagectomies for cancer in all Ontario hospitals was conducted using linked health data (2000-2012) including the ability to identify ED visits at non-index hospitals. Ontario has a single-payer healthcare system with a population of 13.8-million people. Multivariable regression was used to identify independent factors associated with ED visits and FEDU (≥3 ED visits) within 1 year after oesophagectomy. RESULTS: There were 3344 oesophagectomies with in-hospital mortality of 5.8% (n = 193). Of those discharged, 16.4% (n = 549), 36.0% (n = 1203) and 55.8% (n = 1866) had ED visits within 30 days, 90 days and 1 year, respectively. Higher comorbidity [adjusted odds ratio (aOR) = 1.08, 95% confidence interval (CI): 1.05-1.11, P < 0.0001], rurality (aOR = 1.40, 95% CI: 1.10-1.78, P = 0.006) and receipt of chemotherapy and/or radiation therapy (aOR = 2.55, 95% CI: 2.12-3.08, P < 0.0001) were independent risk factors for ED visits within 1 year of oesophagectomy. Thoracoscopic-assisted surgery was independently associated with decreased ED visits (aOR = 0.67, 95% CI: 0.45-0.99, P = 0.049). Eight hundred and thirteen (24.3%) patients had FEDU. Higher comorbidity (aOR = 1.11, 95% CI: 1.08-1.14, P < 0.0001), rurality (aOR = 1.66, 95% CI: 1.31-2.10, P < 0.0001) and receipt of chemotherapy and/or radiation therapy (aOR = 2.38, 95% CI: 1.93-2.93, P < 0.0001) were independent risk factors for FEDU. One health region had more ED visits (P = 0.04) and more FEDU (P = 0.001) when compared with the other regions. There were higher ED visits and FEDU in the later years of the study period (both P < 0.0001). CONCLUSIONS: ED visits are common after oesophagectomy with almost 25% of patients having ≥3 visits and >50% having ≥1 visit within 1 year of oesophagectomy. We have identified demographic, surgical and regional risk factors for the potential targeted quality improvement.

Ectopic thymoma managed by neck dissection & video-assisted thoracoscopic thymectomy.

Ectopic thymoma in the neck is a rare phenomenon, with fewer than 20 cases reported worldwide. Evidence for management of ectopic thymoma comes from literature for mediastinal thymoma despite clinical features that distinguish the two. Here we present a case of a 31-year-old female with an asymptomatic neck mass who was found to have an ectopic cervical thymoma with concomitant mediastinal thymic hyperplasia. The decision was made to perform a left-sided neck dissection and a video-assisted thoracoscopic surgery (VATS) thymectomy. We suggest that this approach be considered for a minimally invasive management of this rare but important condition.